bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Improvised Pulmonary Telerehabilitation Program for Postacute COVID-19 Patients Would Be Feasible and Acceptable in a Low-Resource Setting
Authors: Bickton Fanuel Meckson , Chisati Enock , Rylance Jamie , Morton Ben 
Published: January 2021

Abstract
Postacute COVID-19 patients are at risk of long-term functional impairment, and the rehabilitation community is calling for action preparing for a “tsunami of rehabilitation needs” in this patient population. In the absence of standard guidelines and local evidence, a 3-wk pulmonary telerehabilitation program was successfully delivered to a postacute severe COVID-19 patient in Malawi. The patient experienced persistent dyspnea and fatigue, with a remarkable impact on his health status. On the final assessment, all his respiratory severity scores had fallen by more than their thresholds for clinical significance. He reported no continued or new complaints, was walking longer distances, had returned to work, and was discharged from follow-up. Our case shows that an improvised pulmonary telerehabilitation program for postacute COVID-19 patients could be feasible and acceptable in a low-resource setting. Benefits include reducing risk of transmission and use of personal protective equipment.
Mechanical Stretch Inhibition Sensitizes Proprioceptors to Compressive Stresses
Authors: Das Ravi , Lin Li-Chun , Català-Castro Frederic , Malaiwong Nawaphat , Sanfeliu Neus , Porta-de-la-Riva Montserrat , Pidde Aleksandra , Krieg Michael 
Published: January 2021

AbstractA repetitive gait cycle is an archetypical component within the behavioural repertoire of many if not all animals including humans. It originates from mechanical feedback within proprioceptors to adjust the motorprogram during locomotion and thus leads to a periodic orbit in a low dimensional space. Here, we investigate the mechanics, molecules and neurons responsible for proprioception inCaenorhabditis (C.) elegansto gain insight into how mechanosensation shapes the orbital trajectory to a well-defined limit cycle. We used genome editing, force spectroscopy and multiscale modeling and found that alternating tension and compression with the spectrin network of a single proprioceptor encodes body posture and informs TRP-4/NOMPC and TWK-16/TREK2 homologs of mechanosensitive ion channels during locomotion. In contrast to a widely accepted model of proprioceptive ‘stretch’ reception, we found that proprioceptors activated under compressive stressesin vivoandin vitro, and speculate that this property is conserved across function and species.
A low-cost mouse cage warming system provides improved intra-ischemic and post-ischemic body temperature control – application for reducing variability in experimental stroke studies
Authors: Hong Sung-Ha , Hong Jeong-Ho , Lahey Matthew T. , Zhu Liang , Stephenson Jessica M. , Marrelli Sean P. 
Published: January 2021

AbstractExperimental guidelines have been proposed to improve the rigor and reproducibility of experimental stroke studies in rodents. As brain temperature is a strong determinant of ischemic injury, tight management of brain or body temperature (Tcore) during the experimental protocol is highly recommended. However, little guidance is provided regarding how or for how long temperature support should be provided. We compared a commonly used heat support method (cage on heating pad) with a low-cost custom built warm ambient air cage (WAAC) system. Both heat support systems were evaluated for the middle cerebral artery occlusion (MCAo) model in mice. The WAAC system provided improved temperature control (more normothermic Tcore and less Tcore variation) during the intra-ischemic period (60 min) and post-ischemic period (3 hrs). Neurologic deficit score showed significantly less variance at post-stroke day 1 (PSD1) in WAAC system mice. Mean infarct volume was not statistically different by heat support system, however, standard deviation was 54% lower in the WAAC system group. In summary, we provide a simple low-cost heat support system that provides superior Tcore management in mice during the intra-ischemic and post-ischemic periods, which results in reduced variability of experimental outcomes.HighlightsWe describe the fabrication of a low-cost mouse cage warming system (warmed ambient air cage; WAAC system) that can be assembled and applied in any stroke laboratory.The WAAC system provides more precise control of post-stroke mouse body temperature compared with traditional heating pad warming system.The more precise control of post-stroke core temperature reduces variability in some experimental measures in more severely injured mice.
Methylsulfonylmethane and sesame seed oil improve hyperlipidemia and polyunsaturated fatty acid metabolism in thedb/dbmouse
Authors: Fili Cameron V. , Lin Ling , Chapman Jonathan , Hamilton David , Yates Charles R. 
Published: January 2021

