bluuebunny/crossref_metadata_2025_split huggingface dataset:
One of these morphs is not like the others: orange morphs exhibit different escape behavior than other morphs in a color polymorphic lizard
Authors: Brock Kinsey M. , Madden Indiana E. 
Published: December 2021

ABSTRACTVariation in color morph behavior is an important factor in the maintenance of color polymorphism. Alternative anti-predator behaviors are often associated with morphological traits such as coloration, possibly because predator-mediated viability selection favors certain combinations of anti-predator behavior and color. The Aegean wall lizard,Podarcis erhardii, is color polymorphic and populations can have up to three monochromatic morphs: orange, yellow, and white. We investigated whether escape behaviors differ among coexisting color morphs, and if morph behaviors are repeatable across different populations with the same predator species. Specifically, we assessed color morph flight initiation distance (FID), distance to the nearest refuge (DNR), and distance to chosen refuge (DR) in two populations of Aegean wall lizards from Naxos island. We also analyzed the type of refugia color morphs selected and their re-emergence behavior following a standardized intrusion event. We found that orange morphs have different escape behaviors from white and yellow morphs, and these differences are consistent in both of the populations we sampled. Orange morphs have shorter FIDs, DNRs, and DRs, select different refuge types, and re-emerge less often after an intruder event compared to white and yellow morphs. Observed differences in color morph escape behaviors support the idea that morphs have evolved alternative behavioral strategies that may play a role in population-level morph maintenance and loss.
Neural mechanism of experience-dependent sensory gain control in C. elegans
Authors: Ikejiri Yosuke , Tanimoto Yuki , Fujita Kosuke , Hiramatsu Fumie , Yamazaki Shuhei J. , Endo Yuto , Iwatani Yasushi , Fujimoto Koichi , Kimura Koutarou D. 
Published: December 2021

ABSTRACTAnimals’ sensory systems adjust their responsiveness to environmental stimuli that vary greatly in their intensity. Here we report the neural mechanism of experience-dependent sensory adjustment, especially gain control, in the ASH nociceptive neurons in Caenorhabditis elegans. Using calcium imaging under gradual changes in stimulus intensity, we find that the ASH neurons of naive animals respond to concentration increases in a repulsive odor 2-nonanone regardless of the magnitude of the concentration increase. However, after preexposure to the odor, the ASH neurons exhibit significantly weak responses to a small gradual increase in odor concentration while their responses to a large gradual increase remain strong. Thus, preexposure changes the slope of stimulus–response relationships (i.e., gain control). Behavioral analysis suggests that this gain control contributes to the preexposure-dependent enhancement of odor avoidance behavior. Mathematical analysis reveals that the ASH response consists of fast and slow components, and that the fast component is specifically suppressed by preexposure. In addition, genetic analysis suggests that G protein signaling is required for the fast component. Thus, our integrative study demonstrates how prior experience dynamically modulates stimulus–response relationships in sensory neurons, eventually leading to adaptive modulation of behavior.
Potential and action mechanism of favipiravir as an antiviral against Junin virus
Authors: Zadeh Vahid Rajabali , Urata Shuzo , Afowowe Tosin Oladipo , Yasuda Jiro 
Published: December 2021

ABSTRACTFavipiravir is a nucleoside analogue that inhibits the replication and transcription of a broad spectrum of RNA viruses, including pathogenic arenaviruses. In this study, we isolated a favipiravir-resistant mutant of Junin virus (JUNV), which is the causative agent of Argentine hemorrhagic fever, and analyzed the antiviral mechanism of favipiravir against JUNV. Two amino acid substitutions, N462D in the RNA-dependent RNA polymerase (RdRp) and A168T in the glycoprotein precursor GPC, were identified in the mutant. GPC-A168T substitution enhanced the efficiency of JUNV internalization, which explains the robust replication kinetics of the mutant in the virus growth analysis. Although RdRp-N462D substitution did not affect polymerase activity levels in a minigenome system, comparisons of RdRp error frequencies showed that the virus with RdRp-D462 possessed a significantly higher fidelity. We also provided experimental evidence for the first time that favipiravir inhibited JUNV through the accumulation of transition mutations, confirming its role as a purine analogue against arenaviruses. Moreover, we showed that treatment with a combination of favipiravir and either ribavirin or remdesivir inhibited JUNV replication in a synergistic manner, blocking the generation of the drug-resistant mutant. Our findings provide new insights for the clinical management and treatment of Argentine hemorrhagic fever.
The homolog of human ecto-nucleoside triphosphate diphosphohydrolase MIG-23 is involved in sperm migration by modulating extracellular ATP levels in Ascaris suum
Authors: Wang Qiushi , He Ruijun , Chen Lianwan , Zhang Qi , Shan Jin , Zhao Yanmei , Wang Xia 
Published: December 2021

