bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of the transcription factor REST regulatory networks in IDH-mutant and IDH-wild type glioma cells and gliomas
Authors: Perycz Malgorzata , Dabrowski Michal J. , Jardanowska Marta , Roura Adria-Jaume , Gielniewski Bartlomiej , Stepniak Karolina , Dramiński Michał , Kaminska Bozena , Wojtas Bartosz 
Published: July 2022

AbstractREST is a widely expressed, dual role transcription factor that acts either as a transcriptional repressor or transcriptional activator depending on the genomic and cellular context. REST is an important oncogenic factor, a key player in brain cell differentiation and has a role in establishing DNA methylation status in proximity of its binding sites. Mutations in IDH cause significant changes to the epigenome contributing to blocking cell differentiation and are considered an oncogenic driver in glioma. We aimed at defining the REST role in the IDH mutation-related phenotype in gliomas accounting for its role in gene activation and repression. We studied the effects of REST knockdown, REST binding sites, and REST motifs methylation in context of IDH mutation, and found that both REST binding patterns and TF motif composition proximal to REST binding sites differed in IDH wild-type and mutant glioma. Among such REST targets were genes involved in glial cell differentiation and ECM organization. REST knockdown differently impacted glioma cell invasion depending on the IDH phenotype. DNA methylation of REST activated gene promoters showed positive correlation with gene expression. The canonical REST-repressed gene targets correlated with NPC-like cellular state properties in IDH-MUT grade 2/3 gliomas. The identified REST targets, gene regulatory networks and putative REST cooperativity with other TFs point to differential control of REST target gene expression in IDH-WT and IDH-MUT gliomas. We conclude that REST could be considered as a key factor in the design of targeted glioma therapies.
Toward unraveling the correlates of fatigue in glioma
Authors: Röttgering Jantine G. , Belgers Vera , De Witt Hamer Philip C. , Knoop Hans , Douw Linda , Klein Martin 
Published: July 2022

AbstractBackgroundEven though fatigue is one of the most prevalent and burdensome symptoms in patients with glioma, its etiology and determinants are still poorly understood. We aimed to identify which demographic, tumor- and treatment-related characteristics and patient-reported outcome measures (PROMs) are associated with or are predictors of fatigue in glioma.MethodsIn this retrospective observational study, we included glioma patients with preoperative and postoperative assessments including PROMs on fatigue, depression, cognitive functioning, and health-related quality of life (HRQoL). Linear mixed models were used to identify which clinical factors and PROMs were associated with fatigue and linear multiple regression was used to detect predictors of postoperative fatigue.ResultsIn this study, 222 patients were included (78% grade II-III glioma, 22% grade IV). These patients had performed 333 assessments (193 preoperative and 116 one year postoperatively). Of all assessments, 39% was indicative of severe fatigue. Several HRQoL domains, depression, and right-sided tumors were significantly associated with fatigue (marginalR2= 0.63). Contrary to common expectations, tumor type, treatment-related factors and timing of the assessment, were not associated with fatigue. In a subgroup of seventy patients with follow-up assessments, preoperative fatigue and physical functioning were predictors of postoperative fatigue (adjustedR2= 0.31).ConclusionFatigue is a complex symptom, which should not solely be attributed to the tumor or its treatment, but is instead related to different aspects of mood and HRQoL. These insights are of importance in understanding fatigue and could guide symptom management, especially in patients with lower grade tumors.Key pointsUp to 40% of patients are severely fatigued, regardless of tumor type or timing of assessment HRQoL, depression, and right-sided tumor explain 63% of variance in fatigue severity Demographics, tumor type and treatment are not associated with fatigue severityImportance of the StudyDespite fatigue being one of the most frequent and burdensome symptoms in patients with glioma, its etiology remains poorly understood. We aimed to unravel the impact of demographic, tumor- and treatment-related factors, symptoms, and HRQoL to grasp the complexity of fatigue in 222 glioma patients. Our findings demonstrate that fatigue is associated with several domains of HRQoL and depression, as well as having a tumor in the right hemisphere. What stands out is that fatigue is not associated with tumor type, treatment-related characteristics or phase of the disease. These findings could be important in symptom management since tumor- and treatment-related factors are non-modifiable, whilst depressive symptoms and social and physical functioning could be more suitable treatment targets. These results underscore the need for timely screening and symptom management focusing not only on fatigue but also on mood and diminished HRQoL.
Investigation of Association Between microRNA Variants and Risk of Rheumatoid Arthritis
Authors: Ullah Irfan , Tariq Muhammad Haseeb , Shah Aftab Ali , Uzair Muhammad , Nawaz Mohsin 
Published: July 2022