AbstractBackgroundAn estimated 463 million people worldwide suffer from diabetes, and that number is projected to rise significantly to 700 million by 2045. One of the hallmarks of type 2 diabetes and metabolic syndrome is alterations in the lipid profile and polyunsaturated fatty acid metabolism.ObjectiveThe objective of this study was to identify lipid alterations in leptin receptor deficientdb/dbmice, a type 2 diabetes model, to establish a baseline biological signature for the evaluation of natural products with purported lipid-altering activity.MethodsSix-week old maledb/dbmice (n = 10/group) were randomized to the following groups: 1) diabetic control with no treatment, 2) methylsulfonylmethane (MSM) treatment (3.81 ± 0.33 g/kg), 3) sesame seed oil (SSO) treatment (23.54 ± 2.91 mg/kg), and 4) MSM and SSO combination treatment, receiving the same dosages of MSM and SSO as the single treatment groups. Eight-week old male C57BL6/J mice (n=10) were used as a non-diabetic control group.ResultsSerum triglycerides and total cholesterol were significantly increased in thedb/db model compared to nondiabetic control, mimicking diabetes in people. High-density lipoprotein (HDL) was significantly increased in alldb/dbtreatment groups, with the most significant effect in the MSM and SSO combination group, with a corresponding decrease in non-HDL cholesterol. Serum total polyunsaturated fatty acid (PUFA) levels were significantly reduced in diabetic mice compared with control mice. In contrast, treatment with SSO alone reversed this effect such that fed mice exhibited serum PUFA levels comparable to control mice.ConclusionsTreatment ofdb/dbmice with MSM and SSO improved commonly measured clinical parameters in serum lipid panels. The combination of MSM and SSO treatment’s effects on HDL and non-HDL cholesterol and fatty acid metabolism could lead to improved clinical outcomes in diabetics, such as reduced incidence of atherosclerosis and hepatic steatosis.
Bovine neutrophils release extracellular traps and cooperate with macrophages inMycobacterium aviumsubsp.paratuberculosisclearancein vitro
Authors: Ladero-Auñon I , Molina E , Holder A , Kolakowski J , Harris H , Urkitza A , Anguita J , Werling D , Elguezabal N 
Published: January 2021

AbstractMycobacterium aviumsubsp.paratuberculosis(Map) is the underlying pathogen causing bovine paratuberculosis (PTB), an enteric granulomatous disease that mainly affects ruminants and for which an effective treatment is needed. Macrophages are the primary target cells for Map, which survives and replicates intracellularly by inhibiting phagosome maturation. Neutrophils are present at disease sites during the early stages of the infection, but seem to be absent in the late stage, in contrast to healthy tissue. Although neutrophil activity has been reported to be impaired following Map infection, their role in PTB pathogenesis has not been fully defined. Neutrophils are capable of releasing extracellular traps consisting of extruded DNA and proteins that immobilize and kill microorganisms, but this mechanism has not been evaluated against Map. Our main objective was to study the interaction of neutrophils with macrophages during anin vitromycobacterial infection. For this purpose, neutrophils and macrophages from the same animal were cultured alone or together in the presence of Map orMycobacterium bovisBacillus-Calmette-Guérin (BCG). Extracellular trap release, mycobacteria killing as well as IL-1β and IL-8 release were assessed. Neutrophils released extracellular traps against mycobacteria when cultured alone and in the presence of macrophages without direct cell contact, but resulted inhibited in direct contact. Macrophages were extremely efficient at killing BCG, but ineffective at killing Map. In contrast, neutrophils showed similar killing rates for both mycobacteria. Co-cultures infected with Map showed the expected killing effect of combining both cell types, whereas co-cultures infected with BCG showed a potentiated killing effect beyond the expected one, indicating a potential synergistic cooperation. In both cases, IL-1β and IL-8 levels were lower in co-cultures, suggestive of a reduced inflammatory reaction. These data indicate that cooperation of both cell types can be beneficial in terms of decreasing the inflammatory reaction while the effective elimination of Map can be compromised. These results suggest that neutrophils are effective at Map killing and can exert protective mechanisms against Map that seem to fail during PTB disease after the arrival of macrophages at the infection site.
Inference of emergent spatio-temporal processes from single-cell sequencing reveals feedback betweende novoDNA methylation and chromatin condensates
Authors: Olmeda Fabrizio , Lohoff Tim , Clark Stephen J , Benson Laura , Krüger Felix , Reik Wolf , Rulands Steffen 
Published: January 2021

