bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of Age-related Respiratory Changes in Daphnia
Authors: Anderson Cora E. , Ekwudo Millicent N. , Jonas-Closs Rachael A , Cho Yongmin , Peshkin Leonid , Kirschner Marc W. , Yampolsky Lev Y. 
Published: June 2021

AbstractAging is a multifaceted process of accumulation of damages and waste in cells and tissues; age-related changes in mitochondria and in respiratory metabolism have been in the focus of aging research for decades. Here we investigated age-related changes in respiration rates, lactate/pyruvate ratio, a commonly used proxy for NAD+/NADH balance, and mitochondrial membrane potential in 4 genotypes of an emerging model organism for aging research, a cyclic parthenogen Daphnia magna. We show that total body weight-adjusted respiration rate decreases with age, although this decrease is small in magnitude and not observed in anaesthetized animals, thus likely to be accounted for by decrease in locomotion and feeding activity. Lactate/pyruvate ratio and mitochondrial membrane potential (Ψmt) showed no age-related changes, with a possible exception of Ψmt measured in the optical lobe and in epipodites (excretory organs) in which Ψmt showed a maximum at middle age. We conclude that actuarial senescence in Daphnia is not caused by a decline in respiratory metabolism and discuss possible mechanisms of maintaining mitochondrial healthspan throughout the lifespan.
Adaptable and Automated Rodent Behavior Maze System
Authors: Olson Jacob M , Leppla Christopher A , Bladon John H , Jadhav Shantanu P 
Published: June 2021

AbstractMazes are a fundamental and widespread tool in behavior and systems neuroscience research in rodents. However, their form and inflexibility often restrict potential experimental paradigms that involve multiple or adaptive maze designs. Unique layouts often cost substantial engineering and time investments from trainee scientists. To alleviate these issues, we have developed an automated modular maze system that is flexible and scalable. This system will allow for experiments with multiple track configurations in rapid succession. Additionally, the flexibility can expedite prototyping of behaviors. Finally, the standardized componentry enhances experimental reproducibility and repeatability. This maze system presents advantages over current maze options and can facilitate novel behavior and systems neuroscience research.HighlightsModular maze system enables same-day behavior recordings from multiple flexibly-configured maze environments.High degree of experimental reproducibility and repeatability.Automated lick-detection, liquid reward delivery, and movable barriers.Electronics interface with SpikeGadgets hardware for plug-and-play automated control.Flexibility enables rapid experimental piloting.
Long-COVID following mild SARS CoV-2 infection: characteristic T cell alterations and response to antihistamines
Authors: Glynne Paul , Tahmasebi Natasha , Gant Vanya , Gupta Rajeev 
Published: June 2021

ABSTRACTBackgroundLong-COVID is characterised by the emergence of multiple debilitating symptoms following SARS CoV2 infection. Its aetiology is unclear, and it often follows a mild acute illness. Anecdotal reports of gradual clinical responses to histamine receptor antagonists (HRA) suggest a histamine-dependent mechanism distinct from anaphylaxis. Histamine is a paracrine regulator of T-cells: although T-cell perturbations are reported in acute COVID-19, the T-cell landscape in recovered patients and its relationship to long-COVID remains under-explored.ObjectiveTo survey T-cell populations in patients recovered from mild COVID-19, comparing those with long-COVID and asymptomatic individuals, and to analyse these data in light of symptoms and response to HRA.DesignProspective observational cohort study.SettingSingle-site outpatient clinicParticipants65 (87 to 408 days post mild COVID-19). None had sought treatment for acute COVID-19. 16 recovered uneventfully (asymptomatic group), 49 presented with long-COVID (symptomatic group), of whom 25 received HRA.MeasurementsStructured long-COVID symptom questionnaire; quantification of T-cell subsets using a standard diagnostic assay.ResultsHRA significantly reduced mean symptom burden. T-cell profiles distinguished asymptomatic and long-COVID groups, but did not predict response to HRA. Long-COVID patients had reduced CD4+ and CD8+ effector memory (EM) cells and increased PD-1 expression on central memory (CM) cells. Asymptomatic controls had reduced CD8+ EM cells and increased CD28 expression on CM cells.ConclusionHRA reduce long-COVID symptoms. T-cell perturbations persist for up to 400 days following mild acute COVID-19 irrespective of long-COVID symptoms.LimitationsPreliminary, single health system study.Primary Funding SourcePhilanthropic donations from The Dominvs Group and Sir Peter Wood
Immunogenicity of the ChAdOx1 nCoV-19 and the BBV152 Vaccines in Patients with Autoimmune Rheumatic Diseases
Authors: Shenoy Padmanabha , Ahmed Sakir , Cherian Somy , Paul Aby , Shenoy Veena , Vijayan Anuroopa , Reji Reshma , Thampi Arya , Sageer Babu AS , Mohan Manju 
Published: June 2021

