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South Pacific archipelagos are central in the biogeographic debate on the relative importance of vicariance and dispersal in shaping the distribution of species. However, each taxonomic group was subject to different processes and histories, and here, we reveal the historical biogeography of the diverse Eumolpinae leaf beetles, widely distributed in the region. Extensive taxon sampling focusing on South Pacific Eumolpinae was used to infer the first molecular phylogeny of the group using three single‐copy protein‐coding nuclear and two mitochondrial markers. Upon assessing the clade of interest for lineage‐specific variation in substitution rates, the age of the most recent common ancestors was estimated using out‐group calibration and multi‐gamma site models (MGSMs). Biogeographic analyses used standard event‐based inferences also incorporating phylogenetic uncertainty. Zealandian Eumolpinae are monophyletic and appear to have split from their global relatives in the transition from the Cretaceous to the Paleogene. Variation in the rates of molecular evolution affected the in‐group stem branch, with a significant drop in the substitution rate, and the MGSM correction recovered the crown age of Zealandian Eumolpinae during the Late Eocene–Oligocene transition. Biogeographic inference resolved the origin of the radiation in New Caledonia, favouring a null model without island age constraints, and repeated dispersal events to the other islands, including three independent but synchronous colonisations of New Zealand during the Miocene. New Caledonia, with a highly diverse Eumolpinae fauna of uncertain origin, acted as a hub and pump of biodiversity of these beetles in the entire South Pacific region, sending migrants to other islands through long‐distance dispersal with lineages establishing when land became available. [ABSTRACT FROM AUTHOR]

People living with HIV (PWH) have been shown to bear a higher burden of hepatitis B virus (HBV) due to shared routes and risk factors for transmission. Populations such as men who have sex with men (MSM) are at an increased risk of both being infected with HBV and HIV, that places them at higher risk of hepatocellular carcinoma. Using weighted and adjusted multilevel logistic regression, we characterized the prevalence and correlates of hepatitis B surface antigen (HBsAg) among MSM living with HIV across 12 Indian cities from 2012 to 2013. Overall, the prevalence of HBsAg was 8% (range across cities: 0.5%–19%). Being between the ages of 25–34, and 35–44 increased the odds of having chronic HBV infection compared to MSM 24 years or younger. Daily or seasonal employment and being unemployed increased the odds of HBsAg prevalence compared to those with monthly or weekly wages. Sexual risk behaviours such as having had sex with both men and women in the prior 6 months and history of sex work increased the odds of having HBV. Ever having insertive sex with a man or hijra (assigned male at birth, currently identifies as female/nonbinary) was negatively associated with HBV. Despite the existence of efficacious vaccines, HBV continues to have high prevalence among PWHs. Programmes to increase early screening, vaccinations and HBV literacy are urgently needed. Integrating HBV and HIV programmes for MSM populations could be critical in addressing this dual burden and improving outcomes for both infections. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Agricultural Economics is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Late Ediacaran opening of the Iapetus Ocean is typically considered to reflect separation of Baltica and Laurentia during final breakup of the Rodinia supercontinent, with subsequent closure during the Caledonian Orogeny. However, evidence of the pre‐opening juxtaposition of Baltica and Laurentia is limited to purportedly similar apparent polar wander paths and correlation of Rodinia‐forming orogenic events. We show that a range of existing data do not unequivocally support correlation of these orogens, and that geologic and palaeomagnetic data instead favour separation of Baltica and Laurentia as early as 1.1–1.2 Ga. Furthermore, new detrital zircon U–Pb age and Ar–Ar thermochronological data from Norway point towards an active western Baltican margin throughout most of the Neoproterozoic and early Palaeozoic. These findings are inconsistent with the majority of palaeogeographic reconstructions that place Baltica near the core of the Rodinia supercontinent. [ABSTRACT FROM AUTHOR]

We examine how increased female participation in top executive leadership affects corporate social responsibility (CSR). Applying a long‐window, event study approach with matching, we first document that CSR ratings improve with increased female participation in the top executive team, consistent with expectations based on previous research. Then, we examine specific ways that female participation impacts CSR decision‐making. We predict and find that increased female participation brings more attention to remediating CSR concerns. We also predict and find that, in the uncertain economic times following the global financial crisis, increased female participation moderated addition of new CSR strengths. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to identify predictors in common between different clinical and magnetic resonance imaging (MRI) outcomes in multiple sclerosis (MS) by comparing predictive models. Methods: We analyzed 704 patients from our center seen at MS onset, measuring 37 baseline demographic, clinical, treatment, and MRI predictors, and 10‐year outcomes. Our primary aim was identifying predictors in common among clinical outcomes: aggressive MS, benign MS, and secondary‐progressive (SP)MS. We also investigated MRI outcomes: T2 lesion volume (T2LV) and brain parenchymal fraction (BPF). The performance of the full 37‐predictor model was compared with a least absolute shrinkage and selection operator (LASSO)‐selected model of predictors in common between each outcome by the area under the receiver operating characteristic curves (AUCs). Results: The full 37‐predictor model was highly predictive of clinical outcomes: in‐sample AUC was 0.91 for aggressive MS, 0.81 for benign MS, and 0.81 for SPMS. After variable selection, 10 LASSO‐selected predictors were in common between each clinical outcome: age, Expanded Disability Status Scale, pyramidal, cerebellar, sensory and bowel/bladder signs, timed 25‐foot walk ≥6 seconds, poor attack recovery, no sensory attacks, and time‐to‐treatment. This reduced model had comparable cross‐validation AUC as the full 37‐predictor model: 0.84 versus 0.81 for aggressive MS, 0.75 versus 0.73 for benign MS, and 0.76 versus 0.75 for SPMS, respectively. In contrast, 10‐year MRI outcomes were more strongly influenced by initial T2LV and BPF than clinical outcomes. Interpretation: Early prognostication of MS is possible using LASSO modeling to identify a limited set of accessible clinical features. These predictive models can be clinically usable in treatment decision making once implemented into web‐based calculators. ANN NEUROL 2022;92:87–96 [ABSTRACT FROM AUTHOR]

