bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Ecological Risk Assessment of Heavy Metals Based on Species Sensitivity Distribution in Aquatic of Coastal Areas in Hong Kong
Authors: Rong Shaowei , Wu Jin , Cao Xiaoyuan , Sun Yue
Published: October 2022

In recent decades, the ecological environment of some coastal areas in China has been seriously affected by terrestrial pollutants, and there is an urgent need for ecological risk assessment of China’s coastal environment. The assessment of heavy metal pollution in Hong Kong waters was carried out using different environmental and ecological indicators. The heavy metal contents (Cu, Pb, Zn, Cd, As, Cr, and Hg) in the near coast of Hong Kong were analyzed for two different seasons of the year 2018 (April—spring and September—autumn). We assessed the distribution and enrichment of heavy metals in the near coast of Hong Kong, and the potential biohazardous effects were assessed using the species sensitivity distribution method. The results showed that only Pb, Zn, and Hg in seawater exceeded the Class I standard. Pb, Zn, Cd, and As in organisms exceeded the standard, and no heavy metals exceeded the standard in sediments. The species sensitivity distribution method indicated that the biohazardous factor of heavy metals of the Hong Kong coast is higher in spring than in autumn, and the potential hazard ratio has the characteristics of high northwest and low southeast, which leads to its msPAF also having these characteristics. From the correlational analyses among heavy metals, we found that the pH change in seawater was related to the concentration of heavy metals, the concentration of heavy metals in seawater was proportional to the salinity of seawater, Pb and Cu were likely to have the same source, and Zn and Cd may not have the same emission sources as the other heavy metals. Overall, heavy metal contamination of seawater, sediments, and organisms near the Hong Kong coast was within acceptable limits, but the problem of heavy metal dispersion should be prevented.
Long-Term Influence of Locus of Control and Quality of Life on Metabolic Profile in Elderly Subjects with Type 2 Diabetes
Authors: Giandalia Annalisa , Ragonese Marta , Alessi Eugenio , Ruffo Maria C. , Sardella Alberto , Cuttone Alessandro , Aragona Maria A. , Versace Antonio G. , Basile Giorgio , Cucinotta Domenico , Squadrito Giovanni , Russo Giuseppina T.
Published: October 2022

Background: The Locus of Control (LOC) is a mental disposition indicating the individuals’ belief that disease-related outcomes are under their own control (Internal), dependent on others (External), or dependent on chance (Chance). Quality of Life (QoL) and LOC may have complex effects on self-care activities and diabetes management in subjects with type 2 diabetes (T2D). The aim of the present study was to evaluate the predictive role of LOC and QoL scores on metabolic control in elderly T2D outpatients, secondly evaluating potential gender differences. Methods: An extensive set of questionnaires was administered to a group of consecutive elderly T2D outpatients on oral glucose-lowering drugs attending a single diabetes center. Personal and clinical variables were analyzed at baseline (between 1 February and 31 March 2015) and after 6 years of follow-up. Results: At baseline, study participants showed an overall good metabolic control. Diabetes Specific Quality of Life (DSQoL) scores indicated an overall good QoL in both genders, with a higher DSQoL satisfaction score in women. Both genders presented higher scores in the LOC-Internal domain, with men reaching higher scores in the LOC-External domain than women. At the 6-years follow-up, subjects with baseline higher LOC-External score presented better metabolic outcome. In the regression analysis, LOC-External score was an independent predictor of good metabolic control maintenance, but this result was only statistically significant in men. Conclusions: LOC scores may influence long-term glycemic control in elderly T2D patients on oral glucose-lowering drugs.
Extraction of Urban Built-Up Areas Based on Data Fusion: A Case Study of Zhengzhou, China
Authors: Chen Yaping , Zhang Jun
Published: October 2022

Urban built-up areas are not only the spatial carriers of urban activities but also the direct embodiment of urban expansion. Therefore, it is of great practical significance to accurately extract urban built-up areas to judge the process of urbanization. Previous studies that only used single-source nighttime light (NTL) data to extract urban built-up areas can no longer meet the needs of rapid urbanization development. Therefore, in this study, spatial location big data were first fused with NTL data, which effectively improved the accuracy of urban built-up area extraction. Then, a wavelet transform was used to fuse the data, and multiresolution segmentation was used to extract the urban built-up areas of Zhengzhou. The study results showed that the precision and kappa coefficient of urban built-up area extraction by single-source NTL data were 85.95% and 0.7089, respectively, while the precision and kappa coefficient of urban built-up area extraction by the fused data are 96.15% and 0.8454, respectively. Therefore, after data fusion of the NTL data and spatial location big data, the fused data compensated for the deficiency of single-source NTL data in extracting urban built-up areas and significantly improved the extraction accuracy. The data fusion method proposed in this study could extract urban built-up areas more conveniently and accurately, which has important practical value for urbanization monitoring and subsequent urban planning and construction.
Blockade of Wnt Secretion Attenuates Myocardial Ischemia–Reperfusion Injury by Modulating the Inflammatory Response
Authors: Meyer Ingmar Sören , Li Xue , Meyer Carina , Voloshanenko Oksana , Pohl Susann , Boutros Michael , Katus Hugo Albert , Frey Norbert , Leuschner Florian
Published: October 2022