IntroductionThere is limited information on the effectiveness of COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD).Methods136 consecutive patients with rheumatic diseases who never had a diagnosis of COVID-19 previously, and had completed vaccination with either the ChAdOx1 or BBV152 vaccines were recruited. Their IgG antibody titres to the Spike protein were estimated 1 month after the second dose.Results102 patients had AIRD while the 34 had non-AIRD. Lesser patients with AIRD (92/102) had positive antibodies titres than ones with non-AIRD(33/34) [p<0.001]. Amongst patients who received the ChAdOX1 vaccine, the AIRD group had lower antibody titres. Although the AIRD patients receiving BBV152 had similarly lower titres numerically, this did not attain statistical significance probably due to lesser numbers. Comparing the two vaccines, 114(95%) of those who received ChAdOx1 (n=120) and 11(68.7%) of those who received BBV152(n=16) had detectable antibodies [p=0.004]. Antibody titres also were higher in ChAdOx1 recipients when compared to BBV152.To validate the findings, we estimated antibody titres in 30 healthy people each who had received either vaccine. All 30 who had received ChAdOX1 and only 23/30 of those who had received BBV152 had positive antibodies (p=0.011).ConclusionIn this preliminary analysis, patients with AIRD had lower seroconversion rates as well as lower antibody titres as compared to patients with non-AIRD. Also,the humoral immunogenicity of the BBV152 vaccine appears to be less than that of the ChAdOX1 vaccine. Validation using larger numbers and testing of cellular immunity is urgently required.
Estimating body segment parameters from three-dimensional human body scans
Authors: Kudzia Pawel , Jackson Erika , Dumas Genevieve 
Published: June 2021

AbstractBody segment parameters are inputs for a range of applications. The estimation of body segment parameters that are participant-specific is desirable as it requires fewer prior assumptions and can reduce outcome measurement errors. Commonly used methods for estimating participant-specific body segment parameters are either expensive and out of reach (medical imaging), have many underlying assumptions (geometrical modelling) or are based on a specific subset of a population (regression models). Our objective was to develop a participant-specific 3D scanning and body segmentation method that estimates body segment parameters without any assumptions about the geometry of the body, ethnic background, and gender, is low-cost, fast, and can be readily available. Using a Microsoft Kinect camera, we developed a 3D surface scanning protocol that estimated participant-specific body segment parameters. To evaluate our system, we performed repeated 3D scans of 21 healthy participants (10 male, 11 female). We used open-source software to segment each body scan into 16 segments (head, torso, abdomen, pelvis, left and right hand, forearm, upper arm, foot, shank and thigh) and wrote custom software to estimate each segment’s mass, mass moment of inertia in the three principal orthogonal axes relevant to the center of the segment, longitudinal length, and center of mass. We compared our body segment parameter estimates to those obtained using two comparison methods and found that our system was consistent in estimating total body volume between repeated scans (male p=0.1194, female p = 0.2240), estimated total body mass without significant differences when compared to our comparison method and a medical scale (male p=0.8529, female p = 0.6339), and generated consistent and comparable estimates across all of the body segment parameters of interest. The work here outlines an inexpensive 3D surface scanning approach for estimating a range of participant-specific body segment parameters.
A cross-biomes bacterial diversity shed light on ocean-atmosphere microbial transmission
Authors: Lang-Yona Naama , Flores J. Michel , Haviv Rotem , Alberti Adriana , Poulain Julie , Belser Caroline , Trainic Miri , Gat Daniella , Ruscheweyh Hans-Joachim , Wincker Patrick , Sunagawa Shinichi , Rudich Yinon , Koren Ilan , Vardi Assaf 
Published: June 2021

