Disruption of MAM integrity in mutant FUS oligodendroglial progenitors from hiPSCs.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder, characterized by selective loss of motor neurons (MNs). A number of causative genetic mutations underlie the disease, including mutations in the fused in sarcoma (FUS) gene, which can lead to both juvenile and late-onset ALS. Although ALS results from MN death, there is evidence that dysfunctional glial cells, including oligodendroglia, contribute to neurodegeneration. Here, we used human induced pluripotent stem cells (hiPSCs) with a R521H or a P525L mutation in FUS and their isogenic controls to generate oligodendrocyte progenitor cells (OPCs) by inducing SOX10 expression from a TET-On SOX10 cassette. Mutant and control iPSCs differentiated efficiently into OPCs. RNA sequencing identified a myelin sheath-related phenotype in mutant OPCs. Lipidomic studies demonstrated defects in myelin-related lipids, with a reduction of glycerophospholipids in mutant OPCs. Interestingly, FUSR521H OPCs displayed a decrease in the phosphatidylcholine/phosphatidylethanolamine ratio, known to be associated with maintaining membrane integrity. A proximity ligation assay further indicated that mitochondria-associated endoplasmic reticulum membranes (MAM) were diminished in both mutant FUS OPCs. Moreover, both mutant FUS OPCs displayed increased susceptibility to ER stress when exposed to thapsigargin, and exhibited impaired mitochondrial respiration and reduced Ca2+ signaling from ER Ca2+ stores. Taken together, these results demonstrate a pathological role of mutant FUS in OPCs, causing defects in lipid metabolism associated with MAM disruption manifested by impaired mitochondrial metabolism with increased susceptibility to ER stress and with suppressed physiological Ca2+ signaling. As such, further exploration of the role of oligodendrocyte dysfunction in the demise of MNs is crucial and will provide new insights into the complex cellular mechanisms underlying ALS.

Aquimarina aquimarini sp. nov. and Aquimarina spinulae sp. nov., novel bacterial species with versatile natural product biosynthesis potential isolated from marine sponges.

This study describes two Gram-negative, flexirubin-producing, biofilm-forming, motile-by-gliding and rod-shaped bacteria, isolated from the marine sponges Ircinia variabilis and Sarcotragus spinosulus collected off the coast of Algarve, Portugal. Both strains, designated Aq135T and Aq349T, were classified into the genus Aquimarina by means of 16S rRNA gene sequencing. We then performed phylogenetic, phylogenomic and biochemical analyses to determine whether these strains represent novel Aquimarina species. Whereas the closest 16S rRNA gene relatives to strain Aq135T were Aquimarina macrocephali JAMB N27T (97.8 %) and Aquimarina sediminis w01T (97.1 %), strain Aq349T was more closely related to Aquimarina megaterium XH134T (99.2 %) and Aquimarina atlantica 22II-S11-z7T (98.1 %). Both strains showed genome-wide average nucleotide identity scores below the species level cut-off (95 %) with all Aquimarina type strains with publicly available genomes, including their closest relatives. Digital DNA-DNA hybridization further suggested a novel species status for both strains since values lower than 70 % hybridization level with other Aquimarina type strains were obtained. Strains Aq135T and Aq349T grew from 4 to 30°C and with between 1-5 % (w/v) NaCl in marine broth. The most abundant fatty acids were iso-C17 : 03-OH and iso-C15 : 0 and the only respiratory quinone was MK-6. Strain Aq135T was catalase-positive and ß-galactosidase-negative, while Aq349T was catalase-negative and ß-galactosidase-positive. These strains hold unique sets of secondary metabolite biosynthetic gene clusters and are known to produce the peptide antibiotics aquimarins (Aq135T) and the trans-AT polyketide cuniculene (Aq349T), respectively. Based on the polyphasic approach employed in this study, we propose the novel species names Aquimarina aquimarini sp. nov. (type strain Aq135T=DSM 115833T=UCCCB 169T=ATCC TSD-360T) and Aquimarina spinulae sp. nov. (type strain Aq349T=DSM 115834T=UCCCB 170T=ATCC TSD-361T).

