bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Tyrosyl-DNA Phosphodiesterase 1 Possesses Transphosphooligonucleotidation Activity With Primary Alcohols
Authors: Dyrkheeva Nadezhda , Anarbaev Rashid , Lebedeva Natalia , Kuprushkin Maxim , Kuznetsova Alexandra , Kuznetsov Nikita , Rechkunova Nadejda , Lavrik Olga
Published: December 2020

Human tyrosyl-DNA phosphodiesterase 1 (TDP1) belongs to the phospholipase D superfamily, whose members contain paired catalytic histidine and lysine residues within two conserved motifs and hydrolyze phosphodiester bonds. TDP1 is a DNA repair enzyme that processes 3′ DNA end blocking lesions and a wide range of synthetic DNA adducts as a substrate. TDP1 hydrolyzes DNA-adducts via two coordinated SN2 nucleophilic attacks mediated by the action of two histidine residues and leads to the formation of the covalent intermediate. Hydrolysis of this intermediate is proposed to be carried out by a water molecule that is activated by the His493 residue acting as a general base. It was known that phospholipase D enzymes are able to catalyze not only hydrolysis but also a transphosphatidylation reaction in the presence of primary alcohols in which they transfer the substrate to the alcohol instead of water. Here, we first demonstrated that TDP1 is able to undergo a “transphosphooligonucleotidation” reaction, transferring the substrate residue to the alcohol, thus inducing the formation of covalent DNA adducts with different primary alcohol residues. Such adducts can be accumulated in the conditions of high concentration of alcohol. We demonstrated that glycerol residue was efficiently cleaved from the 3′-end by TDP1 but not by its mutant form associated with the disease spinocerebellar ataxia with axonal neuropathy. Therefore, the second reaction step can be carried out not only by a water molecule but also by the other small nucleophilic molecules, e.g., glycerol and ethanol. Thus, in some cases, TDP1 can be regarded not only as a repair enzyme but also as a source of DNA damage especially in the case of mutation. Such damages can make a negative contribution to the stability of cell vitality.
Planar Cell Polarity and E-Cadherin in Tissue-Scale Shape Changes in Drosophila Embryos
Authors: Kong Deqing , Großhans Jörg
Published: December 2020

Planar cell polarity and anisotropic cell behavior play critical roles in large-scale epithelial morphogenesis, homeostasis, wound repair, and regeneration. Cell–Cell communication and mechano-transduction in the second to minute scale mediated by E-cadherin complexes play a central role in the coordination and self-organization of cellular activities, such as junction dynamics, cell shape changes, and cell rearrangement. Here we review the current understanding in the interplay of cell polarity and cell dynamics during body axis elongation and dorsal closure inDrosophilaembryos with a focus on E-cadherin dynamics in linking cell and tissue polarization and tissue-scale shape changes.
CRISPR Genome Editing Applied to the Pathogenic Retrovirus HTLV-1
Authors: Panfil Amanda R. , Green Patrick L. , Yoder Kristine E.
Published: December 2020

CRISPR editing of retroviral proviruses has been limited to HIV-1. We propose human T-cell leukemia virus type 1 (HTLV-1) as an excellent model to advance CRISPR/Cas9 genome editing technologies against actively expressing and latent retroviral proviruses. HTLV-1 is a tumorigenic human retrovirus responsible for the development of both leukemia/lymphoma (ATL) and a neurological disease (HAM/TSP). The virus immortalizes and persists in CD4+ T lymphocytes that survive for the lifetime of the host. The most important drivers of HTLV-1-mediated transformation and proliferation are the tax and hbz viral genes. Tax, transcribed from the plus-sense or genome strand, is essential for de novo infection and cellular immortalization. Hbz, transcribed from the minus-strand, supports proliferation and survival of infected cells in both its protein and mRNA forms. Abrogating the function or expression of tax and/or hbz by genome editing and mutagenic double-strand break repair may disable HTLV-1-infected cell growth/survival and prevent immune modulatory effects and ultimately HTLV-1-associated disease. In addition, the HTLV-1 viral genome is highly conserved with remarkable sequence homogeneity, both within the same host and even among different HTLV isolates. This offers more focused guide RNA targeting. In addition, there are several well-established animal models for studying HTLV-1 infection in vivo as well as cell immortalization in vitro. Therefore, studies with HTLV-1 may provide a better basis to assess and advance in vivo genome editing against retroviral infections.
Long-Term Land Use Land Cover Change in Urban Centers of Southwest Ethiopia From a Climate Change Perspective
Authors: Dessu Tesfaye , Korecha Diriba , Hunde Debela , Worku Adefires
Published: December 2020

