bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of major depressive disorder on glycaemic control in type 2 diabetes: a longitudinal cohort study using UK Biobank primary care records
Authors: Gillett Alexandra C , Hagenaars Saskia P , Handley Dale , Casanova Francesco , Young Katherine G , Green Harry , Lewis Cathryn M , Tyrrell Jess 
Published: January 2022

AbstractBackgroundThis study evaluates longitudinal associations between glycaemic control (mean and within-patient variability of glycated haemaglobin (HbA1c) levels) in individuals with type 2 diabetes (T2D) and major depressive disorder (MDD), focusing on the timings of these diagnoses.MethodsIn UK Biobank, T2D was defined using self-report and linked health outcome data, then validated using polygenic scores. Repeated HbA1c measurements (mmol/mol) over the 10 years following T2D diagnosis were outcomes in mixed effects models, with T2D disease duration included using restricted cubic splines. Four MDD exposures were considered: MDD diagnosis prior to T2D diagnosis (pre-T2D MDD), time between pre-T2D MDD diagnosis and T2D, new MDD diagnosis during follow-up (post-T2D MDD) and time since post-T2D MDD diagnosis. Models with and without covariate adjustment were considered.ResultsT2D diagnostic criteria were robustly associated with T2D polygenic scores. In 11,837 T2D cases (6.9 year median follow-up), pre-T2D MDD was associated with a 0.92 increase in HbA1c (95% CI: [0.00, 1.84]), but earlier pre-T2D MDD diagnosis correlated with lower HbA1c. These pre-T2D MDD effects became non-significant after covariate adjustment. Post-T2D MDD individuals demonstrated increasing HbA1c with years since MDD diagnosis (/3 = 0.51, 95% CI: [0.17, 0.86]). Retrospectively, looking across all follow-up, within-patient variability in HbA1c was 1.16 (95% CI: 1.13-1.19) times higher in post-T2D MDD.ConclusionsThe timing of MDD diagnosis is important for understanding glycaemic control in T2D. Poorer control was observed in MDD diagnosed post-T2D, highlighting the importance of depression screening in T2D, and closer monitoring for individuals who develop MDD after T2D.
Immunogenicity of convalescent and vaccinated sera against clinical isolates of ancestral SARS-CoV-2, beta, delta, and omicron variants
Authors: Banerjee Arinjay , Lew Jocelyne , Kroeker Andrea , Baid Kaushal , Aftanas Patryk , Nirmalarajah Kuganya , Maguire Finlay , Kozak Robert , McDonald Ryan , Lang Amanda , Gerdts Volker , Straus Sharon E. , Gilbert Lois , Li Angel Xinliu , Mozafarihasjin Mohammad , Walmsley Sharon , Gingras Anne-Claude , Wrana Jeffrey L. , Mazzulli Tony , Colwill Karen , McGeer Allison J. , Mubareka Samira , Falzarano Darryl 
Published: January 2022

ABSTRACTThe omicron variant of concern (VOC) of SARS-CoV-2 was first reported in November 2021 in Botswana and South Africa. Omicron has evolved multiple mutations within the spike protein and the receptor binding domain (RBD), raising concerns of increased antibody evasion. Here, we isolated infectious omicron from a clinical specimen obtained in Canada. The neutralizing activity of sera from 65 coronavirus disease (COVID-19) vaccine recipients and convalescent individuals against clinical isolates of ancestral SARS-CoV-2, beta, delta, and omicron VOCs was assessed. Convalescent sera from unvaccinated individuals infected by the ancestral virus during the first wave of COVID-19 in Canada (July, 2020) demonstrated reduced neutralization against beta and omicron VOCs. Convalescent sera from unvaccinated individuals infected by the delta variant (May-June, 2021) neutralized omicron to significantly lower levels compared to the delta variant. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of the omicron variant relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Importantly, infection alone, either with ancestral SARS-CoV-2 or the delta variant was not sufficient to induce high neutralizing antibody titers against omicron. This data will inform current booster vaccination strategies, and we highlight the need for additional studies to identify longevity of immunity against SARS-CoV-2 and optimal neutralizing antibody levels that are necessary to prevent infection and/or severe COVID-19.
Rapid and specific degradation of endogenous proteins in mouse models using auxin-inducible degrons
Authors: Macdonald Lewis , Taylor Gillian , Brisbane Jennifer , Christodoulou Ersi , Scott Lucy , Von Kriegsheim Alex , Rossant Janet , Gu Bin , Wood Andrew 
Published: January 2022

