bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissecting a Zombie: Joint Analysis of Density and Resistivity Models Reveals Shallow Structure and Possible Sulfide Deposition at Uturuncu Volcano, Bolivia
Authors: MacQueen Patricia , Gottsmann Joachim , Pritchard Matthew E. , Young Nicola , Ticona J Faustino , Ticona Eusebio (Tico) , Tintaya Ruben
Published: September 2021

The recent identification of unrest at multiple volcanoes that have not erupted in over 10 kyr presents an intriguing scientific problem. How can we distinguish between unrest signaling impending eruption after kyr of repose and non-magmatic unrest at a waning volcanic system? After ca. 250 kyr without a known eruption, in recent decades Uturuncu volcano in Bolivia has exhibited multiple signs of unrest, making the classification of this system as “active”, “dormant”, or “extinct” a complex question. Previous work identified anomalous low resistivity zones at <10 km depth with ambiguous interpretations. We investigate subsurface structure at Uturuncu with new gravity data and analysis, and compare these data with existing geophysical data sets. We collected new gravity data on the edifice in November 2018 with 1.5 km spacing, ±15 μGal precision, and ±5 cm positioning precision, improving the resolution of existing gravity data at Uturuncu. This high quality data set permitted both gradient analysis and full 3-D geophysical inversion, revealing a 5 km diameter, positive density anomaly beneath the summit of Uturuncu (1.5–3.5 km depth) and a 20 km diameter arc-shaped negative density anomaly around the volcano (0.5–7.5 depth). These structures often align with resistivity anomalies previously detected beneath Uturuncu, although the relationship is complex, with the two models highlighting different components of a common structure. Based on a joint analysis of the density and resistivity models, we interpret the positive density anomaly as a zone of sulfide deposition with connected brines, and the negative density arc as a surrounding zone of hydrothermal alteration. Based on this analysis we suggest that the unrest at Uturuncu is unlikely to be pre-eruptive. This study shows the value of joint analysis of multiple types of geophysical data in evaluating volcanic subsurface structure at a waning volcanic center.
Late Permian High-Ti Basalt in Western Guangxi, SW China and Its Link With the Emeishan Large Igneous Province: Geochronological and Geochemical Perspectives
Authors: Zhang Chenguang , Zeng Renyu , Li Changming , Jiang Jian , Wang Tianguo , Shi Xingjun
Published: September 2021

High-Ti (Ti/Y) flood basalts are widely distributed in the Late Permian Emeishan large igneous province (LIP), SW China, and their spatial distribution and genetic mechanism are important to reveal the role of plume-lithosphere interactions in the LIP origin. Western Guangxi is located on the eastern edge of Emeishan LIP. To explore the genesis of the high-Ti basalt in western Guangxi and any genetic link with the Emeishan LIP, we performed whole-rock geochemical and Sr-Nd isotope and zircon U-Pb-Hf isotope analyses on the Longlin basalts from western Guangxi. The results indicate that the Longlin basalt from Tongdeng area has relatively high SiO2 but low MgO and TFe2O3 contents. The rocks have zircon εHf(t) = −0.42 to 6.41, whole-rock (87Sr/86Sr)i = 0.707167–0.707345, and εNd(t) = −2.5 to −2.14. In contrast, the Longlin basalt from Zhoudong area has relatively low SiO2 but high MgO and TFe2O3 contents. The rocks have whole-rock (87Sr/86Sr)i = 0.706181–0.706191 and εNd(t) = −0.57 to 0.69. Four Longlin basalt samples display LREE enrichments and HREE depletions, and with indistinct δEu and δCe anomalies. LA-ICP-MS zircon U-Pb dating on three Longlin basalt samples (from different localities) yielded consistent weighted average age of 257.9 ± 2.6 Ma (MSWD = 0.55), 259.5 ± 0.75 Ma (MSWD = 3.0), and 256.7 ± 2.0 Ma (MSWD = 0.68), indicating a Late Permian emplacement. Considering the similar age and geochemical features between the Longlin basalt and Emeishan flood basalts, we interpret that the former is spatially, and temporally associated with the Emeishan LIP. Geochemical features show that the high-Ti basalts in western Guangxi resemble Deccan-type continental flood basalts (CFBs), which were derived by decompression melting of the mantle plume. Combined with previous geochemical studies, we suggest that the difference in Ti content and Ti/Y ratio in CFBs are related to the depth and melting degree of mantle source, in which high-Ti features may have been linked to low degree of partial melting in the deep mantle.
Detailed Processes and Potential Mechanisms of Pliocene Salty Lake Evolution in the Western Qaidam Basin
Authors: Su Qingda , Riegel Hannah , Gong Lisha , Heermance Richard , Nie Junsheng
Published: September 2021

Hyperarid climate and salty lakes prevail in the current Qaidam Basin, but this basin was once a large paleolake until the early Quaternary. However, its evolution history and relationship with climate and tectonics are still elusive. Here we present detailed stratigraphic descriptions combined with total organic carbon content and weight ratio of organic carbon to total nitrogen records from fluvio-lacustrine sediments in the western Qaidam Basin to infer how the lake evolved during the late Pliocene-early Pleistocene. These data reveal a drying trend since 3.3 Ma, which we attribute to low latitude forcing and/or local tectonic activities. However, this trend was interrupted during 2.84–2.48 Ma, in which climate wetting was observed. We attribute the climate wetting during 2.84–2.48 Ma to intensified East Asian summer monsoon as is documented by the Chinese Loess Plateau records. Halite and gypsum content increased dramatically after 2.5 Ma, indicating the formation of salty lake in the western Qaidam Basin. These data improve our understanding of the detailed processes of Qaidam aridification and its potential forcing mechanisms.
Activating Social Capital: How Peer and Socio-Emotional Mentoring Facilitate Resilience and Success for Community College Students
Authors: Beals Rebecca , Zimny Sean , Lyons Faith , Bobbitt Olivia
Published: September 2021

