bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational analysis of SARS-CoV-2. ORF8 and the evolution of the Delta and Omicron variants
Authors: Trieu Gopika , Trieu Vuong N 
Published: December 2021

ABSTRACTSARS-CoV-2 the virus responsible for the current pandemic. This virus is continually evolving, adapting to both innate and acquired immune responses and therapeutic drugs. Therefore, it is important to understand how the virus evolving to design the appropriate therapeutic and vaccine in preparation for future variants. Here, we used the online SARS-CoV-2 databases, Nextstrain and Ourworld, to map the evolution and epidemiology of the virus. We identified 30 high entropy residues which underwent a progressive evolution to arrive at the current dominant variant - Delta variant. The virus underwent mutational waves with the first wave made up of structural proteins important in its infectivity and the second wave made up of the ORFs important for its contagion. The most important driver of the second wave is ORF8 mutations at residue 119 and 120. Further mutations of these two residues are creating new clades that are offshoots from the Delta backbone. More importantly the further expansion of the S protein in the Omicron variant is now followed with the acquisition of ORF8 mutations 119 and 120. These findings demonstrate how SARS-CoV-2 mutates and points to two evolutionary paths; 1) Mutational expansion on the Delta backbone among the ORFs and 2) Mutational expansion of the S protein on other backbone follow with mutational wave among the ORFs. Both are happening at the same time right now with the Omicron variant early in the first wave to follow with a more aggressive second wave of mutations.HIGHLIGHTSMutational waves in the evolution of SARS-CoV-2. S protein as the driver of the first wave improving the minimum inhaled viral load required to cause infection and ORF8 mutations 119 and 120 as the driver of the second mutational wave to improve the Contagion Airborne Transmission value.
COVID-19 pandemic dynamics in South Africa and epidemiological characteristics of three variants of concern (Beta, Delta, and Omicron)
Authors: Yang Wan , Shaman Jeffrey 
Published: December 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have been key drivers of new coronavirus disease 2019 (COVID-19) pandemic waves. To better understand variant epidemiologic characteristics, here we apply a model-inference system to reconstruct SARS-CoV-2 transmission dynamics in South Africa, a country that has experienced three VOC pandemic waves (i.e. Beta, Delta, and Omicron). We estimate key epidemiologic quantities in each of the nine South African provinces during March 2020 – Feb 2022, while accounting for changing detection rates, infection seasonality, nonpharmaceutical interventions, and vaccination. Model validation shows that estimated underlying infection rates and key parameters (e.g., infection-detection rate and infection-fatality risk) are in line with independent epidemiological data and investigations. In addition, retrospective predictions capture pandemic trajectories beyond the model training period. These detailed, validated model-inference estimates thus enable quantification of both the immune erosion potential and transmissibility of three major SARS-CoV-2 VOCs, i.e., Beta, Delta, and Omicron. These findings help elucidate changing COVID-19 dynamics and inform future public health planning.
A lineage-specific Exo70 is required for receptor kinase-mediated immunity in barley
Authors: Holden Samuel , Bergum Molly , Green Phon , Bettgenhaeuser Jan , Hernández-Pinzón Inmaculada , Thind Anupriya , Clare Shaun , Russell James M. , Hubbard Amelia , Taylor Jodi , Smoker Matthew , Gardiner Matthew , Civolani Laura , Cosenza Francesco , Rosignoli Serena , Strugala Roxana , Molnár István , Šimková Hana , Doležel Jaroslav , Schaffrath Ulrich , Barrett Matthew , Salvi Silvio , Moscou Matthew J. 
Published: December 2021

AbstractIn the evolution of land plants, the plant immune system has experienced expansion in immune receptor and signaling pathways. Lineage-specific expansions have been observed in diverse gene families that are potentially involved in immunity, but lack causal association. Here, we show that Rps8-mediated resistance in barley to the fungal pathogen Puccinia striiformis f. sp. tritici (wheat stripe rust) is conferred by a genetic module: LRR-RK and Exo70FX12, which are together necessary and sufficient. The Rps8 LRR-RK is the ortholog of rice extracellular immune receptor Xa21 and Exo70FX12 is a member of the Poales-specific Exo70FX clade. The Exo70FX clade emerged after the divergence of the Bromeliaceae and Poaceae, and comprises from 2 to 75 members in sequenced grasses. These results demonstrate the requirement of a lineage-specific Exo70FX12 in Rps8 LRR-RK immunity and suggest that the Exo70FX clade may have evolved a specialized role in receptor kinase signaling.
Epidemiology study of SARS-CoV-2 pandemic in India, the first and second wave
Authors: Chaudhuri Dwaipayan , Datta Joyeeta , Majumder Satyabrata , Giri Kalyan 
Published: December 2021