Long-term urban land use land cover change (LULCC) dynamics and climate change trends in Southwest Ethiopia's four urban centers were examined for 60 years. Remote sensing, aerial photos, and Landsat, temperature, and rainfall data were analyzed from a climate change perspective over the Jimma, Bedelle, Bonga, and Sokorru urban centers of southwest Ethiopia from 1953 to 2018. Based on geospatial analysis and maximum likelihood supervised image classification techniques to classify LULCC categories, the Mann-Kendall test was applied to perform trend analyses on temperature and rainfall. The LULCC analysis revealed that built-up areas over the urban centers had shown an increasing trend, with the highest increment by 2,360 hectares over Jimma, while vegetation, wetland, and cropland declined due to conversion of plain lands to built-up areas and other similar zones. The pronounced decline of vegetation coverage was 1,427, 185,116, and 32 hectares in Jimma, Bedelle, Bonga, and Sokorru, respectively. Mann-Kendall test results showed a significant sign of intra-seasonal and inter-annual variability of rainfall while the summer and annual rainfall patterns remained less variable compared to other seasons. This study's findings revealed that when the mean between the two climatic normals of 1953–86 is compared with 1987–2018, the temperature has significantly increased in the latter three decades. The rapid expansion of built-up areas coupled with a sharp decline of green space or vegetation and agricultural/croplands could lead to gradual changes in LULCC classes, which have contributed to the changing of the local climate, especially the surface temperature and rainfall over the urban centers of southwest Ethiopia. Therefore, we recommend that the local urban administrations emphasize sustainable urban development by integrating urban planning policies with land use to protect the environment by adopting local municipal adaptation and national climate change strategies. Restoration of the local environment and creation of climate-smart cities could be critical to the resilience of urban dwellers and ecosystems to the changing climate by enhancing grass-root climate services. To that end, we recommend further advanced research to understand how urban LULC-related changes and other factors contribute to local and regional climates, as urban areas of Southwest Ethiopia are undergoing a rapid transformation of their rural surroundings.
Focusing on Emotional and Social Intelligence Stimulation of People With Dementia by Playing a Serious Game—Proof of Concept Study
Authors: Berenbaum Rakel , Tziraki Chariklia , Baum Reem , Rosen Adi , Reback Tuvia , Abikhzer Judith , Naparstek Daphna , Ben-David Boaz M.
Published: December 2020

Context: Dementia is one of the top five chronic diseases, which has an overwhelming impact on patients' life quality, family, and caregivers. Currently, research relating to people with dementia (PwD) focuses on the deterioration of cognitive abilities. A more innovative approach, and the one taken by this paper, is focusing on methods to maintain and improve functionality, communication and quality of life of PwD by building on remaining capacities in the yet unexplored domain of emotional and social intelligence (ESI). The use of serious games for PwD (SG4D) aimed at building social and emotional capacity is a budding field of research.

Objectives: Proof of concept that the, low cost, easy to deploy SG4D, called “My Brain Works” (MBW), co-designed with PwD, enhances ESI, based on the Bar-On ESI model.

Methods: 27 PwD, clients at MELABEV dementia day center, participated in a mixed methods 12 weeks pilot, proof of concept study using a tablet SG4D co-designed with PwD. Quantitative performance data was collected automatically by the tablet during game sessions. In this paper we focus on the analysis of the qualitative and quantitative data related to ESI, observed by 10 different researchers, during each game session.

Results: Quantitative data revealed: both the PwD with high and low MoCA scores had similar average ESI scores. Qualitative analysis revealed that the PwD demonstrated 9 sub-components of the Bar-On ESI Model.

Conclusion: While there is no drug to stop cognitive decline associated with dementia, interventions related to ESI, on the other hand, may improve functioning and quality of life. Despite declines in cognitive abilities, our study shows that a tablet based SG4D can stimulate their ESI and evoke responses in self-awareness, empathy, social and communication capacities. Using SG4D to exercise and maintain social skills is an area that may be promising in the future and may help counter the negative effects of social isolation and loneliness. Such games, while not focusing on cognitive improvement, may also impact on cognitive functioning and help bridge the gap between caregiver and PwD. More research is needed with larger sample sizes.
Investigating the Potential for Ultraviolet Light to Modulate Morbidity and Mortality From COVID-19: A Narrative Review and Update
Authors: Gorman Shelley , Weller Richard B.
Published: December 2020

During the COVID-19 (coronavirus disease of 2019) pandemic, researchers have been seeking low-cost and accessible means of providing protection from its harms, particularly for at-risk individuals such as those with cardiovascular disease, diabetes and obesity. One possible way is via safe sun exposure, and/or dietary supplementation with induced beneficial mediators (e.g., vitamin D). In this narrative review, we provide rationale and updated evidence on the potential benefits and harms of sun exposure and ultraviolet (UV) light that may impact COVID-19. We review recent studies that provide new evidence for any benefits (or otherwise) of UV light, sun exposure, and the induced mediators, vitamin D and nitric oxide, and their potential to modulate morbidity and mortality induced by infection with SARS-CoV-2 (severe acute respiratory disease coronavirus-2). We identified substantial interest in this research area, with many commentaries and reviews already published; however, most of these have focused on vitamin D, with less consideration of UV light (or sun exposure) or other mediators such as nitric oxide. Data collected to-date suggest that ambient levels of both UVA and UVB may be beneficial for reducing severity or mortality due to COVID-19, with some inconsistent findings. Currently unresolved are the nature of the associations between blood 25-hydroxyvitamin D and COVID-19 measures, with more prospective data needed that better consider lifestyle factors, such as physical activity and personal sun exposure levels. Another short-coming has been a lack of measurement of sun exposure, and its potential to influence COVID-19 outcomes. We also discuss possible mechanisms by which sun exposure, UV light and induced mediators could affect COVID-19 morbidity and mortality, by focusing on likely effects on viral pathogenesis, immunity and inflammation, and potential cardiometabolic protective mechanisms. Finally, we explore potential issues including the impacts of exposure to high dose UV radiation on COVID-19 and vaccination, and effective and safe doses for vitamin D supplementation.
Effects of Obesity and Thrombophilia on the Risk of Abortion in Women Undergoing In Vitro Fertilization
Authors: Candeloro Matteo , Di Nisio Marcello , Ponzano Adalisa , Tiboni Gian Mario , Potere Nicola , Tana Marco , Rutjes Anne W. S. , Porreca Ettore
Published: December 2020

Introduction

Obesity is associated with a higher risk of abortion in women undergoing in vitro fertilization (IVF). Whether thrombophilia amplifies this risk is currently unclear. The aim of this study was to evaluate the effects of thrombophilia on the risk of abortion in obese women treated with IVF.

