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Abstract White-rot fungi are efficient organisms for the mineralization of lignin and polysaccharides into CO2 and H2O. Despite their biotechnological potential, WRF metabolism remains underexplored. Building on recent findings regarding the utilization of lignin-related aromatic compounds as carbon sources by WRF, we aimed to gain further insights into these catabolic processes. For this purpose, Trametes versicolor and Gelatoporia subvermispora were incubated in varying conditions – in static and agitation modes and different antioxidant levels – during the conversion of 4-hydroxybenzoic acid (a lignin-related compound) and cellobiose. Their metabolic responses were assessed via transcriptomics, proteomics, lipidomics, metabolomics, and microscopy analyses. These analyses reveal the significant impact of cultivation conditions on sugar and aromatic catabolic pathways, as well as lipid composition of the fungal mycelia. Additionally, this study identifies biosynthetic pathways for the production of extracellular fatty acids and phenylpropanoids – both products with relevance in biotechnological applications – and provides insights into carbon fate in nature.

In September 2020, the US National Institutes of Health (NIH) allocated $12 million to support engagement with historically marginalized communities hardest hit by COVID-19. The award was designed to mobilize community-engagement in pandemic response, and to support partnerships as part of the NIH Community Engagement Alliance (CEAL) Against COVID-19 Disparities. All aspects of the award were fast-tracked, and NIH utilized a ‘more flexible’ funding mechanism (OTA) to facilitate swift distribution of funds. In this paper, we draw upon an analysis of findings from a 2021 survey conducted with 11 California CEAL sites representing urban and rural settings, private and public universities, and established and new community partners and qualitative analysis of 2020–2022 site-wide meeting minutes. We describe the challenges posed at the federal (e.g. NIH funding), university, and community–university partnership levels as well as opportunities and creative workarounds. Challenges include delays in subcontracts and payments to community partners that undermined trust and reproduced unequal and hierarchical power relationships. We build upon our findings and collective experience to propose a framework for decolonized fiscal relationships between universities and community partners which contains key recommendations for funders, universities, and community partners.

IntroductionThe aim of the current study was to test normobaric 100% oxygen (NBO) (PiO2 = 713 mmHg) for stem cell mobilization and cytokine modulation. Although current oxygen therapy (PiO2 = 1,473–2,233 mmHg) is well known to mobilize stem cells and modulate cytokine, little is known about NBO and its place on the low dose stimulation phase of the hormetic dose curve of oxygen. We asked the question, will NBO mobilize stem cells and modulate cytokines. A positive outcome presents the potential to create and refine oxygen treatment protocols, expand access, and optimize patient outcomes.MethodsHealthy 30–35-year-old volunteers were exposed to 100% normobaric oxygen for 60 min, M-F, for 10 exposures over 2 weeks. Venous blood samples were collected at four time points: 1) prior to the first exposure (serving as the control for each subject), 2) immediately after the first exposure (to measure the acute effect), 3) immediately before the ninth exposure (to measure the chronic effect), and 4) three days after the final exposure (to assess durability). Blinded scientists used flow cytometry to gate and quantify the Stem Progenitor Cells (SPCs).ResultsCD45dim/CD34+/CD133+ and CD45+/CD34+/CD133+ were significantly mobilized following nine daily one-hour exposures to normobaric 100% oxygen. Conversely CD45−/CD34+/CD133+, CD45-/CD34+/CD133− and CD45−/CD34−/CD133+ phenotypes were downregulated suggesting differentiation into more mature phenotypes. The CD133+ phenotype exhibited a maturing from CD45− to CD45dim stem cells. CD45−/CD34, CD45−/CD31 and CD45−/CD105 were downregulated with no changes in related CD45dim and CD45+ phenotypes. The cytokines “macrophage migration inhibitory factor” (MIF) and “a proliferation inducing ligand” (APRIL) were significantly upregulated.ConclusionThis study demonstrates that 100% normobaric oxygen mobilizes stem cells and upregulates the expression of the inflammatory cytokines marking a new point on the low dose stimulation phase of the hormetic dose curve of oxygen.

Abstract The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30–60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections.

Seed storage life in tropical areas is shortened by high humidity and temperature and the general inaccessibility to dehumidifying and refrigeration systems, resulting in rapid decreases in seed viability in storage as well as a high incidence of fungal and insect infestations. The dry chain, based on rapid and deep drying of seeds after harvest followed by packaging in moisture-proof containers, has been proposed as an effective method to maintain seed quality during medium-term storage in humid climates, even without refrigeration. In addition, seed drying with zeolite drying beads can be more effective and economical than sun or heated-air drying under these warm, humid conditions. In this paper, we review recent published literature regarding the dry chain, considering different crop species, storage environments and seed traits. In addition, we provide new original data on the application of dry chain methods and their implementation at larger scales in South Asia, Latin America and Pacific Island Countries. The clear conclusion is that the combination of reusable drying beads and waterproof storage containers enables the implementation of the dry chain in tropical climates, enhancing seed viability and quality in storage of many crop species. The dry chain approach can therefore significantly enhance seed security for farmers in many tropical countries. Finally, we propose actions and strategies that could guide further scaling-up implementation of this technology.

Abstract Background Accurate measurement of disease associated with endemic bacterial agents in pig populations is challenging due to their commensal ecology, the lack of disease-specific antemortem diagnostic tests, and the polymicrobial nature of swine diagnostic cases. The main objective of this retrospective study was to estimate temporal patterns of agent detection and disease diagnosis for five endemic bacteria that can cause systemic disease in porcine tissue specimens submitted to the Iowa State University Veterinary Diagnostic Laboratory (ISU VDL) from 2017 to 2022. The study also explored the diagnostic value of specific tissue specimens for disease diagnosis, estimated the frequency of polymicrobial diagnosis, and evaluated the association between phase of pig production and disease diagnosis. Results S. suis and G. parasuis bronchopneumonia increased on average 6 and 4.3%, while S. suis endocarditis increased by 23% per year, respectively. M. hyorhinis and A. suis associated serositis increased yearly by 4.2 and 12.8%, respectively. A significant upward trend in M. hyorhinis arthritis cases was also observed. In contrast, M. hyosynoviae arthritis cases decreased by 33% average/year. Investigation into the diagnostic value of tissues showed that lungs were the most frequently submitted sample, However, the use of lung for systemic disease diagnosis requires caution due to the commensal nature of these agents in the respiratory system, compared to systemic sites that diagnosticians typically target. This study also explored associations between phase of production and specific diseases caused by each agent, showcasing the role of S. suis arthritis in suckling pigs, meningitis in early nursery and endocarditis in growing pigs, and the role of G. parasuis, A. suis, M. hyorhinis and M. hyosynoviae disease mainly in post-weaning phases. Finally, this study highlighted the high frequency of co-detection and -disease diagnosis with other infectious etiologies, such as PRRSV and IAV, demonstrating that to minimize the health impact of these endemic bacterial agents it is imperative to establish effective viral control programs. Conclusions Results from this retrospective study demonstrated significant increases in disease diagnosis for S. suis, G. parasuis, M. hyorhinis, and A. suis, and a significant decrease in detection and disease diagnosis of M. hyosynoviae. High frequencies of interactions between these endemic agents and with viral pathogens was also demonstrated. Consequently, improved control programs are needed to mitigate the adverse effect of these endemic bacterial agents on swine health and wellbeing. This includes improving diagnostic procedures, developing more effective vaccine products, fine-tuning antimicrobial approaches, and managing viral co-infections.

