bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis and clinical significance of Human bocavirus 1 in children hospitalized for lower acute respiratory infection: molecular detection in respiratory secretions and serum
Authors: Colazo Salbetti Maria Belen , Boggio Gabriel Amilcar , Abbiatti Giuliana , Montañez Sandoz Agustina , Villarreal Veronica , Torres Erika , Pedranti Mauro , Zalazar Jose Alberto , Moreno Laura , Adamo Maria Pilar
Published: October 2022

Introduction. Human bocavirus 1 (HBoV1) infection occurs with viral genome presence in respiratory secretions (RS) and serum, and therefore both samples can be used for diagnosis.

Gap statement. The diagnostic sensitivity of HBoV1 DNA detection in serum and the duration of DNAaemia in severe clinical cases have not been elucidated.

Aim. To determine HBoV1 DNA in serum and RS of paediatric patients hospitalized for lower acute respiratory infection (LARI) and to analyse the clinical–epidemiological features of positive cases.

Methodology. This was a prospective, transverse study. Physicians selected the clinical situations and obtained paired clinical samples (RS and serum) that were tested by PCR/qPCR for HBoV1. Positive cases were analysed considering time of specimen collection, co-detection, clinical manifestations and viral load; statistical significant level was set at α=0.05.

Results. HBoV1 was detected in 98 of 402 cases included (24 %); 18/98 (18 %) patients had the virus detectable in serum and 91/98 (93 %) in RS (P<0.001). Positivity rates were not significantly different in patients with RS and serum collected within or beyond 24 h of admission. Single HBoV1 infection was identified in 39/98 patients (40 %), three patients had HBoV1 in both clinical samples (3/39, 8 %) and 32 (32/39, 82 %) only in RS, 22 of them (69 %) with both clinical samples within 24 h of admission. Cough (P=0.001) and rhinitis (P=0.003) were significantly frequent among them and most patients were diagnosed with bronchiolitis (22/39, 56 %) and pneumonia (9/39, 23 %), which was more frequent compared to cases with co-infection (P=0.04). No significant differences were identified among patients with high, medium or low viral load of HBoV1 regarding rate of positivity in both clinical samples, the time of collection of RS and serum, co-detection, first episode of LARI, clinical manifestations, comorbidity or requirement for assisted ventilation. Intensive care unit (ICU) patients had a significantly higher frequency of detection (P<0.001) and co-detection (P=0.001) compared to patients on standard care.

Conclusions. HBoV1 is prevalent among infant patients hospitalized for LARI and including it in the standard testing can add to the aetiological diagnosis in these cases, especially for patients admitted to the ICU. HBoV1 detection in serum did not contribute significantly to the diagnosis as compared to detection in respiratory secretions.
A Neuroimaging-based Precision Medicine Framework for Depression
Authors: Xiao Yao , Dong Shuai , Zhu Rongxin , Womer Fay Y. , Zhang Ran , Yang Jingyu , Zhang Luheng , M.D. Juan Liu , Zhang Weixiong , Liu Zhongchun , Zhang Xizhe , Wang Fei
Published: October 2022

Objective

Developing a neuroimaging-based precision medicine framework for depression.

Methods

The study was conducted in two stages at two sites: development of a neuroimaging-based subtyping and precise repetitive transcranial magnetic stimulation (rTMS) strategy for depression at Center 1 and its clinical application at Center 2. Center 1 identified depression subtypes and subtype-specific rTMS targets based on amplitude of low frequency fluctuation (ALFF) in a cohort of 238 major depressive disorder patients and 66 healthy controls (HC). Subtypes were identified using a Gaussian Mixture Model, and subtype-specific rTMS targets were selected based on dominant brain regions prominently differentiating depression subtypes from HC. Subsequently, one classifier trained per Center 1 findings for subtyping and subtype-specific rTMS targets were employed to deliver two-week precise rTMS to 72 hospitalized, depressed youths at Center 2. MRI and clinical assessments were obtained at baseline, midpoint, and treatment completion for evaluation.

Results

Two neuroimaging subtypes of depression, archetypal and atypical depression, were identified based on distinct frontal-posterior functional imbalance patterns as measured by ALFF. The dorsomedial prefrontal cortex was identified as the rTMS target for archetypal depression, and the occipital cortex for atypical depression. Following precise rTMS, ALFF alterations were normalized in both archetypal and atypical depressed youths, corresponding with symptom response of 90.00% in archetypal depression and 70.73% in atypical depression.

Conclusions

A precision medicine framework for depression was developed based on frontal-posterior functional imbalance and implemented with promising results. Future randomized controlled trials are warranted.

Chinese Clinical Trial Registry identifier: ChiCTR2100045391
Allele frequency differences of causal variants have a major impact on low cross-ancestry portability of PRS
Authors: Saitou Marie , Dahl Andy , Wang Qingbo , Liu Xuanyao
Published: October 2022

