bluuebunny/crossref_metadata_2025 huggingface dataset:
Documentation and prevalence of prenatal and neonatal outcomes in a cohort of individuals with KBG syndrome
Authors: Kierzkowska Ola , Sarino Kathleen , Carter Drake , Marchi Elaine , Voronova Anastassia , Lyon Gholson J.
Published: January 2023

Mutations in the Ankyrin Repeat Domain 11 (ANKRD11) gene are associated with KBG syndrome, a developmental disability that affects multiple organ systems and presents with a variety of skeletal, cardiac, gastrointestinal, and neuropsychiatric manifestations. The function ofANKRD11in human growth and development is not well understood, but its importance is established by the fact that constitutive or conditional gene knockout or mutation are lethal in mice embryos and/or pups. In addition, it plays a vital role in chromatin regulation, transcription, and development. Individuals with KBG syndrome are often misdiagnosed or undiagnosed until later in life, due to a combination of varying phenotypes, lack of targeted prenatal screening, and lack of documentation of prenatal and neonatal symptoms. The present study aims to report perinatal outcomes in individuals with KBG syndrome and their families and compare them to the prevalence in the overall population. We obtained data from 42 individuals through videoconferences, notes, and emails. Our results show that 45.2% of our cohort was born by C-section, 33.3% had a congenital heart defect, 23.8% were born before 37-weeks ‘ gestation, 23.8% were admitted to the NICU, 14.3% were small for gestational age, and 14.3% of the families in our cohort had a history of miscarriage. The prevalence of birth by C-section, premature birth, NICU admission, and small for gestational age was higher in our cohort compared to the overall population, including non-Hispanic and Hispanic populations. Other reports included feeding difficulties (21.4%), neonatal jaundice (14.3%), decreased fetal movement (7.14%), and pleural effusionsin utero(4.67%). These findings suggest that there may be an association betweenANKRD11variants or microdeletions and perinatal complications, and further research is needed to better assess the mechanisms behind this relationship. Comprehensive perinatal studies about KBG syndrome and updated documentation of its phenotypes can facilitate earlier detection, diagnosis, and treatment.
Evaluation of Potential Adverse Events Following COVID-19 mRNA Vaccination Among Adults Aged 65 Years and Older: A Self-Controlled Study in the U.S
Authors: Shoaibi Azadeh , Lloyd Patricia C. , Wong Hui-Lee , Clarke Tainya C. , Chillarige Yoganand , Do Rose , Hu Mao , Jiao Yixin , Kwist Andrew , Lindaas Arnstein , McEvoy Rowan , Ondari Michelle , Parulekar Shruti , Shi Xiangyu , Wang Jing , Lu Yun , Obidi Joyce , Zhou Cindy K. , Kelman Jeffrey A. , Forshee Richard A. , Anderson Steven A.
Published: January 2023

Background

Our near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevations in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluations of the potential associations.

Methods

We conducted self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged 65 years and older. Adjusted incidence rate ratio (IRRs) and 95% confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following booster doses for AMI, PE, ITP, Bell ‘s Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri).

Results

Among 3,360,981 individuals who received 6,388,542 primary series doses and 6,156,100 individuals with monovalent booster doses of either BNT162b2 or mRNA-1273, AE counts were: AMI (3,653 primary series, 16,042 booster), inpatient PE (2,470 primary, 5,085 booster), ITP (1,085 primary, 88 booster), DIC (254 primary), BP (3,268 booster), and Myo/Peri (1,295 booster). The IRR for inpatient PE cases following BNT162b2 primary series and booster was 1.19 (95% CI: 1.03 to 1.38) and 0.86 (95% CI: 0.78 to 0.95), respectively; and for mRNA-1273 primary series and booster, 1.15 (95% CI: 0.94 to 1.41) and 0.87 (95% CI: 0.79 to 0.96), respectively. The IRR for BP following BNT162b2 and mRNA-1273 booster was 1.17 (95% CI: 1.06 to 1.29) and 1.16 (95% CI: 1.05 to 1.29), respectively.

Conclusion

In these two studies of the U.S. elderly we did not find an increased risk for AMI, ITP, DIC, and Myo/Peri; the results were not consistent for PE; and there was a small elevated risk of BP after exposure to COVID-19 mRNA vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the elderly.

HIGHLIGHTS

There was no increased risk for four of six outcomes following COVID-19 monovalent mRNA vaccines. There was a small elevated risk of Bell ‘s Palsy after exposure to COVID-19 monovalent mRNA vaccines. Risk of pulmonary embolism was not consistent after exposure to COVID-19 monovalent mRNA vaccines.
ONE ASSAY TO TEST THEM ALL: COMPARING MULTIPLEX ASSAYS FOR EXPANSION OF RESPIRATORY VIRUS SURVEILLANCE
Authors: Boukli Narjis , Flamand Claude , Chea Kim Lay , Heng Leangyi , Keo Seangmai , Sour Kimhoung , In Sophea , Chhim Panha , Chhor Bunthea , Kruy Lomor , Feenstra Jelena D M , Gandhi Manoj , Okafor Obiageli , Ulekliev Camilla , Auerswald Heidi , Horm Viseth Srey , Karlsson Erik A
Published: January 2023

Background

Molecular multiplex assays (MPAs) for simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza and respiratory syncytial virus (RSV) in a single RT-PCR reaction reduce time and increase efficiency to identify multiple pathogens with overlapping clinical presentation but different treatments or public health implications.