Wnt (a portmanteau of Wingless and Int-1) signaling in the adult heart is largely quiescent. However, there is accumulating evidence that it gets reactivated during the healing process after myocardial infarction (MI). We here tested the therapeutic potential of the Wnt secretion inhibitor LGK-974 on MI healing. Ischemia/reperfusion (I/R) injury was induced in mice and Wnt signaling was inhibited by oral administration of the porcupine inhibitor LGK-974. The transcriptome was analyzed from infarcted tissue by using RNA sequencing analysis. The inflammatory response after I/R was evaluated by flow cytometry. Heart function was assessed by echocardiography and fibrosis by Masson’s trichrome staining. Transcriptome and gene set enrichment analysis revealed a modulation of the inflammatory response upon administration of the Wnt secretion inhibitor LGK-974 following I/R. In addition, LGK-974-treated animals showed an attenuated inflammatory response and improved heart function. In an in vitro model of hypoxic cardiomyocyte and monocyte/macrophage interaction, LGK974 inhibited the activation of Wnt signaling in monocytes/macrophages and reduced their pro-inflammatory phenotype. We here show that Wnt signaling affects inflammatory processes after MI. The Wnt secretion inhibitor LGK-974 appears to be a promising compound for future immunomodulatory approaches to improve cardiac remodeling after MI.
Association between Circulating MicroRNAs (miR-21-5p, miR-20a-5p, miR-29b-3p, miR-126-3p and miR-101-3p) and Chronic Allograft Dysfunction in Renal Transplant Recipients
Authors: Chen Yu-Jen , Hsu Chia-Tien , Tsai Shang-Feng , Chen Cheng-Hsu
Published: October 2022

Chronic allograft dysfunction (CAD) is a major condition affecting long-term kidney graft survival. Serum microRNA (miRNA) has been reported as a biomarker for various conditions of allograft injuries. The upregulation of miR-21 is the best-known miRNA change in graft tissue, urine and plasma. However, the correlation of plasma miR-21 with the severity of CAD remains unclear. In our study, 40 kidney transplantation recipients with late graft survival for more than 10 years were enrolled. The CAD group (n = 20) had either an eGFR between 15 to 60 mL/min or a biopsy-proved chronic allograft nephropathy or rejection. The control group (n = 20) had an eGFR ≥ 60 mL/min without proteinuria and hematuria for a consecutive 3 months before the study. We performed RNA sequencing to profile the miRNAs expression. There were six differentially expressed miRNAs in the CAD group. Among them, miR-21-5p and miR-101-3p were decreased, and miR-20a-5p was increased. We found that miR-21-5p, miR-20a-5p and miR-101-3p all participated in the TGF-beta pathway. We demonstrated that decreased miR-21-5p and miR-101-3p, and increased miR-20a-5p were the novel CAD-associated miRNAs in the TGF-beta pathway. These findings may pave the way for developing early prediction miRNAs biomarkers for CAD, and possibly developing therapeutic tools in the field of kidney transplantation.
Ojeoksan Ameliorates Cisplatin-Induced Acute Kidney Injury in Mice by Downregulating MAPK and NF-κB Pathways
Authors: Kim Dong-Uk , Kweon Bitna , Oh Jin-Young , Seo Chang-Seob , Kim Dong-Gu , Kim Hye-Yoom , Lee Ho-Sub , Park Sung-Joo , Bae Gi-Sang
Published: October 2022

Acute kidney injury (AKI) is a major side effect of cisplatin, a crucial anticancer agent. Therefore, it is necessary to develop drugs to protect against cisplatin-induced nephrotoxicity. Ojeoksan (OJS), a traditional blended herbal prescription, is mostly used in Korea; however, there are no reports on the efficacy of OJS against cisplatin-induced AKI. To investigate the reno-protective effect of OJS on AKI, we orally administered 50, 100, and 200 mg/kg of OJS to mice 1 h before intraperitoneal injection with 20 mg/kg of cisplatin. OJS inhibited the increase of blood urea nitrogen (BUN) and serum creatinine (SCr) levels and reduced histological changes in the kidney, like loss of brush borders, renal tubular necrosis, and cast formation. Administration of OSJ reduced the levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. In addition, OJS inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways in cisplatin-induced AKI. These results suggest that OJS attenuates cisplatin-induced AKI by downregulating the MAPK and NF-κB pathways.
Microbial Precipitation of Pb(II) with Wild Strains of Paraclostridium bifermentans and Klebsiella pneumoniae Isolated from an Industrially Obtained Microbial Consortium
Authors: Neveling Olga , Ncube Thato M. C. , Ngxongo Ziyanda P. , Chirwa Evans M. N. , Brink Hendrik G.
Published: October 2022

