bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein painting reveals pervasive remodeling of conserved proteostasis machinery in response to pharmacological stimuli
Authors: Cox Dezerae , Ormsby Angelique R. , Reid Gavin E. , Hatters Danny M. 
Published: May 2022

AbstractAccurate spatio-temporal organization of the proteome is essential for cellular homeostasis. However, a detailed mechanistic understanding of this organization and how it is altered in response to external stimuli in the intact cellular environment is as-yet unrealized. To address this need, ‘protein painting’ methods have emerged as a way to gain insight into the conformational status of proteins within cells at the proteome-wide scale. For example, tetraphenylethene maleimide (TPE-MI) has previously been used to quantify the engagement of quality control machinery with client proteins in cell lysates. Here, we showcase the ability of TPE-MI to additionally reveal proteome network remodeling in whole cells in response to a cohort of commonly used pharmacological stimuli of varying specificity. We report specific, albeit heterogeneous, responses to individual stimuli that coalesce on a conserved set of core cellular machineries. This work expands our understanding of proteome conformational remodeling in response to cellular stimuli, and provides a blueprint for assessing how these conformational changes may contribute to disorders characterized by proteostasis imbalance.
Pathway and directional specificity of Hebbian plasticity induction in the cortical visual motion processing network
Authors: Bevilacqua Michele , Huxlin Krystel R. , Hummel Friedhelm C. , Raffin Estelle 
Published: May 2022

AbstractCortico-cortical paired associative stimulation (ccPAS), which repeatedly pairs single pulse TMS over two distant brain regions with a specific time interval, is thought to modulate synaptic plasticity. Applied to the motion cortical pathway, ccPAS has been shown to improve motion discrimination when specifically targeting backward projections, stimulating the medio-temporal area (MT) followed by the primary visual cortex (V1). However, there is no direct neuroimaging evidence of the spatial selectivity of the ccPAS effects (i.e., pathway or direction specificity) or detailing the exact nature of the ccPAS effects (i.e., the oscillatory signature, timing…). In this study, we applied ccPAS along the motion discrimination pathway, in the top-down direction (MT-to-V1: “Backward ccPAS”) and in the bottom-up direction (V1-to-MT: “Forward ccPAS”) in sixteen healthy volunteers and compared changes in visual network activity in response to single pulse TMS over V1 and MT using spectral granger causality (sGC). The sGC results showed common increases in direct V1-to-MT and V1-to-IPS bottom-up inputs in the high Beta/low Gamma band (25-40 Hz) for both ccPAS, probably reflecting task exposure. However, a clear distinction in information transfer occurred in the re-entrant MT-to-V1 signals, which were only modulated by Backward ccPAS. This difference was predictive of the behavioural improvements at the motion discrimination task. Our results support the view of the possibility to specifically enhance re-entrant Alpha oscillatory signals from MT-to-V1 to promote motion discrimination performance through Backward ccPAS. These findings contribute to better understanding visual processing in healthy subjects and how it can be modulated to pave the way to clinical translation in vision handicapped patients. The changes in re-entrant MT-to-V1 inputs could help to provide single-subject prediction scenarios in patients suffering from a visual system stroke, in whom visual recovery might partly rely on the top-down inputs to the spared V1 neurons.
DNA binding domain undergoes dynamic and selective protein–protein interactions to facilitate CTCF insulation
Authors: Rong Zhou , Kai Tian , Jie Huang , Wenjia Duan , Hongye Fu , Ying Feng , Hui Wang , Yongpeng Jiang , Yuanjun Li , Rui Wang , Jiazhi Hu , Hanhui Ma , Zhi Qi , Xiong Ji 
Published: May 2022