Background: In peritoneal dialysis (PD) patients, information on the immunogenicity and tolerability of SARS‐CoV‐2 vaccination is still scarce. We compared the immunogenicity and tolerability of SARS‐CoV‐2 vaccination of PD patients with that of medical personnel. Methods: In a prospective observational cohort study, PD patients and immunocompetent medical personnel were evaluated for SARS‐CoV‐2 spike‐IgG‐ and Nucleocapsid‐IgG‐antibody‐levels before, 2 weeks after the first, and 6 weeks after the second SARS‐CoV‐2 vaccination and vaccine tolerability after the first and second vaccination. Results: In COVID‐19‐naïve PD patients (N = 19), lower SARS‐CoV‐2‐spike‐IgG‐levels were found compared with COVID‐19‐naïve medical personnel (N = 24) 6 weeks after second vaccination (median 1438 AU/ml [25th–75th percentile 775–5261] versus 4577 [1529–9871]; p = 0.045). This finding resulted in a lower rate of strong vaccine response (spike‐IgG ≥ 1000 AU/ml) of COVID‐19‐naïve PD patients compared with medical personnel (58% versus 92%; p = 0.013), but not for seroconversion rate (spike‐IgG ≥ 50 AU/ml: 100% vs. 100%; p > 0.99). After first vaccination, COVID‐naïve PD patients presented with significantly fewer side effects than medical personnel (number of any side effect: 1 [1–2] vs. 4 [1–7]; p = 0.015). A similar pattern with slightly decreased frequencies of side effects was observed for tolerability of second SARS‐CoV‐2 vaccination in PD patients and medical personnel (number of any side effects: 1 [1–1] vs. 2 [1–5]; p = 0.006). Conclusions: SARS‐CoV‐2 vaccination in COVID‐19‐naïve PD patients appeared to induce a very high rate of seroconversion but a substantially lower rate of patients with a strong response compared with medical personnel. Vaccination appeared to be safe in the PD patients studied. [ABSTRACT FROM AUTHOR]

Background: Infection by coronaviruses cause gastrointestinal disease in many species. Little is known about its prevalence and importance in goats. Objective: Identify the etiology, demographics, and clinical features of an outbreak of diarrhea in adult goats. Hypothesis: Bovine coronavirus (BCoV) PCR would detect viral material in feces of goats in the herds involved in the diarrhea outbreak. Animals: Twelve herds with 4 to 230 adult goats were affected. Goats sampled for fecal PCR were ≥1‐year‐old: 25 from affected herds and 6 from a control herd. Methods: This is a cross‐sectional descriptive study of an outbreak of diarrheal disease in adult goats. BCoV PCR primers for the spike (S) or nucleocapsid (N) proteins were used to test fecal material from affected goats. The N protein sequencing and phylogenetic analysis was performed. Herd records and owner surveys were used to characterize morbidity, clinical signs, and treatment. Results: In 2 affected herds 18/25 of animals had at least 1 positive BCoV PCR test. Goats from affected herds were significantly more likely to be PCR positive than the control herd (OR 8.75, 95% CI 1.11‐104, P =.05). The most common clinical signs were change in fecal consistency (19/20) and decreased milk production (14/15). Phylogenetic analysis of the N protein showed this virus was closely related to a bovine‐like coronavirus isolated from a giraffe. Conclusions and Clinical Importance: Bovine coronavirus primers detected nucleic acids of the N and S proteins in feces of goats in affected herds. Coronavirus shedding frequency was temporally associated with the outbreak. [ABSTRACT FROM AUTHOR]

Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is an inherited arrhythmogenic disorder caused by missense mutations in the cardiac ryanodine receptors (RyR2), that result in increased β‐adrenoceptor stimulation‐induced diastolic Ca2+ leak. We have previously shown that exercise training prevents arrhythmias in CPVT1, potentially by reducing the oxidation of Ca2+/calmodulin‐dependent protein kinase type II (CaMKII). Therefore, we tested whether an oxidation‐resistant form of CaMKII protects mice carrying the CPVT1‐causative mutation RyR2‐R2474S (RyR2‐RS) against arrhythmias. Antioxidant treatment (N‐acetyl‐L‐cysteine) reduced the frequency of β‐adrenoceptor stimulation‐induced arrhythmogenic Ca2+ waves in isolated cardiomyocytes from RyR2‐RS mice. To test whether the prevention of CaMKII oxidation exerts an antiarrhythmic effect, mice expressing the oxidation‐resistant CaMKII‐MM281/282VV variant (MMVV) were crossed with RyR2‐RS mice to create a double transgenic model (RyR2‐RS/MMVV). Wild‐type mice served as controls. Telemetric ECG surveillance revealed an increased incidence of ventricular tachycardia and an increased arrhythmia score in both RyR2‐RS and RyR2‐RS/MMVV compared to wild‐type mice, both following a β‐adrenoceptor challenge (isoprenaline i.p.), and following treadmill exercise combined with a β‐adrenoceptor challenge. There were no differences in the incidence of arrhythmias between RyR2‐RS and RyR2‐RS/MMVV mice. Furthermore, no differences were observed in β‐adrenoceptor stimulation‐induced Ca2+ waves in RyR2‐RS/MMVV compared to RyR2‐RS. In conclusion, antioxidant treatment reduces β‐adrenoceptor stimulation‐induced Ca2+ waves in RyR2‐RS cardiomyocytes. However, oxidation‐resistant CaMKII‐MM281/282VV does not protect RyR2‐RS mice from β‐adrenoceptor stimulation‐induced Ca2+ waves or arrhythmias. Hence, alternative oxidation‐sensitive targets need to be considered to explain the beneficial effect of antioxidant treatment on Ca2+ waves in cardiomyocytes from RyR2‐RS mice. [ABSTRACT FROM AUTHOR]

Introduction: Many factors associated with colonic diverticulitis are also part of the clinical definition of the metabolic syndrome. Computed tomography (CT) is commonly performed in symptomatic patients, such as those with suspected or known acute diverticulitis, and could add additional value for the health of these patients by identifying and reporting CT biomarkers of metabolic syndrome, if present and detectable. The purpose of this study was to identify CT biomarkers of metabolic syndrome in patients with acute colonic diverticulitis. Methods: We retrospectively reviewed 243 patients (mean‐60 yrs, M:F:126:117) diagnosed with colonic diverticulitis on CT between March 2015 and March 2017 for hepatic steatosis, vascular calcifications, abdominal diameters and fat volumes. Criteria of metabolic syndrome were obtained from medical records. Differences in imaging biomarkers were compared using chi‐square comparisons stratified by metabolic syndrome, abdominal diameter and fat volume. Results: Of 243 patients, 33% demonstrated hepatic steatosis and 71% atherosclerotic vascular calcifications on CT. 28% met criteria for metabolic syndrome. Patients with metabolic syndrome had higher occurrence of hepatic steatosis, sagittal diameter ≥ 35 cm, visceral fat > 5000 cm3 and subcutaneous fat > 8300 cm3 (P < 0.05), but not vascular calcifications (P > 0.05). Conclusions: CT biomarkers of metabolic syndrome are commonly encountered in patients with acute diverticulitis. Recognizing and reporting these findings can guide towards further evaluation for metabolic syndrome. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to investigate the gut microbiome in progressive multiple sclerosis (MS) and how it relates to clinical disease.Methods: We sequenced the microbiota from healthy controls and relapsing-remitting MS (RRMS) and progressive MS patients and correlated the levels of bacteria with clinical features of disease, including Expanded Disability Status Scale (EDSS), quality of life, and brain magnetic resonance imaging lesions/atrophy. We colonized mice with MS-derived Akkermansia and induced experimental autoimmune encephalomyelitis (EAE).Results: Microbiota β-diversity differed between MS patients and controls but did not differ between RRMS and progressive MS or differ based on disease-modifying therapies. Disease status had the greatest effect on the microbiome β-diversity, followed by body mass index, race, and sex. In both progressive MS and RRMS, we found increased Clostridium bolteae, Ruthenibacterium lactatiformans, and Akkermansia and decreased Blautia wexlerae, Dorea formicigenerans, and Erysipelotrichaceae CCMM. Unique to progressive MS, we found elevated Enterobacteriaceae and Clostridium g24 FCEY and decreased Blautia and Agathobaculum. Several Clostridium species were associated with higher EDSS and fatigue scores. Contrary to the view that elevated Akkermansia in MS has a detrimental role, we found that Akkermansia was linked to lower disability, suggesting a beneficial role. Consistent with this, we found that Akkermansia isolated from MS patients ameliorated EAE, which was linked to a reduction in RORγt+ and IL-17-producing γδ T cells.Interpretation: Whereas some microbiota alterations are shared in relapsing and progressive MS, we identified unique bacteria associated with progressive MS and clinical measures of disease. Furthermore, elevated Akkermansia in MS may be a compensatory beneficial response in the MS microbiome. ANN NEUROL 2021;89:1195-1211. [ABSTRACT FROM AUTHOR]

