bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis Of Redox Status At The Erythrocyte Level
Authors: Adorbley Bright , Preko Michael Ofosu , Fodil Faiza , Kharoubi Omar 
Published: May 2022

ABSTRACTErythrocytes constitute a significant target for oxidative stress because of their principal function as oxygen-carrying cells. Erythrocytes are constantly exposed to reactive oxygen species as they circulate through the bloodstream. As a result, these erythrocytes have developed a complex antioxidant defense system that comprises both enzymatic and non-enzymatic antioxidants, which mitigates and maintains the erythrocytes in a redox state.This study aimed to explore the in vitro analysis of the redox status by determining the activities of Catalase, Glutathione S transferase, Thiobarbituric Acid reactive species, and total proteins at the erythrocyte level after exposure to aluminum. The experiment was carried out by incubation of erythrocytes.The erythrocytes were distributed into sterile Petri dishes in four groups (control group, Al intoxicated group, and intoxicated with Al and treated with quercetin groups (2mg/l and 5mg/l). The experiment was observed over three intervals (24H, 48H, and 72H).Evaluations were made on oxidative stress and biochemical parameters. Results obtained showed that Al treatment significantly increased the activity of thiobarbituric acid reactive substance and decreased the activity of glutathione S-transferase (GST), activities of catalase, and protein in the erythrocyte of rats. Following administration with quercetin significantly decreased the levels of free radicals and increased the activity of GST, Catalase, and protein activities. Quercetin alleviated the toxic effects of aluminum on the studied parameters.These results indicate that Al-induced oxidative stress in the erythrocytes of rats. Following administration of quercetin, the activities of the oxidative stress parameters tested were improved significantly, indicating the overall good antioxidant properties of the quercetin. In conclusion, quercetin proved to be an effective antioxidant against free radicals produced in the erythrocytes due to aluminum exposure.HIGHLIGHTSErythrocytes are exposed to reactive Oxygen Species as they circulate in the bloodstream.Aluminum induces oxidative stress in erythrocytes of Wistar rats.Aluminum increases the activity of TBARS and decreases the activity of GST and CAT in incubated erythrocytes.Quercetin alleviates the toxic effects of aluminum on biochemical and oxidative stress parameters.
Strategies for improved xylitol production in batch fermentation of sugarcane hydrolysate using Saccharomyces cerevisiae
Authors: Lizarazo Frank Uriel Suarez , Pereira Gonçalo Amarante Guimarães , de Mello Fellipe da Silveira Bezerra 
Published: May 2022

ABSTRACTA plethora of studies have focused on improvements of xylitol production. The challenges of establishing a biotechnological route for the industrial production of this sugar have been explored using different microorganisms and renewable feedstock. Nevertheless, sugarcane biomass has been neglected as the pentose source for xylitol production using Saccharomyces cerevisiae. Therefore, here we investigate the use of an industrial S. cerevisiae strain for xylitol production in batch fermentation of non-detoxified sugarcane straw hydrolysate, envisioning the diversification of the current infrastructure used for second-generation bioethanol production from the same lignocellulosic material. In order to optimize the xylose conversion in a non-fed cultivation system, guidelines in cell inoculum and medium supplementation are suggested, as well as the first attempt to use electro-fermentation for this purpose. Accordingly, our results show that the increase in initial cell density and hydrolysate supplementation allows a xylitol production of 19.24 ± 0.68 g/L, representing 0,132 g/L.h productivity.
A missense mutation in zinc finger homeobox-3 (ZFHX3) impedes growth and alters metabolism and hypothalamic gene expression in mice
Authors: Nolan Patrick M. , Banks Gareth , Bourbia Nora , Wilcox Ashleigh G. , Bentley Liz , Moir Lee , Kent Lee , Hillier Rosie , Wilson Dana , Barrett Perry , Dumbell Rebecca 
Published: May 2022