AbstractIn nematodes, spermiogenesis, which is also called sperm activation, is a process in which nonmotile spermatids are transformed into crawling spermatozoa, which is accompanied by a series of morphological, physiological and biochemical changes. Sperm motility acquisition during this process is essential for successful fertilization. However, the mechanisms of sperm motility regulation in nematodes remain to be clarified. Herein, we found that extracellular adenosine-5’-triphosphate (ATP) level mediation by MIG-23, which is a homolog of human ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), was required for major sperm protein (MSP) filament dynamics and sperm motility in the nematode Ascaris suum. MIG-23 was localized on the sperm plasma membrane. During sperm activation, mitochondrial activity was increased dramatically, and a large amount of ATP was produced and stored in refringent granules (RGs). In addition, a portion of the produced ATP was released to the extracellular space through ATP channels, which were composed of innexins and localized on the sperm plasma membrane. Spermatozoa, instead of spermatids, hydrolyzed exogenous ATP and processed ecto-ATPase activity. MIG-23 contributed to the ecto-ATPase activity of spermatozoa. Once MIG-23 activity was interrupted, spermatozoa also decreased their ATP hydrolysis activity. Blocking MIG-23 activity resulted in an increase in the depolymerization rate of MSP filaments in pseudopodia, which eventually affected nematode sperm migration. Overall, our data imply that MIG-23, which contributes to the ecto-ATPase activity of spermatozoa, regulates sperm migration by modulating extracellular ATP levels.HighlightsATP is released to extracellular space through innexin channels which are identified in worm sperm.Worm spematozoa show ecto-ATPase activity.MIG-23 contributes to the ecto-ATPase activity of spermatozoa and regulates extracellular ATP level.MIG-23 is required for MSP-based filament dynamics and sperm migration.
Artificial intelligence to solve the X-ray crystallography phase problem: a case study report
Authors: Barbarin-Bocahu Irène , Graille Marc 
Published: December 2021

AbstractThe determination of three dimensional structures of macromolecules is one of the actual challenge in biology with the ultimate objective of understanding their function. So far, X-ray crystallography is the most popular method to solve structure, but this technique relies on the generation of diffracting crystals. Once a correct data set has been obtained, the calculation of electron density maps requires to solve the so-called «phase problem » using different approaches. The most frequently used technique is molecular replacement, which relies on the availability of the structure of a protein sharing strong structural similarity with the studied protein. Its success rate is directly correlated with the quality of the models used for the molecular replacement trials. The availability of models as accurate as possible is then definitely critical.Very recently, a breakthrough step has been made in the field of protein structure prediction thanks to the use of machine learning approaches as implemented in the AlphaFold or RoseTTAFold structure prediction programs. Here, we describe how these recent improvements helped us to solve the crystal structure of a protein involved in the nonsense-mediated mRNA decay pathway (NMD), an mRNA quality control pathway dedicated to the elimination of eukaryotic mRNAs harboring premature stop codons.
Arl15 upregulates the TGFβ family signaling by promoting the assembly of the Smad-complex
Authors: Shi Meng , Tie Hieng Chiong , Mahajan Divyanshu , Sun Xiuping , Zhou Yan , Boh Boon Kim , Vardy Leah A. , Lu Lei 
Published: December 2021

