bluuebunny/crossref_metadata_2025 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

REST 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.
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

Rheumatoid 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

Introduction

The 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.

Methods

On 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).

Results

1,528,431 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.

Conclusion

Booster 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

Contraceptive 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

We 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

As 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

Peroxisomes 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

Double 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

The 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

Females 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.

Highlights

BDNF Met/Met mice performed worse than BDNF Val/Val mice in middle-age

Aerobic training (AT) increased cognitive performance in BDNF Met/Met mice

AT increased neurogenesis in middle-aged BDNF Val/Val mice only

Female BDNF Val/Val mice had better cognitive flexibility than males regardless of AT

AT 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

Waste 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.
Geobacter sulfurreducens’ unique metabolism results in cells with a high iron and lipid content
Authors: Howley Ethan , Ki Dongwon , Krajmalnik-Brown Rosa , Torres César I.
Published: July 2022

Geobacter sulfurreducens is a ubiquitous iron reducing bacterium in soils, and in engineered systems it can respire an electrode to produce measurable electric current. Its unique metabolism, heavily dependent on an extensive network of cytochromes, requires a unique cell composition. In this work we used metallomics, cell fraction and elemental analyses, and transcriptomics to study and analyze the cell composition of G. sulfurreducens. Elemental composition studies (C,H,O,N, ash content) showed a high C:O and H:O ratios of approximately 1.7:1 and 0.25:1, indicative of more reduced cell composition that is consistent with a high lipid content. Our study shows that G. sulfurreducens cells have a large amount of iron (2 ± 0.2 μg/gdw) and lipids (32 ± 0.5% dw/dw) and that this composition does not change whether the cells are grown with a soluble or an insoluble electron acceptor. The high iron concentration, higher than similar microorganisms, is attributed to the production of cytochromes that are abundant in transcriptomic analyses in both solid and soluble electron acceptor growth. The unique cell composition of G. sulfurreducens must be considered when growing this microorganism for lab studies and commercial applications.

Importance

Geobacter sulfurreducens is an electroactive microorganism. In nature, it grows on metallic minerals by transferring electrons to them, effectively ‘breathing’ metals. In a manmade system, it respires an electrode to produce an electric current. It has become a model organism for the study of electroactive organisms. There are potential biotechnological applications of an organism that can bridge the gap between biology and electrical signal, and as a ubiquitous iron reducer in soils around the world, G. sulfurreducens and its relatives impact the global iron cycle. We measured the concentrations of metals, macromolecules, and basic elements in G. sulfurreducens to define this organism’s composition. We also used gene expression data to discuss which proteins those metals could be associated with. We found that G. sulfurreducens has a large amount of lipid and iron compared to other bacteria — these observations are important for future microbiologists and biotechnologists working with the organism.
Programmable acetylation modification of bacterial proteins by a Cas12a-guided acetyltransferase
Authors: Liu Yanqiang , Zuo Ni , Jiang Weihong , Gu Yang
Published: July 2022

Protein lysine acetylation (PLA) is a crucial post-translational modification in organisms that regulates a variety of metabolic and physiological activities. Many advances have been made in PLA-related research; however, the quick and accurate identification of causal relationships between specific protein acetylation events and phenotypic outcomes at the proteome level remains unattainable due to the lack of in situ targeted modification techniques. In this study, based on the characteristics of transcription-translation coupling in bacteria, we designed and constructed an in situ targeted protein acetylation (TPA) system fusing the dCas12a protein, guiding element crRNA, and bacterial acetylase At2. Rapid identification of multiple independent protein acetylation and cell phenotypic analyses in gram-negativeE. coliand gram-positiveC. ljungdahliidemonstrated that TPA is a specific and efficient targeting tool for protein modification studies and engineering.
No evidence for a common blood microbiome based on a population study of 9,770 healthy humans
Authors: Tan Cedric C.S. , Ko Karrie K.K. , Chen Hui , Liu Jianjun , Loh Marie ,   SG10K_Health Consortium, Chia Minghao , Nagarajan Niranjan
Published: July 2022