AbstractA protein altering variant in the gene encoding zinc finger homeobox-3 (ZFHX3) has recently been associated with lower BMI in a human genome-wide association study. We investigated metabolic parameters in mice harbouring a missense mutation inZfhx3(Zfhx3Sci/+) and looked for alteredin situexpression of transcripts that are associated with energy balance in the hypothalamus to understand how ZFHX3 may influence growth and metabolic effects. One year old male and femaleZfhx3Sci/+mice weighed less, had shorter body length, reduced fat mass, smaller mesenteric fat depots, and lower circulating insulin, leptin, and insulin-like growth factor-1 (IGF1) concentrations thanZfhx3+/+littermates. In a second cohort of 9 – 20-week-old males and females,Zfhx3Sci/+mice ate less than wildtype controls, in proportion to body weight. In a third cohort of female-onlyZfhx3Sci/+andZfhx3+/+mice that underwent metabolic phenotyping from 6 - 14 weeks old,Zfhx3Sci/+mice weighed less and had lower lean mass and energy expenditure, but fat mass didn’t differ. We detected increased expression of somatostatin, and decreased expression of growth hormone-releasing hormone and growth hormone-receptor mRNAs in the arcuate nucleus (ARC). Similarly, ARC expression of orexigenic neuropeptide Y was decreased and ventricular ependymal expression of orphan G protein-coupled receptorGpr50was decreased. We demonstrate for the first time an energy balance effect of theZfhx3Scimutation, likely by altering expression of key ARC neuropeptides to alter growth, food intake and energy expenditure.
Effect of Puerarin on PI3K-AKT Signaling Pathway in Osteoclast
Authors: Yang Yiqiu , Li Lan , Zhao Na , Kuang Shanshan , Zhang Yaowen , Xie Jisheng 
Published: May 2022

AbstractobjectiveThis study intends to explore the role of PI3K-AKT signaling pathway in the effect of Puerarin on the proliferation, activity, and function of osteoclasts from the perspective of antioxidation.MethodsRAW264. 7 cells were divided into control group, induction group treated with 20ng/mL M-CSF and 50ng/mL RANKL, puerarin group treated with 20ng/mL M-CSF, 50ng/mL RANKL, and 50μmol/L puerarin. The staining of osteoclasts before and after puerarin intervention was measured by TRAP staining and cell count. The changes of related molecules before and after puerarin intervention in osteoclasts were detected by real-time fluorescence quantitative PCR and Western Blot, including TRAP, MMP-9, Cathepsin K, NFATc1, PTEN, Catalase, PI3K, AKT, P-AKT(ser473), FoxO1, P-FoxO1.ResultsTRAP staining showed that puerarin inhibited the proliferation and differentiation of RAW264.7 cells into osteoclasts. The results of qRT-PCR and WB showed that compared with the control group, the gene expression of TRAP, MMP-9, cathepsin K and NFATc1 in the induction group was up-regulated, while the gene expression of Catalase was down-regulated. PTEN gene had no significant changes before and after puerarin intervention. The expression of P-AKT (ser473) and NFATc1 protein was up-regulated, while the expression of PI3K and AKT protein had no change. Compared with the induction group, the gene expression of TRAP, MMP-9, Cathepsin K, and NFATc1 in the puerarin group decreased, the gene expression of Catalase increased, the protein expression of PI3K and AKT remained unchanged, the protein expression of P-AKT (ser473), P-FoxO1 and NFATc1 decreased, and the protein expression of FoxO1 and Catalase increased.ConclusionPuerarin may promote the transcriptional activity of FoxO1, increase the expression of catalase protein and exert its antioxidant activity by regulating the PI3K-AKT signal pathway, so as to inhibit the proliferation and differentiation of osteoclasts.
MHC class I Ligands of Rhesus Macaque Killer-Cell Immunoglobulin-Like Receptors
Authors: Anderson Jennifer L. , Sandstrom Kjell , Smith Willow R. , Wetzel Molly , Klenchin Vadim A. , Evans David T. 
Published: May 2022