This article details the impact of the intensive mentoring model, through faculty-to-student and peer-to-peer mentoring, utilized in WAESO-LSAMP community colleges. We pay particular attention to the practice of socio-emotional mentoring, the development of a “mentoring chain,” and the impact of communities of support on student and faculty participants. Specifically, we discuss how these separate modes of mentoring impact students from underrepresented students in developing and activating social capital, developing collaborative support systems, fostering confidence and self-efficacy, combatting impostor syndrome and stereotype threat, and embracing the importance of failure in the scientific process. Methods and data include qualitative analysis of forty-six in-depth interviews with program participants, including faculty mentors and community college students, at three community college sites within the WAESO-LSAMP alliance. We address specific implications for faculty working with underrepresented STEM community college students and provide evidence of best practices for setting up a community of support that leads to academic and personal success.
The Effect of Low and Moderate Exercise on Hyperuricemia: Protocol for a Randomized Controlled Study
Authors: Hou Yuning , Ma Renyan , Gao Song , Kaudimba Keneilwe Kenny , Yan Hongmei , Liu Tiemin , Wang Ru
Published: September 2021

Background

Hyperuricemia (HUA) is a metabolic disease by purine metabolism disorders. It is a risk factor for many chronic diseases, including diabetes, hypertension, and heart disease. Studies have shown that exercise can effectively reduce serum uric acid (SUA), but the optimal exercise dose, intensity, and mode of exercise for improving HUA have not been verified in clinical studies. Therefore, this study aims to explore the effect of different exercise intensities in improving SUA of patients with HUA.

Methods and Analysis

A randomized, single-blind, parallel controlled trial will be conducted in this study. 186 HUA patients who meet the inclusion criteria will be randomly divided into a 1:1:1 ratio (1): control group (2), low-intensity exercise group (brisk walking, 57-63% maximum heart rate, 150 min/week, 12 months), and (3) moderate-intensity exercise group (jogging, 64-76% maximum heart rate, 150 min/week, 12 months). The three groups of subjects will receive the same health education and prohibition of high-purine diet during the intervention period. The primary outcomes will be SUA concentration, SUA concentration change (mg/dL), SUA change rate (%), and the proportion of HUA patients. Secondary outcomes will include anthropometric parameters (body weight, waist circumference, hip circumference, BMI); physiological indicators (blood pressure, grip, vital capacity, maximum oxygen); biochemical indicators (blood lipid, blood sugar, liver enzyme, creatinine, and blood urea nitrogen). Each group of patients will go through an assessment at baseline, 3rd, 6th, and 12th months.

Discussion

This study will evaluate the effect of 12-month low-intensity exercise and moderate-intensity exercise on HUA patients. We hypothesize that both low-intensity and moderate-intensity exercise would improve HUA as compared with no-exercise control, and that moderate-intensity exercise would be more effective than low-intensity exercise in improving HUA. These results can provide a basis for the current physical activity guidelines for HUA’s healthy lifestyle management.

Ethics and Dissemination

This study has been approved by the Ethical Review Committee of the Shanghai University of Sport (approval number: 102772020RT005). Informed consent will be obtained from all participants or their guardians. The authors intend to submit the study findings to peer-reviewed journals or academic conferences to be published.

Clinical Trial Registration

Chinese Clinical Trial Registry, identifier ChiCTR2100042643.
Causal Effect of Visceral Adipose Tissue Accumulation on the Human Longevity: A Mendelian Randomization Study
Authors: Yan Bin , Yang Jian , Zhao Binbin , Wu Yanhua , Bai Ling , Ma Xiancang
Published: September 2021

Objective

Observational studies have demonstrated a close relationship between obesity and longevity. The aim of this Mendelian randomization (MR) study is to investigate whether genetic determinants of visceral adipose tissue (VAT) accumulation are causally associated with longevity.

Methods

In this two-sample MR study, we used summary data of genetic determinants (single-nucleotide polymorphisms; p < 5 × 10−8) of VAT accumulation based on genome-wide association studies (GWASs). Longevity was defined as an age beyond the 90th or 99th survival percentile. The causal association of VAT accumulation with longevity was estimated with the inverse variance-weighted (IVW) method. Sensitivity analyses, including weighted median, MR-Egger, and MR–pleiotropy residual sum and outlier (PRESSO), were also employed to assess the stability of the IVW results.

Results

Our MR analysis used 221 genetic variants as instrumental variables to explore the causal association between VAT accumulation and longevity. In the standard IVW methods, VAT accumulation (per 1-kg increase) was found to be significantly associated with lower odds of surviving to the 90th (odds ratio [OR] = 0.69; 95% confidence interval [CI] 0.55 to 0.86, p = 8.32 × 10−4) and 99th (OR = 0.67; 95% CI 0.49 to 0.91, p = 0.011) percentile ages. These findings remained stable in sensitivity analysis.