Methods

Patient characteristics, presence of inherited or acquired thrombophilia, and comorbidities were prospectively collected before the procedure in consecutive women undergoing IVF. The primary outcome was the incidence of abortion among women who achieved a clinical pregnancy.

Results

A total of 633 non-obese and 49 obese Caucasian women undergoing IVF were included. 204 (32%) women achieved clinical pregnancy, of whom six had an ectopic pregnancy and 63 experienced an abortion. The incidence of abortion was higher in obese women compared to non-obese women after adjusting for age (64.3% vs. 29.3%, odds ratio [OR] 4.41; 95% CI 1.41 to 13.81). Women with one or more thrombophilia were at increased risk of abortion relative to those without thrombophilia (OR 2.70; 95% CI 1.34 to 5.45), and the risk seemed to be higher with hereditary (OR 5.12; 95% CI 1.77 to 14.8) than acquired thrombophilia (OR 1.92; 95% CI 0.52 to 5.12; p for interaction 0.194). Among obese women, the presence of one or more thrombophilia seemed associated with a substantially increased risk of abortion (unadjusted OR 14.00; 95% CI 0.94 to 207.6).

Conclusions

Obese women undergoing IVF have a high risk of abortion which seems further amplified by the concomitant presence of thrombophilia.
An Ordinary Differential Equation Model for Simulating Local-pH Change at Electrochemical Interfaces
Authors: Mukouyama Yoshiharu , Nakanishi Shuji
Published: December 2020

The local pH value at an electrochemical interface (pHs) inevitably changes during redox reactions involving the transfer of H+ or OH− ions. It is important to quantitatively estimate pHs during polarization, as this parameter has a significant impact on the activity and selectivity of electrochemical reactions. Numerical simulation is an effective means of estimating pHs because it is not subject to experimental constraints. As demonstrated in a number of studies, pHs can be estimated by solving partial differential equations that describe diffusion process. In the present work, we propose a method to consider the process by using ordinary differential equations (ODEs), which can significantly reduce the computational resources required for estimating pHs values. In the ODE-based model, the description of the diffusion process was achieved by considering the reaction plane in the diffusion layer over which the H+ and OH− concentrations are balanced while assuming that the concentration profiles in the layer are in a steady state. The resulting model successfully reproduces experimental voltammograms characterized by local pH changes in association with the hydrogen evolution and hydrogen peroxide reduction reactions.
Population Estimate, Habitat-Use and Activity Patterns of the Honey Badger in a Dry-Deciduous Forest of Central India
Authors: Chatterjee Nilanjan , Nigam Parag , Habib Bilal
Published: December 2020

Studies on carnivores are skewed toward larger species in India, limiting ecological information of the smaller ones. Basic ecological understanding like population density, distribution, habitat-use patterns of small carnivores is lacking. This inadequate knowledge has led to disagreement between conservation approaches in different landscapes. Honey badgers (Mellivora capensis) are cryptic carnivores distributed across large areas of Africa and Asia; however, fundamental ecological knowledge is scarce. The species is thought to exist at low population densities throughout its range. We used a large camera trap dataset from a tiger reserve in Maharashtra State, India to understand the population density, habitat preference, and diel activity pattern of the species. We applied an extension of the spatial count model for the estimation of population. Habitat preference analyses were carried out using generalized linear models and activity patterns were analyzed using kernel-density functions. The population density was estimated as 14.09 (95% CI 10–22.25) individuals per 100 km2. Habitat use revealed a positive association with forest cover and negative association with elevation. This may expose the species to other large carnivores in the habitat but honey badger activity pattern peaked at midnight retaining minimum temporal overlap with other large carnivores (e.g., tiger Panthera tigris, leopard Panthera pardus, and dhole Cuon alpinus) and moderate overlap with small carnivores (e.g., jungle cat Felis chaus, rusty-spotted cat Prionailurus rubiginosus). These behaviors, in turn, may facilitate the coexistence of species at such high density even with high carnivore density. We hope the findings of this study will fill the existing knowledge gap of this species and aid in guiding the conservation of the species in other landscapes and reserves.
Territory Quality Predicts Avian Vocal Performance Across an Urban-Rural Gradient
Authors: Phillips Jennifer N. , Cooper W. Justin , Luther David A. , Derryberry Elizabeth P.
Published: December 2020

