bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transmission dynamics of COVID-19 in Ghana and the impact of public health interventions
Authors: Ofori Sylvia K. , Schwind Jessica S. , Sullivan Kelly L. , Cowling Benjamin J. , Chowell Gerardo , Fung Isaac Chun-Hai 
Published: July 2021

AbstractThe study characterized COVID-19 transmission in Ghana in 2020-21 by estimating the time-varying reproduction number (Rt) and exploring its association with various public health interventions at the national and regional levels. Ghana experienced four pandemic waves with epidemic peaks in July 2020, and January, August and December, 2021. The epidemic peak was the highest nationwide in December 2021 with Rt ≥2. Throughout 2020-21, per-capita cumulative case count by region increased with population size. Mobility data suggested negative correlation between Rt and staying home in the first 90 days of the pandemic. The relaxation of movement restrictions and religious gatherings were not associated with increased Rt in the regions with lower case burdens. Rt decreased from above 1 when schools reopened in January 2021 to below 1 after vaccination rollout in March 2021. Findings indicated most public health interventions were associated with Rt reduction at the national and regional levels.
Sulfation of O-glycans on mucin-type proteins from serous ovarian epithelial tumors
Authors: Thomsson Kristina A. , Vitiazeva Varvara , Mateoiu Constantina , Jin Chunsheng , Liu Jining , Holgersson Jan , Weijdegard Birgitta , Sundfeldt Karin , Karlsson Niclas G. 
Published: July 2021

ABSTRACTDespite that sulfated O-linked glycans are abundant on ovarian cancer (OC) glycoproteins, their regulation during cancer development and involvement in cancer pathogenesis remain unexplored. We characterized O-glycans carrying sulfation on galactose residues and compared their expression to defined sulfotransferases regulated during OC development. Desialylated sulfated oligosaccharides were released from acidic glycoproteins in the cyst fluid from one patient with a benign serous cyst and one patient with serous OC. Oligosaccharides characterized by LC-MSn were identified as core 1 and core 2 O-glycans up to the size of decamers, and with 1-4 sulfates linked to GlcNAc residues and to C-3 and/or C-6 of Gal. To study the specificity of the potential ovarian sulfotransferases involved, Gal3ST2 (Gal-3S)-, Gal3ST4 (Gal-3S)-, and CHST1 (Gal-6S)-encoding expression plasmids were transfected individually into CHO cells also expressing the P-selectin glycoprotein ligand-1/mouse immunoglobulin G2b (PSGL-1/mIg G2b) fusion protein and the human core 2 transferase (GCNT1). Characterization of the PSGL-1/mIg G2b O-glycans showed that Gal3ST2 preferentially sulfated Gal on the C-6 branch of core 2 structures and Gal3ST4 preferred Gal on the C-3 branch independently if core-1 or-2. CHST1 sulfated Gal residues on both the C-3 (core 1/2) and C-6 branches of core 2 structures. Using serous ovarian tissue micro array, Gal3ST2 was found to be decreased in tissue classified as malignant compared to tissues classified as benign or borderline, with the lowest expression in poorly differentiated malignant tissue. Neither Gal3ST4 nor CHST1 were differentially expressed in benign, borderline or malignant tissue, and there was no correlation between expression level and differentiation stage. The data displays a complex sulfation pattern of O-glycans on OC glycoproteins and that aggressiveness of the cancer is associated with a decreased expression of the Gal3ST2 transferase.
Assessment of COVID-19 risk and prevention effectiveness among spectators of mass gathering events
Authors: Yasutaka Tetsuo , Murakami Michio , Iwasaki Yuichi , Naito Wataru , Onishi Masaki , Fujita Tsukasa , Imoto Seiya 
Published: July 2021

