bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive Aging in Caenorhabditis elegans: From Molecules to Ecology
Authors: Scharf Andrea , Pohl Franziska , Egan Brian M. , Kocsisova Zuzana , Kornfeld Kerry
Published: September 2021

Aging animals display a broad range of progressive degenerative changes, and one of the most fascinating is the decline of female reproductive function. In the model organism Caenorhabditis elegans, hermaphrodites reach a peak of progeny production on day 2 of adulthood and then display a rapid decline; progeny production typically ends by day 8 of adulthood. Since animals typically survive until day 15 of adulthood, there is a substantial post reproductive lifespan. Here we review the molecular and cellular changes that occur during reproductive aging, including reductions in stem cell number and activity, slowing meiotic progression, diminished Notch signaling, and deterioration of germ line and oocyte morphology. Several interventions have been identified that delay reproductive aging, including mutations, drugs and environmental factors such as temperature. The detailed description of reproductive aging coupled with interventions that delay this process have made C. elegans a leading model system to understand the mechanisms that drive reproductive aging. While reproductive aging has dramatic consequences for individual fertility, it also has consequences for the ecology of the population. Population dynamics are driven by birth and death, and reproductive aging is one important factor that influences birth rate. A variety of theories have been advanced to explain why reproductive aging occurs and how it has been sculpted during evolution. Here we summarize these theories and discuss the utility of C. elegans for testing mechanistic and evolutionary models of reproductive aging.
Approaches to Study Native Chromatin-Modifying Complex Activities and Functions
Authors: Galloy Maxime , Lachance Catherine , Cheng Xue , Distéfano-Gagné Félix , Côté Jacques , Fradet-Turcotte Amelie
Published: September 2021

The modification of histones—the structural components of chromatin—is a central topic in research efforts to understand the mechanisms regulating genome expression and stability. These modifications frequently occur through associations with multisubunit complexes, which contain active enzymes and additional components that orient their specificity and read the histone modifications that comprise epigenetic signatures. To understand the functions of these modifications it is critical to study the enzymes and substrates involved in their native contexts. Here, we describe experimental approaches to purify native chromatin modifiers complexes from mammalian cells and to produce recombinant nucleosomes that are used as substrates to determine the activity of the complex. In addition, we present a novel approach, similar to the yeast anchor-away system, to study the functions of essential chromatin modifiers by quickly inducing their depletion from the nucleus. The step-by-step protocols included will help standardize these approaches in the research community, enabling convincing conclusions about the specificities and functions of these crucial regulators of the eukaryotic genome.
Terahertz Wave Absorption Property of all Mixed Organic–Inorganic Hybrid Perovskite Thin Film MA(Sn, Pb)(Br, I)3 Fabricated by Sequential Vacuum Evaporation Method
Authors: Maeng Inhee , Tanaka Hiroshi , Mag-usara Valynn Katrine , Nakajima Makoto , Nakamura Masakazu , Jung Min-Cherl
Published: September 2021

All mixed hybrid perovskite (MA(Sn, Pb)(Br,I)3) thin film was fabricated by sequential vacuum evaporation method. To optimize the first layer with PbBr2 and SnI2, we performed different annealing treatments. Further, MA(Sn, Pb)(Br, I)3 thin film was synthesized on the optimized first layer by evaporating MAI and post-annealing. The formed hybrid perovskite thin film exhibited absorptions at 1.0 and 1.7 THz with small absorbance (<10%). Moreover, no chemical and structural defect-incorporated absorption was found. In this study, the possibility of changing terahertz absorption frequency through the mixture of metal cations (Sn+ and Pb+) and halogen anions (Br− and I−) was verified.
Comprehensive Characterization of Microbial Community in the Female Genital Tract of Reproductive-Aged Women in China
Authors: Sun Ningxia , Ding Haixia , Yu Hongjing , Ji Yixuan , Xifang Xiuyue , Pang Wenjuan , Wang Xiang , Zhang Qing , Li Wen
Published: September 2021

The microbiota in the human body play critical roles in many physiological and pathological processes. However, the diversity and dynamics of the female genital tract (FGT) microbiota have not been fully unveiled. In this study, we characterized the microbiome variations in reproductive-aged Chinese women, and we revealed that the cervicovaginal microbiota were dominated by Lactobacillus. Overall, the composition of microbiota in the uterine cavity was more diverse than that in the vagina and cervix. A positive correlation between Lactobacillus iners and Lactobacillus crispatus was observed in both the vagina and the cervix, suggesting that these two species might have a symbiotic relationship in the cervicovaginal microbiota. Moreover, we, for the first time, stratified the reproductive-aged Chinese women into subgroups, based on their microbiome profiles. Furthermore, we identified the bacteria whose abundance changed in the uterine cavity of infertile patients when compared with healthy controls, such as L. iners and L. crispatus. Functionally, the metabolism-related pathways, neurotrophin signaling pathway, and adipocytokine signaling pathway were predominantly dysregulated in the uterine cavity of infertile patients. In conclusion, we characterized a comprehensive microbial landscape in FGT, as well as their functional roles in female infertility of the Chinese population.
Evaluation of the SARS-CoV-2 Inactivation Efficacy Associated With Buffers From Three Kits Used on High-Throughput RNA Extraction Platforms
Authors: Thom Ruth E. , Eastaugh Lin S. , O’Brien Lyn M. , Ulaeto David O. , Findlay James S. , Smither Sophie J. , Phelps Amanda L. , Stapleton Helen L. , Hamblin Karleigh A. , Weller Simon A.
Published: September 2021