AbstractBackground and objectivesSARS-CoV-2 has wrecked the world for the past 17 months. India has been hit by the second wave of the virus which has been characterized by new symptoms. This study focuses on the pattern of infection over the last 13 months utilizing epidemic model to predict course of the pandemic.Material and methodsThe data was collected from covid19india.org to perform analysis based on age and gender distribution. Statistical analysis was performed to determine the relation between confirmed and recovered cases while SIR epidemic model was used to determine the course of the pandemic in the country and the changes that have occurred from the first to the second wave.Results and discussionsResults show infectivity rate to be higher in ages 20-50 while mortality is higher in 50-80 age group while 60-70% of the infected population are males. Each of the 9 states have their own salient feature curves of infection. It was seen that the confirmed and recovered cases are more correlated at present than previous wave. The curves for both waves show a polynomial distribution while the reproduction number data shows an almost U-shaped curve indicating decrease of infection spread in the middle phase when the first wave was on a decline before picking up again owing to the second wave.Interpretations and conclusionThe gender and age distribution shows that although lower age group is more infected, mortality is high for higher age groups, on the other hand males are more prone to the infection. The statistical analysis shows the nature of spread of the disease, the data of which is quantified by the SIR model based study.
O-methylated N-glycans Distinguish Mosses from Vascular Plants
Authors: Stenitzer David , Mocsai Reka , Zechmeister Harald , Reski Ralf , Decker Eva L. , Altmann Friedrich 
Published: December 2021

AbstractIn the animal kingdom, a stunning variety of N-glycan structures has emerged with phylogenetic specificities of various kinds. In the plant kingdom, however, N-glycosylation appears as strictly conservative and uniform. From mosses to all kinds of gymno- and angiosperms, land plants mainly express structures with the common pentasaccharide core substituted with xylose, core α1,3-fucose, maybe terminal GlcNAc residues and Lewis A determinants. In contrast, green algae biosynthesize unique and unusual N-glycan structures with uncommon monosaccharides, a plethora of different structures and various kinds of O-methylation. Mosses, a group of plants that are separated by at least 400 million years of evolution from vascular plants, were hitherto seen as harbouring an N-glycosylation machinery identical to that of vascular plants. To challenge this view, we have analysed the N-glycomes of several moss species using MALDI-TOF/TOF, PGC-MS/MS and GC-MS. While all species contained the plant-typical heptasaccharide with no, one or two terminal GlcNAc residues (MMXF, MGnXF and GnGnXF, respectively), many species exhibited MS signals with 14.02 Da increments as characteristic for O-methylation. Throughout all analysed moss N-glycans the level of methylation differed strongly even in the same family. In some species, methylated glycans dominated, while others had no methylation at all. GC-MS revealed the main glycan from Funaria hygrometrica to contain 2,6-O-methylated terminal mannose. Some mosses additionally presented very large, likewise methylated complex-type N-glycans. This first finding of methylation of N-glycans in land plants mirrors the presumable phylogenetic relation of mosses to green algae, where O-methylation of mannose and many other monosaccharides is a common trait.
Neonatal enthesis healing involves non-inflammatory formation of acellular scar through ECM secretion by resident cells
Authors: Vinestock Ron Carmel , Felsenthal Neta , Assaraf Eran , Katz Eldad , Rubin Sarah , Heinemann-Yerushalmi Lia , Krief Sharon , Dezorella Nili , Levin-Zaidman Smadar , Tsoory Michael , Thomopoulos Stavros , Zelzer Elazar 
Published: December 2021

