bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for a prospective cohort study on the feasibility of application of nutritional ultrasound in the diagnosis and follow-up of patients with nutritional risk at hospital discharge: Study on body composition and function (DRECO)
Authors: García Almeida José Manuel , Guerrero Diego Bellido , de Luis Román Daniel , Rolo Germán Guzmán , Olveira Gabriel 
Published: December 2022

SUMMARYBackgroundThe application of nutritional ultrasound for the morphological and structural study of muscle mass is an emerging technique in clinical nutrition. Currently, all definitions of malnutrition include the measurement of muscle mass involvement, however, there is no single way to assess it. It is necessary to develop new techniques to identify muscle involvement in malnutrition that are valid, standardized, reliable, accurate and profitable.ObjectivesThe objective of this study is to value the new muscle ultrasound techniques aimed to measure muscle and functional status, to make a more accurate diagnosis and a better prediction of complications and morbidity and mortality in patients at nutritional risk. Primary outcome: to assess the feasibility of ultrasound or muscle ultrasound techniques in both nutritional diagnosis and follow-up, over 3 to 6 months, in a nutritional intervention program.MethodsDRECO (Disease-Related caloric-protein malnutrition EChOgraphy) is a prospective, multicenter, uncontrolled clinical study in standard clinical practice to value the usefulness of nutritional ultrasound (muscle ultrasound) in the nutritional diagnosis and follow-up of patients over a period of 3 to 6 consecutive months, after standard nutritional clinical practice intervention, and physical activity to control their disease-related malnutrition.DiscussionThis study will standardize nutritional ultrasound measures. It will validate and define specific cut-off values for nutritional ultrasound and get its correlation with already well-known nutritional tools such as SGA (Subjective Global Assessment) or GLIM (Global Leadership Initiative on Malnutrition) criteria. Thus, muscle ultrasound will become not only a tool to assess the diagnosis of malnutrition, but it will be integrated in the routine clinical practices to evaluate nutritional interventions.RegistrationThis study is registered atclinicaltrials.gov(NCT05433831), registered on June 27th, 2022.https://clinicaltrials.gov/ct2/show/NCT05433831.
Identification of a key genetic factor governing arabinan utilization in the gut microbiome suggests a novel therapeutic target for constipation
Authors: Zhang Chengcheng , Yu Leilei , Ma Chenchen , Jiang Shuaiming , Wang Shunhe , Tian Fengwei , Xue Yuzheng , Zhao Jianxin , Zhang Hao , Liu Liming , Chen Wei , Huang Shi , Zhang Jiachao , Zhai Qixiao 
Published: December 2022

SUMMARYProbiotics have been widely used to improve impaired gastro-intestinal motility, yet their efficacy varied substantially across strains. Here, by a large-scale genetic screen plusin vivomeasurements, we identified a key genetic factor (abfAcluster governing arabinan utilization) in probioticBifidobacterium longumharnessing the treatment efficacy against functional constipation (FC). Intriguingly, it also presents in a range of gut resident microbiota and played a protective role against FC. Next, our longitudinal multi-omics study in humans revealed that the exogenousabfA-cluster- carryingB. longumcan well establish itself in the gut, and enrich arabinan-utilization residents and beneficial metabolites (e.g., acetate, butyrate, chenodeoxycholic acid and uracil). Finally, transplantation ofabfA-cluster-enriched human microbiota to FC- induced germ-free mice recapitulated the marked gut-motility improvement and elevated production of beneficial metabolites. Collectively, our proof-of-concept study actively demonstrated a critical yet underexplored role of microbialabfAcluster in ameliorating FC, establishing generalizable principles for developing functional-genomics-directed probiotic therapies.
A reductionist paradigm for high-throughput behavioural fingerprinting inDrosophila melanogaster
Authors: Jones Hannah , Willis Jenny A , Firth Lucy C , Giachello Carlo N G , Gilestro Giorgio F 
Published: December 2022