Conclusion

This MR analysis identified a causal relationship between genetically determined VAT accumulation and longevity, suggesting that visceral adiposity may have a negative effect on longevity.
The Effect of Local Renin Angiotensin System in the Common Types of Cancer
Authors: Almutlaq Moudhi , Alamro Abir Abdullah , Alamri Hassan S. , Alghamdi Amani Ahmed , Barhoumi Tlili
Published: September 2021

The Renin Angiotensin System (RAS) is a hormonal system that is responsible for blood pressure hemostasis and electrolyte balance. It is implicated in cancer hallmarks because it is expressed locally in almost all of the body’s tissues. In this review, current knowledge on the effect of local RAS in the common types of cancer such as breast, lung, liver, prostate and skin cancer is summarised. The mechanisms by which RAS components could increase or decrease cancer activity are also discussed. In addition to the former, this review explores how the administration of AT1R blockers and ACE inhibitors drugs intervene with cancer therapy and contribute to the outcomes of cancer.
Integrated Energy System Planning Based on Life Cycle and Emergy Theory
Authors: Wang Jun , Du Wei , Yang Dongmei
Published: September 2021

Integrated energy system (IES) is of great significance in the construction of the modern energy system. Reasonable planning is one of the important means to improve the economy of the IES and promote the consumption of renewable energy. However, the complex coupling characteristics between energy sources make it difficult to quantify the production efficiency of multi-energy heterogeneous resources uniformly in the economic benefit model during the planning cycle. Quantifying the production efficiency of the IES for planning is currently an urgent problem to be solved. This study proposes a planning method for the IES based on the life cycle and emergy theory. First, emergy theory is applied to quantify the production efficiency of the IES. A complete economic benefit model is established based on life cycle theory. Second, a bi-level planning model of the IES is established. The upper-level model aims at minimizing the whole life cycle cost of the IES to plan the capacity and location of the coupling equipment. The lower-level model aims at maximizing the emergy yield ratio of the IES to provide the operating data for the upper level. Finally, comparing experimental evaluations with traditional planning schemes considering annual average cost and energy quality coefficient, the method in this study reduces planning costs by 23.16% and increases the consumption rate of renewable energy by 4.26%. It can be seen that the planning method proposed in this study improves the planning economy and the level of renewable energy consumption of the IES.
Assessment of Conventional Full-Scale Treatment for the Removal of Endocrine Disruptors and Pharmaceuticals Present in the Tibagi River (Paraná State, Brazil)
Authors: Fazolo Ajadir , Batista Lígia Flávia Antunes , Nonaka Fernanda Martins , Sanson Ananda Lima , Alves Mariana Corrêa Pessato , Afonso Robson José de Cássia Franco , Aquino Sérgio Francisco de
Published: September 2021

The concentrations of 25 pharmaceuticals and endocrine disruptors were monitored in the water coming from the Tibagi River (State of Paraná, Brazil) and in a conventional water treatment plant over 13 sampling campaigns. In raw water, only 3 compounds (bisphenol A, dexamethasone and losartan) were detected with high frequency (>75%) and 4 drugs (estradiol, diclofenac, loratadine and naproxen) were found with moderate frequency (between 30 and 70%). In addition, 7 micropollutants (paracetamol, ethinylestradiol, caffeine, propanolol, diltiazem, benzafibrate and promethazine) were not detected in any of the samples analyzed and 11 other compounds were quantified at low frequency (up to 25%). The conventional treatment process employed at WTP- Jataizinho has proven to be very efficient in removing dexamethasone (∼99%), moderately efficient in reducing bisphenol A (∼47%) concentration and inefficient in removing losartan (∼22%) and loratadine (not removed). The greatest removals were observed during the water clarification stage using aluminum sulfate as coagulant. In general, the dry and rainy seasons did not influence the concentrations of pharmaceuticals and endocrine disruptors in raw water. In terms of the 5 most prevalent micropollutants in treated water (bisphenol A, losartan, dexamethasone, loratadine and naproxen), the human health risk associated with ingesting contaminated water was assessed and considered negligible.
Textile Industry Wastewaters From Jetpur, Gujarat, India, Are Dominated by Shewanellaceae, Bacteroidaceae, and Pseudomonadaceae Harboring Genes Encoding Catalytic Enzymes for Textile Dye Degradation
Authors: Kumar Dinesh , Patel Zarna , Pandit Priti , Pandit Ramesh , Patel Amrutlal , Joshi Madhvi , Joshi Chaitanya
Published: September 2021

Textile industries play an important role in uplifting the national economies worldwide. Nevertheless, they generate a huge amount of intensive colored effluent, which is a serious threat to the environment. The microbial communities present in these highly polluted environmental sites help in remediating pollutants naturally. However, little is known about their genes and enzymes in the textile wastewater systems. In this study, we explored the microbial community structure and their functional capability in three different wastewater systems, i.e., industry sites, effluent treatment plant (ETP), and common effluent treatment plant (CETP). Our findings based on shotgun metagenomics highlight the varied bacterial diversity at the three industry sites. Overall, the major dominant phyla in the industry site and CETP samples were Proteobacteria and Bacteroidetes, while in the ETP site, Firmicutes, Cyanobacteria, and Proteobacteria were predominant. The final discharge sample site was having a higher proportion of the Proteobacteria and Bacteroidetes. Aeromonas caviae, Desulfovibrio desulfuricans, Klebsiella pneumoniae, Pseudomonas stutzeri, Shewanella decolorationis, Shewanella oneidensis, Shewanella putrefaciens, and Vibrio cholera were the abundant species across the three sites. Furthermore, this research study identified the key microbial genes encoding enzymes having a known role in textile dye and aromatic compound degradation. Functional annotation of the shotgun metagenome samples indicates the presence of reductase, azoreductase, nitrate/nitrite reductase, and oxidoreductase enzyme encoding genes. Our findings provide the shotgun metagenomics-based approach for mining the textile dye degrading genes and genomic insights into the bioremediation of textile industrial effluent.
Increasing Establishment of Non-native Fish Species in the Seine River Basin: Insights From Medium- and Long-Term Approaches
Authors: Belliard Jérôme , Beslagic Sarah , Boucault Julien , Zahm Amandine
Published: September 2021