Abstract Background Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment. Methods To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics modalities. Results Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection. Conclusion This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

Abstract Background A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity. Methods This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at high risk, including those with comorbidities (hypertension, diabetes, obesity, reactive airway disease, smokers), racial and ethnic minorities, elderly, teachers, police, restaurant wait-staff, delivery personnel, health care workers who are defined as personnel working in a healthcare setting, at a hospital, medical center or clinic (veterinary, dental, ophthalmology), and first responders (paramedics, firefighters, or law enforcement), will be randomly assigned to two treatment groups. The treatment groups will receive intradermal administration of BCG vaccine or placebo (saline) with groups at a 1:1 ratio. Individuals will be tracked for evidence of SARS-CoV-2 infection and severity as well as obtaining whole blood to track immunological markers, and a sub-study will include cognitive function and brain imaging. The majority of individuals will be followed for 6 months, with an option to extend for another 6 months, and the cognitive sub-study duration is 2 years. We will plot Kaplan-Meier curves that will be plotted comparing groups and hazard ratios and p-values reported using Cox proportional hazard models. Discussion It is expected this trial will allow evaluation of the effects of BCG vaccination at a population level in high-risk healthcare individuals through a mitigated clinical course of SARS-CoV-2 infection and inform policy making during the ongoing epidemic. Trial registration ClinicalTrials.gov NCT04348370. Registered on April 16, 2020.

Aggregated diagnostic data collected over time from swine production systems is an important data source to investigate swine productivity and health, especially when combined with records concerning the pre-weaning and post-weaning phases of production. The combination of multiple data streams collected over the lifetime of the pigs is the essence of the whole-herd epidemiological investigation. This approach is particularly valuable for investigating the multifaceted and ever-changing factors contributing to wean-to-finish (W2F) swine mortality. The objective of this study was to use a retrospective dataset (“master table”) containing information on 1,742 groups of pigs marketed over time to identify the major risk factors associated with W2F mortality. The master table was built by combining historical breed-to-market performance and health data with disease diagnostic records (Dx Codes) from marketed groups of growing pigs. After building the master table, univariate analyses were conducted to screen for risk factors to be included in the initial multivariable model. After a stepwise backward model selection approach, 5 variables and 2 interactions remained in the final model. Notably, the diagnosis variable significantly associated with W2F mortality was porcine reproductive and respiratory syndrome virus (PRRSV). Closeouts with clinical signs suggestive of Salmonella spp. or Escherichia coli infection were also associated with higher W2F mortality. Source sow farm factors that remained significantly associated with W2F mortality were the sow farm PRRS status, average weaning age, and the average pre-weaning mortality. After testing for the possible interactions in the final model, two interactions were significantly associated with wean-to-finish pig mortality: (1) sow farm PRRS status and a laboratory diagnosis of PRRSV and (2) average weaning age and a laboratory diagnosis of PRRS. Closeouts originating from PRRS epidemic or PRRS negative sow farms, when diagnosed with PRRS in the growing phase, had the highest W2F mortality rates. Likewise, PRRS diagnosis in the growing phase was an important factor in mortality, regardless of the average weaning age of the closeouts. Overall, this study demonstrated the utility of a whole-herd approach when analyzing diagnostic information along with breeding-to-market productivity and health information, to measure the major risk factors associated with W2F mortality in specified time frames and pig populations.

Abstract Background Microbiomes contribute to multiple ecosystem services by transforming organic matter in the soil. Extreme shifts in the environment, such as drying-rewetting cycles during drought, can impact the microbial metabolism of organic matter by altering microbial physiology and function. These physiological responses are mediated in part by lipids that are responsible for regulating interactions between cells and the environment. Despite this critical role in regulating the microbial response to stress, little is known about microbial lipids and metabolites in the soil or how they influence phenotypes that are expressed under drying-rewetting cycles. To address this knowledge gap, we conducted a soil incubation experiment to simulate soil drying during a summer drought of an arid grassland, then measured the response of the soil lipidome and metabolome during the first 3 h after wet-up. Results Reduced nutrient access during soil drying incurred a replacement of membrane phospholipids, resulting in a diminished abundance of multiple phosphorus-rich membrane lipids. The hot and dry conditions increased the prevalence of sphingolipids and lipids containing long-chain polyunsaturated fatty acids, both of which are associated with heat and osmotic stress-mitigating properties in fungi. This novel finding suggests that lipids commonly present in eukaryotes such as fungi may play a significant role in supporting community resilience displayed by arid land soil microbiomes during drought. As early as 10 min after rewetting dry soil, distinct changes were observed in several lipids that had bacterial signatures including a rapid increase in the abundance of glycerophospholipids with saturated and short fatty acid chains, prototypical of bacterial membrane lipids. Polar metabolites including disaccharides, nucleic acids, organic acids, inositols, and amino acids also increased in abundance upon rewetting. This rapid metabolic reactivation and growth after rewetting coincided with an increase in the relative abundance of firmicutes, suggesting that members of this phylum were positively impacted by rewetting. Conclusions Our study revealed specific changes in lipids and metabolites that are indicative of stress adaptation, substrate use, and cellular recovery during soil drying and subsequent rewetting. The drought-induced nutrient limitation was reflected in the lipidome and polar metabolome, both of which rapidly shifted (within hours) upon rewet. Reduced nutrient access in dry soil caused the replacement of glycerophospholipids with phosphorus-free lipids and impeded resource-expensive osmolyte accumulation. Elevated levels of ceramides and lipids with long-chain polyunsaturated fatty acids in dry soil suggest that lipids likely play an important role in the drought tolerance of microbial taxa capable of synthesizing these lipids. An increasing abundance of bacterial glycerophospholipids and triacylglycerols with fatty acids typical of bacteria and polar metabolites suggest a metabolic recovery in representative bacteria once the environmental conditions are conducive for growth. These results underscore the importance of the soil lipidome as a robust indicator of microbial community responses, especially at the short time scales of cell-environment reactions. Video Abstract

