bluuebunny/crossref_metadata_2025_split huggingface dataset:
A proprioceptive feedback circuit drivesC. eleganslocomotor adaptation through dopamine signaling
Authors: Ji Hongfei , Fouad Anthony D. , Li Zihao , Ruba Andrew , Fang-Yen Christopher 
Published: October 2022

AbstractAn animal adapts its motor behavior to navigate the external environment. This adaptation depends on proprioception, which provides feedback on an animal’s body postures. How proprioception mechanisms interact with motor circuits and contribute to locomotor adaptation remains unclear. Here we describe and characterize proprioception-mediated homeostatic control of undulatory movement in the roundwormCaenorhabditis elegans. We found the worm responds to optogenetically or mechanically induced decreases in midbody bending amplitude by increasing its anterior amplitude. Conversely, it responds to increased midbody amplitude by decreasing the anterior amplitude. Using genetics, microfluidic and optogenetic perturbation response analyses, and optical neurophysiology, we elucidated the neural circuit underlying this compensatory postural response. The dopaminergic PDE neurons proprioceptively sense midbody bending and signal to AVK interneurons via the D2-like dopamine receptor DOP-3. The FMRFamide-like neuropeptide FLP-1, released by AVK, regulates SMB head motor neurons to modulate anterior bending. We propose that this homeostatic behavioral control optimizes locomotor efficiency. Our findings demonstrate a mechanism in which proprioception works with dopamine and neuropeptide signaling to mediate motor control, a motif that may be conserved in other animals.
The impact of the ABO/Rh blood group on susceptibility and severity among COVID-19 patients in Luanda, Angola
Authors: Sebastião Cruz S. , Teixeira Alice , Luísa Ana , Arrais Margarete , Tchonhi Chissengo , Cogle Adis , Sacomboio Euclides , Cardoso Bruno , Morais Joana , de Vasconcelos Jocelyne Neto , Brito Miguel 
Published: October 2022

AbstractSARS-CoV-2 is a public health concern worldwide. Identification of biological factors that could influence transmission and worsen the disease has been the subject of extensive investigation. Herein, we investigate the impact of the ABO/Rh blood group on susceptibility and severity among COVID-19 patients in Luanda, Angola. This was a multicentric cohort study conducted with 101 COVID-19 patients. Chi-square and logistic regression were calculated to check factors related to the worsening of the disease and deemed significant when p<0.05. Blood type O (51.5%) and Rh-positive (93.1%) were the most frequent. Patients from blood type O had a high risk to severe disease [OR: 1.33 (95% CI: 0.42 - 4.18), p=0.630] and hospitalization [OR: 2.59 (95% CI: 0.84 - 8.00), p=0.099]. Also, Rh-positive blood type presented a high risk for severe disease (OR: 10.6, p=0.007) and hospitalization (OR: 6.04, p=0.026). We find a high susceptibility, severity, hospitalization, and mortality, respectively, among blood group O and Rh-positive patients, while blood group AB presented a low susceptibility, severity, hospitalization, and mortality, respectively. Our findings add to the body of evidence suggesting that ABO/Rh blood groups play an important role in the course of SARS-CoV-2 infection.
So ManyFolds, So Little Time: Efficient Protein Structure Prediction With pLMs and MSAs
Authors: Barrett Thomas D. , Villegas-Morcillo Amelia , Robinson Louis , Gaujac Benoit , Adméte David , Saquand Elia , Beguir Karim , Flajolet Arthur 
Published: October 2022

