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Plasmodium lactate dehydrogenase (pLDH) is a common target in malaria rapid diagnostic tests (RDTs). These commercial antibody capture assays target either Plasmodium falciparum–specific pLDH (PfLDH), P. vivax–specific pLDH (PvLDH), or a conserved epitope in all human malaria pLDH (PanLDH). However, there are no assays specifically targeting P. ovale, P. malariae or zoonotic parasites such as P. knowlesi and P. cynomolgi. A malaria multiplex array, carrying the specific antibody spots for PfLDH, PvLDH, and PanLDH has been previously developed. This study aimed to assess potential cross-reactivity between pLDH from various Plasmodium species and this array. We tested recombinant pLDH proteins, clinical samples for P. vivax, P. falciparum, P. ovale curtisi, and P. malariae; and in vitro cultured P. knowlesi and P. cynomolgi. P. ovale-specific pLDH (PoLDH) and P. malariae-specific pLDH (PmLDH) cross-reacted with the PfLDH and PanLDH spots. Plasmodium Knowlesi-specific pLDH (PkLDH) and P. cynomolgi-specific pLDH (PcLDH) cross-reacted with the PvLDH spot, but only PkLDH was recognized by the PanLDH spot. Plasmodium ovale and P. malariae can be differentiated from P. falciparum by the concentration ratios of PanLDH/PfLDH, which had mean (range) values of 4.56 (4.07–5.16) and 4.56 (3.43–6.54), respectively, whereas P. falciparum had a lower ratio of 1.12 (0.56–2.61). Plasmodium knowlesi had a similar PanLDH/PvLDH ratio value, with P. vivax having a mean value of 2.24 (1.37–2.79). The cross-reactivity pattern of pLDH can be a useful predictor to differentiate certain Plasmodium species. Cross-reactivity of the pLDH bands in RDTs requires further investigation.

Electrochemical hydrogenation of N2 under ambient conditions is attractive for sustainable and distributable NH3 production but is limited by the lack of selective electrocatalysts. Herein, we describe active site motifs based on the Chevrel phase chalcogenide Fe2Mo6S8 that exhibit intrinsic activities for converting N2 to NH3 in aqueous electrolytes. Despite having a very low specific surface area of ∼2 m2/g, this catalyst exhibited a Faradaic efficiency of 12.5% and an average rate of 70 μg h-1 mgcat-1 for NH3 production at -0.20 V vs RHE. Such activities were attributed to the unique composition and structure of Fe2Mo6S8 that provide synergistic multisites for activating and associating key reaction intermediates. Specifically, Fe/Mo sites assist adsorption and activation of N2, whereas S sites stabilize hydrogen intermediate Had* for N2 hydrogenation. Fe in Fe2Mo6S8 enhances binding of S with Had* and thus inhibits the competing hydrogen evolution reaction. The spatial geometry of Fe, Mo, and S sites in Fe2Mo6S8 promotes conversion of N2-Had* association intermediates, reaching a turnover frequency of ∼0.23 s-1 for NH3 production.

Outmigrating, juvenile Chinook salmon Oncorhynchus tshawytscha, with access to floodplains (e.g., Yolo Bypass California, USA), grow faster than those restricted to the main channel of the Sacramento River. How these young salmon might use rooted, vegetative structure (e.g., to decrease energy expenditures) while holding positions in flowing water on floodplains and flooded riparian zones is unknown. We conducted daytime experiments in a large (24.4 m long) flume containing a planted area (9.76 m × 1.22 m) of sandbar willows, Salix interior. Flume water was maintained at 1.5 m depth and 16 °C over a 15–90 cm s−1 test velocity range. Fish were videoed using 19 cameras to determine positional behavior, including their depth, use of vegetation, and tail-beat (body-undulation) frequencies (TBFs). These TBFs were replicated with similarly-sized salmon in a calibrated, Brett-type swimming respirometer, where oxygen consumption rates were measured. Using these laboratory measurements, we estimated their swimming velocities and energetic costs associated with occupying sandbar willow habitats in the flume. As flume velocities increased and the leafy canopies of the willows were bent over from the flow, salmon occupied deeper water, among the thick stems of the willows, and maintained their positions. Even at the highest (90 cm s−1) nominal flume velocities, their estimated swimming velocities were only 35.6 cm s−1, within the bottom 15 cm of the water column. This resulted in unchanged energetic costs, compared with those estimated at lower nominal water velocities. The use of vegetated (e.g., with sandbar willow common to the riparian zone) floodplains, rather than non-vegetated ones, can potentially provide energy-saving, growth-promoting daytime habitat for migrating juvenile salmonids during river-flow periods that include floodplain inundation.

Cardiac regeneration is the outcome of the highly regulated interplay of multiple processes, including the inflammatory response, cardiomyocyte dedifferentiation and proliferation, neovascularization and extracellular matrix turnover. Species-specific traits affect these injury-induced processes, resulting in a wide variety of cardiac regenerative potential between species. Indeed, while mammals are generally considered poor regenerators, certain amphibian and fish species like the zebrafish display robust regenerative capacity post heart injury. The species-specific traits underlying these differential injury responses are poorly understood. In this review, we will compare the injury induced processes of the mammalian and zebrafish heart, describing where these processes overlap and diverge. Additionally, by examining multiple species across the animal kingdom, we will highlight particular traits that either positively or negatively affect heart regeneration. Last, we will discuss the possibility of overcoming regeneration-limiting traits to induce heart regeneration in mammals.

Macrophages engulf “foreign” cells and particles, but phagocytosis of healthy cells and cancer cells is inhibited by expression of the ubiquitous membrane protein CD47 which binds SIRPα on macrophages to signal “self”. Motivated by some clinical efficacy of anti-CD47 against liquid tumors and based on past studies of CD47-derived polypeptides on particles that inhibited phagocytosis of the particles, here we design soluble, multivalent peptides to bind and block SIRPα. Bivalent and tetravalent nano-Self peptides prove more potent (K(eff) ~ 10 nM) than monovalent 8-mers as agonists for phagocytosis of antibody opsonized cells, including cancer cells. Multivalent peptides also outcompete soluble CD47 binding to human macrophages, consistent with SIRPα binding, and the peptides suppress phosphotyrosine in macrophages, consistent with inhibition of SIRPα’s “self” signaling. Peptides exhibit minimal folding, but functionality suggests an induced fit into SIRPα’s binding pocket. Pre-clinical studies in mice indicate safety, with no anemia that typifies clinical infusions of anti-CD47. Multivalent nano-Self peptides thus constitute an alternative approach to promoting phagocytosis of “self”, including cancer cells targeted clinically.

Tecovirimat (TPOXX®; ST-246) was approved for the treatment of symptomatic smallpox by the USFDA in July of 2018 and has been stockpiled by the US government for use in a smallpox outbreak. While there has not been a reported case of smallpox since 1978 it is still considered a serious bioterrorism threat.A brief history of smallpox from its proposed origins as a human disease through its eradication in the late 20th century is presented. The current smallpox threat and the current public health response plans are described. The discovery, and development of tecovirimat through NDA submission and subsequent approval for treatment of smallpox are discussed. Google Scholar and PubMed were searched over all available dates for relevant publications.Approval of tecovirimat to treat smallpox represents an important milestone in biosecurity preparedness. Incorporating tecovirimat into the CDC smallpox response plan, development of pediatric liquid and intravenous formulations, and approval for post-exposure prophylaxis would provide additional health security benefit.Tecovirimat shows broad efficacy against orthopoxviruses in vitro and in vivo and could be developed for use against emerging orthopoxvirus diseases such as monkeypox, vaccination-associated adverse events, and side effects of vaccinia oncolytic virus therapy.

The study investigated the leaf architecture and petiole anatomy of eight Dipterocarpus (Dipterocarpaceae) species growing in Mount Makiling Forest Reserve (MMFR) in the Philippines to delineate the species, especially during their non-flowering phase. Leaf and petiole samples from MMFR were examined following the manual on leaf architecture studies. Freehand technique was used to examine the stomata and petiole characters. A UPGMA phenogram was then generated to determine the relationships among Dipterocarpus species using 26 leaf and petiole characters. The most useful characters to delineate Dipterocarpus species are the presence of trichomes, the arrangement of vascular bundles (medullary and outer vascular bundles), areolation, fimbrial vein, and leaf size. Other characters viz., the laminar ratio, blade class, laminar shape, base shape, margin type, and intersecondary, and layers and shape of parenchyma and collenchyma cells were useful as unifying characters. Therefore, certain characters of the leaf architecture and petiole anatomy may be used as taxonomic markers to delineate and correlate the Dipterocarpus species in the Philippines particularly during the nonflowering phase of the species. However, further investigations using samples from the wild populations of the species and molecular techniques may be done to elucidate the taxonomic use of the characters presented in this study. Bangladesh J. Plant Taxon. 27(1): 1-14, 2020 (June)

BACKGROUND: To determine the prevalence and severity of acute kidney injury (AKI) at different time frames in relation to gestational age (GA) and birthweight (BW) in extremely low gestational age neonates (ELGAN). Our hypothesis is that ELGAN with lower GA and lower BW have higher AKI rates. METHODS: 923 ELGAN enrolled in the Preterm Erythropoietin Neuroprotection Trial were evaluated from birth until death or hospital discharge. AKI was defined according to kidney disease: improving global outcomes (KDIGO) definition from clinically-derived serum creatinine (SCr) measurements. Severe AKI was defined as stage 2 or higher. RESULTS: For the entire cohort, 351/923 (38.0%, CI = 34.8–41.3%) had at least one episode of stage 1 or higher AKI and 168/923 (18.2%, CI = 15.7–20.7%) had at least one episode of severe (stage 2 or higher) AKI. The prevalence of AKI stage 1 or higher for the entire cohort during the early (days 3–7), middle (days 8–14) and late follow-up period (after day 14) was 112/923 (12.1%, CI = 10.0–14.3%), 142/891 (15.9%, CI = 13.5–18.4%) and 249/875 (28.5%, CI = 25.4–31.5%), respectively. The rates of severe AKI during the hospital course were 27.8%, 21.9%, 13.6%, and 9.4% for the 24, 25, 26 and 27 week GA groups respectively. AKI rates were significantly higher with decreasing GA and decreasing BW for stated time trends (all p < 0.01 using tests for trend). CONCLUSIONS: AKI is relatively common in ELGAN during their initial hospital course, and is associated with lower GA and BW.

Aquatic ecosystems worldwide face growing threats from elevated levels of contaminants from human activities. Toxic levels of selenium (Se) shown to cause deformities in birds, fish, and mammals can transfer from parents to progeny during embryonic development or accumulate through Se-enriched diets. For migratory species that move across landscapes, tracking exposure to elevated Se is vital to mitigating vulnerabilities. Yet, traditional toxicological investigations resolve only recent Se exposure. Here, we use a novel combination of X-ray fluorescence microscopy and depositional chronology in a biomineral to reveal for the first time provenance, life stage, and duration of toxic Se exposure over the lifetime of an organism. Spinal deformities observed in wild Sacramento Splittail (Pogonichthys macrolepidotus), an imperiled migratory minnow, were attributed to elevated Se acquired through maternal transfer and juvenile feeding on contaminated prey. This novel approach paves the way for diagnosing sources, pathways, and potential for a cumulative exposure of Se relevant for conservation.

Naturally occurring smallpox has been eradicated but research stocks of variola virus (VARV), the causative agent of smallpox, still exist in secure laboratories. Clandestine stores of the virus or resurrection of VARV via synthetic biology are possible and have led to concerns that VARV could be used as a biological weapon. The US government has prepared for such an event by stockpiling smallpox vaccines and TPOXX®, SIGA Technologies' smallpox antiviral drug. While vaccination is effective as a pre-exposure prophylaxis, protection is limited when administered following exposure. Safety concerns preclude general use of the vaccine unless there is a smallpox outbreak. TPOXX is approved by the FDA for use after confirmed diagnosis of smallpox disease. Tecovirimat, the active pharmaceutical ingredient in TPOXX, targets a highly conserved orthopoxviral protein, inhibiting long-range dissemination of virus. Although indications for use of the vaccine and TPOXX do not overlap, concomitant use is possible, especially if the TPOXX indication is expanded to include post-exposure prophylaxis. It is therefore important to understand how vaccine and TPOXX may interact. In studies presented here, monkeys were vaccinated with the ACAM2000TM live attenuated smallpox vaccine and concomitantly treated with tecovirimat or placebo. Immune responses to the vaccine and protective efficacy versus a lethal monkeypox virus (MPXV) challenge were evaluated. In two studies, primary and anamnestic humoral immune responses were similar regardless of tecovirimat treatment while the third study showed reduction in vaccine elicited humoral immunity. Following lethal MPXV challenge, all (12 of 12) vaccinated/placebo treated animals survived, and 12 of 13 vaccinated/tecovirimat treated animals survived. Clinical signs of disease were elevated in tecovirimat treated animals compared to placebo treated animals. This suggests that TPOXX may affect the immunogenicity of ACAM2000 if administered concomitantly. These studies may inform on how vaccine and TPOXX are used during a smallpox outbreak.