AbstractDefinition of MHC class I ligands of rhesus macaque KIRs is fundamental to NK cell biology in this species as an animal model for infectious diseases, reproductive biology, and transplantation. To provide a more complete foundation for studying NK cell responses, rhesus macaque KIRs representing common allotypes of lineage IIKIRgenes were tested for interactions with MHC class I molecules representing diverseMamu-A, -B, -E, -F, -Iand-AGalleles. KIR-MHC class I interactions were identified by co-incubating reporter cell lines bearing chimeric KIR-CD3ζ receptors with target cells expressing individual MHC class I molecules and were corroborated by staining with KIR IgG-Fc fusion proteins. Ligands for 11 KIRs of previously unknown specificity were identified that fell into two general categories: interactions with multiple Mamu-Bw4 molecules or with Mamu-A-related molecules, including several allotypes of Mamu-AG and the hybrid Mamu-B*045:03 molecule. Although both groups include inhibitory and activating receptors, the majority of KIRs found to interact with Mamu-Bw4 are inhibitory, whereas most of the KIRs that interact with Mamu-AG are activating. We also identified Mamu-A1*012:01 as a ligand for KIR3DLw03*002, which belongs to a phylogenetically distinct group of macaque KIRs with a three amino acid deletion in D0 that is also present in human KIR3DL1/S1 and KIR3DL2. This study more than doubles the number of rhesus macaque KIRs with defined MHC class I ligands and identifies novel interactions with Mamu-AG, -B*045, and -A1*012. These findings support overlapping, but nonredundant, patterns of ligand recognition that reflects extensive functional diversification of these receptors.
An interaction between β’-COP and the ArfGAP, Glo3, maintains post-Golgi cargo recycling
Authors: Xie Boyang , Guillem Clara , Jung Christian , Kendall Amy K. , Date Swapneeta , Best Jordan T. , Graham Todd R. , Jackson Lauren P. 
Published: May 2022

AbstractThe essential COPI vesicular coat mediates retrieval of key transmembrane proteins at the Golgi and endosomes following recruitment by the small GTPase, Arf1. ArfGAP proteins regulate COPI coats, but molecular details for COPI recognition by ArfGAP proteins remain elusive. Biochemical and biophysical data reveal how β’-COP propeller domains directly engage the yeast ArfGAP, Glo3, with a low micromolar binding affinity (KD ~1 µM). Calorimetry data demonstrate both β’-COP propeller domains are required to bind Glo3 using electrostatic interactions. An acidic patch on β’-COP (D437/D450) interacts with Glo3 lysine residues located within the BoCCS (Binding of Coatomer, Cargo, and SNAREs) region. Targeted point mutations in either Glo3 BoCCS or β’-COP abrogate the interaction in vitro, and loss of the β’-COP/Glo3 interaction drives Ste2 mis-sorting to the vacuole and aberrant Golgi morphology in budding yeast. Together, these data suggest cells require the β’-COP/Glo3 interaction for cargo recycling via endosomes and the TGN, where β’-COP may serve as a molecular platform to coordinate binding to multiple protein partners, including Glo3, Arf1, and the COPI F-subcomplex.
Genetic Architecture And Clinical Outcomes Of The Fredrickson-Levy-Lees Dyslipoproteinemias
Authors: Gilliland Thomas , Dron Jaqueline S. , Selvaraj Margaret Sunitha , Trinder Mark , Paruchuri Kaavya , Urbut Sarah M. , Haidermota Sara , Bernardo Rachel , Uddin Md Mesbah , Honigberg Michael C. , Peloso Gina , Natarajan Pradeep 
Published: May 2022