Methods

Clinical performance of XpertXpress®SARS-CoV-2/Flu/RSV (Cepheid, GX), TaqPath™ COVID-19, FluA/B, RSV Combo kit (Thermo Fisher Scientific, TP), and PowerChek™ SARS-CoV-2/Influenza A&B/RSV Multiplex RT-PCR kit II (KogeneBiotech, PC) was compared to individual Standards of Care (SoC). Thirteen isolates of SARS-CoV-2, human seasonal influenza, and avian influenza served to assess limit of detection (LoD). Then, positive and negative residual nasopharyngeal specimens, collected under public health surveillance and pandemic response served for evaluation. Subsequently, comparison of effectiveness was assessed.

Results

The three MPAs confidently detect all lineages of SARS-CoV-2 and influenza viruses. MPA-LoDs vary from 1-2 Log10 differences from SoC depending on assay and strain. Clinical evaluation resulted in overall agreement between 97% and 100%, demonstrating a high accuracy to detect all targets. Existing differences in costs, testing burden and implementation constraints influence the choice in primary or community settings.

Conclusion

TP, PC and GX, reliably detect SARS-CoV-2, influenza and RSV simultaneously, with reduced time-to-results and simplified workflows. MPAs have the potential to enhancediagnostics, surveillance system, and epidemic response to drive policy on prevention and control of viral respiratory infections.

IMPORTANCE

Viral respiratory infections represent a major burden globally, weighed down by the COVID-19 pandemic, and threatened by spillover of novel zoonotic influenza viruses. Since respiratory infections share clinical presentations, identification of the causing agent for patient care and public health measures requires laboratory testing for several pathogens, including potential zoonotic spillovers. Simultaneous detection of SARS-CoV-2, influenza, and RSV in a single RT-PCR accelerates time from sampling to diagnosis, preserve consumables, and streamline human resources to respond to other endemic or emerging pathogens. Multiplex assays have the potential to sustain and even expand surveillance systems, can utilize capacity/capability developed during the COVID-19 pandemic worldwide, thereby strengthening epidemic/pandemic preparedness, prevention, and response.
Evidence against a cortical module for processing communicative gaze
Authors: Görner Marius , Dicke Peter W , Thier Peter
Published: January 2023

Where we look lets others know what we are interested in and allows them to join our focus of attention. In several studies our group investigated the neuronal basis of gaze following behavior in humans and macaques and described agaze following patch(GFP) in the posterior temporal cortex as being of central importance for this function. To our knowledge, this makes the GFP the most promising neurobiological correlate of Simon Baron-Cohen’seye direction detector(EDD), an integral part of hismindreading system. With the latter, Baron-Cohen proposed a set of domain-specific neurocognitive modules implementing a functional framework he suggested to be necessary to establish a Theory of Mind - the attribution of mental states to others. The tenet of domain-specificity requires that the EDD processes exclusively eye-like stimuli. In this preregistered fMRI study, we aimed to critically test if the GFP fulfills this criterion. Contrary to previous studies, the present results clearly demonstrate that GFP activity is not exclusively correlated with the perception of other people’s gaze direction and thus does not fulfill the criterion of domain-specificity. Furthermore, we show that it cannot be functionally dissociated from the MT+ complex, with which it overlaps anatomically. In the context of our previous studies which were specifically designed to capture the full behavioral relevance of active gaze following and to reveal the EDD, the results of the present study provide evidence that such a domain specific module does not exist. Therefore, the plausibility of Baron-Cohen’smindreading modelas a set of domain-specific modules is put into question.

Significance statement.

The presented results demonstrate that a brain area previously thought to be a domain-specific cortical module specialized in processing other people’s focus of visual attention is, in fact, domain-general. More specifically, we show that it is indistinguishable from cortical areas involved in the processing of visual motion. These findings add to a growing body of evidence arguing against domain-specific accounts in social neuroscience which posit that the functional building blocks of social behaviors are facilitated by dedicated neurocognitive modules.
Vascular and neural transcriptomics reveal stage-dependent pathways to inflammation and cognitive dysfunction in a rat model of hypertension
Authors: Ulbrich Philipp , Morton Lorena , Briese Michael , Lämmlin Naomi , Mattern Hendrik , Hasanuzzaman Md. , Westhues Melina , Khoshneviszadeh Mahsima , Appenzeller Silke , Gündel Daniel , Toussaint Magali , Brust Peter , Kniess Torsten , Oelschlegel Anja , Goldschmidt Jürgen , Meuth Sven , Heinze Hans-Jochen , Debska-Vielhaber Grazyna , Vielhaber Stefan , Becker Axel , Dityatev Alexander , Jandke Solveig , Sendtner Michael , Dunay Ildiko , Schreiber Stefanie
Published: January 2023