Genome-wide association studies (GWAS) are overwhelmingly biased toward European ancestries. Nearly all existing studies agree that transferring genetic predictions from European ancestries to other populations results in a substantial loss of accuracy. This is commonly referred to as low portability of polygenic risk scores (PRS) and is one of the most important barriers to the ethical clinical deployment of PRS. Yet, it remains unclear how much various genetic factors, such as linkage disequilibrium (LD) differences, allele frequency differences or causal effect differences, contribute to low PRS portability. In this study, we used gene expression levels in lymphoblastoid cell lines (LCLs) as a simplified model of complex traits with minimal environmental variation, in order to understand how much each genetic factor contributes to PRS portability from European to African populations. We found thatcis-genetic effects on gene expression are highly similar between European and African individuals (). This stands in stark contrast to the very low estimates ofcis-genetic correlation between Europeans and Africans in previous studies, which we demonstrate are artifacts of statistical bias. We showed that portability decreases with increasing LD differences in thecis-regions. We also found that allele frequency differences of causal variants have a striking impact on PRS portability. For example, PRS portability is reduced by more than 32% when the causalcis-variant is common (minor allele frequency, MAF > 5%) in European samples (training population) but is rarer (MAF < 5%) in African samples (prediction population). While large allele frequency differences can decrease PRS portability through increasing LD differences, we also show that causal allele frequency can significantly impact portability independently of LD. This observation suggests that improving statistical fine-mapping alone does not overcome the loss of portability caused by causal allele frequency differences. Lastly, we also found that causal allele frequency is the main genetic factor underlying differential gene expression levels across ancestries. We conclude that causal genetic effects are highly similar in Europeans and Africans, and low PRS portability is primarily due to allele frequency differences.
Fish-microbe systems in the hostile but highly biodiverse Amazonian blackwaters
Authors: Sylvain François-Étienne , Leroux Nicolas , Normandeau Eric , Custodio Jaqueline , Mercier Pierre-Luc , Bouslama Sidki , Holland Aleicia , Barroso Danilo , Val Adalberto Luis , Derome Nicolas
Published: October 2022

Amazonian blackwaters are extremely biodiverse systems containing some of the most naturally acidic, dissolved organic carbon-rich and ion-poor waters on Earth. Physiological adaptations of fish facing these ionoregulatory challenges are unresolved but could involve microbially-mediated processes. Here, we characterize the physiological response of 964 fish-microbe systems from four blackwater Teleost species along a natural hydrochemical gradient, using dual RNA-Seq and 16S rRNA of gill samples. We find that responses to blackwaters are host-species-specific, but occasionally include the overexpression of Toll-receptors and integrins associated to interkingdom communication. Blackwater gill microbiomes are characterized by a transcriptionally-active betaproteobacterial cluster potentially interfering with epithelial permeability. We explore further blackwater fish-microbe interactions by analyzing transcriptomes of 320 axenic zebrafish larvae exposed to sterile, non-sterile and inverted (non-native bacterioplankton) blackwater. We find that axenic zebrafish do not survive well when exposed to sterile/inverted blackwater, suggesting an essential role of endogenous symbionts in blackwater fish physiology.
A pilot study of exercise training for children and adolescents with inflammatory bowel disease: an evaluation of feasibility, safety, satisfaction, and efficacy
Authors: Bjelica Mila , Walker Rachel G. , Obeid Joyce , Issenman Robert M. , Timmons Brian W.
Published: October 2022

Background

Children with inflammatory bowel disease (IBD) experience extra-intestinal side effects including altered body composition, impaired muscle strength and aerobic capacity. Exercise training may remedy these issues.

Purpose

To assess the feasibility, safety, participant satisfaction and efficacy of a training program for youth with IBD.

Methods

Children with IBD completed 16 weeks of training (2 supervised+1 home sessions per week). Feasibility was assessed by tracking recruitment, adherence, and compliance rates. Safety was assessed by tracking symptoms and adverse events. Post-training interviews gauged satisfaction. Circulating inflammatory markers, body composition, muscle strength, aerobic fitness, and habitual physical activity, were measured at baseline, mid-training (8 weeks), and post-training.

Results

Eleven youth were recruited and 10 completed the study. Participants adhered to 28±1 of 32 prescribed supervised sessions and 8±4 of 16 prescribed home sessions. There were no adverse events, and overall feedback on training was positive. Post-training, we observed an increase in lean mass (+2.4±1.1 kg), bone density (+0.0124±0.015 g•cm-2), aerobic fitness (+2.8±5.7 mL•kgLM-1•min-1), and vigorous physical activity levels (+13.09± 8.95 min•hr-1) but no change in inflammation or muscle strength.

Conclusion

Supervised exercise training is feasible, safe, and effective for youth with IBD and should be encouraged.
Comparison of common respiratory pathogen detection in nasopharyngeal swabs, saline gargle specimens, pleural effusion and lower respiratory tract samples
Authors: Anastasiou Olympia E.
Published: October 2022

Multiplex PCR panels have been used for the diagnosis of viral respiratory infections in the last years. While the types of manufacturer validated and thus officially approved materials are usually limited, the tested materials in the clinical routine or studies often vary, which presents a challenge in light of the new EU-IVDR guideline. Aim of our present study was to evaluate if testing of lower respiratory tract (LRT) or saline gargle specimens (SGS) provided an advantage compared to the testing of nasopharyngeal swabs (NPS) and if the testing of pleural effusions (PE) provided any advantage compared to the testing of LRT samples.

We included 367 NPS vs LRT cases, of which 202 (55%) were negative in both samples, 108 (29%) were positive in both samples, 28 (8%) had a positive NPS and a negative LRT and 29 (8%) had a negative NPS but a positive LRT, with no significant differences between immunocompetent and immunosuppressed cases. We included 46 NPS vs SGS cases, of which 18 (39%) were negative in both samples, 18 (39%) were positive in both samples, 4 (9%) had a positive NPS and a negative SGS and 6 (13%) had a negative NPS but a positive SGS. Out of the 82 tested PE samples, only one (1%) was positive for Influenza B RNA (detected in the PE but not LTR), while for 5 positive LTR samples no viral genome could be detected in the PE. The samples were tested with the FTD respiratory viral panel for common respiratory viruses.

