bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of genetic and environmental factors for body fat mass control: observational study for lifestyle modification and genotyping
Authors: Kang Joon Ho , Kim Heewon , Kim Jinki , Seo Jong-Hwa , Cha Soyeon , Oh Hyunjung , Kim Kyunga , Park Seong-Jin , Kim Eunbin , Kong Sunga , Lee Jae-Hak , Bae Joon Seol , Won Hong-Hee , Joung Je-Gun , Yang Yoon Jung , Kim Jinho , Park Woong-Yang 
Published: June 2021

AbstractPrevious studies suggested that genetic, environmental factors and their interactions could affect body fat mass (BFM). However, studies describing these effects were performed at a single time point in a population. In this study, we investigated the interaction between genetic and environmental factors in affecting BFM and implicate the healthcare utilization of lifestyle modifications from a personalized and genomic perspective. We examined how nutritional intake or physical activity changes in the individuals affect BFM concerning the genetic composition. We conducted an observational study including 259 adult participants with single nucleotide polymorphism (SNP) genotyping and longitudinal lifestyle monitoring, including food consumption and physical activities, by following lifestyle modification guidance. The participants’ lifelog data on exercise and diet were collected through a wearable device for 3 months. Moreover, we measured anthropometric and serologic markers to monitor their potential changes through lifestyle modification. We examined the influence of genetic composition on body fat reduction induced by lifestyle changes using genetic risk scores (GRSs) of three phenotypes: GRS-carbohydrate (GRS-C), GRS-fat (GRS-F), and GRS-exercise (GRS-E). Our results showed that lifestyle modifications affected BFM more significantly in the high GRS class compared to the low GRS class, indicating the role of genetic factors affecting the efficiency of the lifestyle modification-induced BFM changes. Interestingly, the influence of exercise modification in the low GRS class with active lifestyle change was lower than that in the high GRS class with inactive lifestyle change (P = 0.022), suggesting the implication of genetic factors for efficient body fat control.
Electro-steric opening of the clc-2 chloride channel gate
Authors: De Jesús-Pérez José J. , Méndez-Maldonado G. Arlette , López-Romero Ana E. , Esparza-Jasso David , González-Hernández Irma L. , De la Rosa Víctor , Gastélum-Garibaldi Roberto , Sánchez-Rodríguez Jorge E. , Arreola Jorge 
Published: June 2021

AbstractThe widely expressed two-pore homodimeric inward rectifier CLC-2 chloride channel regulates transepithelial chloride transport, extracellular chloride homeostasis, and neuronal excitability. Each pore is independently gated at hyperpolarized voltages by a conserved pore glutamate. Presumably, exiting chloride ions push glutamate outwardly while external protonation stabilizes it. To understand the mechanism of mouse CLC-2 opening we used homology modelling-guided structure–function analysis. Structural modelling suggests that glutamate E213 interacts with tyrosine Y561 to close a pore. Accordingly, Y561A and E213D mutants are activated at less hyperpolarized voltages, re-opened at depolarized voltages, and fast and common gating components are reduced. The double mutant cycle analysis showed that E213 and Y561 are energetically coupled to alter CLC-2 gating. In agreement, the anomalous mole fraction behaviour of the voltage dependence, measured by the voltage to induce half-open probability, was strongly altered in these mutants. Finally, cytosolic acidification or high extracellular chloride concentration, conditions that have little or no effect on WT CLC-2, induced reopening of Y561 mutants at positive voltages presumably by the inward opening of E213. We concluded that the CLC-2 gate is formed by Y561-E213 and that outward permeant anions open the gate by electrostatic and steric interactions.
Association of glomerular filtration rate slope with timely creation of vascular access in incident hemodialysis
Authors: Lim Lee-Moay , Lin Ming-Yen , Hwang Shang-Jyh , Chen Hung-Chun , Chiu Yi-Wen 
Published: June 2021