Chronic arterial hypertension causes cerebral microvascular dysfunction and doubles dementia risk in aging. However, cognitive health preservation by therapeutic blood pressure lowering alone is limited and depends on disease duration, the degree of irreversible tissue damage and whether microvascular function can be restored. This study aimed to understand molecular and cellular temporo-spatial pathomechanisms in the course of hypertension. We investigated the effects of initial, early chronic and late chronic hypertension in the frontal brain of rats by applying behavioral tests, histopathology, immunofluorescence, FACS, microvascular/neural tissue RNA sequencing as well as18F-FDG PET imaging. Chronic hypertension caused frontal brain-specific behavioral deficits. Our results highlight stage-dependent responses to continuous microvascular stress and wounding by hypertension. Early responses included a fast recruitment of activated microglia to the blood vessels, immigration of peripheral immune cells, blood-brain-barrier leakage and an energy-demanding hypermetabolic state. Vascular adaptation mechanisms were observed in later stages and included angiogenesis and vessel wall strengthening by upregulation of cellular adhesion molecules and extracellular matrix. Additionally, we identified late chronic accumulation of Igfbp-5 in the brains of hypertensive rats, which is also a signature of Alzheimer’s dementia and attenuates protective Igf-1 signaling. Our study advances the knowledge of involved pathomechanisms and highlights the stage-dependent nature of hypertensive pathobiology. This groundwork might be helpful for basic and clinical research to identify stage-dependent markers in the human disease course, investigate stage-dependent interventions besides blood pressure lowering and better understand the relationship between poor vascular health and neurodegenerative diseases.
Mitochondrial Genome Analysis and Phylogeny and Divergence Time Evaluation of theStrix aluco
Authors: Wang Yeying , Zhan Haofeng , Zhang Yu , Long Zhengmin , Yang Xiaofei
Published: January 2023

In this study, a complete mitochondrial genome of theStrix alucowas reported for the first time, with a total length of 18,632 bp. There were 37 genes, including 22 tRNAs, 2 rRNAs, 13 protein-coding genes (PCGs), and 2 non-coding control regions (D-loop). The second-generation sequencing of the complete mitochondrial genome of theS. alucowas conducted using the Illumina platform, and then Tytoninae was used as the out-group, PhyloSuite software was applied to build the ML-tree and BI-tree of the Strigiformes, and finally, the divergence time tree was constructed using Beast2.6.7 software, the age ofMiosurnia diurnafossil-bearing sediments (6.0-9.5 Ma) was set as the internal correction point. The common ancestor of theStrixwas confirmed to have diverged during the Pleistocene(2.59~0.01Ma). The dramatic uplift of the Qinling Mountains in the Middle Pleistocene and the climate oscillation of the Pleistocene together causedStrixdivergence between the northern and southern parts of mainland China. The isolation of glacial-interglacial rotation and glacier refuge was the main reason for the divergence of the common ancestor of theStrix uralensisand theS. alucoduring this period. This study provides a reference for the evolution history of theStrix.

Summary statement

This study was the first time to assemble the complete mitochondrial genome ofStrix aluco, and report the divergence time ofStrix. A full discussion was made, and it was inferred that the uplift of the Qinling Mountains and the glacial refuge led to the differentiation of this genus.
PyriculariaPopulations are Mostly Host-Specialized with Limited Reciprocal Cross-Infection Between Wheat and Endemic Grasses in Minas Gerais, Brazil
Authors: Ascari João P. , Cazón Luis I. , Rahnama Mostafa , Lamour Kurt , Fernandes José M. C. , Farman Mark L. , Del Ponte Emerson M.
Published: January 2023

Wheat blast, caused byPyricularia oryzaeTriticum (PoT), is an emergent threat to wheat production. Current understanding of the evolution and population biology of the pathogen and epidemiology of the disease has been based on phylogenomic studies that compared the wheat blast pathogen with isolates collected from grasses that were invasive to Brazilian wheat fields. Genetic similarity between isolates from wheat and grasses lead to the conclusion that significant cross-infection occurs, especially on signalgrass (Urochloa spp.); and this in turn prompted speculation that its widespread use as forage is a key driver of the disease’s epidemiology. We reanalyzed data from those studies and found that all but one of the isolates from non-wheat hosts were members of PoT and the relatedLolium-adapted lineage (PoL1), which meant that thePyriculariapopulations typically found on endemic grasses had not yet been sampled. To address this shortcoming, we performed a comprehensive sampling of blast lesions in wheat crops and endemic grasses found in and away from wheat fields in Minas Gerais. A total 1,368 diseased samples were collected (976 leaves of wheat and grasses and 392 wheat heads) which yielded a working collection of 564Pyriculariaisolates. We show that, contrary to earlier implications, PoT was rarely found on endemic grasses and, conversely, members of grass-adapted populations were rarely found on wheat. Instead, most populations were host-specialized with constituent isolates usually grouping according to their host-of-origin. With regard to the dominant role proposed for signalgrass in wheat blast epidemiology, we found only one PoT member in 67 isolates collected from signalgrass grown away from wheat fields, and only three members ofUrochloa-adapted populations among hundreds of isolates from wheat. Cross-inoculation assays on wheat and a signalgrass used in pastures (U. brizantha) suggested that the limited cross-infection observed in the field may be due to innate compatibility differences. Whether or not the observed level of cross-infection would be sufficient to provide an inoculum reservoir, or serve as a bridge between wheat growing regions, is questionable and, therefore, deserves further investigation.
Improving genome quality through artificial truncating purifying selection using heat shock: case of carps
Authors: Kuzmin Aleksandr , Evgenii Vinogradov , Balashov Dmitrii , Kozenkova Elena , Iliushchenko Dmitrii , Mikhailova Alina G. , Patlay Nataliya , Ekaterina Zakharenko , Ivan Kozenkov , Ivan Ptashnik , Timonina Valeriia , Tretiakov Evgenii , Galimov Yan , Haag Christoph , Efimenko Bogdan , Gunbin Konstantin , Mizgirev Igor , Mugue Nikolai , Popadin Konstantin
Published: January 2023