AbstractUnderstanding how the brain encodes behaviour is the ultimate goal of neuroscience and the ability to objectively and reproducibly describe and quantify behaviour is a necessary milestone on this path. Recent technological progresses in machine learning and computational power have boosted the development and adoption of systems leveraging on high-resolution video recording to track an animal pose and describe behaviour in all four dimensions. However, the high temporal and spatial resolution that these systems offer must come as a compromise with their throughput and accessibility. Here we describecoccinella, an open-source reductionist framework combining high-throughput analysis of behaviour using real-time tracking on a distributed mesh of microcomputers (ethoscopes) with resource-lean statistical learning (HCTSA/Catch22). Coccinella is a reductionist system, yet outperforms state-of-the-art alternatives when exploring the pharmacobehaviour inDrosophila melanogaster.
A ligand-receptor interactome atlas of the zebrafish
Authors: Chodkowski Milosz , Zieleziński Andrzej , Anbalagan Savani 
Published: December 2022

SummaryStudies in zebrafish can unravel the functions of cellular communication and thus identify novel bench-to-bedside drugs targeting cellular communication signaling molecules. Due to the incomplete annotation of zebrafish proteome, the knowledge of zebrafish receptome, secretome and tools to explore their interactome is limited. To address this gap, wede novopredicted the cellular localization of zebrafish reference proteome using deep learning algorithm. We combined the predicted and existing annotations on cellular localization of zebrafish proteins, and created repositories of zebrafish secretome, receptome, and interactome as well as associated diseases and targeting drugs. Unlike other tools, our interactome atlas is primarily based on physical interaction data of zebrafish proteome. The resources are available as R and Python scripts (https://github.com/DanioTalk).DanioTalkprovides a novel resource for researchers interested in targeting cellular communication in zebrafish, as we demonstrate in applications studying synapse and axo-glial interactome.
Cryo-EM structures of chronic traumatic encephalopathy tau filaments with PET ligand flortaucipir
Authors: Shi Yang , Ghetti Bernardino , Goedert Michel , Scheres Sjors H.W. 
Published: December 2022

AbstractPositron emission tomography (PET) imaging allows monitoring the progression of amyloid aggregation in the living brain. [18F]-Flortaucipir is the only approved PET tracer compound for the visualisation of tau aggregation. Here, we describe cryo-EM experiments on tau filaments in the presence and absence of flortaucipir. We used tau filaments isolated from the brain of an individual with Alzheimer’s disease (AD), and from the brain of an individual with primary age-related tauopathy (PART) with a co-pathology of chronic traumatic encephalopathy (CTE). Unexpectedly, we were unable to visualise additional cryo-EM density for flortaucipir for AD paired helical or straight filaments (PHFs or SFs), but we did observe density for flortaucipir binding to CTE Type I filaments from the case with PART. In the latter, flortaucipir binds in a 1:1 molecular stoichiometry with tau, adjacent to lysine 353 and aspartate 358. By adopting a tilted geometry with respect to the helical axis, the 4.7 Å distance between neighbouring tau monomers is reconciled with the 3.5 Å distance consistent with π-π-stacking between neighbouring molecules of flortaucipir.
Neural Correlates of Temporal Anticipation
Authors: Grabenhorst Matthias , Michalareas Georgios 
Published: December 2022

AbstractTemporal anticipation is a fundamental process underlying complex neural functions such as associative learning, decision-making, and motor-preparation. Here we study event anticipation in its simplest form in human participants using magnetoencephalography. We distributed events in time according to different probability density functions and presented the stimuli separately in two different sensory modalities. We found that the temporal dynamics in right parietal cortex correlate with reaction times to anticipated events. Specifically,afteran event occurred, event probability was represented in right parietal activity, hinting at a functional role of event-related potential component P300 in temporal expectancy. The results are consistent across both visual and auditory modalities. The right parietal cortex seems to play a central role in the processing of event probability density. Overall, this work contributes to the understanding of the neural processes involved in the anticipation of events in time.
A framework for community curation of interspecies interactions literature
Authors: Cuzick Alayne , Seager James , Wood Valerie , Urban Martin , Rutherford Kim , Hammond-Kosack Kim E. 
Published: December 2022