Rapid and demonstrable inactivation of SARS-CoV-2 is crucial to ensure operator safety during high-throughput testing of clinical samples. The inactivation efficacy of SARS-CoV-2 was evaluated using commercially available lysis buffers from three viral RNA extraction kits used on two high-throughput (96-well) RNA extraction platforms (Qiagen QIAcube HT and the Thermo Fisher KingFisher Flex) in combination with thermal treatment. Buffer volumes and sample ratios were chosen for their optimised suitability for RNA extraction rather than inactivation efficacy and tested against a representative sample type: SARS-CoV-2 spiked into viral transport medium (VTM). A lysis buffer mix from the MagMAX Pathogen RNA/DNA kit (Thermo Fisher), used on the KingFisher Flex, which included guanidinium isothiocyanate (GITC), a detergent, and isopropanol, demonstrated a minimum inactivation efficacy of 1 × 105 tissue culture infectious dose (TCID)50/ml. Alternative lysis buffer mixes from the MagMAX Viral/Pathogen Nucleic Acid kit (Thermo Fisher) also used on the KingFisher Flex and from the QIAamp 96 Virus QIAcube HT Kit (Qiagen) used on the QIAcube HT (both of which contained GITC and a detergent) reduced titres by 1 × 104 TCID50/ml but did not completely inactivate the virus. Heat treatment alone (15 min, 68°C) did not completely inactivate the virus, demonstrating a reduction of 1 × 103 TCID50/ml. When inactivation methods included both heat treatment and addition of lysis buffer, all methods were shown to completely inactivate SARS-CoV-2 inactivation against the viral titres tested. Results are discussed in the context of the operation of a high-throughput diagnostic laboratory.
Effects of Helicobacter pylori Infection on the Oral Microbiota of Reflux Esophagitis Patients
Authors: Liang Tian , Liu Fang , Liu Lijun , Zhang Zhiying , Dong Wenxue , Bai Su , Ma Lifeng , Kang Longli
Published: September 2021

The human oral microbiota plays a vital role in maintaining metabolic homeostasis. To explore the relationship between Helicobacter pylori (Hp) and reflux esophagitis, we collected 86 saliva samples from reflux esophagitis patients (RE group) and 106 saliva samples from healthy people (C group) for a high-throughput sequencing comparison. No difference in alpha diversity was detected between the RE and the C groups, but beta diversity of the RE group was higher than the C group. Bacteroidetes was more abundant in the RE group, whereas Firmicutes was more abundant in the C group. The linear discriminant analysis effect size analysis demonstrated that the biomarkers of the RE group were Prevotella, Veillonella, Leptotrichia, and Actinomyces, and the biomarkers of the C group were Lautropia, Gemella, Rothia, and Streptococcus. The oral microbial network structure of the C group was more complex than that of the RE group. Second, to explore the effect of Hp on the oral microbiota of RE patients, we performed the 14C-urea breath test on 45 of the 86 RE patients. We compared the oral microbiota of 33 Hp-infected reflux esophagitis patients (REHpp group) and 12 non-Hp-infected reflux esophagitis patients (REHpn group). No difference in alpha diversity was observed between the REHpn and REHpp groups, and beta diversity of the REHpp group was significantly lower than that of the REHpn group. The biomarkers in the REHpp group were Veillonella, Haemophilus, Selenomonas, Megasphaera, Oribacterium, Butyrivibrio, and Campylobacter; and the biomarker in the REHpn group was Stomatobaculum. Megasphaera was positively correlated with Veillonella in the microbial network of the REHpp group. The main finding of this study is that RE disturbs the human oral microbiota, such as increased beta diversity. Hp infection may inhibit this disorderly trend.
COVID-19 Vaccination in Pregnancy and Lactation: Current Research and Gaps in Understanding
Authors: Shook Lydia L. , Fallah Parisa N. , Silberman Jason N. , Edlow Andrea G.
Published: September 2021

The COVID-19 pandemic has demonstrated the urgent need to develop vaccine strategies optimized for pregnant people and their newborns, as both populations are at risk of developing severe disease. Although not included in COVID-19 vaccine development trials, pregnant people have had access to these vaccines since their initial release in the US and abroad. The rapid development and distribution of novel COVID-19 vaccines to people at risk, including those who are pregnant and lactating, presents an unprecedented opportunity to further our understanding of vaccine-induced immunity in these populations. In this review, we aim to summarize the literature to date on COVID-19 vaccination in pregnancy and lactation and highlight opportunities for investigation that may inform future maternal vaccine development and implementation strategies.
A Prospective Study of Grip Strength Trajectories and Incident Cardiovascular Disease
Authors: Liu Weida , Chen Runzhen , Song Chenxi , Wang Chuangshi , Chen Ge , Hao Jun , Wang Yang , Yu Chenxi
Published: September 2021

Background: A single measurement of grip strength (GS) could predict the incidence of cardiovascular disease (CVD). However, the long-term pattern of GS and its association with incident CVD are rarely studied. We aimed to characterize the GS trajectory and determine its association with the incidence of CVD (myocardial infarction, angina, stroke, and heart failure).

Methods: This study included 5,300 individuals without CVD from a British community-based cohort in 2012 (the baseline). GS was repeatedly measured in 2004, 2008, and 2012. Long-term GS patterns were identified by the group-based trajectory model. Cox proportional hazard models were used to examine the associations between GS trajectories and incident CVD. We identified three GS trajectories separately for men and women based on the 2012 GS measurement and change patterns during 2004–2012.