Efficacy and Safety of Monoclonal Antibodies for the Treatment of Eosinophilic Esophagitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: Monoclonal antibodies (MAbs) have clinical benefits for treating several atopic diseases. However, consensus on its use for eosinophilic esophagitis (EoE) is lacking. The present meta-analysis aimed to compare the efficacy and safety of MAbs versus placebo for treating EoE. METHODS: We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcomes were changes in peak esophageal eosinophils count/high power field (HPF) and mean esophageal eosinophils count/HPF. The secondary outcomes were changes in the EoE-Histology Scoring System (EoE-HSS), Endoscopic Reference Score (EREFS), dysphagia score, and adverse events (AEs). We compared binary outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD) or standardized mean difference (SMD), with 95% confidence interval (CI). Considering the diversity of mechanistic properties of MAbs, a pre-specified subgroup analysis by MAb mechanism of action was performed for all outcomes, provided that at least two studies were in each subgroup. Heterogeneity was assessed using Cochran's Q test and I2 statistics. RESULTS: 6 RCTs were included (533 patients). Compared to placebo, MAbs led to a significant reduction in peak esophageal eosinophils count/HPF (MD -0.78; CI 95% -0.87, -0.6801) and mean esophageal eosinophils count/HPF (SMD -0.79; CI 95% -1.5, -0.08). Moreover, MAbs significantly reduced EoE-HSS scores (grade score: SMD -9.31; 95% CI -13.95, -4.6701; stage score: SMD -10.18; 95% CI -15.06, -5.31), EREFS (SMD -5.95; CI 95% -9.19, -2.71) and dysphagia score (SMD -1.79; CI 95% -3.36, -0.23) without increasing AEs compared to placebo. Among those MAbs whose mechanism of action includes the blockage of the receptor for IL-13 (Dupilumab, QAX576, and RPC4046), the scores of EoE-HSS grade, EoE-HSS stage, EREFS, and dysphagia were significantly reduced, and they presented a similar risk of overall and serious AEs compared to placebo. CONCLUSION: MAbs seem effective and safe in reducing esophageal eosinophil infiltrate, EoE-HSS score, EREFS score, and dysphagia symptoms in patients with EoE. However, further evidence is needed to establish its place in EoE management.

Navigating concussion - community rugby players' experiences of a concussion management initiative in New Zealand.

OBJECTIVE: Concussion is a serious concern in sport, with the potential to cause short- and long-term health consequences. These concerns highlight the need for the translation of concussion management guidelines into use in real-world sports settings. This qualitative study explores community rugby players' concussion experiences as part of New Zealand Rugby's concussion management pathway. METHODS: Semi-structured interviews were conducted with 36 rugby players (35 males and 1 female; 22 played at school and 14 at club-level; mean age 19.8 ± 4.8) Thematic analysis was utilized to analyze data. RESULTS: Four themes were identified i) the symptom journey, ii) the role of a dedicated concussion management pathway in shaping players' experiences, iii) the influence of coaches and physiotherapists, and iv) rugby culture. Support received as part of the concussion management pathway, and from individuals who were part of players' concussion journey, deeply impacted their overall experience. However, players identified insufficient guidance while returning to school/work. At times, the sport's collective cultural values made it difficult for players to enact positive concussion management behavior. CONCLUSION: The findings highlight the importance of a defined management pathway to support players' recovery. Addressing negative aspects of rugby's collectivist culture remains critical for optimal concussion management and recovery.

A methodology to estimate postdisaster unmet housing needs using limited data: Application to the 2017 California wildfires.