The study focused on determining the microbial precipitation abilities of bacterial strains that were isolated from an industrially obtained Pb(II)-resistant microbial consortium. Previous research has demonstrated the effectiveness of the consortium on the bioprecipitation and adsorption of Pb(II) from solution. The bioremediation of Pb(II) using microbial precipitation provides an alternative option for Pb(II) removal from wastewater. Both strains, Klebsiella pneumoniae and Paraclostridium bifermentans, were successfully isolated from the consortium obtained from a battery recycling plant in South Africa. The experiments were conducted over both 30 h and 5 d, providing insight into the short- and long-term precipitation abilities of the bacteria. Various initial concentrations of Pb(II) were investigated, and it was found that P. bifermentans was able to remove 83.8% of Pb(II) from solution with an initial Pb(II) concentration of 80 mg L−1, while K. pneumoniae was able to remove 100% of Pb(II) with the same initial Pb(II) concentration after approximately 5 d. With the same initial Pb(II) concentration, P. bifermentans was able to remove 86.1% of Pb(II) from solution, and K. pneumoniae was able to remove 91.1% of Pb(II) from solution after 30 h. The identities of the precipitates obtained for each strain vary, with PbS and Pb0 being the main species precipitated by P. bifermentans and PbO with either PbCl or Pb3(PO4)2 precipitated by K. pneumoniae. Various factors were investigated in each experiment, such as metabolic activity, nitrate concentration, residual Pb(II) concentration, extracellular and intracellular Pb(II) concentration and the precipitate identity. These factors provide a greater understanding of the mechanisms utilised by the bacteria in the bioprecipitation and adsorption of Pb(II). These results can be used as a step towards applying the process on an industrial scale.
ppGpp, the General Stress Response Alarmone, Is Required for the Expression of the α-Hemolysin Toxin in the Uropathogenic Escherichia coli Isolate, J96
Authors: Fernández-Vázquez Jorge , Cabrer-Panes Juan David , Åberg Anna , Juárez Antonio , Madrid Cristina , Gaviria-Cantin Tania , Fernández-Coll Llorenç , Vargas-Sinisterra Andrés Felipe , Jiménez Carlos Jonay , Balsalobre Carlos
Published: October 2022

ppGpp is an intracellular sensor that, in response to different types of stress, coordinates the rearrangement of the gene expression pattern of bacteria to promote adaptation and survival to new environmental conditions. First described to modulate metabolic adaptive responses, ppGpp modulates the expression of genes belonging to very diverse functional categories. In Escherichia coli, ppGpp regulates the expression of cellular factors that are important during urinary tract infections. Here, we characterize the role of this alarmone in the regulation of the hlyCABDII operon of the UPEC isolate J96, encoding the toxin α-hemolysin that induces cytotoxicity during infection of bladder epithelial cells. ppGpp is required for the expression of the α-hemolysin encoded in hlyCABDII by stimulating its transcriptional expression. Prototrophy suppressor mutations in a ppGpp-deficient strain restore the α-hemolysin expression from this operon to wild-type levels, confirming the requirement of ppGpp for its expression. ppGpp stimulates hlyCABDII expression independently of RpoS, RfaH, Zur, and H-NS. The expression of hlyCABDII is promoted at 37 °C and at low osmolarity. ppGpp is required for the thermoregulation but not for the osmoregulation of the hlyCABDII operon. Studies in both commensal and UPEC isolates demonstrate that no UPEC specific factor is strictly required for the ppGpp-mediated regulation described. Our data further support the role of ppGpp participating in the coordinated regulation of the expression of bacterial factors required during infection.
Optogenetic fMRI for Brain-Wide Circuit Analysis of Sensory Processing
Authors: Lee Jeong-Yun , You Taeyi , Woo Choong-Wan , Kim Seong-Gi
Published: October 2022

Sensory processing is a complex neurological process that receives, integrates, and responds to information from one’s own body and environment, which is closely related to survival as well as neurological disorders. Brain-wide networks of sensory processing are difficult to investigate due to their dynamic regulation by multiple brain circuits. Optogenetics, a neuromodulation technique that uses light-sensitive proteins, can be combined with functional magnetic resonance imaging (ofMRI) to measure whole-brain activity. Since ofMRI has increasingly been used for investigating brain circuits underlying sensory processing for over a decade, we systematically reviewed recent ofMRI studies of sensory circuits and discussed the challenges of optogenetic fMRI in rodents.
Omics Data and Data Representations for Deep Learning-Based Predictive Modeling
Authors: Tsimenidis Stefanos , Vrochidou Eleni , Papakostas George A.
Published: October 2022

Medical discoveries mainly depend on the capability to process and analyze biological datasets, which inundate the scientific community and are still expanding as the cost of next-generation sequencing technologies is decreasing. Deep learning (DL) is a viable method to exploit this massive data stream since it has advanced quickly with there being successive innovations. However, an obstacle to scientific progress emerges: the difficulty of applying DL to biology, and this because both fields are evolving at a breakneck pace, thus making it hard for an individual to occupy the front lines of both of them. This paper aims to bridge the gap and help computer scientists bring their valuable expertise into the life sciences. This work provides an overview of the most common types of biological data and data representations that are used to train DL models, with additional information on the models themselves and the various tasks that are being tackled. This is the essential information a DL expert with no background in biology needs in order to participate in DL-based research projects in biomedicine, biotechnology, and drug discovery. Alternatively, this study could be also useful to researchers in biology to understand and utilize the power of DL to gain better insights into and extract important information from the omics data.
Effects of Sex and Obesity on LEP Variant and Leptin Level Associations in Intervertebral Disc Degeneration
Authors: Chen Hsing-Hong , Hsu Hsien-Ta , Liao Mei-Hsiu , Teng Ming-Sheng
Published: October 2022