AbstractIn recent years, machine learning approaches forde novoprotein structure prediction have made significant progress, culminating in AlphaFold which approaches experimental accuracies in certain settings and heralds the possibility of rapidin silicoprotein modelling and design. However, such applications can be challenging in practice due to the significant compute required for training and inference of such models, and their strong reliance on the evolutionary information contained in multiple sequence alignments (MSAs), which may not be available for certain targets of interest. Here, we first present a streamlined AlphaFold architecture and training pipeline that still provides good performance with significantly reduced computational burden. Aligned with recent approaches such as OmegaFold and ESMFold, our model is initially trained to predict structure from sequences alone by leveraging embeddings from the pretrained ESM-2 protein language model (pLM). We then compare this approach to an equivalent model trained on MSA-profile information only, and find that the latter still provides a performance boost – suggesting that even state-of-the-art pLMs cannot yet easily replace the evolutionary information of homologous sequences. Finally, we train a model that can make predictions from either the combination, or only one, of pLM and MSA inputs. Ultimately, we obtain accuracies in any of these three input modes similar to models trained uniquely in that setting, whilst also demonstrating that these modalities are complimentary, each regularly outperforming the other.
A context-dependent switch from sensing to feeling in the primate amygdala
Authors: Martin Anne B. , Cardenas Michael A. , Andersen Rose K. , Bowman Archer I. , Hillier Elizabeth A. , Bensmaia Sliman , Fuglevand Andrew J. , Gothard Katalin M. 
Published: October 2022

SUMMARYThe skin transmits affective signals that integrate into our social vocabulary. As the socio-affective aspects of touch are likely processed in the amygdala, we compared neural responses to social grooming and gentle airflow recorded from the amygdala and the primary somatosensory cortex of non-human primates. Neurons in the somatosensory cortex responded to both types of tactile stimuli. In the amygdala, however, neurons did not respond to individual grooming sweeps even though grooming elicited autonomic states indicative of positive affect. Instead, many showed changes in baseline firing rates that persisted throughout the grooming bout. Such baseline fluctuations were attributed to social context because the presence of the groomer alone could account for the observed changes in baseline activity. It appears, therefore, that during grooming, the amygdala stops responding to external inputs on a short time scale but remains responsive to social context (or the associated affective states) on longer time scales.
In vitrofloral development in poplar: Insights into seed trichome and trimonoecy regulation
Authors: Ortega María A. , Zhou Ran , Chen Margot S.S. , Bewg William P. , Simon Bindu , Tsai Chung-Jui 
Published: October 2022

SummaryWoody perennials includingPopulusspp. (poplars) have a juvenile phase that ranges from several years to decades in length. This and the year-long floral development process are major impediments to breeding and to fundamental research of reproductive traits. Here we report a CRISPR-empoweredin vitroflowering system and demonstrate its application using three reproductive traits: sex, seed trichomes, and a previously undescribed potential for trimonoecy in poplar.
Mrj an Hsp40 family chaperone regulates the oligomerization of Orb2 and long-term memory
Authors: Desai Meghal , Hemant  , Deo Ankita , Naik Jagyanseni , Bose Tania , Majumdar Amitabha 
Published: October 2022

AbstractOrb2 the Drosophila homolog of Cytoplasmic polyadenylation element binding protein (CPEB) forms prion-like oligomers. These oligomers consist of Orb2A and Orb2B isoforms and their formation are dependent on the oligomerization of the Orb2A isoform. Drosophila with a mutation diminishing Orb2A’s prion-like oligomerization forms long-term memory but fails to maintain it over time. Since, this prion-like oligomerization of Orb2A plays a crucial role in the maintenance of memory, here we aim to find what regulates this oligomerization. In an immunoprecipitation-based screen, we identify interactors of Orb2A in the Hsp40 and Hsp70 families of proteins. Amongst these, we find an Hsp40 family protein Mrj as a regulator of the conversion of Orb2A to its prion-like form. Mrj interacts with Hsp70 proteins and acts as a chaperone by interfering with the aggregation of pathogenic Huntingtin. Unlike its mammalian homolog, we find Drosophila Mrj is neither an essential gene nor causes any gross neurodevelopmental defect. We observe a loss of Mrj results in a reduction in Orb2 oligomers. Further, the knockdown of Mrj in the mushroom body neurons results in a deficit in long-term memory. Our work implicates a chaperone Mrj in mechanisms of memory regulation through controlling the oligomerization of Orb2A and its association with the translating polysomes.
Fluvoxamine for Outpatient Treatment of COVID-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial
Authors: McCarthy Matthew W. , Naggie Susanna , Boulware David R. , Lindsell Christopher J. , Stewart Thomas G. , Felker G. Michael , Jayaweera Dushyantha , Sulkowski Mark , Gentile Nina , Bramante Carolyn , Singh Upinder , Dolor Rowena J. , Ruiz-Unger Juan , Wilson Sybil , DeLong Allison , Remaly April , Wilder Rhonda , Collins Sean , Dunsmore Sarah E. , Adam Stacey J. , Thicklin Florence , Hanna George , Ginde Adit A. , Castro Mario , McTigue Kathleen , Shenkman Elizabeth , Hernandez Adrian F. ,   the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group
Published: October 2022