In the United States, assistance from the Department of Housing and Urban Development (HUD) plays an essential role in supporting the postdisaster recovery of states with unmet housing needs. HUD requires data on unmet needs to appropriate recovery funds. Ground truth data are not available for months after a disaster, however, so HUD uses a simplified approach to estimate unmet housing needs. State authorities argue that HUD's simplified approach underestimates the state's needs. This article presents a methodology to estimate postdisaster unmet housing needs that is accurate and relies only on data obtained shortly after a disaster. Data on the number of damaged buildings are combined with models for expected repair costs. Statistical models for aid distributed by the Federal Emergency Management Agency (FEMA) and the Small Business Administration (SBA) are then developed and used to forecast funding provided by those agencies. With these forecasts, the unmet need to be funded by HUD is estimated. The approach can be used for multiple states and hazard types. As validation, the proposed methodology is used to estimate the unmet housing needs following disasters that struck California in 2017. California authorities suggest that HUD's methodology underestimated the state's needs by a factor of 20. Conversely, the proposed methodology can replicate the estimates by the state authorities and provide accounts of losses, the amount of funding from FEMA and SBA, and the total unmet housing needs without requiring data unavailable shortly after a disaster. Thus, the proposed methodology can help improve HUD's funding appropriation without delays.

Is the link between the Dark Tetrad and the acceptance of sexual violence mediated by sexual machismo?

Previous studies have established relationships between the Dark Tetrad traits and sexual violence and its acceptance through myths about this type of violence. Sexual violence is positively associated with machismo, with sexist beliefs having been found to be linked with the Dark Tetrad and with the acceptance of sexual violence. Using a community sample comprising 362 adults between the ages of 18 and 70 (M = 35.6, SD = 14.3) and three self-report measures, this cross-sectional study aimed to explore the mediating role of sexual machismo in the relationship between each of the Dark Tetrad traits and the acceptance of sexual violence, both in the overall sample and by gender, as well as whether a significant variance in this acceptance is explained by the "dark" traits, sexual machismo, and gender. In the regression, sexual machismo (the male) gender, and only Machiavellianism were uniquely associated with the acceptance of sexual violence, and sexual machismo partially mediated the associations between the Dark Tetrad and the acceptance of sexual violence. These findings indicate that being male and higher in sexism is more closely linked with the acceptance of sexual violence than most Dark Tetrad traits. Moreover, the associations between the Dark Tetrad, sexual machismo, and the acceptance of sexual violence were stronger in men, consistent with the notion that these traits facilitate a "male" exploitive mating strategy, which likely also extends to victim-blaming and positive attitudes about sexual violence more broadly. Lastly, the results emphasize the pervasiveness of beliefs about male superiority over women and its relationship with victim-blaming even in women.

Tag SNP selection for prediction of adaptation traits in Braford and Hereford cattle using Bayesian methods.

This study utilized Bayesian inference in a genome-wide association study (GWAS) to identify genetic markers associated with traits relevant to the adaptation of Hereford and Braford cattle breeds. We focused on eye pigmentation (EP), weaning hair coat (WHC), yearling hair coat (YHC), and breeding standard (BS). Our dataset comprised 126,290 animals in the pedigree. Out of these, 233 sires were genotyped using high-density (HD) chips, and 3750 animals with medium-density (50 K) single-nucleotide polymorphism (SNP) chips. Employing the Bayes B method with a prior probability of π = 0.99, we identified and tagged single nucleotide polymorphisms (Tag SNPs), ranging from 18 to 117 SNPs depending on the trait. These Tag SNPs facilitated the construction of reduced SNP panels. We then evaluated the predictive accuracy of these panels in comparison to traditional medium-density SNP chips. The accuracy of genomic predictions using these reduced panels varied significantly depending on the clustering method, ranging from 0.13 to 0.65. Additionally, we conducted functional enrichment analysis that found genes associated with the most informative SNP markers in the current study, thereby providing biological insights into the genomic basis of these traits.