During continental collision, large tracts of crust are mobilized along major shear zones. The metamorphic conditions at which these zones operate, the duration of thrusting, and the deformation processes that facilitated hundreds of km of tectonic transport are still unclear. In the Scandinavian Caledonides, the Lower Seve Nappe displays a main mylonitic foliation with thickness of ~1 km. This foliation is overprinted by a brittle‐to‐ductile deformation pattern localized in C‐ and C′‐type shear bands proximal to the tectonic contact with the underlying Särv Nappe. Thermobarometry of amphibolites and micaschists suggests a first high‐pressure stage at 400–500°C and 1–1.3 GPa recorded in mineral relics. The main mylonitic foliation developed under epidote amphibolite facies conditions along the retrograde path from 600°C and 1 GPa to 500°C and 0.5 GPa. Age dating of synkinematic titanite grains in the amphibolites indicates that this mylonitic fabric formed at around 417 ± 9 Ma but older ages spanning 460–430 Ma could represent earlier stages of mylonitization. The shear bands developed at lower metamorphic conditions of 300–400°C and ~0.3 GPa. In the micaschists, the recrystallized grain size of quartz decreases toward the shear bands. Monomineralic quartz layers are eventually dismembered to form polyphase aggregates deforming by dominant grain size sensitive creep accompanied by slip in muscovite and chlorite. Plagioclase zoning truncations suggest that the shear bands originated by fracturing followed by ductile deformation. The results suggest protracted and long‐lasting shearing under amphibolite to greenschist facies conditions during the juxtaposition, stacking, and exhumation of the Lower Seve Nappe. Key Points: In the Lower Seve Nappe 1 km‐thick mylonitic foliation formed at amphibolite facies conditions between ~460 and ~417 MaToward the base of the nappe the foliation is overprinted by a brittle‐to‐ductile fabric of greenschist facies conditions (~417 to 400 Ma)These fabrics formed due to protracted and long‐lasting shearing during the exhumation and assembly of the Seve Nappe Complex [ABSTRACT FROM AUTHOR]

When Thomas Nagel originally coined the expression "moral luck," he used the term "luck" to mean lack of control. This use was a matter of stipulation, as Nagel's target had little to do with luck itself, but the question of how control is related to moral responsibility. Since then, we have seen several analyses of the concept of luck itself, and recent contributors to the moral luck literature have often assumed that any serious contribution to the moral luck debate must begin with a robust concept of luck simpliciter. I argue here that this assumption is a mistake, on the basis of three reasons: the issue was originally conceived as an issue about responsibility and control, analyses of luck tend to distort and needlessly complicate what is at issue when shoehorned into the moral luck debate, and these analyses have very little (if anything) to contribute to the discussion. [ABSTRACT FROM AUTHOR]

Abstract: Melt onset (MO) on Arctic sea ice has been monitored using satellite‐based passive microwave (PMW) observations since 1979. In this work, surface air temperatures from the International Arctic Buoy Programme/Polar Exchange at the Sea Surface and NASA's Atmospheric Infrared Sounder are used to derive MO date estimates using three threshold methods which are then compared with a record of PMW‐based MO dates. Results from the PMW data indicate a shift toward increasingly early MO timing, with significant trends as large as −9.45 days/decade in the E. Siberian Sea and −5.69 days/decade for the entire Arctic, consistent with other studies highlighting the overall decline of Arctic sea ice. Results indicate that the surface air temperature‐based MO date estimates produced using a −1 °C threshold are ~11 days later than the PMW‐based MO date estimates Arctic wide. A statistical comparison of the Polar Exchange at the Sea Surface and PMW‐based MO dates indicate that despite the ~11‐day bias, correlations between the MO date time series are generally good (≥0.6) for most of the Arctic Ocean while the Atmospheric Infrared Sounder and PMW‐based MO dates are generally better at capturing the statistically similar long‐term trends in MO dates for the Arctic and several Arctic subregions. Application of these results can contribute to the development of new methods to monitor the sea ice melting state. [ABSTRACT FROM AUTHOR]

Background and Purpose: Enlarged perivascular spaces (EPVSs) have been associated with relapses and brain atrophy in multiple sclerosis (MS). We investigated the association of EPVS with clinical and MRI features of disease worsening in a well-characterized cohort of relapsing-remitting MS patients prospectively followed for up to 10 years.Methods: Baseline EPVSs were scored on 1.5T MRI in 30 converters to moderate-severe disability, and 30 nonconverters matched for baseline characteristics.Results: EPVS scores were not significantly different between converters and nonconverters, nor associated with accrual of lesions or brain atrophy.Conclusions: Our preliminary findings from a relatively small study sample argue against a potential use of EPVS as early indicator of risk for disease worsening in relapsing-remitting MS patients in a clinical setting. Although the small sample size and clinical 1.5T MRI may have limited our ability to detect a significant effect, we provided estimates of the association of EPVS with clinical and MRI indicators of disease worsening in a well-characterized cohort of MS patients. [ABSTRACT FROM AUTHOR]

Three Latin mistranslations of Josephus' Jewish War I.61 between the fourth and the seventh centuries ce reflect the expansion of a series of charitable institutions, called xenodocheia and nosokomeia, around the Mediterranean in late antiquity and the early medieval period. In the late fourth century, authors known as pseudo-Rufinus and pseudo-Hegesippus independently mistranslated Josephus' report that the Hasmonean ruler John Hyrcanus hired mercenary troops at the conclusion of a Seleucid siege of Jerusalem. In their confusion, these authors both interpreted this as a charitable action and pseudo-Hegesippus anachronistically imported the xenodocheion into the Hellenistic period. In the early seventh century Isidore of Seville expanded upon pseudo-Hegesippus' mistake to transform the hiring of mercenaries into the genesis of both the xenodocheion and the nosokomeion. Isidore's inclusion of these institutions in his Etymologiae indicated their ubiquity and popularity by the seventh century, while for later writers his work canonized the mistaken origin. [ABSTRACT FROM AUTHOR]