Human blood is conventionally considered sterile. Recent studies have challenged this, suggesting the presence of a blood microbiome in healthy humans. We present the largest investigation to date of microbes in blood, based on shotgun sequencing libraries from 9,770 healthy subjects. Leveraging the availability of data from multiple cohorts, we stringently filtered for laboratory contaminants to identify 117 microbial species detected in the blood of sampled individuals, some of which had signatures of DNA replication. These primarily comprise of commensals associated with human body sites such as the gut (n=40), mouth (n=32), and genitourinary tract (n=18), which are species that are distinct from common pathogens detected in clinical blood cultures based on more than a decade of records from a tertiary hospital. Contrary to the expectations of a shared blood microbiome, no species were detected in 84% of individuals, while only a median of one microbial species per individual was detected in the remaining 16%. Futhermore, microbes of the same species were detected in <5% of individuals, no co-occurrence patterns similar to microbiomes in other body sites was observed, and no associations between host phenotypes (e.g. demographics and blood parameters) and microbial species could be established. Overall, these results do not support the hypothesis of a consistent core microbiome endogenous to human blood. Rather, our findings support the transient and sporadic translocation of commensal microbes, or their DNA, from other body sites into the bloodstream.
The differing roles of flavins and quinones in extracellular electron transfer in Lactiplantibacillus plantarum
Authors: Tolar Joe G. , Li Siliang , Ajo-Franklin Caroline M.
Published: July 2022

Lactiplantibacillus plantarum is a lactic acid bacteria that is commonly found in the human gut and fermented food products. Despite its overwhelmingly fermentative metabolism, this microbe can perform extracellular electron transfer (EET) when provided with an exogenous quinone, 1,4-dihydroxy-2-naphthoic acid (DHNA) and riboflavin. However, the separate roles of DHNA and riboflavin in EET in L. plantarum has remained unclear. Here we seek to understand the role of quinones and flavins for EET by monitoring iron and anode reduction in the presence and absence of these small molecules. We found that either addition of DHNA or riboflavin can support robust iron reduction, indicating electron transfer to extracellular iron occurs through both flavin-dependent and DHNA-dependent routes. Using genetic mutants of L. plantarum, we found that flavin-dependent iron reduction requires Ndh2 and EetA, while DHNA-dependent iron reduction largely relies on Ndh2 and PplA. In contrast to iron reduction, DHNA-containing media supported more robust anode reduction than riboflavin-containing media, suggesting electron transfer to an anode proceeds most efficiently through the DHNA-dependent pathway. Furthermore, we found that flavin-dependent anode reduction requires EetA, Ndh2, and PplA, while DHNA-dependent anode reduction requires Ndh2 and PplA. Taken together, we identify multiple EET routes utilized by L. plantarum and show that the EET route depends on access to environmental biomolecules and on the extracellular electron acceptor. This work expands our molecular-level understanding of EET in Gram-positive microbes and provides additional opportunities to manipulate EET for biotechnology.

Importance

Lactic acid bacteria are named because of their nearly exclusive fermentative metabolism. Thus, the recent observation of EET activity - typically associated with anaerobic respiration - in this class of organisms has forced researchers to rethink the rules governing microbial metabolic strategies. Our identification of multiple routes for EET in L. plantarum that depend on two separate redox active small molecules expands our understanding of how microbes metabolically adapt to different environments to gain an energetic edge and how these processes can be manipulated for biotechnological uses. Understanding the role of EET in lactic acid bacteria is of great importance due to the significance of lactic acid bacteria in agriculture, bioremediation, food production, and gut health. Furthermore, the maintenance of multiple EET routes speak to the importance of this process to function in a variety of environmental conditions.
Higher Perceived Stress during the COVID-19 pandemic increased Menstrual Dysregulation and Menopause Symptoms
Authors: de leon Romina Garcia , Baaske Alexandra , Albert Arianne Y , Booth Amy , Racey C. Sarai , Gordon Shanlea , Smith Laurie W. , Gottschlich Anna , Sadarangani Manish , Kaida Angela , Ogilvie Gina S. , Brotto Lori A. , Galea Liisa A.M.
Published: July 2022

Objective

The increased stress the globe has experienced with the COVID-19 pandemic has affected mental health, disproportionately affecting women. However, how perceived stress in the first year affected menstrual and menopausal symptoms has not yet been investigated.