Intervertebral disc degeneration (IVDD), for which obesity and genetics are known risk factors, is a chronic process that alters the structure and function of the intervertebral discs (IVD). Circulating leptin is positively correlated with body weight and is often measured to elucidate the pathogenesis of IVD degeneration. In this study, we examined the associations of LEP single nucleotide polymorphisms (SNPs) genetic and environmental effects with IVDD. A total of 303 Taiwanese patients with IVDD (mean age, 58.6 ± 12.7 years) undergoing cervical discectomy for neck pain or lumbar discectomy for back pain were enrolled. Commercially available enzyme-linked immunosorbent assay (ELISA) kits measured the circulating plasma leptin levels. TaqMan SNP genotyping assays genotyped the LEP SNPs rs2167270 and rs7799039. Leptin levels were significantly increased in obese individuals (p < 0.001) and non-obese or obese women (p < 0.001). In the dominant model, recoded minor alleles of rs2167270 and rs7799039 were associated with higher leptin levels in all individuals (p = 0.011, p = 0.012). Further, the association between these LEP SNPs and leptin levels was significant only in obese women (p = 0.025 and p = 0.008, respectively). There was an interaction effect between sex and obesity, particularly among obese women (interaction p = 0.04 and 0.02, respectively). Our findings demonstrate that these SNPs have sex-specific associations with BMI in IVDD patients, and that obesity and sex, particularly among obese women, may modify the LEP transcription effect.
Identification of the Extracellular Nuclease Influencing Soaking RNA Interference Efficiency in Bursaphelenchus xylophilus
Authors: Wang Ruijiong , Li Yongxia , Li Dongzhen , Zhang Wei , Wang Xuan , Wen Xiaojian , Liu Zhenkai , Feng Yuqian , Zhang Xingyao
Published: October 2022

RNA interference (RNAi) efficiency dramatically varies among different nematodes, which impacts research on their gene function and pest control. Bursaphelenchus xylophilus is a pine wood nematode in which RNAi-mediated gene silencing has unstable interference efficiency through soaking in dsRNA solutions, the factors of which remain unknown. Using agarose gel electrophoresis, we found that dsRNA can be degraded by nematode secretions in the soaking system which is responsible for the low RNAi efficiency. Based on the previously published genome and secretome data of B. xylophilus, 154 nucleases were screened including 11 extracellular nucleases which are potential factors reducing RNAi efficacy. To confirm the function of nucleases in RNAi efficiency, eight extracellular nuclease genes (BxyNuc1-8) were cloned in the genome. BxyNuc4, BxyNuc6 and BxyNuc7 can be upregulated in response to dsGFP, considered as the major nuclease performing dsRNA degradation. After soaking with the dsRNA of nucleases BxyNuc4/BxyNuc6/BxyNuc7 and Pat10 gene (ineffective in RNAi) simultaneously for 24 h, the expression of Pat10 gene decreased by 23.25%, 26.05% and 11.29%, respectively. With soaking for 36 h, the expression of Pat10 gene decreased by 43.25% and 33.25% in dsBxyNuc6+dsPat10 and dsBxyNuc7+dsPat10 groups, respectively. However, without dsPat10, dsBxyNuc7 alone could cause downregulation of Pat10 gene expression, while dsBxyNuc6 could not disturb this gene. In conclusion, the nuclease BxyNuc6 might be a major barrier to the RNAi efficiency in B. xylophilus.
GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway
Authors: Wang Zongkui , Jiang Peng , Liu Fengjuan , Du Xi , Ma Li , Ye Shengliang , Cao Haijun , Sun Pan , Su Na , Lin Fangzhao , Zhang Rong , Li Changqing
Published: October 2022

Growth differentiation factor 11 (GDF11), belonging to the transforming factor-β superfamily, regulates anterior-posterior patterning and inhibits neurogenesis during embryonic development. However, recent studies recognized GDF11 as a rejuvenating (or anti-ageing) factor to reverse age-related cardiac hypertrophy, repair injured skeletal muscle, promote cognitive function, etc. The effects of GDF11 are contradictory and the mechanism of action is still not well clarified. The objective of the present study was to investigate effects of GDF11 on PC12 neural stem cells in vitro and to reveal the underlying mechanism. We systematically assessed the effects of GDF11 on the life activities of PC12 cells. GDF11 significantly suppressed cell proliferation and migration, promoted differentiation and apoptosis, and arrested cell cycle at G2/M phase. Both TMT-based proteomic analysis and phospho-antibody microarray revealed PI3K-Akt pathway was enriched when treated with GDF11. Inhibition of ALK5 or PI3K obviously attenuated the effects of GDF11 on PC12 neural stem cells, which exerted that GDF11 regulated neural stem cells through ALK5-dependent PI3K-Akt signaling pathway. In summary, these results demonstrated GDF11 could be a negative regulator for neurogenesis via ALK5 activating PI3K-Akt pathway when it directly acted on neural stem cells.
Aphelenchoides besseyi Ab-FAR-1 Interacts with Arabidopsis thaliana AtADF3 to Interfere with Actin Cytoskeleton, and Promotes Nematode Parasitism and Pathogenicity
Authors: Ding Shanwen , Cheng Xi , Wang Dongwei , Chen Chun , Yang Sihua , Wang Jiafeng , Xu Chunling , Xie Hui
Published: October 2022