The process of domestication is associated with decrease in effective population size, which in turn leads to accumulation of slightly-deleterious mutations due to genetic drift. To maintain genome quality at a high level, we propose to use a stress-induced strong purifying selection, which based on negative epistasis, can effectively eliminate organisms with an excess of deleterious variants. Here, to identify stress factors, which interact with the effect of deleterious mutations we performed a proof-of-principle experiment with several regimes of a heat shock. We observed that fitness of mutated versus wild-type carp lines drops stronger after heat shock, which is a signature of a negative epistasis. Although the observed trend is promising, the effect of the epistasis is weak and unstable from family to family. Thus, more deep tuning of heat shock regimes is needed to uncover the most efficient combination of factors (absolute temperature, duration, stage of the embryo development) aggravating the burden of deleterious mutations and thus exposing them to the selection.
A vocalization-processing network in marmosets
Authors: Jafari Azadeh , Dureux Audrey , Zanini Alessandro , Menon Ravi S. , Gilbert Kyle M. , Everling Stefan
Published: January 2023

Vocalizations play an important role in the daily life of primates and likely form the basis of human language. Functional imaging studies have demonstrated that listening to language or reading activates a left-lateralized fronto-temporal language network in human participants. Here we acquired whole-brain ultrahigh field (9.4 Tesla) fMRI in awake marmosets (Callithrix jacchus) and demonstrate that these highly vocal small New World primates possess a similar fronto-temporal network, including subcortical regions, that is activated by the presentation of conspecific vocalizations. The findings suggest that the human language network has evolved from an ancestral vocalization network that predates the separation of New and Old World primates.
Texture-Based Image Analysis For the Assessment of Soybeans
Authors: Lee Alexander , Hoffseth Kevin
Published: January 2023

At 4.44 billion bushels worth an estimated $57.7 billion dollars, soybeans are one of the most produced crops in the United States and are appraised using a standard grading system set by the USDA(NASS, 2022). The grading and inspection process is based on twenty factors, including six that are visual based (USDA, 2020). The aim of this research is to apply texture-based image analysis to assess visual indicators of damage in soybeans and demonstrate potential use in increasing efficiency and consistency in soybean grading. Surface texture is one of the characteristics that is examined by inspectors as part of assessing soybean damage, while “image texture” is a calculated set of parameters that are used in image processing and analysis to quantify the apparent actual texture captured in an image. In this study, texture analysis using Haralick textural features is performed on sets of soybean images to assess damage types (as defined by the USDA inspection handbook and visual reference images) and improve soybean classification.
Decomposing intraspecific phenotypic variation: implications for species and functional diversity
Authors: Worthy Samantha J. , Umaña María N. , Zhang Caicai , Lin Luxiang , Cao Min , Swenson Nathan G.
Published: January 2023

Researchers have a history of seeking explanation for and understanding of diversity patterns. High-dimensional trait-based trade-offs have been hypothesized as important for maintaining species and functional diversity. These relationships have primarily been investigated at the community-level, despite the importance of intraspecific variation to diversity maintenance. The goal of this research is to determine if alternative phenotypes are present within species and the impacts of this on diversity in a tropical seedling community in China. We ask 1) do trait combinations found across species, at the community-level, also exist within species?; 2) how consistent are alternative phenotypes and their contributions to growth across species?; and 3) how do findings align with species co-occurrence patterns? We model species-specific growth with individual-level trait measurements, environmental data, and their interactions, allowing for identification of intraspecific alternative phenotypes and quantification of the contribution of variables to growth. We find that two of three species have intraspecific alternative phenotypes. Specifically, individuals within these species share a trait combination, but how they combine the traits differs depending on the type and level of soil nutrients. Furthermore, we find that similarity among species in alternative phenotypes and variables that contribute most to growth may lead to negative spatial co-occurrence of species. Overall, we find that multiple traits or interactions between traits and the environment drive species-specific strategies for growth. These results highlight how individuals are highly variable, with phenotypically different individuals having similar growth performance, and suggest how high species and functional diversity can be maintained in communities.
VRPG: an interactive visualization framework for reference-projected pangenome graph
Authors: Miao Zepu , Yue Jia-Xing
Published: January 2023