AbstractThe quantity and complexity of data being generated and published in biology has increased substantially, but few methods exist for capturing knowledge about phenotypes derived from molecular interactions between diverse groups of species, in such a way that is amenable to data-driven biology and research. To improve access to this knowledge, we have constructed a framework for the curation of the scientific literature studying interspecies interactions, using data curated for the Pathogen-Host Interactions Database (PHI-base) as a case study. The framework provides a curation tool, phenotype ontology and controlled vocabularies to curate pathogen-host interaction data (at the level of the host, pathogen, strain, gene and genotype). The concept of a multispecies genotype, the ‘metagenotype’, is introduced to facilitate capturing changes in the pathogens’ disease-causing abilities, and host resistance or susceptibility observed by gene alterations. We report on this framework and describe PHI-Canto, a community curation tool for use by publication authors.
Unlocking the therapeutic potential of the corneal endothelium: Intravital imaging reveals endogenous regenerative capabilities
Authors: Marshall Maxwell , Ramarapu Raneesh , Ohman Lisa , Samasa Bakary , Papp Tyler , Hamideh Parhiz , Park Sangwan , Leonard Brian C. , Thomasy Sara M. , Rompolas Panteleimon 
Published: December 2022

AbstractLoss of vision due to corneal endothelial dysfunction affects millions worldwide. The development of new treatments is hampered by the incomplete knowledge of the regenerative capacity of corneal endothelial cellsin vivo. Herein, we developed a mouse model to directly monitor corneal endothelial regeneration in real time, and at the single cell level, by two-photon microscopy. We show that the mouse corneal endothelium recapitulates the main features of human endothelial physiology, including complete cellular quiescence and a decline in cell density with aging. Critically, we demonstrate the endogenous regenerative potential of the tissue by capturing the proliferation of corneal endothelial cells during repair of large injuries. By single cell lineage tracing analysis, we provide evidence that corneal endothelial cells are equipotent in their ability to activate the cell cycle and contribute to tissue regeneration. Based on these findings we developed a feasible therapeutic approach to stimulate the regeneration of the corneal endothelium, using modified mRNA technology. To reprogram corneal endothelial cells in vivo and unlock their ability to escape quiescence, we combined five modified mRNAs encoding for proteins involved in cell cycle activation. Injection of the encapsulated mRNAs directly into the eye of older mice induced transient proliferation of corneal endothelial cells that led to an increase in endothelial cell density, effectively reversing the effect of aging. This therapeutic strategy offers a compelling paradigm for treating ocular disease and modulating tissue regeneration in organs with limited endogenous ability.
Soaring migrants flexibly respond to sea-breeze in a migratory bottleneck: using first derivatives to identify behavioural adjustments over time
Authors: Becciu Paolo , Troupin David , Dinevich Leonid , Leshem Yossi , Sapir Nir 
Published: December 2022