Abstract Climate change is globally affecting rainfall patterns, necessitating the improvement of drought tolerance in crops. Sorghum bicolor is a relatively drought‐tolerant cereal. Functional stay‐green sorghum genotypes can maintain green leaf area and efficient grain filling during terminal post‐flowering water deprivation, a period of ~10 weeks. To obtain molecular insights into these characteristics, two drought‐tolerant genotypes, BTx642 and RTx430, were grown in replicated control and terminal post‐flowering drought field plots in California's Central Valley. Photosynthetic, photoprotective, and water dynamics traits were quantified and correlated with metabolomic data collected from leaves, stems, and roots at multiple timepoints during control and drought conditions. Physiological and metabolomic data were then compared to longitudinal RNA sequencing data collected from these two genotypes. The unique metabolic and transcriptomic response to post‐flowering drought in sorghum supports a role for the metabolite galactinol in controlling photosynthetic activity through regulating stomatal closure in post‐flowering drought. Additionally, in the functional stay‐green genotype BTx642, photoprotective responses were specifically induced in post‐flowering drought, supporting a role for photoprotection in the molecular response associated with the functional stay‐green trait. From these insights, new pathways are identified that can be targeted to maximize yields under growth conditions with limited water.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study, TM9 was effective against three murine coronavirus strains, demonstrating that the therapeutic window is large enough to allow the use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber, and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from the liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

IntroductionHyperbaric air (HBA) was first used pharmaceutically in 1662 to treat lung disease. Extensive use in Europe and North America followed throughout the 19th century to treat pulmonary and neurological disorders. HBA reached its zenith in the early 20th century when cyanotic, moribund “Spanish flu pandemic” patients turned normal color and regained consciousness within minutes after HBA treatment. Since that time the 78% Nitrogen fraction in HBA has been completely displaced by 100% oxygen to create the modern pharmaceutical hyperbaric oxygen therapy (HBOT), a powerful treatment that is FDA approved for multiple indications. Current belief purports oxygen as the active element mobilizing stem progenitor cells (SPCs) in HBOT, but hyperbaric air, which increases tensions of both oxygen and nitrogen, has been untested until now. In this study we test HBA for SPC mobilization, cytokine and chemokine expression, and complete blood count.MethodsTen 34–35-year-old healthy volunteers were exposed to 1.27ATA (4 psig/965 mmHg) room air for 90 min, M-F, for 10 exposures over 2-weeks. Venous blood samples were taken: (1) prior to the first exposure (served as the control for each subject), (2) directly after the first exposure (to measure the acute effect), (3) immediately prior to the ninth exposure (to measure the chronic effect), and (4) 3 days after the completion of tenth/final exposure (to assess durability). SPCs were gated by blinded scientists using Flow Cytometry.ResultsSPCs (CD45dim/CD34+/CD133-) were mobilized by nearly two-fold following 9 exposures (p = 0.02) increasing to three-fold 72-h post completion of the final (10th) exposure (p = 0.008) confirming durability.DiscussionThis research demonstrates that SPCs are mobilized, and cytokines are modulated by hyperbaric air. HBA likely is a therapeutic treatment. Previously published research using HBA placebos should be re-evaluated to reflect a dose treatment finding rather than finding a placebo effect. Our findings of SPC mobilization by HBA support further investigation into hyperbaric air as a pharmaceutical/therapy.

Abstract The radical global shift to online teaching that resulted from the initial lockdown of the COVID-19 pandemic forced many science educators into the predicament of translating courses, including teaching laboratories, that were based upon face-to-face or practical goals and conventions into ones that could be delivered online. We used this phenomenon at the scale of a research-intensive, land-grant public institution to understand the various ways that the switch was experienced by a large cohort of 702 undergraduate students taking General Chemistry Laboratory. Data was collected over 3 weeks with identical surveys involving four prompts for open-ended responses. Analysis involved sequential explanatory mixed methods where topic modeling, a machine learning technique, was used to identify 21 topics. As categories of experience, these topics were defined and further delineated into 52 dimensions by inductive coding with constant comparison. Reported strengths and positive implications tie predominantly to the topics of Time Management Across a Lab Activity and a Critique of Instruction. Consistent with other reports of teaching and learning during the pandemic, participants perceived Availability of the Teaching Assistant for Help as a positive implication. Perceptions of weakness were most associated with Having to Work Individually, the Hands On Experience, a Critique of Instruction, and Learning by Doing. Hands on Experience, which was interpreted as the lack thereof, was the only topic made up nearly entirely of weaknesses and negative implications. The topic of Learning by Doing was the topic of greatest occurrence, but was equally indicated as strengths, positive implication, weakness, and negative implication. Ramifications are drawn from the weaknesses indicated by students who identified as members of an underrepresented ethnic minority. The results serve as a reminder that the student experience must be the primary consideration for any educational endeavor and needs to continue as a principal point of emphasis for research and development for online science environments.

During spring 2021, AZD1222 and BNT162b2 were used as prime and BNT162b2 as booster COVID-19 vaccines in Denmark. We obtained self-reported information on systemic reactogenicity day-by-day during two weeks for 2862 healthcare workers vaccinated with heterologous AZD1222 + BNT162b2 or homologous BNT162b2 + BNT162b2 regimens and compared prevalences of symptoms with unvaccinated healthcare workers. We found comparable systemic reactogenicity during the first week in the two vaccine regimens and no reactogenicity during the second week. Most of the symptoms returned to a level equal to the control population four days after booster vaccination.

Chronic lung allograft dysfunction (CLAD) is the leading cause of death in lung transplant recipients. CLAD is characterized clinically by a persistent decline in pulmonary function and histologically by the development of airway-centered fibrosis known as bronchiolitis obliterans. There are no approved therapies to treat CLAD, and the mechanisms underlying its development remain poorly understood. We performed single-cell RNA-Seq and spatial transcriptomic analysis of explanted tissues from human lung recipients with CLAD, and we performed independent validation studies to identify an important role of Janus kinase–signal transducer and activator of transcription (JAK-STAT) signaling in airway epithelial cells that contributes to airway-specific alloimmune injury. Specifically, we established that activation of JAK-STAT signaling leads to upregulation of major histocompatibility complex 1 (MHC-I) in airway basal cells, an important airway epithelial progenitor population, which leads to cytotoxic T cell–mediated basal cell death. This study provides mechanistic insight into the cell-to-cell interactions driving airway-centric alloimmune injury in CLAD, suggesting a potentially novel therapeutic strategy for CLAD prevention or treatment.