With the increasing availability of high-quality genome assemblies, pangenome graph is emerging as a new paradigm in the genomics field for identifying, encoding, and interpreting genomic variation landscape at both population and species levels. However, it remains a major challenge in understanding and interpretating pangenome graph via biologically informative visualization. To facilitate a better examination of pangenome graph towards novel biological insights, here we present VRPG, a web-based interactive visualization framework of pangenome graph. VRPG provides dynamic and efficient supports for exploring and annotating pangenome graphs along a reference-based coordinate system. Moreover, VRPG shines with its unique features in highlighting the directed path of any graph-constitutive assembly as well as in denoting copy number variation of genomic segments represented by graph-constitutive nodes, which are highly valuable in genome comparison and variant analysis. Additionally, VRPG enables side-by-side visualization between pangenome graph and reference-based annotation features, bridging the graph and linear genome context. To further demonstrate its features and scalability, we applied VRPG to the cutting-edge yeast and human reference pangenome graphs derived from hundreds of high-quality genome assemblies via a dedicated website (https://www.evomicslab.org/app/vrpg/).

Contact:yuejiaxing@gmail.com

Key points

Developed an intuitive visualization framework for pangenome graph.

Empowered graph-based feature highlighting and variant visualization.

Enabled connecting reference-based annotation features in the context of pangenome graph.
Preterm birth accelerates the maturation of spontaneous and resting activity in the visual cortex
Authors: Witteveen Isabelle F. , McCoy Emily , Holsworth Troy D. , Shen Catherine Z. , Chang Winnie , Nance Madelyn G. , Belkowitz Allison R. , Dougald Avery , Puglia Meghan H. , Ribic Adema
Published: January 2023

Prematurity is among the leading risks for poor neurocognitive outcomes. The brains of preterm infants show alterations in structure and electrical activity, but the underlying circuit mechanisms are unclear. To address this, we performed a cross-species study of the electrophysiological activity in the visual cortices of prematurely born infants and mice. Using electroencephalography (EEG) in a sample of healthy preterm (N=29) and term (N=28) infants, we found that the maturation of the aperiodic EEG component was accelerated in the preterm cohort, with a significantly flatter 1/f slope when compared to the term infants. The flatter slope was a result of decreased spectral power in the theta and alpha bands and was correlated with the degree of prematurity. To determine the circuit and cellular changes that potentially mediate the changes in 1/f slope after preterm birth, we usedin vivoelectrophysiology in preterm mice and found that, similar to infants, preterm birth results in a flattened 1/f slope. We analyzed neuronal activity in the visual cortex of preterm mice (N=6 preterm and 9 term mice) and found suppressed spontaneous firing of neurons. Using immunohistochemistry, we further found an accelerated maturation of inhibitory circuits. In both preterm mice and infants, the functional maturation of the cortex was accelerated, underscoring birth as a critical checkpoint in cortical maturation. Our study points to a potential mechanism of preterm birth-related changes in resting neural activity, highlighting the utility of a cross-species approach in studying the neural circuit mechanisms of preterm birth-related neurodevelopmental conditions.
Developing a robust technique for denoising and extracting speech and breath sounds in voice recordings from asthmatic patients
Authors: Sayed Sania Fatima , Rezwan Faisal I.
Published: January 2023

Auscultation and processing cough, voice and breath sounds play an important role in diagnosis of several pulmonary ailments. There have been a number of studies using machine learning algorithms on such sound files to build classification and prediction algorithms. Since these studies used specialized microphones in controlled environments, it is difficult to test and deploy these algorithms in real-life settings. Recorded speech files consist of breath and wheeze sounds and it is challenging to extract from this single sound file. Hence, several audio processing and editing software are used to demarcate these sounds. The proposed technique uses a combination of a denoiser and an extraction technique to overcome these drawbacks. The developed pipeline ensures that the audio files are free of any environmental and background noises, and the audio can be recorded through any kind of microphone and environmental settings. The extraction technique further is the result of combinations of filters to output the speech and breath sounds as individual sound files, ready for processing and eliminating the need of audio editing and processing software.
Broadly Neutralizing Antibody Epitopes on HIV-1 Particles are exposed after Virus Interaction with Host Cells
Authors: Rao Priyanka Gadam , Lambert Gregory S. , Upadhyay Chitra
Published: January 2023

The envelope glycoproteins (Env) on HIV-1 virions are the sole target of broadly neutralizing antibodies (bNAb) and the focus of vaccines. However, many cross-reactive conserved epitopes are often occluded on virus particles, contributing to the evasion of humoral immunity. This study aimed to identify the Env epitopes that are exposed/occluded on HIV-1 particles and to investigate the mechanisms contributing to their masking. Using a flow cytometry-based assay, three HIV-1 isolates, and a panel of antibodies, we show that only select epitopes including V2i, gp120-g41 interface, and gp41-MPER are accessible on HIV-1 particles, while V3, V2q, and select CD4bs epitopes are masked. These epitopes become accessible after allosteric conformational changes are induced by pre-binding of select Abs, prompting us to test if similar conformational changes are required for these Abs to exhibit their neutralization capability. We tested HIV-1 neutralization where virus-mAb mix was pre-incubated/not pre-incubated for one hour prior to adding the target cells. Similar levels of neutralization were observed under both assay conditions, suggesting that the interaction between virus and target cells sensitizes the virions for neutralization via bNAbs. We further show that lectin-glycan interactions can also expose these epitopes. However, this effect is dependent on the lectin specificity. Given that, bNAbs are the ideal for providing sterilizing immunity and are the goal of current HIV-1 vaccine efforts, these data offer insight on how HIV-1 may occlude these vulnerable epitopes from the host immune response. In addition, the findings can guide the formulation of effective antibody combinations for therapeutic use.