Fatty acid and retinol binding proteins (FAR) are unique proteins found in nematodes and are considered potential targets for controlling these parasites. However, their functions in nematode parasitism and pathogenicity and interaction with hosts are still unclear. In this study, we investigated the specific roles of rice white tip nematodes (RWTNs), Aphelenchoides besseyi, and a protein, Ab-FAR-1, to elucidate the parasitic and pathogenic processes of nematodes. The results showed that the expression level of Ab-far-1 was significantly up-regulated after A. besseyi infection of the plant. The immunofluorescence and subcellular localisation showed that Ab-FAR-1 was secreted into plant tissues mainly through the body wall of nematodes and might act in the nucleus and cytoplasm of plant cells. The pathogenicity of RWTNs was enhanced in Arabidopsis thaliana overexpressing Ab-FAR-1 and inhibited in Ab-far-1 RNAi A. thaliana. Yeast two-hybrid, Co-IP, BiFC, and nematode inoculation experiments showed that Ab-FAR-1 could interact with the A. thaliana actin-depolymerizing factor protein AtADF3, and the A. thaliana adf3 mutant was more susceptible to nematodes. An in vitro actin filament depolymerisation assay demonstrated that Ab-FAR-1 could inhibit AtADF3-mediated depolymerisation of actin filaments, and the turnover process of cellular actin filaments was also affected in A. thaliana overexpressing Ab-FAR-1. In addition, flg22-mediated host defence responses were suppressed in A. thaliana overexpressing Ab-FAR-1 and adf3 mutants. Therefore, this study confirmed that RWTNs can affect the turnover of actin filament remodelling mediated by AtADF3 through Ab-FAR-1 secretion and thus inhibit plant PAMP-triggered immunity (PTI), promoting the parasitism and pathogenicity of nematodes.
Individual and Combined Effect of Bisphenol A and Bisphenol AF on Prostate Cell Proliferation through NF-κB Signaling Pathway
Authors: Wang Kaiyue , Huang Dongyan , Zhou Ping , Su Xin , Yang Rongfu , Shao Congcong , Ma Aicui , Wu Jianhui
Published: October 2022

The ubiquitous environmental endocrine disruptor bisphenol A (BPA) can induce prostatic dysfunction. However, to date, studies have focused little on the perturbations of prostate health initiated by the BPA derivative bisphenol AF (BPAF) and co-exposure to bisphenol compounds. An in vivo study orally administrated male rats with BPA (10, 90 μg/kg), BPAF (10, 90 μg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg). Based on the anatomical analysis, pathological observations and PCNA over-expression, we considered that low-dose BPA and BPAF facilitated ventral prostatic hyperplasia in rats. The results of IHC and ELISA mirrored the regulation of NF-κB p65, COX-2, TNF-α and EGFR in BPA- and BPAF-induced prostatic toxicity. An in vitro study found that the additive effect of combined exposure to BPA (10 nM) and BPAF (10 nM) could cause an elevation in the proliferation of and a reduction in the apoptosis level of human prostate stromal cells (WPMY−1) and fibroblasts (HPrF). Meanwhile, the underlying biomarkers of the NF-κB signaling pathway also involved the abnormal proliferative progression of prostate cells. The findings recapitulated the induction of BPAF exposure and co-treatment with BPA and BPAF on prostatic hyperplasia and emphasized the modulation of the NF-κB signaling pathway.
Towards the Improvement of Ornamental Attributes in Chrysanthemum: Recent Progress in Biotechnological Advances
Authors: Mekapogu Manjulatha , Kwon Oh-Keun , Song Hyun-Young , Jung Jae-A
Published: October 2022