SummaryThe hallmark event of the canonical transforming growth factor β (TGFβ) family signaling is the assembly of the Smad-complex, consisting of the common Smad, Smad4, and phosphorylated receptor-regulated Smads. How the Smad-complex is assembled and regulated is still unclear. Here, we report that active Arl15, an Arf-like small G protein, specifically binds to the MH2 domain of Smad4 and colocalizes with Smad4 at the endolysosome. The binding relieves the autoinhibition of Smad4, which is imposed by the intramolecular interaction between its MH1 and MH2 domains. Activated Smad4 subsequently interacts with phosphorylated receptor-regulated Smads, forming the Smad-complex. Our observations suggest that Smad4 functions as an effector and a GTPase activating protein (GAP) of Arl15. Assembly of the Smad-complex enhances the GAP activity of Smad4 toward Arl15, therefore dissociating Arl15 before the nuclear translocation of the Smad-complex. Our data further demonstrate that Arl15 positively regulates the TGFβ family signaling.
Manganese modulates metabolic activity and redox homeostasis in translationally-blockedLactococcus cremoris, impacting metabolic persistence, cell-culturability, and flavor formation
Authors: Nugroho Avis Dwi Wahyu , van Olst Berdien , Bachtiar Stephanie Agnes , Boeren Sjef , Kleerebezem Michiel , Bachmann Herwig 
Published: December 2021

AbstractManganese (Mn) is an essential trace element that is supplemented in microbial media with varying benefits across species and growth conditions. We found that growth ofLactococcus cremoriswas unaffected by manganese omission from the growth medium. The main proteome adaptation to manganese omission involved increased manganese transporter production (up to 2000-fold), while the remaining 10 significant proteome changes were between 1.4 and 4 fold. Further investigation in translationally-blocked (TB), non-growing cells showed that Mn supplementation (20 μM) led to approximately 1.5X faster acidification compared to Mn-free conditions. However, this faster acidification stagnated within 24 hours, likely due to draining of intracellular NADH that coincides with substantial loss of culturability. Conversely, without manganese, non-growing cells persisted to acidify for weeks, albeit at a reduced rate, but maintaining redox balance and culturability. Strikingly, despite being unculturable, α-keto acid-derived aldehydes continued to accumulate in cells incubated in the presence of manganese, whereas without manganese cells predominantly formed the corresponding alcohols. This is most likely reflecting NADH availability for the alcohol dehydrogenase-catalyzed conversion. Overall, manganese influences the lactococcal acidification rate, and flavor formation capacity in a redox dependent manner. These are important industrial traits especially during cheese ripening, where cells are in a non-growing, often unculturable state.
The effect of anti-SARS-CoV-2 monoclonal antibody, bamlanivimab, on endogenous immune response to COVID-19 vaccination
Authors: Benschop Robert J. , Tuttle Jay L. , Zhang Lin , Poorbaugh Josh , Kallewaard Nicole L. , Vaillancourt Peter , Crisp Melissa , Vy Trinh Thi Ngoc , Freitas Joshua J. , Beasley Stephanie , Daniels Montanea , Haustrup Natalie , Higgs Richard E. , Nirula Ajay , Cohen Myron S. , Marovich Mary 
Published: December 2021

AbstractAs the COVID-19 pandemic evolves, and vaccine rollout progresses, the availability and demand for monoclonal antibodies for the prevention and treatment of SARS-CoV-2 infection are also accelerating. This longitudinal serological study evaluated the magnitude and potency of the endogenous antibody response to COVID-19 vaccination in participants who first received a COVID-19 monoclonal antibody in a prevention study. Over the course of six months, serum samples were collected from the prevention population (nursing home residents and staff) enrolled in the BLAZE-2 clinical trial who had received either bamlanivimab (4200 mg) or placebo. In an unplanned component of this trial, a subset of these participants was subsequently fully vaccinated with two doses of either SpikeVax (Moderna) or Comirnaty (BioNTech/Pfizer) COVID-19 mRNA vaccines, as part of the US vaccination program. This post-hoc analysis assessed the immune response to vaccination for the subset of participants (N=135) without prior SARS-CoV-2 infection. Antibody titers and potency were assessed using three assays against SARS-CoV-2 proteins that bamlanivimab does not significantly bind to, thereby reflecting the endogenous antibody response. All bamlanivimab and placebo participants mounted a robust immune response to full COVID-19 vaccination, irrespective of age, risk-category and vaccine type, with any observed differences unlikely to be clinically meaningful. These findings are pertinent for informing public health policy with results that suggest a complementary role for COVID-19 monoclonal antibodies (mAbs) with COVID-19 vaccines and that the benefit of receiving COVID-19 vaccination at the earliest opportunity outweighs the minimal effect on the endogenous immune response due to prior prophylactic COVID-19 mAb infusion.One Sentence SummaryIndividuals infused with an anti-SARS-CoV-2 antibody demonstrated a robust immune response to subsequent full COVID-19 vaccination.
Heterogenous Cellular and Humoral Immune Trajectories after SARS-CoV-2 Infection: Compensatory Responses in a Population-Based Cohort
Authors: Menges Dominik , Zens Kyra D. , Ballouz Tala , Caduff Nicole , Llanas-Cornejo Daniel , Aschmann Hélène E. , Domenghino Anja , Pellaton Céline , Perreau Matthieu , Fenwick Craig , Pantaleo Giuseppe , Kahlert Christian R. , Münz Christian , Puhan Milo A. , Fehr Jan S. 
Published: December 2021