Objective Improved biomarkers of current disease activity and prediction of relapse are needed in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). For clinical relevance, biomarkers must perform well longitudinally in patients on treatment and in patients with nonsevere flares. Methods Twenty‐two proteins were measured in 347 serum samples from 74 patients with AAV enrolled in a clinical trial. Samples were collected at Month 6 after remission induction, then every 3 months until Month 18, or at the time of flare. Associations of protein concentrations with concurrent disease activity and with future flare were analyzed using mixed‐effects models, Cox proportional hazards models, and conditional logistic regression. Results Forty‐two patients had flares during the 12‐month follow‐up period, and 32 remained in remission. Twenty‐two patients had severe flares. Six experimental markers (CXCL13, IL‐6, IL‐8, IL‐15, IL‐18BP, and matrix metalloproteinase‐3 [MMP‐3]) and ESR were associated with disease activity using all three methods (P

To evaluate trends in bacterial causes of valvular endocarditis in swine, we retrospectively analyzed 321 cases diagnosed at Iowa State University Veterinary Diagnostic Laboratory (Ames, IA, USA) during May 2015–­April 2020. Streptococcus gallolyticus was the causative agent for 7.59% of cases. This emerging infection in swine could aid study of endocarditis in humans.

IntroductionLittle is known about how electrical current passes through the human body except that it follows the physical rule of least resistance. Whether organs remote from the shortest route of the current can be affected is unknown, as different types of tissue vary in resistance. This may explain why some people exposed to electrical injury report symptoms from the central nervous system (CNS). In this study, we examined the association between exposure to cross-body electrical current and immediate CNS symptoms.Material and methodsIn a prospective cohort study, we followed 6960 members of the Danish Union of Electricians for 26 weeks using weekly questionnaires. We identified 2356 electrical shocks, and for each shock we asked whether the exposure was cross-body or same-side. We excluded those who reported exposure to the head as well as those who could not report the entry and exit points of the current. We examined two outcomes: becoming unconscious or having amnesia of the event. We use percentages to describe the data and logistic regression to analyze the results.ResultsWe found that unconsciousness and amnesia following electric shocks were rare events (0.6% and 2.2%, respectively). We found an increased risk of reporting unconsciousness and amnesia in those exposed to cross-body electrical shock exposure compared to those with same-side exposure (Odds Ratio 2.60[0.62 to 10.96] and Odds Ratio 2.18[0.87 to 5.48]).ConclusionAlthough the outcomes investigated are rare, we cannot rule out a possible effect on the CNS when persons are exposed to cross-body electrical current even though it does not pass through the head.

Abstract Background Mixed methods designs are increasingly used in health care research to enrich findings. However, little is known about the frequency of use of this methodology in chiropractic research, or the quality of reporting among chiropractic studies using mixed methods. Objective To quantify the use and quality of mixed methods in chiropractic research, and explore the association of study characteristics (e.g., authorship, expertise, journal impact factor, country and year of publication) with reporting quality. Methods We will conduct a systematic search of MEDLINE, EMBASE, CINAHL, and the Index to Chiropractic Literature to identify all chiropractic mixed methods studies published from inception of each database to December 31, 2020. Articles reporting the use of both qualitative and quantitative methods, or mixed qualitative methods, will be included. Pairs of reviewers will perform article screening, data extraction, risk of bias with the Mixed Methods Appraisal Tool (MMAT), and appraisal of reporting quality using the Good Reporting of A Mixed Methods Study (GRAMMS) guideline. We will explore the correlation between GRAMMS and MMAT scores, and construct generalized estimating equations to explore factors associated with reporting quality. Discussion This will be the first methodological review to examine the reporting quality of published mixed methods studies involving chiropractic research. The results of our review will inform opportunities to improve reporting in chiropractic mixed methods studies. Our results will be disseminated in a peer-reviewed publication and presented publicly at conferences and as part of a doctoral thesis.

Objective: Our study aimed to compare symptoms day by day for non-hospitalized individuals testing positive and negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: In total, 210 positive-test and 630 negative-test healthcare workers in the Central Denmark Region were followed for up to 90 days after testing, between April and June, 2020. Their daily reported COVID-19-related symptoms were compared graphically and by logistic regression. Results: Thirty per cent of the positive-test and close to 0% of the negative-test participants reported a reduced sense of taste and smell during all 90 days (adjusted odds ratio [aOR] 86.07, 95% CI 22.86–323). Dyspnea was reported by an initial 20% of positive-test participants, declining to 5% after 30 days, without ever reaching the level of the negative-test participants (aOR 6.88, 95% CI 2.41–19.63). Cough, headache, sore throat, muscle pain, and fever were temporarily more prevalent among the positive-test participants; after 30 days, no increases were seen. Women and older participants were more susceptible to long-lasting COVID-19 symptoms. Conclusion: The prevalence of long-lasting reduced sense of taste and smell is highly increased in mild COVID-19 patients. This pattern is also seen for dyspnea at a low level, but not for cough, sore throat, headache, muscle pain, or fever.

Borates offer extended structural diversity and promise in diverse applications. Here the authors report a borate with linear BO2 units as well as NMR spectroscopy characterization that provides a quantitative basis for identification of BO2 units in polycrystalline and non-crystalline samples.

Measurement(s) Metabolomics • Lipidomics Technology Type(s) gas chromatography-mass spectrometry • Ultra High-performance Liquid Chromatography/Tandem Mass Spectrometry Factor Type(s) age group • sex Sample Characteristic - Organism Homo sapiens Sample Characteristic - Environment blood plasma material • urine material • cerebrospinal fluid material Sample Characteristic - Location United States of America Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13656581

Careful control over the defect chemistry of crystalline compounds is typically critical to transport phenomena (ion, electron, phonon). In one-dimensional (1D) ion conductors, even small concentrations of defects in the diffusion pathway can be pernicious. Wadsley-Roth block phases are 1D ion conductors with high redox capacity and among the highest diffusivity of any battery electrode materials. The origin of their high-rate transport has been attributed to parallel tunnels that could impart defect tolerance, but direct evidence is limited. Herein, a new lithium-ion battery negative electrode material, NaNb7O18, is described that exhibits extreme defect tolerance. Multimodal characterization combining neutron diffraction, 23Na solid-state NMR spectroscopy, and DFT calculations reveals that more than half of the Na+ in NaNb7O18 is in diffusion tunnel-blocking cuboctahedral environments (similar to the perovskite A-site). Despite the high point-defect concentration, NaNb7O18 can reversibly lithiate to Li7NaNb7O18 and cycle 200 mAh·g-1 in 10 h and 100 mAh·g-1 in 3 min in large 4-23 μm (D10-D90) particles. Operando synchrotron diffraction shows an anisotropic and asymmetric lithiation/delithiation process with two first-order phase transitions including one with nearly zero volume change. LixNaNb7O18 also exhibits evidence for reversible Nb-Nb bond formation. From the same operando diffraction measurements, Nb-Nb distances between edge-sharing octahedra at the block peripheries vary from ca. 3.4 to 2.8 and back to 3.4 Å over one lithium insertion/extraction cycle, in quantitative agreement with the Nb-Nb bond formation charge storage mechanism recently proposed from the computational lithiation of several different Wadsley-Roth compounds.