Incessant development and introduction of novel cultivars with improved floral attributes are vital in the dynamic ornamental industry. Chrysanthemum (Chrysanthemum morifolium) is a highly favored ornamental plant, ranking second globally in the cut flower trade, after rose. Development of new chrysanthemum cultivars with improved and innovative modifications in ornamental attributes, including floral color, shape, plant architecture, flowering time, enhanced shelf life, and biotic and abiotic stress tolerance, is a major goal in chrysanthemum breeding. Despite being an economically important ornamental plant, the application of conventional and molecular breeding approaches to various key traits of chrysanthemum is hindered owing to its genomic complexity, heterozygosity, and limited gene pool availability. Although classical breeding of chrysanthemum has resulted in the development of several hundreds of cultivars with various morphological variations, the genetic and transcriptional control of various important ornamental traits remains unclear. The coveted blue colored flowers of chrysanthemums cannot be achieved through conventional breeding and mutation breeding due to technical limitations. However, blue-hued flower has been developed by genetic engineering, and transgenic molecular breeding has been successfully employed, leading to substantial progress in improving various traits. The recent availability of whole-genome sequences of chrysanthemum offers a platform to extensively employ MAS to identify a large number of markers for QTL mapping, and GWAS to dissect the genetic control of complex traits. The combination of NGS, multi-omic platforms, and genome editing technologies has provided a tremendous scope to decipher the molecular and regulatory mechanisms. However, the application and integration of these technologies remain inadequate for chrysanthemum. This review, therefore, details the significance of floral attributes, describes the efforts of recent advancements, and highlights the possibilities for future application towards the improvement of crucial ornamental traits in the globally popular chrysanthemum plant.
Epigenetic Regulation by Polycomb Complexes from Drosophila to Human and Its Relation to Communicable Disease Pathogenesis
Authors: Scholl Aaron , De Sandip
Published: October 2022

Although all cells in the human body are made of the same DNA, these cells undergo differentiation and behave differently during development, through integration of external and internal stimuli via ‘specific mechanisms.’ Epigenetics is one such mechanism that comprises DNA/RNA, histone modifications, and non-coding RNAs that regulate transcription without changing the genetic code. The discovery of the first Polycomb mutant phenotype in Drosophila started the study of epigenetics more than 80 years ago. Since then, a considerable number of Polycomb Group (PcG) genes in Drosophila have been discovered to be preserved in mammals, including humans. PcG proteins exert their influence through gene repression by acting in complexes, modifying histones, and compacting the chromatin within the nucleus. In this article, we discuss how our knowledge of the PcG repression mechanism in Drosophila translates to human communicable disease research.
Dysregulation of Placental Lipid Hydrolysis by High-Fat/High-Cholesterol Feeding and Gestational Diabetes Mellitus in Mice
Authors: Kuentzel Katharina B. , Bradić Ivan , Mihalič Zala N. , Korbelius Melanie , Rainer Silvia , Pirchheim Anita , Kargl Julia , Kratky Dagmar
Published: October 2022

Advanced maternal age and obesity are the main risk factors to develop gestational diabetes mellitus (GDM). Obesity is a consequence of the increased storage of triacylglycerol (TG). Cytosolic and lysosomal lipid hydrolases break down TG and cholesteryl esters (CE) to release fatty acids (FA), free cholesterol, and glycerol. We have recently shown that intracellular lipases are present and active in the mouse placenta and that deficiency of lysosomal acid lipase alters placental and fetal lipid homeostasis. To date, intracellular lipid hydrolysis in GDM has been poorly studied despite the important role of FA in this condition. Therefore, we hypothesized that intracellular lipases are dysregulated in pregnancies complicated by maternal high-fat/high-cholesterol (HF/HCD) feeding with and without GDM. Placentae of HF/HCD-fed mice with and without GDM were more efficient, indicating increased nutrient transfer to the fetus. The increased activity of placental CE but not TG hydrolases in placentae of dams fed HF/HCD with or without GDM resulted in upregulated cholesterol export to the fetus and placental TG accumulation. Our results indicate that HF/HCD-induced dysregulation of placental lipid hydrolysis contributes to fetal hepatic lipid accumulation and possibly to fetal overgrowth, at least in mice.
Genetics and Epigenetics of the X and Y Chromosomes in the Sexual Differentiation of the Brain
Authors: Cabrera Zapata Lucas E. , Garcia-Segura Luis Miguel , Cambiasso María Julia , Arevalo Maria Angeles
Published: October 2022

For many decades to date, neuroendocrinologists have delved into the key contribution of gonadal hormones to the generation of sex differences in the developing brain and the expression of sex-specific physiological and behavioral phenotypes in adulthood. However, it was not until recent years that the role of sex chromosomes in the matter started to be seriously explored and unveiled beyond gonadal determination. Now we know that the divergent evolutionary process suffered by X and Y chromosomes has determined that they now encode mostly dissimilar genetic information and are subject to different epigenetic regulations, characteristics that together contribute to generate sex differences between XX and XY cells/individuals from the zygote throughout life. Here we will review and discuss relevant data showing how particular X- and Y-linked genes and epigenetic mechanisms controlling their expression and inheritance are involved, along with or independently of gonadal hormones, in the generation of sex differences in the brain.
A Review: Highlighting the Links between Epigenetics, COVID-19 Infection, and Vitamin D
Authors: Foolchand Ashmika , Mazaleni Siyanda , Ghazi Terisha , Chuturgoon Anil A.
Published: October 2022

