bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Rise and Fall of Slow Wave Tides: Vacillations of Slow Wave/Spindle Coupling Shift the Composition of Slow Wave Activity Through Sleep Cycles in Accordance with Depth of Sleep
Authors: McConnell Brice V. , Kronberg Eugene , Medenblik Lindsey M. , Kheyfets Vitaly O. , Ramos Alberto R. , Sillau Stefan H. , Pulver Rachelle L. , Bettcher Brianne M. 
Published: March 2022

AbstractSlow wave activity (SWA) during sleep is associated with synaptic regulation and memory processing functions. Each cycle of non-rapid-eye-movement (NREM) sleep demonstrates a waxing and waning amount of SWA during the transitions between stages N2 and N3 sleep, and the deeper N3 sleep is associated with an increased density of SWA. Further, SWA is an amalgam of different types of slow waves, each identifiable by their temporal coupling to spindle subtypes with distinct physiological features. The objectives of this study were to better understand the neurobiological properties that distinguish different slow wave and spindle subtypes, and to examine the composition of SWA across cycles of NREM sleep. We further sought to explore changes in the composition of NREM cycles that occur among aging adults. To address these goals, we analyzed subsets of data from two well-characterized cohorts of healthy adults: 1) The DREAMS Subjects Database (n=20), and 2) The Cleveland Family Study (n=60). Our analyses indicate that slow wave/spindle coupled events can be characterized as frontal versus central in their relative distribution between electroencephalography (EEG) channels. The frontal predominant slow waves are identifiable by their coupling to late-fast spindles and occur more frequently during stage N3 sleep. Conversely, the central-associated slow waves are identified by coupling to early-fast spindles and favor occurrence during stage N2 sleep. Together, both types of slow wave/spindle coupled events form the composite of SWA, and their relative contribution to the SWA rises and falls across cycles of NREM sleep in accordance with depth of sleep. Exploratory analyses indicated that older adults produce a different composition of SWA, with a shift toward the N3, frontal subtype, which becomes increasingly predominant during cycles of NREM sleep. Overall, these data demonstrate that subtypes of slow wave/spindle events have distinct cortical propagation patterns and differ in their distribution across lighter versus deeper NREM sleep. Future efforts to understand how slow wave sleep and slow wave/spindle coupling impact memory performance and neurological disease may benefit from examining the composition of SWA to avoid potential confounds that may occur when comparing dissimilar neurophysiological events.
The traits of skull anatomy in green frogs of the genus Pelophylax (Anura, Ranidae)
Authors: Natalia Slutska 
Published: March 2022

AbstractDuring dissecting skulls of green frogs of the genus Pelophylax it has found that the description of a number bones and cartilaginous structures requires addition and clarification. In addition, previously undescribed details of anatomical structure of the skull of green frogs has revealed. The traits of anatomical structure of skull of green frogs, characteristic for ancestral forms of Anura found too.
Increased fatty acid metabolism and decreased glycolysis are hallmarks of metabolic reprogramming in the brain during recovery from experimental stroke
Authors: Loppi Sanna H. , Tavera-Garcia Marco A. , Becktel Danielle A. , Maiyo Boaz K. , Johnson Kristos E. , Schnellmann Rick G. , Doyle Kristian P. 
Published: March 2022

AbstractThe goal of this study was to evaluate changes in metabolic homeostasis during the first 12 weeks of recovery in a distal middle cerebral artery occlusion mouse model of stroke. To achieve this goal, we compared the brain metabolomes of ipsilateral and contralateral hemispheres from aged male mice up to 12 weeks after stroke to that of age-matched naïve and sham operated mice. There were 707 biochemicals detected in each sample by liquid chromatography-mass spectroscopy (LC-MS). Mitochondrial fatty acid β-oxidation, indicated by acyl carnitine levels, was increased in stroked tissue at 1 day and 4 weeks following stroke. Glucose and several glycolytic intermediates were elevated in the ipsilateral hemisphere for 12 weeks compared to the aged naïve controls, but pyruvate was decreased. Additionally, itaconate, a glycolysis inhibitor associated with activation of anti-inflammatory mechanisms in myeloid cells, was higher in the same comparisons. These changes correlated with reduced levels of glutamate, dopamine, and adenosine in the ipsilateral hemisphere after stroke. These results indicate that chronic metabolic differences exist between stroked and control tissue, including alterations in fatty acid metabolism and glycolysis for at least 12 weeks after stroke.
Towards a multi-stressor theory for coral reefs in a changing world
Authors: Bieg Carling , Vallès Henri , Tewfik Alexander , Lapointe Brian E. , McCann Kevin S. 
Published: March 2022