Bacteria are part of the insect gut system and influence many physiological traits of their host. Gut bacteria may even reduce or block the transmission of arboviruses in several species of arthropod vectors. Culicoides biting midges are important arboviral vectors of several livestock and wildlife diseases, yet limited information is available on their gut bacterial communities. Addressing this gap will help inform how these communities can be manipulated and ultimately used as novel tools to control pathogens. To assess how bacterial communities change during the life stages of lab-reared C. nubeculosus and C. sonorensis, endosymbiotic bacteria were identified using Illumina sequencing of 16S rRNA and taxonomically characterised. Analyses were conducted to determine how gut bacterial communities in adults are influenced by species identity and geographic distance among biting midge populations. Communities of the two lab-reared Culicoides species significantly changed after pupation and with maturation into 6-day-old adults. Pseudomonas, Burkholderiaceae and Leucobacter bacteria were part of a core community that was trans-stadially transmitted and found throughout their life cycle. Among field-collected biting midges, the bacterial communities were unique for almost each species. Cardinium, Rickettsia and Wolbachia were some of the most abundant bacteria in midges collected from wetlands. Only Pseudomonas was present in high relative abundance in all field-collected species. In this study, species identity, as well as geographic distance, influenced the gut bacterial communities and may partly explain known inter- and intra-species variability in vector competence. Additionally, stably associated bacterial species could be candidates for paratransgenic strategies to control vector-borne pathogens.

Predation is a common cause of early life stage mortality in fishes, with reduced risk as individuals grow and become too large to be consumed by gape‐limited predatory fishes. Large‐bodied species, such as sturgeon, may reach this size‐refuge within the first year. However, there is limited understanding of what this size threshold is despite the value of this information for conservation management. We conducted laboratory‐based predation experiments on juvenile green sturgeon, Acipenser medirostris, to estimate vulnerability to predation during outmigration from their natal reaches in California to the Pacific Ocean. Two highly abundant and non‐native predatory fish species (largemouth bass, Micropterus salmoides, and striped bass, Morone saxatilis) were captured in the wild to be tested with developing juvenile green sturgeon from the UC Davis Green Sturgeon Broodstock Program. Experimental tanks, each containing five predators, received thirty prey for 24‐hr exposures. Between sturgeon prey trials, predators were exposed to alternative prey species to confirm predators were exhibiting normal feeding behaviors. In addition to green sturgeon mortality data, trials were video recorded and predatory behaviors were quantified. Overall, these predator species displayed much lower rates of predation on juvenile green sturgeon than alternate prey. Predation decreased with green sturgeon size, and predation risk diminished to zero once sturgeon reached a length threshold of roughly 20–22 cm total length, or between 38% and 58% of predator total length. Behavioral analyses showed low motivation to feed on green sturgeon, with both predators attempting predation less frequently as sturgeon grew. Results of this study imply that optimizing growth rates for larval and juvenile sturgeon would shorten the time in which they are vulnerable to predation. Future experiments should assess predation risk of juvenile green sturgeon by additional predator species common to the Sacramento‐San Joaquin watershed.

Physicochemical principles such as stoichiometry and fractal assembly can give rise to characteristic scaling between components that potentially include coexpressed transcripts. For key structural factors within the nucleus and extracellular matrix, we discover specific gene-gene scaling exponents across many of the 32 tumor types in The Cancer Genome Atlas, and we demonstrate utility in predicting patient survival as well as scaling-informed machine learning (SIML). All tumors with adjacent tissue data show cancer-elevated proliferation genes, with some genes scaling with the nuclear filament LMNB1, including the transcription factor FOXM1 that we show directly regulates LMNB1. SIML shows that such regulated cancers cluster together with longer overall survival than dysregulated cancers, but high LMNB1 and FOXM1 in half of regulated cancers surprisingly predict poor survival, including for liver cancer. COL1A1 is also studied because it too increases in tumors, and a pan-cancer set of fibrosis genes shows substoichiometric scaling with COL1A1 but predicts patient outcome only for liver cancer—unexpectedly being prosurvival. Single-cell RNA-seq data show nontrivial scaling consistent with power laws from bulk RNA and protein analyses, and SIML segregates synthetic from contractile cancer fibroblasts. Our scaling approach thus yields fundamentals-based power laws relatable to survival, gene function, and experiments.

Background Reprogramming of cancers into normal-like tissues is an innovative strategy for cancer treatment. Recent reports demonstrate that defined factors can reprogram cancer cells into pluripotent stem cells. Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor in humans. Despite multimodal therapy, the outcome for patients with GBM is still poor. Therefore, developing novel therapeutic strategy is a critical requirement. Methods We have developed a novel reprogramming method that uses a conceptually unique strategy for GBM treatment. We screened a kinase inhibitor library to find which candidate inhibitors under reprogramming condition can reprogram GBM cells into neurons. The induced neurons are identified whether functional and loss of tumorigenicity. Results We have found that mTOR and ROCK kinase inhibitors are sufficient to reprogram GBM cells into neural-like cells and “normal” neurons. The induced neurons expressed neuron-specific proteins, generated action potentials and neurotransmitter receptor-mediated currents. Genome-wide transcriptional analysis showed that the induced neurons had a profile different from GBM cells and were similar to that of control neurons induced by established methods. In vitro and in vivo tumorigenesis assays showed that induced neurons lost their proliferation ability and tumorigenicity. Moreover, reprogramming treatment with ROCK-mTOR inhibitors prevented GBM local recurrence in mice. Conclusion This study indicates that ROCK and mTOR inhibitors-based reprogramming treatment prevents GBM local recurrence. Currently ROCK-mTOR inhibitors are used as anti-tumor drugs in patients, so this reprogramming strategy has significant potential to move rapidly toward clinical trials. Electronic supplementary material The online version of this article (10.1186/s13046-018-0857-5) contains supplementary material, which is available to authorized users.

Balamuthia mandrillaris, a pathogenic free-living amoeba, causes cutaneous skin lesions as well as granulomatous amoebic encephalitis, a ‘brain-eating’ disease. As with the other known pathogenic free-living amoebas (Naegleria fowleri and Acanthamoeba species), drug discovery efforts to combat Balamuthia infections of the central nervous system are sparse; few targets have been validated or characterized at the molecular level, and little is known about the biochemical pathways necessary for parasite survival. Current treatments of encephalitis due to B. mandrillaris lack efficacy, leading to case fatality rates above 90%. Using our recently published methodology to discover potential drugs against pathogenic amoebas, we screened a collection of 85 compounds with known antiparasitic activity and identified 59 compounds that impacted the growth of Balamuthia trophozoites at concentrations below 220 µM. Since there is no fully annotated genome or proteome of B. mandrillaris, we sequenced and assembled its transcriptome from a high-throughput RNA-sequencing (RNA-Seq) experiment and located the coding sequences of the genes potentially targeted by the growth inhibitors from our compound screens. We determined the sequence of 17 of these target genes and obtained expression clones for 15 that we validated by direct sequencing. These will be used in the future in combination with the identified hits in structure guided drug discovery campaigns to develop new approaches for the treatment of Balamuthia infections.

A large variety of clinical manifestation in individual pigs occurs after infection with pathogens involved in porcine respiratory disease complex (PRDC). Some pigs are less prone to develop respiratory disease symptoms. The variation in clinical impact after infection and the recovery capacity of an individual animal are measures of its resilience. In this paper, we examined which ones of a range of animal-based factors (rectal temperature, body weight, skin lesion scores, behavior, natural antibody serum levels, serum levels of white blood cells, and type of T and granulocyte subsets) when measured prior to infection are related to disease severity. These animal-based factors and the interaction with housing regimen of the piglets (conventional or enriched) were modeled using linear regression to predict disease severity using a dataset acquired from a previous study using a well-established experimental coinfection model of porcine reproductive and respiratory syndrome virus (PRRSV) and Actinobacillus pleuropneumoniae. Both PRRSV and A. pleuropneumoniae are often involved in PRDC. Histological lung lesion score of each animal was used as a measure for PRDC severity after infection. Prior to infection, higher serum levels of lymphocytes (CD3+), naïve T helper (CD3+CD4+CD8−), CD8+ (as well as higher relative levels of CD8+), and memory T helper (CD3+CD4+CD8+) cells and higher relative levels of granulocytes (CD172a) were related to reduced disease severity in both housing systems. Raised serum concentrations of natural IgM antibodies binding to keyhole limpet hemocyanin (KLH) were also related to reduced disease severity after infection. Increased levels of skin lesions at the central body part (after weaning and before infection) were related to increased disease severity in conventional housing systems only. High resisters showed a lower histological lung lesion score, which appeared unrelated to sex. Body temperature, behavior, and growth prior to infections were influenced by housing regimen but could not explain the variation in lung lesion scores after infection. Raised basal lymphocyte counts and lower skin lesion scores are related to reduced disease severity independent of or dependent on housing system, respectively. In conclusion, our study identifies intrinsic animal-based measures using linear regression analysis that predicts resilience to infections in pigs.

Myocardial infarction causes ventricular muscle loss and formation of scar tissue. The surviving myocardium in the border zone, located adjacent to the infarct, undergoes profound changes in function, structure and composition. How and to what extent these changes of border zone cardiomyocytes are regulated epigenetically is not fully understood. Here, we obtained transcriptomes of PCM-1-sorted mouse cardiomyocyte nuclei of healthy left ventricle and 7 days post myocardial infarction border zone tissue. We validated previously observed downregulation of genes involved in fatty acid metabolism, oxidative phosphorylation and mitochondrial function in border zone-derived cardiomyocytes, and observed a modest induction of genes involved in glycolysis, including Slc2a1 (Glut1) and Pfkp. To gain insight into the underlying epigenetic regulatory mechanisms, we performed H3K27ac profiling of healthy and border zone cardiomyocyte nuclei. We confirmed the switch from Mef2- to AP-1 chromatin association in border zone cardiomyocytes, and observed, in addition, an enrichment of PPAR/RXR binding motifs in the sites with reduced H3K27ac signal. We detected downregulation and accompanying epigenetic state changes at several key PPAR target genes including Ppargc1a (PGC-1α), Cpt2, Ech1, Fabpc3 and Vldrl in border zone cardiomyocytes. These data indicate that changes in epigenetic state and gene regulation underlie the maintained metabolic switch in border zone cardiomyocytes.

Malaria is a major global health problem which predominantly afflicts developing countries. Although many antimalarial therapies are currently available, the protozoan parasite causing this disease, Plasmodium spp., continues to evade eradication efforts. One biological phenomenon hampering eradication efforts is the parasite’s ability to arrest development, transform into a drug-insensitive form, and then resume growth post-therapy. Currently, the mechanisms by which the parasite enters arrested development, or dormancy, and later recrudesces or reactivates to continue development, are unknown and the malaria field lacks techniques to study these elusive mechanisms. Since Plasmodium spp. salvage purines for DNA synthesis, we hypothesized that alkyne-containing purine nucleosides could be used to develop a DNA synthesis marker which could be used to investigate mechanisms behind dormancy. Using copper-catalyzed click chemistry methods, we observe incorporation of alkyne modified adenosine, inosine, and hypoxanthine in actively replicating asexual blood stages of P. falciparum and incorporation of modified adenosine in actively replicating liver stage schizonts of P. vivax. Notably, these modified purines were not incorporated in dormant liver stage hypnozoites, suggesting this marker could be used as a tool to differentiate replicating and non-replicating liver forms and, more broadly, a tool for advancing our understanding Plasmodium dormancy mechanisms.

The free-living amoeba, Naegleria fowleri, which typically dwells within warm, freshwater environments, can opportunistically cause Primary Amoebic Meningoencephalitis (PAM), a disease with a mortality rate of >98%, even with the administration of the best available drug regimens. The lack of positive outcomes for PAM has prompted a push for the discovery and development of more effective therapeutics, but most studies only utilize one or two clinical isolates in their drug discovery assays. The inability to assess possible heterogenic responses to drugs among isolates from varying geographical regions hinders progress in the field due to a lack of proven universal efficacy for novel therapeutics. Herein we conducted drug efficacy and growth rate determinations for 11 different clinical isolates, including one obtained from a successful treatment outcome, by applying a previously developed CellTiter-Glo 2.0 screening technique and flow cytometry. We found some significant differences in the susceptibility of these isolates to 7 of 8 different drugs tested, all of which comprise the cocktail that is recommended to physicians by the Centers for Disease Control. We also discovered significant variances in growth rates among isolates which draws attention to the dissidence among the amoebae populations collected from different patients. The findings of this study reiterate the need for inclusion of additional clinical isolates of varying genotypes in drug assays and highlight the necessity for more targeted therapeutics with universal efficacy across N. fowleri isolates. Our data establishes a needed baseline for drug susceptibility among clinical isolates and provides a segue for future combination therapy studies as well as research related to phenotypic or genetic differences that could shed light on mechanisms of action or predispositions to specific drugs.