The highly transmittable and infectious COVID-19 remains a major threat worldwide, with the elderly and comorbid individuals being the most vulnerable. While vaccines are currently available, therapeutic drugs will help ease the viral outbreak and prevent serious health outcomes. Epigenetic modifications regulate gene expression through changes in chromatin structure and have been linked to viral pathophysiology. Since epigenetic modifications contribute to the life cycle of the virus and host immune responses to infection, epigenetic drugs are promising treatment targets to ameliorate COVID-19. Deficiency of the multifunctional secosteroid hormone vitamin D is a global health threat. Vitamin D and its receptor function to regulate genes involved in immunity, apoptosis, proliferation, differentiation, and inflammation. Amassed evidence also indicates the biological relations of vitamin D with reduced disease risk, while its receptor can be modulated by epigenetic mechanisms. The immunomodulatory effects of vitamin D suggest a role for vitamin D as a COVID-19 therapeutic agent. Therefore, this review highlights the epigenetic effects on COVID-19 and vitamin D while also proposing a role for vitamin D in COVID-19 infections.
Characterization of the RAS/RAF/ERK Signal Cascade as a Novel Regulating Factor in Alpha-Amanitin-Induced Cytotoxicity in Huh-7 Cells
Authors: Kim Doeun , Lee Min Seo , Sung Eunji , Lee Sangkyu , Lee Hye Suk
Published: October 2022

The well-known hepatotoxicity mechanism resulting from alpha-amanitin (α-AMA) exposure arises from RNA polymerase II (RNAP II) inhibition. RNAP Ⅱ inhibition occurs through the dysregulation of mRNA synthesis. However, the signaling pathways in hepatocytes that arise from α-AMA have not yet been fully elucidated. Here, we identified that the RAS/RAF/ERK signaling pathway was activated through quantitative phosphoproteomic and molecular biological analyses in Huh-7 cells. Bioinformatics analysis showed that α-AMA exposure increased protein phosphorylation in a time-dependent α-AMA exposure. In addition, phosphorylation increased not only the components of the ERK signaling pathway but also U2AF65 and SPF45, known splicing factors. Therefore, we propose a novel mechanism of α-AMA as follows. The RAS/RAF/ERK signaling pathway involved in aberrant splicing events is activated by α-AMA exposure followed by aberrant splicing events leading to cell death in Huh-7 cells.
Thermofluor-Based Optimization Strategy for the Stabilization of Recombinant Human Soluble Catechol-O-Methyltransferase
Authors: Gonçalves Ana M. , Pedro Augusto Q. , Oliveira Diana M. , Oliveira Adriana E. , Santos Marino F. A. , Correia Márcia A. S. , Queiroz João A. , Gallardo Eugénia , Romão Maria J. , Passarinha Luís A.
Published: October 2022

Catechol-O-methyltransferase (COMT) has been involved in a number of medical conditions including catechol-estrogen-induced cancers and a great range of cardiovascular and neurodegenerative diseases such as Parkinson’s disease. Currently, Parkinson’s disease treatment relies on a triple prophylaxis, involving dopamine replacement by levodopa, the use of aromatic L-amino acid decarboxylase inhibitors, and the use of COMT inhibitors. Typically, COMT is highly thermolabile, and its soluble isoform (SCOMT) loses biological activity within a short time span preventing further structural and functional trials. Herein, we characterized the thermal stability profile of lysate cells from Komagataella pastoris containing human recombinant SCOMT (hSCOMT) and enzyme-purified fractions (by Immobilized Metal Affinity Chromatography—IMAC) upon interaction with several buffers and additives by Thermal Shift Assay (TSA) and a biological activity assessment. Based on the obtained results, potential conditions able to increase the thermal stability of hSCOMT have been found through the analysis of melting temperature (Tm) variations. Moreover, the use of the ionic liquid 1-butyl-3-methylimidazolium chloride [C4mim]Cl (along with cysteine, trehalose, and glycerol) ensures complete protein solubilization as well as an increment in the protein Tm of approximately 10 °C. Thus, the developed formulation enhances hSCOMT stability with an increment in the percentage of activity recovery of 200% and 70% when the protein was stored at 4 °C and −80 °C, respectively, for 12 h. The formation of metanephrine over time confirmed that the enzyme showed twice the productivity in the presence of the additive. These outstanding achievements might pave the way for the development of future hSCOMT structural and biophysical studies, which are fundamental for the design of novel therapeutic molecules.
PGC-1α and MEF2 Regulate the Transcription of the Carnitine Transporter OCTN2 Gene in C2C12 Cells and in Mouse Skeletal Muscle
Authors: Novakova Katerina , Török Michael , Panajatovic Miljenko , Bouitbir Jamal , Duong François H. T. , Handschin Christoph , Krähenbühl Stephan
Published: October 2022