Importance

The human immunodeficiency virus (HIV-1) envelope (Env) glycoprotein mediates viral entry, and is the sole target of neutralizing antibodies. Our data suggest that antibody epitopes including V2q (e.g., PG9, PGT145), CD4bs (e.g., VRC01, 3BNC117) and V3 (2219, 2557) are masked on HIV-1 particles. The PG9 and 2219 epitopes became accessible for binding after conformational unmasking was induced by pre-binding of select mAbs. Attempts to understand the masking mechanism led to the revelation that interaction between virus and host cells is needed to sensitize the virions for neutralization by broadly neutralizing antibodies (bNAbs). These data provide insight on how bNAbs may gain access to these occluded epitopes to exert their neutralization effects and block HIV-1 infection. These findings have important implications for the way we evaluate the neutralizing efficacy of antibodies and can potentially guide vaccine design.
Intergenerational scaling law determines the precision kinematics of stochastic individual-cell-size homeostasis
Authors: Joshi Kunaal , Biswas Rudro R. , Iyer-Biswas Srividya
Published: January 2023

Individual bacterial cells grow and divide stochastically. Yet they maintain their characteristic sizes across generations within a tightly controlled range. What rules ensure intergenerational stochastic homeostasis of individual cell sizes? Valuable clues have emerged from high-precision longterm tracking of individual statistically-identicalCaulobacter crescentuscells as reported in [1]: Intergenerational cell size homeostasis is an inherently stochastic phenomenon, follows Markovian or memory-free dynamics, and cells obey an intergenerational scaling law, which governs the stochastic map characterizing generational sequences of characteristic cell sizes. These observed emergent simplicities serve as essential building blocks of the first-principles-based theoretical framework we develop here. Our exact analytic fitting-parameter-free results for the predicted intergenerational stochastic map governing the precision kinematics of cell size homeostasis are remarkably well borne out by experimental data, including extant published data on other microorganisms,Escherichia coliandBacillus subtilis. Furthermore, our framework naturally yields the general exact and analytic condition, necessary and sufficient, which ensures that stochastic homeostasis can be achieved and maintained. Significantly, this condition is more stringent than the known heuristic result for the popular quasi-deterministic adder-sizer-timer frameworks. In turn the fully stochastic treat-ment we present here extends and updates extant frameworks, and challenges the notion that the mythical “average cell” can serve as a reasonable proxy for the inherently stochastic behaviors of actual individual cells.
ERK1/2-dependent TSPO overactivation associates with the loss of mitophagy and mitochondrial respiration in ALS
Authors: Magrì Andrea , Rita Lipari Cristiana Lucia , Risiglione Pierpaolo , Zimbone Stefania , Guarino Francesca , Caccamo Antonella , Messina Angela
Published: January 2023

Mitochondrial dysfunction and the loss of mitophagy, aimed at recycling irreversibly damaged organelles, contribute to the onset of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease affecting spinal cord motor neurons. In this work, we showed that the reduction of mitochondrial respiration, exactly oxygen flows linked to ATP production and maximal capacity, correlates with the appearance of the most common ALS motor symptoms in a transgenic mice model expressing SOD1 G93A mutant. This is the result of the equal inhibition in the respiration linked to complex I and II of the electron transport chain, but not their protein levels. Since the overall mitochondrial mass was unvaried, we investigated the expression of the Translocator Protein (TSPO), a small mitochondrial protein whose overexpression was recently linked to the loss of mitophagy in a model of Parkinson’s disease. Here we clearly showed that levels of TSPO are significantly increased in ALS mice. Mechanistically, this increase is linked to the overactivation of ERK1/2 pathway and correlates with a decrease in the expression of the mitophagy-related marker, Atg12, indicating the occurrence of impairments in the activation of mitophagy. Overall, our work sets out TSPO as a key regulator of mitochondrial homeostasis in ALS.
Glycoprotein-glycoprotein receptor binding detection using bioluminescence resonance energy transfer (BRET)
Authors: Adamczuk Kamila , Rivero-Müller Adolfo
Published: January 2023