SUMMARYCTCF is required for three-dimensional chromatin organization and a predominant insulator protein. However, its roles in insulating enhancers have not been fully explained in 3D nuclear organization. Here, we found that the CTCF DNA binding domain (DBD) forms dynamic self-interacting clusters. We next investigated the spatial relationships between these clusters and other transcription regulators with a light-induced imaging system. Strikingly, CTCF DBD clusters were found to incorporate other insulator proteins but are not coenriched with transcriptional activators in the nucleus. This property is not observed in other domains of CTCF or the DBDs of other transcription factors. Moreover, endogenous CTCF shows a phenotype consistent with the DBD by forming small protein clusters and interacts less transcriptional activators bound, CTCF motif arrays. Our results reveal an interesting phenomenon that CTCF DBD interacts with insulator proteins and selectively localizes to nuclear positions with lower concentrations of transcriptional activators, providing new insights into the insulation function of CTCF.
High-content cellular screen image analysis benchmark study
Authors: Bray Mark-Anthony , de Weck Antoine , Durand Eric , Fang Jian , Gabriel Daniela , Janssens Rens , Moutsatsos Ioannis , Spiegel Stephan , Zhang Xian 
Published: May 2022

AbstractRecent development of novel methods based on deep neural networks has transformed how high-content microscopy cellular images are analyzed. Nonetheless, it is still a challenge to identify cellular phenotypic changes caused by chemical or genetic treatments and to elucidate the relationships among treatments in an unsupervised manner, due to the large data volume, high phenotypic complexity and the presence of a priori unknown phenotypes. Here we benchmarked five deep neural network methods and two feature engineering methods on a well-characterized public data set. In contrast to previous benchmarking efforts, the manual annotations were not provided to the methods, but rather used as evaluation criteria afterwards. The seven methods individually performed feature extraction or representation learning from cellular images, and were consistently evaluated for downstream phenotype prediction and clustering tasks. We identified the strengths of individual methods across evaluation metrics, and further examined the biological concepts of features automatically learned by deep neural networks.
The Individualized Neural Tuning Model: Precise and generalizable cartography of functional architecture in individual brains
Authors: Feilong Ma , Nastase Samuel A. , Jiahui Guo , Halchenko Yaroslav O. , Gobbini M. Ida , Haxby James V. 
Published: May 2022

AbstractQuantifying how brain functional architecture differs from person to person is a key challenge in human neuroscience. Current individualized models of brain functional organization are based on brain regions and networks, limiting their use in studying fine-grained vertex-level differences. In this work, we present the Individualized Neural Tuning (INT) model, a fine-grained individualized model of brain functional organization. The INT model is designed to have vertex-level granularity, to capture both representational and topographic differences, and to model stimulus-general neural tuning. Through a series of analyses, we demonstrate that (a) our INT model provides a reliable individualized measure of fine-grained brain functional organization, (b) it accurately predicts individualized brain response patterns to new stimuli, and (c) it requires only 10–20 minutes of data for good performance. The high reliability, specificity, precision, and generalizability of our INT model affords new opportunities for building brain-based biomarkers based on naturalistic neuroimaging paradigms.
Adaptive diversification and niche packing on rugged fitness landscapes
Authors: Rubin Ilan N. , Ispolatov Yaroslav , Doebeli Michael 
Published: May 2022

AbstractExplaining the emergence of diversity and the coexistence of competing types has long been one of the main goals of ecological theory. Rugged fitness landscapes have often been used to explain diversity through the presence of local peaks, or adaptive zones, in the fitness landscape acting as available niches for different species. Alternatively, niche-packing and theories based on limiting similarity describe frequency-dependent selection leading to the organic differentiation of a continuous phenotype space into multiple coexisting types. By combining rugged carrying capacity landscapes with frequency-dependent selection, here we investigate the effects of ruggedness on adaptive diversification and stably maintained diversity. We show that while increased ruggedness often leads to a decreased opportunity for adaptive diversification, it is the shape of the global carrying capacity function, not the local ruggedness, that determines the diversity of the ESS and the total diversity a system can stably maintain.
Effectiveness of integrated care for older adults with depression and hypertension in rural China: a cluster randomized controlled trial
Authors: Chen Shulin , Conwell Yeates , Xue Jiang , Li Lydia , Zhao Tingjie , Tang Wan , Bogner Hillary , Dong Hengjin 
Published: May 2022