AbstractBackground and AimsThe genetic basis and clinical relevance of the classical Fredrickson-Levy-Lees (FLL) dyslipoproteinemia classifications has not been studied in general population-based cohorts. We aimed to evaluate the phenotypic and genetic characteristics of FLL disorders.MethodsAmong UK Biobank participants free of prevalent coronary artery disease (CAD), we used blood lipids and apolipoprotein B concentrations to infer FLL classes (Types I, IIa, IIb, III, IV, and V). For each FLL class, Cox proportional hazards regression estimated risk of incident CAD. Phenome-wide association testing was performed. GWAS were performed, followed by in silico causal gene prioritization and heritability analyses. Prevalence of disruptive Mendelian lipid variants was assessed from whole exome sequencing.ResultsOf 450,636 individuals, 259,289 (57.5%) met criteria for a FLL dyslipoproteinemia: 63 (0.01%) type I; 40,005 (8.9%) type IIa; 94,785 (21.0%) type IIb; 13,998 (3.1%) type III; 110,389 (24.5%) type IV; and 49 (0.01%) type V. Over median 11.1 years follow-up, compared to normolipidemics the type IIb pattern conferred the highest hazard of incident CAD overall (HR 1.92, 95% CI 1.84-2.01, P<0.001) and in meta-analysis across matched non-HDL-C strata (HR 1.45, 95% CI 1.30-1.60). GWAS revealed 250 loci associated with FLL, of which 13 were shared across all classes; compared to GWAS of isolated lipid traits, 72 additional loci were detected. Mendelian lipid variants were rare (2%), but polygenic heritability was high, ranging from 23% (type III) to 54% (type IIb).ConclusionsFLL classes have distinct genetic architectures yielding new insights for cardiometabolic disease beyond single lipid analyses.
A Randomised, Multi-centre Phase II Trial of Weekly Paclitaxel and Vistusertib in Platinum-Resistant Ovarian High-Grade Serous Carcinoma: OCTOPUS Arm 1
Authors: Banerjee S. , Giannone G. , Clamp A. , Ennis D. , Glasspool R. , Herbertson R. , Krell J. , Riisnaes R. , Mirza H.B. , Cheng Z. , McDermott J. , Green C. , Kristeleit R.S. , George A. , Gourley C. , Lewsley L-A , Rai D. , Banerji U. , Hinsley S. , McNeish I.A. 
Published: May 2022

AbstractBackgroundPreclinical studies support targeting PI3K/AKT/mTOR signalling in platinum-resistant ovarian cancer (PROC). A phase I study of the dual mTORC1/mTORC2 inhibitor vistusertib with weekly paclitaxel (wP) showed activity. We report the results of Arm 1 of OCTOPUS, the first randomised trial of weekly paclitaxel and dual mTORC1/2 inhibition in ovarian cancer.MethodsPatients with platinum-resistant or refractory high grade serous carcinoma were randomised (1:1) to wP (80mg/m2 D1,8,15 of 28 day cycle) plus oral vistusertib (50mg BD) or placebo (P). The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS).Results140 patients (median age 63, range: 36-86; 18% platinum-refractory; 54% ≥3 prior therapies) were randomised. There was no difference in PFS (median 4.5 vs 4.1m (HR 0.84; 80% CI (0.67, 1.07); 1-sided p=0.18), OS (median 9.7 vs 11.1m (HR 1.21; 80% CI (0.91, 1.60); 1-sided p=0.80) or RR (odds ratio 0.86; 80% CI (0.55, 1.36); 1-sided p=0.66). Grade 3/4 adverse events were 41.2% (wP+V) vs 36.7% (wP+P). Low tumour PTEN expression was associated with longer PFS in the wP+V arm (9.4 vs 4.1m p=0.003) but not in the wP arm (4.8 vs 4.2m p=0.60). Tumour genome-wide copy number (CN) analysis suggested that high CN signature 4 was associated with worse outcome in the wP+P arm (2.3 vs 4.6m p=0.018) but not the wP+V arm (5.4 vs 3.3m).ConclusionsVistusertib did not improve clinical activity of wP in PROC. However, low tumour cell PTEN expression may be a predictive biomarker for vistusertib activity.Translational RelevancePreclinical studies suggest that activation of the PI3K/AKT/mTOR signalling pathway contributes to platinum-resistance in ovarian high grade serous carcinoma (HGSC). Based on activity in a phase I study, we evaluated the clinical efficacy of the dual mTORC1/mTORC2 inhibitor vistusertib in combination with weekly paclitaxel in the OCTOPUS study - a multi-centre, randomised, placebo-controlled, phase II trial in platinum-resistant ovarian (HGSC). In the first randomised trial of weekly paclitaxel and dual mTORC1/2 inhibition in ovarian cancer, vistusertib did not improve clinical activity of weekly paclitaxel. However, translational analyses indicated that low tumour cell PTEN expression may be a predictive biomarker for vistusertib activity. We also showed genome-wide copy number (CN) analysis, in particular high exposure to CN signature 4, may also allow identification of patients with greater chance of benefit from dual mTORC inhibition. Potential predictive biomarkers identified in our study should be evaluated in ongoing/future studies.
iGWAS: image-based genome-wide association of self-supervised deep phenotyping of human medical images
Authors: Xie Ziqian , Zhang Tao , Kim Sangbae , Lu Jiaxiong , Zhang Wanheng , Lin Cheng-Hui , Wu Man-Ru , Davis Alexander , Channa Roomasa , Giancardo Luca , Chen Han , Wang Sui , Chen Rui , Zhi Degui 
Published: May 2022