Results: After a median follow-up of 6.1 years (during 2012–2019), 392 participants developed major CVD, including 114 myocardial infarction, 119 angina, 169 stroke, and 44 heart failure. Compared with the high stable group, participants with low stable GS was associated with a higher incidence of CVD incidence [hazards ratio (HR): 2.17; 95% confidence interval (CI): 1.52–3.09; P <0.001], myocardial infarction (HR: 2.01; 95% CI: 1.05–3.83; P = 0.035), stroke (HR: 1.96; 95% CI: 1.11–3.46; P = 0.020), and heart failure (HR: 6.91; 95% CI: 2.01–23.79; P = 0.002) in the fully adjusted models.

Conclusions: The low GS trajectory pattern was associated with a higher risk of CVD. Continuous monitoring of GS values could help identify people at risk of CVD.
Stepwise Weakening of Aeolian Activities During the Holocene in the Gannan Region, Eastern Tibetan Plateau
Authors: Yang Shengli , Liu Xiaojing , Cheng Ting , Luo Yuanlong , Li Qiong , Liu Li , Chen Zixuan
Published: September 2021

Aeolian sediments hold key information on aeolian history and past environmental changes. Aeolian desertification and extensive land degradation have seriously affected the eco-environment in the Gannan region on the eastern Tibetan Plateau. Understanding the history of aeolian activities can deepen our understanding of the impacts of climatic changes on aeolian activities in the future. This study uses a detailed chronology and multiple proxy analyses of a typical aeolian section in Maqu to reconstruct aeolian activities in the region during the Holocene. Our results showed that aeolian activities have occurred in the eastern Tibetan Plateau since the early Holocene. Magnetic susceptibility, grain size records, and paleosols formation indicated a trend of stepwise weakening in aeolian activities from the early Holocene to the present. The weakening of aeolian activities was divided into three stages: ∼10.0–8.0 ka BP, ∼8.0–4.0 ka BP, and ∼4.0 ka BP to the present. Paleosols were primarily formed after ∼8.0 ka BP, and episodically interrupted aeolian activities processes in the Gannan region. Aeolian activity may increase in the Gannan region as the climate gradually warms. Climatic changes and local hydrological conditions have jointly affected the history of aeolian activities in this region.
Successful Diagnoses and Remarkable Metabolic Disorders in Patients With Solitary Hypothalamic Mass: A Case Series Report
Authors: Xiang Boni , Sun Quanya , He Min , Wu Wei , Lu Bin , Zhang Shuo , Zhang Zhaoyun , Yang Yehong , Li Yiming , Wu Yue , Yao Zhenwei , Cheng Haixia , Pan Li , Miao Qing , Wang Yongfei , Ye Hongying
Published: September 2021

Background

Solitary intracranial hypothalamic mass occurs rarely. The etiological diagnosis of solitary hypothalamus lesion is challenging and often unachievable. Although previous studies indicated that lesions affecting the hypothalamus often cause significant metabolic disorders, few reports about the metabolic disturbances of patients with solitary hypothalamic mass have been reported.

Method

Twenty-five patients with solitary hypothalamus lesions who had been evaluated and treated in Huashan Hospital from January 2010 to December 2020 were retrospectively enrolled. The clinical manifestations, radiological features, endocrine and metabolic disorders, and pathology were analyzed.

Results

The male to female ratio was 5/20. The median age of onset was 22 (19, 35) years old. The most common initial symptom was polydipsia/polyuria (19/25, 76.0%) and amenorrhea (9/20, 45.0%). A high prevalence of hypopituitarism of different axes was found, with almost all no less than 80%. Central hypogonadism (21/22, 95.5%) and central diabetes insipidus (19/21, 90.5%) were the top two pituitary dysfunctions. Conclusive diagnoses were achieved by intracranial surgical biopsy/resection or stereotactic biopsy in 16 cases and by examining extracranial lesions in 3 cases. The pathological results were various, and the most common diagnoses were Langerhans cell histiocytosis (7/19) and hypothalamitis (5/19). The mean timespan from onset to diagnosis in the 19 cases was 34 ± 26 months. Metabolic evaluations revealed remarkable metabolic disorders, including hyperlipidemia (13/16, 81.3%), hyperglycemia (10/16, 62.5%), hyperuricemia (12/20, 60%), overweight/obesity (13/20, 65.0%), and hepatic adipose infiltration (10/13, 76.6%).

Conclusion

Either surgical or stereotactic biopsy will be a reliable and relatively safe procedure to help to confirm the pathological diagnosis of solitary hypothalamic mass. Metabolic disorders were severe in patients with solitary hypothalamic mass. The management of such cases should cover both the treatment of the primary disease, as well as the endocrine and metabolic disorders
Numerical Simulation on the Diffusion of Alien Phytoplankton in Bohai Bay
Authors: Zhang Beibei , Pu Amin , Jia Peng , Xu Chenglong , Wang Qinggai , Tang Wenhao
Published: September 2021

In order to investigate the motion feature of alien phytoplankton in the Bohai Bay area, this manuscript builds a two-dimensional tide hydrodynamic model coupled with a particle tracking model to simulate the alien phytoplankton movement trajectory and the diffusion processes with different specific growth rates in three major ports of Bohai Bay (Caofeidian port, Tianjin port, and Huanghua port). The results show that the movement of alien phytoplankton is mainly affected by the tidal circulation near the port, and the diffusion trend is basically consistent with the residual flow in Bohai Bay. The distribution density of alien phytoplankton is directly affected by the specific growth rate of the population and is positively related to specific growth rate. The released alien phytoplankton in the three major ports are all concentrated around the ports area. The largest distribution density is in Tianjin port, and the possibility of red tide disasters is also greatest here compared with the other two major ports. It is necessary to strengthen the monitoring of alien organisms in the port area and actively prevent alien phytoplankton from entering Bohai Bay through ship ballast water.
Soil Carbon Stabilization Under Coniferous, Deciduous and Grass Vegetation in Post-mining Reclaimed Ecosystems
Authors: Nickels Meghan C. L. , Prescott Cindy E.
Published: September 2021