AbstractMicrobes are ubiquitous in the oceans and the atmosphere, playing essential roles in biogeochemical processes. The bio-exchanges between the two environments can provide important insights into microbial distribution and diversity but are still not well understood. We simultaneously surveyed the genomic diversity of airborne and marine bacterial communities across 15 000 kilometers in the Atlantic and Pacific oceans. Higher variability of microbial community composition was observed in the atmosphere than in the ocean surface waters. In addition, a greater similarity was observed between oceans than their overlaying atmosphere, and between atmospheric samples than with the ocean beneath. We additionally detected a higher coverage rate and relative abundance of marine bacteria in the Pacific atmosphere as compared to the Atlantic, while the dominant fraction in the Atlantic atmosphere was annotated as soil-associated bacteria. This study advances our understanding of microbial dispersion in the ocean, the atmosphere, and the exchange between them, as well as their potential impact on microbial composition, ecology, and biogeochemistry.
Expression of extracellular Hsp90 is a molecular signature of T cell activation, providing a means to image and target T Cell activation in autoimmune disease
Authors: Scarneo Scott A. , Smith Aaron P. , Favret Jacob , O’Connell Robert , Pickeral Joy , Yang Kelly W. , Ferrari Guido , Loiselle David R. , Hughes Philip F. , Kulkarni Manjusha M , Gargesha Madhusudhana , Scott Bryan , Roy Debashish , Haynes Barton F. , Kwiek Jesse J. , Haystead Timothy A. J. 
Published: June 2021

AbstractHeat shock protein 90 (Hsp90) maintains cellular proteostasis during stress and has been under investigation as a therapeutic target in cancer for over two decades. We and others have identified an extracellularly expressed form of Hsp90, eHsp90, that previously appeared to be restricted to rapidly proliferating cells exhibiting a metastatic phenotype. Here, we used HS-131, a fluor-tethered eHsp90 inhibitor, to quantify the effect of T cell activation on the expression of eHsp90 in human and mouse T cells. In cell based assays, stimulation of human T cells induced a 20-fold increase in eHsp90 expression at the plasma membrane, suggesting trafficking of eHsp90 is acutely regulated by TCR and inflammatory mediated signaling. Following injection of HS-131 in mouse models of human rheumatoid arthritis and inflammatory bowel disease, we detected localization of the probe at sites of active disease, consistent with immune cell invasion. Moreover, despite rapid hepatobiliary clearance, HS-131 demonstrated efficacy in delaying the onset and progression of disease in the arthritis model. Our results suggest eHsp90 expression at the plasma membrane of T cells is a molecular marker of autoimmune induced activation and potentially a therapeutic target for chronic diseases such as rheumatoid arthritis and inflammatory bowel disease.PerspectiveT cells mediate many maladaptive disease pathologies such as autoimmune disorders. Many immunosuppressants in clinical use act by preventing the activation of T cells. However, this approach can lead to increased rates of opportunistic infection and malignancy. Here, we show for the first time that eHsp90 is upregulated during T cell activation in response to exogenous ligands. Therefore, pharmacological inhibition of eHsp90 may provide a means to target only activated T cells for immunosuppression. Selective targeting of only activated T cells could be efficacious against autoimmune disease without increasing the incidence of undesirable outcomes. Additionally, the presence of eHsp90 on the surface of activated T cells could be diagnostically useful to track the status and progression of autoimmune disease in patients.
Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant
Authors: Thorne Lucy G , Bouhaddou Mehdi , Reuschl Ann-Kathrin , Zuliani-Alvarez Lorena , Polacco Ben , Pelin Adrian , Batra Jyoti , Whelan Matthew V.X. , Ummadi Manisha , Rojc Ajda , Turner Jane , Obernier Kirsten , Braberg Hannes , Soucheray Margaret , Richards Alicia , Chen Kuei-Ho , Harjai Bhavya , Memon Danish , Hosmillo Myra , Hiatt Joseph , Jahun Aminu , Goodfellow Ian G. , Fabius Jacqueline M. , Shokat Kevan , Jura Natalia , Verba Klim , Noursadeghi Mahdad , Beltrao Pedro , Swaney Danielle L. , Garcia-Sastre Adolfo , Jolly Clare , Towers Greg J. , Krogan Nevan J. 
Published: June 2021