AbstractBackgroundThe effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic coronavirus disease 2019 (COVID-19) is unclear.DesignACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 non-hospitalized adults aged ≥30 years with confirmed COVID-19 experiencing ≥2 symptoms of acute infection for ≤7 days prior to randomization were randomized to receive fluvoxamine 50 mg or placebo twice daily for 10 days. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent or emergency care visit by day 28.ResultsOf 1331 participants randomized (mean [SD] age, 48.5 [12.8] years; 57% women; 67% reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (n=614 placebo, n=674 fluvoxamine). Median time to recovery was 13 days (IQR 12–13) in the placebo group and 12 days (IQR 11–14) in the fluvoxamine group (hazard ratio [HR] 0.96, 95% credible interval [CrI] 0.86–1.07; posterior probability for benefit [HR>1]=0.22). Twenty-six participants (3.9%) in the fluvoxamine group were hospitalized or had urgent or emergency care visits compared with 23 (3.8%) in the placebo group (HR 1.1, 95% CrI 0.6–1.8; posterior probability for benefit [HR<1]=0.340). One participant in the fluvoxamine group and 2 in the placebo group were hospitalized; no deaths occurred. Adverse events were uncommon in both groups.ConclusionsTreatment with fluvoxamine 50 mg twice daily for 10 days did not improve time to recovery, compared with placebo, among outpatients with mild to moderate COVID-19. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.
Reptarenavirus Co- and Superinfection in Cell Culture Sheds Light on the S and L Segment Accumulation in Captive Snakes
Authors: Lintala Annika , Szirovicza Leonora , Kipar Anja , Hetzel Udo , Hepojoki Jussi 
Published: October 2022

ABSTRACTBoid inclusion body disease (BIBD) caused by reptarenaviruses affects collections of captive constrictor snakes worldwide. The disease manifests by formation of cytoplasmic inclusion bodies (IBs) in various tissues. Curiously, a snake with BIBD most often carries more than a single pair of genetically distinct reptarenavirus S and L segments, and the tissues of an infected individual can show variation in the variety of different S and L segment species. The role of reptarenavirus coinfection in development of BIBD remains unknown, and it is unclear how the infection affects the susceptibility to reptarenavirus superinfection or to secondary infection by other agents. Because cell culture studies with mammarenaviruses have demonstrated persistently infected cultures to resist superinfection by genetically similar viruses, we hypothesized that coinfection would only occur if the infecting viruses were of two different species. To study the hypothesis, we employed boa constrictor kidney- and brain-derived cell cultures to perform a set of co- and superinfection experiments with five reptarenavirus and one hartmanivirus isolates. Analysis of viral RNA released from coinfected cells using qRT-PCR did not demonstrate evident competition between reptarenaviruses of the same or different species in the boa constrictor kidney-derived cell line. The experiments on the brain-derived cell line revealed considerable differences in the replication ability of the reptarenaviruses tested, suggesting varying tissue specificity or target cell spectra for reptarenavirus species. Finally, experiments on persistently reptarenavirus infected cell lines showed reduced replication of closely related reptarenaviruses while the replication of reptarenaviruses from different species appeared unaffected.IMPORTANCESnakes with boid inclusion body disease (BIBD) often display reptarenavirus coinfections, or presence of unbalanced S and L segment ratios. Studies on mammarenaviruses suggest replication interference between closely but not between more distantly related viruses. In the study, we provide evidence that similar interference or competition between segments occurs also in the case of reptarenaviruses. Conversely, the results show that there is very little or no competition between more distantly related L or S segments, the cells release similar amounts of viral RNA segments in the case of mono and coinfection. Successful superinfections of persistently infected cell cultures suggest that the unbalanced S and L segment pools often seen in the infected animals could be a result of segment accumulation through sequential reptarenavirus co- and superinfections during breeding in captivity.
RNA structural dynamics modulate EGFR-TKIs resistance through controllingYRDCtranslation in NSCLC cells
Authors: Shi Boyang , An Ke , Wang Yueqin , Fei Yuhan , Guo Caixia , Zhang Qiangfeng Cliff , Yang Yun-gui , Tian Xin , Kan Quancheng 
Published: October 2022

SUMMARYEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) positively affect the initial control of non-small cell lung cancer (NSCLC). The rapidly acquired TKIs resistance accounts for a major hurdle in successful treatment. However, the mechanisms controlling EGFR-TKIs resistance remain largely unknown. RNA structures have widespread and crucial roles in various biological processes; but, their role in regulating cancer drug resistance remains unclear. Here, the PARIS method is used to establish the higher-order RNA structure maps of EGFR-TKI resistant- and sensitive-cells of NSCLC. According to our results, RNA structural regions are enriched in UTRs and correlate with translation efficiency. Moreover,YRDCfacilitates resistance to EGFR-TKIs in NSCLC cells, and RNA structure formation inYRDC3’UTR suppress ELAVL1 binding leading to EGFR-TKIs sensitivity by impairingYRDCtranslation. A potential cancer therapy strategy is provided by using antisense oligonucleotide (ASO) to perturb the interaction between RNA and protein. Our study reveals an unprecedented mechanism in which the RNA structure switch modulates EGFR-TKIs resistance by controllingYRDCmRNA translation in an ELAVL1-dependent manner.
Antiviral immune response reveals host-specific virus infections in natural ant populations
Authors: Viljakainen Lumi , Fürst Matthias A. , Grasse Anna V. , Jurvansuu Jaana , Oh Jinook , Tolonen Lassi , Eder Thomas , Rattei Thomas , Cremer Sylvia 
Published: October 2022

AbstractHosts can carry many viruses in their bodies, but not all of them cause disease. We studied ants as a social host to determine both their overall viral repertoire and the subset of actively infecting viruses across natural populations of three subfamilies: the Argentine ant (Linepithema humile, Dolichoderinae), the invasive garden ant (Lasius neglectus, Formicinae) and the red ant (Myrmica rubra, Myrmicinae). We used a dual sequencing strategy to reconstruct complete virus genomes by RNA-seq and to simultaneously determine the small interfering RNAs (siRNAs) by small RNA sequencing (sRNA-seq), which constitute the host antiviral RNAi immune response. This approach led to the discovery of 41 novel viruses in ants and revealed a host-ant specific RNAi response (21 vs. 22 nt siRNAs) in the different ant species. The efficiency of the RNAi response (sRNA/RNA read count ratio) depended on the virus and the respective ant species, but not its population. Overall, we found the highest virus abundance and diversity per population inLi. humile, followed byLa. neglectusandM. rubra. Argentine ants also shared a high proportion of viruses between populations, whilst overlap was nearly absent inM. rubra. Only a single of the total 59 viruses in our study caused active infection in more than one ant species, whilst six viruses infected one, but only contaminated another ant species. Disentangling active infection from contamination thus allowed us to show high host-specificity of active viral infections versus a decent degree of spillover of non-infecting viral contaminants across ant species, providing relevant information for ecosystem management.
Overexpression of the plastidal pseudo-proteaseAtFtsHi3confers drought tolerance without penalizing growth
Authors: Cook Sam D. , Mishra Laxmi S. , Isaksson Hanna , Straub Isabella R. , Abele Miriam , Mishra Sanatkumar , Ludwig Christina , Libby Eric , Funk Christiane 
Published: October 2022