Testing of a lower respiratory tract sample after a negative upper respiratory tract sample may have an incremental diagnostic value. Gargle and nasopharyngeal swab samples seem to have a comparable diagnostic performance, while pleural effusion is a substandard material for the diagnosis of common respiratory virus infections.
Morpho-electric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex
Authors: Chartrand Thomas , Dalley Rachel , Close Jennie , Goriounova Natalia A. , Lee Brian R. , Mann Rusty , Miller Jeremy A. , Molnar Gabor , Mukora Alice , Alfiler Lauren , Baker Katherine , Bakken Trygve E. , Berg Jim , Bertagnolli Darren , Braun Thomas , Brouner Krissy , Casper Tamara , Csajbok Eva Adrienn , Dee Nick , Egdorf Tom , Enstrom Rachel , Galakhova Anna A. , Gary Amanda , Gelfand Emily , Goldy Jeff , Hadley Kristen , Heistek Tim S. , Hill DiJon , Jorstad Nik , Kim Lisa , Kocsis Agnes Katalin , Kruse Lauren , Kunst Michael , Leon Gabriela , Long Brian , Mallory Matthew , McGraw Medea , McMillen Delissa , Melief Erica J. , Mihut Norbert , Ng Lindsay , Nyhus Julie , Omstead Victoria , Peterfi Zoltan , Pom Alice , Potekhina Lydia , Rajanbabu Ramkumar , Rozsa Marton , Ruiz Augustin , Sandle Joanna , Sunkin Susan M. , Szots Ildiko , Tieu Michael , Toth Martin , Trinh Jessica , Vargas Sara , Vumbaco David , Williams Grace , Wilson Julia , Yao Zizhen , Barzo Pal , Cobbs Charles , Ellenbogen Richard G. , Esposito Luke , Ferreira Manuel , Gouwens Nathan W. , Grannan Benjamin , Gwinn Ryder P. , Hauptman Jason S. , Jarsky Tim , Keene C.Dirk , Ko Andrew L. , Koch Christof , Ojemann Jeffrey G. , Patel Anoop , Ruzevick Jacob , Silberberg Daniel L. , Smith Kimberly , Sorensen Staci A. , Tasic Bosiljka , Ting Jonathan T. , Waters Jack , de Kock Christiaan P.J. , Mansvelder Huib D. , Tamas Gabor , Zeng Hongkui , Kalmbach Brian , Lein Ed S.
Published: October 2022

Neocortical layer 1 (L1) is a site of convergence between pyramidal neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neuron types with extensive branching in L1, but whether L1 interneurons are similarly diverse is underexplored. Using patch-seq recordings from human neurosurgically resected tissues, we identified four transcriptomically defined subclasses, unique subtypes within those subclasses and additional types with no mouse L1 homologue. Compared with mouse, human subclasses were more strongly distinct from each other across all modalities. Accompanied by higher neuron density and more variable cell sizes compared with mouse, these findings suggest L1 is an evolutionary hotspot, reflecting the increasing demands of regulating the expanding human neocortical circuit.

One Sentence Summary

Using transcriptomics and morpho-electric analyses, we describe innovations in human neocortical layer 1 interneurons.
Sex-specific effects of voluntary wheel running on behavior and the gut microbiota-immune-brain axis in mice
Authors: Williams Zoë AP , Szyszkowicz Joanna Kasia , Osborne Natasha , Allehyany Bshaier , Nadon Christophe , Udechukwu Maryann Chinonye , Santos Ana , Audet Marie-Claude
Published: October 2022

Physical exercise has been positioned as a promising strategy to prevent and/or alleviate anxiety and depression, but the mechanisms underlying its effects on mental health have yet to be entirely determined. Although the prevalence of depression and anxiety in women is about twice that of men, very few studies have examined whether physical exercise could affect mental health differently according to sex. This study examined, in mice, the sex-specific effects of voluntary exercise on body weight, depressive- and anxiety-like behaviors, as well as different markers along the gut microbiota-immune-brain axis. Male and female C57BL/6N mice had voluntary access to running wheels in their home-cages for 24 days or were left undisturbed in identical home-cages without running wheels. Behaviors were then examined in the open field, Splash, elevated plus maze, and tail suspension tests. Gene expression of pro-inflammatory cytokines, microglia activation-related genes, and tight junction proteins was determined in the jejunum and the hippocampus, while microbiota composition and predicted function were verified in cecum contents. Voluntary exercise limited weight gains, reduced anxiety-like behaviors, and altered grooming patterns in males exclusively. Although the exercise intervention resulted in changes to brain inflammatory activity and to cecal microbiota composition and inferred function in both sexes, reductions in the jejunal expression of pro-inflammatory markers were observed in females only. These findings support the view that voluntary exercise, even when performed during a short period, is beneficial for mental and intestinal health and that its sex-specific effects on behavior could be, at least in part, mediated by the gut microbiota-immune-brain axis.
Skeletal muscle nuclei in mice are not post-mitotic
Authors: Borowik Agnieszka K , Davidyan Arik , Peelor Frederick F , Voloviceva Evelina , Doidge Stephen , Bubak Matthew P , Mobley Christopher B , McCarthy John J , Dupont-Versteegden Esther E , Miller Benjamin F
Published: October 2022