OBJECTIVES To evaluate whether extremely preterm infants regulate iron status via hepcidin. STUDY DESIGN In this retrospective analysis of infants from the Preterm Epo Neuroprotection (PENUT) Trial, urine hepcidin (Uhep) normalized to creatinine (Uhep/UCr) was evaluated among infants randomized to erythropoietin (Epo) or placebo. RESULTS The correlation (r) between Uhep/UCr and serum markers of iron status (ferritin and zinc protoporphyrin-to-heme ratio [ZnPP/H]) and iron dose was assessed. A total of 243 urine samples from 76 infants born at 24-276/7 weeks gestation were analyzed. The median Uhep/UCr concentration was 0.3, 1.3, 0.4, and 0.1 ng/mg at baseline, 2 weeks, 4 weeks, and 12 weeks, respectively, in placebo-treated infants. The median Uhep/UCr value in Epo-treated infants were not significantly different, with the exception of the value at the 2-week time point (median Uhep/UCr, 0.1 ng/mg; P

Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade.

Fibroblasts are activated to repair the heart following injury. Fibroblast activation in the mammalian heart leads to a permanent fibrotic scar that impairs cardiac function. In other organisms, such as zebrafish, cardiac injury is followed by transient fibrosis and scar-free regeneration. The mechanisms that drive scarring versus scar-free regeneration are not well understood. Here, we show that the homeobox-containing transcription factor Prrx1b is required for scar-free regeneration of the zebrafish heart as the loss of Prrx1b results in excessive fibrosis and impaired cardiomyocyte proliferation. Through lineage tracing and single-cell RNA sequencing, we find that Prrx1b is activated in epicardial-derived cells where it restricts TGFβ ligand expression and collagen production. Furthermore, through combined in vitro experiments in human fetal epicardial-derived cells and in vivo rescue experiments in zebrafish, we conclude that Prrx1 stimulates Nrg1 expression and promotes cardiomyocyte proliferation. Collectively, these results indicate that Prrx1 is a key transcription factor that balances fibrosis and regeneration in the injured zebrafish heart. This article has an associated ‘The people behind the papers’ interview., Summary: Epicardial-expressed Prrx1 ensures a balance between the fibrotic response and myocardial regeneration post-injury in zebrafish.

Healthcare professionals must be aware that babesiosis caused by reinfection might occur., Babesiosis developed in a 62-year-old immunocompetent physician, who had an uneventful recovery after receiving atovaquone and azithromycin. Three years later, babesiosis developed again, and he was again successfully given treatment. Clinical and laboratory evidence were highly supportive of Babesia reinfection. Healthcare professionals should be aware that reinfection might occur in babesiosis.

Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN. Publisher’s Note A first version of this text was prepared by the first eight authors and the last one, given here. The other listed co-authors in the article PDF support the content, and their actual contributions varied from only support to additions that substantially improved the content. The full details of all co-authors, with their affiliations, are included in Supplementary Table 1 after p.175 of the article for reasons of clarity and space. Slavomír Adamčík Institute of Botany, Plant Science and Biodiversity Centre, Slovak Academy of Sciences, Dúbravská cesta 9, 845 23 Bratislava, Slovakia Teuvo Ahti Finnish Museum of Natural History, P.O. Box 7, 00014 University of Helsinki, Finland M. Catherine Aime Purdue University, 915 W. State St., West Lafayette, Indiana 47907, U.S.A. A. Martyn Ainsworth Royal Botanic Gardens, Kew, Richmond, Surrey, TW9 3AB, United Kingdom László Albert Hungarian Mycological Society, 1087 Könyves Kálmán krt. 40, Budapest, Hungary Edgardo Albertó Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, Universidad Nacional de San Martin-Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina Alberto Altés García Facultad de Biología, Ciencias Ambientales y Química, Universidad de Alcalá, 28805 Alcalá de Henares, Madrid, Spain Dmitry Ageev SIGNATEC Ltd., 630090, Novosibirsk, Akademgorodok (Novosibirsk Scientific Center), Inzhenernaya str., 22, Russia Reinhard Agerer Ludwig-Maximilians-Universität München, Menzinger Str. 67, 80638 München, Germany Begona Aguirre-Hudson Royal Botanic Gardens, Kew, Richmond, Surrey, TW9 3AB, United Kingdom Joe Ammirati University of Washington, Seattle, Washington 98195-1800, U.S.A. Harry Andersson Eichhahnweg 29a, 38108 Braunschweig, Germany Claudio Angelini Jardín Botánico Nacional Dr. Rafael Ma. Moscoso, Apartado 21-9, Santo Domingo, Dominican Republic Vladimír Antonín Moravian Museum, Zeny trh 6, 659 37 Brno, Czech Republic Takayuki Aoki Genetic Resources Center, National Agriculture and Food Research Organization, 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8602, Japan André Aptroot ABL Herbarium, G.v.d.Veenstraat 107, 3762 XK Soest, The Netherlands Didier Argaud 40 rue du Justemont, 57290 Fameck, France Blanca Imelda Arguello Sosa Instituto Tecnológico de Ciudad Victoria, Tecnológico Nacional de México, Ciudad Victoria, Tamaulipas, Mexico Arne Aronsen Torødveien 54, 3135 Torød, Norway Ulf Arup Biological Museum, Lund University, Box 117, 221 00 Lund, Sweden Bita Asgari Iranian Research Institute of Plant Protection, Agricultural Research, Education and Extension Organization, Tehran, Iran Boris Assyov Institute of Biodiversity and Ecosystem Research, Bulgarian Academy of Sciences, 2 Gagarin Str., 1113 Sofia, Bulgaria Violeta Atienza Facultad de Ciencias Biológicas, Universitat de València, C/Dr Moliner 50, 46100, Burjasot, Valencia, Spain Ditte Bandini Panoramastr 47, 69257 Wiesenbach, Germany João Luís Baptista-Ferreira Instituto de Biossistemas e Ciências Integrativas, Faculdade de Ciências da Universidade de Lisboa, 1749-016 Lisboa, Portugal Hans-Otto Baral Blaihofstr. 42, 72074 Tübingen, Germany Tim Baroni The State University of New York, 340 Bowers Hall, P.O. Box 2000, Cortland, New York 13045, U.S.A. Robert Weingart Barreto Universidade Federal de Viçosa, 36570-000, Viçosa, Minas Gerais, Brazil Henry Beker (1) Royal Holloway, University of London, United Kingdom; (2) Botanic Garden Meise, Nieuwelaan 38, 1860 Meise, Belgium Ann Bell 45 Gurney Road, Lower Hutt, New Zealand Jean-Michel Bellanger CEFE UMR5175, CNRS, Université de Montpellier, Université Paul-Valéry Montpellier, EPHE, INSERM, 1919 Route de Mende, 34293 Montpellier Cédex 5, France Francesco Bellù Naturmusem of Bolzano, CP 104, 39100, Bolzano, Italy Martin Bemmann Kleingemünderstraße 111, 69118 Heidelberg, Germany Mika Bendiksby NTNU, University Museum, Norwegian University of Science and Technology, 7491 Trondheim, Norway Egil Bendiksen Norwegian Institute for Nature Research, Gaustadalleen 21, 0349 Oslo, Norway Katriina Bendiksen Natural History Museum, University of Oslo, P.O. Box 1172 Blindern, 0318 Oslo, Norway Lajos Benedek Szent Istvan University, Hungary Anna Bérešová-Guttová Institute of Botany, Plant Science and Biodiversity Centre, Slovak Academy of Sciences, Dúbravská cesta 9, 845 23 Bratislava, Slovakia Franz Berger University of Salzburg, Salzburg, Austria Reinhard Berndt Herbaria Z+ZT, ETH Zürich, CHN D37, Universitätstr. 16, 8092 Zürich, Switzerland Annarosa Bernicchia Via A. Guidotti 39, 40134 Bologna, Italy Alona Yu. Biketova Institute of Biochemistry, BRC-HAS, 6726 Szeged, Temesvari krt. 62, 6726 Szeged, Hungary Enrico Bizio Società Veneziana di Micologia, Società Veneziana di Scienze Naturali, Fontego dei Turchi, Santa Croce 1730, 30135 Venice, Italy Curtis Bjork UBC Herbarium, Beaty Biodiversity Museum, University of British Columbia, Canada Teun Boekhout (1) Westerdijk Fungal Biodiversity Institute, P.O. Box 85167, 3508 AD, Utrecht, The Netherlands; (2) Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, The Netherlands David Boertmann Aarhus University, Frederiksborgvej 399, 4000 Roskilde, Denmark Tanja Böhning AG Geobotanik Schleswig-Holstein & Hamburg, c/o University of Kiel, Olshausenstraße 75, 24098 Kiel, Germany Florent Boittin Ascomycete.org, 36 rue de la Garde, 69005 Lyon, France Carlos G. Boluda Conservatoire et Jardin botaniques de la Ville de Genève, 1292 Genève, Switzerland Menno W. Boomsluiter T.v.Lohuizenstraat 34, 8172xl, Vaassen, The Netherlands Jan Borovička Institute of Geology, Czech Academy of Sciences, Rozvojova 269, 165 00 Prague 6, Czech Republic Tor Erik Brandrud Norwegian Institute for Nature Research, Gaustadalleen 21, 0349 Oslo, Norway Uwe Braun Martin-Luther-Universität, Institut für Biologie, Bereich Geobotanik, und Botanischer Garten, Herbarium, Neuwerk 21, 06099 Halle, Germany Irwin Brodo Canadian Museum of Nature, 240 McLeod Street, Ottawa, Ontario, Canada Tatiana Bulyonkova A.P. Ershov Institute of Informatics Systems, Russian Academy of Sciences, Siberian Branch, 6 Acad. Lavrentjev pr., Novosibirsk 630090, Russia Harold H. Burdsall Jr. Fungal & Decay Diagnostics, LLC, 9350 Union Valley Road, Black Earth, Wisconsin 53515, U.S.A. Bart Buyck Muséum National d’Histoire Naturelle, CP 39, ISYEB, UMR 7205 CNRS MNHN UPMC EPHE, 12 rue Buffon, 75005 Paris, France Ana Rosa Burgaz Facultad de Ciencias Biológicas, Universidad Complutense de Madrid, 28040 Madrid, Spain Vicent Calatayud Fundación CEAM, c/ Charles R. Darwin, 14, Parque Tecnológico, 46980 Paterna, Valencia, Spain Philippe Callac INRA, MycSA, CS 20032, 33882 Villenave d’Ornon, France Emanuele Campo Associazione Micologica Bresadola, Via Alessandro Volta 46, 38123 Trento, Italy Massimo Candusso Via Ottone Primo 90, 17021, Alassio, Savona, Italy Brigitte Capoen Queffioec, rue de Saint Gonval, 22710 Penvenan, France Joaquim Carbó Roser, 60, 17257 Torroella de Montgrí, Girona, Spain Matteo Carbone Via Don Luigi Sturzo 173 16148 Genova, Italy Rafael F. Castañeda-Ruiz Instituto de Investigaciones Fundamentales en Agricultura, Tropical ‘Alejandro de Humboldt’, OSDE, Grupo Agrícola, Calle 1 Esq. 2, Santiago de Las Vegas, C. Habana 17200, Cuba Michael A. Castellano USDA, Forest Service, Northern Research Station, Corvallis, Oregon 97330, U.S.A. Jie Chen Mae Fah Luang University, Chang Wat Chiang Rai 57100, Thailand Philippe Clerc Conservatoire et Jardin botaniques de la Ville de Genève, 1292 Genève, Switzerland Giovanni Consiglio Via C. Ronzani 61, 40033 Casalecchio Bologna, Italy Gilles Corriol National Botanical Conservatory for Pyrenees and Midi-Pyrénées Region of France and BBF Herbarium, Vallon de Salut. B.P. 315. 65203 Bagnères-de-Bigorre, France Régis Courtecuisse Université Lille, Fac. Pharma. Lille, EA4483 IMPECS, 59000 Lille, France Ana Crespo Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain Cathy Cripps Plant Sciences & Plant Pathology, 119 Plant Biosciences Building, Montana State University, Bozeman, Montana 59717, U.S.A. Pedro W. Crous Westerdijk Fungal Biodiversity Institute, P.O. Box 85167, 3508 AD, Utrecht, The Netherlands Gladstone Alves da Silva Universidade Federal de Pernambuco, Centro de Biociências, Avenida da Engenharia, S/N, Cidade Universitária, Recife, Pernambuco, Brazil Meiriele da Silva Universidade Federal de Viçosa, 36570-000, Viçosa, Minas Gerais, Brazil Marjo Dam Hooischelf 13, 6581 SL Malden, The Netherlands Nico Dam Hooischelf 13, 6581 SL Malden, The Netherlands Frank Dämmrich The Bavarian Natural History Collections (SNSB Munich), Menzinger Strasse 71, 80638, München, Germany Kanad Das Botanical Survey of India, Cryptogamic Unit, P.O. Botanic Garden, Howrah 711103, W.B., India Linda Davies Centre for Environmental Policy, Imperial College London, SW7 2AZ, United Kingdom Eske De Crop Ghent University K.L. Ledeganckstraat 35, 9000 Ghent, Belgium Andre De Kesel Botanic Garden Meise, Nieuwelaan 38, 1860 Meise, Belgium Ruben De Lange Ghent University, K.L. Ledeganckstraat 35, 9000 Gent, Belgium Bárbara De Madrignac Bonzi Instituto de Botánica del Nordeste, Universidad Nacional de Nordeste-Consejo Nacional de Investigaciones Científicas y Técnicas, Sargento Cabral 2131, CC 209, Corrientes Capital, Argentina Thomas Edison E. dela Cruz University of Santo Tomas, Espana 1008 Manila, Philippines Lynn Delgat Ghent University, K.L. Ledeganckstraat 35, 9000 Gent, Belgium Vincent Demoulin Institut de Botanique, B.22, Université de Liège, 4000 Liège I, Belgium Dennis E. Desjardin HD Thiers Herbarium (SFSU), San Francisco State University, 1600 Holloway Ave, San Francisco, California 94132, U.S.A. Paul Diederich Musée national d’histoire naturelle, 25 rue Münster, 2160 Luxembourg, Luxembourg Bálint Dima (1) Institute of Biology, Eötvös Loránd University, Pázmány Péter sétány 1/c, 1117 Budapest, Hungary; (2) Viikki Plant Science Centre, University of Helsinki, P.O. Box 65, 00014 Helsinki, Finland Maria Martha Dios Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Catamarca, Av Belgrano 300, 4700 San Fernando del Valle de Catamarca, Argentina Pradeep Kumar Divakar Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain Clovis Douanla-Meli Julius Kühn-Institut, Federal Research Centre for Cultivated Plants, Institute for National and International Plant Health, Messeweg 11-12, 38104 Braunschweig, Germany Brian Douglas Royal Botanic Gardens, Kew, Richmond, Surrey, TW9 3AB, United Kingdom Elisandro Ricardo Drechsler-Santos Universidade Federal de Santa Catarina, Campus Universitário Reitor João David Ferreira Lima, Trindade, Florianópolis, Santa Catarina CEP 88040-900, Brazil Paul S. Dyer School of Life Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom Ursula Eberhardt Abt. Botanik, Staatliches Museum für Naturkunde Stuttgart, Rosenstein 1, 70191 Stuttgart, Germany Damien Ertz Botanic Garden Meise, Nieuwelaan 38, 1860 Meise, Belgium Fernando Esteve-Raventós Facultad de Biología, Ciencias Ambientales y Química, Universidad de Alcalá, 28805 Alcalá de Henares, Madrid, Spain Javier Angel Etayo Salazar Navarro Villoslada 16, 3º dcha., 31003 Pamplona, Navarra, Spain Vera Evenson Sam Mitchel Herbarium of Fungi, Denver Botanic Gardens, 1007 York Street, Denver, Colorado 80206, U.S.A. Guillaume Eyssartier Muséum national d’histoire naturelle, Jardin des plantes, 57 rue Cuvier, 75005 Paris, France Edit Farkas Institute of Ecology and Botany, MTA Centre for Ecological Research, 2163 Vácrátót, Hungary Alain Favre Fédération Mycologique et Botanique Dauphiné Savoie, Le Prieuré, 144 Place de l’Eglise, 74320 Sevrier, France Anna G. Fedosova Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Mario Filippa Regione Monsarinero 36, 14041 Agliano Terme, Italy Péter Finy 8000 Székesfehérvár, Zsombolyai u. 56, Hungary Adam Flakus W. Szafer Institute of Botany, Polish Academy of Sciences, Lubicz 46, 31-512 Krakow, Poland Simón Fos Facultad de Ciencias Biológicas, Universitat de València, C/Dr Moliner 50, 46100, Burjasot, Valencia, Spain Jacques Fournier Las Muros, F. 09420 Rimont, France André Fraiture Botanic Garden Meise, Nieuwelaan 38, 1860 Meise, Belgium Paolo Franchi Associazione Micologica Bresadola, Via Alessandro Volta 46, 38123 Trento, Italy Ana Esperanza Franco Molano Escuela de Microbiología, Universidad de Antioquia, AA1226, Fundación Biodiversa Colombia, Medellín, Colombia Gernot Friebes Centre of Natural History, Botany & Mycology, Universalmuseum Joanneum, Weinzöttlstraße 16, 8045 Graz, Austria Andreas Frisch NTNU, University Museum, Norwegian University of Science and Technology, 7491 Trondheim, Norway Alan Fryday Michigan State University, East Lansing, Michigan 48824, U.S.A. Giuliana Furci The Fungi Foundation, Paseo Bulnes 79 of. 112A, Santiago, Chile Ricardo Galán Márquez Facultad de Biología, Ciencias Ambientales y Química, Universidad de Alcalá, 28805 Alcalá de Henares, Madrid, Spain Matteo Garbelotto University of California, 130 Mulford Hall #3114 Berkeley, California 94720, U.S.A. Joaquina Maria Garcia-Martin Real Jardín Botánico-CSIC, Plaza de Murillo 2, 28014, Madrid, Spain Mónica A. García Otálora Herbaria Z+ZT, ETH Zürich, CHN D37, Universitätstr. 16, 8092 Zürich, Switzerland Dania García Sánchez Universitat Rovira i Virgili, C/ Sant Llorenç 21, 43201 Reus, Tarragona, Spain Alain Gardiennet 14 rue Roulette, 21260 Véronnes, France Sigisfredo Garnica Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Isla Teja Campus, Casilla 567, Valdivia, Chile Isaac Garrido Benavent Real Jardín Botánico-CSIC, Plaza de Murillo 2, 28014, Madrid, Spain Genevieve Gates Tasmanian Institute of Agriculture, Private Bag 54, Hobart, Tasmania 7001, Australia Alice da Cruz Lima Gerlach Conservatoire et Jardin Botaniques de la ville de Genève, Genève, Switzerland Masoomeh Ghobad-Nejhad Iranian Research Organization for Science and Technology, P.O. Box 15815-3538, Tehran 15819, Iran Tatiana B. Gibertoni Universidade Federal de Pernambuco, Centro de Biociências, Avenida da Engenharia, S/N, Cidade Universitária, Recife, Pernambuco, Brazil Tine Grebenc Slovenian Forestry Institute, Vecna pot 2, 100 Ljubljana, Slovenia Irmgard Greilhuber University of Vienna, Rennweg 14, 1030 Vienna, Austria Bella Grishkan Institute of Evolution, University of Haifa, Aba Khoushi Ave. 199, Mt. Carmel, Haifa 3498838, Israel Johannes Z. Groenewald Westerdijk Fungal Biodiversity Institute, P.O. Box 85167, 3508 AD, Utrecht, The Netherlands Martin Grube Institute of Biology, University of Graz, Holteiasse 6, 8010 Graz, Austria Gérald Gruhn Office National des Forêts, 2 Avenue de Saint-Mandé, 75570 Paris Cedex 12, France Cécile Gueidan CSIRO — Australian National Herbarium, Clunies Ross Street, Canberra ACT 2601, Australia Gro Gulden Natural History Museum, University of Oslo, P.O. Box 1172 Blindern, 0318 Oslo, Norway Luis FP Gusmão Universidade Estadual de Feira de Santana, Av. Transnordestina, s/n, Bairro Novo Horizonte, CEP:44036-900, Feira de Santana, Bahia, Brazil Josef Hafellner Institute of Biology, University of Graz, Holteiasse 6, 8010 Graz, Austria Michel Hairaud 2 Impasse des Marronniers, 79360 Poivendre de Marigny, France Marek Halama Museum of Natural History, Wrocław University, ul. H. Sienkiewicza 5, 50-335 Wrocław, Poland Nils Hallenberg University of Gothenburg, Box 461, 40530 Göteborg, Sweden Roy E. Halling Institute of Systematic Botany, New York Botanical Garden, 2900 Southern Blvd, Bronx, New York 10458-5126, U.S.A. Karen Hansen Swedish Museum of Natural History, P.O. Box 50007, 104 05 Stockholm, Sweden Christoffer Bugge Harder Texas Tech University, Box 42122, Lubbock, Texas 79409, U.S.A. Jacob Heilmann-Clausen Natural History Museum of Denmark, Universitetsparken 15, 2100 København, Denmark Stip Helleman Sweelinck 78, 5831KT Boxmeer, The Netherlands Alain Henriot Mycological Society of France, 20 rue Rottembourg, 12th arrondissement, Paris, France Margarita Hernandez-Restrepo Westerdijk Fungal Biodiversity Institute, P.O. Box 85167, 3508 AD, Utrecht, The Netherlands Raphaël Herve 24 rue des Fougères, 86550 Mignaloux-Beauvoir, France Caroline Hobart 84 Stafford Road, Sheffield, South Yorkshire S2 2SF, United Kingdom Mascha Hoffmeister Julius Kühn-Institut, Institute for Epidemiology and Pathogen Diagnostics, Braunschweig, Germany Klaus Høiland University of Oslo, P.O.Box 1066, Blindern, 0316 Oslo, Norway Jan Holec National Museum, Herbarium PRM, Cirkusová 1740, 193 00 Praha 9, Czech Republic Håkon Holien Faculty of Bioscience and Aquaculture, NORD University, P.O. Box 2501, 7729 Steinkjer, Norway Karen Hughes University of Tennessee, Knoxville, Tennessee 37996, U.S.A. Vit Hubka Faculty of Science, Charles University, Benátská 2, 128 01 Praha 2, Czech Republic Seppo Huhtinen Herbarium TUR, Biodiversity Unit, University of Turku, 20014 Turku, Finland Boris Ivančević Natural History Museum, Njegoševa 51, P.O. Box 401, 11000 Belgrade, Serbia Marian Jagers Reelaan 13, 7522 LR Enschede, The Netherlands Walter Jaklitsch Institute of Forest Entomology, Forest Pathology and Forest Protection, University of Natural Resources and Life Sciences Vienna, Vienna, Austria AnnaElise Jansen Stationsstraat 10, 6701 AM Wageningen, the Netherlands Ruvishika S. Jayawardena Mae Fah Luang University, Chang Wat Chiang Rai 57100, Thailand Thomas Stjernegaard Jeppesen Global Biodiversity Information Facility, Universitetsparken 15, 2100 København Ø, Denmark Mikael Jeppson Lilla Håjumsgatan 4, 46135 Trollhättan, Sweden Peter Johnston Manaaki Whenua Landcare Research, Private Bag 92170, Auckland 1072, New Zealand Per Magnus Jørgensen University of Bergen, Allégaten 41, P.O. Box 7800, 5020 Bergen, Norway Ingvar Kärnefelt Biological Museum, Lund University, Box 117, 221 00 Lund, Sweden Liudmila B. Kalinina Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Gintaras Kantvilas Tasmanian Herbarium (HO), Tasmanian Museum and Art Gallery, P.O. Box 5058, UTAS LP.O., Sandy Bay, Tasmania 7005, Australia Mitko Karadelev Institute of Biology, Faculty of Natural Science and Mathematics, Ss. Cyril and Methodius University, Arhimedova 5, 1000 Skopje, Republic of Macedonia Taiga Kasuya Faculty of Risk and Crisis Management, Chiba Institute of Science, 3 Shiomi-cho, Choshi, Chiba 288-0025, Japan Ivona Kautmanová Natural History Museum, Slovak National Museum, Bratislava, Slovakia Richard W. Kerrigan RWK Research, Kittanning, Pennsylvania 16201, U.S.A. Martin Kirchmair Institut für Mikrobiologie, Universität Innsbruck, Technikerstraße 25, 6020 Innsbruck, Austria Anna Kiyashko Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Dániel G. Knapp Institute of Biology, Eötvös Loránd University, Pázmány Péter sétány 1/c, 1117 Budapest, Hungary Henning Knudsen Natural History Museum of Denmark, Universitetsparken 15, 2100 København, Denmark Kerry Knudsen Faculty of Environmental Sciences, University of Life Sciences at Prague, Prague, Czech Republic Tommy Knutsson Nedra Västerstad 111, 380 62 Mörbylånga, Sweden Miroslav Kolařík Institute of Microbiology ASCR, Videnska 1083, 142 20 Prague 4, Czech Republic Urmas Kõljalg Institute of Ecology and Earth Sciences, 40 Lai Street, Tartu 51005, Estonia Alica Košuthová Swedish Museum of Natural History, P.O. Box 50007, 104 05 Stockholm, Sweden Attila Koszka Faculty of Agricultural and Environmental Sciences, Kaposvar University, 7400 Kaposvar, Hungary Heikki Kotiranta Finnish Environment Institute, P.O. Box 140, 00251 Helsinki, Finland Vera Kotkova Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Ondřej Koukol Faculty of Science, Charles University, Benátská 2, 128 01 Praha 2, Czech Republic Jiří Kout University of West Bohemia, Faculty of Education, Klatovska 51, 306 19 Pilsen, Czech Republic Gábor M. Kovács Institute of Biology, Eötvös Loránd University, Pázmány Péter sétány 1/c, 1117 Budapest, Hungary Martin Kříž Faculty of Science, Charles University, Benátská 2, 128 01 Praha 2, Czech Republic Åsa Kruys Museum of Evolution, Uppsala University, Norbyvägen 16, 75236 Uppsala, Sweden Viktor Kučera Institute of Botany, Plant Science and Biodiversity Centre, Slovak Academy of Sciences, Dúbravská cesta 9, 845 23 Bratislava, Slovakia Linas Kudzma 37 Maple Ave. Annandale, New Jersey 08801, U.S.A. Francisco Kuhar Instituto Multidisciplinario de Biología Vegetal, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba, Casilla de Correo 495, 5000 Córdoba, Argentina Martin Kukwa Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland T. K. Arun Kumar The Zamorin’s Guruvayurappan College, Kozhikode, Kerala 673014, India Vladimír Kunca Technical University in Zvolen, Ul. T. G. Masaryka 24, 960 53 Zvolen,Slovakia Ivana Kušan Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia Thomas W. Kuyper Wageningen University & Research, Droevendaalsesteeg 4, 6708 PB Wageningen, The Netherlands Carlos Lado Real Jardín