Vegetation plays an important role in determining soil organic carbon (SOC) stocks, and influences the mechanisms through which SOC is stabilized within the soil. The type of vegetation selected for use in reclamation may therefore influence the accumulation rate and residence time of SOC in these ecosystems. Earlier studies at reclaimed sites in the Alberta Oil Sands demonstrated that reclaimed ecosystems planted with deciduous trees accumulated the most soil organic matter in the top 10 cm of reclamation material, followed by grass sites, while coniferous sites accumulated the least SOM. The objective of this study was to assess differences in SOC stabilization in the upper 10 cm of soil among revegetated deciduous, coniferous and grass ecosystems 20–40 years following reclamation. We compared soil C in unprotected, physically protected, and chemically protected forms among the three reclamation treatments using density flotation to isolate free particulate (unprotected) SOC from the soil sample, and size fractionation to separate the remaining sample into heavy particulate (physically protected) SOC and mineral-associated (chemically protected) SOC. In addition to this analysis, we used NaOCl oxidation to distinguish chemically resistant and chemically oxidizable C stocks. Chemically resistant C was consistent across all vegetation treatments at approximately 25% of total soil C, while the remaining 75% was chemically oxidizable. Total SOC stocks were also not significantly different among vegetation treatments. Deciduous sites had 57.8 Mg ha–1 SOC, grass sites had 52.7 Mg ha–1 SOC, and coniferous sites had 43.7 Mg ha–1 SOC. Two-thirds of total SOC at grass sites was in protected forms, compared to half of total SOC at coniferous sites and one-third of total SOC at deciduous sites (33.6, 22.6, and 15.6 Mg ha–1, respectively). Grass sites had significantly more physically protected SOC than deciduous sites while deciduous sites had more unprotected SOC than grass sites. Our findings indicate that the type of vegetation selected for reclaimed areas has important implications for soil carbon in persistent versus unprotected pools.
Investigation of FADS Gene Cluster Single Nucleotide Polymorphisms in End-Stage Renal Disease Compared With Normal Controls
Authors: Miladipour Amirhossein , Gholipour Mahdi , Honarmand Tamizkar Kasra , Abak Atefe , Kholghi Oskooei Vahid , Taheri Mohammad , Ghafouri-Fard Soudeh
Published: September 2021

End-stage renal disease (ESRD) is a public health problem with a high burden. The condition is associated with abnormalities in lipid metabolism. The fatty acid desaturase (FADS) gene cluster includes three genes that are significantly correlated with a number of pathologic conditions related to abnormal lipid levels. In the current study, we genotyped rs174556, rs99780, and rs7115739 single nucleotide polymorphisms within the FADS cluster in a population of ESRD patients and healthy controls. The rs174556 of the FADS1 gene and rs99780 of the FADS2 gene were not associated with the risk of ESRD in any inheritance model. However, the rs7115739 of FADS3 was associated with the risk of ESRD in all models except for the recessive model. The T allele of this SNP was significantly less prevalent among cases compared with controls [odds ratio (OR) (95% CI) = 0.44 (0.25–0.77), P value = 0.004]. GT and TT genotypes has been shown to decrease the risk of ESRD in a codominant model [OR (95% CI) = 0.49 (0.26–0.92) and OR (95% CI) = 0.18 (0.02–1.6), respectively; P value = 0.019]. In the dominant model, GT + TT status was associated with lower risk of ESRD [OR (95% CI) = 0.45 (0.24–0.82), P value = 0.0078]. Assessment of association between this SNP and risk of ESRD in an overdominant model revealed that GT genotype decreases the risk of this condition [OR (95% CI) = 0.5 (0.27–0.94), P value = 0.029]. Taken together, the rs7115739 of FADS3 is suggested as a putative modulator of the risk of ESRD in the Iranian population.
High-Quality de novo Chromosome-Level Genome Assembly of a Single Bombyx mori With BmNPV Resistance by a Combination of PacBio Long-Read Sequencing, Illumina Short-Read Sequencing, and Hi-C Sequencing
Authors: Tang Min , He Suqun , Gong Xun , Lü Peng , Taha Rehab H. , Chen Keping
Published: September 2021

The reference genomes of Bombyx mori (B. mori), Silkworm Knowledge-based database (SilkDB) and SilkBase, have served as the gold standard for nearly two decades. Their use has fundamentally shaped model organisms and accelerated relevant studies on lepidoptera. However, the current reference genomes of B. mori do not accurately represent the full set of genes for any single strain. As new genome-wide sequencing technologies have emerged and the cost of high-throughput sequencing technology has fallen, it is now possible for standard laboratories to perform full-genome assembly for specific strains. Here we present a high-quality de novo chromosome-level genome assembly of a single B. mori with nuclear polyhedrosis virus (BmNPV) resistance through the integration of PacBio long-read sequencing, Illumina short-read sequencing, and Hi-C sequencing. In addition, regular bioinformatics analyses, such as gene family, phylogenetic, and divergence analyses, were performed. The sample was from our unique B. mori species (NB), which has strong inborn resistance to BmNPV. Our genome assembly showed good collinearity with SilkDB and SilkBase and particular regions. To the best of our knowledge, this is the first genome assembly with BmNPV resistance, which should be a more accurate insect model for resistance studies.
Cholesterol-Lowering Drugs on Akt Signaling for Prevention of Tumorigenesis
Authors: Kumar Navneet , Mandal Chandi C.
Published: September 2021