AbstractRheumatoid arthritis (RA) is a chronic autoimmune disorder that affects and damages the joints of human beings. It causes swelling, discomfort, and inflammation in and around the joints and affects other body organs; that affects 1% of the world’s population, with 6 to 60 people out of 100,000 developing the disease each year. However, a recent study describes that there are several factors involved in the regulation of RA disease, including genetic factors like MicroRNAs (miRNAs) variants, which are tiny molecules that bind to complementary target RNA molecules to regulate the protein-coding region of the genome, these non-coding short RNA molecules attach to target mRNA molecules at 3′-untranslated regions (UTR). The current study aimed to investigate the impact of variants rs11614913, rs6505162, and rs3746444 located in MIR196A2, MIR423, and MIR499, respectively, in RA patients. These SNPs were genotyped in RA patients and age- and gender-matched healthy controls using allele-specific T-ARMS-PCR. Allelic and genotypic frequencies of each variant were noted. Furthermore, from the selected variants, the association of rs11614913 and rs6505162 variants with the risk of RA was measured using a statistically odds ratio and confidence of interval (95%). In co-dominant models, the genotypic frequency of MIR423 variant rs6505162 was in cases A/A 75(35.21%), C/C 108 (50.7%) and A/C 30 (14.08%) while in controls A/A 34(16%), C/C 94(44.1%) and A/C 85(40%). These values indicate the best relationship between C/C and A/C, which were higher in cases and found significant association according to P-value and χ2. [χ2=14.03; P value=0.0009]. This concludes that SNPs (rs6505162) in MIR423 are the susceptibility factors for RA in the Pakistani Population. While SNPs rs11614913 in MIR196A2 have shown no association with RA.
Comparative effectiveness of BNT162b2 versus mRNA-1273 boosting in England: a cohort study in OpenSAFELY-TPP
Authors: Hulme William J , Horne Elsie MF , Parker Edward PK , Keogh Ruth H , Williamson Elizabeth J , Walker Venexia , Palmer Tom , Curtis Helen J , Walker Alex , Mehrkar Amir , Morley Jessica , MacKenna Brian , Bacon Sebastian CJ , Goldacre Ben , Hernán Miguel A , Sterne Jonathan AC ,   the OpenSAFELY collaborative
Published: July 2022

AbstractIntroductionThe COVID-19 booster vaccination programme in England used both BNT162b2 and mRNA-1273 vaccines. Direct comparisons of the effectiveness against severe COVID-19 of these two vaccines for boosting have not been made in trials or observational data.MethodsOn behalf of NHS England, we used the OpenSAFELY-TPP database to match adult recipients of each vaccine type on date of vaccination, primary vaccine course, age, and other characteristics. Recipients were eligible if boosted between 29 October 2021 and 31 January 2022, and followed up for 12 weeks. Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death. We estimated the cumulative incidence of each outcome, and quantified comparative effectiveness using risk differences (RD) and hazard ratios (HRs).Results1,528,431 people were matched in each group, contributing a total 23,150,504 person-weeks of follow-up. The 12-week risks per 1,000 people of positive SARS-CoV-2 test were 103.2 (95%CI 102.4 to 104.0) for BNT162b2 and 96.0 (95.2 to 96.8) for mRNA-1273: the HR comparing mRNA-1273 with BNT162b2 was 0.92 (95%CI 0.91 to 0.92). For COVID-19 hospitalisations the 12-week risks per 1,000 were 0.65 (95%CI 0.56 to 0.75) and 0.44 (0.36 to 0.54): HR 0.67 (95%CI 0.58 to 0.78). COVID-19 deaths were rare: the 12-week risks per 1,000 were 0.03 (95%CI 0.02 to 0.06) and 0.01 (0.01 to 0.02): HR 1.23 (95%CI 0.59 to 2.56). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, prior SARS-CoV-2 infection and clinical vulnerability.ConclusionBooster vaccination with mRNA-1273 COVID-19 vaccine was more effective than BNT162b2 in preventing SARS-CoV-2 infection and COVID-19 hospitalisation during the first 12 weeks after vaccination, during a period of Delta followed by Omicron variant dominance.
FACTORS INFLUENCING CONTRACEPTIVE USE AMONG ADOLESCENTS IN TECHIMAN MUNICIPALITY, GHANA
Authors: Kpiinfaar Titus N. , Owusu-Asubonteng Gerald , Dassah Edward T. 
Published: July 2022