AbstractCoral reefs are facing a constant barrage of human impacts, including eutrophication, overharvesting and climate change. While the local effects of overharvesting have been well-studied, regional nutrient loading from anthropogenic activities on land and global climate change-induced disturbances are increasing in magnitude and necessitating cross-scale multi-stressor approaches for coral reef ecology. Here, we expand on longstanding theory to develop an integrated multi-stressor framework for coral reefs. We show that: i) the geometry of a simple, empirically-motivated model suggests nutrients and harvesting can operate similarly, and synergistically, in driving shifts from coral- to algae-dominated reefs, resulting in clear context-dependent management implications; and ii) this same geometry suggests climate-driven coral mortality can drive the presence of long transients and climate-driven alternate states, even in moderately-impacted ecosystems. Reefs seemingly in a “safe space” based on individual stressors may in fact be much more susceptible to increasingly frequent storms and bleaching events in multi-stressor conditions. By integrating these findings with general ecological and theoretical concepts, we suggest that responses in benthic composition may act as “signatures of change” to multi-stressors, allowing us to develop a predictive and generalizable multi-stressor framework for coral reefs under global change. In line with this theory, we detail empirical evidence from Barbados of historical changes in reef composition and multi-stressor impacts within our framework. By bridging coral reef ecology and general ecological concepts, we can better understand ecosystem functioning and resilience in these important yet highly threatened systems.Manuscript HighlightsTheoretical understanding of synergistic multi-stressor impacts on coral reefsUnexpected climate-driven alternate states, related to long transientsTheoretical framework predicts “signatures of change” based on dominant stressor
Structure and influence in an interconnected world: neurocomputational mechanism of real-time distributed learning on social networks
Authors: Jiang Yaomin , Mi Qingtian , Zhu Lusha 
Published: March 2022

AbstractMany social species are embedded on social networks, including our own. The structure of social networks shapes our decisions by constraining what information we learn and from whom. But how does the brain incorporate social network structures into learning and decision-making processes, and how does learning in networked environments differ from learning from isolated partners? Combining a real-time distributed learning task with computational modeling, fMRI, and social network analysis, we investigated the process by which humans learn from observing others’ decisions on 7-node networks with varying topological structures. We show that learning on social networks can be realized by means similar to the well-established reinforcement learning algorithm, supported by an action prediction error encoded in the lateral prefrontal cortex. Importantly, learning is flexibly weighted toward well-connected neighbors, according to activity in the dorsal anterior cingulate cortex, but only insofar as neighbors’ actions vary in their informativeness. These data suggest a neurocomputational mechanism of network-dependent filtering on the sources of information, which may give rise to biased learning and the spread of misinformation in an interconnected society.
Vaccine Adverse Event Reporting System (VAERS): Evaluation of 31 Years of Reports and Pandemics’ Impact
Authors: Almadani Ohoud A. , Alshammari Thamir M. 
Published: March 2022