The spread of non-native species is nowadays recognized as a major threat to the biodiversity of freshwater ecosystems. However, for a very long time the introduction and acclimatization of new species has been perceived mainly as a source of wealth for human societies. Here, we examined the establishment of non-native fish species in the Seine River basin from a historical perspective by adopting a twofold approach. In a first step, at the whole basin scale, considering various written and archeological sources, we traced the chronology, over the last millennium, of the establishments of non-native species. In a second step, by analyzing fish monitoring from several hundred sites covering the diversity of rivers and streams, we examined the changes in numbers and abundance of non-native species in local fish communities over the last three decades. The first documented species introduction dates back to the 13th century but it is from the middle of the 19th century that the introduction attempts accelerated. Today, these introductions have reached an unprecedented level and 46% of the species recorded in the basin are non-native. During the last three decades, non-native species have continued to increase within fish communities both in terms of number of species and abundance of individuals. The most pronounced increases are noted on large rivers and sites where anthropic pressures are strong. Waterways connecting European basins, globalization of trade, and ongoing climate change provide a general background suggesting that the increase in the proportion of non-native species in the fish communities of the Seine River basin is likely to continue for several decades.
Soil Bacterial Community Responses to N Application and Warming in a Qinghai-Tibetan Plateau Alpine Steppe
Authors: Mu Zhiyuan , Dong Shikui , Li Yaoming , Li Shuai , Shen Hao , Zhang Jing , Han Yuhui , Xu Yudan , Zhao Zhenzhen
Published: September 2021

Nitrogen deposition and climate warming can alter soil bacterial communities. However, the response of soil bacteria in an alpine steppe to these changes is largely unknown. In this study, a field experiment was performed on the northeastern Qinghai-Tibetan Plateau to determine the changes in soil bacterial communities of alpine steppes in response to nitrogen application and warming. The experiment consisted of four treatments, namely no-N application with no-warming (CK), N application (8 kg N ha−1 year−1) with no-warming (N), warming with no-N application (W), and N application (8 kg N ha−1 year−1) with warming (W&N). This study aimed to investigate (1) the changes in soil bacterial diversity and community structure under simulated nitrogen deposition and warming conditions, and (2) the key environmental factors responsible for these changes. Based on the results, soil bacterial diversity and community composition did not change significantly in the short term. Warming had a significant effect on overall bacterial composition, rare species composition, and individual bacterial taxa. Besides, the interaction between nitrogen application and warming had a significant effect on community β-diversity. Above-ground plant variables were highly correlated with bacterial community characteristics. Nitrogen application and warming did not significantly alter the distribution range of the bacterial community. Overall, this study suggests that soil bacterial communities can remain relatively stable at the level of simulated nitrogen application and warming and that short-term climatic changes may have no significant impacts on soil bacterial communities.
The Promise of Lung Organoids for Growth and Investigation of Pneumocystis Species
Authors: Tisdale-Macioce Nikeya , Green Jenna , Perl Anne-Karina T. , Ashbaugh Alan , Wiederhold Nathan P. , Patterson Thomas F. , Cushion Melanie T.
Published: September 2021

Pneumocystis species (spp.) are host-obligate fungal parasites that colonize and propagate almost exclusively in the alveolar lumen within the lungs of mammals where they can cause a lethal pneumonia. The emergence of this pneumonia in non-HIV infected persons caused by Pneumocystis jirovecii (PjP), illustrates the continued importance of and the need to understand its associated pathologies and to develop new therapies and preventative strategies. In the proposed life cycle, Pneumocystis spp. attach to alveolar type 1 epithelial cells (AEC1) and prevent gas exchange. This process among other mechanisms of Pneumocystis spp. pathogenesis is challenging to observe in real time due to the absence of a continuous ex vivo or in vitro culture system. The study presented here provides a proof-of-concept for the development of murine lung organoids that mimic the lung alveolar sacs expressing alveolar epithelial type 1 cells (AEC1) and alveolar type 2 epithelial cells (AEC2). Use of these 3-dimensional organoids should facilitate studies of a multitude of unanswered questions and serve as an improved means to screen new anti- PjP agents.
Profiling of 3D Genome Organization in Nasopharyngeal Cancer Needle Biopsy Patient Samples by a Modified Hi-C Approach
Authors: Animesh Sambhavi , Choudhary Ruchi , Wong Bertrand Jern Han , Koh Charlotte Tze Jia , Ng Xin Yi , Tay Joshua Kai Xun , Chong Wan-Qin , Jian Han , Chen Leilei , Goh Boon Cher , Fullwood Melissa Jane
Published: September 2021