Field data from an orogenic foreland and an orogenic belt (the Mesozoic rocks of southern England and the Umbria-Marche Apennines of Italy respectively) indicate the following. Firstly, stress evolution during the tectonic cycle, between maximum compressive stress (σ1) being vertical during extension and least compressive stress (σ3) being vertical during contraction, can involve phases when the intermediate compressive stress (σ2) is vertical, promoting strike-slip deformation. Secondly, variations in the relative magnitudes of the stress axes are caused by variations in overburden and tectonic forces. Thirdly, overpressure can develop because of compaction during burial, and, as overburden is reduced during uplift and erosion, the vertical stress (σV) reduces but fluid pressure ( Pf) remains approximately constant. Brittle deformation, including transient strike-slip faults, reverse-reactivated normal faults and normal-reactivated thrusts, is preferentially developed in overpressured areas because high Pf promotes faulting. [ABSTRACT FROM AUTHOR]

The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular andmolecular mechanisms that underlie neural-cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados. [ABSTRACT FROM AUTHOR]

The autoimmune regulator (Aire) was initially identified as the gene causing multiorgan system autoimmunity in humans, and deletion of this gene in mice also resulted in organ-specific autoimmunity. Aire regulates the expression of tissue-specific antigens (TSAs) in medullary thymic epithelial cells (mTECs), which play a critical role in the negative selection of autoreactive T cells and the generation of regulatory T cells. More recently, the role of Aire in the development of mTECs have helped elucidate its ability to present the spectrum of TSAs needed to prevent autoimmunity. Molecular characterization of the functional domains of Aire has revealed multiple binding partners that assist Aire's function in altering gene transcription and chromatin remodeling. These recent advances have further highlighted the importance of Aire in central tolerance. [ABSTRACT FROM AUTHOR]

Eukaryotic cell-free protein synthesis (CFPS) is limited by the dependence on costly high-energy phosphate compounds and exogenous enzymes to power protein synthesis ( e.g. , creatine phosphate and creatine kinase, CrP/CrK). Here, we report the ability to use glucose as a secondary energy substrate to regenerate ATP in a Saccharomyces cerevisiae crude extract CFPS platform. We observed synthesis of 3.64 ± 0.35 μg mL −1 active luciferase in batch reactions with 16 mM glucose and 25 mM phosphate, resulting in a 16% increase in relative protein yield (μg protein/$ reagents) compared to the CrP/CrK system. Our demonstration provides the foundation for development of cost-effective eukaryotic CFPS platforms. [ABSTRACT FROM AUTHOR]

Copyright of Conservation Biology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An introduction to the special section of "Conservation Biology," focusing on conserving nature's stage, is presented.

Conservationists need methods to conserve biological diversity while allowing species and communities to rearrange in response to a changing climate. We developed and tested such a method for northeastern North America that we based on physical features associated with ecological diversity and site resilience to climate change. We comprehensively mapped 30 distinct geophysical settings based on geology and elevation. Within each geophysical setting, we identified sites that were both connected by natural cover and that had relatively more microclimates indicated by diverse topography and elevation gradients. We did this by scoring every 405 ha hexagon in the region for these two characteristics and selecting those that scored >SD 0.5 above the mean combined score for each setting. We hypothesized that these high-scoring sites had the greatest resilience to climate change, and we compared them with sites selected by The Nature Conservancy for their high-quality rare species populations and natural community occurrences. High-scoring sites captured significantly more of the biodiversity sites than expected by chance (p < 0.0001): 75% of the 414 target species, 49% of the 4592 target species locations, and 53% of the 2170 target community locations. Calcareous bedrock, coarse sand, and fine silt settings scored markedly lower for estimated resilience and had low levels of permanent land protection (average 7%). Because our method identifies-for every geophysical setting-sites that are the most likely to retain species and functions longer under a changing climate, it reveals natural strongholds for future conservation that would also capture substantial existing biodiversity and correct the bias in current secured lands. [ABSTRACT FROM AUTHOR]

Medullary thymic epithelial cells (m TECs) facilitate the deletion of developing self-reactive T cells by displaying a diverse repertoire of tissue-specific antigens, a process which largely depends on the expression of the autoimmune regulator (Aire) gene. Mature micro RNAs (mi RNAs) that regulate gene expression post-transcriptionally are generated in a multistep process. The microprocessor complex, including DGCR8, cleaves canonical mi RNAs, but alternative DGCR8-independent mi RNA biogenesis pathways exist as well. In order to study the role of canonical mi RNAs in thymic epithelial cells ( TECs), we ablated Dgcr8 using a FoxN1-Cre transgene. We report that DGCR8-deficient TECs are unable to maintain proper thymic architecture and exhibit a dramatic loss of thymic cellularity. Importantly, DGCR8-deficient TECs develop a severe loss of Aire+ m TECs. Using a novel immunization approach to amplify and detect self-reactive T cells within a polyclonal TCR repertoire, we demonstrate a link between the loss of Aire expression in DGCR8-deficient TECs and the breakdown of negative selection in the thymus. Thus, DGCR8 and canonical mi RNAs are important in TECs for supporting central tolerance. [ABSTRACT FROM AUTHOR]

