bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Longitudinal Study of Age-Based Change in Blood Pressure Reactivity and Negative Affect Reactivity to Natural Stressors
Authors: Koffer Rachel E. , Kamarck Thomas W. 
Published: April 2022

ABSTRACT

Objective
Aging is theoretically accompanied by emotional gains, but physiological self-regulatory losses. Emotional and physiological regulation can be operationalized as the extent of an increase in negative affect and blood pressure upon experiencing a stressor (i.e., reactivity). The direction of age-based changes in negative affect reactivity to stressors is uncertain. In addition, evidence for age-based increases in blood pressure reactivity to stressors is based largely on age-based differences observed in cross-sectional and laboratory-based studies. The present study is the first to examine long-term longitudinal changes in stress-related reactivity for both blood pressure and negative affect in the natural environment.

Methods
A total of 375 healthy adults aged 50 to 70 years completed 6 days of hourly ambulatory blood pressure assessment and electronic diary reports of social conflict and task demand and control. Two hundred fifty-five participants repeated 3 days of assessment in a 6-year follow-up. With reactivity operationalized as the change in an outcome in association with momentary social conflict, task strain, or task demand (i.e., a model-derived slope parameter), multilevel models were used to assess aging-based change in blood pressure and negative affect reactivity over the course of the 6-year follow-up.

Results
Aging is associated with increased diastolic blood pressure reactivity to social conflict and task demand (β
social_conflict = 0.48, p = .007; β
task_demand = 0.19, p = .005), increases in negative affect reactivity to social conflict and task strain (β
social_conflict = 0.10, p < .001; β
task_strain = 0.08, p = .016), and increases in systolic blood pressure reactivity to task-based stress (β
task_strain = 1.29, p = .007; β
task_demand = 0.23 p = .032).

Conclusion
Findings suggest age-based increases in affective and cardiovascular reactivity to natural stressors.
Psychological Predictors of Response to Open-Label Versus Double-Blind Placebo in a Randomized Controlled Trial in Irritable Bowel Syndrome
Authors: Ballou Sarah , Haas Julia W. , Iturrino Johanna , Nee Judy , Kirsch Irving , Rangan Vikram , Cheng Vivian , Lembo Anthony , Kaptchuk Ted J. , Kelley John M. 
Published: April 2022

ABSTRACT

Objective
There is growing evidence that open-label placebo (OLP) may be an efficacious treatment of chronic and functional conditions. However, patient-level predictors of response to OLP have not been clearly identified. The aim of this study is to evaluate the psychological predictors of response to OLP and to compare this to double-blind placebo (DBP) and no-pill control (NPC).

Methods
This study is a secondary analysis of data collected in a 6-week randomized controlled trial evaluating placebo effects in irritable bowel syndrome (IBS). The primary outcome was change in IBS severity. Hierarchical linear regression identified predictors of placebo response in general and compared them between those randomized to OLP, DBP, and NPC. Predictor variables included personality traits, generalized anxiety, depression, visceral sensitivity (a measure of symptom-specific anxiety), and pain catastrophizing.

Results
A total of 210 participants (mean age = 42.3 years, 73.3% female) were included. Regression models revealed that visceral sensitivity was a predictor of response to OLP and NPC but not DBP. Interestingly, the effects were opposite, with high visceral sensitivity predicting less improvement in NPC and more improvement in OLP. Pain catastrophizing was a negative predictor of response to OLP (i.e., high pain catastrophizing was associated with less improvement in OLP). Neither visceral sensitivity nor pain catastrophizing played a significant role for response to DBP.

Conclusions
IBS participants who score low on the Pain Catastrophizing Scale but high on the Visceral Sensitivity Index seem to benefit particularly from OLP. Our study suggests that different psychological mechanisms may be involved in DBP and OLP interventions.
Coronary Artery Calcifications Are Associated With More Severe Multiorgan Failure in Patients With Severe Coronavirus Disease 2019 Infection
Authors: Martens Bibi , Driessen Rob G.H. , Brandts Lloyd , Hoitinga Puck , van Veen Fauve , Driessen Mariëlle , Weberndörfer Vanessa , Kietselaer Bas , Ghossein-Doha Chahinda , Gietema Hester A. ,   MaastrICCht Collaborators, Vernooy Kevin , van der Horst Iwan C.C. , Wildberger Joachim E. , van Bussel Bas C.T. , Mihl Casper 
Published: April 2022

Purpose:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is regarded as a multisystemic disease. Patients with preexisting cardiovascular disease have an increased risk for a more severe disease course. This study aimed to investigate if a higher degree of coronary artery calcifications (CAC) on a standard chest computed tomography (CT) scan in mechanically ventilated patients was associated with a more severe multiorgan failure over time.