AbstractBackgroundEffectiveness of integrated care management for common, comorbid physical and mental disorders has been insufficiently examined in low- and middle-income countries. We tested hypotheses that older adults treated in rural Chinese primary care clinics with integrated care management of comorbid depression and HTN would show greater improvements in depression symptom severity and hypertension (HTN) control than those who received usual care.Methods and findingsThe study was a 12-month cluster randomized controlled trial conducted from 2014 through 2017, with analyses conducted in 2020-2021. Subjects were rural village clinics of randomly selected towns in Zhejiang Province, China. Ten towns with a total of 218 rural village primary care clinics were randomized, five towns each, to deliver the Chinese Older Adult Collaborations in Health (COACH) intervention or enhanced care-as-usual (eCAU). The COACH intervention consisted of algorithm-driven treatment of depression and HTN by village primary care doctors supported by village lay workers with consultation from centrally-located psychiatrists. Subjects included clinic patients aged ≥60 years with a diagnosis of HTN and clinically significant depressive symptoms (PHQ-9 score ≥10). Of 2899 eligible subjects, 2365 (82%) agreed to participate and were followed for 12 months. Observers were blinded to study hypotheses but not to group assignment. Primary outcomes specified a priori were change in depression symptom severity and proportion with controlled HTN.Compared with 1133 subjects who received eCAU, 1232 COACH subjects showed greater reduction in depressive symptoms (Cohen’s d [±SD] = -0.21 [-0.25, -0.17]) and greater likelihood of achieving HTN control (OR [95% CI] = 18.24 [8.40, 39.63]). Exploratory post hoc analyses showed that COACH subjects who accepted an antidepressant had greater symptom reduction than either those who declined the medication or received eCAU. HTN control improved in COACH subjects regardless of antidepressant use.ConclusionsThe COACH model appears effective in managing comorbid depression and HTN in older adult residents of rural Chinese villages. Integrated care management of comorbid depression and common medical illness may be a useful approach in other low resourced settings in which specialty geriatric mental health care is lacking.
Multiple Burdens of Road Traffic Crashes in Pokhara, Nepal: A Patient Approach
Authors: Bishwokarma Sapana , Adhikari Chiranjivi , Khatri Dhurba , Gauchan Bikash , Sapkota Vishnu Prasad , Ranabhat Chhabi Lal 
Published: May 2022

AbstractBackgroundThe economic burden and cost-related evidence from primary data of road traffic crashes (RTCs) in Nepal are limited.AimThis study assessed the disability-adjusted life years (DALYs), the cost associated with RTCs, and socio-demographic and injury related factors.MethodsWe carried out a retrospective cross-sectional, institution-based survey of the RTC victims in the last one year to 45 days prior to the survey, in Pokhara and the surroundings in Kaski district, a mid-hilly district and the headquarter of Gandaki province of Nepal. A sample of 107 RTC victims, registered in different hospitals, police offices and health insurance offices, were retrospectively approached. A semi-structured interview schedule was used to collect data. Data were entered into EpiData before being imported, and analysed in the Statistical Package for Social Sciences (SPSS) and MS-Excel. Descriptive statistics were generated by calculating costs and DALYs, and inferential analysis was used to investigate the relationship between DALYs and independent variables.ResultsMore than one-third (37.4%) of the 107 victims were between the ages of 25 and 44, and more than half (60.7%) were men. The cost per million person-years of RTC was around US $ 82,800. Similarly, around 1021 DALYs per million person-years are attributed to RTC, and more than 99% of them are shared by YLL. We observed the highest number of frequencies of young (p<.01), having university degree (p<.01), unemployed (p<.05), motorcyclists (p<.01), highest economic quintile (p<.01), and seriously injured (p<.01). In addition, we also observed a low positive correlation (r=0.33, p<.01) between DALYs and the victim’s indirect cost.ConclusionThe cost and DALYs associated by RTC of Kaski district were around US $ 82,800 and 1021 per million person-years in 2017, respectively. Young unemployed motorcyclists were the most frequent victims. Victim’s indirect cost is increased with DALYs, suggesting a policy implication.
Predictors of 90-Day Colectomy in Hospitalized Patients Receiving Infliximab for Acute Severe Ulcerative Colitis at a Tertiary Care Center
Authors: Berinstein Jeffrey A. , Atkuri Neelakanta Anurag , Berinstein Elliot M. , Sheehan Jessica L. , Johnson Laura A. , Cohen-Mekelburg Shirley A. , Jiang Hui , Wakim Nicole I. , Kidwell Kelley M. , Nahum-Shani Inbal Billie , Robert  , Waljee Akbar K. , Higgins Peter D.R. 
Published: May 2022