Botánico-CSIC, Plaza de Murillo 2, 28014, Madrid, Spain Thomas Læssøe Natural History Museum of Denmark, Universitetsparken 15, 2100 København, Denmark Patrice Lainé 123 rue Saint Antoine, 75004, Paris, France Ewald Langer University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany Ellen Larsson University of Gothenburg, Box 461, 40530 Göteborg, Sweden Karl-Henrik Larsson Natural History Museum, University of Oslo, P.O. Box 1172 Blindern, 0318 Oslo, Norway Gary Laursen Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska 99775-7000, U.S.A. Christian Lechat Ascofrance, 64 route de Chizé, 79360 Villiers en Bois, France Serena Lee Herbarium Singapore Botanic Gardens, National Parks Board, Singapore James C. Lendemer (1) Institute of Systematic Botany, New York Botanical Garden, 2900 Southern Blvd, Bronx, New York 10458-5126, U.S.A.; (2) Graduate Center, City University of New York, 365 5th Ave, New York, New York 10016, U.S.A. Laura Levin University of Buenos Aires, Junin 956, 1113, Buenos Aires, Argentina Uwe Lindemann Landesmuseum für Naturkunde, Münster, Germany Håkan Lindström Östansjö 150, 840 64 Kälarne, Sweden Xingzhong Liu Institute of Microbiology, Chinese Academy of Sciences, No 3 Park 1, Beichen West Road, Chaoyang District, Beijing 100101, China Regulo Carlos Llarena Hernandez Facultad de Ciencias Biológicas y Agropecuarias, Peñuela, Universidad Veracruzana, Amatlán de los Reyes, Ver., Mexico Esteve Llop Facultat de Biologia, Universitat de Barcelona, Av. Diagonal, 643, 08028 Barcelona, Spain Csaba Locsmándi Hungarian Natural History Museum, 1087 Budapest, Hungary Deborah Jean Lodge USDA Forest Service, NRS, P.O. Box 1377, Luquillo, Puerto Rico 00773-1377, U.S.A. Michael Loizides P.O. Box 58499, 3734 Limassol, Cyprus László Lőkös Hungarian Natural History Museum, 1087 Budapest, Hungary Jennifer Luangsa-ard National Center for Genetic Engineering and Biotechnology (BIOTEC), NSTDA, 113 Thailand Science Park, Phaholyothin Rd., Klong Nueng, Klong Luang, Pathum Thani 12120, Thailand Matthias Lüderitz AG Geobotanik Schleswig-Holstein & Hamburg, c/o University of Kiel, Olshausenstraße 75, 24098 Kiel, Germany Thorsten Lumbsch Field Museum, 1400 S. Lake Shore Dr., Chicago, Illinois 60605, U.S.A. Matthias Lutz Institute of Evolution and Ecology, University of Tübingen, Auf der Morgenstelle 5, 72076 Tübingen, Germany Dan Mahoney Callaghan Innovation, 69 Gracefield Road, Lower Hutt 5010, New Zealand Ekaterina Malysheva Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Vera Malysheva Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Patinjareveettil Manimohan University of Calicut, Kerala, 673 635, India Yasmina Marin-Felix Westerdijk Fungal Biodiversity Institute, P.O. Box 85167, 3508 AD, Utrecht, The Netherlands Guilhermina Marques Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Tras-os-Montes and Alto Douro, Laboratory of Mycology and Soil Microbiology, 5000-801 Vila Real, Portugal Rubén Martínez-Gil Ascomycete.org, 36 rue de la Garde, 69005 Lyon, France Guy Marson Musée national d’histoire naturelle, 25 rue Münster, 2160 Luxembourg, Luxembourg Gerardo Mata Instituto de Ecología, A.C., Carretera antigua a Coatepec 351, El Haya, Xalapa 91070, Veracruz, Mexico P. Brandon Matheny University of Tennessee, Knoxville, Tennessee 37996, U.S.A. Geir Harald Mathiassen Tromsø University Museum, University of Tromsø — The Arctic University of Norway, 9037 Tromsø, Norway Neven Matočec Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia Helmut Mayrhofer Institute of Biology, University of Graz, Holteiasse 6, 8010 Graz, Austria Mehdi Mehrabi Iranian Research Institute of Plant Protection, Agricultural Research, Education and Extension Organization, Tehran, Iran Ireneia Melo Botanical Garden, National Museum of Natural History and Science, University of Lisbon, Portugal Armin Mešić Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia Andrew S. Methven Savannah State University, Savannah, Georgia 31404, U.S.A Otto Miettinen Finnish Museum of Natural History, P.O. Box 7, 00014 University of Helsinki, Finland Ana M. Millanes Romero Universidad Rey Juan Carlos, 28933 Móstoles, Madrid, Spain Andrew N. Miller Illinois Natural History Survey, University of Illinois Urbana-Champaign, 1816 South Oak Street, Champaign, Illinois 61820-6970, U.S.A. James K. Mitchell Harvard University, 22 Divinity Avenue, Cambridge, Massachusetts 02138, U.S.A. Roland Moberg Museum of Evolution, Uppsala University, Norbyvägen 16, 75236 Uppsala, Sweden Pierre-Arthur Moreau Université Lille, Fac. Pharma. Lille, EA4483 IMPECS, 59000 Lille, France Gabriel Moreno Facultad de Biología, Ciencias Ambientales y Química, Universidad de Alcalá, 28805 Alcalá de Henares, Madrid, Spain Olga Morozova Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Asunción Morte Facultad de Biología, Universidad de Murcia, Campus de Espinardo, 30100 Murcia, Spain Lucia Muggia University of Trieste, via L. Giorgieri 10, 34127 Trieste, Italy Guillermo Muñoz González Avda Valvanera N.32, 5D, 26500 Calahorra, La Rioja, Spain Leena Myllys Finnish Museum of Natural History, P.O. Box 7, 00014 University of Helsinki, Finland István Nagy Institute of Biology, Eötvös Loránd University, Pázmány Péter sétány 1/c, 1117 Budapest, Hungary László G. Nagy Institute of Biochemistry, BRC-HAS, 6726 Szeged, Temesvari krt. 62, 6726 Szeged, Hungary Maria Alice Neves Universidade Federal de Santa Catarina, Campus Universitário Reitor João David Ferreira Lima, Trindade, Florianópolis, Santa Catarina CEP 88040-900, Brazil Tuomo Niemelä Finnish Museum of Natural History, P.O. Box 7, 00014 University of Helsinki, Finland Pier Luigi Nimis University of Trieste, via L. Giorgieri 10, 34127 Trieste, Italy Nicolas Niveiro Instituto de Botánica del Nordeste, Universidad Nacional de Nordeste-Consejo Nacional de Investigaciones Científicas y Técnicas, Sargento Cabral 2131, CC 209, Corrientes Capital, Argentina Machiel E. Noordeloos Naturalis Biodiversity Center, P.O. Box 9517, 2300 RA, Leiden, The Netherlands Anders Nordin Museum of Evolution, Uppsala University, Norbyvägen 16, 75236 Uppsala, Sweden Sara Raouia Noumeur Faculty of Natural and Life Sciences, University of Batna 2, 05000 Batna, Algeria Yuri Novozhilov Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Jorinde Nuytinck Naturalis Biodiversity Center, P.O. Box 9517, 2300 RA Leiden, The Netherlands Esteri Ohenoja Botanical Museum, University of Oulu, Finland Patricia Oliveira Fiuza Universidade Estadual de Feira de Santana, Av. Transnordestina, s/n, Bairro Novo Horizonte, CEP:44036-900, Feira de Santana, Bahia, Brazil Alan Orange National Museum of Wales, Cardiff CF10 3NP, United Kingdom Alexander Ordynets University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany Beatriz Ortiz-Santana USDA Forest Service, Northern Research Station, One Gifford Pinchot Dr, Madison, Wisconsin 53726, U.S.A. Leticia Pacheco Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, 09340 México, D. F., Mexico Ferenc Pál-Fám Faculty of Agricultural and Environmental Sciences, Kaposvar University, 7400 Kaposvar, Hungary Melissa Palacio Universidade Federal do Rio Grande do Sul, Brazil Zdeněk Palice Faculty of Science, Charles University, Benátská 2, 128 01 Praha 2, Czech Republic Viktor Papp Szent Istvan University, 1118 Budapest, Menesi st. 44, Hungary Kadri Pärtelv Institute of Ecology and Earth Sciences, 40 Lai Street, Tartu 51005, Estonia Julia Pawlowska Faculty of Biology, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland Aurelia Paz Urb. La Llosa, 219, 39509 Villanueva de la Peña, Mazcuerras, Cantabria, Spain Ursula Peintner Institut für Mikrobiologie, Universität Innsbruck, Technikerstraße 25, 6020 Innsbruck, Austria Shaun Pennycook Manaaki Whenua Landcare Research, Private Bag 92170, Auckland 1072, New Zealand Olinto Liparini Pereira Universidade Federal de Viçosa, 36570-000, Viçosa, Minas Gerais, Brazil Pablo Pérez Daniëls University of Córdoba, 14071, Córdoba, Spain Miquel À. Pérez-De-Gregorio Capella C/ Pau Casals, 6, 1º, 1ª, 17001, Girona, Spain Carlos Manuel Pérez del Amo C/ Luis de Ulloa, 1, 7º I, 26004 Logroño, Navarra, Spain Sergio Pérez Gorjón Universidad de Salamanca, Avda. Licenciado Mendez Nieto s/n, 37007 Salamanca, Spain Sergio Pérez-Ortega Real Jardín Botánico-CSIC, Plaza de Murillo 2, 28014, Madrid, Spain Israel Pérez-Vargas Facultad de Farmacia, Universidad de La Laguna, c/ Astrofísico Sánchez s/n 38071 La Laguna, Tenerife, Canary Islands, Spain Brian A. Perry California State University East Bay, Hayward, California 94542, U.S.A. Jens H. Petersen Nøruplundvej 2, 8400 Ebeltoft, Denmark Ronald H. Petersen University of Tennessee, Knoxville, Tennessee 37996, U.S.A. Donald H. Pfister Harvard University, 22 Divinity Avenue, Cambridge MA 02138, U.S.A. Chayanard Phukhamsakda Mae Fah Luang University, Chang Wat Chiang Rai 57100, Thailand Marcin Piątek W. Szafer Institute of Botany, Polish Academy of Sciences, Lubicz 46, 31-512 Krakow, Poland Meike Piepenbring Faculty of Biosciences, Goethe University Frankfurt am Main, Germany Raquel Pino-Bodas Real Jardín Botánico-CSIC, Plaza de Murillo 2, 28014, Madrid, Spain Juan Pablo Pinzón Esquivel Universidad Autónoma de Yucatán, Carretera Mérida-Xmatkuil Km. 15.5, Apdo. Postal: 4-116 Itzimná,C.P: 97100, Merida, Yucatan, Mexico Paul Pirot Rue des Peupliers 10, 6840 Neufchâteau, Belgium Eugene S. Popov Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Orlando Popoff Instituto de Botánica del Nordeste, Universidad Nacional de Nordeste-Consejo Nacional de Investigaciones Científicas y Técnicas, Sargento Cabral 2131, CC 209, Corrientes Capital, Argentina María Prieto Álvaro Universidad Rey Juan Carlos, 28933 Móstoles, Madrid, Spain Christian Printzen Senckenberg Forschungsinstitut und Naturmuseum Frankfurt, Abteilung Botanik und Molekulare Evolutionsforschung, Herbarium Senckenbergianum (FR), Senckenberganlage 25, 60325 Frankfurt am Main, Germany Nadezhda Psurtseva Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Witoon Purahong Helmholtz Centre for Environmental Research GmbH — UFZ, Theodor-Lieser-Straße 4, 06120 Halle, Germany Luis Quijada Harvard University, 22 Divinity Avenue, Cambridge, Massachusetts 02138, U.S.A. Gerhard Rambold University of Bayreuth, Universitätsstrasse 30, 95447 Bayreuth, Germany Natalia A. Ramírez Instituto de Botánica del Nordeste, Universidad Nacional de Nordeste-Consejo Nacional de Investigaciones Científicas y Técnicas, Sargento Cabral 2131, CC 209, Corrientes Capital, Argentina Huzefa Raja University of North Carolina at Greensboro, 435 Sullivan Science Building, PO Box 26170, Greensboro North Carolina 27402-6170, U.S.A. Olivier Raspé Botanic Garden Meise, Nieuwelaan 38, 1860 Meise, Belgium Tania Raymundo Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Miguel Hidalgo, Santo Tomás, 11340 Ciudad de México, Mexico Martina Réblová Institute of Botany, Czech Academy of Sciences, Pruhonice, Czech Republic Yury A. Rebriev Southern Scientific Center, Russian Academy of Sciences, 41 Chehova str., Rostov-on-Don, 344006, Russia Juan de Dios Reyes García Paseo Virgen de Linarejos 6 2 D, Linares, Jaen, Spain Miguel Ángel Ribes Ripoll Avda. Pablo Neruda 120 F, 2°D, 28018 Madrid, Spain Franck Richard CEFE UMR5175, CNRS, Université de Montpellier, Université Paul-Valéry Montpellier, EPHE, INSERM, 1919 Route de Mende, 34293 Montpellier Cédex 5, France Mike J. Richardson Royal Botanic Garden Edinburgh, 20A Inverleith Row, Edinburgh, EH3 5LR, United Kingdom Víctor J. Rico Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain Gerardo Lucio Robledo Instituto Multidisciplinario de Biología Vegetal, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba, Casilla de Correo 495, 5000 Córdoba, Argentina Flavia Rodrigues Barbosa Universidade Federal de Mato Grosso, Av. Alexandre Ferronato, 1200, Setor Industrial, Sinop, Mato Grosso, Brazil Cristina Rodriguez-Caycedo UT Southwestern Medical Center, Dallas, Texas 75390, U.S.A. Pamela Rodriguez-Flakus W. Szafer Institute of Botany, Polish Academy of Sciences, Lubicz 46, 31-512 Krakow, Poland Anna Ronikier W. Szafer Institute of Botany, Polish Academy of Sciences, Lubicz 46, 31-512 Krakow, Poland Luis Rubio Casas Ul. Andrieja Sacharowa 1/1, 30-806 Kraków, Poland Katerina Rusevska Institute of Biology, Faculty of Natural Science and Mathematics, Ss. Cyril and Methodius University, Arhimedova 5, 1000 Skopje, Republic of Macedonia Günter Saar Dammenmühle 7, 77933 Lahr-Sulz, Germany Irja Saar Institute of Ecology and Earth Sciences, 40 Lai Street, Tartu 51005, Estonia Isabel Salcedo University of the Basque Country (UPV/EHU), Apdo 644, 48080 Bilbao, Spain Sergio M. Salcedo Martínez Facultad de Ciencias Biológicas, UANL. Ave. Pedro de Alba s/n esq. Manuel Barragán Cd. Universitaria, San Nicolás de los Garza Nuevo León, CP. 66451, Mexico Carlos A. Salvador Montoya Instituto de Botánica del Nordeste, Universidad Nacional de Nordeste-Consejo Nacional de Investigaciones Científicas y Técnicas, Sargento Cabral 2131, CC 209, Corrientes Capital, Argentina Santiago Sánchez-Ramírez University of Toronto, 100 Queen’s Park, Toronto, Ontario M5S 2C6, Canada J. Vladimir Sandoval-Sierra Health Science Centre, University of Tennessee, U.S.A. Sergi Santamaria Facultat de Biociències, Edifici C, Despatx C1/331, Campus de la UAB, 08193 Bellaterra, (Cerdanyola del Vallès), Barcelona, Spain Josiane Santana Monteiro Botany Coordination, Museu Paraense Emílio Goeldi, 66077-830, Belém, Pará, Brazil Hans Josef Schroers Agricultural Institute of Slovenia, Hacquetova ulica 17, 1000 Ljubljana, Slovenia Barbara Schulz Institute of Microbiology, Technische Universität Braunschweig, Germany Geert Schmidt-Stohn Burgstr. 25, 29553 Bienenbüttel, Germany Trond Schumacher University of Oslo, P.O.Box 1066, Blindern, 0316 Oslo, Norway Beatrice Senn-Irlet RU Biodiversity and Conservation Biology, Swiss Federal Institute for Forest, Snow and Landscape Research WSL, Zürcherstr. 111, 8903 Birmensdorf, Switzerland Hana Ševčíková Moravian Museum, Zeny trh 6, 659 37 Brno, Czech Republic Oleg Shchepin Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Takashi Shirouzu Graduate School of Bioresources, Mie University, 1577 Kurima-machiya, Tsu, Mie 514-8507, Japan Anton Shiryaev Institute of Plant & Animal Ecology Ural Branch of the Russian Academy of Sciences, 620144 Ekaterinburg, 8 March str., 202/3, Russia Klaus Siepe Geeste 133, 46342 Velen, Germany Esteban B. Sir Fundación Miguel Lillo, Consejo Nacional de Investigaciones Científicas y Técnicas, Miguel Lillo 251, San Miguel de Tucumán 4000, Tucumán, Argentina Mohammad Sohrabi Iranian Research Organization for Science and Technology, P.O. Box 33535111, Tehran, Iran Karl Soop Swedish Museum of Natural History, P.O. Box 50007, 104 05 Stockholm, Sweden Viacheslav Spirin Finnish Museum of Natural History, P.O. Box 7, 00014 University of Helsinki, Finland Toby Spribille University of Alberta, Edmonton, Alberta T6G 2R3, Canada Marc Stadler Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany Joost Stalpers Torenlaan 43, 3742CR Baarn, The Netherlands Soili Stenroos Finnish Museum of Natural History, P.O. Box 7, 00014 University of Helsinki, Finland Ave Suija Institute of Ecology and Earth Sciences, 40 Lai Street, Tartu 51005, Estonia Stellan Sunhede Hökaskog Sandbacken 1, 533 92 Lundsbrunn, Sweden Sten Svantesson University of Gothenburg, Box 461, 40530 Göteborg, Sweden Sigvard Svensson Biological Museum, Lund University, Box 117, 221 00 Lund, Sweden Tatyana Yu. Svetasheva (1) Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia; (2) Department of Technologies of Living Systems, Tula State Lev Tolstoy Pedagogical University, Lenin ave. 125, Tula, 300026, Russia Krzysztof Świerkosz Museum of Natural History, Wrocław University, ul. H. Sienkiewicza 5, 50-335 Wrocław, Poland Heidi Tamm Institute of Ecology and Earth Sciences, 40 Lai Street, Tartu 51005, Estonia Hatira Taskin Faculty of Agriculture, University of Çukurova, 01330 Adana, Turkey Adrien Taudière CEFE UMR5175, CNRS, Université de Montpellier, Université Paul-Valéry Montpellier, EPHE, INSERM, 1919 Route de Mende, 34293 Montpellier Cédex 5, France Jan-Olof Tedebrand Sundsvall Mycological Society, Medelpad, Sweden Raúl Tena Lahoz C/Arreñales del Portillo B 21 1°D, 44003 Teruel, Spain Marina Temina Institute of Evolution, University of Haifa, Aba Khoushi Ave. 199, Mt. Carmel, Haifa 3498838, Israel Arne Thell Biological Museum, Lund University, Box 117, 221 00 Lund, Sweden Marco Thines Faculty of Biosciences, Goethe University Frankfurt am Main, Germany Göran Thor Swedish University of Agricultural Sciences, P. O. Box 7044, 750 07 Uppsala, Sweden Holger Thüs State Museum of Natural History Stuttgart, Rosenstein 1, 70191 Stuttgart, Germany Leif Tibell Evolutionary Biology Centre, Norbyvägen 18D, 75236 Uppsala, Sweden Sanja Tibell Evolutionary Biology Centre, Norbyvägen 18D, 75236 Uppsala, Sweden Einar Timdal Natural History Museum, University of Oslo, P.O. Box 1172 Blindern, 0318 Oslo, Norway Zdenko Tkalčec Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia Tor Tønsberg University of Bergen, Allégaten 41, P.O. Box 7800, 5020 Bergen, Norway Gérard Trichies 5, impasse des Écoles S7700 Neufchef, France Dagmar Triebel Botanische Staatssammlung München, Menzinger Straße 67, 80638 München, Germany Andrei Tsurykau (1) F. Skorina Gomel State University, Sovetskaja Str. 104, 246019 Gomel, Belarus; (2) Institute of Natural Sciences, Samara National Research University, Moskovskoye shosse 34, 443086 Samara, Russia Rodham E. Tulloss Herbarium Amanitarum Rooseveltensis, P. O. Box 57, Roosevelt, New Jersey 08555-0057, U.S.A. Veera Tuovinen University of Alberta, Edmonton, Alberta T6G 2R3, Canada Miguel Ulloa Sosa Universidad Nacional Autónoma de México, Tercer Circuito/Sin Número, Ciudad Universitaria, Ciudad de México, C. P. 04510, Mexico Carlos Urcelay Instituto Multidisciplinario de Biología Vegetal, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba, Casilla de Correo 495, 5000 Córdoba, Argentina François Valade 11 rue haras, le boqueteau, 91240 Saint-Michel-sur-Orge, France Ricardo Valenzuela Garza Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Miguel Hidalgo, Santo Tomás, 11340 Ciudad de México, Mexico Pieter van den Boom Arafura 16, 5691 JA Son, The Netherlands Nicolas Van Vooren Ascomycete.org, 36 rue de la Garde, 69005 Lyon, France Aida M. Vasco-Palacios Escuela de Microbiología, Universidad de Antioquia, AA1226, Fundación Biodiversa Colombia, Medellín, Colombia Jukka Vauras Herbarium TUR, Biodiversity Unit, University of Turku, 20014 Turku, Finland Juan Manuel Velasco Santos 3 C/Pontevedra, 18, 1º C, 37003 Salamanca, Spain Else Vellinga 861 Keeler Avenue, Berkeley, California 94708, U.S.A. Annemieke Verbeken Ghent University, K.L. Ledeganckstraat 35, 9000 Gent, Belgium Per Vetlesen Norges Sopp- og Nyttevekstforbund, Schweigaards gate 34F, 0191 Oslo, Norway Alfredo Vizzini University of Torino, Viale P.A. Mattioli 25, 10125, Torino, Italy Hermann Voglmayr University of Vienna, Rennweg 14, 1030 Vienna, Austria Sergey Volobuev Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia Wolfgang von Brackel Kirchenweg 2, 91341 Röttenbach, Germany Elena Voronina Lomonosov Moscow State University, Biology Faculty, Moscow, Russia Grit Walther Arvid-Harnack-Str. 4, 07743 Jena, Germany Roy Watling Royal Botanic Garden Edinburgh, 20A Inverleith Row, Edinburgh, EH3 5LR, United Kingdom Evi Weber Blaihofstr. 42, 72074 Tübingen, Germany Mats Wedin Swedish Museum of Natural History, P.O. Box 50007, 104 05 Stockholm, Sweden Øyvind Weholt Nord University, Nesna, 8700 Nesna, Norway Martin Westberg Museum of Evolution, Uppsala University, Norbyvägen 16, 75236 Uppsala, Sweden Eugene Yurchenko Polessky State University, Dnyaprouskai flatylii str. 23, 225710, Pinsk, Belarus Petr Zehnálek Faculty of Science, Charles University, Benátská 2, 128 01 Praha 2, Czech Republic Huang Zhang Kunming University of Science & Technology, Kunming, China Mikhail P. Zhurbenko Komarov Botanical Institute of the Russian Academy of Sciences, 2 Prof. Popov Street, St. Petersburg, 197376, Russia The following institutions are also supporting the present text (institutional support means that committees from the mentioned) Asociación Micológica Carlos Spegazzini (Argentina) Austrian Mycological Society (Austria) Croatian Mycological Society (Croatia) Committee of the Czech Scientific Society for Mycology (Czech Republic) The Netherlands Mycological Society (The Netherlands) Sociedad Española de Liquenología (Portugal/Spain) Iberian Mycological Society (which is under constitution, Portugal/Spain) Federación de Asociaciones Micológicas Andaluzas (FAMA) (Spain) Asociación Botánica y Micológica de Jaén (Spain) Asociación Micológica Hispalense Muscaria (Spain) Societat Micològica Valenciana (Spain)

