bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural changes in perineuronal nets and their perforating GABAergic synapses precede motor coordination recovery post stroke
Authors: Dzyubenko Egor , Willig Katrin I. , Yin Dongpei , Sardari Maryam , Tokmak Erdin , Labus Patrick , Schmermund Ben , Hermann Dirk M.
Published: October 2022

Stroke remains one of the leading causes of long-term disability worldwide, and the development of effective restorative therapies is hindered by an incomplete understanding of intrinsic brain recovery mechanisms. Here we explored how perineuronal nets (PNNs), the facet-like extracellular matrix layers surrounding fast-spiking interneurons, contribute to neurological recovery after focal cerebral ischemia in mice with and without induced stroke tolerance. Due to the insufficient resolution of conventional microscopy methods, the contribution of structural changes in PNNs to post stroke brain plasticity remained unknown. Using superresolution stimulated emission depletion (STED) and structured illumination (SR-SIM) microscopy, we revealed that PNN facets become larger and less dense in the post-acute stroke phase. These morphological alterations in PNNs are transient and correlate with the increased surface of contact between activated microglia and PNN-coated neurons. The transient loosening of PNNs after stroke allows for dynamic reorganization of GABAergic axonal terminals on inhibitory interneurons in the motor cortical layer 5. The coherent remodeling of PNNs and their perforating inhibitory synapses precedes the recovery of motor coordination after stroke and depends on the severity of the ischemic injury. Our data suggest a novel mechanism of motor cortical plasticity after stroke, and we propose that prolonging PNN loosening during the post-acute period can extend the opening neuroplasticity window into the chronic stroke phase.

Highlights

PNNs are degraded partially and transiently post-stroke

Transient attenuation of PNNs correlates with GABAergic synapse remodeling

Transient attenuation of PNNs precedes functional recovery post stroke

Activated microglia preferentially contact PNN-coated neurons post stroke

Graphical Abstract
Uncovering footprints of natural selection through time-frequency analysis of genomic summary statistics
Authors: Arnab Sandipan Paul , Amin Md Ruhul , DeGiorgio Michael
Published: October 2022

Natural selection leaves a spatial pattern along the genome, with a distortion in the haplotype distribution near the selected locus that becomes less prominent with increasing distance from the locus. Evaluating the spatial signal of a population-genetic summary statistic across the genome allows for patterns of natural selection to be distinguished from neutrality. Different summary statistics highlight diverse components of genetic variation and, therefore, considering the genomic spatial distribution of multiple summary statistics is expected to aid in uncovering subtle signatures of selection. In recent years, numerous methods have been devised that jointly consider genomic spatial distributions across summary statistics, utilizing both classical machine learning and contemporary deep learning architectures. However, better predictions may be attainable by improving the way in which features used as input to machine learning algorithms are extracted from these summary statistics. To achieve this goal, we apply three time-frequency analysis approaches (wavelet transform, multitaper spectral analysis, and S-transform) to summary statistic arrays. Each analysis method converts a one-dimensional summary statistic arrays to a two-dimensional image of spectral density or visual representation of time-frequency analysis, permitting the simultaneous assessment of temporal and spectral information. We use these images as input to convolutional neural networks and consider combining models across different time-frequency representation approaches through the ensemble stacking technique. Application of our modeling framework to data simulated from neutral and selective sweep scenarios reveals that it achieves almost perfect accuracy and power across a diverse set of evolutionary settings, including population size changes and test sets for which sweep strength, softness, and timing parameters were drawn from a wide range. Moreover, a scan of whole-genome sequencing of central European humans recapitulated previous well-established sweep candidates, as well as predicts novel cancer associated genes as sweeps with high support. Given that this modeling framework is also robust to missing data, we believe that it will represent a welcome addition to the population-genomic toolkit for learning about adaptive processes from genomic data.
Plant functional types and tissue stoichiometry explain nutrient transfer in common arbuscular mycorrhizal networks of temperate grasslands
Authors: Dawson Hilary Rose , Shek Katherine L. , Maxwell Toby M. , Reed Paul B. , Bomfim Barbara , Bridgham Scott D. , Bohannan Brendan J. M. , Silva Lucas C.R.
Published: October 2022

Plants and mycorrhizal fungi form mutualistic relationships that affect how resources flow between organisms and within ecosystems. Common mycorrhizal networks (CMNs) could facilitate preferential transfer of carbon and limiting nutrients, but this remains difficult to predict. Do CMNs favor fungal resource acquisition at the expense of plant resource demands (a fungi-centric view), or are they passive channels through which plants regulate resource fluxes (a plant-centric view)? We used stable isotope tracers (13CO2and15NH3), plant traits, and mycorrhizal DNA to quantify above- and belowground carbon and nitrogen transfer between 18 plant species along a 520-km latitudinal gradient in the Pacific Northwest, USA. Plant functional type and tissue stoichiometry were the most important predictors of interspecific resource transfer. Of “donor” plants, 98% were13C-enriched, but we detected transfer in only 2% of “receiver” plants. However, all donors were15N-enriched and we detected transfer in 81% of receivers. Nitrogen was preferentially transferred to annuals (0.26 ± 0.50 mg N per g leaf mass) compared to perennials (0.13 ± 0.30 mg N per g leaf mass). This corresponded with tissue stoichiometry differences. Our findings suggest that plants and fungi that are located closer together in space and with stronger demand for resources over time are more likely to receive larger amounts of those limiting resources.
Characterization of Integrase and Excisionase Activity in Cell-free Protein Expression System Using a Modeling and Analysis Pipeline
Authors: Pandey Ayush , Rodriguez Makena L. , Poole William , Murray Richard M.
Published: October 2022