AbstractEmergence of SARS-CoV-2 variants, including the globally successful B.1.1.7 lineage, suggests viral adaptations to host selective pressures resulting in more efficient transmission. Although much effort has focused on Spike adaptation for viral entry and adaptive immune escape, B.1.1.7 mutations outside Spike likely contribute to enhance transmission. Here we used unbiased abundance proteomics, phosphoproteomics, mRNA sequencing and viral replication assays to show that B.1.1.7 isolates more effectively suppress host innate immune responses in airway epithelial cells. We found that B.1.1.7 isolates have dramatically increased subgenomic RNA and protein levels of Orf9b and Orf6, both known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation, and Orf9b binding and activity was regulated via phosphorylation. We conclude that B.1.1.7 has evolved beyond the Spike coding region to more effectively antagonise host innate immune responses through upregulation of specific subgenomic RNA synthesis and increased protein expression of key innate immune antagonists. We propose that more effective innate immune antagonism increases the likelihood of successful B.1.1.7 transmission, and may increase in vivo replication and duration of infection.
Microglial CX3CR1I249/M280 variant limits neurogenesis and remyelination in cuprizone-induced multiple sclerosis model
Authors: Mendiola Andrew S. , Church Kaira A. , Cardona Sandra M. , Vanegas Difernando , Garcia Shannon A. , Macklin Wendy , Lira Sergio A. , Ransohoff Richard M. , Kokovay Erzsebet , Lin Chin-Hsing Annie , Cardona Astrid E. 
Published: June 2021

AbstractMicroglia have been implicated in multiple sclerosis (MS) pathogenesis. The fractalkine receptor CX3CR1 regulates the activation of pathogenic microglia in models of MS and the human polymorphic CX3CR1I249/M280 (hCX3CR1I249/M280) variant increases MS disease progression. However, the role of hCX3CR1I249/M280 on microglial activation and central nervous system repair and regenerative mechanisms remain unknown. Therefore, using transgenic mice expressing the hCX3CR1I249/M280 variant, we aimed to determine the contribution of defective CX3CR1 signaling to remyelination and neurogenesis in the cuprizone model of focal demyelination. Here, we report that mice expressing hCX3CR1I249/M280 exhibit marked demyelination and microgliosis follow acute cuprizone treatment. Cuprizone-treated CX3CR1-deficient and fractalkine-deficient mice displayed a comparable phenotype. Nanostring gene expression analysis in demyelinated lesions showed that hCX3CR1I249/M280 upregulates genes associated with inflammation, oxidative stress and disease-associated microglia. In addition, gene expression analysis in the subgranular zone (SGZ) of the hippocampus in hCX3CR1I249/M280 mice was associated with a significant downregulation of gene networks linked to neurogenesis following acute demyelination. Confocal microscopy showed that hCX3CR1I249/M280 or loss of CX3CR1 signaling inhibits the generation of progeny from the neurogenic niche, including cells involved in myelin repair. These results provide evidence for the pathogenic capacity of hCX3CR1I249/M280 on microglia dysfunction and therapeutic targeting of CX3CR1 to promote CNS repair in MS.
Quantitative examination of five stochastic cell-cycle and cell-size control models forEscherichia coliandBacillus subtilis
Authors: Treut Guillaume Le , Si Fangwei , Li Dongyang , Jun Suckjoon 
Published: June 2021

AbstractWe examine five quantitative models of the cell-cycle and cell-size control inEscherichia coliandBacillus subtilisthat have been proposed over the last decade to explain single-cell experimental data generated with high-throughput methods. After presenting the statistical properties of these models, we test their predictions against experimental data. Based on simple calculations of the defining correlations in each model, we first dismiss the stochastic Helmstetter-Cooper model and the Initiation Adder model, and show that both the Replication Double Adder and the Independent Double Adder model are more consistent with the data than the other models. We then apply a recently proposed statistical analysis method and obtain that the Independent Double Adder model is the most likely model of the cell cycle. By showing that the Replication Double Adder model is fundamentally inconsistent with size convergence by the adder principle, we conclude that the Independent Double Adder model is most consistent with the data and the biology of bacterial cell-cycle and cell-size control. Mechanistically, the Independent Adder Model is equivalent to two biological principles: (i) balanced biosynthesis of the cell-cycle proteins, and (ii) their accumulation to a respective threshold number to trigger initiation and division.
5-methylcytosine modification byPlasmodiumNSUN2 stabilizes mRNA and mediates the development of gametocytes
Authors: Liu Meng , Guo Gangqiang , Qian Pengge , Mu Jianbing , Lu Binbin , He Xiaoqin , Shang Xiaomin , Yang Guang , Shen Shijun , Liu Wenju , Wang Liping , Gu Liang , Mu Quankai , Yu Xinyu , Zhao Yuemeng , Culleton Richard , Cao Jun , Jiang Lubin , Wellems Thomas E. , Yuan Jing , Jiang Cizhong , Zhang Qingfeng 
Published: June 2021