AbstractBackgroundVaccine adverse event reporting system (VAERS) was established in the United States (U.S.) as an early warning system with a main purpose of collecting postmarketing adverse events following immunizations (AEFIs) reports to monitor the vaccine safety and to mitigate the risks from vaccines. During the coronavirus diseases 2019 (COVID-19) pandemic, VAERS got more attention as its important role in monitoring the safety of the vaccines. Thus, the aim of this study was to investigate VAERS patterns, reported AEFIs, adverse events of special interest (AESIs), impact of different pandemics since its inception, and surveillance rate of serious vs nonserious AEFIs.MethodsThis was an observational study using VARES data from 2/7/1990 to 12/11/2021. Patterns of reports over years were first described, followed by a comparison of reports statistics per year. Furthermore, a comparison of incidents (death, ER visits, etc.) statistics over years, in addition to statistics of each vaccine were calculated. Moreover, each incident’s statistics for each vaccine were calculated and top vaccines were reported. Finally, survival analysis utilizing cox regression was done, in addition to AESIs distribution stratified by age groups and gender. All analyses were conducted using R (Version 1.4.1717) and Excel for Microsoft 365.ResultsThere were 1,396,280 domestic and 346,210 non-domestic reports during 1990-2021, including 228 vaccines. For both domestic and non-domestic reports, year of 2021 had the highest reporting rate (48.52% and 70.33%), in addition a notable changes in AEFIs patterns were recorded during 1991, 1998, 2000, 2006, 2009, 2011, and 2017. AEFIs were as follow: deaths (1.00% and 4.08%), ER or doctor visits (13.37% and 2.27%), hospitalizations (5.84% and 27.78%), lethal threat (1.42% and 4.38%), and disabilities (1.4% and 7.96%). Pyrexia was the top reported symptom during the past 31 years, except for 2021 where headache was the top one. COVID-19 vaccines namely Moderna, Pfizer-Biontech, and Janssen were the top 3 reported vaccines with headache, pyrexia, and fatigue as the top associated AEFIs. Followed by Zoster, Seasonal Influenza, Pneumococcal, and Human papillomavirus vaccines. Myocarditis or Pericarditis were the top reported AESIs (26.95% and 25.84%). Male (HR:1.15, 1.14 - 1.16) for domestic (HR:1.23, 1.22 -1.25) for nondomestic have a higher probability of having serious AEFIs. In addition, age group ≤ 5 years old in domestic and >84 years old in nondomestic have a higher probability of having AEFIs compared to other age groups.ConclusionsThe large data available in VARES make it a useful tool for detecting and monitoring vaccine AEFIs. However, its usability relies on understating the limitations of this surveillance system, the impact of governmental regulations, availability of vaccines, and public health recommendations on the reporting rate.
Enhanced Recovery After Surgery reduced length of stay after colorectal surgery in a small rural hospital in Ontario
Authors: Roldan Hector A. , Brown Andrew R. , Radey Jane , Hogenbirk John C. , Allen Lisa R. 
Published: March 2022

AbstractBackgroundEnhanced Recovery After Surgery (ERAS) programs include preoperative, intraoperative and postoperative clinical pathways to improve quality of patient care while reducing length of stay and readmission. This study assessed the feasibility and outcomes of an ERAS protocol for colorectal surgery implemented over two-years in a small, resource-challenged rural hospital.Study designA prospective cohort study used retrospectively matched controls to assess the effect of ERAS on LOS in patients undergoing colorectal surgery in a small rural hospital in northern Ontario, Canada. ERAS patients were matched to two patients in the control group based on diagnosis, age and gender. Patients had open or laparoscopic colorectal surgeries, with those in the intervention group treated per ERAS protocol and given instructions on pre- and post-operative self-care.ResultsMost ERAS patients reported adherence to ERAS protocols prior to surgery. Approximately one quarter of patients chose not to complete the postoperative survey. Of those who completed the survey, adherence to protocol was strongest for chewing gum in the days after surgery. Most patients were sitting in a chair for their afternoon meal by the first day and most were walking down the hallway by the second day. The control and ERAS patient groups did not differ significantly (p≥0.07) in age (years, sd=13.1), gender (52% male), nor in the Canadian Classification of Health Interventions 5-character code. The control group significantly higher (p<0.001) malignant neoplasm of colon (C18, 69% vs 35%), and significantly lower malignant neoplasm of rectum (C20, 0% vs 5%), relative to the ERAS group. The control group had an average ln-transformed LOS that was significantly longer (exponentiated as 1.7 days) than ERAS patients (t-test, p<0.001).ConclusionThis study found that ERAS could be implemented in a small rural hospital and provided evidence for a reduced LOS of approximately two days.
Large-scale analysis and computer modeling reveal hidden regularities behind variability of cell division patterns inArabidopsis thalianaembryogenesis
Authors: Laruelle Elise , Belcram Katia , Trubuil Alain , Palauqui Jean-Christophe , Andrey Philippe 
Published: March 2022