Cholesterol has been reported to be accumulated in cancer cells. The metabolic dysregulation of the cholesterol is associated with tumor development and progression. The cholesterol-lowering drugs have been found to be involved in the prevention and treatment of various cancers. Akt, a serine/threonine kinase, can modulate the role of several downstream proteins involved in cell proliferation, migration, invasion, metabolism, and apoptosis. Since its involvement in several signaling pathways, its dysregulation is commonly reported in several cancers. Thus, targeting Akt could be an effective approach for cancer prevention and therapy. Cholesterol-lowering drugs have been found to affect the expression of Akt, and its activation in the cancer cells and thus have shown anticancer activity in different type of cancers. These drugs act on various signaling pathways such as PTEN/Akt, PI3k/Akt, Akt/NF-κB, Akt/FOXO1, Akt/mTOR, etc., which will be discussed in this article. This review article will discuss the significance of cholesterol in cancer cells, cholesterol-lowering drugs, the role of Akt in cancer cells, and the effects of cholesterol-lowering drugs on Akt in the prevention of therapy resistance and metastasis.
Identification of LINC00173 in Myasthenia Gravis by Integration Analysis of Aberrantly Methylated- Differentially Expressed Genes and ceRNA Networks
Authors: Xu Si , Wang Tianfeng , Lu Xiaoyu , Zhang Huixue , Liu Li , Kong Xiaotong , Li Shuang , Wang Xu , Gao Hongyu , Wang Jianjian , Wang Lihua
Published: September 2021

Myasthenia gravis (MG) is an autoimmune disease associated with autoantibody production that leads to skeletal muscle weakness. The molecular mechanisms underlying MG are not fully understood. We analyzed the gene expression profile (GSE85452) and methylation profile (GSE85647) of MG samples from the GEO database to identify aberrantly methylated-differentially expressed genes. By integrating the datasets, we identified 143 hypermethylation-low expression genes and 91 hypomethylation-high expression genes. Then we constructed PPI network and ceRNA networks by these genes. Phosphatase and tensin homolog (PTEN) and Abelson tyrosine-protein kinase (ABL)1 were critical genes in both PPI networks and ceRNA networks. And potential MG associated lncRNAs were selected by comprehensive analysis of the critical genes and ceRNA networks. In the hypermethylation-low expression genes associated ceRNA network, sirtuin (SIRT)1 was the most important gene and the lncRNA HLA complex (HC) P5 had the highest connection degree. Meanwhile, PTEN was the most important gene and the lncRNA LINC00173 had the highest connection degree in the hypomethylation-high expression genes associated ceRNA network. LINC00173 was validated to be upregulated in MG patients by qRT-PCR (P = 0.005), which indicated LINC00173 might be a potential biomarker for MG. These results provide a basis for future studies on the molecular pathogenesis of MG.
Targeting the Transcriptome Through Globally Acting Components
Authors: Parrello Damien , Vlasenok Maria , Kranz Lincoln , Nechaev Sergei
Published: September 2021

Transcription is a step in gene expression that defines the identity of cells and its dysregulation is associated with diseases. With advancing technologies revealing molecular underpinnings of the cell with ever-higher precision, our ability to view the transcriptomes may have surpassed our knowledge of the principles behind their organization. The human RNA polymerase II (Pol II) machinery comprises thousands of components that, in conjunction with epigenetic and other mechanisms, drive specialized programs of development, differentiation, and responses to the environment. Parts of these programs are repurposed in oncogenic transformation. Targeting of cancers is commonly done by inhibiting general or broadly acting components of the cellular machinery. The critical unanswered question is how globally acting or general factors exert cell type specific effects on transcription. One solution, which is discussed here, may be among the events that take place at genes during early Pol II transcription elongation. This essay turns the spotlight on the well-known phenomenon of promoter-proximal Pol II pausing as a step that separates signals that establish pausing genome-wide from those that release the paused Pol II into the gene. Concepts generated in this rapidly developing field will enhance our understanding of basic principles behind transcriptome organization and hopefully translate into better therapies at the bedside.
On Deep Landscape Exploration of COVID-19 Patients Cells and Severity Markers
Authors: Vázquez-Jiménez Aarón , Avila-Ponce De León Ugo Enrique , Matadamas-Guzman Meztli , Muciño-Olmos Erick Andrés , Martínez-López Yoscelina E. , Escobedo-Tapia Thelma , Resendis-Antonio Osbaldo
Published: September 2021