We present a full-stack modeling, analysis, and parameter identification pipeline to guide the modeling and design of biological systems starting from specifications to circuit implementations and parameterizations. We demonstrate this pipeline by characterizing the integrase and excisionase activity in cell-free protein expression system. We build on existing Python tools — BioCRNpyler, AutoReduce, and Bioscrape — to create this pipeline. For enzyme-mediated DNA recombination in cell-free system, we create detailed chemical reaction network models from simple high-level descriptions of the biological circuits and their context using BioCRNpyler. We use Bioscrape to show that the output of the detailed model is sensitive to many parameters. However, parameter identification is infeasible for this high-dimensional model, hence, we use AutoReduce to automatically obtain reduced models that have fewer parameters. This results in a hierarchy of reduced models under different assumptions to finally arrive at a minimal ODE model for each circuit. Then, we run sensitivity analysis-guided Bayesian inference using Bioscrape for each circuit to identify the model parameters. This process allows us to quantify integrase and excisionase activity in cell extracts enabling complex-circuit designs that depend on accurate control over protein expression levels through DNA recombination. The automated pipeline presented in this paper opens up a new approach to complex circuit design, modeling, reduction, and parameterization.
Importance of agriculture for Crop Wild Relatives conservation in Switzerland
Authors: Petitpierre Blaise , Boserup Julie , Möhl Adrian , Römetsch Sibyl , Aubry Sylvain
Published: October 2022

Crop Wild Relatives are a subset of the global plant diversity that is often neglected, as not the primary focus for conservationists or plant breeders. However, a relatively large portion of the wild flora, up to 60% in Switzerland for example, do share genetic relationships with cultivated species and therefore can be considered as Crop Wild Relatives. Their conservation appears simultaneously a challenge to conservation programmes but also a considerable levy to mobilize other sectors, like agriculture, to contribute to the conservation of biodiversity at large. Here, we provide a comprehensive checklist of Swiss Crop Wild Relatives representing 2,226 taxa, of which 285 prioritised taxa, referred to as “Crop wild relatives Of Concern”, were designated. Following a taxa-specific ecogeographic analysis, we analysed the extent to which CWR of concern are already contained in existing protected areas as well as their distribution in the agricultural area. Prioritised Crop Wild Relatives species richness was compared to modelled species richness to identify potential conservation gaps. About a fifth of CWR of concern is not significantly better protected than a random species by existing protected areas. However, 28.8 % and 15.5 % of these taxa are more frequently distributed in agricultural and summer grazing areas respectively than random expectations. A clear deficit of species richness for these Crop Wild Relatives of concern was inferred on low lands, possibly related to a lower sampling effort. We further identified a network of 39 sites that contains all taxa of Swiss CWR of concern and that could be used as a primary conservation infrastructure. More generally, our results could be generalized to other countries and support better consideration of CWR in agriculture areas, an important “reservoir” for expanding specific measures of conservation that are crucial to meet the future global goals of diversity conservation frameworks.
Philosophy of Maternity Nursing: Women Centered Care
Authors: Nastiti Aria Aulia , Pandin Moses Glorino Rumambo , Nursalam
Published: October 2022

Introduction

Maternity nursing is a discipline part of nursing that focuses on the degree of health of women in this stage of life as the main object. Various women’s health problems that occur at this time along with the rapid development of technology have become a challenge for maternity nursing as a comprehensive care service to continue to develop for the better and collaborate with other sciences. The purpose of this paper is to explain the current conditions in Indonesia and the world regarding maternity nursing that supports women’s health and quality of life.

Method

This article was compiled through a literature search for the authenticity of this study using articles in English, Sciencedirect, PubMed, Scopus, Research Gate, and Google Scholar from 2015 to 2022.

Result

The results of the literature search show that currently, maternity nursing continues to develop and is centered on women at every stage of life. Research is currently being carried out on women’s welfare, autonomy and women’s empowerment, such as the decision to use contraception and the best care during pregnancy and childbirth.
Adverse birth outcomes and associated factors among newborns delivered in a western African country: a case‒control study
Authors: Vasconcelos Alexandra , Sousa Swasilanne , Bandeira Nelson , Alves Marta , Papoila Ana Luísa , Pereira Filomena , Machado Maria Céu
Published: October 2022

Background

Newborns with one or more adverse birth outcomes (ABOs) are at greater risk of mortality or long-term morbidity with health impacts into adulthood. Hence, identifying ABO-associated factors is crucial for devising comprehensive and relevant interventions. The aim of this study was to identify factors that are associated with the occurrence of ABO – prematurity (PTB), low birth weight (LBW), macrosomia, congenital anomalies, asphyxia, and sepsis - among babies delivered at the only hospital of Sao Tome & Principe (STP), a resource-constrained sub-Saharan Western African country.