AbstractNoise plays a major role in cellular processes and in the development of tissues and organs. Several studies have examined the origin, the integration or the accommodation of noise in gene expression, cell growth and elaboration of organ shape. By contrast, much less is known about variability in cell division plane positioning, its origin and links with cell geometry, and its impact on tissue organization. Taking advantage of the first-stereotyped-then-variable division patterns in the embryo of the model plant Arabidopsis thaliana, we combined 3D imaging and quantitative cell shape and cell lineage analysis together with mathematical and computer modeling to perform a large scale, systematic analysis of variability in division plane orientation. Our results reveal that, paradoxically, variability in cell division patterns ofArabidopsisembryos is accompanied by a progressive reduction of cell shape heterogeneity. The paradox is solved by showing that variability operates within a reduced repertoire of possible division plane orientations that is related to cell geometry. We show that in several domains of the embryo, a recently proposed geometrical division rule recapitulates observed variable patterns, thus suggesting that variable patterns emerge from deterministic principles operating in a variable geometrical context. Our work highlights the importance of emerging patterns in the plant embryo under iterated division principles, but also reveal domains where deviations between rule predictions and experimental observations point to additional regulatory mechanisms.
Conserved patterns across ion channels correlate with variant pathogenicity and clinical phenotypes
Authors: Brünger Tobias , Pérez-Palma Eduardo , Montanucci Ludovica , Nothnagel Michael , Møller Rikke S. , Schorge Stephanie , Zuberi Sameer , Symonds Joseph , Lemke Johannes R. , Brunklaus Andreas , Traynelis Stephen F. , May Patrick , Lal Dennis 
Published: March 2022

AbstractClinically identified genetic variants in ion channels can be benign or cause disease by increasing or decreasing the protein function. Consequently, therapeutic decision-making is challenging without molecular testing of each variant. Our biophysical knowledge of ion channel structures and function is just emerging, and it is currently not well understood which amino acid residues cause disease when mutated.We sought to systematically identify biological properties associated with variant pathogenicity across all major voltage and ligand-gated ion channel families. We collected and curated 3,049 pathogenic variants from hundreds of neurodevelopmental and other disorders and 12,546 population variants for 30 ion channel or channel subunits for which a high-quality protein structure was available. Using a wide range of bioinformatics approaches, we computed 163 structural features and tested them for pathogenic variant enrichment. We developed a novel 3D spatial distance scoring approach that enables comparisons of pathogenic and population variant distribution across protein structures.We discovered and independently replicated that several pore residue properties and proximity to the pore axis were most significantly enriched for pathogenic variants compared to population variants. Using our novel 3D scoring approach, we showed that the strongest pathogenic variant enrichment was observed for pore-lining residues and alpha-helix residues within 5Å distance from the pore axis center and not involved in gating. Within the subset of residues located at the pore, the hydrophobicity of the pore was the feature most strongly associated with variant pathogenicity. We also found an association between the identified properties and both clinical phenotypes and fucntional in vitro assays for voltage-gated sodium channels (SCN1A, SCN2A, SCN8A) and N-methyl-D-aspartate (NMDA) receptor (GRIN1, GRIN2A, GRIN2B) encoding genes. In an independent expert-curated dataset of 1,422 neurodevelopmental disorder pathogenic patient variants, and 679 electrophysiological experiments that pore axis distance is associated with seizure age of onset and cognitive performance as well as differential gain vs. loss-of-channel function.In summary, we identified biological properties associated with ion-channel malfunction and show that these are correlated with in vitro functional read-outs and clinical phenotypes in patients with neurodevelopmental disorders. Our results suggest that clinical decision support algorithms that predict variant pathogenicity and function are feasible in the future.
Mitochondrial phosphoproteomes are functionally specialized across tissues
Authors: Hansen Fynn M. , Kremer Laura S. , Karayel Ozge , Kühl Inge , Bludau Isabell , Larsson Nils-Göran , Mann Matthias 
Published: March 2022