Social paleontology is a burgeoning field of research that seeks to understand the natural world through the collection, preparation, curation, and study of fossils via online communities. Such a community represents an ideal case for examining scientific practice as the expression of conversation topics in relation to the people who participate. Using Communities of Practice as a theoretical framework, we consider interactions within an egocentric Twitter network over a 397-day period to identify topic archetypes within the community, examine how such topic archetypes act as expressions of behavior that are indicative of community processes, and provide empirical evidence for detecting and indicating the health of an online community. Data were collected continuously and analyzed with a combination of topic modeling and social network analysis. Four unique archetypes were characterized based on the level of activity and longevity of interest. Participants for each were diverse, but not different. Structural differences in each network were noted with high levels of inter-group information flow within certain archetypes. Archetypes were interpreted using the life cycle states for Communities of Practice; sustained conversations and piques of interest indicate healthy online communities. These findings can inform efforts to design, implement, and research online, scientific communities.

Introduction Electric shocks may have neurological consequences for the victims. Although the literature on the neurological consequences of electric shocks is limited by retrospective designs, case studies and studies of selected patient groups, previous research provides some evidence of a link between electric shocks, and diseases and symptoms of the central nervous system (CNS)(e.g. epilepsy, migraine and vertigo) and the peripheral nervous system (PNS)(e.g. loss of sensation, neuropathy and muscle weakness). This study aims to employ a register-based, matched cohort study, to investigate whether individuals demonstrate a greater risk of neurological diseases and symptoms of the CNS or PNS in the years following an electrical injury. Materials and methods We identified 14,112 electrical injuries over a period of 19 years in two Danish registries, and matched these with three different groups of persons in a prospective matched cohort study: (1) patients with dislocation/sprain injuries, (2) patients with eye injuries and (3) persons employed in the same occupation. Year of injury, sex and age were used as matching variables. The outcomes we identified comprised neurological disorders and central or peripheral nervous system symptoms that covered a range of diagnoses in the Danish National Patient Register. The associations were analysed using conditional logistic regression for a range of time periods (six months to five years) and conditional Cox regression for analyses of the complete follow-up period (up to 20 years). Results For victims of electric shock, the CNS sequelae we identified included an increased risk of epilepsy, convulsions, abnormal involuntary movements, headache, migraine and vertigo. We also identified an uncertain, increased risk of spinal muscular atrophy and dystonia, whereas we identified no increased risk of Parkinson’s disease, essential tremor, multiple sclerosis or other degenerative diseases of the nervous system. For victims of electric shock, the PNS sequelae we identified included an increased risk of disturbances of skin sensation, mononeuropathy in the arm or leg and nerve root and plexus disorders. We also identified an uncertain, increased risk of facial nerve disorders, other mononeuropathy, and polyneuropathy. Conclusion Our results confirm that electrical injuries increase the risk of several neurological diseases and symptoms of the CNS or PNS in the years following the injury. Most often the diseases and symptoms are diagnosed within the first six months of the injury, but delayed onset of up to 5 years cannot be ruled out for some symptoms and diagnoses. Some of the conditions were rare in our population, which limited our ability to identify associations, and this warrants cautious interpretation. Therefore, further studies are needed to confirm our findings, as are studies that examine the mechanisms underlying these associations.

T cell polyfunctionality is a hallmark of protective immunity against pathogens and cancer, yet the molecular mechanism governing it remains mostly elusive. We found that canonical Wnt agonists inhibited human memory CD8+ T cell differentiation while simultaneously promoting the generation of highly polyfunctional cells. Downstream effects of Wnt activation persisted after removal of the drug, and T cells remained polyfunctional following subsequent cell division, indicating the effect is epigenetically regulated. Wnt activation induced a gene expression pattern that is enriched with stem cell–specific gene signatures and upregulation of protein arginine methyltransferase 1 (PRMT1), a known epigenetic regulator. PRMT1+CD8+ T cells are associated with enhanced polyfunctionality, especially the ability to produce IL-2. In contrast, inhibition of PRMT1 ameliorated the effects of Wnt on polyfunctionality. Chromatin immunoprecipitation revealed that H4R3me2a, a permissive transcription marker mediated by PRMT1, increased at the IL-2 promoter loci following Wnt activation. In vivo, Wnt-treated T cells exhibited superior polyfunctionality and persistence. When applied to cytomegalovirus (CMV) donor–seropositive, recipient-seronegative patients (D+/R–) lung transplant patient samples, Wnt activation enhanced CMV-specific T cell polyfunctionality, which is important in controlling CMV diseases. These findings reveal a molecular mechanism governing T cell polyfunctionality and identify PRMT1 as a potential target for T cell immunotherapy.

ABSTRACT Lipids play a fundamental role in fungal cell biology, being essential cell membrane components and major targets of antifungal drugs. A deeper knowledge of lipid metabolism is key for developing new drugs and a better understanding of fungal pathogenesis. Here, we built a comprehensive map of the Histoplasma capsulatum lipid metabolic pathway by incorporating proteomic and lipidomic analyses. We performed genetic complementation and overexpression of H. capsulatum genes in Saccharomyces cerevisiae to validate reactions identified in the map and to determine enzymes responsible for catalyzing orphan reactions. The map led to the identification of both the fatty acid desaturation and the sphingolipid biosynthesis pathways as targets for drug development. We found that the sphingolipid biosynthesis inhibitor myriocin, the fatty acid desaturase inhibitor thiocarlide, and the fatty acid analog 10-thiastearic acid inhibit H. capsulatum growth in nanomolar to low-micromolar concentrations. These compounds also reduced the intracellular infection in an alveolar macrophage cell line. Overall, this lipid metabolic map revealed pathways that can be targeted for drug development. IMPORTANCE It is estimated that 150 people die per hour due to the insufficient therapeutic treatments to combat fungal infections. A major hurdle to developing antifungal therapies is the scarce knowledge on the fungal metabolic pathways and mechanisms of virulence. In this context, fungal lipid metabolism is an excellent candidate for developing drugs due to its essential roles in cellular scaffolds, energy storage, and signaling transductors. Here, we provide a detailed map of Histoplasma capsulatum lipid metabolism. The map revealed points of this fungus lipid metabolism that can be targeted for developing antifungal drugs.

