Abstract
The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPathDB projects. As a Bioinformatics ...Resource Center funded by the National Institutes of Health, with additional support from the Welllcome Trust, VEuPathDB supports >500 organisms comprising invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Designed to empower researchers with access to Omics data and bioinformatic analyses, VEuPathDB projects integrate >1700 pre-analysed datasets (and associated metadata) with advanced search capabilities, visualizations, and analysis tools in a graphic interface. Diverse data types are analysed with standardized workflows including an in-house OrthoMCL algorithm for predicting orthology. Comparisons are easily made across datasets, data types and organisms in this unique data mining platform. A new site-wide search facilitates access for both experienced and novice users. Upgraded infrastructure and workflows support numerous updates to the web interface, tools, searches and strategies, and Galaxy workspace where users can privately analyse their own data. Forthcoming upgrades include cloud-ready application architecture, expanded support for the Galaxy workspace, tools for interrogating host-pathogen interactions, and improved interactions with affiliated databases (ClinEpiDB, MicrobiomeDB) and other scientific resources, and increased interoperability with the Bacterial & Viral BRC.
Sport-related concussions (SRC) occur at alarming rates among high school athletes (ages 13-18), which made the Center for Disease Control and Prevention and other agencies classify it as an ...“epidemic”. If improperly managed, physical, mental, and emotional consequences can occur for SRC patients. Due to these consequences all 50 states in the US have passed legislation requiring medical release from a practitioner before a student-athlete can return to athletics following an SRC, yet there is no universally accepted consensus on how to medically manage this common injury. A 22-item, validated survey was distributed to Michigan practitioners who sign off on SRC. The purpose of this study was to compare the management of SRC between urban and rural practitioners in the following critical areas: 1) practitioner demographics in urban and rural settings, 2) return-to-learn and return-to-play protocols used by practitioners, 3) sport-related concussion diagnostic tools used by practitioners, 4) the working relationship between practitioners and athletic trainers in the secondary school setting, and 5) practitioner’s knowledge of the Michigan Sports Concussion Law. A total of 20 participants were included in this research (8 urban, 12 rural). One significant finding of this study was that rural practitioners rely very heavily on the results and recommendations of the ImPACT Application, p = 0.040, compared to their urban counterparts. The information collected in this study can be used to recognize the strengths and weaknesses of current protocols and aid in reforming the current policy surrounding sport-related concussions in the state of Michigan.
The ecological success of shallow water reef-building corals has been linked to the symbiosis between the coral host and its dinoflagellate symbionts (herein 'symbionts'). As mixotrophs, symbiotic ...corals depend on nutrients 1) transferred from their photosynthetic symbionts (autotrophy) and 2) acquired by host feeding on particulate organic resources (heterotrophy). However, coral species differ in the extent to which they depend on heterotrophy for nutrition and these differences are typically poorly defined. Here, a multi-tracer fatty acid approach was used to evaluate the trophic strategies of three species of common reef-building coral (Galaxea fascicularis, Pachyseris speciosa, and Pocillopora verrucosa) whose trophic strategies had previously been identified using carbon stable isotopes. The composition and various indices of fatty acids were compared to examine the relative contribution of symbiont autotrophy and host heterotrophy in coral energy acquisition. A linear discriminant analysis (LDA) was used to estimate the contribution of polyunsaturated fatty acids (PUFA) derived from various potential sources to the coral hosts. The total fatty acid composition and fatty acid indices revealed differences between the more heterotrophic (P. verrucosa) and more autotrophic (P. speciosa) coral hosts, with the coral host G. fascicularis showing overlap with the other two species and greater variability overall. For the more heterotrophic P. verrucosa, the fatty acid indices and LDA results both indicated a greater proportion of copepod-derived fatty acids compared to the other coral species. Overall, the LDA estimated that PUFA derived from particulate resources (e.g., copepods and diatoms) comprised a greater proportion of coral host PUFA in contrast to the lower proportion of symbiont-derived PUFA. These estimates provide insight into the importance of heterotrophy in coral nutrition, especially in productive reef systems. The study supports carbon stable isotope results and demonstrates the utility of fatty acid analyses for exploring the trophic strategies of reef-building corals.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit ...SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines.