The skeletal muscle research field generally accepts that nuclei in skeletal muscle fibers (i.e., myonuclei) are post-mitotic and unable to proliferate. Because our deuterium oxide (D2O) labeling studies showed DNA synthesis in skeletal muscle tissue, we hypothesized that resident myonuclei can replicatein vivo. To test this hypothesis, we used a mouse model that temporally labeled myonuclei with GFP followed by D2O labeling during normal cage activity, functional overload, and with satellite cell ablation. During normal cage activity, we observed deuterium enrichment into myonuclear DNA in 7 out of 7 plantaris (PLA), 6 out of 6 tibialis anterior (TA), 5 out of 7 gastrocnemius (GAST) and 7 out of 7 quadriceps (QUAD). The average fractional synthesis rates (FSR) of DNA in myonuclei were: 0.0202 ± 0.0093 in PLA, 0.0239 ± 0.0040 in TA, 0.0076 ± 0. 0058 in GAST, and 0.0138 ± 0.0039 in QUAD, while there was no replication in myonuclei from EDL. These FSR values were largely reproduced in the overload and satellite cell ablation conditions although there were higher synthesis rates in the overloaded PLA muscle. We further provided evidence that myonuclear replication is through endoreplication that results in polyploidy. These novel findings contradict the dogma that skeletal muscle nuclei are post-mitotic and open potential avenues to harness the intrinsic replicative ability of myonuclei for muscle maintenance and growth.

Graphical Abstract
Machine learning unveils latent architecture of superiority illusion that predicts visual illusion perception and metacognitive performance
Authors: Matsuyoshi Daisuke , Isato Ayako , Yamada Makiko
Published: October 2022

Humans are typically inept at evaluating their abilities and predispositions, while often disregarding such lack of metacognitive insight into their capacities and even augmenting (albeit illusorily) self-evaluation such that they should have more desirable traits than an average peer. This superiority illusion helps maintain a healthy mental state. However, the scope and range of its influence on broader human behavior, especially perceptual tasks, remain elusive. As belief shapes the way people perceive and recognize, the illusory self-superiority belief potentially regulates our perceptual and metacognitive performance. In this study, we used hierarchical Bayesian estimation and machine learning of signal detection theoretic measures to understand how superiority illusion influences visual perception and metacognition for Ponzo illusion. Our results demonstrated that superiority illusion correlated with visual illusion magnitude and metacognitive performance. Next, we used machine learning with a relaxed elastic net and unveiled the latent architecture that underlies the correlations. We revealed that the “extraversion” superiority dimension tapped into visual illusion magnitude and metacognitive ability. In contrast, the “honesty-humility” and “neuroticism” dimensions were only predictive of visual illusion magnitude and metacognitive ability, respectively. These results suggest common and distinct influences of superiority features on perceptual sensitivity and metacognition. Our findings contribute to the accumulating body of evidence indicating that the superiority illusion leverage is far-reaching, even to visual perception.

Significance Statements

People have a cognitive bias to overestimate their abilities above the mean (superiority illusion) and thereby help maintain a healthy mental state. In this work, we show that the influences of superiority illusion are more extensive than previously thought. We find that superiority illusion correlated with visual illusion magnitude and metacognitive performance. Furthermore, using hierarchical Bayesian estimation and machine learning, we unveil the latent architecture (i.e., overlapping yet dissociable superiority features) that predicts visual illusion magnitude and metacognitive performance. These findings suggest that superiority illusion is a cardinal cognitive bias that involves a vast assortment of behavior as an illusion is an efficient and adaptive tool for humans to somehow thrive in a world of ambiguity.
Signal Peptide Peptidase-Like 2b affects APP cleavage and exhibits a biphasic Aβ-mediated expression in Alzheimer’s disease
Authors: Maccioni Riccardo , Travisan Caterina , Zerial Stefania , Wagener Annika , Andrade-Talavera Yuniesky , Picciau Federico , Grassi Caterina , Chen Gefei , Lemoine Laetitia , Fisahn André , Jiang Richeng , Fluhrer Regina , Mentrup Torben , Schröder Bernd , Nilsson Per , Tambaro Simone
Published: October 2022

Alzheimer’s disease (AD) is a multifactorial disorder driven by abnormal amyloid β-peptide (Aβ) levels. To identify new druggable pathways involved in the Aβ cascade we here investigated the AD pathophysiological role of the presenilin-like intramembrane protease signal peptide peptidase-like 2b (SPPL2b). Aβ42 induced a biphasic modulation of SPPL2b expression in human cell lines and ex vivo mouse brain slices. In addition, SPPL2b was elevated inAppNL-G-Fknock-in AD mice as well as in human AD samples. Early high neuronal expression of SPPL2b was followed by a downregulation in late AD pathology in bothAppNL-G-Fmice and Braak stage V AD brains. Importantly, SPPL2b overexpression or its genetic deletion significantly increased or reduced APP cleavage and Aβ production, respectively. Thus, our results strongly support the involvement of SPPL2b in AD pathology. The early Aβ-induced SPPL2b upregulation may enhance Aβ production in a vicious cycle further aggravating the Aβ pathology suggesting SPPL2b as a potential anti-Aβ drug target.
Needing: an active inference process for physiological motivation
Authors: Bosulu J. , Pezzulo G. , Hétu S.
Published: October 2022

Need states are internal states that arise from deprivation of crucial biological stimuli. They direct motivation, independently of external learning. Despite their separate origin, they interact with reward processing systems that respond to external stimuli. This paper aims to illuminate the functioning of the needing system through the lens of active inference, a framework for understanding brain and cognition.

We propose that need states exert a pervasive influence on the organism, which in active inference terms translates to a “pervasive surprise” - a measure of the distance from the organism’s preferred state. Crucially, we define needing as an active inference process that seeks to reduce this pervasive surprise.

