bluuebunny/crossref_metadata_2025_split huggingface dataset:
Networks of descending neurons transform command-like signals into population-based behavioral control
Authors: Braun Jonas , Hurtak Femke , Wang-Chen Sibo , Ramdya Pavan 
Published: September 2023

AbstractTo transform intentions into actions, movement instructions must pass from the brain to downstream motor circuits through descending neurons (DNs). These include small sets of command-like neurons that are sufficient to drive behaviors—the circuit mechanisms for which remain unclear. Here, we show that command-like DNs inDrosophiladirectly recruit networks of additional DNs to orchestrate flexible behaviors. Specifically, we found that optogenetic activation of command-like DNs previously thought to drive behaviors alone in fact co-activate larger populations of DNs. Connectome analysis revealed that this functional recruitment can be explained by direct excitatory connections between command-like DNs and networks of interconnected DNs in the brain. The size of downstream DN networks is predictive of whether descending population recruitment is necessary to generate a complete behavior: DNs with many downstream descending partners require network recruitment to drive flexible behaviors, while neurons with fewer partners can alone drive stereotyped behaviors and simple movements. Finally, DN networks reside within behavior-specific clusters that inhibit one another. These results support a mechanism for command-like descending control whereby a continuum of stereotyped to flexible behaviors are generated through the recruitment of increasingly large DN networks which likely construct a complete behavior by combining multiple motor subroutines.
Helminth ecological requirements shape the impact of climate change on the hazard of infection
Authors: Vanalli Chiara , Mari Lorenzo , Casagrandi Renato , Gatto Marino , Cattadori Isabella M. 
Published: September 2023

AbstractOutbreaks and spread of infectious diseases are often associated with seasonality and changes caused by global warming. Free-living stages of soil-transmitted helminths are highly susceptible to environmental drivers, however, how multiple climatic variables affect helminth species, and the long-term consequences of these interactions, is poorly understood. We used experiments on nine trichostrongylid species to develop a temperature- and humidity-dependent model of infection hazard, which was then implemented at the European scale under climate change scenarios. Intestinal and stomach helminths exhibited contrasting climatic responses, with the former group strongly affected by temperature while the latter primarily impacted by humidity. These differences generated seasonal changes in the timing and intensity of the infection hazard and spatial heterogeneities within and between the two groups. A future range expansion of both groups toward northern latitudes is expected to create new opportunities for the co-circulation of the studied helminth species.
A large effect fitness trade-off across environments is explained by a single mutation affecting cold acclimation
Authors: Lee Gwonjin , Sanderson Brian J. , Ellis Thomas J. , Dilkes Brian P. , McKay John K. , Ågren Jon , Oakley Christopher G. 
Published: September 2023

AbstractIdentifying the genetic basis of local adaptation and fitness trade-offs across environments is a central goal of evolutionary biology. Cold acclimation is an adaptive plastic response for surviving seasonal freezing, and costs of acclimation may be a general mechanism for fitness trade-offs across environments in temperate zone species. Starting with locally adapted ecotypes ofArabidopsis thalianafrom Italy and Sweden, we examined the fitness consequences of a naturally occurring functional polymorphism inCBF2. This gene encodes a transcription factor that is a major regulator of cold-acclimated freezing tolerance, and resides within a locus responsible for a genetic trade-off for long-term mean fitness. We estimated the consequences of alternate genotypes ofCBF2on 5-year mean fitness and fitness components at the native field sites by comparing near isogenic lines with alternate genotypes ofCBF2to their genetic background ecotypes. The effects ofCBF2were validated at the nucleotide level using gene edited lines in the native genetic backgrounds grown in simulated parental environments. The foreignCBF2genotype in the local genetic background reduced long-term mean fitness in Sweden by more than 10%, primarily via effects on survival. In Italy, fitness was reduced by more than 20%, primarily via effects on fecundity. At both sites, the effects were temporally variable and much stronger in some years. The gene edited lines confirmed thatCBF2encodes the causal variant underlying this genetic trade-off. Additionally, we demonstrated a substantial fitness cost of cold acclimation, which has broad implications for potential maladaptive responses to climate change.
Septoria tritici blotch resistance geneStb15encodes a lectin receptor-like kinase
Authors: Hafeez Amber N. , Chartrain Laetitia , Feng Cong , Cambon Florence , Clarke Martha , Griffiths Simon , Hayta Sadiye , Jiang Mei , Keller Beat , Kirby Rachel , Kolodziej Markus C. , Powell Oliver R. , Smedley Mark , Steuernagel Burkhard , Xian Wenfei , Wingen Luzie U. , Cheng Shifeng , Saintenac Cyrille , Wulff Brande B. H. , Brown James K. M. 
Published: September 2023