Methods

Residents in British Columbia, Canada, were surveyed online as part of the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex (RESPPONSE). A subgroup (n=4171) who were assigned female sex at birth (age 25-69) and were surveyed within the first 6-12 months of the pandemic (August 2020-February 2021), prior to the widespread rollout of vaccines, were retrospectively asked if they noticed changes in their menstrual or menopausal symptoms, as well as completing validated measures of stress, depression, and anxiety.

Results

We found that 27.8% reported menstrual cycle disturbances and 6.7% reported increased menopause symptoms. Those who scored higher on perceived stress, depression, and anxiety scales were more likely to have reproductive cycle disturbances. Free text responses revealed that reasons for disturbances were perceived to be related to the pandemic.

Conclusions

The COVID-19 pandemic has highlighted the need to research women’s health issues, such as menstruation. Our data indicates that in the first year of the pandemic, almost a third of the menstruating population reported disturbances in their cycle, which is approximately two times higher than in non-pandemic situations and four times higher than any reported changes in menopausal symptoms across that first year of the pandemic.

Summary Sentences

Women+ with higher anxiety, depression or perceived stress scores during the first year of the pandemic were more likely to have experienced menstrual cycle phase disturbance or menopausal status disruption. Younger women were particularly prone to disturbances in their reproductive cycles.
Detecting salivary host-microbiome RNA signature for aiding diagnosis of oral and throat cancer
Authors: Banavar Guruduth , Ogundijo Oyetunji , Julian Cristina , Toma Ryan , Camacho Francine , Torres Pedro J. , Hu Lan , Kenny Liz , Vasani Sarju , Batstone Martin , Dimitrova Nevenka , Vuyisich Momchilo , Amar Salomon , Punyadeera Chamindie
Published: July 2022

Objectives

Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are the two major subtypes of head and neck cancer (HNC) that can go undetected resulting in late detection and poor outcomes. We describe the development and validation of a convenient and easy-to-use test, called CancerDetect for Oral & Throat cancer™ (CDOT), to detect markers of OSCC and/or OPSCC within a high-risk population using salivary metatranscriptomics.

Materials and Methods

We collected saliva samples from 1,175 unique individuals who were 50 years or older, or adults who had a history of tobacco use. All saliva samples were processed through a metatranscriptomic method to isolate microbial organisms and functions, as well as human transcripts. Of the 1175 samples, 945 were used to train a classifier using machine learning methods, resulting in a salivary RNA metatranscriptomic signature. The classifier was then independently validated on the 230 remaining samples unseen by the classifier, consisting of 20 OSCC (all stages), 76 OPSCC (all stages), and 134 negatives (including 14 pre-malignant).

Results

On the validation cohort, the specificity of the CDOT test was 94%, sensitivity was 90% for participants with a histopathological diagnosis of OSCC, and 84.2% for participants with a diagnosis of OPSCC. Similar classification results were observed among people in early stage (stages I & II) vs late stage (stages III & IV) of OSCC and OPSCC.

Conclusions

CDOT is a non-invasive test that can be easily administered in dentist offices, primary care centers and specialized cancer clinics for early detection of OPSCC and OSCC. This test, having received breakthrough designation by the US Food and Drug Administration (FDA), will broadly enable early diagnosis of OSCC and OPSCC, saving lives and significantly reducing healthcare expenditure.
A single dose of intravenous human amniotic membrane-derived mesenchymal stem cells limits transmural infarction, reduces fibrosis size, and improves left ventricular systolic function in the myocardial ischemic/reperfusion model of rats
Authors: Sung Jia-Wei , Yeh Yen-Ting , Peng Fu-Shiang , Chen Yi-Chen , Li Ai-Hsien , Wu Shinn-Chih
Published: July 2022