Transcriptomics analysis of human iPSC-derived dopaminergic neurons reveals a novel model for sporadic Parkinson's disease.

Parkinson's disease (PD) is a progressive, neurodegenerative disease affecting over 1% of the population beyond 65 years of age. Although some PD cases are inheritable, the majority of PD cases occur in a sporadic manner. Risk factors comprise next to heredity, age, and gender also exposure to neurotoxins from for instance pesticides and herbicides. As PD is characterized by a loss of dopaminergic neurons in the substantia nigra, it is nearly impossible to access and extract these cells from patients for investigating disease mechanisms. The emergence of induced pluripotent stem (iPSC) technology allows differentiating and growing human dopaminergic neurons, which can be used for in vitro disease modeling. Here, we differentiated human iPSCs into dopaminergic neurons, and subsequently exposed the cells to increasing concentrations of the neurotoxin MPP+. Temporal transcriptomics analysis revealed a strong time- and dose-dependent response with genes over-represented across pathways involved in PD etiology such as "Parkinson's Disease", "Dopaminergic signaling" and "calcium signaling". Moreover, we validated this disease model by showing robust overlap with a meta-analysis of transcriptomics data from substantia nigra from post-mortem PD patients. The overlap included genes linked to e.g. mitochondrial dysfunction, neuron differentiation, apoptosis and inflammation. Our data shows, that MPP+-induced, human iPSC-derived dopaminergic neurons present molecular perturbations as observed in the etiology of PD. Therefore we propose iPSC-derived dopaminergic neurons as a foundation for a novel sporadic PD model to study the pathomolecular mechanisms of PD, but also to screen for novel anti-PD drugs and to develop and test new treatment strategies.

Use of iRNA in the post-transcriptional gene silencing of necrosis-inducing Phytophthora protein 1(NPP1) in Phytophthora cinnamomi.

BACKGROUND: Phytophthora cinnamomi is an Oomycetes associated with soil, this Oomycete is one of the most destructive species of Phytophthora, being responsible for the decline of more than 5000 ornamental, forest, or fruit plants. It can secrete a class of protein NPP1 (Phytophthora necrosis inducing protein 1), responsible for inducing necrosis in leaves and roots of plants, leading to their death. OBJECTIVE: This work will report the characterization of the Phytophthora cinnamomi NPP1 gene responsible for the infection of Castanea sativa roots and will characterize the mechanisms of interaction between Phytophthora cinnamomi and Castanea sativa, by gene silencing NPP1 from Phytophthora cinnamomi mediated by RNAi. METHODS AND RESULTS: For silencing a part of the coding region of the NPP1 gene, was placed in the sense and antisense directions between an intron and ligated to the integrative vector pTH210. Cassette integration was confirmed by PCR and sequencing on the hygromycin-resistant Phytophthora cinnamomi transformants. Transformants obtained with the silenced gene was used to infect Castanea sativa. CONCLUSIONS: Plants infected with these transformants showed a great reduction in disease symptoms, confirming iRNA as a potential alternative biological tool in the study of molecular factors, and in the control and management of Phytophthora cinnamomi.

CRISPR/Cas9 screen in human iPSC-derived cortical neurons identifies NEK6 as a novel disease modifier of C9orf72 poly(PR) toxicity.

INTRODUCTION: The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are hexanucleotide repeats in chromosome 9 open reading frame 72 (C9orf72). These repeats produce dipeptide repeat proteins with poly(PR) being the most toxic one. METHODS: We performed a kinome-wide CRISPR/Cas9 knock-out screen in human induced pluripotent stem cell (iPSC) -derived cortical neurons to identify modifiers of poly(PR) toxicity, and validated the role of candidate modifiers using in vitro, in vivo, and ex-vivo studies. RESULTS: Knock-down of NIMA-related kinase 6 (NEK6) prevented neuronal toxicity caused by poly(PR). Knock-down of nek6 also ameliorated the poly(PR)-induced axonopathy in zebrafish and NEK6 was aberrantly expressed in C9orf72 patients. Suppression of NEK6 expression and NEK6 activity inhibition rescued axonal transport defects in cortical neurons from C9orf72 patient iPSCs, at least partially by reversing p53-related DNA damage. DISCUSSION: We identified NEK6, which regulates poly(PR)-mediated p53-related DNA damage, as a novel therapeutic target for C9orf72 FTD/ALS.