AbstractSeptoria tritici blotch (STB), caused by the Dothideomycete fungusZymoseptoria tritici, is of one of the most damaging diseases of bread wheat (Triticum aestivum)1and the target of costly fungicide applications2. In line with the fungus’ apoplastic lifestyle, STB resistance genes isolated to date encode receptor-like kinases (RLKs) including a wall-associated kinase (Stb6) and a cysteine-rich kinase (Stb16q)3,4. Here, we used genome-wide association studies (GWAS) on a panel of 300 whole-genome shotgun-sequenced diverse wheat landraces (WatSeq consortium) to identify a 99 kb region containing six candidates for theStb15resistance gene. Mutagenesis and transgenesis confirmed a gene encoding an intronless G-type lectin RLK (LecRK) asStb15. The characterisation ofStb15exemplifies the unexpected diversity of RLKs conferringZ. triticiresistance in wheat.
Dual inhibition of coronavirus Mproand PLproenzymes by phenothiazines and their antiviral activity
Authors: Forrestall Katrina , Pringle Eric S. , Sands Dane , Duguay Brett A. , Farewell Brett , Woldemariam Tekeleselassie , Falzarano Darryl , Pottie Ian , McCormick Craig , Darvesh Sultan 
Published: September 2023

ABSTRACTCoronavirus (CoV) replication requires efficient cleavage of viral polyproteins into an array of non-structural proteins involved in viral replication, organelle formation, viral RNA synthesis, and host shutoff. Human CoVs (HCoVs) encode two viral cysteine proteases, main protease (Mpro) and papain-like protease (PLpro), that mediate polyprotein cleavage. Using a structure-guided approach, a phenothiazine urea derivative that inhibits both SARS-CoV-2 Mproand PLproprotease activityin vitrowas identified.In silicodocking studies also predicted binding of the phenothiazine to the active sites of Mproand PLprofrom distantly related alphacoronavirus, HCoV-229E (229E) and the betacoronavirus, HCoV-OC43 (OC43). The lead phenothiazine urea derivative displayed broad antiviral activity against all three HCoVs tested in cell culture infection models. It was further demonstrated that the compound inhibited 229E and OC43 at an early stage of viral replication, with diminished formation of viral replication organelles and the RNAs that are made within them, as expected following viral protease inhibition. These observations suggest that the phenothiazine urea derivative inhibits viral replication and may broadly inhibit proteases of diverse coronaviruses.Graphical AbstractHighlightsCoronavirus cysteine proteases Mproand PLproare targets for novel antiviral agentsPhenothiazine ureas inhibit SARS-CoV-2 Mproand PLproprotease activitySome phenothiazine ureas inhibit replication of diverse coronaviruses with minimal cytotoxicityPhenothiazine ureas inhibit early stages of coronavirus replication consistent with failure of viral polyprotein cleavage
Clinicopathologic Dissociation: Robust Lafora Body Accumulation in Malin KO Mice Without Observable Changes in Home-cage Behavior
Authors: Krishnan Vaishnav , Wu Jun , Mazumder Arindam Ghosh , Kamen Jessica L. , Schirmer Catharina , Adhyapak Nandani , Bass John Samuel , Lee Samuel C. , Maheshwari Atul , Molinaro Gemma , Gibson Jay R. , Huber Kimberly M. , Minassian Berge A 
Published: September 2023