ABSTRACTContraceptive use among adolescents in Ghana is low. Factors influencing adolescent contraceptive use in Techiman Municipality have not been investigated. This study aimed to determine factors influencing contraceptive use among adolescents in Techiman Municipality.An analytical cross-sectional community-based study was conducted from January-March, 2018 among adolescents between the ages of 16 and 19 years whoever had sex. Respondents were selected through multi-stage sampling. Data was collected using a pre-tested structured questionnaire. Factors associated with contraceptive use were assessed using logistic regression to generate crude and adjusted odds ratios (AORs) with 95% confidence intervals (CIs). P<0.05 was considered statistically significant. Altogether, 298 adolescents who have ever had sex were studied. The mean age was 17.5 years (standard deviation 1.1 years). About 53% were out-of-school adolescents and 43.6% had sex within the four weeks preceding the interview, with out-of-school adolescents being more likely to have had sex (53.8% vs. 32.1%; p<0.001). Contraceptive knowledge and ever use were 75.0% and 65% respectively. The most commonly used contraceptives were condoms (54%) and emergency contraception (31%). Significant factors influencing contraceptive use were; father’s educational level (AOR4.86; 95% CI 1.70 – 13.91; p<0.001) and prior discussion of contraceptive use with partner (AOR 3.96; 95% CI 1.32 – 11.89; p=0.01). Contraceptive use was high, but few (10%) relied on LARCs. Adolescents should be encouraged to discuss contraceptive use with their sexual partners during sexual health and contraceptive counselling. Strategies for improving LARC uptake among adolescents should be investigated.
PML and PML-like exonucleases restrict retrotransposons in jawed vertebrates
Authors: Mathavarajah Sabateeshan , Vergunst Kathleen L. , Williams Shelby K. , He Raymond , Maliougina Maria , Habib Elias B. , Park Mika , Salsman Jayme , Roy Stéphane , Braasch Ingo , Roger Andrew J. , Langelaan David N. , Dellaire Graham 
Published: July 2022

ABSTRACTWe have uncovered a novel role for the promyelocytic leukemia (PML) gene and novel PML-like DEDDh exonucleases in the maintenance of genome stability through the restriction of LINE-1 (L1) retrotransposition in jawed vertebrates. Although the PML tumour suppressor protein in mammals is SUMOylated and forms nuclear bodies, we found that the spotted gar PML ortholog and related proteins in fish are not SUMOylated and function as cytoplasmic DEDDh exonucleases. In contrast, more closely related avian and turtle PML proteins are predicted to be SUMOylated and localized both to the cytoplasm and to nuclear bodies. We also identified PML-like exon 9 (Plex9) genes in teleost fishes that encode exonucleases sharing homology to gar PML. In an example of convergent evolution and akin to TREX1, gar PML and zebrafish Plex9 proteins suppressed L1 retrotransposition and could complement TREX1 knockout in mammalian cells. We also characterized the first non-mammalian TREX1 homologs in axolotl. Following export to the cytoplasm, the human PML-I isoform also restricted L1 through its conserved C-terminus and suppressed CGAS activation. Thus, PML first emerged as a cytoplasmic suppressor of retroelements, and this function is retained in amniotes despite its role in the assembly of nuclear bodies and the acquisition of SUMO-modification.
The impact of primary colonizers on the community composition of river biofilm
Authors: Angoshtari Roshan , Scribner Kim T. , Marsh Terence L. 
Published: July 2022