Extirpation of the Central Valley spring-run Chinook Salmon ESU (Oncorhynchus tshawytscha) from the San Joaquin River is emblematic of salmonid declines across the Pacific Northwest. Habitat restoration and fish reintroduction efforts are ongoing, but recent telemetry studies have revealed low outmigration survival of juveniles to the ocean. Previous investigations have focused on modeling survival relative to river discharge and geographic regions, but have largely overlooked the effects of habitat variability. To evaluate the link between environmental conditions and survival of juvenile spring-run Chinook Salmon, we combined high spatial resolution habitat mapping approaches with acoustic telemetry along a 150 km section of the San Joaquin River during the spring of 2019. While overall outmigration survival was low (5%), our habitat-based classification scheme described variation in survival of acoustic-tagged smolts better than other candidate models based on geography or distance. There were two regional mortality sinks evident along the longitudinal profile of the river, revealing poor survival in areas that shared warmer temperatures but that diverged in chlorophyll-α, fDOM, turbidity and dissolved oxygen levels. These findings demonstrate the value of integrating river habitat classification frameworks to improve our understanding of survival dynamics of imperiled fish populations. Importantly, our data generation and modeling methods can be applied to a wide variety of fish species that transit heterogeneous and diverse habitat types.

Naegleria fowleri is a pathogenic free-living amoeba that is commonly found in warm freshwater and can cause a rapidly fulminant disease known as primary amoebic meningoencephalitis (PAM). New drugs are urgently needed to treat PAM, as the fatality rate is >97%. Until recently, few advances have been made in the discovery of new drugs for N. fowleri, and one drawback is the lack of validated tools and methods to enhance drug discovery and diagnostics research. In this study, we aimed to validate alternative methods to assess cell proliferation that are commonly used for other cell types and develop a novel drug screening assay to evaluate drug efficacy on N. fowleri replication. EdU (5-ethynyl-2′-deoxyuridine) is a pyrimidine analog of thymidine that can be used as a quantitative endpoint for cell proliferation. EdU incorporation is detected via a copper catalyzed click reaction with an Alexa Fluor-linked azide. EdU incorporation in replicating N. fowleri was validated using fluorescence microscopy, and quantitative methods for assessing EdU incorporation were developed by using an imaging flow cytometer. Currently used PAM therapeutics inhibited N. fowleri replication and EdU incorporation in vitro. EdA (7-deaza-2′-deoxy-7-ethynyladenosine), an adenine analog, also was incorporated by N. fowleri but was more cytotoxic than EdU. In summary, EdU incorporation could be used as a complimentary method for drug discovery for these neglected pathogens.