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•Adenovirus transduction of human ACE2 enables SARS-CoV-2 infection of BALB/c mice•High levels of viral RNA and infectious SARS-CoV-2 accumulate in lungs•Mice transduced with human ACE2 develop viral pneumonia after SARS-CoV-2 infection•Neutralizing mAbs protect from SARS-CoV-2-induced lung infection and inflammation
Laboratory mice transduced with adenoviruses encoding human ACE2 are permissive for SARS-CoV-2 and develop pneumonia. Passive transfer of a neutralizing monoclonal antibody reduces lung infection, inflammation, and disease.
Topographically complex regions on land and in the oceans feature hotspots of biodiversity that reflect geological influences on ecological and evolutionary processes. Over geologic time, topographic ...diversity gradients wax and wane over millions of years, tracking tectonic or climatic history. Topographic diversity gradients from the present day and the past can result from the generation of species by vicariance or from the accumulation of species from dispersal into a region with strong environmental gradients. Biological and geological approaches must be integrated to test alternative models of diversification along topographic gradients. Reciprocal illumination among phylogenetic, phylogeographic, ecological, paleontological, tectonic, and climatic perspectives is an emerging frontier of biogeographic research.
Topographically complex regions today feature high taxonomic and ecological diversity.
Ancient topographic diversity gradients arose and declined over millions of years.
Paleontological and modern data are crucial to understand topographic diversity gradients.
Topographically complex regions have high conservation value.
Intracranial electrical stimulation (iES) of the human brain has long been known to elicit a remarkable variety of perceptual, motor and cognitive effects, but the functional-anatomical basis of this ...heterogeneity remains poorly understood. We conducted a whole-brain mapping of iES-elicited effects, collecting first-person reports following iES at 1,537 cortical sites in 67 participants implanted with intracranial electrodes. We found that intrinsic network membership and the principal gradient of functional connectivity strongly predicted the type and frequency of iES-elicited effects in a given brain region. While iES in unimodal brain networks at the base of the cortical hierarchy elicited frequent and simple effects, effects became increasingly rare, heterogeneous and complex in heteromodal and transmodal networks higher in the hierarchy. Our study provides a comprehensive exploration of the relationship between the hierarchical organization of intrinsic functional networks and the causal modulation of human behaviour and experience with iES.
Tumor cells in vivo encounter diverse types of microenvironments both at the site of the primary tumor and at sites of distant metastases. Understanding how the various mechanical properties of these ...microenvironments affect the biology of tumor cells during disease progression is critical in identifying molecular targets for cancer therapy.
This study uses flexible polyacrylamide gels as substrates for cell growth in conjunction with a novel proteomic approach to identify the properties of rigidity-dependent cancer cell lines that contribute to their differential growth on soft and rigid substrates. Compared to cells growing on more rigid/stiff substrates (>10,000 Pa), cells on soft substrates (150-300 Pa) exhibited a longer cell cycle, due predominantly to an extension of the G1 phase of the cell cycle, and were metabolically less active, showing decreased levels of intracellular ATP and a marked reduction in protein synthesis. Using stable isotope labeling of amino acids in culture (SILAC) and mass spectrometry, we measured the rates of protein synthesis of over 1200 cellular proteins under growth conditions on soft and rigid/stiff substrates. We identified cellular proteins whose syntheses were either preferentially inhibited or preserved on soft matrices. The former category included proteins that regulate cytoskeletal structures (e.g., tubulins) and glycolysis (e.g., phosphofructokinase-1), whereas the latter category included proteins that regulate key metabolic pathways required for survival, e.g., nicotinamide phosphoribosyltransferase, a regulator of the NAD salvage pathway.
The cellular properties of rigidity-dependent cancer cells growing on soft matrices are reminiscent of the properties of dormant cancer cells, e.g., slow growth rate and reduced metabolism. We suggest that the use of relatively soft gels as cell culture substrates would allow molecular pathways to be studied under conditions that reflect the different mechanical environments encountered by cancer cells upon metastasis to distant sites.
Placenta Accreta Spectrum Without Placenta Previa Carusi, Daniela A; Fox, Karin A; Lyell, Deirdre J ...
Obstetrics and gynecology (New York. 1953),
2020-September, Letnik:
136, Številka:
3
Journal Article
Recenzirano
To evaluate placenta accreta spectrum with and without placenta previa with regard to risk factors, antepartum diagnosis, and maternal morbidity.