AbstractThe factors associated with the timely creation of distal vascular access for hemodialysis initiation are unclear. We aimed to explore the association between the slope of estimated glomerular filtration rate (eGFR) and the successful usage of vascular access upon hemodialysis initiation. This single center retrospective cohort study enrolled chronic kidney disease patients who undertook a multidisciplinary care program from 2003 to 2016. Using eGFR slope as predictor, we evaluated the vascular access created timely upon hemodialysis initiation. Among the 987 patients, vascular access was created at a median eGFR of 5.8 min/ml/1.73 m2, with a median duration of 3.1 months before hemodialysis. The proportions of vascular access created timely, created not timely (vascular access immature), and not created were 68.5%, 8.8%, and 22.7%, respectively. There was a significant negative association of eGFR upon vascular access creation with eGFR slope (r = − 0.182, P < 0.001). The fastest eGFR slope patients (the first quartile or < − 10 min/ml/1.73 m2/year) had the lowest percentage of vascular access created timely. In the multivariable logistic regression analysis, only higher eGFR upon vascular access creation (P = 0.001) and eGFR slope (P = 0.009) were significantly associated with vascular access created timely. The adjusted odds ratios of each quartile of eGFR slopes for vascular access created timely were 0.46 (95% confidence interval 0.27–0.86), 1.30 (0.62, 2.72), 1.00 (reference), and 0.95 (0.48–1.87), respectively. eGFR slope is associated with the timely creation of vascular access for the initiation of hemodialysis in a reverse-J-shaped pattern and may help determine the time of vascular access creation.
Ischemic heart injury leads to HIF1-dependent differential splicing of CaMK2γ
Authors: Williams Allison Lesher , Walton Chad B. , Pinell Blake , Khadka Vedbar S. , Dunn Brandyn , Lee Katie , Anagaran M. C. Therese , Avelar Abigail , Shohet Ralph V. 
Published: June 2021

AbstractIschemic heart disease is a leading cause of heart failure and hypoxia inducible factor 1 (HIF1) is a key transcription factor in the response to hypoxic injury. Our lab has developed a mouse model in which a mutated, oxygen-stable form of HIF1α (HIF-PPN) can be inducibly expressed in cardiomyocytes. We observed rapid cardiac dilation and loss of contractility in these mice due to lower expression of excitation–contraction coupling genes and reduced calcium flux. As alternative splicing plays an underappreciated role in transcriptional regulation, we used RNA sequencing to search for splicing changes in calcium-handling genes of HIF-PPN hearts and compared them to previous sequencing data from a model of myocardial infarction (MI) to select for transcripts that are modified in a pathological setting. We found overlap between genes differentially expressed in HIF-PPN and post-MI mice (54/131 genes upregulated in HIF-PPN hearts at 1 day and/or 3 days post-MI, and 45/78 downregulated), as well as changes in alternative splicing. Interestingly, calcium/calmodulin dependent protein kinase II, gamma (CAMK2G) was alternatively spliced in both settings, with variant 1 (v1) substantially decreased compared to variants 2 (v2) and 3 (v3). These findings were also replicated in vitro when cells were transfected with HIF-PPN or exposed to hypoxia. Further analysis of CAMK2γ protein abundance revealed only v1 was detectable and substantially decreased up to 7 days post-MI. Rbfox1, a splicing factor of CAMK2G, was also decreased in HIF-PPN and post-MI hearts. Subcellular fractionation showed CAMK2γ v1 was found in the nuclear and cytoplasmic fractions, and abundance decreased in both fractions post-MI. Chromatin immunoprecipitation analysis of HIF1 in post-MI hearts also demonstrated direct HIF1 binding to CAMK2G. CaMK2 is a key transducer of calcium signals in both physiological and pathological settings. The predominantly expressed isoform in the heart, CaMK2δ, has been extensively studied in cardiac injury, but the specific role of CaMK2γ is not well defined. Our data suggest that loss of CaMK2γ after MI is HIF1-dependent and may play an important role in the heart’s calcium signaling and transcriptional response to hypoxia.
Automated parasitological diagnosis in clinical microbiology laboratories
Authors: Fernández-Rivas Gema , Rivaya Belén , Romaní Nona , Wang Jun Hao Wang , Alcaide Mireya , Matas Lurdes 
Published: June 2021