AbstractAuxin-inducible degrons are a chemical genetic tool for targeted protein degradation and are widely used to study protein function in cultured mammalian cells. Here, we develop CRISPR-engineered mouse lines that enable rapid and highly specific degradation of tagged endogenous proteins in vivo. Most but not all cell types are competent for degradation. Using mouse genetics, we show that degradation kinetics depend upon the dose of the tagged protein, ligand, and the E3 ligase subunit Tir1. Rapid degradation of condensin I and condensin II – two essential regulators of mitotic chromosome structure - revealed that both complexes are individually required for cell division in precursor lymphocytes, but not in their differentiated peripheral lymphocyte derivatives. This generalisable approach provides unprecedented temporal control over the dose of endogenous proteins in mouse models, with implications for studying essential biological pathways and modelling drug activity in mammalian tissues.HighlightsAuxin-inducible degradation of endogenously tagged proteins in living mice and a range of primary cells.Most but not all cell types are competent for degradationDosage of the tagged protein, E3 ligase substrate receptor and ligand can all determine degradation kineticsRapid degradation of condensin subunits in lymphocytes reveals stage-specific requirements during cell division
Site-specific adaptation mechanisms of an oral pathobiont in the oral and gut mucosae
Authors: Guo Yijie , Kitamoto Sho , Caballero-Flores Gustavo , Watanabe Daisuke , Sugihara Kohei , Núñez Gabriel , Alteri Christopher J. , Inohara Naohiro , Kamada Nobuhiko 
Published: January 2022

AbstractPeriodontal inflammation leads to oral dysbiosis with the expansion of oral pathobionts. Besides the pathogenic role of oral pathobionts during periodontal inflammation, studies have revealed that oral pathobionts contribute to diseases in distant organs beyond the oral mucosa. For example, the oral pathobiont Klebsiella aerogenes, which accumulates in the oral mucosa during periodontitis in mice, can exacerbate colitis when it ectopically colonizes the gastrointestinal tract. However, the precise mechanisms by which oral pathobionts establish their colonization in extra-oral mucosal sites remains incompletely understood. We performed high-throughput in vivo genetic screening to identify fitness genes required for the adaptation of the oral pathobiont K. aerogenes to different mucosal sites – the oral and gut mucosae – at the steady state and during inflammation. In addition, the global transcriptome of K. aerogenes in different environments was analyzed. We determined that K. aerogenes employs genes related to iron acquisition and chaperone usher pili, which are encoded on a newly identified genomic locus named “locus of colonization in the inflamed gut” (LIG), for adaptation in the gut mucosa, particularly during inflammation. In contrast, the LIG virulence factors are not required for K. aerogenes to adapt to the oral mucosa. Thus, oral pathobionts likely exploit distinct adaptation mechanisms in their ectopically colonized intestinal niche compared to their original niche.Author SummaryThe symbiotic bacterial community evolves uniquely at each body site. However, under certain circumstances, symbionts may disseminate far from their original niche and colonize a site ectopically. It has been reported that oral resident bacteria associated with periodontal disease, namely oral pathobionts, contribute to gastrointestinal diseases, such as inflammatory bowel disease and colorectal cancer, through ectopic colonization of the gut. However, the molecular mechanisms by which oral pathobionts adapt to the gut environment remain largely unexplored. In this study, using a model oral pathobiont Klebsiella aerogenes, we screened genes essential for the colonization of the pathobiont at different mucosal sites. We discovered that the oral pathobiont uses distinct virulence mechanisms at two different mucosal sites – the oral and gut mucosae. Understanding the strategies of bacteria localized in ectopic organs may lead to the development of strategies to prevent disease caused by the dissemination of pathogenic oral bacteria.
Seasonality and competition select for variable germination behavior in perennials
Authors: Brink Hanna ten , Haaland Thomas R. , Opedal Øystein H. 
Published: January 2022