AbstractThere is a need to evaluate and minimise the risk of novel coronavirus infections at mass gathering events, such as sports. In particular, to consider how to hold mass gathering events, it is important to clarify how the local infection prevalence, the number of spectators, the capacity proportion, and the implementation of preventions affect the infection risk. In this study, we used an environmental exposure model to analyse the relationship between infection risk and infection prevalence, the number of spectators, and the capacity proportion at mass gathering events in football and baseball games. In addition to assessing risk reduction through the implementation of various preventive measures, we assessed how face-mask-wearing proportion affects infection risk. Furthermore, the model was applied to estimate the number of infectors who entered the stadium and the number of newly infected individuals, and to compare them with actual reported cases. The model analysis revealed an 86%–95% reduction in the infection risk due to the implementation of face-mask wearing and hand washing. Among the individual measures, face-mask wearing was particularly effective, and the infection risk increased as the face-mask-wearing proportion decreased. A linear relationship was observed between infection risk at mass gathering events and the infection prevalence. Furthermore, the number of newly infected individuals was also dependent on the number of spectators and the capacity proportion independent of the infection prevalence, confirming the importance of considering spectator capacity in infection risk management. These results highlight that it is beneficial for organisers to ensure prevention compliance and to mitigate or limit the number of spectators according to the prevalence of local infection. Both the estimated and reported numbers of newly infected individuals after the events were small, below 10 per 3–4 million spectators, despite a small gap between these numbers.
Epigenome-wide DNA methylation profiling of healthy COVID-19 recoverees reveals a unique signature in circulating immune cells
Authors: Huoman Johanna , Sayyab Shumaila , Apostolou Eirini , Karlsson Lovisa , Porcile Lucas , Rizwan Muhammad , Sharma Sumit , Das Jyotirmoy , Rosén Anders , Lerm Maria 
Published: July 2021

ABSTRACTBackgroundEpigenetic alterations upon microbial challenge have been described as both a defence strategy and a result of pathogenic manipulation. While most COVID-19 studies focus on inflammatory and immune-mediated responses, little is known about epigenetic modifications in response to SARS-CoV-2 infection.MethodsEpigenome-wide DNA methylation patterns from COVID-19 convalescents were compared to uninfected controls from before and after the pandemic. Peripheral blood mononuclear cell (PBMC) DNA was extracted from uninfected controls, COVID-19 convalescents and symptom-free individuals with SARS-CoV-2-specific T cell-responses, as well as from PBMCs stimulated in vitro with SARS-CoV-2. Subsequently, the Illumina MethylationEPIC 850K array was performed, and statistical/bioinformatic analyses comprised differential DNA methylation, pathway over-representation and module identification analyses.ResultsDifferential DNA methylation patterns distinguished COVID-19 convalescents from uninfected controls, with similar results in an experimental SARS-CoV-2 infection model. A SARS-CoV-2-induced module was identified in vivo, comprising 66 genes of which six (TP53, INS, HSPA4, SP1, ESR1 and FAS) were present in corresponding in vitro analyses. Over-representation analyses revealed involvement in Wnt, muscarinic acetylcholine receptor signalling and gonadotropin-releasing hormone receptor pathways. Furthermore, numerous differentially methylated and network genes from both settings interacted with the SARS-CoV-2 interactome.ConclusionsAltered DNA methylation patterns of COVID-19 convalescents suggest recovery from mild-to-moderate SARS-CoV-2 infection leaves longstanding epigenetic traces. As in vitro SARS-CoV-2 infection corroborated in vivo exposure results, this indicates DNA methylation is involved in immune cell responses to challenge with this virus. Future studies should determine whether this reflects host-induced protective antiviral defence or targeted viral hijacking to evade host defence.
Transient beta modulates decision thresholds during human action-stopping
Authors: Muralidharan Vignesh , Aron Adam R , Schmidt Robert 
Published: July 2021