The glycoprotein receptors, members of the large G protein-coupled receptors (GPCRs) family, are characterized by a large extracellular domains responsible of binding their glycoprotein hormones. Hormone-receptor interactions are traditionally analyzed by ligand-binding assays most often using radiolabeling but also by thermal shift assays. However, the use of radioisotopes requires appropriate laboratory conditions, and moreover, for this purpose, purified cell membranes are most often used instead of living cells. This in turn poses another challenge due to the altered stability of membrane proteins in detergents used for purification. Here, we overcome such limitations by applying bioluminescence resonance energy transfer (BRET) in living cells to determine hormone-receptor interactions between aGaussialuciferase (Gluc) luteinizing hormone/chorionic gonadotropin receptor (LHCGR) fusion and its ligands (yoked human chorionic gonadotropin (yhCG) or luteinizing hormone (LH)) fused to the enhanced green fluorescent protein (eGFP). We first show that the Gluc-LHCGR is expressed on the plasma membrane and is fully functional, as well as the chimeric eGFP-hormones that are properly secreted and able to bind and activate the WT LHCGR. Finally, we applied the method to determine the interactions between clinically relevant mutations in the hormone as well as the receptor and show that this assay is fast and effective, plus safer and cost efficient alternative to radioligand-based assays, to screen for mutations in either the receptor or ligand. It enables kinetic measurements in living cells, detection of biosynthesis of the receptor (membrane expression) and it is compatible with downstream cellular assays - including firefly luciferase-based readouts.
Inconsistent estimates of hybridization frequency in newts revealed by SNPs and microsatellites
Authors: Miralles Aurélien , Secondi Jean , Pabijan Maciej , Babik Wiesław , Lemaire Christophe , Crochet Pierre-André
Published: January 2023

Hybridization between the European smooth and palmate newts has recurrently been mentioned in the literature. The only two studies that attempted to quantify the frequency of hybridization and gene admixture between these two species came to strikingly opposite conclusions. According to Arntzen et al (1998, 42 allozymes), hybrids are rare in nature and introgression negligible, while according to Johanet et al (2011, 6 microsatellites), introgressive hybridization is significant and widespread across the shared distribution range. To clarify this question, we implemented high-throughput SNP genotyping with diagnostic biallelic SNPs on 965 specimens sampled across Europe. Our results are in line with Arntzen et al, since only two F1 hybrids were identified in two distinct French localities, and no further hybrid generations or backcrosses. Moreover, reanalysis of 78 of the samples previously studied by Johanet et al. (2011) using our SNPs panel could not reproduce their results, suggesting that microsatellite-based inference overestimated the hybridization frequency between these two species. Since we did not detect methodological issues with the analyses of Johanet et al., our results suggest that SNP approaches outperform microsatellite-based assessments of hybridization frequency, and that conclusions previously published on this topic with a small number of microsatellite loci should be taken with caution, and ideally be repeated with an increased genomic coverage.
Evolutionarily diverse origins of honey bee deformed wing viruses
Authors: Hasegawa Nonno , Techer Maeva A. , Adjlane Noureddine , al-Hissnawi Muntasser Sabah , Antúnez Karina , Beaurepaire Alexis , Christmon Krisztina , Delatte Helene , Dukku Usman H. , Eliash Nurit , El-Niweiri Mogbel A. A. , Esnault Olivier , Evans Jay D. , Haddad Nizar J. , Locke Barbara , Muñoz Irene , Noël Grégoire , Panziera Delphine , Roberts John M. K. , De la Rúa Pilar , Shebl Mohamed A. , Stanimirovic Zoran , Rasmussen David A. , Mikheyev Alexander S.
Published: January 2023

Novel transmission routes can allow infectious diseases to spread, often with devastating consequences. Ectoparasitic varroa mites vector a diversity of RNA viruses and, having switched hosts from the eastern to western honey bees (Apis ceranatoApis mellifera). They provide an opportunity to explore how novel transmission routes shape disease epidemiology. As the principal driver of the spread of Deformed Wing Viruses (mainly DWV-A and DWV-B), varroa infestation has also driven global honey bee health declines. The more virulent DWV-B strain has been replacing the original DWV-A strain in many regions over the past two decades. Yet, how these viruses originated and spread remains poorly understood. Here we use a phylogeographic analysis based on whole genome data to reconstruct the origins and demography of DWV spread. We found that, rather than reemerging in western honey bees after varroa switched hosts, as suggested by previous work, DWV-A most likely originated in Asia and spread in the mid-20thcentury. It also showed a massive population size expansion following the varroa host switch. By contrast, DWV-B was most likely acquired more recently from a source outside Asia, and appears absent from eastern honey bees, the original varroa host. These results highlight the dynamic nature of viral adaptation, whereby a vector’s host switch can give rise to competing and increasingly virulent disease pandemics. The evolutionary novelty and rapid global spread of these host-virus interactions, together with observed spillover into other species, illustrate how increasing globalisation poses urgent threats to biodiversity and food security.
Evidence for cryptic gene flow in parthenogenetic stick insects of the genusTimema
Authors: Freitas Susana , Parker Darren J. , Labédan Marjorie , Dumas Zoé , Schwander Tanja
Published: January 2023

Obligately parthenogenetic species are expected to be short lived since the lack of sex and recombination should translate into a slower adaptation rate and increased accumulation of deleterious alleles. Some, however, are thought to have been reproducing without males for millions of years. It is not clear how these old parthenogens can escape the predicted long-term costs of parthenogenesis, but an obvious explanation is cryptic sex.