SummaryRecent breakthroughs in single-cell genomics allow probing molecular states of cells with unprecedented detail along the sequence of the DNA. Biological function relies, however, on emergent processes in the three-dimensional space of the nucleus, such as droplet formation through phase separation. Here, we use single-cell multi-omics sequencing to develop a theoretical framework to rigorously map epigenome profiling along the DNA sequence onto a description of the emergent spatial dynamics in the nucleus. Drawing on scNMT-seq multi-omics sequencingin vitroandin vivowe exemplify our approach in the context of exit from pluripotency and globalde novomethylation of the genome. We show how DNA methylation patterns of the embryonic genome are established through the interplay between spatially correlated DNA methylation and topological changes to the DNA. This feedback leads to the predicted formation of 30-40nm sized condensates of methylated DNA and determines genome-scale DNA methylation rates. We verify these findings with orthogonal single cell multi-omics data that combine the methylome with HiC measurements. Notably, this scale of chromatin organization has recently been described by super-resolution microscopy. Using this framework, we identify local methylation correlations in gene bodies that precede transcriptional changes at the exit from pluripotency. Our work provides a general framework of how mechanistic insights into emergent processes underlying cell fate decisions can be gained by the combination of single-cell multi-omics and methods from theoretical physics that have not been applied in the context of genomics before.HighlightsWe develop methodology to infer collective spatio-temporal processes in the physical space of the nucleus from single-cell methylome sequencing experiments.We show that DNA methylation relies on a feedback betweende novomethylation and nanoscale changes in DNA topology, leading to the formation of methylation condensates.Chromatin condensates at this scale have recently been described by high-resolution microscopy but have remained without mechanistic explanation.Using this framework, we identify changes in the distribution of DNA methylation marks in gene bodies that precede gene silencing at the exit from pluripotency.
Fabrication of silver doped nano hydroxyapatite-carrageenan hydrogels for articular cartilage applications
Authors: Swain Subhasmita , Kwon Tae Yub , Rautray Tapash R. 
Published: January 2021

AbstractIt can be found from the results that nano hydroxyapatite- silver -3.0 wt% carageenan (nHA-Ag-CG3.0) improved the mechanical properties of the as-formed hydrogel scaffold after incorporation of higher CG concentration. The Young’s modulus of hydroxyapatite- silver - 1.5wt% carageenan (nHA-Ag-CG1.5) was found to be 0.36 ± 0.07 MPa that increased in case of nHA-Ag-CG3.0 demonstrating better interfacial compatibility of their matrix with respect to the reinforcement. This increase in reinforcement concentration resulted in higher stiffness that dissipated energy. The higher swelling ratio is envisaged to induce better cell adhesion and proliferation. The biodegradability test was performed in phosphate buffered saline at body temperature for 3 weeks. The biodegradability rate of nHA-Ag-CG1.5 was found to be equivalent to nHA-Ag-CG3.0 hydrogels at day 7 while it increased faster in nHA-Ag-CG3.0 on days 14 and 21 that may be ascribed to the possible interaction of nHA and Ag with their CG matrix. The bacterial cell viability ofStaphylococcus aureus(S. aureus)was performed after 10 h, 20 h and 30 h of culture. The nHA-Ag-CG1.5 exhibited restrained growth ofS. aureusas compared to nHA-Ag-CG3.0 and these results were validated by CLSM analysis. Hence, nHA-Ag-CG3.0 may be considered to have more cytocompatibility than nHA-Ag-CG 1.5.
Zebrafish Polycomb repressive complex-2 critical roles are largely Ezh2- over Ezh1-driven and concentrate during early embryogenesis
Authors: Yette Gabriel A. , Stewart Scott , Stankunas Kryn 
Published: January 2021