COVID-19 is a disease with a spectrum of clinical responses ranging from moderate to critical. To study and control its effects, a large number of researchers are focused on two substantial aims. On the one hand, the discovery of diverse biomarkers to classify and potentially anticipate the disease severity of patients. These biomarkers could serve as a medical criterion to prioritize attention to those patients with higher prone to severe responses. On the other hand, understanding how the immune system orchestrates its responses in this spectrum of disease severities is a fundamental issue required to design new and optimized therapeutic strategies. In this work, using single-cell RNAseq of bronchoalveolar lavage fluid of nine patients with COVID-19 and three healthy controls, we contribute to both aspects. First, we presented computational supervised machine-learning models with high accuracy in classifying the disease severity (moderate and severe) in patients with COVID-19 starting from single-cell data from bronchoalveolar lavage fluid. Second, we identified regulatory mechanisms from the heterogeneous cell populations in the lungs microenvironment that correlated with different clinical responses. Given the results, patients with moderate COVID-19 symptoms showed an activation/inactivation profile for their analyzed cells leading to a sequential and innocuous immune response. In comparison, severe patients might be promoting cytotoxic and pro-inflammatory responses in a systemic fashion involving epithelial and immune cells without the possibility to develop viral clearance and immune memory. Consequently, we present an in-depth landscape analysis of how transcriptional factors and pathways from these heterogeneous populations can regulate their expression to promote or restrain an effective immune response directly linked to the patients prognosis.
Dual-Antigen COVID-19 Vaccine Subcutaneous Prime Delivery With Oral Boosts Protects NHP Against SARS-CoV-2 Challenge
Authors: Gabitzsch Elizabeth , Safrit Jeffrey T. , Verma Mohit , Rice Adrian , Sieling Peter , Zakin Lise , Shin Annie , Morimoto Brett , Adisetiyo Helty , Wong Raymond , Bezawada Ashish , Dinkins Kyle , Balint Joseph , Peykov Victor , Garban Hermes , Liu Philip , Bacon Andrew , Bone Pete , Drew Jeff , Sanford Daniel C. , Spilman Patricia , Sender Lennie , Rabizadeh Shahrooz , Niazi Kayvan , Soon-Shiong Patrick
Published: September 2021

We have developed a dual-antigen COVID-19 vaccine incorporating genes for a modified SARS-CoV-2 spike protein (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to increase the potential for MHC class II responses. The vaccine antigens are delivered by a human adenovirus serotype 5 platform, hAd5 [E1-, E2b-, E3-], previously demonstrated to be effective in the presence of Ad immunity. Vaccination of rhesus macaques with the hAd5 S-Fusion + N-ETSD vaccine by subcutaneous prime injection followed by two oral boosts elicited neutralizing anti-S IgG and T helper cell 1-biased T-cell responses to both S and N that protected the upper and lower respiratory tracts from high titer (1 x 106 TCID50) SARS-CoV-2 challenge. Notably, viral replication was inhibited within 24 hours of challenge in both lung and nasal passages, becoming undetectable within 7 days post-challenge.
Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection
Authors: Cui Dawei , Tang Yuan , Jiang Qi , Jiang Daixi , Zhang Yun , Lv Yan , Xu Dandan , Wu Jian , Xie Jue , Wen Chengping , Lu Liwei
Published: September 2021

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious infectious disease that has led to a global pandemic with high morbidity and mortality. High-affinity neutralizing antibody is important for controlling infection, which is closely regulated by follicular helper T (Tfh) cells. Tfh cells play a central role in promoting germinal center reactions and driving cognate B cell differentiation for antibody secretion. Available studies indicate a close relationship between virus-specific Tfh cell-mediated immunity and SARS-CoV-2 infection progression. Although several lines of evidence have suggested that Tfh cells contribute to the control of SARS-CoV-2 infection by eliciting neutralizing antibody productions, further studies are needed to elucidate Tfh-mediated effector mechanisms in anti-SARS-CoV-2 immunity. Here, we summarize the functional features and roles of virus-specific Tfh cells in the immunopathogenesis of SARS-CoV-2 infection and in COVID-19 vaccines, and highlight the potential of targeting Tfh cells as therapeutic strategy against SARS-CoV-2 infection.
Involvement of Epidermis Cell Proliferation in Defense Against Beauveria bassiana Infection
Authors: Huang Wuren , Tang Ruijuan , Li Shirong , Zhang Ying , Chen Rongbing , Gong Liyuan , Wei Xuefei , Tang Yingyu , Liu Qiuning , Geng Lei , Pan Guoqing , Beerntsen Brenda T. , Ling Erjun
Published: September 2021

Entomopathogenic fungi Beauveria bassiana can infect many species of insects and is used as a biological pesticide world-wide. Before reaching the hemocoel, B. bassiana has to penetrate the integument which is composed of a thick chitin layer and epidermal cells. Some chitinase, protease and lipase secreted by B. bassiana are probably involved in the fungal penetration of the integument. While microscopic proof is needed, it is difficult to locate the precise infection sites following the traditional method of immersion infection. Consequently, we developed a new method to inoculate conidia solution into a single fixed-site on the back of one segment. This fixed-site infection method is pathogenic but it is also dose dependent. Using the fixed-site infection protocol, it is also very convenient to track hyphae inside the cuticle layer by light and transmission electron microscopy. The fact that few hyphae were detected inside the chitin layer after fixed-site infection with mutant ΔBPS8, a protease secreted during fungi germination, indicates that this method is suitable for screening genes involved in penetrating the integument in large scale. We also found that melanization occurs before new hyphae penetrate the chitin layer. Most importantly, we discovered that fungal infection can induce epidermal cell proliferation through DNA duplication and cell division, which is essential for the host to defend against fungal infection. Taken together the fixed-site infection method may be helpful to determine the mechanism of fungal and host interaction in the integument so as to effectively exert fungal biological virulence.
Mosaic Hemagglutinin-Based Whole Inactivated Virus Vaccines Induce Broad Protection Against Influenza B Virus Challenge in Mice
Authors: Liu Yonghong , Strohmeier Shirin , González-Domínguez Irene , Tan Jessica , Simon Viviana , Krammer Florian , García-Sastre Adolfo , Palese Peter , Sun Weina
Published: September 2021