AbstractLafora Disease (LD) is a syndrome of progressive myoclonic epilepsy and cumulative neurocognitive deterioration caused by recessively inherited genetic lesions of EPM2A (laforin) or NHLRC1 (malin). Neuropsychiatric symptomatology in LD is thought to be directly downstream of neuronal and astrocytic polyglucosan aggregates, termed Lafora bodies (LBs), which faithfully accumulate in an age-dependent manner in all mouse models of LD. In this study, we applied home-cage monitoring to examine the extent of neurobehavioral deterioration in a model of malin-deficient LD, as a means to identify robust preclinical endpoints that may guide the selection of novel genetic treatments. At 6 weeks, ∼6-7 months and ∼12 months of age, malin deficient mice (“KO”) and wild type (WT) littermates underwent a standardized home-cage behavioral assessment designed to non-obtrusively appraise features of rest/arousal, consumptive behaviors, risk aversion and voluntary wheel-running. At all timepoints, and over a range of metrics that we report transparently, WT and KO mice were essentially indistinguishable. In contrast, within WT mice compared across timepoints, we identified age-related nocturnal hypoactivity, diminished sucrose preference and reduced wheel-running. Neuropathological examinations in subsets of the same mice revealed expected age dependent LB accumulation, gliosis and microglial activation in cortical and subcortical brain regions. At 12 months of age, despite the burden of neocortical LBs, we did not identify spontaneous seizures during an electroencephalographic (EEG) survey, and KO and WT mice exhibited similar spectral EEG features. Using anin vitroassay of neocortical function, paroxysmal increases in network activity (UP states) in KO slices were more prolonged at 3 and 6 months of age, but were similar to WT at 12 months. KO mice displayed a distinct response to pentylenetetrazole, with a greater incidence of clonic seizures and a more pronounced post-ictal suppression of movement, feeding and drinking behavior. Together, these results highlight a stark clinicopathologic dissociation in a mouse model of LD, where LBs accrue substantially without clinically meaningful changes in overall wellbeing. Our findings allude to a delay between LB accumulation and neurobehavioral decline: one that may provide a window for treatment, and whose precise duration may be difficult to ascertain within the typical lifespan of a laboratory mouse.
On the Rotational Structure in Neural Data
Authors: Kuzmina Ekaterina , Kriukov Dmitrii , Lebedev Mikhail 
Published: September 2023

ABSTRACTSpatiotemporal properties of the activity of neuronal populations in cortical motor areas have been the subject of many experimental and theoretical investigations, which generated numerous inter-pretations regarding the mechanisms of preparing and executing limb movements. Two competing models, namely representational and dynamical models, strive to explain the temporal course of neuronal activity and its relationship to different parameters of movements. One proposed dynamical model employs the jPCA method, a dimensionality reduction technique, to holistically characterize oscillatory activity in a population of neurons by maximizing rotational dynamics that are present in the data. Different interpretations have been proposed for the rotational dynamics revealed with jPCA approach in various brain areas. Yet, the nature of such dynamics remains poorly understood. Here we conducted a comprehensive analysis of several neuronal-population datasets. We found that rotational dynamics were consistently accounted for by a travelling wave pattern. To quantify the rotation strength, we developed a complex-valued measure termed the gyration number. Additionally, we identified the parameters influencing the extent of rotation in the data. Overall, our findings suggest that rotational dynamics and travelling waves are the same phenomena, which requires reevaluation of the previous interpretations where they were considered as separate entities.
Prenatal vitamin D deficiency alters immune cell proportions of young adult offspring through alteration of long-term stem cell fates
Authors: Ueda Koki , Chin Shu Shien , Sato Noriko , Nishikawa Miyu , Yasuda Kaori , Miyasaka Naoyuki , Bera Betelehem Solomon , Chorro Laurent , Doña-Termine Reanna , Koba Wade R , Reynolds David , Steidl Ulrich G. , Lauvau Gregoire , Greally John M. , Suzuki Masako 
Published: September 2023