Through a series of simulations, we demonstrate that our proposal successfully captures key aspects of the phenomenology and neurobiology of needing. We show that as need states increase, the tendency to occupy preferred states strengthens, independently of external reward prediction. Furthermore, need states increase the precision of states (stimuli and actions) leading to preferred states, suggesting their ability to amplify the value of reward cues and rewards themselves.

Collectively, our model and simulations provide valuable insights into the directional and underlying influence of need states, revealing how this influence amplifies the wanting or liking associated with relevant stimuli.
Antagonistic roles of canonical and alternative RPA in tandem CAG repeat diseases
Authors: Gall-Duncan Terence , Luo Jennifer , Jurkovic Carla-Marie , Fischer Laura A. , Fujita Kyota , Leib David E. , Li Vanessa , Harding Rachel J. , Tran Stephanie , Chen Ran , Tanaka Hikari , Deshmukh Amit L. , Mason Amanda G. , Lévesque Dominique , Khan Mahreen , Lanni Stella , Sato Nozomu , Caron Marie-Christine , Masson Jean-Yves , Panigrahi Gagan B. , Prasolava Tanya , Wang Peixiang , Lau Rachel , Tippett Lynette , Turner Clinton , La Spada Albert R. , Campos Eric I. , Curtis Maurice A. , Boisvert François-Michel , Faull Richard L.M. , Davidson Beverly L. , Okazawa Hitoshi , Wold Marc S. , Pearson Christopher E.
Published: October 2022

Tandem CAG repeat expansion mutations cause >15 neurodegenerative diseases, where ongoing expansions in patients’ brains are thought to drive disease onset and progression. Repeat length mutations will involve single-stranded DNAs prone to form mutagenic DNA structures. However, the involvement of single-stranded DNA binding proteins (SSBs) in the prevention or formation of repeat instability is poorly understood. Here, we assessed the role of two SSBs, canonical RPA (RPA1-RPA2-RPA3) and the related Alternative-RPA (Alt-RPA, RPA1-RPA4-RPA3), where the primate-specific RPA4 replaces RPA2. RPA is essential for all forms of DNA metabolism, while Alt-RPA has undefined functions. RPA and Alt-RPA are upregulated 2- and 10-fold, respectively, in brains of Huntington disease (HD) and spinocerebellar ataxia type 1 (SCA1) patients. Correct repair of slipped-CAG DNA structures, intermediates of expansion mutations, is enhanced by RPA, but blocked by Alt-RPA. Slipped-DNAs are bound and melted more efficiently by RPA than by Alt-RPA. Removal of excess slipped-DNAs by FAN1 nuclease is enhanced by RPA, but blocked by Alt-RPA. Protein-protein interactomes (BioID) reveal unique and shared partners of RPA and Alt-RPA, including proteins involved in CAG instability and known modifiers of HD and SCA1 disease. RPA overexpression inhibits rampant CAG expansions in SCA1 mouse brains, coinciding with improved neuron morphology and rescued motor phenotypes. Thus, SSBs are involved in repeat length mutations, where Alt-RPA antagonistically blocks RPA from suppressing CAG expansions and hence pathogenesis. The processing of repeat length mutations is one example by which an Alt-RPA↔RPA antagonistic interaction can affect outcomes, illuminating questions as to which of the many processes mediated by canonical RPA may also be modulated by Alt-RPA.
Sign-epistatic centromere drive in panmictic populations
Authors: Brud Evgeny
Published: October 2022

Comparative work has revealed a highly non-random elevation of karyotypic homogeneitywithinmammalian species for either telocentric chromosomes or centric fusions, and a karyotypic bimodalityamongspecies for these binary chromosome morphologies. A verbal theory developed by Pardo-Manuel de Villena and Sapienza argues that morphology-biased segregation in female meiosis explains the corresponding directional evolution in favor of one or the other chromosome form within species, and moreover, periodic reversals of meiotic spindle asymmetry explain the pattern of bimodality observed among species. Here I investigate a population genetic model in which I assume that the direction of the spindle asymmetry is under the control of a modifier gene, either linked or unlinked to a focal karyotypic mutant (linkage being to a centric fusion, say), and I derive the corresponding invasion conditions for the modifier-centric-fusion gene complex. I demonstrate that the scenario put forth in the verbal theory can be explained by a two-step process in which (1) a centric-fusion invades to fixation while the linked modifier winds up at an intermediate frequency by hitchhiking, and then (2) subsequent fixations of unlinked centric fusions occur. Via numerical iteration of the model, I demonstrate that the typical post-hitchhiking frequency of the linked modifier (from step 1) is broadly sufficient for subsequent unlinked invasions (step 2). Sign-reversing modifier evolution is therefore concluded to be a plausible mechanism instantiating the principles of a female drive theory of karyotype evolution.
A rapid review of Supplementary air filtration systems in health service settings. September 2022
Authors: Bowles Charlotte , Winfield Tom , Elston Lauren , Hasler Elise , Needham Antonia , Cooper Alison , Lewis Ruth , Edwards Adrian
Published: October 2022

The aerosol spread of SARS-CoV-2 has been a major challenge for healthcare facilities and there has been increased use of supplementary air filtration to mitigate SARS-CoV-2 transmission. Appropriately sized supplementary room air filtration systems could greatly reduce aerosol levels throughout ward spaces. Portable air filtration systems, such as those combining high efficiency particulate air (HEPA) filters and ultraviolet (UVC) light sterilisation, may be a scalable solution for removing respiratory viruses such as SARS-CoV-2. This rapid review aimed to assess the effectiveness of supplementary air cleaning devices in health service settings such as hospitals and dental clinics (including, but not limited to HEPA filtration, UVC light and mobile UVC light devices) to reduce the transmission of SARS-CoV-2.