Despite the advances in coronary reperfusion in acute myocardial infarction (MI), post-MI heart failure is still a large burden of public health. Transmural infarction and extended fibrosis contribute largely to post-MI systolic dysfunction and heart failure, and thus cardioprotective strategies are crucial. Human amniotic membrane-derived mesenchymal stem cells (hAMSCs) have been shown with properties of immunomodulation, anti-inflammation, and low immunogenicity, which make them good candidates for cell therapies. In this study, a myocardial ischemia/reperfusion (I/R) model was established in rats, and hAMSCs were administered via the tail vein during coronary reperfusion. Compared to the control group, the rats receiving hAMSCs during the I/R procedure (hAMSC group) exhibited significantly better left ventricular ejection fractions after MI. Histological examinations of the hearts in hAMSC group showed minimal transmural infarction 4 weeks after the I/R procedure. Compared to the control group, hAMSC group had reduced size of cardiac fibrosis and less thinning of myocardial wall. In conclusion, intravenous hAMSCs limit transmural infarction, reduce fibrosis size, and improve left ventricular systolic function after MI in the animal model.
KAP is the neuronal organelle adaptor for Kinesin-2 KIF3AB and KIF3AC
Authors: Garbouchian Alex , Montgomery Andrew , Gilbert Susan P. , Bentley Marvin
Published: July 2022

Kinesin-driven organelle transport is crucial for neuron development and maintenance, yet the mechanisms by which kinesins specifically bind their organelle cargoes remain undefined. In contrast to other transport kinesins, the neuronal function and specific organelle adaptors of heterodimeric Kinesin-2 family members KIF3AB and KIF3AC remain unknown. We developed a novel microscopy-based assay to define protein–protein interactions in intact neurons. The experiments found that KIF3AB and KIF3AC both bind KAP. These interactions are mediated by the distal C-terminal tail regions and not the coiled-coil domain. We used live-cell imaging in cultured hippocampal neurons to define the localization and trafficking parameters of KIF3AB and KIF3AC organelle populations. We discovered that KIF3AB/KAP and KIF3AC/KAP bind the same organelle populations and defined their transport parameters in axons and dendrites. The results also show that ∼12% of KIF3 organelles contain the RNA binding protein, adenomatous polyposis coli. These data point towards a model in which KIF3AB and KIF3AC use KAP as their neuronal organelle adaptor and that these kinesins mediate transport of a range of organelles.
Enhanced production of natural shiga toxin by overexpressing A subunit of Stx2e in Stx2e-producing Escherichia coli isolated in South Korea
Authors: Seo Byoung Joo , Yu Jeong Hee , Kim Seung Chai , Yu Yeong Ju , Park Byung Yong , Park Jung Hee , Kim Won Il , Hur Jin
Published: July 2022

This study explored the optimal culture conditions for maximizing shiga toxin production in Stx2e-producing Escherichia coli (STEC) 150229, isolated from porcine edema disease (ED), with the goal of preparing a Stx2e toxoid vaccine candidate. High cytotoxicity was observed for this strain [tissue culture cytotoxic dose 50% (104 TCCD50/100 µl)] from 48 h after incubation. Stx2e was overexpressed by transforming pStx2e A into STEC 150229, resulting in the production of recombinant Stx2e A/B complex combined with intrinsic Stx2e B. The enhanced production of Stx2e was evaluated based on the level of cytotoxicity against Vero cells. The highest cytotoxicity (105 TCCD50/100 µl) was observed with the samples of recombinant Stx2e A/B complex eluted with 500 mM imidazole at 48 h of incubation. In conclusion, the recombinant Stx2e A protein forms an active protein complex with the intrinsic Stx2e B component from STEC 150229, producing high levels of shiga toxin.
An ERAD-independent role for rhomboid pseudoprotease Dfm1 in mediating sphingolipid homeostasis
Authors: Bhaduri Satarupa , Aguayo Analine , Ohno Yusuke , Proietto Marco , Jung Jasmine , Wang Isabel , Kandel Rachel , Singh Narinderbir , Ibrahim Ikran , Fulzele Amit , Bennett Eric , Kihara Akio , Neal Sonya E.
Published: July 2022