Methods

Hospital-based unmatched case‒control study conducted in STP among newborns from randomly selected mothers from July 2016 to November 2018. Newborns with one or more ABO (gestational age <37 weeks, LBW < 2.5 kg, BW >4 kg, 5-minute Apgar score <7, major congenital anomalies, and probable sepsis based on clinical criteria) were the cases (ABO group), while healthy newborns without ABO were the controls (no-ABO group). Data were collected by a face-to-face interview and abstracted from antenatal pregnancy cards and medical records. Multivariable logistic regression analysis was performed to identify ABO risk factors considering a level of significance α=0.05.

Results

A total of 519 newborns (176 with ABO and 343 with no-ABO) were enrolled. The mean gestational age and birth weight of cases and controls were 36 (SD=3.7) weeks with 2659 (SD=881.44) g and 39.6 (SD=1.0) weeks with 3256 (SD=345.83) g, respectively. In a multivariable analysis, twin pregnancy [aOR 4.92, 95% CI 2.25–10.74], prolonged rupture of membranes [aOR 3.43, 95% CI 1.69–6.95], meconium-stained amniotic fluid [aOR 1.59, 95% CI 0.97-2.62], and fewer than eight antenatal care (ANC) visits [aOR 0.33, 95% CI 0.18–0.60] were significantly associated with adverse birth outcomes.

Conclusion

Modifiable factors were associated with ABOs in this study and should be considered in cost-effectiveness interventions. The provision of high-quality ANC with eight or more visits should be a priority at ANC service delivery in STP. Twin pregnancies as well as intrapartum factors such as prolonged rupture of membranes and meconium-stained amniotic fluid are red flags for adverse birth outcomes that should receive prompt intervention and follow-up.
Barriers to accessing mother, new-born and child health services in urban Gambia during COVID-19: An interview-based qualitative study
Authors: Bah Abdourahman , Russo Giuliano
Published: October 2022

Abstract

Introduction

Evidence is being consolidated that shows that the utilisation of mother, newborn, and child health (MNCH) services has declined in low-income countries (LICs) during the COVID-19 pandemic. Very little is known about the effects of the pandemic on MNCH service utilisation in the Gambia. We set out to explore the COVID-19-related factors affecting the utilisation of antenatal and immunisation services in the Gambia.

Methods

A qualitative methodology was used to explore patients’ and providers’ experiences of MNCH services during the pandemic in two Local Government Areas (LGAs) in the Gambia. Thirty-one study participants were recruited from four health facilities, applying a theory-driven sampling framework, including health workers as well as female patients. Qualitative evidence was collected through theory-driven semi-structured interviews, and was recorded, translated into English, transcribed, and analysed thematically, applying a social-ecological framework.

Results

In our interviews, we identified five main themes, ranging from individual factors to interpersonal, community, institutional and policy factors. Individual factors revolved around patients’ fear of being infected in the facilities, and of being quarantined, and their anxiety about passing on infections to family members. Interpersonal factors involved the reluctance of partners and family members, as well as perceived negligence and disrespect by health workers. Community factors included misinformation within the community and mistrust of vaccines. Institutional factors included the shortage of health workers, closures of health facilities, and the lack of personal protective equipment (PPEs) and essential medicines. Finally, policy factors revolved around the consequences of COVID-19 prevention measures, particularly the shortage of transport options and mandatory wearing of face masks.

Conclusions

Our findings suggest that patients’ fears of contagion, perceptions of poor treatment in the health system, and a general anxiety around the imposing of prevention measures, undermined the uptake of MNCH services. In future emergencies, the government in the Gambia, and governments in other LICs, will need to consider the unintended consequences of epidemic control measures on the uptake of MNCH services.
Systematic Review and Meta-Analysis of the Efficacy and Effectiveness of Pneumococcal Vaccines in Adults
Authors: Farrar Jennifer L , Childs Lana , Ouattara Mahamoudou , Akhter Fahmina , Britton Amadea , Pilishvili Tamara , Kobayashi Miwako
Published: October 2022

The 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) were previously recommended for adults in the United States. To help inform discussions on recently licensed 15- and 20-valent pneumococcal vaccine use among adults, we conducted a systematic review of PCV13 and PPSV23 efficacy or effectiveness. We conducted a search on PCV13 and PPSV23 efficacy or effectiveness (VE) studies against vaccine type (VT) invasive pneumococcal disease (IPD) and VT-pneumococcal pneumonia in adults. Nineteen studies were included: 13 on VT-IPD (four on PCV13, nine on PPSV23) and eight on VT-pneumococcal pneumonia (three on PCV13, four on PPSV23, one on PCV13 and PPSV23). One randomized-controlled trial (RCT) evaluated PCV13 and observed an efficacy of 75% and 45% against VT-IPD and VT-pneumococcal pneumonia, respectively. No RCTs reported PPSV23 efficacy. PCV13 effectiveness estimates against VT-IPD ranged from 47% to 68%. Pooled PPSV23 effectiveness against VT-IPD was 45% (95% CI: 37%, 51%; I2=0%). PCV13 VE estimates against VT-pneumonia ranged from –2 to 46%. Pooled PPSV23 VE against VT-pneumococcal pneumonia was 18% (95% CI: -4%, 35%; I2=0%). Evidence suggests PCV13 and PPSV23 are effective against VT-IPD and VT-pneumococcal pneumonia in adults; this was used to inform PCV15 and PCV20 policy decisions.
Metagenomic analysis reveals novel dietary-related viruses in the gut virome of marmosets hybrids (Callithrix jacchus x Callithrix penicillata), Brazil
Authors: Miranda Thamiris dos Santos , Schiffler Francine Bittencourt , D’arc Mirela , Moreira Filipe Romero Rebello , Cosentino Matheus Augusto Calvano , Coimbra Amanda , Mouta Ricardo , Medeiros Gabriel , Girardi Déa Luiza , Wanderkoke Victor , Soares Caique Ferreira Amaral , Francisco Talitha Mayumi , Henry Malinda Dawn , Afonso Bianca Cardozo , Soffiati Flávio Landim , Ferreira Suelen Sanches , Ruiz-Miranda Carlos Ramon , Soares Marcelo Alves , dos Santos André Felipe Andrade
Published: October 2022