ABSTRACTBACKGROUND & AIMSAcute severe ulcerative colitis (ASUC) is a life-threatening presentation of ulcerative colitis requiring prompt treatment. Infliximab (IFX) rescue therapy can prevent colectomy in patients with ASUC.METHODSWe performed a cohort study of adult patients hospitalized with ASUC between 01/2014 – 02/2021 who received infliximab rescue therapy. Using multivariable logistic regression, baseline and longitudinal laboratory predictors of colectomy within 90 days of index hospitalization were identified and used to develop a risk prediction model and prognostic scoring system to identifying patients at risk for colectomy. Model performance was assessed using area under the receiver operator characteristic curve (AUC) analysis.RESULTS166 patients with ASUC who received infliximab rescue therapy were identified. Overall, 24.7% (n=41) underwent colectomy within 90 days. Multivariate analysis revealed that colectomy within 90 days could be predicted by having a calculated IFX clearance of >53L/d (OR 2.28, 95% CI 0.99, 5.22), a day 0 absolute C-reactive protein (CRP) > 91mg/L (OR 3.49, 95% CI 1.58 to 8.08), a decrease in CRP of < 43% from day 0 to day 3 (OR 4.13, 95% CI 1.84 to 9.94), and a decrease in CRP of < 9% from the day of IFX administration to one day post-IFX administration (OR 4.20, 95% CI 1.74 to 10.4). Using these predictors, two highly accurate prognostic scoring system were developed to identify patients at risk for requiring colectomy both prior to administering infliximab (AUC 0.76) and after administer infliximab rescue therapy (AUC 0.81).CONCLUSIONWe identified important baseline and longitudinal laboratory predictors of colectomy within 90-days among patients with ASUC receiving infliximab rescue therapy and developed accurate prognostic scores to determine risk of colectomy. These scores can be used risk-stratify patients and facilitate personalized management.
From recency to central tendency biases in working memory: a unifying network model
Authors: Boboeva Vezha , Pezzotta Alberto , Clopath Claudia , Akrami Athena 
Published: May 2022

AbstractThe central tendency bias, or contraction bias, is a phenomenon where the judgment of the magnitude of items held in working memory appears to be biased towards the average of past observations. It is assumed to be an optimal strategy by the brain, and commonly thought of as an expression of the brain’s ability to learn the statistical structure of sensory input. On the other hand, recency biases such as serial dependence are also commonly observed, and are thought to reflect the content of working memory. Recent results from an auditory delayed comparison task in rats, suggest that both biases may be more related than previously thought: when the posterior parietal cortex (PPC) was silenced, both short-term and contraction biases were reduced. By proposing a model of the circuit that may be involved in generating the behavior, we show that a volatile working memory content susceptible to shifting to the past sensory experience – producing short-term sensory history biases – naturally leads to contraction bias. The errors, occurring at the level of individual trials, are sampled from the full distribution of the stimuli, and are not due to a gradual shift of the memory towards the sensory distribution’s mean. Our results are consistent with a broad set of behavioral findings and provide predictions of performance across different stimulus distributions and timings, delay intervals, as well as neuronal dynamics in putative working memory areas. Finally, we validate our model by performing a set of human psychophysics experiments of an auditory parametric working memory task.
Reemergence of the Murine Bacterial Pathogen Chlamydia muridarum in Laboratory Mouse Colonies
Authors: Mishkin Noah , Ricart Arbona Rodolfo J , Carrasco Sebastian E , Lawton Samira , Henderson Kenneth S. , Momtsios Panagiota , Sigar Ira M , Ramsey Kyle H , Cheleuitte-Nieves Christopher , Monette Sebastien , Lipman Neil S 
Published: May 2022