Materials and Methods:
All mechanically ventilated intensive care unit patients with SARS-CoV-2 infection who underwent a chest CT were prospectively included. CT was used to establish the extent of CAC using a semiquantitative grading system. We categorized patients into 3 sex-specific tertiles of CAC: lowest, intermediate, and highest CAC score. Daily, the Sequential Organ Failure Assessment (SOFA) scores were collected to evaluate organ failure over time. Linear mixed-effects regression was used to investigate differences in SOFA scores between tertiles. The models were adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, cardiovascular risk factors, and chronic liver, lung, and renal disease.

Results:
In all, 71 patients were included. Patients in the highest CAC tertile had, on average, over time, 1.8 (0.5-3.1) points higher SOFA score, compared with the lowest CAC tertile (P=0.005). This association remained significant after adjustment for age, sex, and APACHE II score (1.4 [0.1-2.7], P=0.042) and clinically relevant after adjustment for cardiovascular risk factors (1.3 [0.0-2.7], P=0.06) and chronic diseases (1.3 [−0.2 to 2.7], P=0.085).

Conclusion:
A greater extent of CAC is associated with a more severe multiorgan failure in mechanically ventilated coronavirus disease 2019 patients.
Novel Privacy Considerations for Large Scale Proteomics
Authors: Hill Andrew C. , Litkowski Elizabeth M. , Manichaikul Ani , Lange Leslie , Pratte Katherine A. , Kechris Katerina J. , DeCamp Matthew , Coors Marilyn , Ortega Victor E. , Rich Stephen S. , Rotter Jerome I. , Gerzsten Robert E. , Clish Clary B. , Curtis Jeffery , Hu Xiaowei , Ngo Debby , O’Neal Wanda K , Meyers Deborah , Bleecker Eugene , Hobbs Brian D. , Cho Michael H. , Banaeikashani Farnoush , Bowler Russell P. 
Published: April 2022

AbstractIntroductionPrivacy protection is a core principle of genomic research but needs further refinement for high-throughput proteomic platforms.MethodsWe identified independent single nucleotide polymorphism (SNP) quantitative trait loci (pQTL) from COPDGene and Jackson Heart Study (JHS) and then calculated genotype probabilities by protein level for each protein-genotype combination (training). Using the most significant 100 proteins, we applied a naïve Bayesian approach to match proteomes to genomes for 2,812 independent subjects from COPDGene, JHS, SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) and Multi-Ethnic Study of Atherosclerosis (MESA) with SomaScan 1.3K proteomes and also 2,646 COPDGene subjects with SomaScan 5K proteomes (testing). We tested whether subtracting mean genotype effect for each pQTL SNP would obscure genetic identity.ResultsIn the four testing cohorts, we were able to correctly match 90%-95% their proteomes to their correct genome and for 95%-99% we could match the proteome to the 1% most likely genome. With larger profiling (SomaScan 5K), correct identification was > 99%. The accuracy of matching in subjects with African ancestry was lower (∼60%) unless training included diverse subjects. Mean genotype effect adjustment reduced identification accuracy nearly to random guess.ConclusionLarge proteomic datasets (> 1,000 proteins) can be accurately linked to a specific genome through pQTL knowledge and should not be considered deidentified. These findings suggest that large scale proteomic data be given privacy protections of genomic data, or that bioinformatic transformations (such as adjustment for genotype effect) should be applied to obfuscate identity.
Disrupting ACE2 Dimerization Mitigates the Infection by SARS-COV-2
Authors: Zhu Jiaqi , Su Yue , Tang Young 
Published: April 2022