We conducted a retrospective cohort study of ...pathology-confirmed placenta accreta spectrum deliveries with hysterectomy from two U.S. referral centers from January 2010-June 2019. Maternal, pregnancy, and delivery characteristics were compared among placenta accreta spectrum cases with (previa PAS group) and without (nonprevia PAS group) placenta previa. Surgical outcomes and a composite of severe maternal morbidities were evaluated, including eight or more blood cell units transfused, reoperation, pulmonary edema, acute kidney injury, thromboembolism, or death. Logistic regression was used with all analyses controlled for delivery location.
Of 351 deliveries, 106 (30%) had no placenta previa at delivery. When compared with the previa group, nonprevia placenta accreta spectrum was less likely to be identified antepartum (38%, 95% CI 28-48% vs 87%, 82-91%), less likely to receive care from a multidisciplinary team (41%, 31-51% vs 86%, 81-90%), and less likely to have invasive placenta increta or percreta (51% 41-61% vs 80%, 74-84%). The nonprevia group had more operative hysteroscopy (24%, 16-33% vs 6%, 3-9%) or in vitro fertilization (31%, 22-41% vs 9%, 6-13%) and was less likely to have had a prior cesarean delivery (64%, 54-73% vs 93%, 89-96%) compared with the previa group, though the majority in each group had a prior cesarean delivery. Rates of severe maternal morbidity were similar in the two groups, at 19% (nonprevia) and 20% (previa), even after controlling for confounders (adjusted odds ratio for the nonprevia group 0.59, 95% CI 0.30-1.17).
Placenta accreta spectrum without previa is less likely to be diagnosed antepartum, potentially missing the opportunity for multidisciplinary team management. Despite the absence of placenta previa and less placental invasion, severe maternal morbidity at delivery was not lower. Broader recognition of patients at risk for placenta accreta spectrum may improve early clinical diagnosis and patient outcomes.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). ...Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.
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•A replicating VSV-SARS-CoV-2 vaccine induces high-titer neutralizing antibodies•Infectious SARS-CoV-2 is undetectable in the lung of vaccinated mice post-challenge•SARS-CoV-2-induced lung inflammation and pathology is decreased in vaccinated mice•Transfer of vaccine-derived immune sera to naive mice protects against SARS-CoV-2
Case, Rothlauf et al. report the efficacy of a replicating VSV-based SARS-CoV-2 vaccine. Immunized hACE2-expressing mice challenged with SARS-CoV-2 are protected against lung infection, inflammation, and pneumonia. Neutralizing antibodies are a correlate of this protection, as passive transfer of vaccine-derived immune sera protects naive mice from subsequent SARS-CoV-2 challenge.
This trial assessed the feasibility, acceptability, tolerability, and efficacy of an Internet-based therapist-assisted cognitive-behavioral indicated prevention intervention for prolonged grief ...disorder (PGD) called Healthy Experiences After Loss (HEAL). Eighty-four bereaved individuals at risk for PGD were randomized to either an immediate treatment group (n = 41) or a waitlist control group (n = 43). Assessments were conducted at four time-points: prior to the wait-interval (for the waitlist group), pre-intervention, post-intervention, 6 weeks later, and 3 months later (for the immediate group only). Intent-to-treat analyses indicated that HEAL was associated with large reductions in prolonged grief (d = 1.10), depression (d = .71), anxiety (d = .51), and posttraumatic stress (d = .91). Also, significantly fewer participants in the immediate group met PGD criteria post-intervention than in the waitlist group. Pooled data from both groups also yielded significant reductions and large effect sizes in PGD symptom severity at each follow-up assessment. The intervention required minimal professional oversight and ratings of satisfaction with treatment and usability of the Internet interface were high. HEAL has the potential to be an effective, well-tolerated tool to reduce the burden of significant pre-clinical PGD. Further research is needed to refine HEAL and to assess its efficacy and mechanisms of action in a large-scale trial.
•Healthy Experiences After Loss is a web-based prevention for prolonged grief.•We examined efficacy, acceptability, and impact of professional oversight.•84 Patients with early prolonged grief entered the wait-list controlled pilot trial.•HEAL led to large reductions in prolonged grief and lower incidence rates.•Satisfaction and usability were high and professional oversight very low.
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