ABSTRACT Precise regulation of bone resorption is critical for skeletal homeostasis. We report a 32-year-old man with a panostotic expansile bone disease and a massive hemorrhagic mandibular tumor. Originally from Mexico, he was deaf at birth and became bow-legged during childhood. There was no family history of skeletal disease. Puberty occurred normally, but during adolescence he experienced difficulty straightening his limbs, sustained multiple fractures, and developed a bony tumor on his chin. By age 18 years, all limbs were misshapen. The mandibular mass grew and protruded from the oral cavity, extending to the level of the lower ribs. Other bony defects included a similar maxillary mass and serpentine limbs. Upon referral at age 27 years, biochemical studies showed serum alkaline phosphatase of 1760 U/L (Nl: 29-111) and other elevated bone turnover markers. Radiography of the limbs showed medullary expansion and cortical thinning with severe bowing. Although the jaw tumors were initially deemed inoperable, mandibular mass excision and staged partial maxillectomy were eventually performed. Tumor histopathology showed curvilinear trabeculae of woven bone on a background of hypocellular fibrous tissue. Fibrous dysplasia of bone was suspected, but there was no mutation in codon 201 of GNAS in samples from blood or tumor. His clinical and radiographic findings, elevated serum markers, and disorganized bone morphology suggested amplified receptor activator of NF-κB (RANK) signaling, even though his disorder differed from conditions with known constitutive activation of RANK signaling (eg, familial expansile osteolysis). We found a unique 12-base pair duplication in the signal peptide of TNFRSF11A, the gene that encodes RANK. No exon or splice site mutations were found in the genes encoding RANK ligand or osteoprotegerin. Alendronate followed by pamidronate therapies substantially decreased his serum alkaline phosphatase activity. This unique patient expands the phenotypes and genetic basis of the mendelian disorders of RANK signaling activation. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

This article examines transracial/cultural placement of children for fostering and adoption as discussed within the context of expert evidence in applications for permanent placement. Transracial/cultural placement raises the issues of attachment and identity. The undesirability of the child being raised apart from the natural biological family's culture and ethnicity, the undesirability of disrupting secure attachments, and the significance of birth parents' parenting capacity are placed in stark contrast. The benefits of contact in reducing sense of abandonment and loss of parental care and culture of origin are also examined. The best practice for transracial placements depends upon the cultural prominence determined to be in the child's best interests. Placements favored are those where attachment is secure and parenting capacity is judged superior. The child's best interests may generally be considered by the courts in the short to medium term to be enhanced by placement with the person(s) with whom the child has the strongest attachments. The longer term issue is more problematic and not determined with confidence. Keypoints Cultural preservation of children's birth culture in out-of-home placements for fostering and adoption, Placement of children-issues for attachment and identity, Best practice and cultural dominance in placement where ethnically and racially diverse environments of origin of placement and child, Best interests principle Considerations for secure attachment and parenting capacity [ABSTRACT FROM AUTHOR]

Staphylococcus aureus encodes the specialized ESAT-6 Secretion System ( ESS). EsxA and EsxB are secreted by the ESS pathway, and share sequence features of ESAT-6 and CFP-10 of the Type VII Secretion System ( T7 SS) of Mycobacterium tuberculosis. Unlike ESAT-6 and CFP-10, EsxA and EsxB do not interact. Instead, EsxB associates with a novel substrate, EsxD, and EsxA dimerizes with itself or EsxC ( EsaC). Unlike EsxA and EsxB, EsxC and EsxD do not share obvious sequence features of WXG100 proteins nor PE/ PPE and Esp families of proteins, all of which belong to the pfam EsxAB clan of mycobacterial T7 SS. EsxD carries the C-terminal motif YxxxD/ E that has been proposed to target T7 substrates for secretion in mycobacteria. Here, we find that deletion, but not amino acid substitutions, in this motif prevent secretion of EsxA and EsxC but not EsxB or EsxD. This is unlike the genetic inactivation of esxA , esxB , esxC or esxD that leads to loss of secretion of all four substrates. Thus, substrate secretion can be uncoupled by deleting the last six amino acids of EsxD. The physical association of EsxC and EsxD with canonical WXG100 proteins suggests that these proteins belong to the EsxAB clan. [ABSTRACT FROM AUTHOR]