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has caused over 6 million death and 460 million reported cases globally. More effective antiviral medications are needed to curb the continued spread of this disease. The infection by SARS-COV-2 virus is initiated via the interaction between the receptor binding domain (RBD) of the viral glycoprotein Spike (S protein) and the N-term peptidase domain (PD) of the angiotensin-converting enzyme 2 (ACE2) expressed on host cell membrane. ACE2 forms protein homodimer primarily through its ferredoxin-like fold domain (aka. Neck-domain). We investigated whether the dimerization of ACE2 receptor plays a role in SARS-COV-2 virus infection. We report here that the ACE2 receptor dimerization enhances the recognition of SARS-COV-2 S protein. A 43 amino acid peptide based on the N-term of Neck-domain could block the ACE2 dimerization and the interaction between RBD and ACE2, and mitigate the SARS-COV-2/host cell interaction. Our study illustrated a new route to develop potential therapeutics for the prevention and treatment of SARS-COV-2 viral infection.
Wake respirometry may quantify stress and energetics of free-living animals
Authors: Rose Kayleigh , Wilson Rory P , Ramenda Claudia , Robotka Hermina , Wikelski Martin , Shepard Emily L C 
Published: April 2022

SUMMARYQuantifying activity-specific energy expenditure in free-living animals is a major challenge as current methods require calibration in the lab and animal capture. We propose “wake respirometry”, a new method of quantifying fine-scale changes in CO2 production in unrestrained animals, using a non-dispersive infrared CO2 sensor positioned downwind of the animal i.e. in its wake. We parameterise the dispersion of CO2 in a wake using known CO2 concentrations, flow rates and wind speeds. Tests with three bird species in a wind tunnel demonstrated that the system can resolve breath-by-breath changes in CO2 concentration, with clear exhalation signatures increasing in period and integral with body size. Changes in physiological state were detectable following handling, flight and exposure to a perceived threat. We discuss the potential of wake respirometry to quantify stress and respiratory patterns in wild animals and estimate activity-specific metabolic rates through the full integration of CO2 production across the wake.
ReDisX: a Continuous Max Flow-based framework to redefine the diagnosis of diseases based on identified patterns of genomic signatures
Authors: Yip Hiu Fung , Chowdhury Debajyoti , Wang Kexin , Liu Yujie , Gao Yao , Lan Liang , Zheng Chaochao , Guan Daogang , Lam Kei Fong , Zhu Hailong , Tai Xuecheng , Lu Aiping 
Published: April 2022

AbstractDiseases originate at the molecular-genetic layer, manifest through altered biochemical homeostasis, and develop symptoms later. Hence symptomatic diagnosis is inadequate to explain the underlying molecular-genetic abnormality and individual genomic disparities. The current trends include molecular-genetic information relying on algorithms to recognize the disease subtypes through gene expressions. Despite their disposition toward disease-specific heterogeneity and cross-disease homogeneity, a gap still exists to describe the extent of homogeneity within the heterogeneous subpopulation of different diseases. They are limited to obtaining the holistic sense of the whole genome-based diagnosis resulting in inaccurate diagnosis and subsequent management.To fill those gaps, we proposed ReDisX framework, a scalable machine learning algorithm that uniquely classifies patients based on their genomic signatures. It was deployed to re-categorizes the patients with rheumatoid arthritis and coronary artery disease. It reveals heterogeneous subpopulations within a disease and homogenous subpopulations across different diseases. Besides, it identifiesGZMBas a subpopulation-differentiation marker that plausibly serves as a prominent indicator forGZMB-targeted drug repurposing.The ReDisX framework offers a novel strategy to redefine disease diagnosis through characterizing personalized genomic signatures. It may rejuvenate the landscape of precision and personalized diagnosis, and a clue to drug repurposing.
scTAM-seq enables targeted high-confidence analysis of DNA methylation in single cells
Authors: Bianchi Agostina , Scherer Michael , Zaurin Roser , Quililan Kimberly , Velten Lars , Beekman Renée 
Published: April 2022