ABSTRACTAction-stopping in humans involves bursts of beta oscillations in prefrontal-basal ganglia regions. To determine the functional role of these beta bursts we took advantage of the Race Model framework describing action-stopping. We incorporated beta bursts in three race model variants, each implementing a different functional contribution of beta to action-stopping. In these variants, we hypothesized that a transient increase in beta could 1) modulate decision thresholds, 2) change stop accumulation rates, or 3) promote the interaction between the Stop and the Go process. We then tested the model predictions using EEG recordings in humans performing a Stop-signal task. We found that the model variant in which beta increased decision thresholds for a brief period of time best explained the empirical data. The model parameters fitted to the empirical data indicated that beta bursts involve a stronger decision threshold modulation for the Go process than for the Stop process. This suggests that prefrontal beta influences stopping by temporarily holding the response from execution. Our study further suggests that human action-stopping could be multi-staged with the beta acting as a pause, increasing the response threshold for the Stop process to modulate behavior successfully. Our novel approach of introducing transient oscillations into the race model and testing against human neurophysiological data allowed us to discover potential mechanisms of prefrontal beta, possibly generalizing its role in situations requiring executive control over actions.
Projecting genetic associations through gene expression patterns highlights disease etiology and drug mechanisms
Authors: Pividori Milton , Lu Sumei , Li Binglan , Su Chun , Johnson Matthew E. , Wei Wei-Qi , Feng Qiping , Namjou Bahram , Kiryluk Krzysztof , Kullo Iftikhar , Luo Yuan , Sullivan Blair D. , Voight Benjamin F. , Skarke Carsten , Ritchie Marylyn D. , Grant Struan F.A. , Greene Casey S. 
Published: July 2021

AbstractGenes act in concert with each other in specific contexts to perform their functions. Determining how these genes influence complex traits requires a mechanistic understanding of expression regulation across different conditions. It has been shown that this insight is critical for developing new therapies. In this regard, the role of individual genes in disease-relevant mechanisms can be hypothesized with transcriptome-wide association studies (TWAS), which have represented a significant step forward in testing the mediating role of gene expression in GWAS associations. However, modern models of the architecture of complex traits predict that gene-gene interactions play a crucial role in disease origin and progression. Here we introduce PhenoPLIER, a computational approach that maps gene-trait associations and pharmacological perturbation data into a common latent representation for a joint analysis. This representation is based on modules of genes with similar expression patterns across the same conditions. We observed that diseases were significantly associated with gene modules expressed in relevant cell types, and our approach was accurate in predicting known drug-disease pairs and inferring mechanisms of action. Furthermore, using a CRISPR screen to analyze lipid regulation, we found that functionally important players lacked TWAS associations but were prioritized in trait-associated modules by PhenoPLIER. By incorporating groups of co-expressed genes, PhenoPLIER can contextualize genetic associations and reveal potential targets missed by single-gene strategies.
Bioactivity, chemical profiling, and 16S rRNA-based phylogeny of haloalkaliphilic Nocardiopsis sp. GhM-HA-6 isolated from the Gulf of Khambhat
Authors: Trivedi Nisha D. , Thumar Jignasha T. 
Published: July 2021

AbstractObjectivesActinomycetes are well known sources of antibiotics, however; recently the focus of antimicrobial research has been turning towards actinomycetes of extreme environments. Therefore, present work would highlight the isolation, identification and characterization of antimicrobial metabolites produced by marine haloalkaliphilic actinomycetes.MethodsSaline soil sample was collected from Ghogha coast (Gulf of Khambhat), Bhavnagar, Western India. Isolation was carried out using selective media while identification was done based on morphological, cultural and molecular characterization. The antimicrobial potential was checked by spot inoculation method. Optimization was carried out by the one variable at a time (OVAT) method. The antimicrobial compounds were extracted using ethyl acetate and characterized by GC-MS.ResultsThe haloalkaliphilic actinomycetes Nocardiopsis sp. GhM-HA-6 was isolated from saline soil of Ghogha coast using starch agar with 10% w/v NaCl and pH 9 and was identified as Nocardiopsis sp. based on morphology, cultural characteristics and 16S rRNA phylogenetic analysis (NCBI Genbank Accession number: KF384492). The organism showed antimicrobial activity against five Gram positive and three Gram negative bacteria while the isolate didn’t show any antifungal activity. Results of optimization showed that the highest production of antimicrobial compounds was obtained using starch broth with 0.5% w/v starch, 1% w/v yeast extract, 10% w/v NaCl and pH 9. GC-MS analysis of ethyl acetate extract of the isolate showed presence of total 18 compounds including various antimicrobial compounds like 2, 4-bis (1, 1-dimethylethyl)-Phenol, various types of alkanes and their derivatives.ConclusionHaloalkaliphilic actinomycete Nocardiopsis sp. GhM-HA-6, from a rarely explored marine habitat, can be a source of antimicrobial compounds with the novel biotechnological applications.
Mitochondrial dysfunction and oxidative stress contribute to cognitive and motor impairment in FOXP1 syndrome
Authors: Wang Jing , Fröhlich Henning , Torres Felipe Bodaleo , Silva Rangel Leal , Agarwal Amit , Rappold Gudrun A. 
Published: July 2021