AbstractExisting imaging genetics studies have been mostly limited in scope by using imaging-derived phenotypes defined by human experts. Here, leveraging new breakthroughs in self-supervised deep representation learning, we propose a new approach, image-based genome-wide association study (iGWAS), for identifying genetic factors associated with phenotypes discovered from medical images using contrastive learning. Using retinal fundus photos, our model extracts a 128-dimensional vector representing features of the retina as phenotypes. After training the model on 40,000 images from the EyePACS dataset, we generated phenotypes from 130,329 images of 65,629 British White participants in the UK Biobank. We conducted GWAS on three sets of phenotypes: raw image phenotype, phenotypes derived from the original photos; retina color, the average color of the center region of the retinal fundus photos; and vessel-enriched phenotypes, phenotypes derived from vasculature-segmented images. GWAS of raw image phenotypes identified 14 loci with genome-wide significance (p<5×10-8and intersection of hits from left and right eyes), while GWAS of retina colors identified 34 loci, 7 are overlapping with GWAS of raw image phenotype. Finally, a GWAS of vessel-enriched phenotypes identified 34 loci. While 25 are overlapping with the raw image loci and color loci, 9 are unique to vessel-enriched GWAS. We found that vessel-enriched GWAS not only retains most of the loci from raw image GWAS but also discovers new loci related to vessel development. Our results establish the feasibility of this new framework of genomic study based on self-supervised phenotyping of medical images.
How is the COVID-19 pandemic impacting our life, mental health, and well-being? Design and preliminary findings of the pan-Canadian longitudinal COHESION Study
Authors: Gabet Stephan , Thierry Benoit , Wasfi Rania , De Groh Margaret , Simonelli Guido , Hudon Catherine , Lessard Lily , Dubé Ève , Nasri Bouchra , Kestens Yan , Moullec Grégory 
Published: May 2022