One systematic review (Daga et al. 2021), three observational studies (Conway Morris et al. 2022, Thuresson et al. 2022, Sloof et al. 2022), one modelling study, (Buchan et al. 2020) and two experimental studies (Barnewall & Bischoff 2021, Snelling et al. 2022) were found. Outcome measures included symptom scores, presence of SARS-CoV-2 RNA in sample counts, general particulate matter counts, viral counts, and relative risk of SARS-CoV-2 exposure. From real world settings, the systematic review assessed the effectiveness of HEPA filtration in dental clinics (Daga et al. 2021), two additional observational studies assessed HEPA and UV light in UK hospital settings (Conway Morris et al. 2022, Sloof et al. 2022) and one observational study included mobile HEPA-filtration units in Swedish hospitals (Thuresson et al. 2022). Studies were published from 2020 onwards.

Real world evidence suggests supplementary air systems have the potential to reduce SARS-CoV-2 in the air and subsequently reduce transmission or infection rates but further research, with study designs having lower risk of bias, is required. HEPA filters alongside UVC light could provide the most notable reductions in SARS-CoV-2 counts, although the supporting evidence relates to HEPA/UVC filtration, and this review does not provide evidence on the effectiveness of other potential supplementary air filtration systems that could be used. Evidence is limited on the optimum air changes per hour needed and the positioning of air filtration units in rooms.

Funding statement

The Wales Centre for Evidence Based Care was funded for this work by the Wales COVID-19 Evidence Centre, itself funded by Health & Care Research Wales on behalf of Welsh Government.
On the frontlines in Shanghai: Stress, burnout and perceived benefit among COVID-19 testers and other personnel during the Omicron wave lockdown
Authors: Xu Zhimin , Liu Xia , de Melo Ghisi Gabriela Lima , Cui Lixian , Grace Sherry L
Published: October 2022

Background

COVID-19 control measure stringency including testing has been among the highest globally in China. Psychosocial impact on pandemic workers in Shanghai, and their pandemic-related attitudes were investigated.

Methods

Participants in this cross-sectional study were healthcare providers (HCP) and other support workers. A Mandarin self-report survey was administered via Wenjuanxing between April-June 2022 during the omicron-wave lockdown. The Perceived Stress Scale (PSS) and Maslach Burnout Inventory were administered, as well as pandemic-specific questions.

Results

887 workers participated, of which 691 (77.9%) were HCPs. They were working a mean of 6.25±1.24 days/week for 9.77±4.28 hours/day. Most participants were burnt-out, with 143(16.1%) moderately and 98(11.0%) seriously. Total PSS was 26.85±9.92/56, with 353(39.8%) participants having elevated stress. Workers perceived their families primarily as fully supportive (n=610, 68.8%), or also extremely concerned (n=203, 22.9%). Most wanted counselling and stress relief, but half(n=430) reported no time for it; indeed, 2/3rds wanted a few days off to rest (n=601).Many workers perceived benefits: that they fostered more cohesive relationships (n=581, 65.5%), they will be more resilient (n=693, 78.1%), and were honored to serve (n=747, 84.2%).Negative impacts were greater in HCPs, those with economic insecurity, and that did not perceive benefit (allp<.05).In adjusted analyses, those perceiving benefits showed significantly less burnout (OR=0.573, 95% CI=0.411 - 0.799), among other correlates.

Conclusions

Pandemic work, including among non-HCP, is stressful, but some can derive benefits.
Adding meaning to memories: How parietal cortex combines semantic content with episodic experience
Authors: Lee Hongmi , Keene Paul A. , Sweigart Sarah C. , Hutchinson J. Benjamin , Kuhl Brice A.
Published: October 2022

Neuroimaging studies of human memory have consistently found that univariate responses in parietal cortex track episodic experience with stimuli (whether stimuli are ‘old’ or ‘new’). More recently, pattern-based fMRI studies have shown that parietal cortex also carries information about the semantic content of remembered experiences. However, it is not well understood how memory-based and content-based signals are integrated within parietal cortex. Here, we used voxel-wise encoding models and a recognition memory task to predict the fMRI activity patterns evoked by complex natural scene images based on (a) the episodic history and (b) the semantic content of each image. Models were generated and compared across distinct subregions of parietal cortex and for occipitotemporal cortex. We show that parietal and occipitotemporal regions each encode memory and content information, but they differ in how they combine this information. Among parietal subregions, angular gyrus was characterized by robust and overlapping effects of memory and content. Moreover, subject-specific semantic tuning functions revealed that successful recognition shifted the amplitude of tuning functions in angular gyrus but did not change the selectivity of tuning. In other words, effects of memory and content were additive in angular gyrus. This pattern of data contrasted with occipitotemporal cortex where memory and content effects were interactive: memory effects were preferentially expressed by voxels tuned to the content of a remembered image. Collectively, these findings provide unique insight into how parietal cortex combines information about episodic memory and semantic content.
Gap-free nuclear and mitochondrial genomes ofUstilaginoidea virensstrain JS60-2, a fungal pathogen causing rice false smut
Authors: Wang Yin , Yang Lei , Yang Qun , Dong Jie , Wang Yufu , Duan Yuhang , Yin Weixiao , Zheng Lu , Sun Wenxian , Fan Jing , Luo Chao-Xi , Li Guotian
Published: October 2022