ABSTRACTVitamin D deficiency is a common deficiency worldwide, particularly among women of reproductive age. During pregnancy, it increases the risk of immune-related diseases in offspring later in life. However, exactly how the body remembers exposure to an adverse environment during development is poorly understood. Herein, we explore the effects of prenatal vitamin D deficiency on immune cell proportions in offspring using vitamin D deficient mice established by dietary manipulation. We found that prenatal vitamin D deficiency alters immune cell proportions in offspring by changing the transcriptional properties of genes downstream of vitamin D receptor signaling in hematopoietic stem and progenitor cells of both the fetus and adults. Our results suggest the role of cellular differentiation properties of the hematopoiesis as the long-term memories of prenatal exposure at the adult stage. Moreover, further investigations of the associations between maternal vitamin D levels and cord blood immune cell profiles from 75 healthy pregnant women and their term babies also confirm that maternal vitamin D levels in the second trimester significantly affect immune cell proportions in the babies. This highlights the importance of providing vitamin D supplementation at specific stages of pregnancy.
An obligate aerobe adapts to hypoxia by hybridising fermentation with carbon storage
Authors: Gillett David L , Hutchinson Tess , Mudaliyar Manasi , Watts Thomas D. , Wong Wei Wen , Locop Jake , Jimenez Luis , Hanchapola Iresha , Lee Han-Chung , Tanuwidjaya Erwin , Steele Joel R. , Schittenhelm Ralf B. , Barlow Christopher K. , Grinter Rhys , Ghosal Debnath , Cook Perran L. M. , Greening Chris 
Published: September 2023

AbstractIn soil ecosystems, obligately aerobic bacteria survive oxygen deprivation (hypoxia) by entering non-replicative persistent states. Little is known about how these bacteria rewire their metabolism to stay viable in these states. The model obligate aerobeMycobacterium smegmatismaintains redox homeostasis during hypoxia by mediating fermentative hydrogen production. However, the fate of organic carbon during fermentation, and the associated remodeling of carbon metabolism, is unresolved. Here we systematically profiled the metabolism ofM. smegmatisduring aerobic growth, hypoxic persistence, and the transition between these states. Using differential isotope labelling, and paired metabolomics and proteomics, we observed rerouting of central carbon metabolism through the pentose phosphate pathway and Entner-Doudoroff pathway during hypoxia. We show thatM. smegmatisexcretes high levels of hydrogen concurrently with upregulating triacylglyceride synthases and accumulating glycerides as carbon stores. Using electron cryotomography (cryo-ET), we observed the presence of large spheroid structures consistent with the appearance of lipid droplets. Thus, in contrast to obligately and facultative anaerobic fermentative bacteria,M. smegmatisstores rather than excretes organic carbon during hypoxia. This novel hybrid metabolism likely provides a competitive advantage in resource-variable environments by allowingM. smegmatisto simultaneously dispose excess reductant during hypoxia and maintain carbon stores to rapidly resume growth upon reoxygenation.
WELPCR: Low-cost polymerase chain reaction (PCR) thermal cycler for nucleic acid amplification and sensing
Authors: Mandal Poulami , Dhakane Vivekanand , Kulkarni Avani , Tallur Siddharth 
Published: September 2023