Nasopharyngeal cancer (NPC), a cancer derived from epithelial cells in the nasopharynx, is a cancer common in China, Southeast Asia, and Africa. The three-dimensional (3D) genome organization of nasopharyngeal cancer is poorly understood. A major challenge in understanding the 3D genome organization of cancer samples is the lack of a method for the characterization of chromatin interactions in solid cancer needle biopsy samples. Here, we developed Biop-C, a modified in situ Hi-C method using solid cancer needle biopsy samples. We applied Biop-C to characterize three nasopharyngeal cancer solid cancer needle biopsy patient samples. We identified topologically associated domains (TADs), chromatin interaction loops, and frequently interacting regions (FIREs) at key oncogenes in nasopharyngeal cancer from the Biop-C heatmaps. We observed that the genomic features are shared at some important oncogenes, but the patients also display extensive heterogeneity at certain genomic loci. On analyzing the super enhancer landscape in nasopharyngeal cancer cell lines, we found that the super enhancers are associated with FIREs and can be linked to distal genes via chromatin loops in NPC. Taken together, our results demonstrate the utility of our Biop-C method in investigating 3D genome organization in solid cancers.
Molecular Characterization and Expression Analysis of the Na+/H+ Exchanger Gene Family in Capsicum annuum L.
Authors: Luo Xirong , Yang Shimei , Luo Yong , Qiu Huarong , Li Tangyan , Li Jing , Chen Xiaocui , Zheng Xue , Chen Yongdui , Zhang Jie , Zhang Zhongkai , Qin Cheng
Published: September 2021

The Na+/H+ exchangers (NHXs) are a class of transporters involved in ion balance during plant growth and abiotic stress. We performed systematic bioinformatic identification and expression-characteristic analysis of CaNHX genes in pepper to provide a theoretical basis for pepper breeding and practical production. At the whole-genome level, the members of the CaNHX gene family of cultivated and wild pepper were systematically identified using bioinformatics methods. Sequence alignment and phylogenetic tree construction were performed using MEGA X software, and the gene functional domain, conserved motif, and gene structure were analyzed and visualized. At the same time, the co-expression network of CaNHX genes was analyzed, and salt-stress analysis and fluorescence quantitative verification of the Zunla-1 cultivar under stress conditions were performed. A total of 9 CaNHX genes were identified, which have typical functional domains of the Na+/H+ exchanger gene. The physical and chemical properties of the protein showed that the protein was hydrophilic, with a size of 503–1146 amino acids. Analysis of the gene structure showed that Chr08 was the most localized chromosome, with 8–24 exons. Cis-acting element analysis showed that it mainly contains cis-acting elements such as light response, salicylic acid response, defense, and stress response. Transcriptom and co-expression network analysis showed that under stress, the co-expressed genes of CaNHX genes in roots and leaves were more obvious than those in the control group, including ABA, IAA, and salt. The transcriptome and co-expression were verified by qRT-PCR. In this study, the CaNHX genes were identified at the genome level of pepper, which provides a theoretical foundation for improving the stress resistance, production, development, and utilization of pepper in genetic breeding.
Suppression of ANT2 by miR-137 Inhibits Prostate Tumorigenesis
Authors: Zhang Heyuan , Chen Nanhui , Deng Zhihai , Mai Yang , Deng Limin , Chen Guo , Li Yutong , Pan Bin , Zhong Weifeng
Published: September 2021

Prostate cancer (PCa) is a serious disease that affects men’s health. To date, no effective and long-lasting treatment option for this condition is available in clinical practice. ANT2 is highly expressed in a variety of hormone-related cancers, but its relationship and regulatory mechanism with PCa are unclear. In this study, we found that ANT2 expression was significantly upregulated in PCa tissues relative to control samples. Genetic knockdown of ANT2 effectively inhibited, while overexpression promoted, proliferation, migration, and invasion of PCa cells. In addition, miR-137 expression was reduced in prostate cancer tissues relative to control tissues. We identified a regulatory site for miR-137 in the 3′-UTR of ANT2 mRNA; luciferase reporter assays indicated that ANT2 is a direct target gene for miR-137. Transfecting cells with miR-137 mimics and/or an ANT2-encoding plasmid revealed that ANT2 promotes proliferation, migration, and invasion of PCa, whereas co-expression of miR-137 mimics inhibited these behaviors. These observations suggest that miR-137 mimics inhibit development of PCa by antagonizing expression of ANT2. Furthermore, tumorigenic assays in nude mice showed that miR-137 inhibitors abolished the inhibitory effect of ANT2 knockdown on PCa tumor growth. Collectively, our findings suggest that ANT2, a target gene of miR-137, is intimately involved in development of PCa, providing new evidence for the mechanism underlying pathogenesis of PCa as well as new options for targeted therapy.
Breeding Strategies for Weather Resilience in Small Ruminants in Atlantic and Mediterranean Climates
Authors: Ramón Manuel , Carabaño María Jesús , Díaz Clara , Kapsona Vanessa Varvara , Banos Georgios , Sánchez-Molano Enrique
Published: September 2021