AbstractAlthough there is a low prevalence of parasitological infections in Europe, the diagnosis of intestinal parasites is still difficult and laborious for microbiology laboratories. Currently, antigen detection assays and molecular biology allow a more accurate diagnosis, but these techniques have limitations as they cannot detect all the possible parasites present in the samples. The objective of the study was to evaluate the accuracy and the usefulness of automated microscopy SediMAX2 (77 Elektronika, Budapest, Hungary) in the detection of parasitic infections from feces. A total of 197 formol-fixed stool samples were processed in parallel by wet mount examination and by SediMAX2. Sensitivities, specificities and predictive values were analyzed, reaching a sensitivity of 89.51% and a specificity of 98.15% and a very good positive predictive value (99.22%). SediMAX2 is a good tool for a reliable diagnosis of intestinal parasitic infections. The rapid processing and the flexibilty of storage of images analyzed make its incorporation into the day to day laboratory routine recommendable.
Crayfish hemocytes develop along the granular cell lineage
Authors: Li Fang , Zheng Zaichao , Li Hongyu , Fu Rongrong , Xu Limei , Yang Feng 
Published: June 2021

AbstractDespite the central role of hemocytes in crustacean immunity, the process of hemocyte differentiation and maturation remains unclear. In some decapods, it has been proposed that the two main types of hemocytes, granular cells (GCs) and semigranular cells (SGCs), differentiate along separate lineages. However, our current findings challenge this model. By tracking newly produced hemocytes and transplanted cells, we demonstrate that almost all the circulating hemocytes of crayfish belong to the GC lineage. SGCs and GCs may represent hemocytes of different developmental stages rather than two types of fully differentiated cells. Hemocyte precursors produced by progenitor cells differentiate in the hematopoietic tissue (HPT) for 3 ~ 4 days. Immature hemocytes are released from HPT in the form of SGCs and take 1 ~ 3 months to mature in the circulation. GCs represent the terminal stage of development. They can survive for as long as 2 months. The changes in the expression pattern of marker genes during GC differentiation support our conclusions. Further analysis of hemocyte phagocytosis indicates the existence of functionally different subpopulations. These findings may reshape our understanding of crustacean hematopoiesis and may lead to reconsideration of the roles and relationship of circulating hemocytes.
Gelsolin and dCryAB act downstream of muscle identity genes and contribute to preventing muscle splitting and branching in Drosophila
Authors: Bertin Benjamin , Renaud Yoan , Jagla Teresa , Lavergne Guillaume , Dondi Cristiana , Da Ponte Jean-Philippe , Junion Guillaume , Jagla Krzysztof 
Published: June 2021

AbstractA combinatorial code of identity transcription factors (iTFs) specifies the diversity of muscle types in Drosophila. We previously showed that two iTFs, Lms and Ap, play critical role in the identity of a subset of larval body wall muscles, the lateral transverse (LT) muscles. Intriguingly, a small portion of ap and lms mutants displays an increased number of LT muscles, a phenotype that recalls pathological split muscle fibers in human. However, genes acting downstream of Ap and Lms to prevent these aberrant muscle feature are not known. Here, we applied a cell type specific translational profiling (TRAP) to identify gene expression signatures underlying identity of muscle subsets including the LT muscles. We found that Gelsolin (Gel) and dCryAB, both encoding actin-interacting proteins, displayed LT muscle prevailing expression positively regulated by, the LT iTFs. Loss of dCryAB function resulted in LTs with irregular shape and occasional branched ends also observed in ap and lms mutant contexts. In contrast, enlarged and then split LTs with a greater number of myonuclei formed in Gel mutants while Gel gain of function resulted in unfused myoblasts, collectively indicating that Gel regulates LTs size and prevents splitting by limiting myoblast fusion. Thus, dCryAB and Gel act downstream of Lms and Ap and contribute to preventing LT muscle branching and splitting. Our findings offer first clues to still unknown mechanisms of pathological muscle splitting commonly detected in human dystrophic muscles and causing muscle weakness.
Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells
Authors: Follain Gautier , Osmani Naël , Gensbittel Valentin , Asokan Nandini , Larnicol Annabel , Mercier Luc , Garcia-Leon Maria Jesus , Busnelli Ignacio , Pichot Angelique , Paul Nicodème , Carapito Raphaël , Bahram Seiamak , Lefebvre Olivier , Goetz Jacky G. 
Published: June 2021

AbstractTumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified pro-metastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis of endothelial cells revealed that blood flow enhanced VEGFR signaling, among others. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented upon specific inhibition of VEGFR tyrosine kinase and subsequent signaling. Inhibitory targeting of VEGFRs reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of VEGFR-dependent endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression.
Computational biomechanical modelling of the rabbit cranium during mastication
Authors: Watson Peter J. , Sharp Alana C. , Choudhary Tarun , Fagan Michael J. , Dutel Hugo , Evans Susan E. , Gröning Flora 
Published: June 2021

AbstractAlthough a functional relationship between bone structure and mastication has been shown in some regions of the rabbit skull, the biomechanics of the whole cranium during mastication have yet to be fully explored. In terms of cranial biomechanics, the rabbit is a particularly interesting species due to its uniquely fenestrated rostrum, the mechanical function of which is debated. In addition, the rabbit processes food through incisor and molar biting within a single bite cycle, and the potential influence of these bite modes on skull biomechanics remains unknown. This study combined the in silico methods of multi-body dynamics and finite element analysis to compute musculoskeletal forces associated with a range of incisor and molar biting, and to predict the associated strains. The results show that the majority of the cranium, including the fenestrated rostrum, transmits masticatory strains. The peak strains generated over all bites were found to be attributed to both incisor and molar biting. This could be a consequence of a skull shape adapted to promote an even strain distribution for a combination of infrequent incisor bites and cyclic molar bites. However, some regions, such as the supraorbital process, experienced low peak strain for all masticatory loads considered, suggesting such regions are not designed to resist masticatory forces.
Coordinated gas release among the physostomous fish sprat (Sprattus sprattus)
Authors: Kaartvedt Stein , Ugland Karl I. , Heuschele Jan , Solberg Ingrid 
Published: June 2021

AbstractPrevious experimental studies suggest that the production of sound associated with expelling gas from an open swimbladder may play a role in communication. This would suggest non-random gas release. We used deployed echosounders to study patterns of gas release among a fjord population of sprat (Sprattus sprattus). The echosounder records concurrently revealed individual fish and their release of gas. The gas release primarily occurred at night, partly following recurrent temporal patterns, but also varying between nights. In testing for non-randomness, we formulated a data-driven simulation approach. Non-random gas release scaled with the length of the analyzed time intervals from 1 min to 6 h, and above 30 min the release events in more than 50% of the intervals were significantly connected.
Comparison of the on-line effects of different motor simulation conditions on corticospinal excitability in healthy participants
Authors: Pfenninger C. , Grosprêtre S. , Remontet A. , Lapole T. 
Published: June 2021

AbstractIn healthy participants, corticospinal excitability is known to increase during motor simulations such as motor imagery (MI), action observation (AO) and mirror therapy (MT), suggesting their interest to promote plasticity in neurorehabilitation. Further comparing these methods and investigating their combination may potentially provide clues to optimize their use in patients. To this end, we compared in 18 healthy participants abductor pollicis brevis (APB) corticospinal excitability during MI, AO or MT, as well as MI combined with either AO or MT. In each condition, 15 motor-evoked potentials (MEPs) and three maximal M-wave were elicited in the right APB. Compared to the control condition, mean normalized MEP amplitude (i.e. MEP/M) increased during MI (P = .003), MT (P < .001) and MT + MI (P < .001), without any difference between the three conditions. No MEP modulation was evidenced during AO or AO + MI. Because MI provided no additional influence when combined with AO or MT, our results may suggest that, in healthy subjects, visual feedback and unilateral movement with a mirror may provide the greatest effects among all the tested motor simulations.
Diurnal rhythms of urine volume and electrolyte excretion in healthy young men under differing intensities of daytime light exposure
Authors: Nakamoto Isuzu , Uiji Sayaka , Okata Rin , Endo Hisayoshi , Tohyama Sena , Nitta Rina , Hashimoto Saya , Matsushima Yoshiko , Wakimoto Junko , Hashimoto Seiji , Nishiyama Yukiko , Kanikowska Dominika , Negoro Hiromitsu , Wakamura Tomoko 
Published: June 2021