AbstractThe COVID-19 pandemic highlighted the need for sensitive and cost-effective diagnostics. The gold standard test to diagnose infectious diseases such as COVID-19 is quantitative polymerase chain reaction (qPCR). Although there have been multiple advances in nucleic acid testing, PCR thermocyclers are expensive and typically not affordable for offering hands-on training to PCR in instructional laboratory courses in undergraduate colleges. We introduce a low-cost, portable, and automated real-time PCR device designed at the Wadhwani Electronics Lab (WEL) at IIT Bombay, christened WELPCR. WELPCR is an open-source design, and capable of reverse transcription PCR (RT-PCR) for complementary DNA synthesis, as well as end-point PCR of small amount of DNA in a test sample. The WELPCR design enables ramp rate up to 2 °C/s, weighs less than 2 kg, and is easy to assemble. The built-in LED display and keypad provides an intuitive and seamless user interface to configure and set up WELPCR. With bill of materials (BOM) cost less than INR Rs. 10 000, WELPCR is an attractive solution for bringing PCR technology to instructional and research laboratories in a cost-effective manner.
Investigating potential myopia risk factors, including chronotype, in Estonian adolescents
Authors: Palumaa Teele , Linntam Delis , Rebane Reili , Tammaru Marika , Palumaa Kadi 
Published: September 2023

AbstractPurposeTo evaluate chronotype, lifestyle factors, and parental myopia in relation to myopia, and characterise the effect of cycloplegia on spherical equivalent refraction (SER) in Estonian secondary school students.MethodsOne hundred twenty-three students aged between 15 and 17 years from three secondary schools in Estonia participated in the study. They underwent a comprehensive ocular examination, including cycloplegic refraction and ocular biometry. Chronotype was evaluated with the Morningness–Eveningness Questionnaire. Participants also completed a questionnaire about their daily activities, including time spent outdoors, time spent on near-work and mid-working distance activities, and parental myopia. Myopia was defined as cycloplegic SER ≤–0.50 D. Logistic regression analysis was performed to assess the association of the studied factors with myopia.ResultsIn a multivariate regression model, having two myopic parents was associated with higher odds of myopia (OR 3.78, 95% CI 1.15–12.42). We found no association between myopia and chronotype. Notably, time spent outdoors, and doing near-work and mid-working distance activities, did not affect the likelihood of having myopia. Non-cycloplegic SER was significantly more myopic than cycloplegic SER on average by 0.86 D (p< 0.0001, Wilcoxon matched-pairs signed rank test).ConclusionConsistent with previous reports, we identified parental myopia as a myopia risk factor. Chronotype was not associated with myopia in our study sample. Interestingly, there was no association between myopia and time spent outdoors or near work. Using non-cycloplegic refraction would lead to a significant overestimation of myopia.
Randomized Controlled Trials Evaluating AI in Clinical Practice: A Scoping Evaluation
Authors: Han Ryan , Acosta Julián N. , Shakeri Zahra , Ioannidis John P.A. , Topol Eric J. , Rajpurkar Pranav 
Published: September 2023

ABSTRACTBackgroundArtificial intelligence (AI) has emerged as a promising tool in healthcare, with numerous studies indicating its potential to perform as well or better than clinicians. However, a considerable portion of these AI models have only been tested retrospectively, raising concerns about their true effectiveness and potential risks in real-world clinical settings.MethodsWe conducted a systematic search for randomized controlled trials (RCTs) involving AI algorithms used in various clinical practice fields and locations, published between January 1, 2018, and August 18, 2023. Our study included 84 trials and focused specifically on evaluating intervention characteristics, study endpoints, and trial outcomes, including the potential of AI to improve care management, patient behavior and symptoms, and clinical decision-making.ResultsOur analysis revealed that 82·1% (69/84) of trials reported positive results for their primary endpoint, highlighting AI’s potential to enhance various aspects of healthcare. Trials predominantly evaluated deep learning systems for medical imaging and were conducted in single-center settings. The US and China had the most trials, with gastroenterology being the most common field of study. However, we also identified areas requiring further research, such as multi-center trials and diverse outcome measures, to better understand AI’s true impact and limitations in healthcare.ConclusionThe existing landscape of RCTs on AI in clinical practice demonstrates an expanding interest in applying AI across a range of fields and locations. While most trials report positive outcomes, more comprehensive research, including multi-center trials and diverse outcome measures, is essential to fully understand AI’s impact and limitations in healthcare.