Viral metagenomics has contributed enormously to the characterization of a wide range of viruses infecting animals of all phyla in the last decades. Among Neotropical primates, especially those free-living introduced, knowledge about viral diversity remains poorly studied. Therefore, through the use of metagenomics based on virus enrichment, we explored the viral microbiota present in the feces of introduced common marmosets (Callithrix sp.) in three locations from the Silva Jardim region in the State of Rio de Janeiro, Brazil. Fecal samples were collected from nine marmosets, pooled into three sample pools and sequenced on Illumina MiSeq platform. Sequence reads were analyzed using a viral metagenomic analysis pipeline and two novel insect viruses belonging to the Parvoviridae and Baculoviridae families were identified. The complete genome of a densovirus (Parvoviridae family) of 5,309 nucleotides (nt) was obtained. The NS1 and VP1 proteins share lower than 32% sequence identity with the corresponding proteins of known members of the subfamily Densovirinae. Phylogenetic analysis suggests that this virus represents a new genus, named Tritonambidensovirus due to telomeric structures at the 3’ and 5’ ends of the genome. The novel species received the name Fecalis tritonambidensovirus 1. The complete circular genome of a baculovirus of 107,191 nt was also obtained, showing 60.8% sequence identity with the most closely related member of the Baculoviridae family. Phylogenetic analysis suggests that this virus represents a new species of Betabaculovirus, named Callithrix fecalis granulovirus. In addition, sequences from several families of arthropods in the three pools evaluated were characterized (contigs ranging from 244 to 6,750 nt), corroborating the presence of possible insect hosts with which these new viruses may be associated. Our study expands the knowledge about two viral families known to infect insects, an important component of the marmosets’ diet. This identification in hosts’ feces samples demonstrates one of the many uses of this type of data and could serve as a basis for future research characterizing viruses in wildlife using noninvasive samples.
Impacts of Biostimulation and Bioaugmentation on Woodchip Bioreactor Microbiomes
Authors: Wang Hao , Feyereisen Gary W. , Wang Ping , Rosen Carl , Sadowsky Michael J. , Ishii Satoshi
Published: October 2022

Woodchip bioreactors (WBRs) are used to remove nutrients, especially nitrate, from subsurface drainage. The nitrogen removal efficiency of WBRs, however, is limited by low temperature and availability of labile carbon. Bioaugmentation and biostimulation are potential approaches to enhance nitrate removal of WBRs under cold conditions, but their effectiveness is still unclear. Here, we clarified the effects of bioaugmentation and biostimulation on the microbiomes and nitrate removal rates of WBRs. As a bioaugmentation treatment, we inoculated WBR-borne cold-adapted denitrifying bacteria Cellulomonas cellasea strain WB94 and Microvirgula aerodenitrificans strain BE2.4 into the WBRs located at Willmar, MN, USA. As a biostimulation treatment, acetate was added to the WBRs to promote denitrification. Woodchip samples were collected from multiple locations in each WBR before and after the treatments and used for the microbiome analysis. The 16S rRNA gene amplicon sequencing showed that the microbiomes changed by the treatments and season. The high-throughput quantitative PCR for nitrogen cycle genes revealed a higher abundance of denitrification genes at locations closer to the WBR inlet, suggesting that denitrifiers are unevenly present in WBRs. In addition, a positive relationship was identified between the abundance of M. aerodenitrificans strain BE2.4 and those of norB and nosZ in the WBRs. Based on generalized linear modeling, the abundance of norB and nosZ was shown to be useful in predicting the nitrate removal rate of WBRs. Taken together, these results suggest that the bioaugmentation and biostimulation treatments can influence denitrifier populations, thereby influencing the nitrate removal of WBRs.

IMPORTANCE

Nitrate pollution is a serious problem in agricultural areas in the U.S. Midwest and other parts of the world. Woodchip bioreactor is a promising technology that uses microbial denitrification to remove nitrate from agricultural subsurface drainage, although the reactor’s nitrate removal performance is limited under cold conditions. This study showed that the inoculation of cold-adapted denitrifiers (i.e., bioaugmentation) and the addition of labile carbon (i.e., biostimulation) can influence the microbial populations and enhance the reactor’s performance under cold conditions. This finding will help establish a strategy to mitigate nitrate pollution.
Epithelial Outgrowth Through Mesenchymal Rings Drives Alveologenesis
Authors: Negretti Nicholas M. , Son Yeongseo , Crooke Philip , Plosa Erin J. , Benjamin John T. , Jetter Christopher S. , Bunn Claire , Mignemi Nicholas , Marini John , Hackett Alice N. , Ransom Meaghan , Nichols David , Guttentag Susan H. , Pua Heather H. , Blackwell Timothy S. , Zacharias William , Frank David B. , Kozub John A. , Mahadevan-Jansen Anita , Kropski Jonathan A. , Wright Christopher V.E. , Millis Bryan , Sucre Jennifer M. S.
Published: October 2022