AbstractThere is increasing evidence that mitochondrial homeostasis - influenced by both genetic and environmental factors - is crucial in neurodevelopment. FOXP1 syndrome is a neurodevelopmental disorder that manifests motor dysfunction, intellectual disability, autism and language impairment. In this study, we used aFoxp1+/−mouse model to address whether cognitive and motor deficits in FOXP1 syndrome are associated with mitochondrial dysfunction and oxidative stress. Here we show that genes with a role in mitochondrial biogenesis and dynamics (e.g.Foxo1,Pgc-1α,Tfam,Opa1, andDrp1)were dysregulated in the striatum ofFoxp1+/−mice at different postnatal stages. Furthermore, in the striatum ofFoxp1+/−animals, mitochondrial membrane potential was disrupted, and reactive oxygen species, lipid peroxidation and cytochrome c release were significantly elevated. These features can explain the reduced neurite branching, learning and memory, endurance, and motor coordination that we observed in these animals. Taken together, we provide strong evidence of mitochondrial dysfunction inFoxp1+/−mice, suggesting that insufficient energy supply and excessive oxidative stress underlies the cognitive and motor impairment in FOXP1 deficiency.
U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors
Authors: Urabe Veronica K. , Stevers Meredith , Ghosh Arun K. , Jurica Melissa S. 
Published: July 2021

AbstractU2 snRNP is an essential component of the spliceosome. It is responsible for branch point recognition in the spliceosome A-complex via base-pairing of U2 snRNA with an intron to form the branch helix. Small molecule inhibitors target the SF3B component of the U2 snRNP and interfere with A-complex formation during spliceosome assembly. We previously found that the first SF3B inhibited-complex is less stable than A-complex and hypothesized that SF3B inhibitors interfere with U2 snRNA secondary structure changes required to form the branch helix. Using RNA chemical modifiers, we probed U2 snRNA structure in A-complex and SF3B inhibited splicing complexes. The reactivity pattern for U2 snRNA in the SF3B inhibited-complex is indistinguishable from that of A-complex, suggesting that they have the same secondary structure conformation, including the branch helix. This observation suggests SF3B inhibited-complex instability does not stem from an alternate RNA conformation and instead points to the inhibitors interfering with protein component interactions that normally stabilize U2 snRNP’s association with an intron. In addition, we probed U2 snRNA in the free U2 snRNP in the presence of SF3B inhibitor and again saw no differences. However, increased protection of nucleotides upstream of Stem I in the absence of SF3A and SF3B proteins suggests a change of secondary structure at the very 5′ end of U2 snRNA. Chemical probing of synthetic U2 snRNA in the absence of proteins results in similar protections and predicts a previously uncharacterized extension of Stem I. Because this stem must be disrupted for SF3A and SF3B proteins to stably join the snRNP, the structure has the potential to influence snRNP assembly and recycling after spliceosome disassembly.
p53-mediated neurodegeneration in the absence of the nuclear protein Akirin2
Authors: Peek Stacey L. , Bosch Peter J. , Bahl Ethan , Iverson Brianna J. , Parida Mrutyunjaya , Bais Preeti , Manak J. Robert , Michaelson Jacob J. , Burgess Robert W. , Weiner Joshua A. 
Published: July 2021