AbstractMillions of birds travel every year between Europe and Africa detouring ecological barriers and funnelling through migratory corridors where they face variable weather conditions. Little is known regarding the response of migrating birds to mesoscale meteorological processes during flight. Specifically, sea-breeze has a daily cycle that may directly influence the flight of diurnal migrants. We collected radar tracks of soaring migrants using modified weather radar in Latrun, central Israel, in 7 autumns between 2005 and 2016. We investigated how migrating soaring birds adjusted their flight speed and direction under the effects of daily sea-breeze circulation. We analysed the linear and, uniquely, the non-linear effects of wind on bird ground-, air- and sideways speed as function of time along the day using Generalized Additive Mixed Models and calculated first derivatives to identify when birds adjusted their response to the wind over time. Using data collected during a total of 148 days, we characterised the diel dynamics of horizontal wind flow in its two vectorial components relative to soaring migration goal (South), finding a consistent rotational movement of the wind blowing towards the East (morning) and to the South-East (late afternoon), with highest speed of crosswind component around mid-day and increasing tailwinds towards the late afternoon. We found that the airspeed of radar detected birds decreased consistently with increasing tailwind throughout the day, resulting in a rather stable groundspeed of 16-17 m/s. In addition, birds increased their sideways speed when crosswinds were at their maximum to an extent similar to that of the wind’s sideways component, meaning a full compensation to wind drift, which decreased after the time of crosswind maximum. Using a simple, novel and broadly applicable statistical method, we studied, for the first time, how wind influences bird flight by highlighting non-linear effects over time, providing new insights regarding the behavioural adjustments in the response of soaring birds to wind conditions. Our work enhances our understanding of how migrating birds respond to changing wind conditions during their journeys in order to exploit migratory corridors.
Tau regulates Arc stability in neuronal dendrites via a proteasome-sensitive but ubiquitin-independent pathway
Authors: Yakout Dina W. , Shroff Ankit , Thaker Vishrut , Allen Zachary D. , Nazarko Taras Y. , Mabb Angela M. 
Published: December 2022

AbstractTauopathies are neurodegenerative disorders characterized by the deposition of aggregates of the microtubule associated protein tau, a main component of neurofibrillary tangles. Alzheimer’s disease (AD) is the most common type of tauopathy and dementia, with amyloid-beta pathology as an additional hallmark feature of the disease. Besides the role of tau in stabilizing microtubules, it is localized at postsynaptic sites and can disrupt synaptic plasticity when knocked out or overexpressed. The activity-regulated cytoskeleton-associated protein (Arc), is an immediate early gene that plays a key role in synaptic plasticity, learning and memory. Arc has been implicated in AD pathogenesis, where it was found to regulate activity-dependent release of amyloid-beta (Aβ). Here we show that Arc protein is upregulated in the hippocampus of tau knockout (Tau KO) mice and in dendrites of Tau KO primary hippocampal neurons. Conversely, overexpression of tau decreased Arc stability exclusively in neuronal dendrites and was coupled to an increase in the expression of dendritic and somatic surface GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The Tau-dependent decrease in Arc was proteasome sensitive, yet independent of Arc ubiquitination and required the endophilin-binding domain of Arc, which is essential for promoting the endocytosis of AMPA receptors. Importantly, these effects on Arc stability and GluA1 localization were not observed in the commonly studied tau mutant, P301L. Our findings show a physiological role for tau in regulating Arc and implicate specific variants of tau in regulating Arc stability and AMPA receptor targeting, which may in part explain observed deficits in synaptic plasticity in select types of tauopathies.
Multiple pathways for reestablishing PAR polarity inC. elegansembryo
Authors: Koch Laurel A. , Rose Lesilee S. 
Published: December 2022

AbstractAsymmetric cell divisions, where cells divide with respect to a polarized axis and give rise to daughter cells with different fates, are critically important during development. In many such divisions, the conserved PAR polarity proteins accumulate in distinct cortical domains in response to a symmetry breaking cue. The one-cellC. elegansembryo has been a paradigm for understanding mechanisms of PAR polarization, but much less is known about polarity reestablishment during subsequent divisions. Here, we investigate the polarization of the P1 cell of the two-cell embryo. A posterior PAR-2 domain forms in the first four minutes of the birth of P1, and polarization becomes stronger over time. Initial polarization depends on the PKC-3 and PAR-1 kinases. However, inpar-1mutants, delayed polarization can occur, at a time when centrosome-associated AIR-1 is near the posterior cortex and myosin flows towards the anterior. Loss of myosin andpar-1function together results in more severe polarity defects. Based on these and other results, we propose that PAR polarity in the P1 cell is generated by at least two redundant mechanisms: There is a novel early pathway dependent on PAR-1, PKC-3 and cytoplasmic polarity, and a late pathway that resembles symmetry breaking in the one-cell embryo and requires myosin flow and PKC-3.
Parahippocampal neurons encode task-relevant information for goal-directed navigation
Authors: Gonzalez Alexander , Giocomo Lisa M. 
Published: December 2022