Human activity around the globe is a growing source of selection pressure on animal behavior and communication systems. Some animals can modify their vocalizations to avoid masking from anthropogenic noise. However, such modifications can also affect the salience of these vocalizations in functional contexts such as competition and mate choice. Such is the case in the well-studied Nuttall's white-crowned sparrow (Zonotrichia leucophrys nuttalli), which lives year-round in both urban San Francisco and nearby rural Point Reyes. A performance feature of this species' song is salient in territorial defense, such that higher performance songs elicit stronger responses in simulated territorial intrusions; but songs with lower performance values transmit better in anthropogenic noise. A key question then is whether vocal performance signals male quality and ability to obtain high quality territories in urban populations. We predicted white-crowned sparrows with higher vocal performance will be in better condition and will tend to hold territories with lower noise levels and more species-preferred landscape features. Because white-crowned sparrows are adapted to coastal scrub habitats, we expect high quality territories to contain lower and less dense canopies, less drought, more greenness, and more flat open ground for foraging. To test our predictions, we recorded songs and measured vocal performance and body condition (scaled mass index and fat score) for a set of urban and rural birds (N = 93), as well as ambient noise levels on their territories. Remote sensing metrics measured landscape features of territories, such as drought stress (NDWI), greenness (NDVI), mean canopy height, maximum height, leaf area density (understory and canopy), slope, and percent bare ground for a 50 m radius on each male territory. We did not find a correlation between body condition and performance but did find a relationship between noise levels and performance. Further, high performers held territories with lower canopies and less dense vegetation, which are species-preferred landscape features. These findings link together fundamental aspects of sexual selection in that habitat quality and the quality of sexually selected signals appear to be associated: males that have the highest performing songs are defending territories of the highest quality.
Presence and Genetic Identity of Symbiodiniaceae in the Bioeroding Sponge Genera Cliona and Spheciospongia (Clionaidae) in the Spermonde Archipelago (SW Sulawesi), Indonesia
Authors: van der Windt Niels , van der Ent Esther , Ambo-Rappe Rohani , de Voogd Nicole J.
Published: December 2020

Members of the family Symbiodiniaceae form symbiotic relationships with several metazoan groups on coral reefs, most notably scleractinian corals. However, despite their importance to the health of coral reefs, their relationship with other host organisms such as bioeroding sponges (Clionaidae) is still relatively understudied. In this study we investigate the presence and identity of Symbiodiniaceae in Clionaidae species in Indonesia and evaluate findings related to the evolution and ecology of the host-symbiont relationship. Clionaidae were collected throughout the Spermonde Archipelago in Indonesia. Morphological and molecular techniques were used to identify the sponge host (28S ribosomal DNA) and their Symbiodiniaceae symbionts (ITS2). Seven Clionaidae species were found, of which four species contained Symbiodiniaceae. Cliona aff. orientalis, Cliona thomasi and Spheciospongia maeandrina were host to Cladocopium, while Spheciospongia digitata contained Durusdinium and Freudenthalidium. In the remaining species: Cliona sp., Cliona utricularis and Spheciospongia trincomaliensis no evidence of the presence of Symbiodiniaceae was found. Our results provide the first record of Symbiodiniaceae in the sponge genus Spheciospongia. Additionally, we provide the first findings of Freudenthalidium and first molecular evidence of Durusdinium in bioeroding sponges. Our results indicate coevolution between Spheciospongia digitata, Spheciospongia maeandrina and their symbionts. We discuss that the diversity of Symbiodiniaceae within bioeroding sponges is likely far greater than currently reported in literature. Considering the threat bioeroding sponges can pose to the health of coral reefs, it is crucial to understand Symbiodiniaceae diversity within Clionaidae and their effect on the functioning of Clionaidae species. We propose that the identity of the symbiont species is mostly related to the host species, but we did observe a potential case of environmental adaptation related to environmental stressors.
Forest Management Under Megadrought: Urgent Needs at Finer Scale and Higher Intensity
Authors: Field Jason P. , Breshears David D. , Bradford John B. , Law Darin J. , Feng Xiao , Allen Craig D.
Published: December 2020

Drought and warming increasingly are causing widespread tree die-offs and extreme wildfires. Forest managers are struggling to improve anticipatory forest management practices given more frequent, extensive, and severe wildfire and tree die-off events triggered by “hotter drought”—drought under warmer than historical conditions. Of even greater concern is the increasing probability of multi-year droughts, or “megadroughts”—persistent droughts that span years to decades, and that under a still-warming climate, will also be hotter than historical norms. Megadroughts under warmer temperatures are disconcerting because of their potential to trigger more severe forest die-off, fire cycles, pathogens, and insect outbreaks. In this Perspective, we identify potential anticipatory and/or concurrent options for non-timber forest management actions under megadrought, which by necessity are focused more at finer spatial scales such as the stand level using higher-intensity management. These management actions build on silvicultural practices focused on growth and yield (but not harvest). Current management options that can be focused at finer scales include key silvicultural practices: selective thinning; use of carefully selected forward-thinking seed mixes; site contouring; vegetation and pest management; soil erosion control; and fire management. For the extreme challenges posed by megadroughts, management will necessarily focus even more on finer-scale, higher-intensity actions for priority locations such as fostering stand refugia; assisted stand recovery via soil amendments; enhanced root development; deep soil water retention; and shallow water impoundments. Drought-induced forest die-off from megadrought likely will lead to fundamental changes in the structure, function, and composition of forest stands and the ecosystem services they provide.
Selective Sweeps Lead to Evolutionary Success in an Amazonian Hyperdominant Palm
Authors: Melo Warita A. , Vieira Lucas D. , Novaes Evandro , Bacon Christine D. , Collevatti Rosane G.
Published: December 2020