AbstractMitochondria are essential organelles involved in critical biological processes such as energy metabolism and cell survival. Their dysfunction is linked to numerous human pathologies that often manifest in a tissue-specific manner. Accordingly, mitochondrial fitness depends on versatile proteomes specialized to meet diverse tissue-specific requirements. Furthermore, increasing evidence suggests that phosphorylation may also play an important role in regulating tissue-specific mitochondrial functions and pathophysiology. We hypothesized that recent advances in mass spectrometry (MS)-based proteomics would now enable in-depth measurement to quantitatively profile mitochondrial proteomes along with their matching phosphoproteomes across tissues. We isolated mitochondria from mouse heart, skeletal muscle, brown adipose tissue, kidney, liver, brain, and spleen by differential centrifugation followed by separation on Percoll gradients and high-resolution MS analysis of the proteomes and phosphoproteomes. This in-depth map substantially quantifies known and predicted mitochondrial proteins and provides a resource of core and tissue modulated mitochondrial proteins (mitophos.de). We also uncover tissue-specific repertoires of dozens of kinases and phosphatases. Predicting kinase substrate associations for different mitochondrial compartments indicates tissue-specific regulation at the phosphoproteome level. Illustrating the functional value of our resource, we reproduce mitochondrial phosphorylation events on DRP1 responsible for its mitochondrial recruitment and fission initiation and describe phosphorylation clusters on MIGA2 linked to mitochondrial fusion.
CD4 binding-site antibodies induced by a subtype B HIV-1 envelope trimer
Authors: Schorcht Anna , van den Kerkhof Tom L.G.M. , Torres Jon , Schermer Edith , LaBranche Celia C. , Bontjer Ilja , Brinkkemper Mitch , Gulzar Naveed , Han Alvin X. , Burger Judith , Ozorowski Gabriel , Scott Jamie K. , Schuitemaker Hanneke , Montefiori David , van Gils Marit J. , Ward Andrew B. , Sanders Rogier 
Published: March 2022

AbstractIn the last decade considerable advances have been made towards the design of HIV-1 vaccines that induce neutralizing antibodies (NAbs). Despite the progress, no vaccine is able to consistently elicited broadly neutralizing antibodies (bNAbs). Here we present a case study of a rabbit that was immunized with a subtype B native like envelope glycoprotein (Env) trimer, AMC016 SOSIP.v4.2, with a dense and intact glycan shield, followed by a trivalent combination of subtype B trimers. After the priming phase serum from this animal neutralized several heterologous subtype B neutralization resistant (tier 2) viruses. Subsequent immunization with the trivalent combination of subtype B trimers further increased the breadth and potency of the NAb response. EM based polyclonal epitope mapping revealed that a cross reactive CD4 binding-site (CD4bs) antibody response, that was present after priming with the monovalent trimer and boosting with the trivalent combination, was most likely responsible for the broad neutralization. While anecdotal, this study provides proof-of-concept that native-like Env trimers are capable of inducing CD4bs-directed bNAb responses and should guide efforts to improve the consistency with which such responses are generated.
Connexin36 expression in the cochlear nucleus complex of the echolocating bat, Eptesicus fuscus
Authors: Accomando Alyssa W. , Johnson Mark A. , McLaughlin Madeline A. , Simmons James A. , Simmons Andrea Megela 
Published: March 2022

ABSTRACTGap junctions and electrical synapses in the central nervous system are associated with rapid temporal processing and coincidence detection. Using histology, immunohistochemistry, and in situ hybridization, we investigated the distribution of Connexin36 (Cx36), a protein that comprises neuronal gap junctions, throughout the cochlear nucleus complex of the echolocating big brown bat, Eptesicus fuscus, a species exhibiting extreme behavioral sensitivity to minute temporal changes in ultrasonic echoes. For comparison, we visualized Cx36 expression in the cochlear nucleus of transgenic Cx36 reporter mice, species that hear ultrasound but do not echolocate. We observed Cx36 expression in the anteroventral and dorsal cochlear nucleus, with more limited expression in the posteroventral cochlear nucleus, of both species. Several different morphological cell types were labeled, including globular and spherical bushy, octopus, stellate, and fusiform cells. Labeled Cx36 puncta were also observed. Cx36 expression in the bat was spread throughout a relatively smaller area of the cochlear nucleus than in the mouse, even though the bat cochlear nucleus is hypertrophied. In the bat, the anteroventral cochlear nucleus showed higher percent area label than the dorsal cochlear nucleus, with a trend towards the opposite result in the mouse. The presence of gap junctions appears to be a conserved feature of the mammalian cochlear nucleus and thus not uniquely tied to the temporal hyperacuity of echolocation.