Nearly one-third of nascent proteins are initially targeted to the endoplasmic reticulum (ER) where they are correctly folded and assembled before being delivered to their final cellular destinations. To prevent the accumulation of misfolded membrane proteins, ER-associated-degradation (ERAD) removes these clients from the ER membrane to the cytosol in a process known as retrotranslocation. Our recent work demonstrates that rhomboid pseudoprotease, Dfm1, is involved in the retrotranslocation of ubiquitinated integral membrane ERAD substrates. To survey for potential interaction partners of Dfm1, we performed protein-proximity labeling by BioID (proximity-dependent biotin identification) followed by mass spectrometry and identified several interacting proteins known to play a role in the sphingolipid biosynthesis pathway. Specifically, we found that Dfm1 physically interacts with the SPOTS complex, which is composed of serine palmitoyltransferase (SPT) enzymes and accessory components and is critical for catalyzing the first rate-limiting step of the sphingolipid biosynthesis pathway. We demonstrate for the first time that Dfm1 has a role in ER export, a function that is independent of Dfm1’s canonical ERAD retrotranslocation function. Specifically, we show that loss of Dfm1 results in the accumulation of phosphorylated Orm2 at the ER, suggesting a novel role for Dfm1 in controlling Orm2 export from the ER and its subsequent degradation by EGAD. Moreover, recruitment of Cdc48 by Dfm1, which is critical for its role in ERAD retrotranslocation, is dispensable for Dfm1’s role in ER export. Given that the accumulation of human Orm2 homologs, ORMDLs, are associated with many maladies, our study serves as a molecular foothold for understanding how dysregulation of sphingolipid metabolism leads to various diseases.
A genome-wide association study of Chinese and English language abilities in Hong Kong Chinese children
Authors: Lin Yu-Ping , Shi Yujia , Zhang Ruoyu , Xue Xiao , Rao Shitao , Lui Kevin Fai-Hong , Pan Dora Jue , Maurer Urs , Choy Richard Kwong-Wai , Paracchini Silvia , McBride Catherine , So Hon-Cheong
Published: August 2022

Background

Reading and language skills are important and known to be heritable, and dyslexia and developmental language disorder are commonly recognized learning difficulties worldwide. However, the genetic basis underlying these skills remains poorly understood. In particular, most previous genetic studies were performed on Westerners. To our knowledge, few or no previous genome-wide association studies (GWAS) have been conducted on literacy skills in Chinese as a native language or English as a second language (ESL) in a Chinese population.

Methods

We conducted GWAS and related bioinformatics analyses on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; N=1046). We performed association tests at the single-variant, gene, pathway levels, and transcriptome-wide association studies (TWAS) to explore how imputed expression changes might affect the phenotypes. In addition, we tested genetic overlap of these cognitive traits with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis.

Results

Totally 9 independent loci (LD-clumped at r2=0.01) reached genome-wide significance (p<5e-08) (filtered by imputation quality metric Rsq>0.3 and having at least 2 correlated SNPs(r2>0.5) with p<1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, dictation and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with intelligence, EA other neuropsychiatric phenotypes, such as MANEA, TNR, PLXNC1 and SHTN1. We also revealed significantly enriched genes and pathways based on SNP-based analysis. In PRS analysis, EA and CP showed significant polygenic overlap with a variety of language traits, especially English literacy skills. ADHD PRS showed a significant association with English vocabulary score.

Conclusions

This study revealed numerous genetic loci that may be associated with Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings and elucidate the mechanisms involved.
Accuracy of sensor-based classification of clinically relevant motor activities in daily life of children with mobility impairments
Authors: Rast Fabian Marcel , Jucker Florence , Labruyère Rob
Published: August 2022

Background

Wearable inertial sensors enable objective, long-term monitoring of motor activities in the children’s habitual environment after rehabilitation. However, sophisticated algorithms are needed to derive clinically relevant outcome measures. Therefore, we developed three independent algorithms based on the needs of pediatric rehabilitation. The first algorithm estimates the duration of lying, sitting, and standing positions and the number of sit-to-stand transitions with data of a trunk and a thigh sensor. The second algorithm detects active wheeling periods and distinguishes it from passive wheeling with data of a wrist and a wheelchair sensor. The third algorithm detects walking periods, discriminates between free and assisted walking, and estimates the covered altitude change during stair climbing with data of a single ankle sensor and a sensor placed on walking aids.

Research question

This study aimed to determine the accuracy of each algorithm in children undergoing rehabilitation.

Methods

Thirty-one children and adolescents with various medical diagnoses and levels of mobility impairments performed a semi-structured activity circuit. They wore inertial sensors on both wrists, the sternum, and the thigh and shank of the less-affected side. Video recordings, which were labeled by two independent researchers, served as reference criteria to determine the algorithms’ performance.