Determining how alveoli are formed and maintained is critical to understanding lung organogenesis and regeneration after injury. While technological barriers have heretofore limited real-time observation of alveologenesis, we have now used scanned oblique plane illumination microscopy of living lung slices to observe specific cellular behaviors at high resolution over several days. Contrary to the prevailing paradigm that alveoli form by airspace subdivision via ingrowing septa, we find that alveoli form by ballooning epithelial outgrowth supported by stable mesenchymal ring structures. Our systematic analysis allowed creation of a computational model of finely-timed cellular structural changes that drive alveologenesis under normal conditions or with perturbed intercellular Wnt signaling. This new paradigm and platform can be leveraged for mechanistic studies and screening for therapies to promote lung regeneration.

One-Sentence Summary

Long-term live analysis of neonatal lungs supports a dynamic epithelial outgrowth model for alveologenesis.
Inhibition of the proton-activated chloride channel PAC by PIP2
Authors: Mihaljević Ljubica , Ruan Zheng , Osei-Owusu James , Lü Wei , Qiu Zhaozhu
Published: October 2022

Proton-Activated Chloride (PAC) channel is a ubiquitously expressed pH-sensing ion channel that regulates endosomal acidification and macropinosome shrinkage by releasing chloride from the organelle lumens. It is also found at the cell surface, where it is activated under pathological conditions related to acidosis and contributes to acid-induced cell death. However, the pharmacology of the PAC channel is poorly understood. Here, we report that phosphatidylinositol (4,5)-bisphosphate (PIP2) potently inhibits PAC channel activity. We solved the cryo-electron microscopy structure of PAC with PIP2 at pH 4.0 and identified its binding site, which, surprisingly, locates on the extracellular side of the transmembrane domain (TMD). While the overall conformation resembles the previously resolved PAC structure in the desensitized state, the TMD undergoes remodeling upon PIP2-binding. Structural and electrophysiological analyses suggest that PIP2 inhibits the PAC channel by stabilizing the channel in a desensitized-like conformation. To our knowledge, PAC is the first chloride channel reported to be inhibited by PIP2. Our findings identify PIP2 as a new pharmacological tool for the PAC channel and lay the foundation for future drug discovery targeting this channel.
Single-cell allele-specific expression analysis reveals dynamic and cell-type-specific regulatory effects
Authors: Qi Guanghao , Strober Benjamin J. , Popp Joshua M. , Ji Hongkai , Battle Alexis
Published: October 2022

Allele-specific expression, which measures the expression of two alleles of a gene in a diploid individual, is a powerful signal to study cis-regulatory effects. Comparing ASE across conditions, or differential ASE, can reveal context-specific gene regulation. Recently, single-cell RNA sequencing (scRNA-seq) has allowed the measurement of ASE at the resolution of individual cells, but there is a lack of statistical methods to analyze such data. We develop DAESC, a statistical method for differential ASE analysis across any condition of interest using scRNA-seq data from multiple individuals. DAESC includes a baseline model based on beta-binomial regression with random effects accounting for multiple cells from the same individual (DAESC-BB), and an extended mixture model that incorporates implicit haplotype phasing (DAESC-Mix). We demonstrate through simulations that DAESC accurately captures differential ASE effects in a wide range of scenarios. Application to scRNA-seq data from 105 induced pluripotent stem cell lines identifies 657 genes that are dynamically regulated during endoderm differentiation. A second application identifies several genes that are differentially regulated in pancreatic endocrine cells between type 2 diabetes patients and controls. In conclusion, DAESC is a powerful method for single-cell differential ASE analysis and can facilitate the discovery of context-specific regulatory effects.
Comparison of COVID-19 Antigen Rapid Test (Oral Fluid) and Real-Time RT-PCR in the laboratory diagnosis of SARS-CoV-2 infection
Authors: Mense Lotte M. , Ouburg Sander
Published: October 2022

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first diagnosed in December 2019. Since then this virus has caused an ongoing wide pandemic. Accurate diagnostic tests for SARS-CoV-2 are used to prevent the virus from spreading. However, these tests could not keep up with the demand and were not available in all places. Self-testing devices are easy-to-use-tests and reduce the demand in the diagnostic laboratories. The Antigen Rapid Test evaluated in this study uses oral fluid which is a non-invasive technique compared to nasopharyngeal swabs.

In this study the COVID-19 Antigen Rapid Test (Oral fluid) was evaluated with 150 SARS-CoV-2 positive saliva specimens and 350 SARS-CoV-2 negative saliva specimens. The Antigen Rapid Test was performed according to the instruction manual. SARS-CoV-2 Real-time RT-PCR was used as Golden Standard.