AbstractSingle-cell DNA methylation profiling currently suffers from excessive noise and/or limited cellular throughput. We developed scTAM-seq, a targeted bisulfite-free method for profiling up to 650 CpGs in up to 10,000 cells per experiment, with a dropout rate of less than seven percent. scTAM-seq focuses sequencing coverage on informative, variably methylated CpGs that in many tissues and cell types make up a minor fraction of all CpGs. By applying scTAM-seq to B cells from blood and bone marrow, we demonstrate that it can resolve DNA methylation dynamics across B-cell differentiation at unprecedented resolution, identifying intermediate differentiation states that were previously masked. scTAM-seq additionally queries surface protein expression and somatic mutations, thus enabling integration of single-cell DNA methylation information with cell atlas data, and opening applications in tumor profiling. In summary, scTAM-seq is the first high-throughput, high-confidence method for analyzing DNA methylation at single-CpG resolution across thousands of single cells.
A potent synthetic nanobody with broad-spectrum activity neutralizes SARS-Cov-2 virus and Omicron variant through a unique binding mode
Authors: Zhao Dongping , Liu Liqin , Liu Xinlin , Zhang Jinlei , Yin Yuqing , Luan Linli , Jiang Dingwen , Yang Xiong , Li Lei , Xiong Hualong , Xing Dongming , Zheng Qingbing , Xia Ningshao , Tao Yuyong , Li Shaowei , Huang Haiming 
Published: April 2022

AbstractThe major challenge to control COVID pandemic is the rapid mutation rate of the SARS-Cov-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-Cov-2 variants. Here, we reported a synthetic nanobody (named C5G2) obtianed by phage display and subsequent antibody engineering. C5G2 has a single digit nanomolar binding affinity to RBD domain and inhibits its binding to ACE2 with an IC50 of 3.7 nM. Pseudovirus assay indicated that the monovalent C5G2 could protect the cells from the infection of SARS-Cov-2 wild type virus and most of the virus of concern, i.e. Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against Omicron among all the variants with the IC50 of 4.9ng/mL. The Cryo-EM structure of C5G2 in complex with the Spike trimer showed that C5G2 bind to RBD mainly through its CDR3 at a conserved region that not overlapping with the ACE2 binding surface. Additionally, C5G2 bind simultaneously to the neighboring NTD domain of spike trimer through the same CDR3 loop, which may further increase its potency against the virus infection. Third, the steric hindrance caused by FR2 of C5G2 could inhibit the binding of ACE2 to RBD as well. Thus, this triple-function nanobody may be served as an effective drug for the prophylaxis and therapy against Omicron as well as future variants.
Elp1 is required for development of visceral sensory peripheral and central circuitry
Authors: Tolman Zariah , Chaverra Marta , George Lynn , Lefcort Frances 
Published: April 2022

AbstractCardiovascular instability and a blunted respiratory drive in hypoxic conditions, are hallmark features of the genetic sensory and autonomic neuropathy, familial dysautonomia (FD). FD results from a mutation in the gene ELP1, whose encoded protein is a scaffolding subunit of the six subunit Elongator complex. In mice, we and others have shown that Elp1 is essential for the normal development of neural crest derived-dorsal root ganglia (DRG) sensory neurons. Whether Elp1 is also required for development of ectodermal placode-derived visceral sensory receptors which are required for normal baroreception and chemosensory responses, has not been investigated. Using mouse models for FD, our data indicate that in fact the entire circuitry underlying baroreception and chemoreception is impaired due to a requirement for Elp1 not only in the visceral sensory neuron ganglia, but also for normal peripheral target innervation, and in their CNS synaptic partners in the medulla. Thus Elp1 is required in both placode- and neural crest-derived sensory neurons and its reduction aborts the normal development of neuronal circuitry essential for autonomic homeostasis and interoception.Summary statementDue to faulty afferent sensory signaling, patients with Familial dysautonomia (FD) have a diminished sensory arm of the baroreflex which would normally modulate blood pressure, and they have a blunted response to hypoxia and hypercapnia (Norcliffe-Kaufmann et al. 2010). Using mouse models for FD, we reveal here the underlying pathology which may underlie these severely impaired homeostatic reflex pathways in FD.
Long-range morphogen gradient formation by cell-to-cell signal propagation
Authors: Dickmann Johanna E. M. , Rink Jochen C. , Jülicher Frank 
Published: April 2022