Despite the global importance of tropical ecosystems, few studies have identified how natural selection has shaped their megadiversity. Here, we test for the role of adaptation in the evolutionary success of the widespread, highly abundant Neotropical palmMauritia flexuosa.We used a genome scan framework, sampling 16,262 single-nucleotide polymorphisms (SNPs) with target sequence capture in 264 individuals from 22 populations in rainforest and savanna ecosystems. We identified outlier loci as well as signal of adaptation using Bayesian correlations of allele frequency with environmental variables and detected both selective sweeps and genetic hitchhiking events. Functional annotation of SNPs with selection footprints identified loci affecting genes related to adaptation to environmental stress, plant development, and primary metabolic processes. The strong differences in climatic and soil variables between ecosystems matched the high differentiation and low admixture in population Bayesian clustering. Further, we found only small differences in allele frequency distribution in loci putatively under selection among widespread populations from different ecosystems, with fixation of a single allele in most populations. Taken together, our results indicate that adaptive selective sweeps related to environmental stress shaped the spatial pattern of genetic diversity inM. flexuosa, leading to high similarity in allele frequency among populations from different ecosystems.
Prognosis-Predictive Signature and Nomogram Based on Autophagy-Related Long Non-coding RNAs for Hepatocellular Carcinoma
Authors: Jia Yu , Chen Yan , Liu Jiansheng
Published: December 2020

Autophagy plays a vital role in hepatocellular carcinoma (HCC) pathogenesis. Long non-coding RNAs (lncRNAs) are considered regulators of autophagy, and the aim of the present study was to investigate the prognostic value of autophagy-related lncRNA (ARlncRNA) and develop a new prognostic signature to predict the 1-year and 3-year overall survival (OS) of HCC patients. Transcriptome and clinical survival information of HCC patients was obtained from The Cancer Genome Atlas database. A set of ARlncRNAs was identified by co-expression analysis, from which seven ARlncRNAs (AC005229.4, AL365203.2, AL117336.3, AC099850.3, ELFN1-AS1, LUCAT1, and AL031985.3) were selected for use as a predictive signature. Risk scores were derived for each patient, who were then divided into high-risk and low-risk groups according to the median risk value. The OS of high-risk patients was significantly lower than that of low-risk patients (P < 0.0001). The 1- and 3-year time-dependent ROC curves were used to evaluate the predictive ability of the risk score (AUC = 0.785 of 1 year, 0.710 of 3 years), and its predictive ability was found to be better than TNM stage. Moreover, the risk score was significantly, linearly related to pathological grade and TNM stage (P < 0.05). Overall, a novel nomogram to predict the 1-year and 3-year OS of HCC patients was developed, which shows good reliability and accuracy, for use in improved treatment decision-making.
Prospects for the Analysis and Reduction of Damaging Behaviour in Group-Housed Livestock, With Application to Pig Breeding
Authors: Canario Laurianne , Bijma Piter , David Ingrid , Camerlink Irene , Martin Alexandre , Rauw Wendy Mercedes , Flatres-Grall Loïc , Zande Lisette van der , Turner Simon P. , Larzul Catherine , Rydhmer Lotta
Published: December 2020

Innovations in the breeding and management of pigs are needed to improve the performance and welfare of animals raised in social groups, and in particular to minimise biting and damage to group mates. Depending on the context, social interactions between pigs can be frequent or infrequent, aggressive, or non-aggressive. Injuries or emotional distress may follow. The behaviours leading to damage to conspecifics include progeny savaging, tail, ear or vulva biting, and excessive aggression. In combination with changes in husbandry practices designed to improve living conditions, refined methods of genetic selection may be a solution reducing these behaviours. Knowledge gaps relating to lack of data and limits in statistical analyses have been identified. The originality of this paper lies in its proposal of several statistical methods for common use in analysing and predicting unwanted behaviours, and for genetic use in the breeding context. We focus on models of interaction reflecting the identity and behaviour of group mates which can be applied directly to damaging traits, social network analysis to define new and more integrative traits, and capture-recapture analysis to replace missing data by estimating the probability of behaviours. We provide the rationale for each method and suggest they should be combined for a more accurate estimation of the variation underlying damaging behaviours.
Genetic Determinism Exists for the Global DNA Methylation Rate in Sheep
Authors: Hazard Dominique , Plisson-Petit Florence , Moreno-Romieux Carole , Fabre Stéphane , Drouilhet Laurence
Published: December 2020