ABSTRACTWound healing is a well-orchestrated process that typically recruits the immune and vascular systems to restore the structure and function of the injured tissue. Injuries to the enthesis, a hypocellular and avascular tissue, often result in fibrotic scar formation and loss of mechanical properties, thereby severely affecting musculoskeletal function and life quality. This raises questions about the healing capabilities of the enthesis.Here, we established an injury model to the Achilles entheses of neonatal mice to study the possibility that at an early age, the enthesis can heal more effectively. Histology and immunohistochemistry analyses revealed an atypical process that did not involve inflammation or angiogenesis. Instead, neonatal enthesis healing was mediated by secretion of collagen types I and II by resident cells, which formed a permanent hypocellular and avascular scar. Transmission electron microscopy showed that the cellular response to injury, including ER stress, autophagy and cell death, varied between the tendon and cartilage ends of the enthesis. Single-molecule in situ hybridization, immunostaining, and TUNEL assays verified these differences. Finally, gait analysis showed that these processes effectively restored function of the injured leg.Collectively, these findings reveal a novel healing mechanism in neonatal entheses, whereby local ECM secretion by resident cells forms an acellular ECM deposit in the absence of inflammation markers, allowing gait restoration. These insights into the healing mechanism of a complex transitional tissue may lead to new therapeutic strategies for adult enthesis injuries.
OligoTRAFTACs: A Generalizable Method for Transcription Factor Degradation
Authors: Samarasinghe Kusal T. G. , An Elvira , Genuth Miriam A. , Chu Ling , Holley Scott A. , Crews Craig M. 
Published: December 2021

AbstractDysregulated transcription factors (TFs) that rewire gene expression circuitry are frequently identified as key players in disease. Although several TFs have been drugged with small molecules, the majority of oncogenic TFs are not currently pharmaceutically tractable due to their paucity of ligandable pockets. The first generation of transcription factor targeting chimeras (TRAFTACs) was developed to target TFs for proteasomal degradation by exploiting their DNA binding ability. In the current study, we have developed the second generation TRAFTACs (“oligoTRAFTACs”) comprised of a TF- binding oligonucleotide and an E3 ligase-recruiting ligand. Herein, we demonstrate the development of oligoTRAFTACs to induce the degradation of two oncogenic TFs, c-Myc and brachyury. In addition, we show that brachyury can be successfully degraded by oligoTRAFTACs in chordoma cell lines. Furthermore, zebrafish experiments demonstrate in vivo oligoTRAFTAC activity. Overall, our data demonstrate oligoTRAFTACs as a generalizable platform towards difficult-to-drug TFs and their degradability via the proteasomal pathway.
FUCCI-based live imaging platform reveals cell cycle dynamics and identifies pro-proliferative compounds in human iPSC-derived cardiomyocytes
Authors: Murganti Francesca , Derks Wouter , Baniol Marion , Simonova Irina , Neumann Katrin , Khattak Shahryar , Guan Kaomei , Bergmann Olaf 
Published: December 2021

AbstractOne of the major goals in cardiac regeneration research is to replace lost ventricular tissue with new cardiomyocytes. However, cardiomyocyte proliferation drops to low levels in neonatal hearts and is no longer efficient in compensating for the loss of functional myocardium in heart disease. We generated a human induced pluripotent stem cell (iPSC)-derived cardiomyocyte-specific cell cycle indicator system (TNNT2-FUCCI) to characterize regular and aberrant cardiomyocyte cycle dynamics. We visualized cell cycle progression in TNNT2-FUCCI and found G2 cycle arrest in endoreplicating cardiomyocytes. Moreover, we devised a live-cell compound screening platform to identify pro-proliferative drug candidates. We found that the alpha-adrenergic receptor agonist clonidine induced cardiomyocyte proliferation in vitro and increased cardiomyocyte cell cycle entry in neonatal mice. In conclusion, the TNNT2-FUCCI system is a valuable tool to characterize cardiomyocyte cell cycle dynamics and identify pro-proliferative candidates with regenerative potential in the mammalian heart.
The influence factors of mean particle size and positive quality control of bacterial filtration efficiency system
Authors: Yi Yayi , Shi Dianlong 
Published: December 2021