In this study we screen for signatures of cryptic sex in eight populations of four parthenogenetic species ofTimemastick insects, some estimated to be older than 1M yrs. Low genotype diversity, homozygosity of individuals and high linkage disequilibrium (LD) unaffected by marker distances support exclusively parthenogenetic reproduction in six populations. However, in two populations (namely, of the speciesTimema douglasiandT. monikensis) we find strong evidence for cryptic sex, most likely mediated by rare males. These populations had comparatively high genotype diversities, lower LD, and a clear LD decay with genetic distance. Rare sex in species that are otherwise largely parthenogenetic could help explain the unusual success of parthenogenesis in theTimemagenus and raises the question whether episodes of rare sex are in fact the simplest explanation for the persistence of many old parthenogens in nature.
Hippocampal subfield volumes contribute to working memory interference control in aging: Evidence from longitudinal associations over 5 years
Authors: Andersson P , Samrani G , Andersson M , Persson J
Published: January 2023

In memory, familiar but no longer relevant information may disrupt encoding and retrieval of to-be-learned information. While it has been demonstrated that the ability to resolve proactive interference (PI) in working memory (WM) is reduced in aging, the neuroanatomical components of this decline have yet to be determined. Hippocampal (HC) involvement in age- related decline in control of PI is currently not known. In particular, the association between HC subfield volumes and control of PI in WM has not been examined previously. Here we investigate the associations between mean level and 5-year trajectories of gray matter subfield volumes and PI in WM across the adult life span (N = 157). Longitudinal analyses over 5- years across all participants revealed that reduced volume in the subiculum was related to impaired control of PI. Age-stratified analyses showed that this association was most pronounced in older adults. Furthermore, we found that in older adults the effect of age on PI was mediated by GM volume in the HC. The current results show that HC volume is associated with the ability to control PI in WM, and that these associations are modulated by age.
Implications of gene tree heterogeneity on downstream phylogenetic analyses: A case study employing the Fair Proportion index
Authors: Wicke Kristina , Haque Md Rejuan , Kubatko Laura
Published: January 2023

Many questions in evolutionary biology require the specification of a phylogeny for downstream phylogenetic analyses. However, with the increasingly widespread availability of genomic data, phylogenetic studies are often confronted with conflicting signal in the form of genomic heterogeneity and incongruence between gene trees and the species tree. This raises the question of determining what data and phylogeny should be used in downstream analyses, and to what extent the choice of phylogeny (e.g., gene trees versus species trees) impacts the analyses and their outcomes.

In this paper, we study this question in the realm of phylogenetic diversity indices, which provide ways to prioritize species for conservation based on their relative evolutionary isolation on a phylogeny, and are thus one example of downstream phylogenetic analyses. We use the Fair Proportion (FP) index, also known as the evolutionary distinctiveness score, and explore the variability in species rankings based on gene trees as compared to the species tree for several empirical data sets. Our results indicate that prioritization rankings among species vary greatly depending on the underlying phylogeny, suggesting that the choice of phylogeny is a major influence in assessing phylogenetic diversity in a conservation setting.

While we use phylogenetic diversity conservation as an example, we suspect that other types of downstream phylogenetic analyses such as ancestral state reconstruction are similarly affected by genomic heterogeneity and incongruence. Our aim is thus to raise awareness of this issue and inspire new research on which evolutionary information (species trees, gene trees, or a combination of both) should form the basis for analyses in these settings.
Dynamics of blood cells during a routine laboratory examination
Authors: Taye Mesfin Asfaw
Published: January 2023

Centrifugation is a commonly performed laboratory procedure that helps to separate blood cells such as red blood cellsRBCs, white bood cellsWBCs, and platelets from plasma or serum. Although centrifugation is a routine procedure in most medical laboratories, factors that affect the efficacy of the centrifugation process have never been studied analytically. In this paper, we examine the effect of centrifugation time on the efficacy of the centrifugation process by studying the dynamics of blood cells via the well-known Langevin equation or equivalently, by solving the Fokker-Plank equation. Our result depicts that the speed of the centrifuge is one of the determinant factors concerning the efficacy of the centrifugation process. As angular speed increases, centrifugal force increases and as a result, the particles are forced to separate from plasma or serum. The room temperature also considerably affects the dynamics of the sample during centrifugation. Most importantly, the generation of heat during centrifugation increases the temperature within a centrifuge, and as a result, not only the stability of the sample but also the mobility of analyse is affected. We show that as the temperature within the centrifuge intensifies, the velocity of the cells as well as the displacement of the cells in the fluid increases. We then study the dynamics of the whole blood during capillary action where in this case the blood flows upward in a narrow space without the assistance of external forces. Previous investigations show that the height that the fluid rises increases as surface tension steps up. The viscosity of the fluid also affects the capillary action but to date, the dependence of the height on viscosity has never been explored due to the lack of a mathematical correlation between the viscosity of blood and surface tension [1]. In this work, we first examine the correlation between surface tension and viscous friction via data fitting. Our result exhibits that the viscosity of the blood increases linearly as surface tension increases. The mathematical relation between the height and viscous friction is derived. It is shown that the height of the blood that rises in the capillary increases as the viscous friction intensifies. As the temperature of the room steps up, the height also decreases. The dependence of erythrocytes sedimentation rate on surface tension is also studied. The results obtained in this work show that the erythrocyte sedimentation rate ESR increases as surface tension steps down.

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