An important challenge for primary or secondary analysis of cytometry data is how to facilitate productive collaboration between domain and quantitative experts. Domain experts in cytometry laboratories and core facilities increasingly recognize the need for automated workflows in the face of increasing data complexity, but by and large, still conduct all analysis using traditional applications, predominantly FlowJo. To a large extent, this cuts domain experts off from the rapidly growing library of Single Cell Data Science algorithms available, curtailing the potential contributions of these experts to the validation and interpretation of results. To address this challenge, we developed FlowKit, a Gating-ML 2.0-compliant Python package that can read and write FCS files and FlowJo workspaces. We present examples of the use of FlowKit for constructing reporting and analysis workflows, including round-tripping results to and from FlowJo for joint analysis by both domain and quantitative experts.

The theoretical framework of communities of practice (CoP) is often used for framing research into online communities. However, there is an absence of measures and empirical work that evaluates knowledge-sharing within such communities. This represents a substantial gap in our understanding of informal learning for diverse people and in the case of communities that support participation in science, a potential loss of capacity for an enterprise that serves a critical function for society. Our objective is to operationalize "practice" within a designed online, scientific community and evaluate these behaviors as representative of seven theorized high-level groups. For this case study, content and social network analysis were applied to forums (n = 1858), activity posts (n = 1300), and direct messages (n = 667). Content analysis showed that community members most often used practices that were coded as social and not domain-specific. Differences existed in the ways that forums, messages, and activity posts were used as well as between education and outreach members and members of the public and scientists. Social network analysis revealed two domain-specific practices were central to the knowledge-sharing discourse. The seven theorized high-level groups were reduced to three. We provide a new empirically-based framework for use in identifying practices within the digital spaces as well as recommendations for designing online science communities that emphasize knowledge creation.

Lithium-rich early transition metal oxides are the source of excess removeable lithium that affords high energy density to lithium-rich battery cathodes. They are also candidates for solid electrolytes in all-solid-state batteries. These highly ionic compounds are sparse on phase diagrams of thermodynamically stable oxides, but soft chemical routes offer an alternative to explore new alkali-rich crystal chemistries. In this work, a new layered polymorph of Li3NbO4 with coplanar [Nb4O16]12- clusters is discovered through ion exchange chemistry. A more detailed study of the ion exchange reaction reveals that it takes place almost instantaneously, changing the crystal volume by more than 22% within seconds. The transformation of coplanar [Nb4O16]12- in L-Li3NbO4 into the supertetrahedral [Nb4O16]12- clusters found in the stable cubic c-Li3NbO4 is also explored. Furthermore, this synthetic pathway is extended to access a new layered polymorph of Li3TaO4. NMR crystallography with 6,7Li, 23Na, and 93Nb NMR, X-ray diffraction, neutron diffraction, and first-principles calculations is applied to A3MO4 (A = Li, Na; M = Nb, Ta) to identify local and long-range atomic structure, to monitor the unusually rapid reaction progression, and to track the phase transitions from the metastable layered phases to the known compounds found using high-temperature synthesis. A mechanism is proposed whereby some sodium is retained at short reaction times, which then undergoes proton exchange during water washing, forming a phase with hydrogen bonds bridging the coplanar [Nb4O16]12- clusters. This study has implications for lithium-rich transition metal oxides and associated battery materials and for ion exchange chemistry in non-framework structures. The role of techniques that can detect light elements, local structure, and subtle structural changes in soft-chemical synthesis is emphasized.

We determined normative data for plasma cytokines established from a cohort of 126 carefully screened healthy adults aged 18 to 64 years. Participants were enrolled to ensure an even age and sex distribution and to include at least 30% non-Caucasians. Plasma cytokines for 18 analytes were tested by multiplex immunoassay. The data are presented by age cohort (18–29 years, 30–39, 40–49, and 50–66), as well as by sex and racial background. This dataset complements published normative ranges of cellular subsets generated by comprehensive polychromatic flow cytometry analysis of the healthy human immune system [1]. These data are available to researchers and have value as a reference range for research involving peripheral cytokines.

Introducción: Se describe una nueva especie botánica, Senecio huaynaputinaensis. Se discute su morfología comparada con especies relacionadas. Además, se presenta una descripción del hábitat, suelo y se brinda un mapa de distribución. M&M: La nueva especie aquí descrita fue encontrada durante las exploraciones realizadas entre Puquina y Quinistaquillas (departamento de Moquegua) en el año 2017. Para su identificación se comparó con materiales de herbario, de repositorios virtuales, con material fresco colectado en campo y se revisaron referencias bibliográficas sobre distribución del género Senecio en zonas áridas de la región de los Andes. La especie se ilustra mediante imágenes de lupa estereoscópica y microscopio óptico. Resultados: Como resultado se identifica que la entidad evaluada corresponde a una nueva especie de Senecio, diferente de las ya conocidas. Se describe e ilustra una nueva especie de Compositae, Senecio huaynaputinaensis, de la región andina del sur de Perú, departamento de Moquegua, la cual se diferencia de su pariente más cercano, Senecio yurensis Rusby por la densa pubescencia que cubre la planta, la presencia de filodios en la base de las hojas, por tener capítulo, involucro y brácteas del involucro de menor longitud, presencia de tricomas en los pedicelos de las lígulas, forma oblonga del estambre, aquenios alargados con textura cubierta por tricomas engrosados, y por los vilanos de menor longitud. Conclusión: Senecio huaynaputinaensis es una nueva especie para la ciencia, aparentemente restringida al sur de Perú.