Rice false smut (RFS), caused byUstilaginoidea virens, has become a major disease in recent years, and mycotoxins produced byU. virensoften threaten food safety. To study fungal pathogenesis and identify potential targets for developing new fungicides, gap-free nuclear and complete mitochondrial genomes ofU. virensJS60-2 were sequenced and assembled. Using the second and third generation sequencing data, we assembled a 38.02-Mb genome that consists of seven contigs with the contig N50 being 6.32-Mb. In total, 8,486 protein-coding genes were annotated in the genome, including 21 secondary metabolism gene clusters. We also assembled the complete mitochondrial genome, which is 102,498 bp, with 28% GC content. The JS60-2 genomes assembled in this study will facilitate research onU. virensand contribute to RFS control.
Benchmarking water-limited yield potential and yield gaps of Shiraz in the Barossa and Eden Valleys
Authors: Bonada Marcos , Phogat Vinod , Collins Cassandra , Petrie Paul R. , Sadras Victor
Published: October 2022

Background and Aims

Vineyard performance is impacted by water availability including the amount and seasonality of rainfall and evapotranspiration and irrigation volume. We benchmarked water-limited yield potential (Yw), calculated yield gaps as the difference between Yw and actual yield, and explored the underlying environmental and management causes of these gaps.

Methods and Results

The yield and its components in two sections of 24 Shiraz vineyards was monitored during three vintages in the Barossa zone (GI). The frequency distribution of yield was L-shaped, with half the vineyards below 5.2 t ha-1, and an extended tail of the distribution that reached 24.9 t ha-1. The seasonal ratio of actual crop evapotranspiration and reference evapotranspiration was below 0.48 in 85% of cases, with a maximum of 0.65, highlighting a substantial water deficit in these vineyards. A boundary function relating actual yield and seasonal rainfall was fitted to quantify Yw. Yield gaps increased with increasing vine water deficit, quantified by the carbon isotope composition in the fruit. The yield gap was smaller with higher rainfall before budburst, putatively favouring early-season vegetative growth and allocation to reproduction, and with higher rainfall between flowering and veraison, putatively favouring fruit set and berry growth. The gap was larger with higher rainfall and lower radiation between budburst and flowering. The yield gap increased linearly with vine age between 6 and 33 yr at a rate of 0.3 t ha-1yr-1. The correlation between yield gap and yield components ranked bunch weight ≈ berries per bunch > bunch number > berry weight; the minimum to close the yield gap was 185,000 bunches ha-1, 105 g bunch-1, 108 berries bunch-1and 1.1 g berry-1.

Conclusions

Water deficit and vine age were major causes of yield gaps. Winter irrigation provides an opportunity to improve productivity. The cost of dealing with older, less productive vines needs to be weighed against the rate of increase in yield gap with vine age.

Significance of the Study

A boundary function to estimate water-limited yield potential returned viticulturally meaningful yield gaps and highlighted potential targets to improve vineyard productivity.
The Relationship Between Terroir and The Phenology of Barossa Shiraz
Authors: Bonada Marcos , Sadras Victor , Thomas Dane , Collins Cassandra , Schmidtke Leigh , Phogat Vinod , Petrie Paul
Published: October 2022

Background and Aims

Vine phenology results from the interaction between the genotype, environment and management, with implications for fruit, and wine composition. The impact of weather, site and management practices, underlying elements of terroir, impacting the timing of key phenological stages were explored across the Barossa Zone (GI).

Methods and Results

Vine phenology was assessed in three zones of 24 vineyards over three vintages using the E-L scale before veraison, and total soluble sugars (TSS) in berries during ripening. We explored the associations between weather, plant traits and viticultural variables, and development in four periods: pre-budburst, budburst-flowering, flowering-veraison and veraison-maturity. The spatial structure of the timing of phenological events suggested three main groups of vineyards. This structure followed gradients in topography and soils across the landscape, and were maintained despite the effect of the season (vintage). On average, differences between early and late groups of vineyards were 13 days at budburst, 20 days at flowering and 24 days at TSS = 24 °Brix. Phenology responded mainly to temperature until flowering, and to temperature and canopy size from flowering to maturity. The strength of the relationship between the duration of the period and temperature ranked pre-budburst (r2= 0.94) > budburst-flowering (r2= 0.40) > veraison-maturity (r2= 0.17). Duration of pre-budburst and budburst-flowering periods was shortened at 6 d °C-1, compared to 2 d °C-1for veraison-maturity. The duration from veraison to maturity increased with yield (r2= 0.29,Pa< 0.0001).

Conclusions

The spatial variation in development was maintained despite vintage effects and management practices. Variation in temperature due to topography and elevation were the major drivers of vine phenological development until flowering. During ripening, development was driven by temperature and carbon capture and partitioning.

Significance of the Study

This is the first attempt to show spatial variability on phenology across the Barossa Valley GI. The observed switch on drivers on phenology during development from temperature-driven processed before flowering to resource-dominated processes during ripening have implications for modelling and vineyard management.
Male-dominated courtship in an unexpectedly late-breeding Andean Lapwing (Vanellus resplendens) population
Authors: Dillenseger Guillaume , Rimoldi Andreas , Barreto Santiago , Ugarte-Lewis L. Mauricio , Kubelka Vojtěch
Published: October 2022

Sexual behavior, namely courtship and mating strategies, remain unexplored for numerous tropical birds. Andean Lapwing (Vanellus resplendens) is a shorebird inhabiting High Andes, and its reproductive biology is poorly known. Here, we performed standardized 49 observations of 20 pairs of Andean Lapwings at Laguna de Salinas, Peru (4315 m a.s.l.) during 2021–2022 breeding season. Lapwings in this studied population show social monogamy, a defined breeding season apparently triggered by rainfall, starting later than what is known according to the literature, and male-biased investment in courtship and territorial defense. These observations increase our knowledge on this understudied Neotropical species breeding at high elevations.