SummaryProper gene regulation is critical for both neuronal development and maintenance as the brain matures. We previously demonstrated that Akirin2, an essential nuclear protein that interacts with transcription factors and chromatin remodeling complexes, is required for the embryonic formation of the cerebral cortex. Here we show that Akirin2 plays a mechanistically distinct role in maintaining healthy neurons during cortical maturation. Restricting Akirin2 loss to excitatory cortical neurons resulted in progressive neurodegeneration via necroptosis and severe cortical atrophy with age. Comparing transcriptomes from Akirin2-null postnatal neurons and cortical progenitors revealed that targets of the tumor suppressor p53, a regulator of both proliferation and cell death encoded by Trp53, were consistently upregulated. Heterozygous deletion of Trp53 rescued neurodegeneration in Akirin2-null neurons. These data: 1) implicate Akirin2 as a critical neuronal maintenance protein; 2) identify p53 pathways as mediators of Akirin2 functions; and 3) suggest Akirin2 dysfunction may be relevant to neurodegenerative diseases.
Tracing the evolution of human gene regulation and its association with shifts in environment
Authors: Colbran Laura L. , Johnson Maya R. , Mathieson Iain , Capra John A. 
Published: July 2021

AbstractAs humans spread throughout the world, they adapted to variation in many environmental factors, including climate, diet, and pathogens. Because many of these adaptations were likely mediated by multiple non-coding variants with small effects on gene regulation, it has been difficult to link genomic signals of selection to specific genes, and to describe the regulatory response to selection. To overcome this challenge, we adapted PrediXcan, a machine learning method for imputing gene regulation from genotype data, to analyze low-coverage ancient human DNA (aDNA). First, we used simulated genomes to benchmark strategies for adapting gene regulatory prediction to increase robustness to incomplete aDNA data. Applying the resulting models to 490 ancient Eurasians, we found that genes with the strongest divergent regulation among ancient populations with hunter-gatherer, pastoralist, and agricultural lifestyles are enriched for metabolic and immune functions. Next, we explored the contribution of divergent gene regulation to two traits with strong evidence of recent adaptation: dietary metabolism and skin pigmentation. We found enrichment for divergent regulation among genes previously proposed to be involved in diet-related local adaptation, and in many cases, the predicted effects on regulation provide explanations for previously observed signals of selection, e.g., atFADS1,GPX1, andLEPR. For skin pigmentation, we applied new models trained in melanocytes to a time series of 2999 ancient Europeans spanning ~38,000 years BP. In contrast to diet, skin pigmentation genes show little regulatory change over time, suggesting that adaptation mainly involved large-effect coding variants. This work demonstrates how aDNA can be combined with present-day genomes to shed light on the biological differences among ancient populations, the role of gene regulation in adaptation, and the relationship between ancient genetic diversity and the present-day distribution of complex traits.
Message in a Bottle – Metabarcoding Enables Biodiversity Comparisons Across Ecoregions
Authors: Steinke D , deWaard SL , Sones JE , Ivanova NV , Prosser SWJ , Perez K , Braukmann TWA , Milton M , Zakharov EV , deWaard JR , Ratnasingham S , Hebert PDN 
Published: July 2021

AbstractBackgroundTraditional biomonitoring approaches have delivered a basic understanding of biodiversity, but they cannot support the large-scale assessments required to manage and protect entire ecosystems. This study employed DNA metabarcoding to assess spatial and temporal variation in species richness and diversity in arthropod communities from 52 protected areas spanning three Canadian ecoregions.ResultsThis study revealed the presence of 26,263 arthropod species in the three ecoregions and indicated that at least another 3,000–5,000 await detection. Results further demonstrate that communities are more similar within than between ecoregions, even after controlling for geographical distance. Overall α-diversity declined from east to west, reflecting a gradient in habitat disturbance. Shifts in species composition were high at every site with turnover greater than nestedness, suggesting the presence of many transient species.ConclusionsDifferences in species composition among their arthropod communities confirm that ecoregions are a useful synoptic for biogeographic patterns and for structuring conservation efforts. The present results also demonstrate that metabarcoding enables large-scale monitoring of shifts in species composition, making it possible to move beyond the biomass measurements that have been the key metric employed in prior efforts to track change in arthropod communities.