ABSTRACTPolycomb repressive complex-2 (PRC2) methylation of histone H3 lysine-27 (H3K27me) is associated with stable transcriptional repression. PRC2 famously silencesHoxgenes to maintain anterior-posterior segment identities but also enables early cell fate specification, restrains progenitor cell differentiation, and canalizes cell identities. Zebrafish PRC2 genetic studies have focused onezh2,which, with its paralogezh1, encodes the H3K27 methyltransferase component.ezh2loss-of-function mutants reinforce essential vertebrate PRC2 functions during early embryogenesis albeit with limited contributions to body plan establishment. However, redundancy withezh1and the lethality of maternal-zygotic homozygousezh2nulls could obscure additional early developmental and organogenesis roles of PRC2. Here, we combine new and existing zebrafishezh1andezh2alleles to show collective maternal/zygoticezh2exclusively provides earliest embryonic PRC2 H3K27me3 activity. Zygoticezh1, which becomes progressively expressed asezh2levels dissipate, has minor redundant and noncompensatory larval roles but itself is not required for viability or fertility. Zygotic Ezh2/PRC2 promotes correct craniofacial bone shape and size by maintaining proliferative pre-osteoblast pools. Anezh2allelic series including disrupted maternalezh2uncovers axial skeleton homeotic transformations and pleiotropic organogenesis defects. Further, once past a critical early window, we show zebrafish can develop near normally with minimal bulk H3K27me3. Our results suggest Ezh2-containing PRC2 stabilizes rather than instructs early developmental decisions while broadly contributing to organ size and embellishment.
The DAXX-SREBP axis promotes oncogenic lipogenesis and tumorigenesis
Authors: Mahmud Iqbal , Tian Guimei , Wang Jia , Lewis Jessica , Waddell Aaron , Lydon McKenzie L. , Zhao Lisa Y. , Li Jian-Liang , Purayil Hamsa Thayele , Huo Zhiguang , Daaka Yehia , Garrett Timothy J. , Liao Daiqing 
Published: January 2021

ABSTRACTDe novo lipogenesis produces lipids for membrane biosynthesis and cell signaling. Elevated lipogenesis is a major metabolic feature in cancer cells. In breast and other cancer types, genes involved in lipogenesis are highly upregulated, but the mechanisms that control their expression remain poorly understood. DAXX modulates gene expression through binding to diverse transcription factors although the functional impact of these diverse interactions remains to be defined. Our recent analysis indicates that DAXX is overexpressed in diverse cancer types. However, mechanisms underlying DAXX’s oncogenic function remains elusive. Using global integrated transcriptomic and lipidomic analyses, we show that DAXX plays a key role in lipid metabolism. DAXX depletion attenuates, while its overexpression enhances, lipogenic gene expression, lipid synthesis and tumor growth. Mechanistically, DAXX interacts with SREBP1 and SREBP2 and activates SREBP-mediated transcription. DAXX associates with lipogenic gene promoters through SREBPs. Underscoring the critical roles for the DAXX-SREBP interaction for lipogenesis, SREBP2 knockdown attenuates tumor growth in cells with DAXX overexpression, and a DAXX mutant unable to bind SREBPs are incapable of promoting lipogenesis and tumor growth. Our results identify the DAXX-SREBP axis as an important pathway for tumorigenesis.
A new method for improving extraction efficiency and purity of urine and plasma cell-free DNA
Authors: Lin Selena Y. , Luo Yue , Marshall Matthew M. , Johnson Barbara J. , Park Sung R. , Wang Zhili , Su Ying-Hsiu 
Published: January 2021

AbstractThis study assessed three commercially available cell-free DNA (cfDNA) extraction kits and the impact of a PEG-based DNA cleanup procedure (DNApure) on cfDNA quality and yield. Six normal donor urine and plasma samples, and specimens from four pregnant (PG) women carrying male fetuses underwent extractions with the JBS cfDNA extraction kit (kit J), MagMAX Cell-Free DNA Extraction kit (kit M), and QIAamp Circulating Nucleic Acid Kit (kit Q). Recovery of a PCR product spike-in, endogenousTP53,and Y-chromosome DNA was used to assess kit performance. Nucleosomal-sized DNA profiles varied among the kits, with prominent multi-nucleosomal-sized peaks present in urine and plasma DNA isolated by kits J and M only. Kit J recovered significantly more spike-in DNA compared with kit M or Q (p<0.001) from urine, and similar amounts from plasma (p=0.12). Applying DNApure to kit M- and Q-isolated DNA significantly improved the amplification efficiency of spike-in DNA from urine (p<0.001) and plasma (p≤0.013). Furthermore, kit J isolated significantly more Y-chromosome DNA from PG urine compared to kit Q (p=0.05). We conclude that DNApure provides an efficient means of improving the yield and purity of cfDNA and minimizing effects of pre-analytical biospecimen variability on liquid biopsy assay performance.
PEDF and Derived Peptides Prevent Apoptosis and Promote Differentiation of Retinal Photoreceptors
Authors: Michelis Germán , German Olga Lorena , Villasmil Rafael , Rotstein Nora P. , Politi Luis , Becerra S Patricia 
Published: January 2021