AbstractIn humans, most renal functions, including urine volume and electrolyte excretions, have a circadian rhythm. Light is a strong circadian entrainment factor and daytime-light exposure is known to affect the circadian rhythm of rectal temperature (RT). The effects of daytime-light exposure on the diurnal rhythm of urinary excretion have yet to be clarified. The aim of this study was to clarify whether and how daytime exposure to bright-light affects urinary excretions. Twenty-one healthy men (21–27 years old) participated in a 4-day study involving daytime (08:00–18:00 h) exposure to two light conditions, Dim (< 50 lx) and Bright (~ 2500 lx), in a random order. During the experiment, RT was measured continuously. Urine samples were collected every 3 ~ 4 h. Compared to the Dim condition, under the Bright condition, the RT nadir time was 45 min earlier (p = 0.017) and sodium (Na), chloride (Cl), and uric acid (UA) excretion and urine volumes were greater (allp < 0.001), from 11:00 h to 13:00 h without a difference in total daily urine volume. The present results suggest that daytime bright light exposure can induce a phase shift advance in urine volume and urinary Na, Cl, and UA excretion rhythms.
A new non-classical fold of varroa odorant-binding proteins reveals a wide open internal cavity
Authors: Amigues Beatrice , Zhu Jiao , Gaubert Anais , Arena Simona , Renzone Giovanni , Leone Philippe , Fischer Isabella Maria , Paulsen Harald , Knoll Wolfgang , Scaloni Andrea , Roussel Alain , Cambillau Christian , Pelosi Paolo 
Published: June 2021

AbstractOdorant-binding proteins (OBPs), as they occur in insects, form a distinct class of proteins that apparently has no closely related representatives in other animals. However, ticks, mites, spiders and millipedes contain genes encoding proteins with sequence similarity to insect OBPs. In this work, we have explored the structure and function of such non-insect OBPs in the mite Varroa destructor, a major pest of honey bee. Varroa OBPs present six cysteines paired into three disulphide bridges, but with positions in the sequence and connections different from those of their insect counterparts. VdesOBP1 structure was determined in two closely related crystal forms and appears to be a monomer. Its structure assembles five α-helices linked by three disulphide bridges, one of them exhibiting a different connection as compared to their insect counterparts. Comparison with classical OBPs reveals that the second of the six α-helices is lacking in VdesOBP1. Ligand-binding experiments revealed molecules able to bind only specific OBPs with a moderate affinity, suggesting that either optimal ligands have still to be identified, or post-translational modifications present in the native proteins may be essential for modulating binding activity, or else these OBPs might represent a failed attempt in evolution and are not used by the mites.
NetCleave: an open-source algorithm for predicting C-terminal antigen processing for MHC-I and MHC-II
Authors: Amengual-Rigo Pep , Guallar Victor 
Published: June 2021

AbstractAntigens presented on the cell surface have been subjected to multiple biological processes. Among them, C-terminal antigen processing constitutes one of the main bottlenecks of the peptide presentation pathways, as it delimits the peptidome that will be subjected downstream. Here, we present NetCleave, an open-source and retrainable algorithm for the prediction of the C-terminal antigen processing for both MHC-I and MHC-II pathways. NetCleave architecture consists of a neural network trained on 46 different physicochemical descriptors of the cleavage site amino acids. Our results demonstrate that prediction of C-terminal antigen processing achieves high accuracy on MHC-I (AUC of 0.91), while it remains challenging for MHC-II (AUC of 0.66). Moreover, we evaluated the performance of NetCleave and other prediction tools for the evaluation of four independent immunogenicity datasets (H2-Db, H2-Kb, HLA-A*02:01 and HLA-B:07:02). Overall, we demonstrate that NetCleave stands out as one of the best algorithms for the prediction of C-terminal processing, and we provide one of the first evidence that C-terminal processing predictions may help in the discovery of immunogenic peptides.