Recent studies showed that epigenetic marks, including DNA methylation, influence production and adaptive traits in plants and animals. So far, most studies dealing with genetics and epigenetics considered DNA methylation sites independently. However, the genetic basis of the global DNA methylation rate (GDMR) remains unknown. The main objective of the present study was to investigate genetic determinism of GDMR in sheep. The experiment was conducted on 1,047 Romane sheep allocated into 10 half-sib families. After weaning, all the lambs were phenotyped for global GDMR in blood as well as for production and adaptive traits. GDMR was measured by LUminometric Methylation Analysis (LUMA) using a pyrosequencing approach. Association analyses were conducted on some of the lambs (n= 775) genotyped by using the Illumina OvineSNP50 BeadChip. Blood GDMR varied among the animals (average 70.7 ± 6.0%). Female lambs had significantly higher GDMR than male lambs. Inter-individual variability of blood GDMR had an additive genetic component and heritability was moderate (h2= 0.20 ± 0.05). No significant genetic correlation was found between GDMR and growth or carcass traits, birthcoat, or social behaviors. Association analyses revealed 28 QTLs associated with blood GDMR. Seven genomic regions on chromosomes 1, 5, 11, 17, 24, and 26 were of most interest due to either high significant associations with GDMR or to the relevance of genes located close to the QTLs. QTL effects were moderate. Genomic regions associated with GDMR harbored several genes not yet described as being involved in DNA methylation, but some are already known to play an active role in gene expression. In addition, some candidate genes,CHD1,NCO3A, KDM8, KAT7, andKAT6Ahave previously been described to be involved in epigenetic modifications. In conclusion, the results of the present study indicate that blood GDMR in domestic sheep is under polygenic influence and provide new insights into DNA methylation genetic determinism.
Case Report: Humanized Selective CD19CAR-T Treatment Induces MRD-Negative Remission in a Pediatric B-ALL Patient With Primary Resistance to Murine-Based CD19CAR-T Therapy
Authors: Wang Kai , Zhao Yu , Wang Xuan , Wang Bin , Qin Maoquan , Zhu Guanghua , Wu Huantong , Liu Zhongfeng , Zheng Xueling , Zheng Huyong , Chen Zhiguo
Published: December 2020

Background

CD19 chimeric antigen receptor T cell (CD19CAR-T) has shown great potential to treat acute B cell lymphoblastic leukemia (B-ALL) and B cell lymphoma, and most of anti-CD19 scFv are derived from murine antibody sequences. However, about 10–20% of B-ALL patients exhibit primary resistance to murine-based CD19CAR-T (CD19mCAR-T). Herein, we report that a humanized selective CD19CAR-T (CD19hsCAR-T) may offer a solution to this problem.

Case Description

A 10-year old boy was diagnosed with high-risk B-ALL in Mar., 2013, and relapsed in Oct., 2018, after he underwent haplo-identical hematopoietic stem cell transplantation (HSCT) in 2017. The patient then received haplo-identical CD19mCAR-T infusions twice following induction chemotherapy with Vincristine, Dexamethasone and Asparaginase (VDL), but no response was observed. We further treated this patient with CD19hsCAR-T following chemotherapy with Vindesine, Idarubicin, Dexamethasone, and Pegylated Asparaginase (VDLD) plus bortezomib. The patient achieved minimal residual disease-negative (MRDneg) complete remission with incomplete hematopoietic recovery (CRi), and remained in CRi for more than 8 months with manageable side effect. The patient, unfortunately, died of unidentified pulmonary infection on Jan. 25 2020.

Conclusion

CD19hsCAR-T may have the potential to induce remission in patients who are primarily refractory to CD19mCAR-T.
COVID-19: Coronavirus Vaccine Development Updates
Authors: Zhao Jing , Zhao Shan , Ou Junxian , Zhang Jing , Lan Wendong , Guan Wenyi , Wu Xiaowei , Yan Yuqian , Zhao Wei , Wu Jianguo , Chodosh James , Zhang Qiwei
Published: December 2020

Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a newly emerged coronavirus, and has been pandemic since March 2020 and led to many fatalities. Vaccines represent the most efficient means to control and stop the pandemic of COVID-19. However, currently there is no effective COVID-19 vaccine approved to use worldwide except for two human adenovirus vector vaccines, three inactivated vaccines, and one peptide vaccine for early or limited use in China and Russia. Safe and effective vaccines against COVID-19 are in urgent need. Researchers around the world are developing 213 COVID-19 candidate vaccines, among which 44 are in human trials. In this review, we summarize and analyze vaccine progress against SARS-CoV, Middle-East respiratory syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, including inactivated vaccines, live attenuated vaccines, subunit vaccines, virus like particles, nucleic acid vaccines, and viral vector vaccines. As SARS-CoV-2, SARS-CoV, and MERS-CoV share the common genus,Betacoronavirus, this review of the major research progress will provide a reference and new insights into the COVID-19 vaccine design and development.
Integrated Analysis of the ETS Family in Melanoma Reveals a Regulatory Role of ETV7 in the Immune Microenvironment
Authors: Qu Hui , Zhao Hui , Zhang Xi , Liu Yang , Li Feng , Sun Liyan , Song Zewen
Published: December 2020

The ETS family modulates immune response and drug efficiency to targeted therapies, but their role in melanoma is largely unclear. In this study, the ETS family was systematically analyzed in multiple public data sets. Bioinformatics tools were used to characterize the function of ETV7 in melanoma. A prognostic model was constructed using the LASSO Cox regression method. We found that ETV7 was the only differentially expressed gene with significant prognostic relevance in melanoma. Enrichment analysis of seven independent data sets indicated ETV7 participation in various immune-related pathways. ETV7 particularly showed a strong positive correlation with CD8+ T cell infiltration. The prognostic model based on ETV7 and its hub genes showed a relatively good predictive value in training and testing data sets. Thus, ETV7 can potentially regulate the immune microenvironment in melanoma.
CRISPR/Cas12a-Mediated Gene Editing in Geodia barretti Sponge Cell Culture
Authors: Hesp Kylie , Flores Alvarez John L. , Alexandru Ana-Maria , van der Linden Jip , Martens Dirk E. , Wijffels Rene H. , Pomponi Shirley A.
Published: December 2020