AbstractThe common occurrence of within-population variation in germination behavior and associated traits such as seed size has long fascinated evolutionary ecologists. In annuals, unpredictable environments are known to select for bet-hedging strategies causing variation in dormancy duration and germination strategies. Variation in germination timing and associated traits is also commonly observed in perennials, and often tracks gradients of environmental predictability. Although bet-hedging is thought to occur less frequently in long-lived organisms, these observations suggest a role of bet-hedging strategies in perennials occupying unpredictable environments. We use complementary analytical and evolutionary simulation models of within-individual variation in germination behavior in seasonal environments to show how bet-hedging interacts with fluctuating selection, life-history traits, and competitive asymmetries among germination strategies. We reveal substantial scope for bet-hedging to produce variation in germination behavior in long-lived plants, when ‘false starts’ to the growing season results in either competitive advantages or increased mortality risk for alternative germination strategies. Additionally, we find that lowering adult survival may, in contrast to classical bet-hedging theory, result in less spreading of germination by decreasing density-dependent competition. These models extend insights from bet-hedging theory to perennials and explore how competitive communities may be affected by ongoing changes in climate and seasonality patterns.
Continuous B- to A-Transition in Protein-DNA Binding - How Well Is It Described by Current AMBER Force Fields?
Authors: Jurečka Petr , Zgarbová Marie , Černý Filip , Salomon Jan 
Published: January 2022

AbstractWhen DNA interacts with a protein, its structure often undergoes significant conformational adaptation. Perhaps the most common is the transition from canonical B-DNA towards the A-DNA form, which is not a two-state, but rather a continuous transition. The A- and B-forms differ mainly in sugar pucker P (north/south) and glycosidic torsion χ (high-anti/anti). The combination of A-like P and B-like χ (and vice versa) represents the nature of the intermediate states lying between the pure A- and B- forms. In this work, we study how the A/B equilibrium and in particular the A/B intermediate states, which are known to be over-represented at protein-DNA interfaces, are modeled by current AMBER force fields. Eight protein-DNA complexes and their naked (unbound) DNAs were simulated with OL15 and bsc1 force fields as well as an experimental combination OL15χOL3. We found that while the geometries of the A-like intermediate states in the molecular dynamics (MD) simulations agree well with the native X-ray geometries found in the protein-DNA complexes, their populations (stabilities) are significantly underestimated. Different force fields predict different propensities for A-like states growing in the order OL15 < bsc1 < OL15χOL3, but the overall populations of the A-like form are too low in all of them. Interestingly, the force fields seem to predict the correct sequence-dependent A-form propensity, as they predict larger populations of the A-like form in naked (unbound) DNA in those steps that acquire A-like conformations in protein-DNA complexes. The instability of A-like geometries in current force fields may significantly alter the geometry of the simulated protein-DNA complex, destabilize the binding motif, and reduce the binding energy, suggesting that refinement is needed to improve description of protein-DNA interactions in AMBER force fields.
Relative pitch representations and invariance to timbre
Authors: McPherson Malinda J. , McDermott Josh H. 
Published: January 2022

ABSTRACTInformation in speech and music is often conveyed through changes in fundamental frequency (f0), perceived by humans as “relative pitch”. Relative pitch judgments are complicated by two facts. First, sounds can simultaneously vary in timbre due to filtering imposed by a vocal tract or instrument body. Second, relative pitch can be extracted in two ways: by measuring changes in constituent frequency components from one sound to another, or by estimating the f0 of each sound and comparing the estimates. We examined the effects of timbral differences on relative pitch judgments, and whether any invariance to timbre depends on whether judgments are based on constituent frequencies or their f0. Listeners performed up/down and interval discrimination tasks with pairs of spoken vowels, instrument notes, or synthetic tones, synthesized to be either harmonic or inharmonic. Inharmonic sounds lack a well-defined f0, such that relative pitch must be extracted from changes in individual frequencies. Pitch judgments were less accurate when vowels/instruments were different compared to when they were the same, and were biased by the associated timbre differences. However, this bias was similar for harmonic and inharmonic sounds, and was observed even in conditions where judgments of harmonic sounds were based on f0 representations. Relative pitch judgments are thus not invariant to timbre, even when timbral variation is naturalistic, and when such judgments are based on representations of f0.
Proteasome granular localization is regulated through mitochondrial respiration and kinase signaling
Authors: Waite Kenrick A , Roelofs Jeroen 
Published: January 2022