Tuberculosis is one of the most frequent causes of death in humans worldwide. One of the primary reasons tuberculosis remains a public health threat is that diagnosis can take weeks to months, is often not very sensitive and cannot be accomplished in many remote environments. A rapid, sensitive and inexpensive point-of-care (POC) diagnostic would have a major impact on tuberculosis eradication efforts. The tuberculosis diagnostic system REFtb is based on specific detection of the constitutively expressed β-lactamase (BlaC) in Mycobacterium tuberculosis using a custom fluorogenic substrate designated as CDG-3. REFtb has potential as a diagnostic for tuberculosis that could be very inexpensive (

IntroductionElectrical injuries happen every day in homes and workplaces. Not only may these injuries cause physical damage and disability, they may also cause mental disorders. The aim of this study was to investigate if persons with an electrical injury suffer from mental disorders in the following years.Material and methodsIn a prospective matched cohort design, we identified 14.112 electrical injuries in two Danish registries and matched these with persons with dislocation/sprain injuries or eye injuries, respectively, as well as with persons from the workforce from the same occupation, using year of injury, sex and age as matching variables. We identified possible outcomes in terms of mental diagnoses in the Danish National Patient registry, based on literature, including reviews, original studies and case-reports as well as experiences from clinical praxis. The associations were analyzed using conditional cox- and logistic regression.ResultsWe found that the following of the examined outcomes were associated with exposure to an electrical injury compared to the matched controls. Some of the outcomes showed the strongest associations shortly after the injury, namely 'mental disorders due to known physiological condition', 'anxiety and adjustment disorders', and especially the 'Post Traumatic Stress Disorder (PTSD)' subgroup. The same pattern was seen for 'Depression' although the associations were weaker. Other conditions took time to develop ('Somatoform disorders'), or were only present in the time to event analysis ('other non-psychotic mental disorders' and 'sleep disorders'). The findings were consistent in all three matches, with the highest risk estimates in the occupation match.ConclusionElectrical injuries may result in mental disorders, both acute and several years after. However, the absolute risk is limited as most of the outcomes are rare.

Flavor is a key attribute defining melon fruit quality and driving consumer preferences. We characterized and compared fruit ripening patterns (ethylene, respiration), physicochemical properties (rind/flesh color, firmness, soluble solids, acidity), aroma volatiles, and flavor-related sensory attributes in seven melon genotypes differing in shelf life capacity. Fruits were evaluated at optimal maturity and after storage for six days at 5 °C plus one day at room temperature. Total volatile content increased after storage in all genotypes, with esters being dominant. Shorter shelf-life genotypes, displaying a sharper climacteric phase, correlated with fruity/floral/sweet flavor-related descriptors, and with esters, sulfur-containing compounds and a terpenoid. Longer shelf-life types were associated with firmness, green and grassy aroma/flavor and aldehydes. Multivariate regression identified key volatiles that predict flavor sensory perception, which could accelerate breeding of longer shelf-life melons with improved flavor characteristics.

Introduction: Kidney transplantation (KT) demands that patients navigate a complex healthcare system and adhere to lifelong therapy and surveillance. Cultural and linguistic discordance between patients and providers has been identified as a barrier to successful KT. We studied KT outcomes and disparities among a native Somali population living in Minnesota. Methods: Between 1995 and 2015, 2,385 patients underwent KT at our institution; 22 were self-designated Somali nationals. Patient and graft survival and time to first rejection were analyzed. Utilization of interpreter services was evaluated. Results: Patient survival for the Somali cohort at 1 year was 100% and 95.5% at 5 years; compared to 97.2% at 1 year and 89.1% at 5 years for the Caucasian cohort (p = 0.40). Graft survival for the Somali cohort at 1 year was 100% and 95.5% at 5 years; for the Caucasian cohort 94.8% and 81.6% (p = 0.35). Rejection-free survival in the Somali cohort was 100% at 1 and 5 years, for the Caucasian cohort 86.2% and 82.1 (p = 0.41). Among 22 adult Somali KT recipients, 15 (68%) patients frequently utilized interpreter services in their KT-related clinical encounters. Conclusion: Immigrant Somali KT recipients, appear to have comparable KT outcomes compared to a contemporaneous Caucasian cohort.

[This corrects the article DOI: 10.1371/journal.pgen.1008841.].

Previous studies suggest that the presence of antigen-specific polyfunctional T cells is correlated with improved pathogen clearance, disease control, and clinical outcomes; however, the molecular mechanisms responsible for the generation, function, and survival of polyfunctional T cells remain unknown. The study of polyfunctional T cells has been, in part, limited by the need for intracellular cytokine staining (ICS), necessitating fixation and cell membrane permeabilization that leads to unacceptable degradation of RNA. Adopting elements from prior research efforts, we developed and optimized a modified protocol for the isolation of high-quality RNA (i.e., RIN > 7) from primary human T cells following aldehyde-fixation, detergent-based permeabilization, intracellular cytokines staining, and sorting. Additionally, this method also demonstrated utility preserving RNA when staining for transcription factors. This modified protocol utilizes an optimized combination of an RNase inhibitor and high-salt buffer that is cost-effective while maintaining the ability to identify and resolve cell populations for sorting. Overall, this protocol resulted in minimal loss of RNA integrity, quality, and quantity during cytoplasmic staining of cytokines and subsequent flourescence-activated cell sorting. Using this technique, we obtained the transcriptional profiles of functional subsets (i.e., non-functional, monofunctional, bifunctional, polyfunctional) of CMV-specific CD8+T cells. Our analyses demonstrated that these functional subsets are molecularly distinct, and that polyfunctional T cells are uniquely enriched for transcripts involved in viral response, inflammation, cell survival, proliferation, and metabolism when compared to monofunctional cells. Polyfunctional T cells demonstrate reduced activation-induced cell death and increased proliferation after antigen re-challenge. Further in silico analysis of transcriptional data suggested a critical role for STAT5 transcriptional activity in polyfunctional cell activation. Pharmacologic inhibition of STAT5 was associated with a significant reduction in polyfunctional cell cytokine expression and proliferation, demonstrating the requirement of STAT5 activity not only for proliferation and cell survival, but also cytokine expression. Finally, we confirmed this association between CMV-specific CD8+ polyfunctionality with STAT5 signaling also exists in immunosuppressed transplant recipients using single cell transcriptomics, indicating that results from this study may translate to this vulnerable patient population. Collectively, these results shed light on the mechanisms governing polyfunctional T cell function and survival and may ultimately inform multiple areas of immunology, including but not limited to the development of new vaccines, CAR-T cell therapies, and adoptive T cell transfer.