AbstractChlamydia muridarum (Cm) was detected in mice from 2 colonies with lymphoplasmacytic pulmonary infiltrates using PCR and immunohistochemistry. This discovery was unexpected as Cm infection had not been reported in laboratory mice since the 1940’s. A Cm specific PCR assay was developed and testing implemented for resident colonies from 8 vivaria from 3 academic institutions, 58 incoming mouse shipments from 39 academic institutions, and mice received from 55 commercial breeding colonies (4 vendors). To estimate Cm’s global prevalence in laboratory colonies, a database containing 11,387 metagenomic fecal microbiota samples from 120 institutions and a cohort of 900 diagnostic samples from 96 institutions were examined. Results indicate significant prevalence amongst academic institutions with Cm detected in 62.9% of soiled bedding sentinels from 3 institutions; 32.7% of incoming mouse shipments from 39 academic institutions; 14.2% of 120 institutions submitting microbiota samples; and 16.2% of the diagnostic sample cohort. All samples from commercial breeding colonies were negative. Additionally, naïve NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice exposed to Cm shedding mice and their soiled bedding developed clinical disease 21 to 28 days following exposure. These mice had a moderate-to-severe histiocytic and neutrophilic bronchointerstitial pneumonia with respiratory epithelium demonstrating inclusions, chlamydial major outer membrane protein immunostaining, and hybridization with a Cm reference sequence (GenBank accession no. U68436). Cm was isolated on HeLa 229 cells from lungs, cecum, and feces of a Cm infected NSG mouse. The considerable prevalence of Cm is likely attributed to widespread global interinstitutional distribution of unique mouse strains and failure to recognize that some of these mice were from enzootically infected colonies. Given that experimental Cm colonization of mice results in a robust immune response and, on occasion, pathology, natural infection may confound experimental results. Therefore, Cm should be excluded and eradicated from endemically infected laboratory mouse colonies.
Integration of sound and locomotion information by auditory cortical neuronal ensembles
Authors: Vivaldo Carlos Arturo , Lee Joonyeup , Shorkey MaryClaire , Keerthy Ajay , Rothschild Gideon 
Published: May 2022

AbstractThe ability to process and act upon incoming sounds during locomotion is critical for survival. Intriguingly, sound responses of auditory cortical neurons are on average weaker during locomotion as compared to immobility and these results have been suggested to reflect a computational resource allocation shift from auditory to visual processing. However, the evolutionary benefit of this hypothesis remains unclear. In particular, whether weaker sound-evoked responses during locomotion indeed reflect a reduced involvement of the auditory cortex, or whether they result from an alternative neural computation in this state remains unresolved. To address this question, we first used neural inactivation in behaving mice and found that the auditory cortex plays a critical role in sound-guided behavior during locomotion. To investigate the nature of this processing, we used two-photon calcium imaging of local excitatory auditory cortical neural populations in awake mice. We found that underlying a net inhibitory effect of locomotion on sound-evoked response magnitude, spatially intermingled neuronal subpopulations were differentially influenced by locomotion. Further, the net inhibitory effect of locomotion on sound-evoked responses was strongly shaped by elevated ongoing activity. Importantly, rather than reflecting enhanced “noise”, this ongoing activity reliably encoded the animal’s locomotion speed. Prediction analyses revealed that sound, locomotive state and their integration are strongly encoded by auditory cortical ensemble activity. Finally, we found consistent patterns of locomotion-sound integration in electrophysiologically recorded activity in freely moving rats. Together, our data suggest that auditory cortical ensembles are not simply suppressed by locomotion but rather encode it alongside sound information to support sound perception during locomotion.