AbstractPigment epithelium-derived factor (PEDF) is a cytoprotective protein for the retina. We hypothesize that this protein acts on neuronal survival and differentiation of photoreceptor cells in culture. The purpose of the present study was to evaluate the neurotrophic effects of PEDF and its fragments in anin vitromodel of cultured primary retinal neurons that die spontaneously in the absence of trophic factors. Results show that PEDF protected photoreceptor precursors from apoptosis, preserved mitochondrial function and promoted polarization of opsin enhancing their developmental process, as well as induced neurite outgrowth in amacrine neurons. These effects were abolished by an inhibitor of the PEDF receptor or receptor-derived peptides that block ligand/receptor interactions. While all the activities were specifically conferred by short peptide fragments (17 amino acid residues) derived from the PEDF neurotrophic domain, no effects were triggered by peptides from the PEDF antiangiogenic region. The observed effects on retinal neurons imply a specific activation of the PEDF receptor by a small neurotrophic region of PEDF. Our findings support the neurotrophic PEDF peptides as neuronal guardians for the retina, highlighting their potential as promoters of retinal differentiation, and inhibitors of retina cell death and its blinding consequences.
Analysis of next- and third-generation RNA-Seq data reveals the structures of alternative transcription units in bacterial genomes
Authors: Wang Qi , Liu Zhaoqian , Yan Bo , Chou Wen-Chi , Ettwiller Laurence , Ma Qin , Liu Bingqiang 
Published: January 2021

ABSTRACTAlternative transcription units (ATUs) are dynamically encoded under different conditions or environmental stimuli in bacterial genomes, and genome-scale identification of ATUs is essential for studying the emergence of human diseases caused by bacterial organisms. However, it is unrealistic to identify all ATUs using experimental techniques, due to the complexity and dynamic nature of ATUs. Here we present the first-of-its-kind computational framework, named SeqATU, for genome-scale ATU prediction based on next-generation RNA-Seq data. The framework utilizes a convex quadratic programming model to seek an optimum expression combination of all of the to-be-identified ATUs. The predicted ATUs inE. colireached a precision of 0.77/0.74 and a recall of 0.75/0.76 in the two RNA-Sequencing datasets compared with the benchmarked ATUs from third-generation RNA-Seq data. We believe that the ATUs identified by SeqATU can provide fundamental knowledge to guide the reconstruction of transcriptional regulatory networks in bacterial genomes.
A systematic CRISPR screen reveals an IL-20/IL20RA-mediated peritoneal immune crosstalk to prevent the ovarian cancer metastasis
Authors: Li Jia , Qin Xuan , Shi Jie , Wang Xiaoshuang , Li Tong , Xu Mengyao , Chen Xiaosu , Zhao Yujia , Han Jiahao , Piao Yongjun , Zhang Wenwen , Qu Pengpeng , Wang Longlong , Xiang Rong , Shi Yi 
Published: January 2021

AbstractTranscoelomic spread of cancer cells across the peritoneal cavity occurs in most initially diagnosed ovarian cancer (OC) patients and accounts for most cancer-related death. However, how OC cells interact with peritoneal stromal cells to evade the immune surveillance remains largely unexplored. Here, through anin vivogenome-wide CRISPR/Cas9 screen, we identified IL20RA, which decreased dramatically in OC patients during peritoneal metastasis, as a key factor preventing the transcoelomic metastasis of OC. Reconstitution of IL20RA in highly metastatic OC cells greatly suppresses the transcoelomic metastasis. OC cells, when disseminate into the peritoneal cavity, greatly induce peritoneum mesothelial cells to express IL-20 and IL-24, which in turn activate the IL20RA downstream signaling in OC cells to produce mature IL-18, eventually resulting in the polarization of macrophages into the M1-like subtype to clear the cancer cells. Thus, we show an IL-20/IL20RA-mediated crosstalk between OC and mesothelial cells that supports a metastasis-repressing immune microenvironment.