Results

The activity classification accuracy was 97% for the posture detection algorithm, 96% for the wheeling detection algorithm, and 93% for the walking detection algorithm.

Significance

This study presents three novel algorithms that provide a comprehensive and clinically relevant view of the children’s motor activities. These algorithms are described reproducibly and can be applied to other inertial sensor technologies. Moreover, they were validated in children with mobility impairments and can be used in clinical practice and clinical trials to determine the children’s motor performance in their habitual environment. To enable the evaluation of future algorithms, we published the labeled dataset.
Heme Hopping Falls Short: What Explains Anti-Arrhenius Conductivity in a Multi-heme Cytochrome Nanowire?
Authors: Guberman-Pfeffer Matthew J.
Published: August 2022

A helical homopolymer of the outer-membrane cytochrome type S (OmcS) was proposed to electrically connect a common soil bacterium, Geobacter sulfurreducens, with minerals and other microbes for biogeochemically important processes. OmcS exhibits a surprising rise in conductivity upon cooling from 300 to 270 K that has recently been attributed to a restructuring of H-bonds, which in turn modulates heme redox potentials. This proposal is more thoroughly examine herein by (1) analyzing H-bonding at 13 temperatures encompassing the entire experimental range; (2) computing redox potentials with quantum mechanics/molecular mechanics for 10-times more (3000) configurations sampled from 3-times longer (2 μs) molecular dynamics, as well as 3 μs of constant redox and pH molecular dynamics; and (3) modeling redox conduction with both single-particle diffusion and multi-particle flux kinetic schemes. Upon cooling by 30 K, the connectivity of the intra-protein H-bonding network was highly (86%) similar. An increase in the density and static dielectric constant of the filament’s hydration shell caused a −0.002 V/K shift in heme redox potentials, and a factor of 2 decrease in charge mobility. Revision of a too-far negative redox potential in prior work (−0.521 V; expected = −0.350 – +0.150 V; new Calc. = −0.214 V vs. SHE) caused the mobility to be greater at high versus low temperature, opposite to the original prediction. These solution-phase redox conduction models failed to reproduce the experimental conductivity of electrode-absorbed, partially dehydrated, and possibly aggregated OmcS filaments. Some improvement was seen by neglecting reorganization energy from the solvent to model dehydration. Correct modeling of the physical state is suggested to be a prerequisite for reaching a verdict on the operative charge transport mechanism and the molecular basis of its temperature response.
ASM-3D: An attentional search model fashioned after what and where/how pathways for target search in 3D environment
Authors: Kumari Sweta , Shobha Amala V Y , Nivethithan M , Chakravarthy V. Srinivasa
Published: August 2022

We propose a biologically inspired attentional search model for target search in a 3D environment, which has two separate channels for object classification, analogous to the “what” pathway in the human visual system, and for prediction of the next location of the camera, analogous to the “where” pathway. We generated 3D Cluttered Cube datasets that consist of an image on one vertical face, and clutter images on the other faces. The camera goes around each cube on a circular orbit centered on the cube and determines the identity of the image and the face on which it is located. The images pasted on the cube faces were drawn from three: MNIST handwriting digit, QuickDraw, and RGB MNIST handwriting digit datasets. The attentional input of 3 concentric cropped windows resembling the high-resolution central fovea and low-resolution periphery of the retina, flows through a Classifier Network and a Camera Motion Network. The Classifier Network classifies the current view into one of the classes or clutter. The Camera Motion Network predicts the camera’s next position on the orbit (varying the azimuthal angle or ‘θ’). Here the camera performs one of three actions: move right, move left, or don’t move. The Camera-Position Network adds the camera’s current θ information into the higher features level of the Classifier Network and the Camera Motion Network. The Camera Motion Network is trained using Q-learning where the reward is 1 if the classifier network gives the correct classification, otherwise 0. Total loss is computed by adding the mean square loss of temporal difference and cross entropy loss. Then the total loss is backpropagated using Adam optimizer. Results on two grayscale image datasets and one RGB image dataset show that the proposed model is successfully able to discover the desired search pattern to find the target face on the cube, and also classify the target face accurately.