AbstractDrought is one of the most severe environmental stresses affecting plant biomass production and quality, however, the molecular mechanisms of drought response in plants remain unclear. Here, we demonstrate that overexpression of the Arabidopsis gene FTSHi3 under the influence of its endogenous, or the 35S constitutive promoter results in drought-tolerant phenotypes without penalising plant growth. FTSHi3 encodes a pseudo-protease located in the chloroplast envelope and knock-down mutants (ftshi3-1) have previously been found to be drought tolerant, but highly reduced in growth. Changes in FtsHi3 transcript abundance therefore seems to induce drought tolerance inArabidopsis thaliana. Overexpression of FTSHi3 (pFTSHi3-OE) impacts leaf stomatal density, lowers stomatal conductance and increases water use efficiency. To explore the underlying mechanisms behind this, we compared the proteomes offtshi3-1andpFTSHi3-OEto wild type plants grown under drought and watered conditions. Under drought conditions, the drought related processes ‘osmotic stress’, ‘water transport’ and ‘response to abscisic acid’ were enriched, indicating thatpFtsHi3-OEandftshi3-1mutants are more active in their response to drought than the wild-type. The proteins HSP90, HSP93 and TIC110 were more abundant in the knock-down mutant, which suggests that FtsHi3 might play a downstream role in chloroplast pre-protein import. Increased abundance of FtsH7/9 and FtsH11, FtsH12 and FtsHi4 inftshi3-1combined with the fact that FtsH proteases function as homo- or heteromeric complexes suggests that these proteases may be possible interacting partners. To explore this, we constructed mathematical models that show FtsHi3 likely interacts with at least two other (pseudo-) proteases.
DOT1L regulates chromatin reorganization and gene expression during sperm differentiation
Authors: Blanco Mélina , Khattabi Laila El , Gobé Clara , Crespo Marion , Coulée Manon , de la Iglesia Alberto , Ialy-Radio Côme , Lapoujade Clementine , Givelet Maëlle , Delessard Marion , Seller-Corona Ivan , Yamaguchi Kosuke , Vernet Nadège , Van Leeuwen Fred , Lermine Alban , Okada Yuki , Daveau Romain , Oliva Rafael , Fouchet Pierre , Ziyyat Ahmed , Pflieger Delphine , Cocquet Julie 
Published: October 2022

AbstractSpermatozoa have a unique genome organization: their chromatin is almost completely devoid of histones and is formed instead of protamines which confer a high level of compaction and preserve paternal genome integrity until fertilization. Histone-to-protamine transition takes place in spermatids and is indispensable for the production of functional sperm. Here we show that the H3K79-methyltransferase DOT1L controls spermatid chromatin remodelling and subsequent reorganization and compaction of spermatozoon genome. Using a mouse model in whichDot1lis knocked-out (KO) in postnatal male germ cells, we found thatDot1l-KO sperm chromatin is less compact and has an abnormal content, characterized by the presence of transition proteins, immature protamine 2 forms and a higher level of histones. Proteomics and transcriptomics analyses performed on spermatids reveal thatDot1l-KO modifies the chromatin prior to histone removal, and leads to the deregulation of genes involved in flagellum formation and apoptosis during spermatid differentiation. As a consequence of these chromatin and gene expression defects,Dot1l-KO spermatozoa have less compact heads and are less motile which results in impaired fertility.
Mutational scans reveal differential evolvability ofDrosophilapromoters and enhancers
Authors: Li Xueying C. , Fuqua Timothy , van Breugel Maria Elize , Crocker Justin 
Published: October 2022

AbstractRapid enhancer and slow promoter evolution have been demonstrated through comparative genomics. However, it is not clear how this information is encoded genetically and if this can be used to place evolution in a predictive context. Part of the challenge is that our understanding of the potential for regulatory evolution is biased primarily toward natural variation or limited experimental perturbations. Here, to explore the evolutionary capacity of promoter variation, we surveyed an unbiased mutation library for three promoters inDrosophila melanogaster. We found that mutations in promoters had limited to no effect on spatial patterns of gene expression. Compared to developmental enhancers, promoters are more robust to mutations and have more access to mutations that can increase gene expression, suggesting that their low activity might be a result of selection. Consistent with these observations, increasing the promoter activity at the endogenous locus ofshavenbabyled to increased transcription yet limited phenotypic changes. Taken together, developmental promoters may encode robust transcriptional outputs allowing evolvability through the integration of diverse developmental enhancers.Quote“Regulators, mount up [at transcriptional promoters].” - Warren G & Nate Dogg, 1994