Many efforts are being made to cope with negative consequences of climate change (CC) on livestock. Among them, selective breeding of resilient animals to CC is presented as an opportunity to maintain high levels of performance regardless of variation in weather. In the present work, we proposed a set of breeding strategies to improve weather resilience in dairy goats raised in north-western European Atlantic conditions and dairy sheep raised in Mediterranean conditions while improving production efficiency at the same time. Breeding strategies differed in the selection emphasis placed on resilience traits, ranging from 0 to 40% in the index. Simulations were carried out mimicking real breeding programs including: milk yield, length of productive life, age at first kidding and mastitis incidence in dairy goats and milk, fat and protein yields, and fertility for dairy sheep. Considering the particular climatic conditions in the two regions, the predicted future climate scenarios, and genetic correlations among breeding objectives, resilience was defined as stability to weather changes for dairy goats and as the ability to improve performance under heat stress for dairy sheep. A strategy giving a selection weight of 10 and 20% for goat and sheep resilience, respectively, resulted in the best overall genetic response in terms of both, production and resilience ability. Not considering resilience in breeding programs could lead to a major production loss in future climate scenarios, whereas putting too much emphasis on resilience would result in a limited progress in milk production.
The Role of the European Society of Human Genetics in Delivering Genomic Education
Authors: Tobias Edward S. , Avram Elena , Calapod Patricia , Cordier Christophe , den Dunnen Johan T. , Ding Can , Dolzan Vita , Houge Sofia Douzgou , Lynch Sally Ann , O’Byrne James , Patsalis Philippos , Prokopenko Inga , Soares Celia A. , Tobias Adam P. , Newman William G.
Published: September 2021

The European Society of Human Genetics (ESHG) was founded in 1967 as a professional organisation for members working in genetics in clinical practice, research and education. The Society seeks the integration of scientific research and its implementation into clinical practice and the education of specialists and the public in all areas of medical and human genetics. The Society works to do this through many approaches, including educational sessions at the annual conference; training courses in general and specialist areas of genetics; an online resource of educational materials (EuroGEMS); and a mentorship scheme. The ESHG Education Committee is implementing new approaches to expand the reach of its educational activities and portfolio. With changes in technology, appreciation of the utility of genomics in healthcare and the public’s and patients’ increased awareness of the role of genomics, this review will summarise how the ESHG is adapting to deliver innovative educational activity.
Autosomal Recessive Cutis Laxa 1C Mutations Disrupt the Structure and Interactions of Latent TGFβ Binding Protein-4
Authors: Alanazi Yasmene F. , Lockhart-Cairns Michael P. , Cain Stuart A. , Jowitt Thomas A. , Weiss Anthony S. , Baldock Clair
Published: September 2021

Latent TGFβ binding protein-4 (LTBP4) is a multi-domain glycoprotein, essential for regulating the extracellular bioavailability of TGFβ and assembly of elastic fibre proteins, fibrillin-1 and tropoelastin. LTBP4 mutations are linked to autosomal recessive cutis laxa type 1C (ARCL1C), a rare congenital disease characterised by high mortality and severely disrupted connective tissues. Despite the importance of LTBP4, the structure and molecular consequences of disease mutations are unknown. Therefore, we analysed the structural and functional consequences of three ARCL1C causing point mutations which effect highly conserved cysteine residues. Our structural and biophysical data show that the LTBP4 N- and C-terminal regions are monomeric in solution and adopt extended conformations with the mutations resulting in subtle changes to their conformation. Similar to LTBP1, the N-terminal region is relatively inflexible, whereas the C-terminal region is flexible. Interaction studies show that one C-terminal mutation slightly decreases binding to fibrillin-1. We also found that the LTBP4 C-terminal region directly interacts with tropoelastin which is perturbed by both C-terminal ARCL1C mutations, whereas an N-terminal mutation increased binding to fibulin-4 but did not affect the interaction with heparan sulphate. Our results suggest that LTBP4 mutations contribute to ARCL1C by disrupting the structure and interactions of LTBP4 which are essential for elastogenesis in a range of mammalian connective tissues.
A Nomogram Integrating Ferroptosis- and Immune-Related Biomarkers for Prediction of Overall Survival in Lung Adenocarcinoma
Authors: Chai Mengyu , Li Xiuchun , Zhang Yaxin , Tang Yemeng , Shu Pingping , Lin Jing , Shi Keqing , Wang Liangxing , Huang Xiaoying
Published: September 2021

Ferroptosis plays a dual role in cancer, which is known to be affected to antitumor immune responses. However, the association between ferroptosis and antitumor immune responses is uncertain in lung adenocarcinoma (LUAD). In this work, 38 ferroptosis-related genes (FRGs) and 429 immune-related genes (IRGs) were identified as being differentially expressed between tumor and normal samples. Two risk score formulas consisting of seven FRGs and four IRGs, respectively, were developed by Lasso-penalized Cox regression and verified in the GSE13213 dataset. The CIBERSORT algorithm was used to estimate the relative abundance of immune cells in tumors. The correlation between FRGs and immune cells was evaluated using the TIMER database. The results indicated that the development of ferroptosis was synergistic with that of anti-tumor immunity in LUAD. The concordance index and calibration curves showed that the performance of a nomogram that combines clinical staging and risk scores is superior to that of models using a single prognostic factor. In conclusion, ferroptosis might be synergistic with anti-tumor immunity in LUAD. The combined nomogram could reliably predict the probability of overall survival of LUAD patients. These findings may be useful for future investigation of prognostic value and therapeutic potential related to ferroptosis and tumor immunity in LUAD.
Congenital Disorders of Deficiency in Glycosaminoglycan Biosynthesis
Authors: Mizumoto Shuji , Yamada Shuhei
Published: September 2021

Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, and heparan sulfate are covalently attached to specific core proteins to form proteoglycans, which are distributed at the cell surface as well as in the extracellular matrix. Proteoglycans and GAGs have been demonstrated to exhibit a variety of physiological functions such as construction of the extracellular matrix, tissue development, and cell signaling through interactions with extracellular matrix components, morphogens, cytokines, and growth factors. Not only connective tissue disorders including skeletal dysplasia, chondrodysplasia, multiple exostoses, and Ehlers-Danlos syndrome, but also heart and kidney defects, immune deficiencies, and neurological abnormalities have been shown to be caused by defects in GAGs as well as core proteins of proteoglycans. These findings indicate that GAGs and proteoglycans are essential for human development in major organs. The glycobiological aspects of congenital disorders caused by defects in GAG-biosynthetic enzymes including specific glysocyltransferases, epimerases, and sulfotransferases, in addition to core proteins of proteoglycans will be comprehensively discussed based on the literature to date.
Physical and Functional Interaction of Mitochondrial Single-Stranded DNA-Binding Protein and the Catalytic Subunit of DNA Polymerase Gamma
Authors: Ciesielski Grzegorz L. , Kim Shalom , de Bovi Pontes Carolina , Kaguni Laurie S.
Published: September 2021

The maintenance of the mitochondrial genome depends on a suite of nucleus-encoded proteins, among which the catalytic subunit of the mitochondrial replicative DNA polymerase, Pol γα, plays a pivotal role. Mutations in the Pol γα-encoding gene, POLG, are a major cause of human mitochondrial disorders. Here we present a study of direct and functional interactions of Pol γα with the mitochondrial single-stranded DNA-binding protein (mtSSB). mtSSB coordinates the activity of the enzymes at the DNA replication fork. However, the mechanism of this functional relationship is elusive, and no direct interactions between the replicative factors have been identified to date. This contrasts strikingly with the extensive interactomes of SSB proteins identified in other homologous replication systems. Here we show for the first time that mtSSB binds Pol γα directly, in a DNA-independent manner. This interaction is strengthened in the absence of the loop 2.3 structure in mtSSB, and is abolished upon preincubation with Pol γβ. Together, our findings suggest that the interaction between mtSSB and polymerase gamma holoenzyme (Pol γ) involves a balance between attractive and repulsive affinities, which have distinct effects on DNA synthesis and exonucleolysis.
What Mediates Fibrosis in the Tumor Microenvironment of Clear Renal Cell Carcinoma
Authors: Yang Wenbo , Qin Caipeng , Han Jingli , Han Songchen , Bai Wenjun , Du Yiqing , Xu Tao
Published: September 2021

Previous studies have demonstrated that direct targeting of interstitial cancer-associated fibroblasts (CAF) and tumor fibrosis alone seemed to be an unpromising treatment option for malignant tumors. Therefore, it is necessary to further explore the mechanism of the influence of collagen and tumor fibrosis on the biological behavior of malignant tumors. The current study aimed to explore the effect of intratumor fibrosis on the prognosis of renal clear cell carcinoma (ccRCC) and its mechanism. With the bioinformatic analysis of The Cancer Genome Atlas (TCGA) database (n = 537), the study showed that high Collagen type I α 1 (COL1A1) mRNA expression indicated the poor prognosis of ccRCC patients compared with low expression ones. We further used the Two-photon-excited fluorescence (TPEF)/second harmonic generation (SHG) microscopy to determine the intratumor fibrosis of 68 patients with surgical resection of ccRCC and confirmed that a high fibrosis level in the tumor was associated with a poor prognosis compared with patients with low expression (Progression-Free Survival: p = 0.030). We further measured the protein chips of 640 cytokines in ccRCC specimens and found that several cytokines, including prolactin (PRL), were associated with the degree of fibrosis in the tumor, as confirmed by the prolactin receptor (PRLR) immunohistochemical method. In addition, the study showed that PRLR expression decreased significantly in the ccRCC compared with adjacent normal tissue (p < 0.05). Our research shows that low expression of PRLR predicted the poor survival of the patient. We used the Cell Counting Kit-8 experiment, the transwell and the plate clone formation assay to evaluate the role of PRL in the 7860 and the ACHN cell lines. We found that PRL promoted ccRCC cell proliferation and migration. JAK-STAT3 activation was found in the high prolactin expression group by mass spectrum analysis. This study delineated the fibrosis-based tumor microenvironment characteristics of ccRCC. PRL/PRLR may be involved in the fibrosis process and are essential prognostic risk factors for ccRCC.
Tissue Specific DNA Repair Outcomes Shape the Landscape of Genome Editing
Authors: Meyenberg Mathilde , Ferreira da Silva Joana , Loizou Joanna I.
Published: September 2021

The use of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 has moved from bench to bedside in less than 10years, realising the vision of correcting disease through genome editing. The accuracy and safety of this approach relies on the precise control of DNA damage and repair processes to achieve the desired editing outcomes. Strategies for modulating pathway choice for repairing CRISPR-mediated DNA double-strand breaks (DSBs) have advanced the genome editing field. However, the promise of correcting genetic diseases with CRISPR-Cas9 based therapies is restrained by a lack of insight into controlling desired editing outcomes in cells of different tissue origin. Here, we review recent developments and urge for a greater understanding of tissue specific DNA repair processes of CRISPR-induced DNA breaks. We propose that integrated mapping of tissue specific DNA repair processes will fundamentally empower the implementation of precise and safe genome editing therapies for a larger variety of diseases.
DNA Double-Strand Break Repair: All Roads Lead to HeterochROMAtin Marks
Authors: Caron Pierre , Pobega Enrico , Polo Sophie E.
Published: September 2021