El comportamiento sexual, es decir, las estrategias de cortejo y apareamiento, permanecen sin explorarse para numerosas aves tropicales. El Avefría Andina (Vanellus resplendens) es un ave playera que habita los altos Andes, sin embargo, su biología reproductiva es poco conocida. Aquí, realizamos 49 observaciones estandarizadas de 20 parejas de avefrías andinas en Laguna de Salinas, Perú (4315 m.s.n.m.) durante la temporada 2021–2022. Las avefrías en esta población estudiada muestran monogamia social, una temporada reproductiva bien definida provocada por las precipitaciones, comenzando más tarde de lo que es descrito en la literatura, y una inversión predispuesta de machos en el cortejo y la defensa territorial. Estas observaciones aumentan nuestro conocimiento sobre esta especie Neotropical poco estudiada que se reproduce a gran altitud.
TAS2R receptor response helps predict new antimicrobial molecules for the 21stcentury
Authors: Sambu S
Published: October 2022

Artificial intelligence (AI) requires the provision of learnable data to successfully deliver requisite prediction power. In this article, it is demonstrable that standard physico-chemical parameters, while useful, were insufficient for development of powerful antimicrobial prediction algorithms. Initial models that focussed solely on the values extractable from the knowledge on the electrotopological, structural, constitutional descriptors did not meet the acceptance criteria for classifying antimicrobial activity. In contrast, efforts to conceptually define the diametric opposite of an antimicrobial compound helped to advance the category description into a learnable trait. Interestingly, the inclusion of ligand-receptor information using the ability of the molecules to stimulate transmembrane TAS2R receptor helped to increase the ability to distinguish antimicrobial molecules from the inactive ones. This novel approach to the development of AI models has allowed the development of models for the design and selection of newer, more powerful antimicrobial agents. This is especially valuable in an age where antimicrobial resistance could be ruinous to modern health systems.
SNCA Deletion Induced Aberrant Projection of Olfactory Sensory Neurons via NCK2-EphA4 Pathway
Authors: Ren Jing , Wu Chao , Yue Jingjing , Zeng Mengxia , Qu Mingqin , Chen Ning , Gao Ge , Jiang Yuwen , Liu Jing , Hu Baoyang , Yang Hui , Jiang Yin , Meng Fangang , Zhang Jianguo , Lu Ling-ling
Published: October 2022

Synucleinopathies such as Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy are characteristic forα-synuclein aggregates in neurons or glia, and are always manifested olfaction deficits at their primary onsets. It remains elusive why aggregation ofα-synuclein predominantly affect the olfactory system. Employing the knockout mice, we investigate the physiological function of α-synuclein in olfactory system. We found that deletion of α-synuclein primarily interferes the projection of olfactory sensory neurons. iTRAQ based LC-MS identified that 188 proteins are differentially expressed, including 9 that were associated with axon guidance. Among them, NCK2 is most significantly down-regulated, which was indicated to be involved a PPI network of 21 proteins, including 11 players of the Ephrin receptor signaling pathway. Either α-synuclein deletion or NCK2 deficiency can inactivate Eph A4 receptor. Re-expressing α-synuclein in the α-synuclein knockout neurons reverse the NCK2, as well as the phosphorylated Eph A4 (the activated Eph A4). Thus, α-synuclein regulates axon guidance through NCK2-Eph A4 signaling pathway. Malfunction of α-synuclein, whether because of deletion or aggregation, may cause aberrant olfactory neurons projection and subsequent olfaction deficits. This extended our knowledge of effects of α-synuclein in olfactory system, which may explain why olfaction is usually impaired in some synucleinopathy related disorders such as Parkinson’s disease.
Identification of plant-derived microRNAs in human kidney
Authors: Chen Xi , Xie Xishao , Liu Lu , Chen Hongyu , Wang Bo , Li Zheng , Zeng Linghui , Timko Michael P. , Chen Jianghua , Lin Weiqiang , Fan Longjiang
Published: October 2022

Plant-derived microRNAs (miRNAs) have been implicated as functional regulators in human diseases, although conclusive evidence of this effect remains to be reported. To examine their potential functional role, we profiled the plant-derived miRNAs in 139 blood exosome samples from renal transplantation patients and were able to identify 331 plant-derived miRNAs representing 149 families. According to their miRBase annotation, these miRNAs can be traced back to 76 plant species, most of which are foods common to the human diet (e.g., tomato, soybean, potato and rice). We also profiled 41 blood exosome samples from 22 patients with acute immune rejection (AR) of renal transplants and compared them to 21 samples from 11 patients with stable allograft function to explore possible roles of the functional plant miRNAs. We identified three plant-derived miRNAs (miR4995, miR2118/2218 and miR167) associated with allograft AR whose regulatory targets are mRNAs controlling immune response, T cell activation, and other cellular functions. miR4995 mimics were generated, transfected into HEK293T cells, and their function verified. Our findings not only demonstrate the presence of functional plant-derived miRNAs in human cells, but also provide initial evidence that these miRNAs may be involved in malfunction of renal transplantation.