AbstractIn yeast, proteasomes are enriched in cell nuclei where they execute important cellular functions. Nutrient-stress can change this localization indicating proteasomes respond to the cell’s metabolic state. However, the signals that connect these processes remain poorly understood. Carbon starvation triggers a reversible translocation of proteasomes to cytosolic condensates known as proteasome storage granules (PSGs). Surprisingly, we observed strongly reduced PSG levels when cells had active cellular respiration prior to starvation. This suggests the mitochondrial activity of cells is a determining factor in the response of proteasomes to carbon starvation. Consistent with this, upon inhibition of mitochondrial function we observed proteasomes relocalize to granules. These links between proteasomes and metabolism involve specific signaling pathways, as we identified a MAP kinase cascade that is critical to the formation of proteasome granules after respiratory growth but not following glycolytic growth. Furthermore, the yeast homolog of AMP kinase, Snf1, is important for proteasome granule formation induced by mitochondrial inhibitors, while dispensable for granule formation following carbon starvation. We propose a model where mitochondrial activity promotes proteasome nuclear localization.SummaryWe determined a role for mitochondrial respiration in regulating proteasome granule formation and identified the cell integrity MAP kinase pathway and Snf1 kinase as regulatory factors.
Parallel molecular mechanisms underlie convergent evolution of the exaggerated snout phenotype in East African cichlids
Authors: Duenser Anna , Singh Pooja , Lecaudey Laurène Alicia , Sturmbauer Christian , Albertson Craig , Gessl Wolfgang , Ahi Ehsan Pashay 
Published: January 2022

AbstractStudying instances of convergent evolution of novel phenotypes can shed light on the evolutionary constraints that shape morphological diversity. Cichlid fishes from the East African Great Lakes are a prime model to investigate convergent adaptations. However, most studies on cichlid craniofacial morphologies have primarily considered bony structures, while soft tissue adaptations have been less intensely scrutinised. A rare example of an exaggerated soft tissue phenotype is the formation of a snout flap. This tissue flap develops from the upper lip and has evolved in only one cichlid genus from Lake Malawi and one genus from Lake Tanganyika. To investigate the molecular basis of snout flap convergence, we used mRNA sequencing to compare two species with snout flap (Labeotropheus trewavasae and Ophthalmotilapia nasuta) to their close relatives without snout flaps (Tropheops tropheops and Ophthalmotilapia ventralis) from Lake Tanganyika and Malawi. Our analysis revealed a greater complexity of differential gene expression patterns underlying the snout flap in the younger adaptive radiation of Lake Malawi than in the older Lake Tanganyika radiation. We identified 201 genes that were repeatedly differentially expressed between species with and without the snout flap in both lakes, suggesting that the pathway that gives rise to snout flaps is evolutionarily constrained, even though the flaps play very different functions in each species. The convergently expressed genes are involved in proline and hydroxyproline metabolism, which have been linked to human skin and facial deformities. Additionally, we also found enrichment for transcription factor binding sites upstream of differentially expressed genes such as members of the FOX transcription factor family, especially foxf1 and foxa2, which also showed an increased expression in the flapped snout and are linked to nose morphogenesis in mammals, as well as ap4 (tfap4), a transcription factor showing reduced expression in the flapped snout with an unknown role in the development of craniofacial soft tissues. As genes involved in cichlids snout flap development are associated with many human mid-line facial dysmorphologies, our findings imply a conservation of genes involved in mid-line patterning across vastly distant evolutionary lineages of vertebrates.Significance statementThe study of the evolution of similar physical traits across taxa can give insight into the molecular architecture underlying shared phenotypes. This has mostly been studied in bony structures, while soft tissue traits have been less intensely covered. We investigated the exaggerated snout in cichlid species from Lake Malawi and Lake Tanganyika and found that many genes involved in the development of the snout flap are also associated with mid-line dysmorphologies in humans, implying a conservation across distant vertebrate lineages.
Enumeration of Citrus endophytic bacterial communities based on illumine metagenomics technique
Authors: Mushtaq Sehrish , Shafiq Muhammad , Ashraf Tehseen , Saleem Haider Muhammad , Atta Sagheer 
Published: January 2022