Evaluation of the clinical performance of dentures manufactured by computer-aided technology and conventional techniques: A systematic review.

STATEMENT OF PROBLEM: The introduction of computer-aided design and computer-aided manufacturing (CAD-CAM) technology for complete denture fabrication may have improved clinical outcomes compared with conventional techniques. However, systematic reviews comparing these techniques are lacking. PURPOSE: The purpose of this systematic review was to identify, compare, and synthesize the outcomes of published clinical studies related to complete denture fabrication, with respect to the differences between CAD-CAM technology and conventional techniques. MATERIAL AND METHODS: A comprehensive search of studies published up to March 16, 2020, was conducted by using the PubMed/MEDLINE, Web of Science, Cochrane Library, SciELO, and Embase databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement criteria and was registered in the International Prospective Register of Systematic Reviews (PROSPERO ID 42020202614). The population, intervention, comparison, and outcome (PICO) question was: Do CAD-CAM complete dentures have a similar functional performance to those fabricated by conventional techniques? The quality of publications was appraised by using the Critical Appraisal Skills Program (CASP) checklists. RESULTS: Of the 1232 titles, 6 articles were selected. The studies reported better retention of digitally manufactured complete dentures without denture adhesives than that of conventional complete dentures with or without denture adhesives. Other studies reported that dentures manufactured with digital systems were better adapted to tissue surfaces, required less clinical time, were lower in cost, and provided better experience and satisfaction to patients. CONCLUSIONS: The assessment of CAD-CAM planning and manufacturing through clinical studies is ongoing. However, preliminary results indicate better clinical performance and lower overall costs of digital complete dentures than conventional dentures.

Sit to stand test and handgrip strength in men and women with post-COVID-19 syndrome without invasive ventilator support: insights from a Brazilian observational study.

Two valid tests have been used in patients with post-COVID-19 syndrome (coronavirus disease 2019) due to their fast application, feasibility, and accessible procedures, facilitating data collection in large groups: the 1-minute sit-to-stand test (STS) and handgrip strength (HGS) dynamometry. The present study aimed to: i) assess the STS and HGS in men and women with post-COVID-19 syndrome who did not require invasive ventilator support; ii) correlate STS repetitions and HGS with time since the COVID-19 diagnosis. Six hundred and twenty-two men and women with post-COVID-19 syndrome who did not require invasive ventilatory support performed the STS and HGS tests at the beginning of the rehabilitation process at a Reference Hospital Centre. Women over 55 years presented significantly lower results compared to participants under 55 years. For the HGS, the median ranged from 42 to 48 kg and 70 to 81 kg for the female and male groups, respectively. The correlations of time since COVID-19 diagnosis with STS and HGS ranged from -0.16 to 0.02 (p>0.05) for women and men, respectively.The test results could be used for the initial analysis of normality ranges and comparisons with other populations. Although STS repetitions and HGS presented low and non-significant correlations with time since the COVID-19 diagnosis, some COVID-19 sequelae were not measured, so these data should be interpreted with caution.

The Enhancing Role of Emotion Regulation in the Links between Early Positive Memories and Self-harm and Suicidal Ideation in Adolescence.