Although the criteria of the WHO are specific to nasal / nasopharyngeal samples (and not saliva), the specificity of the Antigen Rapid Test meets the criteria of the World Health Organization (WHO; specificity ≥ 97%). The test meets the WHO sensitivity criteria in samples with higher viral loads (Ct<30), showing the better performance of the test in highly positive samples. For positive SARS-CoV-2 specimens with a Ct value lower than 30 a sensitivity of 83.8% (95% CI: 80.1%-86.8%) and an accuracy of 95.9% (95% CI: 93.7%-97.4%) was observed. This shows that this assay with saliva samples is able to meet the high standards set by the WHO. The performance of the test is comparable to other antigen rapid tests reported in meta-analyses. Furthermore, the test allows self-testing which is non-invasive, affordable and straightforward. This antigen rapid test may provide an affordable, quick, and easy to perform method to differentiate between individuals with high and low viral loads.
Drosophila epidermal cells are intrinsically mechanosensitive and modulate nociceptive behavioral outputs
Authors: Yoshino Jiro , Mali Sonali S. , Williams Claire R. , Morita Takeshi , Emerson Chloe E. , Arp Christopher J. , Miller Sophie E. , Yin Chang , Thé Lydia , Hemmi Chikayo , Motoyoshi Mana , Ishii Kenichi , Emoto Kazuo , Bautista Diana M. , Parrish Jay Z.
Published: October 2022

Somatosensory neurons (SSNs) that detect and transduce mechanical, thermal, and chemical stimuli densely innervate an animal’s skin. However, although epidermal cells provide the first point of contact for sensory stimuli. our understanding of roles that epidermal cells play in SSN function, particularly nociception, remains limited. Here, we show that stimulatingDrosophilaepidermal cells elicits activation of SSNs including nociceptors and triggers a variety of behavior outputs, including avoidance and escape. Further, we find that epidermal cells are intrinsically mechanosensitive and that epidermal mechanically evoked calcium responses require the store-operated calcium channel Orai. Epidermal cell stimulation augments larval responses to acute nociceptive stimuli and promotes prolonged hypersensitivity to subsequent mechanical stimuli. Hence, epidermal cells are key determinants of nociceptive sensitivity and sensitization, acting as primary sensors of noxious stimuli that tune nociceptor output and drive protective behaviors.
Talin and kindlin cooperate to control the density of integrin clusters
Authors: Pernier Julien , Dos Santos Marcelina Cardoso , Souissi Mariem , Joly Adrien , Narassimprakash Hemalatha , Rossier Olivier , Giannone Grégory , Helfer Emmanuèle , Sengupta Kheya , Le Clainche Christophe
Published: October 2022

Focal adhesions are important mechanosensitive structures, composed of transmembrane integrins, linking the extracellular matrix to the actomyosin cytoskeleton, via cytoplasmic proteins. Cellular adhesion to the extracellular matrix depends on the activation of integrins by intracellular mechanisms. Talin and kindlin are major activators of integrins that are recruited to the inner membrane and bind to β-integrin cytoplasmic tails. Many studies showed the importance of integrin activation and clustering and how the organization of extracellular ligands guides the nanoscale organization of adhesion complexes. However, the roles of talin and kindlin in this process are poorly understood. To determine the contribution of talin, kindlin, lipids and actomyosin in integrin clustering, we performed experiments using a biomimetic in vitro system, made of Giant Unilamellar Vesicles, containing transmembrane integrins, on which purified talin, kindlin, and actomyosin assemble. Here we first show that talin and kindlin individually have the ability to cluster integrins. When added together, talin and kindlin synergize to induce the formation of larger integrin clusters containing the three proteins. Comparison of protein density in the talin-integrin, kindlin-integrin, and talin-kindlin-integrin clusters reveals that kindlin increases talin and integrin density, whereas talin does not affect kindlin and integrin density. Finally, kindlin significantly enhances the segregation of talin-integrin clusters induced by actomyosin contractility, suggesting that it increases the coupling of these clusters to the actin cytoskeleton. Our study unambiguously demonstrates how kindlin and talin cooperate to induce integrin clustering, which is a major parameter for cell adhesion.
The conserved upstream ORF of the ArabidopsisANAC082gene mediates translational upregulation in response to nucleolar stress
Authors: Sasaki Shun , Murakami Toru , Yasumuro Miharu , Makita Ayaka , Oi Yutaro , Hiragori Yuta , Watanabe Shun , Kudo Rin , Hayashi Noriya , Ohbayashi Iwai , Sugiyama Munetaka , Yamashita Yui , Naito Satoshi , Onouchi Hitoshi
Published: October 2022

Perturbations in ribosome biogenesis cause a type of cellular stress called nucleolar or ribosomal stress, which triggers adaptive responses in both animal and plant cells. The Arabidopsis ANAC082 transcription factor has been identified as a key mediator of the plant nucleolar stress response. The 5′-untranslated region (5′-UTR) ofANAC082mRNA contains an upstream ORF (uORF) encoding an evolutionarily conserved amino acid sequence. Here, we report that this uORF mediates the upregulation ofANAC082translation in response to nucleolar stress. When transgenic Arabidopsis plants containing a luciferase reporter gene under the control of theANAC082promoter and 5′-UTR were treated with reagents that induced nucleolar stress, translation of the reporter gene was enhanced in a uORF sequence-dependent manner. Additionally, we examined the effect of an endoplasmic reticulum (ER) stress-inducing reagent on reporter gene expression because the closest homolog ofANAC082in Arabidopsis,ANAC103, is involved in the ER stress response. However, theANAC082uORF did not respond to ER stress. Interestingly, althoughANAC103has a uORF with an amino acid sequence similar to that of theANAC082uORF, the C-terminal sequence critical for regulation is not well conserved amongANAC103homologs in Brassicaceae. Transient expression assays revealed that unlike theANAC082uORF, theANAC103uORF does not exert a sequence-dependent regulatory effect. Altogether, our findings suggest that theANAC082uORF is important for the nucleolar stress response but not for the ER stress response, and that for this reason, the uORF sequence-dependent translational regulation was lost inANAC103during evolution.
Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets
Authors: Mihalic Filip , Benz Caroline , Kassa Eszter , Lindqvist Richard , Simonetti Leandro , Inturi Raviteja , Aronsson Hanna , Andersson Eva , Chi Celestine N. , Davey Norman E. , Överby Anna K. , Jemth Per , Ivarsson Ylva
Published: October 2022