Sponges and their associated microorganisms are the most prolific source of marine natural products, and many attempts have been made at creating a marine sponge cell line to produce these products efficiently. However, limited knowledge on the nutrients sponge cells require to grow and poor genetic accessibility have hampered progress toward this goal. Recently, a new sponge-specific nutrient medium M1 has been shown to stimulate sponge cells in vitro to divide rapidly. In this study, we demonstrate for the first time that sponge cells growing in M1 can be genetically modified using a CRISPR/Cas12a gene editing system. A short sequence of scrambled DNA was inserted using a single-stranded oligodeoxynucleotide donor template to disrupt the 2′,5′-oligoadenylate synthetase gene of cells from the boreal deep-sea sponge Geodia barretti. A blue fluorescent marker gene appeared to be inserted in an intron of the same gene and expressed by a small number of G. barretti cells. Our results represent an important step toward developing an optimized continuous sponge cell line to produce bioactive compounds.
Obstacles and Considerations Related to Clinical Trial Research During the COVID-19 Pandemic
Authors: Hashem Hasan , Abufaraj Mohammad , Tbakhi Abdelghani , Sultan Iyad
Published: December 2020

The response to the COVID-19 pandemic from the research and science community has been vigorous, with information being released faster than that of any other event in human history. Articles related to the virus were being rapidly published by January 2020. A small fraction of these publications comprised reports of prospective clinical trials (0.25%), and many of these trials have imparted conflicting conclusions, leading to confusion among the public and the scientific community. Additionally, the pandemic has raised many serious scientific and ethical concerns related to clinical research. In this review, we divided the conduct of clinical research trials into three steps and critically reviewed each step, along with the challenges and obstacles arising amid the ongoing crisis. The clinical research steps we reviewed include (1) clinical trial design factors such as social and scientific value, feasibility, single vs. multicenter trials, randomization, control groups, endpoints, off-label and compassionate use of medications, data analysis, and verifying the integrity of data; (2) ethical issues such as committee approvals, efficiency, virtual visits and remote monitoring, informed consent, shipping investigational products, and external monitoring and audits; and (3) publication and sharing of preprints, press releases, social media, and misinformation. The COVID-19 pandemic is adversely affecting existing clinical trials for other ailments and diseases, including cancer, with most trials being delayed or deferred. Although urgency is needed to communicate effective treatment and prevention strategies for COVID-19, research efforts should maintain the same high-quality core ethical principles that governed human subject research before the pandemic. Despite the catastrophic devastation caused by the pandemic, the adoption of more flexible, cost-effective methods of conducting clinical trials (without compromising ethical conduct, safety, or data integrity, while maintaining research efficiency) represents a potential silver lining. Streamlining clinical research will help to congruently address other important health issues, despite the ongoing COVID-19 crisis.
Texture Analysis in the Diagnosis of Primary Breast Cancer: Comparison of High-Resolution Dedicated Breast Positron Emission Tomography (dbPET) and Whole-Body PET/CT
Authors: Satoh Yoko , Hirata Kenji , Tamada Daiki , Funayama Satoshi , Onishi Hiroshi
Published: December 2020

Objective: This retrospective study aimed to compare the ability to classify tumor characteristics of breast cancer (BC) of positron emission tomography (PET)-derived texture features between dedicated breast PET (dbPET) and whole-body PET/computed tomography (CT).

Methods: Forty-four BCs scanned by both high-resolution ring-shaped dbPET and whole-body PET/CT were analyzed. The primary BC was extracted with a standardized uptake value (SUV) threshold segmentation method. On both dbPET and PET/CT images, 38 texture features were computed; their ability to classify tumor characteristics such as tumor (T)-category, lymph node (N)-category, molecular subtype, and Ki67 levels was compared. The texture features were evaluated using univariate and multivariate analyses following principal component analysis (PCA). AUC values were used to evaluate the diagnostic power of the computed texture features to classify BC characteristics.

Results: Some texture features of dbPET and PET/CT were different between Tis-1 and T2-4 and between Luminal A and other groups, respectively. No association with texture features was found in the N-category or Ki67 level. In contrast, receiver-operating characteristic analysis using texture features' principal components showed that the AUC for classification of any BC characteristics were equally good for both dbPET and whole-body PET/CT.

Conclusions: PET-based texture analysis of dbPET and whole-body PET/CT may have equally good classification power for BC.
A Cohort Study of Liver Involvement in Patients With Adult-Onset Still's Disease: Prevalence, Characteristics and Impact on Prognosis
Authors: Chi Huihui , Wang Zhihong , Meng Jianfen , Han Pingyang , Zhai Limin , Feng Tienan , Teng Jialin , Sun Yue , Hu Qiongyi , Zhang Hao , Liu Honglei , Cheng Xiaobing , Ye Junna , Shi Hui , Wu Xinyao , Zhou Zhuochao , Jia Jinchao , Wan Liyan , Liu Tingting , Qiao Xin , Wang Mengyan , Wang Fan , Chen Xia , Yang Chengde , Su Yutong
Published: December 2020

Objective: Adult-onset Still's disease (AOSD) is a systemic disorder commonly accompanied by liver involvement. This study aims to illustrate the detailed information of liver abnormalities in patients with AOSD and evaluate the impact on the prognosis.