SugarBindDB lists pathogen and biotoxin lectins and their carbohydrate ligands in a searchable format. Information is collected from articles published in peer-reviewed scientific journals. Help files guide the user through the search process and provide a review of structures and names of sugars that appear in human oligosaccharides. Glycans are written in the condensed form of the carbohydrate nomenclature system developed by the International Union of Pure and Applied Chemistry (IUPAC). Since its online publication by The MITRE Corporation in 2005, the database has served as a resource for research on the glycobiology of infectious disease. SugarBindDB is currently hosted by the Swiss Institute of Bioinformatics on the ExPASy server and will be enhanced and linked to related resources as part of the wider UniCarbKB initiative. Enhancements will include the option to display glycans in a variety of formats, including modified 2D condensed IUPAC and symbolic nomenclature. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction Elastic band ( EB) training is a common form of resistance training used by the elderly, individuals with joint problems or those recovering from injury. EB training performed at low intensities by these populations may have little effect on muscle hypertrophy. However, when combined with blood flow restriction ( BFR), low-intensity EB resistance training may result in muscle hypertrophy. Methods Postmenopausal women (61 ± 5 years) were assigned to a moderate-to-high-intensity EB group ( MH, n = 8) or a low-intensity EB group combined with BFR ( LI- BFR, n = 6). Each group performed seated chest press, seated row and seated shoulder press with EB three times a week for eight weeks. EB colours progressed in each group by having participants maintain a rating of 7-9 on the OMNI Resistance for active muscle ( OMNI- RES AM) scale (0-10) throughout training. In the LI- BFR group, BFR pressure progressed during the first 4 weeks of training (80-120 mmHg), after which EB colours were progressed. Results 1-repetition maximum increased for chest press ( P = 0·01), shoulder press ( P = 0·02) and seated row ( P = 0·01), but no differences were found between groups. Only pectoralis major muscle thickness in the upper body increased ( P = 0·04). A trend was found for an increase in total bone-free lean body mass ( P = 0·055). Conclusions The main findings of this study were that moderate-to-high-intensity EB training and low-intensity EB training with BFR resulted in similar increases in strength, total bone-free lean body mass and muscle thickness. [ABSTRACT FROM AUTHOR]

Objectives Dermatophytes, belonging to genera including Trichophyton, Epidermophyton, and Microsporum, are the causative agents of superficial fungal infections, prevalences of which are estimated to be as high as 25% in the worldwide population. This study evaluated the activity of topical formulations of NVC-422 (sodium 2-[dichloroamino]-2-methylpropane-1-sulfonate), the lead compound in a new class of antimicrobials that consist of broad-spectrum, fast-acting, nonantibiotic antimicrobial molecules based on the endogenously produced N-chlorotaurines. Methods The antifungal efficacy of NVC-422 was investigated using a guinea pig model of infection with Trichophyton mentagrophytes. Infected guinea pigs were randomly assigned to four treatment and two control groups. The efficacy of the treatments was assessed clinically and mycologically at 72 hours after the final topical dose. Results The test compound 2% NVC-422 in 1% Noveon Gel demonstrated the highest level of clinical efficacy. Outcomes of treatment with all other test compounds differed significantly from outcomes in the untreated control group ( P = 0.003, P = 0.029, P = 0.012, and P < 0.0001, respectively). Fungal elements were detectable in skin sections from untreated guinea pigs but not in skin sections obtained from any of the treatment groups. Conclusions Evaluation of the efficacy of NVC-422 in the treatment of dermatophytosis using an experimental guinea pig model showed that this compound possesses potent antifungal efficacy as measured by mycological and clinical endpoints. The highest degree of clinical and mycological efficacy was demonstrated by 2% NVC-422 in 1% Noveon Gel. These data show that NVC-422 has potent antifungal activity in vivo. Clinical evaluation of NVC-422 in the treatment of superficial infections caused by dermatophytes, including onychomycosis, is warranted. [ABSTRACT FROM AUTHOR]

. Purpose: N-chlorotaurine (NCT) and its analogues N-monochloro-2,2-dimethyltaurine (NVC-612) and N-dichloro-2,2-dimethyltaurine (NVC-422) are new anti-infectives for topical treatment for conjunctivitis. The aim of this study was to show that these compounds are safe in an EpiOcular model and effective in corneas infected ex vivo. Methods: Corneal buttons were excised from porcine eyes. In 183 of the 229 corneas, erosion and artificial superficial stromal incision were induced. They were bathed in suspensions of Pseudomonas aeruginosa or Staphylococcus aureus for 24 hr at 37°C and incubated in solutions of the test substances at 37°C and pH 7.1. Subsequently, they were subjected to histology ( n = 20) or homogenized followed by quantitative bacterial cultures ( n = 209). Ocular irritation was tested using the EpiOcular™ tissue system (MatTek Corporation). Results: Bacterial accumulations were detected histologically both on the corneal surface and also in the anterior third of the stroma of incised corneal buttons. All three test compounds at a concentration of 55 m m (equals 1% NCT) reduced the bacterial counts of P. aeruginosa and S. aureus by approximately 5 log10 after 60- and 120-min incubation, respectively. Significant killing was observed as early as after 5-min incubation. Also intrastromal bacteria were inactivated. In the EpiOcular™ tissue model, NCT, NVC-422 and NVC-612 had no or very low potential to irritate corneal tissue. Conclusion: N-chlorotaurine, NVC-422 and NVC-612 are non-irritating in cornea and kill P. aeruginosa and S. aureus, even following penetration into the deeper corneal stromal layers. [ABSTRACT FROM AUTHOR]