The infection and replication cycle of all viruses depend on interactions between viral and host proteins. Each of these protein-protein interactions is therefore a potential drug target. These host-virus interactions often involve a disordered protein region on one side of the interface and a folded protein domain on the other. Here, we used proteomic peptide phage display (ProP-PD) to identify peptides from the intrinsically disordered regions of the human proteome that bind to folded protein domains encoded by the SARS-CoV-2 genome. Eleven folded domains of SARS-CoV-2 proteins were found to bind peptides from human proteins. Of 281 high/medium confidence peptides, 23 interactions involving eight SARS-CoV-2 protein domains were tested by fluorescence polarization, and binding was observed with affinities spanning the whole micromolar range. The key specificity determinants were established for six of these domains, two based on ProP-PD and four by alanine scanning SPOT arrays. Finally, two cell-penetrating peptides, targeting Nsp9 and Nsp16, respectively, were shown to function as inhibitors of viral replication. Our findings demonstrate how high-throughput peptide binding screens simultaneously provide information on potential host-virus interactions and identify ligands with antiviral properties.
Mapping connectivity and conservation opportunity on agricultural lands across the conterminous United States
Authors: Suraci Justin P. , Littlefield Caitlin E. , Nicholson Charlie C. , Hunter Mitchell C. , Sorensen Ann , Dickson Brett G.
Published: October 2022

Depending on management practices, agricultural lands can either pose substantial barriers to the movement of native species or can support landscape connectivity by linking areas of high-quality habitat. Balancing connectivity and sustainable food production on agricultural lands is critical to conservation in the conterminous United States (CONUS) where agriculture makes up close to half of total land area. However, limited guidance exists on where to target conservation resources to maximize benefits for native species and food security.

To quantify the potential contribution of agricultural lands to the movement of organisms, we developed a novel method for estimating agricultural management intensity (based on remotely sensed temporal variation in vegetation cover on croplands and pastures) and incorporated these estimates into a CONUS-wide, circuit-theory based model of ecological flow connectivity. We then combined our connectivity results with data on the productivity, versatility, and resilience of agricultural lands (PVR) to identify conservation opportunities that support both biodiversity and food production.

The highest levels of connectivity on agricultural lands occurred on relatively unmodified rangelands and on cropland and pasture in close proximity to large amounts of natural land cover.

Mapping connectivity and PVR across CONUS revealed 10.2 Mha of agricultural lands (2.7%) with high value for both connectivity and food production, as well as large amounts of agricultural land (>140 Mha in total) with high value for either cultivation or supporting biodiversity (e.g., through ecological restoration).

Drawing on these findings, we provide recommendations on the types of conservation approaches most suitable for a given agricultural system and link these recommendations to specific government incentive programs. To help facilitate conservation planning based on our results, we have developed an interactive web application, allowing users to visualize the spatial data developed here within their regions of interest.
Entorhinal grid-like codes and time-locked network dynamics track others navigating through space
Authors: Wagner Isabella C. , Graichen Luise P. , Todorova Boryana , Lüttig Andre , Omer David B. , Stangl Matthias , Lamm Claus
Published: October 2022

Navigating through crowded, dynamically changing social environments requires the ability to keep track of other individuals. Grid cells in the entorhinal cortex are a central component of self-related navigation but whether they also track others’ movement is unclear. Here, we propose that entorhinal grid-like codes make an essential contribution to socio-spatial navigation. Sixty human participants underwent functional magnetic resonance imaging (fMRI) while observing and re-tracing different paths of a demonstrator that navigated a virtual reality environment. Results revealed that grid-like codes in the entorhinal cortex tracked the other individual navigating through space. Further, the activity of grid-like codes was time-locked to increases in co-activation and entorhinal-cortical connectivity that included the striatum, the hippocampus, parahippocampal and right posterior parietal cortices, altogether modulated by accuracy when subsequently re-tracing the paths. This suggests that network dynamics time-locked to entorhinal grid-cell-related activity might serve to distribute information about the ‘socio-spatial map’ throughout the brain.
2,4-Di-tert-butylphenol Induces Adipogenesis in Human Mesenchymal Stem Cells by Activating Retinoid X Receptors
Authors: Ren Xiao-Min , Chang Richard C. , Huang Yikai , Amato Angélica Amorim , Carivenc Coralie , Grimaldi Marina , Kuo Angela Y. , Balaguer Patrick , Bourguet William , Blumberg Bruce
Published: October 2022