AbstractWith the advent of the COVID-19 pandemic, in-person social interactions and opportunities for accessing resources that sustain health and well-being have drastically reduced. We therefore designed the pan-Canadian population-based prospective COVID-19: HEalth and Social Inequities across Neighbourhoods (COHESION) cohort to provide deeper understanding of how the COVID-19 pandemic context affects mental health and well-being, key determinants of health, and health inequities.This paper presents the design of the two-phase COHESION Study, and descriptive results from the first phase conducted between May 2020 and September 2021. During that period, the COHESION research platform collected monthly data linked to COVID-19 such as infection and vaccination status, perceptions and attitudes regarding pandemic-related measures, and information on participants’ physical and mental health, well-being, sleep, loneliness, resilience, substances use, living conditions, social interactions, activities, and mobility.The 1,268 people enrolled in the Phase 1 COHESION Study are for the most part from Ontario (47%) and Quebec (33%), aged 48 ± 16 years [mean ± standard deviation (SD)], and mainly women (78%), White (85%), with a university degree (63%), and living in large urban centers (70%). According to the 298 ± 68 (mean ± SD) prospective questionnaires completed each month in average, the first year of follow-up reveals significant temporal variations in standardized indexes of well-being, loneliness, anxiety, depression, and psychological distress.The COHESION Study will allow identifying trajectories of mental health and well-being while investigating their determinants and how these may vary by subgroup, over time, and across different provinces in Canada, in the unique context of the COVID-19 pandemic.
Spatial-ID: a cell typing method for spatially resolved transcriptomics via transfer learning and spatial embedding
Authors: Shen Rongbo , Liu Lin , Wu Zihan , Zhang Ying , Yuan Zhiyuan , Guo Junfu , Yang Fan , Zhang Chao , Chen Bichao , Liu Chao , Guo Jing , Fan Guozhen , Zhang Yong , Li Yuxiang , Xu Xun , Yao Jianhua 
Published: May 2022

AbstractSpatially resolved transcriptomics (SRT) provides the opportunity to investigate the gene expression profiles and the spatial context of cells in naive state. Cell type annotation is a crucial task in the spatial transcriptome analysis of cell and tissue biology. In this study, we propose Spatial-ID, a supervision-based cell typing method, for high-throughput cell-level SRT datasets that integrates transfer learning and spatial embedding. Spatial-ID effectively incorporates the existing knowledge of reference scRNA-seq datasets and the spatial information of SRT datasets. A series of quantitative comparison experiments on public available SRT datasets demonstrate the superiority of Spatial-ID compared with other state-of-the-art methods. Besides, the application of Spatial-ID on a SRT dataset with 3D spatial dimension measured by Stereo-seq shows its advancement on the large field tissues with subcellular spatial resolution.
Newly raised anti-c-Kit antibody detects interstitial cells of Cajal in the gut of chicken embryos
Authors: Yagasaki Rei , Shikaya Yuuki , Kawachi Teruaki , Inaba Masafumi , Takase Yuta , Takahashi Yoshiko 
Published: May 2022

AbstractThe gut peristaltic movement, a wave-like propagation of a local contraction, is important for the transportation and digestion of ingested materials. Among three types of cells, the enteric nervous system (ENS), smooth muscle cells, and interstitial cells of Cajal (ICCs), the ICCs have been thought to act as a pacemaker, and therefore it is important to decipher the cellular functions of ICCs for the understanding of gut peristalsis. c-Kit, a tyrosine kinase receptor, has widely been used as a marker for ICCs. Most studies with ICCs have been conducted in mammals using commercially available anti-c-Kit antibody. Recently, the chicken embryonic gut has emerged as a powerful model to study the gut peristalsis. However, since the anti-c-Kit antibody for mammals does not work for chickens, cellular mechanisms by which ICCs are regulated have largely been unexplored. Here, we report a newly raised polyclonal antibody against the chicken c-Kit protein. The specificity of the antibody was validated by both Western blotting analyses and immunocytochemistry. Co-immunostaining with the new antibody and anti-α smooth muscle actin (αSMA) antibody successfully visualized ICCs in the chicken developing hindgut in the circular muscle- and longitudinal muscle layers: as previously shown in mice, common progenitors of ICCs and smooth muscle cells at early stages were double positive for αSMA and c-Kit, and at later stages, differentiated ICCs and smooth muscle cells exhibited only c-Kit and αSMA, respectively. A novel ICC population was also found that radially extended from the submucosal layer to circular muscle layer. Furthermore, the new antibody delineated individual ICCs in a cleared hindgut. The antibody newly developed in this study will facilitate the study of peristaltic movement in chicken embryos.