Plasmodium is a genus of apicomplexan parasites which replicate in the liver before causing malaria. Plasmodium vivax can also persist in the liver as dormant hypnozoites and cause clinical relapse upon activation, but the molecular mechanisms leading to activation have yet to be discovered. In this study, we use high-resolution microscopy to characterize temporal changes of the P. vivax liver stage tubovesicular network (TVN), a parasitophorous vacuole membrane (PVM)-derived network within the host cytosol. We observe extended membrane clusters, tubules, and TVN-derived vesicles present throughout P. vivax liver stage development. Additionally, we demonstrate an unexpected presence of the TVN in hypnozoites and observe some association of this network to host nuclei. We also reveal that the host water and solute channel aquaporin-3 (AQP3) associates with TVN-derived vesicles and extended membrane clusters. AQP3 has been previously shown to localize to the PVM of P. vivax hypnozoites and liver schizonts but has not yet been shown in association to the TVN. Our results highlight host-parasite interactions occur in both dormant and replicating liver stage P. vivax forms and implicate AQP3 function during this time. Together, these findings enhance our understanding of P. vivax liver stage biology through characterization of the TVN with an emphasis on the presence of this network in dormant hypnozoites.

Most animals show external bilateral symmetry, which hinders the observation of multiple internal left-right (L/R) asymmetries that are fundamental to organ packaging and function. In vertebrates, left identity is mediated by the left-specific Nodal-Pitx2 axis that is repressed on the right-hand side by the epithelial-mesenchymal transition (EMT) inducer Snail1 (refs 3, 4). Despite some existing evidence, it remains unclear whether an equivalent instructive pathway provides right-hand-specific information to the embryo. Here we show that, in zebrafish, BMP mediates the L/R asymmetric activation of another EMT inducer, Prrx1a, in the lateral plate mesoderm with higher levels on the right. Prrx1a drives L/R differential cell movements towards the midline, leading to a leftward displacement of the cardiac posterior pole through an actomyosin-dependent mechanism. Downregulation of Prrx1a prevents heart looping and leads to mesocardia. Two parallel and mutually repressed pathways, respectively driven by Nodal and BMP on the left and right lateral plate mesoderm, converge on the asymmetric activation of the transcription factors Pitx2 and Prrx1, which integrate left and right information to govern heart morphogenesis. This mechanism is conserved in the chicken embryo, and in the mouse SNAIL1 acts in a similar manner to Prrx1a in zebrafish and PRRX1 in the chick. Thus, a differential L/R EMT produces asymmetric cell movements and forces, more prominent from the right, that drive heart laterality in vertebrates.

Lisch corneal dystrophy is a rare corneal disease characterized by the distinctive feature of highly vacuolated cells. Although this feature is important, the nature of these vacuoles within corneal cells remains unknown. Here, we sought to analyze corneal cells from a patient diagnosed with Lisch dystrophy to characterize the vacuoles within these cells. Analyses using histopathology examination, confocal microscopy, and transmission electron microscopy were all consistent with previous descriptions of Lisch cells. Importantly, the vacuoles within these cells appeared to be autophagosomes and autolysosomes, and could be stained with an anti-microtubule-associated protein 1A/1B-light chain 3 (LC3) antibody. Taken together, these findings indicate that the vacuoles we observed within superficial corneal cells of a patient with Lisch corneal dystrophy constituted autophagosomes and autolysosomes; this finding has not been previously reported and suggests a need for further analyses to define the role of autophagy in this ocular disease. RESUMO A distrofia corneana de Lisch é uma doença rara, caracterizada principalmente pela presença de células altamente vacuoladas. Embora esta característica seja importante, a natureza desses vacúolos dentro das células da córnea permanece des conhecida. Aqui, procuramos analisar as células da córnea de um paciente diagnosticado com distrofia de Lisch para caracte rizar os vacúolos dentro dessas células. Análises utilizando exame histopatológico, microscopia confocal e microscopia eletrônica de transmissão foram todas consistentes com descrições previas de células de Lisch. Importante, os vacúolos dentro dessas células pareciam ser autofagossomos e autolisossomos, e po deriam ser corados com um anticorpo proteico 1A/1B-cadeia leve 3 (LC3) da proteína anti-microtúbulo associado a microtúbulos. Em conjunto, esses achados indicam que os vacúolos observados nas células superficiais da córnea de um paciente com distrofia corneana de Lisch constituíram autofagossomos e autolisossomos. Esse achado não foi relatado anteriormente e sugere a necessidade de mais análises para definir o papel da autofagia nessa doença ocular.

Background: Artemis enzyme, encoded by the DCLRE1C gene, is essential to V(D)J recombination in both T and B lymphocytes. Artemis functions as an important component of the nonhomologous end-joining DNA double-strand break repair pathway. Artemis deficiency leads to a T-B-NK+ severe combined immune deficiency (SCID) associated with radiosensitivity. Clinical presentation: We present a case of a positive newborn screen for SCID in a patient who was subsequently shown to have a T-B-NK+ phenotype. Further immune evaluation showed profound T and B lymphopenia, near-absent response to mitogen stimulation, and absent immunoglobulins A and M. Genetic investigation demonstrated a novel and putative pathogenic variant in the DCLRE1C gene. Conclusion: This case identifies a novel variant in the DCLRE1C gene in a patient with SCID identified by newborn screening. Statement of novelty: This case report identifies a novel variant in the DCLRE1C gene in a patient with T-B-NK+ SCID.

Chronic progressive external ophthalmoplegia (CPEO) is a common presentation of mitochondrial disease. We performed a retrospective evaluation of the molecular genetic testing and genotype-phenotype correlations in a large cohort of adult-onset CPEO patients (N = 111). One hundred percent of patients tested had at least one mitochondrial DNA (mtDNA) deletion. Genetic testing of nuclear genes encoding mitochondrial proteins identified pathogenic/likely pathogenic variants likely to be associated with CPEO in 7.6% of patients. As expected, the nuclear gene most associated with DNA variation was POLG. A single likely pathogenic mitochondrial DNA variant (m.12278T>C) was identified in two unrelated patients. No significant differences were noted in the clinical phenotypes of patients with pathogenic or likely pathogenic nuclear variants in comparison to those with negative nuclear gene testing. Analysis of deletion size and heteroplasmy in muscle-derived mtDNA showed significant correlations with age of symptom onset but not disease severity (number of canonical CPEO features). Results suggest that smaller mtDNA deletions (p = 0.0127, r2 = 0.1201) and higher heteroplasmy of single mtDNA deletions (p = 0.0112, r2 = 0.2483) are associated with an earlier age of onset in CPEO patients.

Author(s): Davis, BE; Hansen, MJ; Cocherell, DE; Nguyen, TX; Sommer, T; Baxter, RD; Fangue, NA; Todgham, AE | Abstract: The effects of water temperature on individual and group movement behaviour in prey fish can affect ecological interactions such as competition and predation, but how variability in temperature influence fish behaviour is less understood. Of particular concern is how increased warming in tidally fluctuating estuaries may impact the native and endangered delta smelt (Hypomesus transpacificus, Osmeridae). To help address this issue, we tested the effects of increased water temperature (fluctuating [17–21°C] and warm [21°C] acclimated treatments) on juvenile delta smelt individual and group behaviour, response to chemical alarm and predator cues, as well as capacity to evade predation. In addition, predation of delta smelt was tested in the presence of a dominant invasive competitor, Mississippi silversides (Menidia beryllina, Atherinopsidae), as well as comparative predation mortality on Mississippi silversides when isolated. After 7ndays of increased temperature treatments, delta smelt in the warm treatment increased swimming velocity, decreased turning angle, and altered group structure with larger inter-individual distances compared to fish in the control (17°C) and fluctuating temperature treatments. Following conspecific and predator chemical alarm cues, delta smelt showed anti-predator responses. Control and fluctuating treatment fish responded to conspecific cues with increased swimming speeds, decreased inter-individual distances and near-neighbour distances, and, after 15nmin, fish recovered back to baseline behaviours. In contrast, fish in the warm treatment had not recovered after 15nmin, and swimming speeds were maintained at roughly 25ncm/s, close to maximum capabilities. Fish in control and fluctuating treatments showed minimal responses to predator cues, whereas delta smelt exposed to warm conditions significantly increased swimming speeds and decreased turning angle. Predation of delta smelt by largemouth bass (Micropterus salmoides, Centrarchidae) was greatest under the warm treatment, correlating with altered behaviours of delta smelt; however, predation of Mississippi silversides was greater than delta smelt, independent of temperature. This study provides novel insight into the group behaviour of delta smelt, their response to predation, and how prolonged exposure to elevated temperature may induce negative individual and group behaviours causing alterations in predator–prey dynamics. This work highlights the importance of testing ecologically realistic temperature fluctuations in experiments as delta smelt had significantly altered responses to elevated temperature, dependent on variability of warming.

This treatise serves as a preliminary monograph and phylogenetic treatment of Marasmius from the African island nation of São Tomé and Príncipe (ST&P), based on data generated from 30 specimens collected in 2008. Twenty-one species are described, seven of which represent species new to science (Marasmius albisubiculosus, M. diversus, M. elaeocephaliformis, M. laranja, M. leptocephalus, M. paratrichotus, M. segregatus), and all represent new distribution records for ST&P. Species are delimited based on comprehensive morphological characters and DNA sequence data. Prior to the collection of these specimens, only one Marasmius species had been documented from these islands. Phylogenetic hypotheses generated from analyses of DNA sequences of the Internal Transcribed Spacer regions (ITS1+5.8S+ITS2) are proposed to explore the evolutionary relationships amongst ST&P Marasmius and global Marasmius diversity. A dichotomous key to aid in identification, illustrations of pertinent micromorphological features, colour photographs of basidiomata, comprehensive descriptions and commentaries are provided.

The entrainment and impingement of fish into water diversion infrastructure is one of the several factors contributing to their decline. Here, controlled experiments assessed the potential for a behavioral guidance device [a light-emitting diode (LED) light array] strobing at various spectra to reduce the entrainment of juvenile Chinook salmon (Oncorhynchus tshawytscha) into a water diversion pipe. Fish were tested during the day and night, and under control conditions (light off) and red, blue, and white spectra strobing at 2 Hz. Fish entrainment into the diversion pipe was evaluated. Results indicated greater entrainment at night compared to day. All trials at night with the LED light strobing had higher entrainment than the control, with blue and white spectra corresponding to greater entrainment than red spectra. During the day, the white spectra treatment was different from the red treatment, with lower entrainment. LED lights employed to repel migratory juvenile salmon away from water intake structures may be ineffectual but there is potential for the light to be used as an attractant to guide fish towards desirable features such as “safe” areas (bypass channels or fishways).

Context: Recent epidemiology studies indicated a steady increase of anterior cruciate ligament (ACL) injury in young athletes. ACL reconstruction (ACLR) is currently a standard of care, but the eff...

Seven species of bioluminescent fungi are recorded from the cloud forests in Mexico. Six represent new species belonging to the genus Mycena, whereas Mycena globulispora is a new distribution record for the country. Descriptions, illustrations, photographs, and an identification key to bioluminescent fungi species from Mexico are provided. Sequences of nuc rDNA internal transcribed spacer (ITS1-5.8S-ITS2 = ITS) region were generated for barcoding purposes and comparisons with similar species.

In highly regulated systems, like large dammed rivers, conservation legislation requires that systems are managed, in part, to avoid adverse impacts on endangered species. However, multiple endangered species can occur in the same system, and management actions that benefit one species may be detrimental to another species. The current water management strategies in the Sacramento River basin are an example of this conflict. Cold-water releases from Shasta Reservoir during the summer and fall months are aimed at protecting Sacramento River winter-run Chinook (SRWRC) salmon by providing suitable incubation temperatures for their eggs. However, the effects of these regulated water temperature releases on another threatened species, green sturgeon, are less well understood. In this study, we applied a simplified dynamic energy budget (DEB) model (aka DEBkiss) to explore the effect of food limitation and water temperature on the growth rates of green sturgeon. This model captures these effects and able to predict the growth of green sturgeon at different food levels and temperature conditions. We then linked the DEB model with a physically‐based water temperature model. We applied the DEB - water temperature linked model for green sturgeon along with a temperature-dependent egg to fry survival model for SRWRC salmon to quantify the consequences of managing water temperatures to improve salmon eggs survival on the growth rate of green sturgeon. We found that mean temperature-dependent egg-to-fry survival of salmon increased across a modeled environmental gradient from critically dry to wet water year types, while the fractional growth rate of juvenile green sturgeon showed the opposite trend, and decreased as water years transitioned from dry to wet conditions. We also found a non-linear negative correlation between temperature-dependent mean growth rate of green sturgeon and mean temperature-dependent egg-to-fry survival of salmon, which indicated there is a river temperature related trade-off between early growth rate of green sturgeon and embryonic stage survival of salmon. However, the relatively small gains in the growth rate of green sturgeon achieved in years when temperature criteria for SRWRC salmon eggs were not met came at the cost of large reduction in temperature-dependent egg-to-fry survival of salmon. Thus, we concluded the current Sacramento River water-temperature management for the eggs of the endangered SRWRC salmon eggs have a relatively small impact on the growth rate of green sturgeon.