2,4-di-tert-butylphenol (2,4-DTBP) is an important commercial antioxidant and a toxic natural secondary metabolite that has been detected in humans. However, there is scant information regarding its toxicological effects. Here we asked whether 2,4-DTBP is a potential obesogen. Using a human mesenchymal stem cell (MSC) adipogenesis assay, we found that exposure to 2,4-DTBP led to increased lipid accumulation and expression of adipogenic marker genes. Antagonist assays revealed that 2,4-DTBP increased lipid accumulation by activating the peroxisome proliferator-activated receptor γ (PPARγ)-retinoid X receptor (RXR) heterodimer. 2,4-DTBP likely activated the PPARγ/RXRα heterodimer by activating RXRα but not directly binding to PPARγ. We confirmed that 2,4-DTBP directly bound to RXRα by solving the crystal structure of this complex, then predicted and demonstrated that related compounds could also activate RXRα. Our study demonstrated that 2,4-DTBP and related chemicals could act as obesogens and endocrine disruptors via RXR. These data showed that 2,4-DTBP belongs to a family of compounds whose endocrine-disrupting and obesogenic effects can be strongly modulated by their chemical composition and that structure-activity studies such as the present one could help guide the rational development of safer antioxidants.

SYNOPSIS

Little research exists on the effects of commercially valuable antioxidants on biological systems. This study reports that di- and tri-tert-butylphenols can act as endocrine disruptors and potential obesogens by activating nuclear hormone receptors.
Multifunctional fibers enable modulation of cortical and deep brain activity during cognitive behavior in macaques
Authors: Garwood Indie C , Major Alex J , Antonini Marc-Joseph , Correa Josefina , Lee Youngbin , Sahasrabudhe Atharva , Mahnke Meredith K , Miller Earl K , Brown Emery N , Anikeeva Polina
Published: October 2022

Recording and modulating neural activityin vivoenables investigations of neural circuits during behavior. However, there is a dearth of tools for simultaneous recording and localized receptor modulation in large animal models. We address this limitation by translating multifunctional fiber-based neurotechnology previously only available for rodent studies to enable cortical and subcortical neural modulation in macaques. We record single unit and local field potential activity before, during, and after intracranial GABA infusions in the premotor cortex and putamen. We apply state-space models to characterize changes in neural activity and investigate how neural activity evoked by a working memory task varies in the presence of local inhibition. The recordings provide detailed insight into the electrophysiological effect of neurotransmitter receptor modulation in both cortical and subcortical structures in an awake, behaving macaque. Our results demonstrate a first-time translation of multifunctional fibers for causal studies in behaving non-human primates.
Dysconnection and cognition in schizophrenia: a spectral dynamic causal modeling study
Authors: Zarghami Tahereh S. , Zeidman Peter , Razi Adeel , Bahrami Fariba , Hossein-Zadeh Gholam-Ali
Published: October 2022

Schizophrenia (SZ) is a severe mental disorder characterized by failure of functional integration (aka dysconnection) across the brain. Recent functional connectivity (FC) studies have adopted functional parcellations to define subnetworks of large-scale networks, and to characterize the (dys)connection between them, in normal and clinical populations. While FC examines statistical dependencies between observations, model-based effective connectivity (EC) can disclose the causal influences that underwrite the observed dependencies. In this study, we investigated resting state EC between the subnetworks of seven large-scale networks, in 66 SZ and 74 healthy subjects from a public dataset. The results showed that a remarkable 33% of the effective connections (among subnetworks) of the cognitive control network had been pathologically modulated in SZ. Further dysconnection was identified within the visual, default mode and sensorimotor networks of SZ subjects, with 24%, 20% and 11% aberrant couplings. Overall, the proportion of diagnostic connections was remarkably larger in EC (24%) than FC (1%) analysis. Subsequently, to study the neural correlates of impaired cognition in SZ, we conducted a canonical correlation analysis between the EC parameters and the cognitive scores of the patients. As such, the self-inhibitions of supplementary motor area and paracentral lobule (in the sensorimotor network) and the excitatory connection from parahippocampal gyrus to inferior temporal gyrus (in the cognitive control network) were significantly correlated with the social cognition, reasoning/problem solving and working memory capabilities of the patients. Future research can investigate the potential of whole-brain EC as a biomarker for diagnosis of brain disorders and for cognitive assessment.
Deep Local Analysis estimates effects of mutations on protein-protein interactions
Authors: Behbahani Yasser Mohseni , Laine Elodie , Carbone Alessandra
Published: October 2022

The spectacular advances in protein and protein complex structure prediction hold promises for the reconstruction of interactomes at large scale at the residue resolution. Beyond determining the 3D arrangement of interacting partners, modeling approaches should be able to sense the impact of sequence variations such as point mutations on the strength of the association. In this work, we report on DLA-mutation, a novel and efficient deep learning framework for accurately predicting mutation-induced binding affinity changes. It relies on a 3D-invariant description of local 3D environments at protein interfaces and leverages the large amounts of available protein complex structures through self-supervised learning. It combines the learnt representations with evolutionary information, and a description of interface structural regions, in a siamese architecture. DLA-mutation achieves a Pearson correlation coefficient of 0.81 on a large collection of more than 2000 mutations, and its generalization capability to unseen complexes is higher than state-of-the-art methods.