Influenza viruses undergo antigenic changes in the immuno-dominant hemagglutinin (HA) head domain, necessitating annual re-formulation of and re-vaccination with seasonal influenza virus vaccines for continuing protection. We previously synthesized mosaic HA (mHA) proteins of influenza B viruses which redirect the immune response towards the immuno-subdominant conserved epitopes of the HA via sequential immunization. As ~90% of current influenza virus vaccines are manufactured using the inactivated virus platform, we generated and sequentially vaccinated mice with inactivated influenza B viruses displaying either the homologous (same B HA backbones) or the heterologous (different B HA backbones) mosaic HAs. Both approaches induced long-lasting and cross-protective antibody responses showing strong antibody-dependent cellular cytotoxicity (ADCC) activity. We believe the B virus mHA vaccine candidates represent a major step towards a universal influenza B virus vaccine.
Changing Stony Coral Tissue Loss Disease Dynamics Through Time in Montastraea cavernosa
Authors: Aeby Greta , Ushijima Blake , Bartels Erich , Walter Cory , Kuehl Joseph , Jones Scott , Paul Valerie J.
Published: September 2021

Stony coral tissue loss disease (SCTLD) is affecting corals across the Western Atlantic and displays species-specific and regional differences in prevalence, incidence, degree of mortality, and lesion morphology. We examined two Florida sites with different temporal histories of disease emergence; Fort Lauderdale where SCTLD is endemic and the Lower Florida Keys where SCTLD has recently emerged. Our objectives were to (1) assess the potential impact of SCTLD on overall reef condition by surveying reefs in each region, (2) in a single common species, Montastraea cavernosa, examine differences in SCTLD prevalence, colony mortality, and lesion morphology in each region, and (3) look for differences in contagion by conducting transmission experiments using lesions from each region. Reef surveys found sites in both regions had low coral cover, high algae cover, and similar coral species composition. SCTLD prevalence was higher in the Lower Keys than at Fort Lauderdale and two of the common species, M. cavernosa and S. siderea at Fort Lauderdale were dominated by smaller colonies (<5 cm) whereas larger colonies occurred in the Lower Keys. Tagged M. cavernosa SCTLD-affected colonies were followed for 2 years at one site in each region. In both years, Fort Lauderdale colonies showed declining disease prevalence, low colony mortality, and disease lesions were mainly bleached spots lacking tissue loss. In contrast, Lower Keys colonies tagged in the first year maintained 100% disease prevalence with high mortality, and disease lesions were predominantly tissue loss with no bleached edges. However, SCTLD dynamics changed, with year two tagged colonies showing declining disease prevalence, low mortality, and lesion morphology switched to a mixture of bleached polyps and tissue loss with or without bleached edges. Lesion morphology on colonies was a significant predictor of amount of tissue loss. Aquaria studies found the rate of SCTLD transmission using lesions from the different zones (emergent and endemic) were similar. Our study highlights that differences in coral mortality from SCTLD are not necessarily linked to host species, lesion morphology is reflective of subsequent rate of mortality, and disease dynamics change through time on reefs where the disease has newly emerged.
Charismatic Species as Indicators of Plastic Pollution in the Río de la Plata Estuarine Area, SW Atlantic
Authors: González Carman Victoria , Denuncio Pablo , Vassallo Martina , Berón María Paula , Álvarez Karina C. , Rodriguez-Heredia Sergio
Published: September 2021

Marine plastic pollution is projected to increase globally in the next few decades. This holds true for South America where the number of species that interacts with plastics is increasing. In this study, we explore for the first time the potential of certain charismatic species of marine turtles, mammals and seabirds as indicators of plastic pollution in the Río de la Plata (RdP), one of the largest and most important estuarine areas of the Southwest Atlantic. Through a revision of published studies integrated with unpublished data, we summarize studies on the interaction of charismatic marine species with plastics in the region and evaluate their role as indicators of plastic pollution in the RdP based on aspects of their local ecology and key attributes (i.e., biological/ecological, methodological, and conservation attributes) of indicator species. We found that at least 45 charismatic marine species interact –whether by ingestion or entanglement– with plastics in the region. Eight of these species were selected as potential indicators given their occurrence, probability of sampling and interaction with plastics in the RdP, namely:Chelonia mydas,Caretta caretta,Dermochelys coriacea,Pontoporia blainvillei,Arctocephalus australis,Otaria flavescens,Larus dominicanus, andSpheniscus magellanicus. The species shared some key attributes of indicator species, e.g., they are relatively well studied, but differed in critical aspects such as their home range and mobility. We discuss whether the species’ attributes are strengths or weaknesses according to the available knowledge on their ecology in the RdP, and propose a multispecies indicator of plastic pollution given that those strengths and weaknesses can be compensated among species. Monitoring plastic pollution through a combination of species would enable a better understanding of plastic pollution in this relevant area.
Hemocyte Responses of the Oyster Crassostrea hongkongensis Exposed to Diel-Cycling Hypoxia and Salinity Change
Authors: Xie Zhe , Wei Shuaishuai , Dong Haomiao , Chen Hui , Zhang Qianqian , Liu Wei , Peng Jinxia , Sokolova Inna M. , Hu Menghong , Wang Youji
Published: September 2021