AbstractAs a strategy for minimizing microbial infections in fish hatcheries, we have investigated how putatively probiotic bacterial populations influence biofilm formation on the surface of eggs. All surfaces that are exposed to the aquatic milieu develop a microbial community through the selective assembly of microbial populations into a surface-adhering biofilm. In the investigations reported herein, we describe laboratory experiments designed to determine how initial colonization of a surface by nonpathogenic isolates from sturgeon eggs influence the subsequent assembly of populations into the existing biofilm from a pelagic river community. All eight of the tested strains altered the assembly of river biofilm in a strain-specific manner. Previously formed isolate biofilm was challenged with natural river populations and after 24 hours, two strains and two isolate combinations proved highly resistant to invasion, comprising at least 80% of the biofilm community, four isolates were intermediate in resistance with at least 45% of the biofilm community and two isolates were reduced to 4% of the biofilm community. Founding biofilms ofSerratiasp, and combinations ofBrevundimonas sp.-Hydrogenophagasp. andBrevundimonassp.-Acidovoraxsp. specifically blocked populations ofAeromonas and Flavobacterium, potential fish pathogens, from colonizing the biofilm. In addition, all isolate biofilms were effective at blocking invading populations ofArcobacter. Several strains, notablyDeinococcussp., recruited specific river populations into the biofilm. The experiments suggest that relatively simple measures can be used to control the assembly of biofilm on the eggs surface and perhaps offer protection from pathogens. In addition, the methodology provides a relatively rapid way to detect potentially strong ecological interactions between bacterial populations in the formation of biofilms.
Dually targeted proteins regulate proximity between peroxisomes and partner organelles
Authors: Stehlik Thorsten , Bittner Elena , Lam Jason , Dimitrov Lazar , Schöck Isabelle , Harberding Jannik , Heymons Nikola , Schuldiner Maya , Zalckvar Einat , Bölker Michael , Schekman Randy , Freitag Johannes 
Published: July 2022

AbstractPeroxisomes play a central role in fatty acid metabolism. To correctly target to peroxisomes, proteins require specialized targeting signals. One mystery in the field is sorting of proteins that carry both a targeting signal for peroxisomes as well as for other organelles such as mitochondria or the endoplasmic reticulum (ER). Exploring several of these dually localized proteins in Saccharomyces cerevisiae, we observed that they can act as dynamic tethers bridging organelles together through an affinity for organelle-destined targeting factors. We show that this mode of tethering involves the peroxisome import machinery, the ER– mitochondria encounter structure (ERMES) in the case of mitochondria and the GET complex in the case of the ER. Depletion of each of the targeting factors resulted in the accumulation of smaller peroxisomes. We propose that dual targeting of proteins occurs at contact sites and that protein import per se contributes to the maintenance of these membrane proximities. This introduces a previously unexplored concept of how targeting of dual affinity proteins can support organelle attachment, growth and communication.
Beta human papillomavirus 8E6 promotes alternative end-joining
Authors: Hu Changkun , Bugbee Taylor , Palinski Rachel , Akinyemi Ibukun A. , McIntosh Michael , MacCarthy Thomas , Bhaduri-McIntosh Sumita , Wallace Nicholas 
Published: July 2022

AbstractDouble strand breaks (DSBs) are one of the most lethal DNA lesions in cells. Previous studies show that the E6 protein of beta-human papillomavirus (HPV8 E6) impairs two major DSB repair pathways homologous recombination (HR) and non-homologous end-joining (NHEJ). However, HPV8 E6 delays but does not eliminate DSB repair capability of cells. How DSBs are repaired in cells with HPV8 E6 remains to be studied. We hypothesis that HPV8 E6 promotes a backup DSB repair pathway, alternative end-joining (Alt-EJ). Using CAS9 based Alt-EJ reporters, we show that HPV8 E6 promotes Alt-EJ. Further, using small molecule inhibitors, CRISPR/CAS9 gene knockout, and HPV8 E6 mutant, we find that HPV8 E6 promotes Alt-EJ by binding p300, an acetyltransferase that facilitates DSB repair by HR and NHEJ. Finally, we analyzed whole genome sequencing data from genomes of human foreskin keratinocytes expressing HPV8 E6 and found they displayed an increased frequency of deletions bearing the microhomology signatures of Alt-EJ. This study fills the knowledge gap how DSB is repaired in cells with HPV8 E6 and the mutagenic consequences of HPV8 E6 mediated p300 destabilization. Broadly, this study supports the hypothesis that beta-HPV promotes cancer formation by increasing genomic instability.
Breaking dormancy in spores of budding yeast transforms its cytoplasm and the solubility of its proteome
Authors: Plante Samuel , Moon Kyung-Mee , Lemieux Pascale , Foster Leonard J. , Landry Christian R. 
Published: July 2022