In response to DNA double-strand breaks (DSBs), chromatin modifications orchestrate DNA repair pathways thus safeguarding genome integrity. Recent studies have uncovered a key role for heterochromatin marks and associated factors in shaping DSB repair within the nucleus. In this review, we present our current knowledge of the interplay between heterochromatin marks and DSB repair. We discuss the impact of heterochromatin features, either pre-existing in heterochromatin domains or de novo established in euchromatin, on DSB repair pathway choice. We emphasize how heterochromatin decompaction and mobility further support DSB repair, focusing on recent mechanistic insights into these processes. Finally, we speculate about potential molecular players involved in the maintenance or the erasure of heterochromatin marks following DSB repair, and their implications for restoring epigenome function and integrity.
Case Report: Identification of a Novel Pathogenic Germline TP53 Variant in a Family With Li–Fraumeni Syndrome
Authors: Paduano Francesco , Fabiani Fernanda , Colao Emma , Trapasso Francesco , Perrotti Nicola , Barbieri Vito , Baudi Francesco , Iuliano Rodolfo
Published: September 2021

Li–Fraumeni syndrome (LFS) is an inherited autosomal dominant disease characterized by a predisposition to many cancers. Germline pathogenic variants in TP53 are primarily responsible for LFS. By performing a targeted sequencing panel in a proband with liver carcinoma having a deceased son affected by osteosarcoma, we found the novel heterozygous frameshift variant c.645del (p.Ser215Argfs*32) in the TP53 gene. This variant co-segregated with typical LFS cancers in the family pedigree, consistent with the pathogenicity of this novel and previously undescribed TP53 variant.
Case Report: Second Report of Joubert Syndrome Caused by Biallelic Variants in IFT74
Authors: Zhongling Ke , Guoming Li , Yanhui Chen , Xiaoru Chen
Published: September 2021

Joubert syndrome (JBTS) is a rare ciliopathy characterized by developmental delay, hypotonia, and distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). We reported a 15-month-old female with dysmorphic features (flat nasal bridge, almond-shaped eye, and a minor midline notch in the upper lips), hypotonia, polydactyly, development delay, and MTS. Whole exome sequencing revealed biallelic heterozygous mutations c.535C>G(p.Q179E/c.853G>T) (p.E285*) in IFT74, which were inherited from the parents. So far, only one article reported JBTS associated with IFT74 gene mutation, and this is the second report of the fifth patient with JBTS due to variants in IFT74. All five patients had developmental delay, postaxial polydactyly, subtle cleft of the upper lip, hypotonia, and MTS, but notably without renal and retinal anomalies or significant obesity, and they shared the same mutation c.535C>G(p.Q179E) in IFT74, and c.853G>T(p.E285*) that we found was a new mutation in IFT74 that related with Joubert syndrome. Those findings highlight the need for the inclusion of IFT74 in gene panels for JBST testing.
Community Health Worker Evaluation of Implementing an mHealth Application to Support Maternal Health Care in Rural India
Authors: Charanthimath Umesh , Katageri Geetanjali , Kinshella Mai-Lei Woo , Mallapur Ashalata , Goudar Shivaprasad , Ramadurg Umesh , Vidler Marianne , Sharma Sumedha , Derman Richard , Magee Laura A. , Dadelszen Peter von , Bellad Mrutyunjaya , Payne Beth A.
Published: September 2021

Introduction: PIERS on the Move (POM) is a mobile health (mHealth) application developed for a smartphone to support community health workers (CHWs) for identification and management of women at risk of adverse outcomes from pre-eclampsia. POM was implemented as an addition to routine antenatal care by accredited social health activists (ASHAs) and auxiliary nurse midwives (ANMs) during the community level intervention for pre-eclampsia (CLIP) Trial in Karnataka state, India (NCT01911494). The objective of this study was to evaluate the experiences of CHWs of using POM in rural India and their perceptions of acceptability and feasibility of this mHealth intervention.

Methods: A posttrial mixed-methods evaluation was designed to measure CHW knowledge and self-efficacy regarding the care of women with pre-eclampsia and perceptions of CHWs on the ease of use and usefulness of POM. A structured survey with open-ended questions was conducted between October and November 2017. The median values on a 5-point Likert scale for knowledge and self-efficacy questions were compared between trial arms by Mann–Whitney U test (p < 0.05 significant). Qualitative analysis was undertaken on NVivo 12 (QSR International, Melbourne, Australia).

Results: A total of 48 ASHAs and ANMs were interviewed, including 24 who used POM (intervention arm) and 24 who did not (control arm). Self-reported knowledge and self-efficacy for the care of women with pre-eclampsia did not differ between groups. The qualitative analysis highlighted that health workers who used POM reported improved interactions with women and families in their communities. POM strengthened the role of ASHA as a CHW beyond a “link-worker” accompanying women to health services. With training, the mHealth application was easy to use even for CHWs who did not have much experience with smartphones.

Conclusions: Community health workers found the POM app easy to use, useful, and well-received by women and their families. POM did not improve care through increased knowledge but built capacity by increasing the recognition of the ASHA and ANM as critical members of the continuum of antenatal healthcare within their communities. These findings support the important role that mHealth technologies can play in strengthening health systems to reach rural, remote, and marginalized populations to reduce disparities in health.