AbstractA behavioral strategy crucial to survival is directed navigation to a goal, such as a food or home location. One potential neural substrate for supporting goal-directed navigation is the parahippocampus, which contains neurons that represent an animal’s position, orientation, and movement through the world, and that change their firing activity to encode behaviorally relevant variables such as reward. However, little prior work on the parahippocampus has considered how neurons encode variables during goal-directed navigation in environments that dynamically change. Here, we recorded single units from rat parahippocampal cortex while subjects performed a goal-directed task. The maze dynamically changed goal-locations via a visual cue on a trial-to-trial basis, requiring subjects to use cue-location associations to receive reward. We observed a mismatch-like signal, with elevated neural activity on incorrect trials, leading to rate-remapping. The strength of this remapping correlated with task performance. Recordings during open-field foraging allowed us to functionally define navigational coding for a subset of the neurons recorded in the maze. This approach revealed that head-direction coding units remapped more than other functional-defined units. Taken together, this work thus raises the possibility that during goal-directed navigation, parahippocampal neurons encode error information reflective of an animal’s behavioral performance.
Implementation of Rapid Genome Sequencing for Infants with Congenital Heart Disease
Authors: Hays Thomas , Hernan Rebecca , Disco Michele , Griffin Emily , Goldshtrom Nimrod , Vargas Diana , Krishnamurthy Ganga , Rehman Atteeq U. , Wilson Amanda T. , Guha Saurav , Phadke Shruti , Okur Volkan , Robinson Dino , Felice Vanessa , Abhyankar Avinash , Jobanputra Vaidehi , Chung Wendy K. 
Published: December 2022

AbstractBackgroundRapid genome sequencing (rGS) has been shown to improve the care of critically ill infants. Congenital heart disease (CHD) is a leading cause of infant mortality, and is often caused by genetic disorders, yet the utility of rGS has not been prospectively studied in this population.MethodsWe conducted a prospective evaluation of the use of rGS to improve the care of infants with CHD in our cardiac neonatal intensive care unit (CNICU).ResultsIn a cohort of 48 infants with CHD, rGS diagnosed 14 genetic disorders in 13 (27%) individuals and led to changes in clinical management in eight (62%) cases with diagnostic results. These included two cases in whom genetic diagnoses helped avert intensive, futile interventions prior to CNICU discharge, as well as three cases in whom eye disease was diagnosed and treated in early childhood. Genetic disorders were associated with small for gestational age birth weight.ConclusionsOur study provides the first prospective evaluation of rGS for infants with CHD to our knowledge. We found that rGS diagnosed genetic disorders in 27% of cases and led to changes in management in 62% of cases with diagnostic results. Our model of care was enabled by multidisciplinary coordination between neonatologists, cardiologists, surgeons, geneticists, and genetic counselors. These findings highlight the important role for rGS in CHD and demonstrate the need for expanded study of how to implement this resource to a broader population of infants with CHD.
A scoring function for the prediction of protein complex interfaces based on the neighborhood preferences of amino acids
Authors: Nagaraju Mulpuri , Liu Haiguang 
Published: December 2022

Proteins often assemble into functional complexes, the structures of which are more difficult to obtain than those of the individual protein molecules. Given the structures of the subunits, it is possible to predict plausible complex models via computational methods such as molecular docking. Assessing the quality of the predicted models is crucial to obtain correct complex structures. Here, an energy-scoring function was developed based on the interfacial residues of structures in the Protein Data Bank. The statistically derived energy function (Nepre) imitates the neighborhood preferences of amino acids, including the types and relative positions of neighboring residues. Based on the preference statistics, a program iNepre was implemented and its performance was evaluated with several benchmarking decoy data sets. The results show that iNepre scores are powerful in model ranking to select the best protein complex structures.