AbstractTo better understand the development of immunity against SARS-CoV-2 over time, we evaluated humoral and cellular responses a population-based cohort of SARS-CoV-2-infected individuals covering the full spectrum of COVID-19 up to 217 days after diagnosis. We characterized anti-Spike (S)-IgA and -IgG antibody responses in 431 individuals and found that about 85% develop and maintain anti-S-IgG responses over time. In a subsample of 64 participants selected for a detailed characterization of immune responses, we additionally evaluated anti-Nucleocapsid (N)-IgG antibodies and T cell responses specific to viral Membrane (M), N, and S proteins. Most participants had detectable T cell responses to at least one of the four peptide pools analyzed, which were more frequent than antibody seropositivity. We found a moderate correlation between antibody and T cell responses, which declined over time and suggests important variability in response patterns between individuals. The heterogeneity of immune trajectories was further analyzed using cluster analyses taking into account joint antibody and T cell responses over time. We identified five distinct immune trajectory patterns, which were characterized by specific antibody, T cell and T cell subset patterns along with disease severity and demographic factors. Higher age, male sex, higher disease severity and being a non-smoker was significantly associated with stronger immune responses. Overall, the results highlight that there is a consistent and maintained antibody response among most SARS-CoV-2-infected individuals, while T cell responses appear to be more heterogenous but potentially compensatory among those with low antibody responses.One Sentence SummaryPresence of heterogenous immune response trajectories after SARS-CoV-2 infection with potential compensatory role of T cells among individuals with low antibody responses.
Antibody-mediated Immunogenicity against SARS-CoV-2 following priming, boosting and hybrid immunity: insights from 11 months of follow-up of a healthcare worker cohort in Israel, December 2020-October 2021
Authors: Edelstein Michael , Beiruti Karine Wiegler , Ben-Amram Hila , Bar-Zeev Naor , Sussan Christian , Asulin Hani , Strauss David , Bathish Younes , Zarka Salman , Jabal Kamal Abu 
Published: December 2021

AbstractBackgroundWe determined circulating anti-S SARS-CoV-2 IgG antibody titres in a vaccinated healthcare workers (HCWs) cohort from Northern Israel in the 11 months following primary vaccination according to age, ethnicity, boosting timing and previous infection status.MethodsAll consenting HCWs were invited to have their circulating IgG levels measured before vaccination and at 6 subsequent timepoints. All HCWs with suspected COVID-19 were PCR tested. We described trends in circulating IgG geometric mean concentration by age, ethnicity, timing of boosting and previous infection status and compared strata using Kruskall-Wallis tests.ResultsAmong 985 vaccinated HCWs. IgG titres gradually decreased in all groups over the study duration. Younger or previously infected individuals had higher initial IgG levels (p<0.001 in both cases); differences substantially decreased or disappeared at 7-9 months, before boosting. Pre-infection IgG levels in infected participants were similar to levels measured at the same timepoint in HCWs who remained uninfected (p>0.3). IgG GMC in those boosted 6-7 months after dose 2 was lower compared with those boosted 8-9 months after (1999-vs 2736, p=0.02).ConclusionsImmunity waned 6 months post-priming in all age groups and in previously infected individuals, reversed by boosting. IgG titres decrease among previously infected individuals and the proportion of reinfected individuals in this group, comparable to the proportion of breakthrough infection in previously uninfected individuals suggests individuals with hybrid immunity (infection+vaccination) may also require further doses. Our study also highlights the difficulty in determining protective IgG levels and the need to clarify the optimal timing in 3 dose regimens
Changing of therapeutic trends between the 1st and 2nd wave did not reduce COVID-19 related mortality of renal transplant recipients: a national registry study
Authors: Berger Bastien , Hazzan Marc , Kamar Nassim , Francois Hélène , Matignon Marie , Greze Clarisse , Gatault Philippe , Frimat Luc , Westeel Pierre F , Goutaudier Valentin , Snanoudj Renaud , Colosio Charlotte , Sicard Antoine , Bertrand Dominique , Mousson Christiane , Bamoulid Jamal , Thierry Antoine , Anglicheau Dany , Couzi Lionel , Chemouny Jonathan M , Duveau Agnes , Moal Valerie , Le Meur Yannick , Blancho Gilles , Tourret Jérôme , Malvezzi Paolo , Mariat Christophe , Rerolle Jean-Philippe , Bouvier Nicolas ,   the French SOT COVID Registry, Caillard Sophie , Thaunat Olivier 
Published: December 2021