Marine hypoxia caused by nutrient enrichment in coastal waters has become a global problem for decades, especially diel-cycling hypoxia that occurs frequently in the summer season. On the contrary, sudden rainstorms, and freshwater discharge make salinity in estuarine and coastal ecosystems variable, which often occurs with hypoxia. We found mass mortality of the Hong Kong oyster Crassostrea hongkongensis in the field where hypoxia and salinity fluctuation co-occur in the summer season during the past several years. To investigate the effects of diel-cycling hypoxia and salinity changes on the hemocyte immune function of C. hongkongensis, oysters were exposed to a combined effect of two dissolved oxygen (DO) concentrations (24 h normal oxygen 6 mg/L, 12 h normal oxygen 6 mg/L, and 12 h hypoxia 2 mg/L) and three salinities (10, 25, and 35‰) for 14 days. Subsequently, all treatments were restored to constant normal oxygen (6 mg/L) and salinity under 25‰ for 3 days to study the recovery of hemocyte immune function from the combined stress. Hemocyte parameters were analyzed by flow cytometry, including hemocyte mortality (HM), total hemocyte count (THC), phagocytosis (PHA), esterase (EST) activity, reactive oxygen species (ROS), lysosomal content (LYSO), and mitochondrial number (MN). The experimental results showed that diel-cycling hypoxia and salinity changes have obvious interactive effects on various immune parameters. In detail, diel-cycling hypoxia and decreases in salinity led to increased HM, and low salinity caused heavier impacts. In addition, low salinity, and diel-cycling hypoxia also led to decreases in LYSO, EST, and THC, while the decrease of PHA only occurs in the early stage. On the contrary, ROS production increased significantly under low salinity and hypoxic conditions. After 3-day recovery, THC, PHA, EST, LYSO, and MN were basically restored to normal, while HM and ROS were still significantly affected by diel-cycling hypoxia and salinity change, indicating that the combined stress of diel-cycling hypoxia and salinity changes had latent effects on the immune function of C. hongkongensis. Our results highlight that diel-cycling hypoxia and salinity change may impair the health and survival of the Hong Kong oyster C. hongkongensis and may be the key factors for the mass mortality of this oyster in the field.
Data-Driven Discovery of 2D Materials for Solar Water Splitting
Authors: Agarwal Abhishek , Goverapet Srinivasan Sriram , Rai Beena
Published: September 2021

Hydrogen economy, wherein hydrogen is used as the fuel in the transport and energy sectors, holds significant promise in mitigating the deleterious effects of global warming. Photocatalytic water splitting using sunlight is perhaps the cleanest way of producing the hydrogen fuel. Among various other factors, widespread adoption of this technology has mainly been stymied by the lack of a catalyst material with high efficiency. 2D materials have shown significant promise as efficient photocatalysts for water splitting. The availability of open databases containing the “computed” properties of 2D materials and advancements in deep learning now enable us to do “inverse” design of these 2D photocatalysts for water splitting. We use one such database (Jain et al., ACS Energ. Lett. 2019, 4, 6, 1410–1411) to build a generative model for the discovery of novel 2D photocatalysts. The structures of the materials were converted into a 3D image–based representation that was used to train a cell, a basis autoencoder and a segmentation network to ascertain the lattice parameters as well as position of atoms from the images. Subsequently, the cell and basis encodings were used to train a conditional variational autoencoder (CVAE) to learn a continuous representation of the materials in a latent space. The latent space of the CVAE was then sampled to generate several new 2D materials that were likely to be efficient photocatalysts for water splitting. The bandgap of the generated materials was predicted using a graph neural network model while the band edge positions were obtained via empirical correlations. Although our generative modeling framework was used to discover novel 2D photocatalysts for water splitting reaction, it is generic in nature and can be used directly to discover novel materials for other applications as well.
Epidemiology of Sports-Related Eye Injuries Among Athletes in Tianjin, China
Authors: Zhang Jingkai , Zhu Xinlei , Sun Zhiyong , Wang Jiaxing , Sun Zhuoyu , Li Jianan , Huang Yunli , Wang Tian , Xie Ruotian , Han Han , Zhao Xiao , Song Yinting , Guo Miao , Yang Tiantian , Zhang Haokun , He Kai , Li Yiming , Lei Yi , Zhu Yanfang , Cui Bohao , Miao Yuyang , Huang Bo , Brant Rodrigo , Yan Hua
Published: September 2021

Purpose: To investigate the incidence, characteristics, and risk factors of sports-related eye injuries among athletes in Tianjin, China.

Methods: A cross-sectional study was carried out from March 2018 to October 2018. In this study, the athletes from Tianjin University of Sports, Tianjin Vocational College of Sports, and Tianjin provincial sports teams were selected for general investigation. In total, 1,673 athletes were invited and 1,413 participated in the study (response rate of 84.5%).

Results: In total, 1,413 athletes were enrolled; 151 had suffered from sports-related eye injuries, with an incidence of 10.7% (95% CI: 9.1–12.0%). Handball (38.5%) was the sport with the highest incidence of eye injuries, followed by water polo (36.4%) and diving (26.7%). Overall, 42.4% of the athletes were injured by ball and 22.5% of injuries came from teammates. The eye injuries usually occurred during training (64.2%) and competitions (14.6%). Adnexa wound (51.7%) was the most common type of injury. About 11.9% of the athletes with eye injuries had the impaired vision; 66.7% failed to see doctors on time. The athletes <18 years of age had a higher risk of eye injuries (odds ratio [OR] =1.60, 95% CI: 1.06–2.40). The athletes with lower family income (<1,000 RMB) were at risk population for sports-related eye injuries (OR = 3.91, 95% CI: 2.24–6.82). Training >4 h a day increased the risk of eye injuries (OR = 2.21, 95% CI: 1.42–3.43).

Conclusion: The incidence of sports-related eye injuries among athletes was 10.7% in Tianjin, China. Handball, water polo, and diving were the most common activities of injury. Age, family income, and training time were the risk factors for sports-related eye injuries.