Adolescence is a critical developmental period associated with an increased variety of interrelated risks and vulnerabilities. Previous studies have found associations between early memories of warmth and safeness, as well as emotion regulation, and self-harm and suicidal ideation in adolescence. Additionally, these early emotional memories have been found to be positively linked with some indicators of emotion regulation during this period. The present cross-sectional study extends prior research by exploring the moderating role of emotion regulation in the relationships between early memories of warmth and safeness, as well as each of the following risk-related outcomes in adolescence, in younger (i.e., 13-15) and older (i.e., 16-19) adolescents: suicidal ideation and self-harm and its associated functions (i.e., automatic and social reinforcement. Three self-report measures of these early emotional memories, emotion regulation, and risk-related outcomes, and a sample of 7918 Portuguese adolescents (53.3% females), with ages ranging from 13 to 19 (Mage = 15.5), were used. In both age groups, at high levels of emotion regulation, early memories of warmth and safeness had a greater (negative) effect on suicidal ideation and the automatic reinforcement function of self-harm, compared to at average and low levels of emotion regulation. These findings highlight the enhancing role of emotion regulation on the associations between early memories of warmth and safeness and some risk-related outcomes in adolescents, both younger and older, which reveals the relevance of targeting emotion regulation when preventing or tackling these outcomes, regardless of adolescents' levels of early memories of warmth and safeness.

"Help Me Control My Impulses!": Adolescent Impulsivity and Its Negative Individual, Family, Peer, and Community Explanatory Factors.

The literature shows that impulsivity, prevalent in adolescence, is negatively linked with a variety of psychosocial factors (e.g., positive interpersonal relationships, emotion regulation); however, there is limited research examining the relative contribution of multiple factors for this trait nor exploring how these factors influence the associations between impulsivity and risk-related outcomes. Drawing on multiple components of the unified theory of development (i.e., psychological variables, peers subsystem, community subsystem, family processes subsystem), this cross-sectional study aims to identify explanatory psychosocial variables (i.e., early memories of warmth and safeness, rational decision-making style, resilience, emotion regulation, coping, parental attachment, social group attachment, satisfaction with school and family-related variables) that are negatively related with impulsivity, in younger (13-15) and older (16-19 years) adolescents, and explore their moderating role in the associations between this trait and some risk-related outcomes (i.e., verbal aggression, anger, self-harm, other high-risk behaviors). A representative sample of 6894 adolescents (52.9% female) living in the Azores (Portugal), with ages ranging from 13 to 19 (M = 15.4), was used. Two stepwise multiple regressions, one for each age group, revealed that only emotion regulation, parental attachment, and social group attachment had a negative effect on impulsivity in both age groups; additionally, satisfaction with teachers also had this effect in younger adolescents. The first three variables weakened the positive associations between impulsivity and the risk-related outcomes. These results suggest that the psychological system and all subsystems of the social context measured play a relevant role in explaining adolescent impulsivity and that it may be reduced by promoting emotion regulation, positive parenting practices, healthier relationships with peers, and healthier relationships with teachers.

Online eye-movement classification with temporal convolutional networks.

The simultaneous classification of the three most basic eye-movement patterns is known as the ternary eye-movement classification problem (3EMCP). Dynamic, interactive real-time applications that must instantly adjust or respond to certain eye behaviors would highly benefit from accurate, robust, fast, and low-latency classification methods. Recent developments based on 1D-CNN-BiLSTM and TCN architectures have demonstrated to be more accurate and robust than previous solutions, but solely considering offline applications. In this paper, we propose a TCN classifier for the 3EMCP, adapted to online applications, that does not require look-ahead buffers. We introduce a new lightweight preprocessing technique that allows the TCN to make real-time predictions at about 500 Hz with low latency using commodity hardware. We evaluate the TCN performance against other two deep neural models: a CNN-LSTM and a CNN-BiLSTM, also adapted to online classification. Furthermore, we compare the performance of the deep neural models against a lightweight real-time Bayesian classifier (I-BDT). Our results, considering two publicly available datasets, show that the proposed TCN model consistently outperforms other methods for all classes. The results also show that, though it is possible to achieve reasonable accuracy levels with zero-length look ahead, the performance of all methods improve with the use of look-ahead information. The codebase, pre-trained models, and datasets are available at https://github.com/elmadjian/OEMC.