Hypomyelination, a neurological condition characterized by decreased production of myelin sheets by glial cells, often has no known etiology. Elucidating the genetic causes of hypomyelination provides a better understanding of myelination, as well as means to diagnose, council, and treat patients. Here, we present evidence that YIPPEE LIKE 3 (YPEL3), a gene whose developmental role was previously unknown, is required for central and peripheral glial cell development. We identified a child with a constellation of clinical features including cerebral hypomyelination, abnormal peripheral nerve conduction, hypotonia, areflexia, and hypertrophic peripheral nerves. Exome and genome sequencing revealed a de novo mutation that creates a frameshift in the open reading frame of YPEL3, leading to an early stop codon. We used zebrafish as a model system to validate that YPEL3 mutations are causative of neuropathy. We found that ypel3 is expressed in the zebrafish central and peripheral nervous system. Using CRISPR/Cas9 technology, we created zebrafish mutants carrying a genomic lesion similar to that of the patient. Our analysis revealed that Ypel3 is required for development of oligodendrocyte precursor cells, timely exit of the perineurial glial precursors from the central nervous system (CNS), formation of the perineurium, and Schwann cell maturation. Consistent with these observations, zebrafish ypel3 mutants have metabolomic signatures characteristic of oligodendrocyte and Schwann cell differentiation defects, show decreased levels of Myelin basic protein in the central and peripheral nervous system, and develop defasciculated peripheral nerves. Locomotion defects were observed in adult zebrafish ypel3 mutants. These studies demonstrate that Ypel3 is a novel gene required for perineurial cell development and glial myelination.

Abstract Background Tuberculosis (TB) caused an estimated 1.4 million deaths and 10.4 million new cases globally in 2015. TB rates in the United States continue to steadily decline, yet rates in the State of Hawaii are perennially among the highest in the nation due to a continuous influx of immigrants from the Western Pacific and Asia. TB in Hawaii is composed of a unique distribution of genetic lineages, with the Beijing and Manila families of Mycobacterium tuberculosis (Mtb) comprising over two-thirds of TB cases. Standard fingerprinting methods (spoligotyping plus 24-loci Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats [MIRU-VNTR] fingerprinting) perform poorly when used to identify actual transmission clusters composed of isolates from these two families. Those typing methods typically group isolates from these families into large clusters of non-linked isolates with identical fingerprints. Next-generation whole-genome sequencing (WGS) provides a new tool for molecular epidemiology that can resolve clusters of isolates with identical spoligotyping and MIRU-VNTR fingerprints. Methods We performed WGS and SNP analysis and evaluated epidemiological data to investigate 19 apparent TB transmission clusters in Hawaii from 2003 to 2017 in order to assess WGS’ ability to resolve putative Mtb clusters from the Beijing and Manila families. This project additionally investigated MIRU-VNTR allele prevalence to determine why standard Mtb fingerprinting fails to usefully distinguish actual transmission clusters from these two Mtb families. Results WGS excluded transmission events in seven of these putative clusters, confirmed transmission in eight, and identified both transmission-linked and non-linked isolates in four. For epidemiologically identified clusters, while the sensitivity of MIRU-VNTR fingerprinting for identifying actual transmission clusters was found to be 100%, its specificity was only 28.6% relative to WGS. We identified that the Beijing and Manila families’ significantly lower Shannon evenness of MIRU-VNTR allele distributions than lineage 4 was the cause of standard fingerprinting’s poor performance when identifying transmission in Beijing and Manila family clusters. Conclusions This study demonstrated that WGS is necessary for epidemiological investigation of TB in Hawaii and the Pacific.

Materials that exhibit synchronous color change and actuation may benefit biomimetic camouflage, but stimuli can be difficult to control. Here the authors report a composite with electricity-driven electrochromic and actuating capabilities for use in a solid-state ionic polymer-metal composite actuator.

Post activation potentiation (PAP) is an acute enhancement of muscular function subsequent to an intense muscle conditioning activity. Practical application of PAP as a physical preparation for enhanced performance is a topic of considerable interest in the sport performance community. The purpose of this study was to determine if a dynamic warm-up (WU) plus a progression of deadlift (DL) sets culminating in a one-repetition maximum DL (1-RM DL) (i.e., a PAP conditioning activity) is more effective in improving the standing long jump (SLJ) as opposed to using a dynamic WU alone. Secondarily, it was of interest to determine if there was a meaningful relationship between the 1-RM DL and SLJ ability. Twenty NCAA Division I male North American football players participated in the study (age=20.3±2.3 years, height=183.5±6.3 cm, mass=96.3±17.1 kg). Participants met three times separated by one week. The initial gathering was an orientation meeting where participants were briefed on the study protocol and height, age and body mass were recorded. During the first data collection the participants completed a dynamic WU immediately followed by a progression of DLs culminating in a 1-RM DL; this served as a PAP conditioning activity. Following the PAP WU (5-6 minutes) the participants completed two trials of SLJs separated by 2-3 minutes. During the second data collection the participants completed the dynamic WU only followed (5-6 minutes) by the participants completing two trials of SLJs separated by 2-3 minutes. A paired t-test was used to compare the maximum SLJ between WU conditions and a Pearson correlation coefficient (r) was calculated to compare 1-RM DLs with SLJ scores. The SLJ was significantly greater (4.3±7.5 cm) following the 1-RM DL PAP warm-up (p

CRISPR/Cas9 is a transformative tool for making targeted genetic alterations. In plants, high mutation efficiencies have been reported in primary transformants. However, many of the mutations analyzed were somatic and therefore not heritable. To provide more insights into the efficiency of creating stable homozygous mutants using CRISPR/Cas9, we targeted LsNCED4 (9-cis-EPOXYCAROTENOID DIOXYGENASE4), a gene conditioning thermoinhibition of seed germination in lettuce. Three constructs, each capable of expressing Cas9 and a single gRNA targeting different sites in LsNCED4, were stably transformed into lettuce (Lactuca sativa) cvs. Salinas and Cobham Green. Analysis of 47 primary transformants (T1) and 368 T2 plants by deep amplicon sequencing revealed that 57% of T1 plants contained events at the target site: 28% of plants had germline mutations in one allele indicative of an early editing event (mono-allelic), 8% of plants had germline mutations in both alleles indicative of two early editing events (bi-allelic), and the remaining 21% of plants had multiple low frequency mutations indicative of late events (chimeric plants). Editing efficiency was similar in both genotypes, while the different gRNAs varied in efficiency. Amplicon sequencing of 20 T1 and more than 100 T2 plants for each of the three gRNAs showed that repair outcomes were not random, but reproducible and characteristic for each gRNA. Knockouts of NCED4 resulted in large increases in the maximum temperature for seed germination, with seeds of both cultivars capable of germinating >70% at 37°. Knockouts of NCED4 provide a whole-plant selectable phenotype that has minimal pleiotropic consequences. Targeting NCED4 in a co-editing strategy could therefore be used to enrich for germline-edited events simply by germinating seeds at high temperature.

Salmonella enterica serotype I 4,[5],12:i:- has been increasingly isolated from swine. However, its pathogenic potential is not well characterized. Analysis of swine cases confirmed a strong positive association between isolation of I 4,[5],12:i:- and lesions of enteric salmonellosis and suggested a similar pathogenic potential as that for Salmonella Typhimurium.