AbstractCitrus is a valuable crop in Pakistan because it is rich in vitamin C and antioxidants. Huanglongbing (HLB) has an influence on citrus production around the world caused by a bacterium “Candidatus liberibacter asiaticus” (CLas), africanus and americanus. The structure and diversity of bacterial species in various ecosystems can be quickly examined using NGS. This approach is considerably quicker and more precise than outdated methods. Healthy or citrus greening infected leaf samples of Grapefruit, Citrus aurantifolia, and Citrus reticulata Blanco was used for diversity analysis. In this study high throughput, NGS technique was used to access the population of both cultivable and non-cultivable bacterial endophytes from citrus leaves, by using PCR amplicons of 16S rDNA sequences (V5–V7 regions) with Illumina Hi seq. As a result, a total number of 68,722 sequences were produced from the test samples. According to the NGS-based diversity classification, the most common genera of exploited bacterial endophytes were Proteobacteria, Firmicutes, Bacteroides, Cyanobacteria, and Actinobacteria. Citrus aurantifolia and Citrus paradisi showed almost equal diversity, whereas Citrus reticulata Blanco had a higher proportion of Proteobacteria and Cyanobacteria in their leaves. To determine alpha diversity (AD), additional data was analyzed using statistical indices such as Shannon, Chao1, and Simpson. According to the inverse Simpson diversity index, the abundance of the microbial population in six different citrus samples was 0.48, 0.567, and 0.163, respectively. The metagenomics of microbiota in plant tissues was successfully recorded by NGS technology, which can help us learn more about the interactions between plants and microbes. This research is the first step toward a better understanding of 16SrRNA-based metagenomics from citrus in Pakistan using Illumina (Hi seq) Technology.
Local-scale virome depiction supports significant differences between Aedes aegypti and Aedes albopictus
Authors: Calle-Tobón Arley , Pérez-Pérez Juliana , Forero-Pineda Nicolás , Chávez Omar Triana , Rojas-Montoya Winston , Rúa-Uribe Guillermo , Gómez-Palacio Andrés 
Published: January 2022

AbstractAedes spp. comprise the primary group of mosquitoes that transmit arboviruses such as dengue, Zika, and chikungunya viruses to humans, and thus these insects pose a significant burden on public health worldwide. Advancements in next-generation sequencing and metagenomics have expanded our knowledge on the richness of RNA viruses harbored by arthropods such as Ae. aegypti and Ae. albopictus; increasing evidence suggests that vectorial competence can be modified by the microbiome (comprising both bacteriome and virome) of mosquitoes present in endemic zones. Using an RNA-seq-based metataxonomic approach, this study determined the virome structure of field-caught Ae. aegypti and Ae. albopictus mosquitoes in Medellín, Colombia, a municipality with a high incidence of mosquito-transmitted arboviruses. The two species are sympatric, but their core viromes differed considerably in richness, diversity, and abundance; the viromes were dominated by a few viruses. BLAST searches of assembled contigs suggested that at least 17 virus species (16 of which are insect-specific viruses [ISVs]) infect the Ae. aegypti population. Dengue virus 3 was detected in one sample. In Ae. albopictus, up to 11 ISVs and one plant virus were detected. Therefore, the virome composition was species-specific. The bacterial endosymbiont Wolbachia was identified in all Ae. albopictus samples and in some Ae. aegypti samples collected after 2017. The presence of Wolbachia sp. in Ae. aegypti was not related to significant changes in the richness, diversity, or abundance of this mosquito’s virome, although it was related to an increase in the abundance of Aedes aegypti To virus 2 (unclassified). The mitochondrial diversity of these mosquitoes suggested that the Ae. aegypti population underwent a change that started in the second half of 2017, which coincides with the release of Wolbachia-infected mosquitoes in Medellín, indicating that the population of wMel-infected mosquitoes has expanded. However, additional studies are required on the dispersal speed and intergenerational stability of wMel in Medellín and nearby areas as well as on the introgression of genetic variants in the native mosquito population.