Cross-Cultural Translation and Adaptation of the Perceived Recovery Status Scale to Brazilian Portuguese.

CONTEXT: One of the primary training variables, although often overlooked, is recovery level achieved before starting subsequent training sessions. To find a more practical measurement that is consonant with the daily training routine, the Perceived Recovery Status (PRS) scale is proposed. In this perspective, the present study aimed to translate and culturally adapt the PRS scale into Brazilian Portuguese. DESIGN: This was a clinical measurement. METHODS: The cross-cultural translation was performed according to guidelines. Linguistic validation consisted of 5 stages: forward translation, translation synthesis, back translation, analysis of inconsistencies, and cognitive debriefing. RESULTS: During forward translation, different interpretations were obtained from the 2 translators (versions V1 and V2). Supported by an expert committee, a combined version (V3) was obtained from V1 and V2. During back translation, different interpretations were obtained from the 2 translators (versions V4 and V5). Discrepancies, applicability, and cultural equivalence were documented and analyzed by the expert committee participating in the cross-cultural translation procedure. During the cognitive debriefing, a group of 5 Brazilian people from the general population were asked to participate in a cognitive debriefing to assess the comprehensibility of the translated items. CONCLUSIONS: The PRS was translated and culturally adapted to Brazilian Portuguese (PRS-Brasil).

Exploration of the Types of Rarity in the Arctic Ocean from the Perspective of Multiple Methodologies.

The Arctic Ocean is facing rapid environmental changes with cascading effects on the entire Arctic marine ecosystem. However, we have a limited understanding of the consequences such changes have on bacteria and archaea (prokaryotes) at the base of the marine food web. In this study, we show how the prokaryotic rare biosphere behaves over a range of highly heterogeneous environmental conditions using 16S rRNA gene reads from amplicon and metagenome sequencing data from seawater samples collected during the Norwegian young sea ICE expedition between late winter and early summer. The prokaryotic rare biosphere was analyzed using different approaches: amplicon sequence variants and operational taxonomic units from the 16S rRNA gene amplicons and operational taxonomic units from the 16S rRNA genes of the metagenomes. We found that prokaryotic rare biosphere communities are specific to certain water masses, and that the majority of the rare taxa identified were always rare and disappeared in at least one sample under changing conditions, suggesting their high sensitivity to environmental heterogeneity. In addition, our methodological comparison revealed a good performance of 16S rRNA gene amplicon sequencing in describing rare biosphere patterns, while the metagenome-derived data were better to capture a significant diversity of so-far uncultivated rare taxa. Our analysis on the dynamics of the rare prokaryotic biosphere, by combining different methodological approaches, improves the description of the types of rarity predicted from Community Assembly theory in the Arctic Ocean.

Insights into the Antimicrobial Activities and Metabolomes of Aquimarina (Flavobacteriaceae, Bacteroidetes) Species from the Rare Marine Biosphere.

Two novel natural products, the polyketide cuniculene and the peptide antibiotic aquimarin, were recently discovered from the marine bacterial genus Aquimarina. However, the diversity of the secondary metabolite biosynthetic gene clusters (SM-BGCs) in Aquimarina genomes indicates a far greater biosynthetic potential. In this study, nine representative Aquimarina strains were tested for antimicrobial activity against diverse human-pathogenic and marine microorganisms and subjected to metabolomic and genomic profiling. We found an inhibitory activity of most Aquimarina strains against Candida glabrata and marine Vibrio and Alphaproteobacteria species. Aquimarina sp. Aq135 and Aquimarina muelleri crude extracts showed particularly promising antimicrobial activities, amongst others against methicillin-resistant Staphylococcus aureus. The metabolomic and functional genomic profiles of Aquimarina spp. followed similar patterns and were shaped by phylogeny. SM-BGC and metabolomics networks suggest the presence of novel polyketides and peptides, including cyclic depsipeptide-related compounds. Moreover, exploration of the 'Sponge Microbiome Project' dataset revealed that Aquimarina spp. possess low-abundance distributions worldwide across multiple marine biotopes. Our study emphasizes the relevance of this member of the microbial rare biosphere as a promising source of novel natural products. We predict that future metabologenomics studies of Aquimarina species will expand the spectrum of known secondary metabolites and bioactivities from marine ecosystems.