AbstractSARS-CoV-2 pandemic evolved in two consecutive waves over 2020 (for France: 1st wave from March 1 to July 31; and 2nd wave from August 1 to December 31). Improvements in the management of COVID-19 led to a reduction of mortality rates in hospitalized patients during the second wave. Whether this progress also benefited to kidney transplant recipients (KTR), a population particularly vulnerable to severe COVID-19, remained unclear.In France, 957 KTR were hospitalized for COVID-19 in 2020 and their data were prospectively collected in the French SOT COVID registry. The presentation, management, and outcomes of the 359 KTR diagnosed during the 1st wave were compared to those of the 598 of the 2nd wave. Baseline comorbidities were largely similar between KTR of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs 58.4%, p<0.001) or CNI (32.1% vs 16.6%, p<0.001) was less frequent during the 2nd wave. Hydroxychloroquine and azithromycin that were commonly used during the 1st wave (21.7% and 30.9%, respectively) were almost abandoned during the 2nd. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, p<0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, p=0.48).We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality in KTR. Our data indirectly support the importance of vaccination and monoclonal neutralizing anti-SARS-CoV-2 antibodies to protect KTR from severe COVID-19.
Patterns of convergence and divergence between bipolar disorder type I and type II: evidence from integrative genomic analyses
Authors: Huang Yunqi , Liu Yunjia , Wu Yulu , Tang Yiguo , Liu Siyi , Xiao Liling , Zhang Mengting , Tao Shiwan , Xie Min , Dai Minhan , Li Mingli , Gui Hongsheng , Wang Qiang 
Published: December 2021

AbstractGenome-wide association studies (GWAS) analyses have revealed genetic evidence of bipolar disorder (BD), but little is known about genetic structure of BD subtypes. We aimed to investigate genetic overlap and distinction of bipolar type I (BDI) & type II (BDII) by conducting integrative post-GWAS analyses. This study utilized single nucleotide polymorphism (SNP)-level approaches to uncover correlated and distinct genetic loci. Transcriptome-wide association analyses (TWAS) were then approached to pinpoint functional genes expressed in specific brain tissues and blood. Next, we performed cross-phenotype analysis including exploring the potential causal associations between BDI & II and drug responses and comparing the difference of genetic structures among four different psychiatric traits. Our results find SNP-level evidence revealed three genomic loci, SLC25A17, ZNF184 and RPL10AP3 shared by BDI & II, while one locus (i.e., MAD1L1) and significant gene sets involved in calcium channel activity, neural and synapsed signals that distinguished two subtypes. TWAS data implicated different genes effecting BDI & II through expression in specific brain regions (e.g., nucleus accumbens for BDI). Cross-phenotype analyses indicated that BDI & II share continuous genetic structures with schizophrenia (SCZ) and major depression disorder (MDD), which help fill the gaps left by the dichotomy of mental disorder. These combined evidences illustrate genetic convergence and divergence between BDI & II and provide an underlying biological and trans-diagnostic insight into major psychiatric disorders.