AbstractThe biophysical properties of the cytoplasm are major determinants of key cellular processes and adaptation. Many yeasts produce dormant spores that can withstand extreme conditions. We show that spores ofSaccharomyces cerevisiæexhibit extraordinary biophysical properties, including a highly viscous and acidic cytosol. These conditions alter the solubility of more than 100 proteins such as metabolic enzymes that become more soluble as spores transit to active cell proliferation upon nutrient repletion. A key regulator of this transition is the heat shock protein Hsp42, which shows transient solubilization and phosphorylation, and is essential for the transformation of the cytoplasm during germination. Germinating spores therefore return to growth through the dissolution of protein assemblies, orchestrated in part by Hsp42 activity. The modulation of spores’ molecular properties are likely key adaptive features of their exceptional survival capacities.
Sex and BDNF Val66Met Polymorphism matter for exercise-induced increase in neurogenesis and cognition in middle-aged mice
Authors: Islas-Preciado Dannia , Splinter Tallinn F.L. , Ibrahim Muna , Black Natasha , Wong Sarah , Lieblich Stephanie E , Liu-Ambrose Teresa , Barha Cindy K , Galea Liisa A.M. 
Published: July 2022

AbstractFemales show greater benefits of exercise on cognition in both humans and rodents, which may be related to brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP), the Val66Met polymorphism, within the humanBDNFgene, causes impaired activity-dependent secretion of neuronal BDNF and impairments to some forms of memory. We evaluated whether sex and BDNF genotype (Val66Met polymorphism (Met/Met) versus wildtype (Val/Val)) influenced the ability of voluntary running to increase cognition and hippocampal neurogenesis in mice. Middle-aged C57BL/6J (13 months) mice were randomly assigned to either a control or an aerobic training (AT) group (running disk access). Mice were trained on the visual discrimination and reversal paradigm in a touchscreen-based technology to evaluate cognitive flexibility. BDNF Met/Met mice had fewer correct responses compared to BDNF Val/Val mice on both cognitive tasks. Female BDNF Val/Val mice showed greater cognitive flexibility compared to male mice regardless of AT. Despite running less than BDNF Val/Val mice, AT improved performance in both cognitive tasks in BDNF Met/Met mice. AT increased neurogenesis in the ventral hippocampus of BDNF Val/Val mice of both sexes and increased the proportion of mature type 3 doublecortin-expressing cells in the dorsal hippocampus of female mice only. Our results indicate AT improved cognitive performance in BDNF Met/Met mice and increased hippocampal neurogenesis in BDNF Val/Val mice in middle age. Furthermore, middle-aged female mice may benefit more from AT than males in terms of neuroplasticity, an effect that was influenced by the BDNF Val66Met polymorphism.HighlightsBDNF Met/Met mice performed worse than BDNF Val/Val mice in middle-ageAerobic training (AT) increased cognitive performance in BDNF Met/Met miceAT increased neurogenesis in middle-aged BDNF Val/Val mice onlyFemale BDNF Val/Val mice had better cognitive flexibility than males regardless of ATAT increased more mature new neurons in middle-aged female mice
Solid-state enzymatic hydrolysis of mixed PET-cotton textiles
Authors: Kaabel Sandra , Arciszewski Jane , Borchers Tristan H. , Therien J.P. Daniel , Friščić Tomislav , Auclair Karine 
Published: July 2022

AbstractWaste polyester textiles trap copious amounts of useful polymers, which are not recycled due to separation challenges and partial structural degradation during use and thermo-mechanical recycling. Chemical recycling of polyethylene terephthalate (PET) through depolymerization can provide a feedstock of recycled monomers to make “as-new” polymers, and reduce the accumulation of plastic waste in landfills. Enzymes are highly specific, renewable, environmentally benign catalysts, with hydrolases available that are active on common PET textile fibers and on cotton. The enzymatic PET recycling methods in development, however, have thus far been limited to clean, high-quality PET feedstocks, and most such processes require an energy-intensive melt-amorphization step ahead of enzymatic depolymerization. Here we report that high-crystallinity PET in mixed PET/cotton textiles can be directly and selectively depolymerized to terephthalic acid (TPA) by using a commercial cutinase from Humicola insolens under moist-solid reaction conditions, affording up to 30 ± 2% yield of TPA. The process is readily combined with cotton depolymerisation through simultaneous application of cellulase enzymes (CTec2®), providing up to 83 ± 4% yield of glucose without any negative influence on the TPA yield. The herein presented selective and/or simultaneous enzymatic hydrolysis of PET/cotton textiles in solid reaction mixtures can expand the biocatalytic recycling processes of PET to less-valuable waste materials, and significantly increase its profitability through operating at very high solid-loading (40%), without the need for melt-amorphization.