Marine Sponge and Octocoral-Associated Bacteria Show Versatile Secondary Metabolite Biosynthesis Potential and Antimicrobial Activities against Human Pathogens.

Marine microbiomes are prolific sources of bioactive natural products of potential pharmaceutical value. This study inspected two culture collections comprising 919 host-associated marine bacteria belonging to 55 genera and several thus-far unclassified lineages to identify isolates with potentially rich secondary metabolism and antimicrobial activities. Seventy representative isolates had their genomes mined for secondary metabolite biosynthetic gene clusters (SM-BGCs) and were screened for antimicrobial activities against four pathogenic bacteria and five pathogenic Candida strains. In total, 466 SM-BGCs were identified, with antimicrobial peptide- and polyketide synthase-related SM-BGCs being frequently detected. Only 38 SM-BGCs had similarities greater than 70% to SM-BGCs encoding known compounds, highlighting the potential biosynthetic novelty encoded by these genomes. Cross-streak assays showed that 33 of the 70 genome-sequenced isolates were active against at least one Candida species, while 44 isolates showed activity against at least one bacterial pathogen. Taxon-specific differences in antimicrobial activity among isolates suggested distinct molecules involved in antagonism against bacterial versus Candida pathogens. The here reported culture collections and genome-sequenced isolates constitute a valuable resource of understudied marine bacteria displaying antimicrobial activities and potential for the biosynthesis of novel secondary metabolites, holding promise for a future sustainable production of marine drug leads.

Validity of range of motion, muscle strength, sensitivity, and Tinel sign tele-assessment in adults with traumatic brachial plexus injury.

BACKGROUND: The COVID-19 pandemic and the need for social distancing created challenges for accessing and providing health services. Telemedicine enables prompt evaluation of patients with traumatic brachial plexus injury, even at a distance, without prejudice to the prognosis. The present study aimed to verify the validity of range of motion, muscle strength, sensitivity, and Tinel sign tele-assessment in adults with traumatic brachial plexus injury (TBPI). METHODS: A cross-sectional study of twenty-one men and women with TBPI admitted for treatment at a Rehabilitation Hospital Network was conducted. The participants were assessed for range of motion, muscle strength, sensitivity, and Tinel sign at two moments: in-person assessment (IPA) and tele-assessment (TA). RESULTS: The TA muscle strength tests presented significant and excellent correlations with the IPA (the intra-rater intraclass correlation coefficient, ICC ranged between 0.79 and 1.00 depending on the muscle tested). The agreement between the TA and IPA range of motion tests ranged from substantial to moderate (weighted kappa coefficient of 0.47-0.76 (p < 0.05) depending on the joint), and the kappa coefficient did not indicate a statistically significant agreement in the range of motion tests of supination, wrist flexors, shoulder flexors, and shoulder external rotators. The agreement between the IPA andTA sensitivity tests of all innervations ranged from substantial to almost perfect (weighted kappa coefficient 0.61-0.83, p < 0.05) except for the C5 innervation, where the kappa coefficient did not indicate a statistically significant agreement. The IPA versus TA Tinel sign test showed a moderate agreement (weighted kappa coefficient of 0.57, p < 0.05). CONCLUSIONS: The present study demonstrated that muscle strength tele-assessment is valid in adults with TBPI and presented a strong agreement for many components of TA range of motion, sensitivity, and Tinel sign tests.