Methods: A total number of 128 hospitalized patients, who met the Yamaguchi criteria of AOSD in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2016 to August 2019 were consecutively enrolled and followed up. The demographic characteristics, clinical features, laboratory tests, treatments and prognosis were recorded. Correlations of liver function tests (LFTs) with disease activity and laboratory parameters were analyzed by the Spearman test. Risk factors of the refractory AOSD were evaluated by multivariate logistic regression analysis.

Results: Liver involvement was presented in 104 (81.3%) patients with AOSD. We observed that 34 (32.7%) patients were with mild elevation, 32 (30.8%) patients were with moderate elevation, and 38 (36.5%) patients were with severe elevation. The majority of elevated ALT, AST and ALP decreased to normal within the range of 2 months, except for GGT. Furthermore, the LFTs were found significantly correlated with disease activity. Besides, we found patients with higher levels of LFTs tended to require more intensive treatments and suffered from poorer prognosis. Multivariate logistic regression analysis showed ALP ≥ 141 IU/L and GGT ≥ 132 IU/L are independent risk factors of refractory AOSD.

Conclusion: Liver involvement is common in patients with AOSD, the levels of LFTs are associated with disease activity and related to the treatment strategies and prognosis.
Case Report: Composite Angioimmunoblastic T-Cell Lymphoma and Epstein-Barr Virus-Positive B-Cell Lymphoproliferative Disorder as Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders
Authors: Kakiuchi Seiji , Yakushijin Kimikazu , Takagi Ikumi , Rikitake Junpei , Akiyama Hiroaki , Matsuba Hiroyuki , Hayashi Yoshitake , Kajimoto Kazuyoshi , Iwata Nobuko
Published: December 2020

Immunosuppressants are widely used to treat patients with rheumatoid arthritis (RA), and their adverse effects have been known to cause other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs). We report a patient with RA who had been treated with methotrexate (MTX) and tacrolimus (TAC) and who developed whole body lymphadenopathy. We simultaneously confirmed angioimmunoblastic T-cell lymphoma (AITL) through a right cervical lymph node biopsy and Epstein-Barr virus-positive B-cell lymphoproliferative disorder (EBV-positive B-LPD) through a bone marrow examination. After cessation of immunosuppressant therapy, both LPDs completely disappeared. Patients with AITL are occasionally reported to develop B-cell lymphoma through reactivation of the EBV, which leads to clonal expansion in the microenvironment. Immunohistochemistry results revealed that both LPD components were positive for EBV-encoded RNA. Moreover, in this patient, the plasma EBV DNA level was found to be high; therefore, EBV infection was a probable etiology. Synchronous coexistence of AITL and B-LPD as an OIIA-LPD has rarely been reported. This case report is the first to discuss the disappearance of both LPDs on withdrawal of immunosuppressants only. AITL occasionally accompany B-LPD; however, this composite lymphoma comprised AITL and B-LPD, and OIIA-LPDs should not be overlooked.
Effects of Soil Tillage, Management Practices, and Mulching Film Application on Soil Health and Peanut Yield in a Continuous Cropping System
Authors: Yang Dongqing , Liu Yan , Wang Ying , Gao Fang , Zhao Jihao , Li Ying , Li Xiangdong
Published: December 2020

Our objective was to optimize soil management practices to improve soil health to increase peanut (Arachis hypogaea L.) yield. We studied the effects of using rotary tillage with mulching film or without [rotary tillage with no mulching (RTNM)], plow tillage with mulching film or without, and green manure with mulching film (GMMF) or without [green manure with no mulching (GMNM)] over 3 years in Tai’an, China. Results showed that compared with RTNM treatment, GMNM and GMMF treatments significantly (P < 0.05) increased soil organic carbon, enzymatic activity, and the available nitrogen, phosphorus, and potassium content. The dominant bacterial phyla in the soil across all treatments were Proteobacteria, Acidobacteria, and Actinobacteria. Bacterial richness and diversity in the soil were significantly (P < 0.05) enhanced after GMMF and GMNM treatments compared with those after RTNM treatment. The linear discriminant analysis effect size analysis indicated that Chloroflexi abundance in the 0–10 and 10–20 cm soil layers changed significantly (P < 0.05) after rotary tillage with mulching film and RTNM treatments, respectively, whereas that of Bacteroidetes changed significantly (P < 0.05) in the 0–10 layer after GMNM treatment. The abundance of the Xanthobacteraceae family of Proteobacteria in both soil layers changed significantly (P < 0.05) after GMNM and GMMF treatments. Redundancy analysis revealed that soil physical (soil bulk density and water content), chemical (soil organic carbon, available nitrogen, phosphorus, and potassium), and biological (soil enzymatic activity and nutrient content) characteristics affect the soil bacterial community. Changed soil quality indices may be favorable for leaf photo-assimilate accumulation. Compared with RTNM treatment, GMNM and GMMF treatments significantly increased photosynthesis rate in the peanut leaf and decreased intercellular carbon dioxide concentration. Our results showed that compared with that after RTNM treatment, the average pod yield after GMMF and GMNM treatments increased by 27.85 and 21.26%, respectively, due to increases in the pods per plant and plant numbers. The highest yield of all treatments was obtained from the GMMF-treated plot, followed by that from the GMNM-treated plots. Thus, taking into consideration the residual pollution caused by plastic films, we propose GMNM as a suitable strategy to improve soil physicochemical and microbial properties and to increase the peanut pod yield.