Author(s): Singer, GP; Hansen, MJ; Ho, KV; Lee, KW; Cocherell, DE; Peter Klimley, A; Rypel, AL; Fangue, NA | Abstract: Acoustic telemetry, a commonly used tool for examining movements and survival of aquatic species, is often applied without a comprehensive understanding of transmitter implantation effects. This can be problematic when the goal of the study is to use telemetry results to make inferences regarding broader populations. Here, we examined juvenile Chinook Salmon Oncorhynchus tshawytscha at varying time intervals after transmitter implantation to assess the behavioral implications of tagging. The following behavioral metrics in response to a novel environment were compared across treatment and control groups: time to emergence from shelter into the open portion of the test arena, rheotactic response, total activity, and rates of exploration. Tagged fish (114–132nmm FL) were tested at 0, 1, or 4nd postsurgery (day-0, day-1, and day-4 groups, respectively), and their behavior was compared to that of similarly handled control fish. Emergence from refuge was the only metric that differed significantly between treatment and control groups. Fish tested on the same day as the surgery were less likely to emerge from the refuge, with only 46% of the day-0 tagged fish emerging compared to 88, 93, and 80% of the day-1, day-4, and control groups, respectively. However, day-0 fish that did emerge from the refuge had rheotactic responses, total activity, and exploration rates similar to those of fish from the other treatment and control groups. This study may have fisheries research and management implications, especially for telemetry studies and monitoring efforts. We encourage researchers using this technology to consider (1) observing a post-transmitter-implantation recovery period of at least 24nh prior to release, adjusting study plans and logistics accordingly; (2) applying sufficient scientific rigor to emerging tagging technology prior to wide-scale adoption; and (3) when possible, conducting concurrent battery life and tag effects studies with any field release of tagged fishes, as differing relationships between fish size, tag size, and tagging techniques may yield variable results.

Phosphatidylethanolamine N-methyltransferase (PEMT) is an important enzyme in hepatic phosphatidylcholine (PC) biosynthesis. Pemt-/- mice fed a high-fat diet are protected from obesity and whole-body insulin resistance. However, Pemt-/- mice develop severe nonalcoholic steatohepatitis (NASH). Because NASH is often associated with hepatic insulin resistance, we investigated whether the increased insulin sensitivity in Pemt-/- mice was restricted to nonhepatic tissues or whether the liver was also insulin sensitive. Strikingly, the livers of Pemt-/- mice compared with those of Pemt+/+ mice were not insulin resistant, despite elevated levels of hepatic triacylglycerols and diacylglycerols, as well as increased hepatic inflammation and fibrosis. Endogenous glucose production was lower in Pemt-/- mice under both basal and hyperinsulinemic conditions. Experiments in primary hepatocytes and hepatoma cells revealed improved insulin signaling in the absence of PEMT, which was not due to changes in diacylglycerols, ceramides, or gangliosides. On the other hand, the phospholipid composition in hepatocytes seems critically important for insulin signaling such that lowering the PC:phosphatidylethanolamine (PE) ratio improves insulin signaling. Thus, treatments to reduce the PC:PE ratio in liver may protect against the development of hepatic insulin resistance.-Van der Veen, J. N., Lingrell, S., McCloskey, N., LeBlond, N. D., Galleguillos, D., Zhao, Y. Y., Curtis, J. M., Sipione, S., Fullerton, M. D., Vance, D. E., Jacobs, R. L. A role for phosphatidylcholine and phosphatidylethanolamine in hepatic insulin signaling.

Life cycles of spirorchiids that infect the vascular system of turtles are poorly understood. Few life cycles of these blood flukes have been elucidated and all intermediate hosts reported are gastropods (Mollusca), regardless of whether the definitive host is a freshwater or a marine turtle. During a recent survey of blood fluke larvae in polychaetes on the coast of South Carolina, USA, spirorchiid-like cercariae were found to infect the polychaetes Amphitrite ornata (Terebellidae) and Enoplobranchus sanguineus (Polycirridae). Cercariae were large, furcate, with a ventral acetabulum, but no eyespots were observed. Partial sequences of D1-D2 domains of the large ribosomal subunit, the internal transcribed spacer 2, and the mitochondrial cytochrome oxidase 1 genes allowed the identification of sporocysts and cercariae as belonging to two unidentified Neospirorchis species reported from the green turtle, Chelonia mydas, in Florida: Neospirorchis sp. (Neogen 13) in A. ornata and Neospirorchis sp. (Neogen 14) in E. sanguineus. Phylogenetic analysis suggests that infection of annelids by blood flukes evolved separately in aporocotylids and spirorchiids. Our results support the contention that the Spirorchiidae is not a valid family and suggest that Neospirorchis is a monophyletic clade within the paraphyletic Spirorchiidae. Since specificity of spirorchiids for their intermediate hosts is broader than it was thus far assumed, surveys of annelids in turtle habitats are necessary to further our understanding of the life history of these pathogenic parasites.

Background: The protein encoded by interleukin-2 receptor common gamma chain (IL2RG) is an important signaling component of many interleukin receptors, including those of interleukin-2, -4, -7, and -21, known as the common gamma chain. Mutations in the gene encoding the common gamma chain of the interleukin-2 receptor cause X-linked severe combined immunodeficiency (SCID). In this report, we present an unknown genetic defect of a patient diagnosed with SCID whose genetic analysis was performed 2 decades later. Methods: Whole genome sequencing and Sanger confirmation were used to identify a novel frameshift mutation in IL2RG. Massively parallel sequencing of genes associated with SCID were performed on the patient’s mother and sister. Results: Next generation sequencing techniques identified a heterozygous frame-shift deletion in the gene encoding the common gamma chain of IL2RG in our patient. The patient’s mother had a low level mosaicism for the same deletion. The sister had no detectable deletion. Conclusion: We have identified a novel mutation in IL2RG resulting in an X-linked SCID phenotype. The genetic analysis of the patient’s mother revealed a mosaicism which was not passed on to his sister. The importance of genetic analysis in family members and SCID patients with an unknown genetic defect should be emphasized for family planning and subsequent genetic counseling. Statement of novelty: Genetic testing is an extremely important component in evaluating severe combined immunodeficiency as it impacts treatment course and prognosis, and allows for genetic analysis and counselling of family members.

Ionizing radiation (IR) therapy is a major cancer treatment modality and an indispensable auxiliary treatment for primary and metastatic cancers, but invariably results in debilitating organ dysfunctions. IR-induced depletion of neural stem/progenitor cells in the subgranular zone of the dentate gyrus in the hippocampus where neurogenesis occurs is considered largely responsible for deficiencies such as learning, memory, and spatial information processing in patients subjected to cranial irradiation. Similarly, IR therapy-induced intestinal injuries such as diarrhea and malabsorption are common side effects in patients with gastrointestinal tumors and are believed to be caused by intestinal stem cell drop out. Hematopoietic stem cell transplantation is currently used to reinstate blood production in leukemia patients and pre-clinical treatments show promising results in other organs such as the skin and kidney, but ethical issues and logistic problems make this route difficult to follow. An alternative way to restore the injured tissue is to preserve the stem cell pool located in that specific tissue/organ niche, but stem cell response to ionizing radiation is inadequately understood at the molecular mechanistic level. Although embryonic and fetal hypersensity to IR has been very well known for many decades, research on embryonic stem cell models in culture concerning molecular mechanisms have been largely inconclusive and often in contradiction of the in vivo observations. This review will summarize the latest discoveries on stem cell radiosensitivity, highlighting the possible molecular and epigenetic mechanism(s) involved in DNA damage response and programmed cell death after ionizing radiation therapy specific to normal stem cells. Finally, we will analyze the possible contribution of stem cell-specific chromatin’s epigenetic constitution in promoting normal stem cell radiosensitivity.

Our results highlight the importance of soil microorganisms in plant disease suppression and the possibility to steer soil microbial community composition by applying organic amendments to the soil., Enhancing soil suppressiveness against plant pathogens or pests is a promising alternative strategy to chemical pesticides. Organic amendments have been shown to reduce crop diseases and pests, with chitin products the most efficient against fungal pathogens. To study which characteristics of organic products are correlated with disease suppression, an experiment was designed in which 10 types of organic amendments with different physicochemical properties were tested against the soilborne pathogen Rhizoctonia solani in sugar beet seedlings. Organic amendments rich in keratin or chitin reduced Rhizoctonia solani disease symptoms in sugar beet plants. The bacterial and fungal microbial communities in amended soils were distinct from the microbial communities in nonamended soil, as well as those in soils that received other nonsuppressive treatments. The Rhizoctonia-suppressive amended soils were rich in saprophytic bacteria and fungi that are known for their keratinolytic and chitinolytic properties (i.e., Oxalobacteraceae and Mortierellaceae). The microbial community in keratin- and chitin-amended soils was associated with higher zinc, copper, and selenium, respectively. IMPORTANCE Our results highlight the importance of soil microorganisms in plant disease suppression and the possibility to steer soil microbial community composition by applying organic amendments to the soil.

BACKGROUND Our understanding of the normative concentrations of urine biomarkers in premature neonates is limited. METHODS We evaluated urine from 750 extremely low gestational age (GA) neonates without severe acute kidney injury (AKI) to determine how GA affects ten different urine biomarkers at birth and over the first 30 postnatal days. Then, we investigated if the urine biomarkers changed over time at 27, 30, and 34 weeks postmenstrual age (PMA). Next, we evaluated the impact of sex on urine biomarker concentrations at birth and over time. Finally, we evaluated if urine biomarkers were impacted by treatment with erythropoietin (Epo). RESULTS We found that all ten biomarker concentrations differ at birth by GA and that some urine biomarker concentrations increase, while others decrease over time. At 27 weeks PMA, 7/10 urine biomarkers differed by GA. By 30 weeks PMA, 5/10 differed, and by 34 weeks PMA, only osteopontin differed by GA. About half of the biomarker concentrations differed by sex, and 4/10 showed different rates of change over time between males vs. females. We found no differences in urine biomarkers by treatment group. CONCLUSIONS The temporal patterns, GA, and sex differences need to be considered in urine AKI biomarker analyses. IMPACT Urine biomarker concentrations differ by GA at birth. Some urine biomarkers increase, while others decrease, over the first 30 postnatal days. Most urine biomarkers differ by GA at 27 weeks PMA, but are similar by 34 weeks PMA. Some urine biomarkers vary by sex in premature neonates. Urine biomarkers did not differ between neonates randomized to placebo vs. Epo.

Spatiotemporal relationships between genes expressed in tissues likely reflect physicochemical principles that range from stoichiometric interactions to co-organized fractals with characteristic scaling. For key structural factors within the nucleus and extracellular matrix (ECM), gene-gene power laws are found to be characteristic across several tumor types in The Cancer Genome Atlas (TCGA) and across single-cell RNA-seq data. The nuclear filamentLMNB1scales with many tumor-elevated proliferation genes that predict poor survival in liver cancer, and cell line experiments showLMNB1regulates cancer cell cycle. Also high in the liver, lung, and breast tumors studied here are the main fibrosis-associated collagens,COL1A1andCOL1A2, that scale stoichiometrically with each other and super-stoichiometrically with a pan-cancer fibrosis gene set. However, high fibrosis predicts prolonged survival of patients undergoing therapy and does not correlate withLMNB1. Single-cell RNA-seq data also reveal scaling consistent with the pan-cancer power laws obtained from bulk tissue, allowing new power law relations to be predicted. Lastly, although noisy data frustrate weak scaling, concepts such as stoichiometric scaling highlight a simple, internal consistency check to qualify expression data.ClassificationApplied Physical Sciences (major) and Cell Biology (minor)Significance StatementNon-linear scaling analyses pervade polymer physics and chemistry and conceivably provide new insight into polymeric assemblies of genes expressed in tissues as well as co-regulated gene sets. Fractal scaling and stoichiometric scaling are among the gene-gene power law results identified here for key structural polymers in nuclei or extracellular matrix in human cancer data. Among nuclear envelope factors that might scale with DNA mass, only one nuclear filament scales with tumor proliferation and predicts poor survival in some cancer types. Collagen-1 scales with fibrosis and also tends to increase in multiple tumor types, but patients in therapy surprisingly survive longest with the highest levels of fibrosis, consistent with a therapeutic response.