Bio-oil from the hydrothermal liquefaction of Eastern White Pine ( Pinus strobus L.) sawdust was methylolated with formaldehyde in the presence of sodium hydroxide. The obtained methylolated bio-oil (MB) was used to synthesize methylolated bio-oil-phenol formaldehyde (MBPF) resol resins with a phenol substitution ratio of up to 75 wt %. All of the resins were used as wood adhesives for the production of a three-layered plywood. The MBPF resol resins were comprehensively characterized for their physical, chemical, thermal, and mechanical properties (e.g., viscosity, nonvolatile content, shelf life, free formaldehyde level, molecular weight and distribution, curing temperature, bonding strength) when used as plywood adhesives. All of the MBPF resins contained similar nonvolatile contents as the reference pure phenol formaldehyde (PF) resin but had higher viscosities and shorter shelf lives, depending on the amount of MB in the MBPF. All of the MBPF resins displayed a lower curing temperature than the reference PF resin, with the main curing peak around 140°C, which was similar to that of the pure PF resin. According to thermogravimetric analysis, the methylolation treatment of bio-oil improved the thermal stability of the MBPF resins compared to the bio-oil-PF resol resins, which used untreated bio-oil. The dry/wet bonding strengths of the plywood specimens glued with the MBPF resol resins with up to 60 wt % phenol substitution exceeded or were comparable to those of the conventional PF resol resin. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]

β-Adrenergic receptor (AR) blockers provide substantial clinical benefits, including improving overall survival and left ventricular (LV) function following myocardial infarction (MI), though the mechanisms remain incompletely defined. The transverse-tubule (T- tubule) system of ventricular myocytes is an important determinant of cardiac excitation-contraction function. T-tubule remodeling occurs early during LV failure. We hypothesized that β-AR blockers prevent T-tubule remodeling and thereby provide therapeutic benefits. A murine model of MI was utilized to examine the effect of β-AR blockers on T-tubule remodeling following LV MI. We applied the in situ imaging of T-tubule structure from Langendorff-perfused intact hearts with laser scanning confocal microscopy. We found that MI caused remark- able T-tubule remodeling near the infarction border zone and moderate LV remodeling remote from the MI. Metoprolol and carvedilol administered 6 d after MI for 4 wk each increased the T-tubule integrity at the remote and border zones. At the molecular level, both β-AR blockers restored border and remote zone expression of junctophilin-2 (JP-2), which is involved in T-tubule organization and formation of the T-tubule/sarcoplasmic reticulum junctions. In contrast, β-AR blockers had no significant effects on caveolin-3 expression. In summary, our data show that β-AR antagonists can protect against T-tubule remodeling after MI, suggesting a novel therapeutic mechanism of action for this drug class. Preservation of JP-2 expression may contribute to the beneficial effects of metoprolol and carvedilol on T-tubule remodeling. [ABSTRACT FROM AUTHOR]

Phenolic bio-oil produced by the direct liquefaction of Eastern white pine ( Pinus Strobus L.) sawdust in a hot-compressed ethanol-water (1:1 w/w) medium at 300 °C was used to partially substitute for phenol in the synthesis of bio-oil-phenol-formaldehyde (BPF) resol resins. Bio-based resol resins with high levels of phenol substitution (up to 75 wt%) could be used as plywood adhesives because of the low molecular weights found for the phenolic bio-oil (weight-average molecular weight = 1072 g/mol, number-average molecular weight = 342 g/mol). The properties of the BPF resol resins were analyzed by differential scanning calorimetry, Fourier transform infrared spectroscopy, gel permeation chromatography, and thermogravimetric analysis. All of the experimental BPF resins possessed broad molecular weight distributions but had similar chemical/thermal properties compared to a conventional phenol-formaldehyde (PF) resol resin reference (or 0 wt % BPF resin). The BPFs exhibited the typical properties of a thermosetting PF resin, for example, an exothermic curing temperature of 140-150°C and an acceptable residual carbon yield of 48-72 wt % nonvolatile content at 700°C. The experimental BPFs were applied as adhesives in the assembly of plywood, and then, the dry/wet tensile strengths were evaluated. The tensile strengths of the dry plywood samples bonded with the BPF resins up to a high ratio value of 75 wt % bio-oil exceeded or were comparable to that of the conventional pure PF resin adhesive. All of the BPF-resin-bonded plywood samples gave wet tensile strengths comparable to those of the conventional PF adhesive. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

Novel plate-type heat exchangers (HXs) with high-power densities are proposed based on novel integrated flow channel designs. Net-shape plates were achieved by the molding of powder mixtures to wood-based composites (WBC's). HX stacks are built by plate-to-plate joining followed by pyrolysis and silicon melt infiltration. The C/SiSiC provided with PyC-SiC coating was gas-tight to helium up to 5.5 MPa. Corrosion tests with coupons were performed using a ternary eutectic fluoride salt (FLiNaK) as the intermediate heat transfer fluid. While SiC is vulnerable to corrosion by the salt, the coating offers a high degree of protection to the ceramic substrate. [ABSTRACT FROM AUTHOR]

The negative selection of self-reactive thymocytes depends on the expression of tissue-specific antigens by medullary thymic epithelial cells. The autoimmune regulator (Aire) protein plays an important role in turning on these antigens, and the absence of even one Aire-induced tissue-specific antigen in the thymus can lead to autoimmunity in the antigen-expressing target organ. Recently, Aire protein has been detected in peripheral lymphoid organs, suggesting that peripheral Aire plays a complementary role here. In these peripheral sites, Aire was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus. Furthermore, transgenic antigen expression in extrathymic Aire-expressing cells (eTACs) can mediate deletional tolerance, but the immunological relevance of Aire-dependent, endogenous tissue-specific antigens remains to be determined. [ABSTRACT FROM AUTHOR]