SummaryBackgroundThe Coronavirus Disease 2019 (COVID-19) has swept the whole world with high mortality. Since aerosol transmission is the main route of transmission, wearing a mask serves as a crucial preventive measure. An important parameter to evaluate the performance of a mask is the bacteria filtration efficiency (BFE). Aerosol mean particle size (MPS) and positive quality control value are two key indexes of BFE system.AimTo study the major influence factors of the mean particle size of bacterial aerosols and positive quality control value of BFE system.Method and ResultsIn this study, we investigated the influence of Anderson sampler, spray flow, medium thickness, and peristaltic pump flow on the MPS of bacterial aerosols and positive quality control value of BFE system, respectively. The results show that the machining accuracy of Anderson sampler has great influence on aerosol MPS and positive quality control value. With the increase of aerosol spray flow rate, the positive quality control value will increase gradually, but the effect on aerosol MPS is not a simple linear relationship. As the agar medium thickness increased, the positive quality control value and aerosol MPS increased gradually. With the increase of peristaltic pump flow, the positive quality control value increased gradually, while the aerosol MPS was basically in a downward trend. When the peristatic pump flow rate was 0.1mL/min, the spray flow rate was 7.2L/min, the agar plate thickness was 27mL, and the Anderson sampler of Beijing Mingjie was used for the experiment, the aerosol MPS and positive quality control value were both within the acceptable range and were the optimal parameters.ConclusionsThis study provides guidance for the manufacturers of the BFE system and improves the protective performance of masks, which is important for the human health, especially during the occurrence of viral pandemics such as “COVID-19”.Abstract Figure
Quantitative detection of SARS-CoV-2 Omicron BA.1 and BA.2 variants in wastewater through allele-specific RT-qPCR
Authors: Lee Wei Lin , Gu Xiaoqiong , Armas Federica , Wu Fuqing , Chandra Franciscus , Chen Hongjie , Xiao Amy , Leifels Mats , Chua Feng Jun Desmond , Kwok Germaine WC , Tay Joey YR , Lim Claire YJ , Thompson Janelle , Alm Eric J 
Published: December 2021

ABSTRACTOn November 26, 2021, the World Health Organisation classified the B.1.1.529 SARS-CoV-2 variant as the Omicron variant of concern (VOC). Reports of higher transmissibility and potential immune evasion triggered flight bans and heightened health control measures across the world to stem its distribution. Wastewater-based surveillance has demonstrated to be a useful complement for community-based tracking of SARS-CoV-2 variants. Using design principles of our previous assays that detect VOCs (Alpha and Delta), here we report three allele-specific RT-qPCR assays that can quantitatively detect and discriminate the Omicron BA.1 and BA.2 variants in wastewater. The first assay targets the nine-nucleotide deletion at the L24-A27S of the spike protein for detection of BA.2. The second targets the six-nucleotide deletion at 69-70 of the spike protein for detection of the Omicron BA.1 variant, and the third targets the stretch of mutations from Q493R to Q498R for simultaneous detection of both Omicron BA.1 and BA.2. This method is open-sourced, can be implemented using commercially available RT-qPCR protocols, and would be an important tool for tracking the introduction and spread of the Omicron variants BA.1 and BA.2 in communities for informed public health responses.
Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South Africa
Authors: Wolter Nicole , Jassat Waasila , Walaza Sibongile , Welch Richard , Moultrie Harry , Groome Michelle , Amoako Daniel Gyamfi , Everatt Josie , Bhiman Jinal N. , Scheepers Cathrine , Tebeila Naume , Chiwandire Nicola , du Plessis Mignon , Govender Nevashan , Ismail Arshad , Glass Allison , Mlisana Koleka , Stevens Wendy , Treurnicht Florette K. , Makatini Zinhle , Hsiao Nei-yuan , Parboosing Raveen , Wadula Jeannette , Hussey Hannah , Davies Mary-Ann , Boulle Andrew , von Gottberg Anne , Cohen Cheryl 
Published: December 2021