Abstract5-methylcytosine (m5C) is an important epitranscriptomic modification involved in mRNA stability and translation efficiency in various biological processes. However, it remains unclear if m5C modification contributes to the dynamic regulation of the transcriptome during the developmental cycles ofPlasmodiumparasites. Here, we characterize the landscape of m5C mRNA modifications at single nucleotide resolution in the asexual replication stages and gametocyte sexual stages of rodent (P. yoelii) and human (P. falciparum) malaria parasites. While different representations of m5C-modified mRNAs are associated with the different stages, the abundance of the m5C marker is strikingly enhanced in the transcriptomes of gametocytes. Our results show that m5C modifications confer stability to thePlasmodiumtranscripts and that aPlasmodiumortholog of NSUN2 is a major mRNA m5C methyltransferase in malaria parasites. Upon knock-out ofP. yoelii nsun2(pynsun2), marked reductions of m5C modification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impaired gametocyte production in rodent and human malaria parasites. Restoration of thensun2gene in the knock-out parasites rescued the gametocyte production phenotype as well as m5C modification of the gametocytogenesis-associated transcripts. Together with the mRNA m5C profiles for two species ofPlasmodium, our findings demonstrate a major role for NSUN2-mediated m5C modifications in mRNA transcript stability and sexual differentiation in malaria parasites.SignificanceModifications of RNA including methylations of cytosine (m5C) and adenosine (m6A) have important roles in RNA metabolism, cellular responses to stress, and biological processes of differentiation and development. Here, we report on the profiles of m5C mRNA modifications in malaria parasites that infect rodents (Plasmodium yoelii) and humans (Plasmodium falciparum). These parasites have genes that encode homologs of human and plant NSUN2 methyltransferases (m5C “writers”). We show that one of these homologs, termed PyNSUN2, stabilizes mRNA transcripts inP. yoeliiand mediates m5C-associated development of the parasite sexual stages (gametocytes). Further research on m5C and other epitranscriptomic modifications may yield new insights into molecular pathways of gametocyte development and mosquito infectivity that can be exploited to interrupt malaria transmission.
Number of Synergies Impacts Sensitivity of Gait to Weakness and Contracture
Authors: Kuska Elijah C. , Mehrabi Naser , Schwartz Michael H. , Steele Katherine M. 
Published: June 2021

AbstractMuscle activity during gait can be described by a small set of synergies, weighted groups of muscles, that are often theorized to reflect underlying neural control. For people with neurologic injuries, like in cerebral palsy or stroke, even fewer (e.g., < 5) synergies are required to explain muscle activity during gait. This reduction in synergies is thought to reflect simplified control strategies and is associated with impairment severity and treatment outcomes. Individuals with neurologic injuries also develop secondary musculoskeletal impairments, like weakness or contracture, that can also impact gait. The combined impacts of simplified control and musculoskeletal impairments on gait remains unclear. In this study, we use a musculoskeletal model constrained to synergies to simulate unimpaired gait. We vary the number of synergies (3-5), while simulating muscle weakness and contracture to examine how altered control impacts sensitivity to muscle weakness and contracture. Our results highlight that reducing the number of synergies increases sensitivity to weakness and contracture. For example, simulations using five-synergy control tolerated 40% and 51% more knee extensor weakness than those using four- and three-synergy control, respectively. Furthermore, the model became increasingly sensitive to contracture and proximal muscle weakness, such as hamstring and hip flexor weakness, when constrained to four- and three-synergy control. However, the model’s sensitivity to weakness of the plantarflexors and smaller bi-articular muscles was not affected by the number of synergies. These findings provide insight into the interactions between altered control and musculoskeletal impairments, emphasizing the importance of incorporating both in future simulation studies.