AbstractMorphogen gradients are a central concept in developmental biology. Their formation often involves the secretion of morphogens from a local source, that spread by diffusion in the cell field, where molecules eventually get degraded. This implies limits to both the time and length scales over which morphogen gradients can form which are set by diffusion coefficients and degradation rates. Towards the goal of identifying plausible mechanisms capable of extending the gradient range, we here use theory to explore properties of a cell-to-cell signaling relay. Inspired by the millimeter-scale Wnt-expression and signaling gradients in flatworms, we consider morphogen-mediated morphogen production in the cell field. We show that such a relay can generate stable morphogen and signaling gradients that emanate from a source of morphogen at a boundary. This gradient formation can be related to an effective diffusion and an effective degradation that result from morphogen production due to signaling relay. If the secretion of morphogen produced in response to the relay is polarized, it further gives rise to an effective drift. We find that signaling relay can generate long-ranged gradients in relevant times without relying on extreme choices of diffusion coefficients or degradation rates, thus exceeding the limits set by physiological diffusion coefficients and degradation rates. A signaling relay is hence an attractive principle to conceptualize long-ranged gradient formation by slowly diffusing morphogens that are relevant for patterning in adult contexts such as regeneration and tissue turn-over.
Linker histone H1 regulates defense priming and immunity in plants
Authors: Sheikh Arsheed H. , Nawaz Kashif , Tabassum Naheed , Trapp Marilia , Alhoraibi Hanna , Rayapuram Naganand , Hirt Heribert 
Published: April 2022

AbstractLinker H1 histones play an important role in animal and human pathogenesis, but their function in plant immunity is poorly understood. Here, we analyzed mutants of the three canonical variants of Arabidopsis H1 histones, namely H1.1, H1.2 and H1.3. We observed that double h1.1h1.2 and triple h1.1h1.2h1.3 (3h1) mutants were resistant to Pseudomonas syringae and Botrytis cinerea infections. Transcriptome analysis of 3h1 mutant plants showed that histone H1s play a key role in regulating the expression of early and late defense genes upon pathogen challenge. Moreover, 3h1 mutant plants showed enhanced production of reactive oxygen species and activation of mitogen activated protein kinases upon pathogen-associated molecular pattern (PAMP) treatment. However, 3h1 mutant plants were insensitive to priming with flg22, a well-known bacterial PAMP (pathogen-associated molecular pattern) which induces enhanced resistance in WT plants. The defective defense response in 3h1 was correlated with the enhanced DNA methylation and reduced H3K56ac levels upon priming. Our data place H1 as a molecular gatekeeper in governing dynamic changes in the chromatin landscape of defense genes during plant pathogen interaction.
RNA-protein interactome at the Hepatitis E virus internal ribosome entry site
Authors: Kumar Shiv , Verma Rohit , Saha Sandhini , Agrahari Ashish , Shukla Shivangi , Anurag  , Maiti Tushar Kanti , Asthana Shailendra , Ranjith-Kumar C.T. , Surjit Milan 
Published: April 2022

AbstractMultiple processes exist in a cell to ensure continuous production of essential proteins either through cap-dependent or cap-independent translation processes. Viruses depend on the host translation machinery for viral protein synthesis. Therefore, viruses have evolved clever strategies to utilize the host translation machinery. Earlier studies have shown that genotype 1-Hepatitis E virus (g1-HEV) utilizes both cap-dependent and cap-independent translation machineries for its replication and proliferation. Cap-independent translation in g1-HEV is driven by an eighty seven nucleotide-long RNA element which acts as a noncanonical, internal ribosome entry site like (IRESl) element. Here, we have identified the RNA-protein interactome of the HEV IRESl element and characterized the functional significance of some of its components. Our study reveals indispensable roles of host ribosomal protein RPL5 and DHX9 (RNA helicase A) in mediating efficient translation from the IRESl element and establish the function of HEV IRESl as a bonafide internal ribosome entry site.Author summaryProtein synthesis is a fundamental process for survival and proliferation of all living organisms. Majority of cellular proteins are produced through cap-dependent translation. Cells also utilize a variety of cap-independent translation processes to synthesize essential proteins during stress. Viruses depend on the host cell translation machinery to synthesize their own proteins. Hepatitis E virus is a major cause of hepatitis worldwide. The viral genome is a capped positive strand RNA. Viral non-structural and structural proteins are synthesized through a cap-dependent translation process. An earlier study from our laboratory reported the presence of a fourth ORF in genotype 1-HEV, which produced the ORF4 protein using a cap-independent internal ribosome entry site-like (IRESl) element. In the current study, we identified the host proteins that associate with the HEV-IRESl RNA and generated the RNA-protein interactome. Through a variety of experimental approaches, our data proves that HEV-IRESl is a bonafide internal ribosome entry site.