ABSTRACTBackgroundThe SARS-CoV-2 Omicron variant of concern (VOC) almost completely replaced other variants in South Africa during November 2021, and was associated with a rapid increase in COVID-19 cases. We aimed to assess clinical severity of individuals infected with Omicron, using S Gene Target Failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy.MethodsWe performed data linkages for (i) SARS-CoV-2 laboratory tests, (ii) COVID-19 case data, (iii) genome data, and (iv) the DATCOV national hospital surveillance system for the whole of South Africa. For cases identified using Thermo Fisher TaqPath COVID-19 PCR, infections were designated as SGTF or non-SGTF. Disease severity was assessed using multivariable logistic regression models comparing SGTF-infected individuals diagnosed between 1 October to 30 November to (i) non-SGTF in the same period, and (ii) Delta infections diagnosed between April and November 2021.ResultsFrom 1 October through 6 December 2021, 161,328 COVID-19 cases were reported nationally; 38,282 were tested using TaqPath PCR and 29,721 SGTF infections were identified. The proportion of SGTF infections increased from 3% in early October (week 39) to 98% in early December (week 48). On multivariable analysis, after controlling for factors associated with hospitalisation, individuals with SGTF infection had lower odds of being admitted to hospital compared to non-SGTF infections (adjusted odds ratio (aOR) 0.2, 95% confidence interval (CI) 0.1-0.3). Among hospitalised individuals, after controlling for factors associated with severe disease, the odds of severe disease did not differ between SGTF-infected individuals compared to non-SGTF individuals diagnosed during the same time period (aOR 0.7, 95% CI 0.3-1.4). Compared to earlier Delta infections, after controlling for factors associated with severe disease, SGTF-infected individuals had a lower odds of severe disease (aOR 0.3, 95% CI 0.2-0.5).ConclusionEarly analyses suggest a reduced risk of hospitalisation among SGTF-infected individuals when compared to non-SGTF infected individuals in the same time period. Once hospitalised, risk of severe disease was similar for SGTF- and non-SGTF infected individuals, while SGTF-infected individuals had a reduced risk of severe disease when compared to earlier Delta-infected individuals. Some of this reducton is likely a result of high population immunity.
Breakthrough Covid-19 infections during periods of circulating Beta, Delta and Omicron variants of concern, among health care workers in the Sisonke Ad26.COV2.S vaccine trial, South Africa
Authors: Goga Ameena , Bekker Linda-Gail , Garrett Nigel , Reddy Tarylee , Yende-Zuma Nonhlanhla , Fairall Lara , Moultrie Harry , Takalani Azwidihwi , Trivella Valentina , Faesen Mark , Bailey Veronique , Seocharan Ishen , Gray Glenda E 
Published: December 2021

AbstractBackgroundWe report breakthrough infections (BTIs) during periods of circulating Beta, Delta and Omicron variants of concern, among health care workers (HCW) participating in the Sisonke phase 3B Ad26.COV2.S vaccine trial (ClinicalTrials.gov number, NCT04838795). Data were gathered between 17 February and 15 December 2021. Duration of each period in this study was 89 days for Beta, 180 days or Delta and 30 days for Omicron.ResultsA total of 40 538 BTIs were observed, with 609 during Beta, 22 279 during Delta and 17 650 during Omicron. By 15 December, daily infections during Omicron were three times that seen during the peak observed during Delta. However, unlike the Delta period, with Omicron there was a clear and early de-coupling of hospitalisation from cases as a percentage of the Delta peak curves. Omicron significantly infected a greater proportion of HCW in the 18-30 year age-group, compared with the 55+ age group. There were 1 914 BTI-related hospitalisations - 77, 1 429 and 408 in the Beta (89 days), Delta (180 days) and Omicron (30 days) periods, respectively. During Omicron, 91% hospitalized HCWs required general ward care, 6% high care and 3% intensive care, compared with 89% general ward care, 4% high care and 7% intensive care, during Delta and 78% general care, 7% high care and 16% intensive care during Beta (p<0.001). During Beta and Beta 43% of hospitalized HCW needed supplementary oxygen and 7-8% needed ventilation, compared with 16% and 0.2% respectively during the Omicron period (p<0.001). Median length of hospitalization was significantly lower with Omicron compared with Beta and Delta (3 days compared with 5-6 days, p<0.001).ConclusionsWe illustrate more BTIs but reassuringly less severe Covid-19 with Omicron. Re-infections and Omicron-driven primary infections were likely driven by high population SARS-CoV-2 seroprevalence, waning vaccine effectiveness over time, increased Omicron infectivity, Omicron immune evasion or a combination of these and need further investigation. Follow-up of this cohort will continue and reports will be updated, as time and infections accrue.