OCTN2 (SLC22A5) is a carnitine transporter whose main function is the active transport of carnitine into cells. In skeletal muscle and other organs, the regulation of the SLC22A5 gene transcription has been shown to depend on the nuclear transcription factor PPAR-α. Due to the observation that the muscle OCTN2 mRNA level is maintained in PPAR-α knock-out mice and that PGC-1α overexpression in C2C12 myoblasts increases OCTN2 mRNA expression, we suspected additional regulatory pathways for SLC22A5 gene transcription. Indeed, we detected several binding sites of the myocyte-enhancing factor MEF2 in the upstream region of the SLC22A5 gene, and MEF2C/MEF2D stimulated the activity of the OCTN2 promoter in gene reporter assays. This stimulation was increased by PGC-1α and was blunted for a SLC22A5 promoter fragment with a mutated MEF2 binding site. Further, we demonstrated the specific binding of MEF2 to the SLC22A5 gene promoter, and a supershift of the MEF2/DNA complex in electrophoretic mobility shift assays. In immunoprecipitation experiments, we could demonstrate the interaction between PGC-1α and MEF2. In addition, SB203580, a specific inhibitor of p38 MAPK, blocked and interferon-γ stimulated the transcriptional activity of the SLC22A5 gene promoter. Finally, mice with muscle-specific overexpression of OCTN2 showed an increase in OCTN2 mRNA and protein expression in skeletal muscle. In conclusion, we detected and characterized a second stimulatory pathway of SLC22A5 gene transcription in skeletal muscle, which involves the nuclear transcription factor MEF2 and co-stimulation by PGC-1α and which is controlled by the p38 MAPK signaling cascade.
The Challenge of Long COVID-19 Management: From Disease Molecular Hallmarks to the Proposal of Exercise as Therapy
Authors: Scurati Raffaele , Papini Nadia , Giussani Paola , Alberti Giampietro , Tringali Cristina
Published: October 2022

Long coronavirus disease 19 (COVID-19) is the designation given to a novel syndrome that develops within a few months after infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and that is presenting with increasing incidence because of the numerous cases of infection. Long COVID-19 is characterized by a sequela of clinical symptoms that concern different organs and tissues, from nervous, respiratory, gastrointestinal, and renal systems to skeletal muscle and cardiovascular apparatus. The main common molecular cause for all long COVID-19 facets appears to be related to immune dysregulations, the persistence of inflammatory status, epigenetic modifications, and alterations of neurotrophin release. The prevention and management of long COVID-19 are still inappropriate because many aspects need further clarification. Exercise is known to exert a deep action on molecular dysfunctions elicited by long COVID-19 depending on training intensity, duration, and continuity. Evidence suggests that it could improve the quality of life of long COVID-19 patients. This review explores the main clinical features and the known molecular mechanisms underlying long COVID-19 in the perspective of considering exercise as a co-medication in long COVID-19 management.
A Perspective on the (Rise and Fall of) Protein β-Turns
Authors: de Brevern Alexandre G.
Published: October 2022

The β-turn is the third defined secondary structure after the α-helix and the β-sheet. The β-turns were described more than 50 years ago and account for more than 20% of protein residues. Nonetheless, they are often overlooked or even misunderstood. This poor knowledge of these local protein conformations is due to various factors, causes that I discuss here. For example, confusion still exists about the assignment of these local protein structures, their overlaps with other structures, the potential absence of a stabilizing hydrogen bond, the numerous types of β-turns and the software’s difficulty in assigning or visualizing them. I also propose some ideas to potentially/partially remedy this and present why β-turns can still be helpful, even in the AlphaFold 2 era.
Aquaporin Gating: A New Twist to Unravel Permeation through Water Channels
Authors: Ozu Marcelo , Alvear-Arias Juan José , Fernandez Miguel , Caviglia Agustín , Peña-Pichicoi Antonio , Carrillo Christian , Carmona Emerson , Otero-Gonzalez Anselmo , Garate José Antonio , Amodeo Gabriela , Gonzalez Carlos
Published: October 2022

Aquaporins (AQPs) are small transmembrane tetrameric proteins that facilitate water, solute and gas exchange. Their presence has been extensively reported in the biological membranes of almost all living organisms. Although their discovery is much more recent than ion transport systems, different biophysical approaches have contributed to confirm that permeation through each monomer is consistent with closed and open states, introducing the term gating mechanism into the field. The study of AQPs in their native membrane or overexpressed in heterologous systems have experimentally demonstrated that water membrane permeability can be reversibly modified in response to specific modulators. For some regulation mechanisms, such as pH changes, evidence for gating is also supported by high-resolution structures of the water channel in different configurations as well as molecular dynamics simulation. Both experimental and simulation approaches sustain that the rearrangement of conserved residues contributes to occlude the cavity of the channel restricting water permeation. Interestingly, specific charged and conserved residues are present in the environment of the pore and, thus, the tetrameric structure can be subjected to alter the positions of these charges to sustain gating. Thus, is it possible to explore whether the displacement of these charges (gating current) leads to conformational changes? To our knowledge, this question has not yet been addressed at all. In this review, we intend to analyze the suitability of this proposal for the first time.
Role of Micronutrients and Gut Microbiota-Derived Metabolites in COVID-19 Recovery
Authors: Hernández-Flores Teresita de Jesús , Pedraza-Brindis Eliza Julia , Cárdenas-Bedoya Jhonathan , Ruíz-Carrillo José Daniel , Méndez-Clemente Anibal Samael , Martínez-Guzmán Marco Alonso , Iñiguez-Gutiérrez Liliana
Published: October 2022

A balanced and varied diet provides diverse beneficial effects on health, such as adequate micronutrient availability and a gut microbiome in homeostasis. Besides their participation in biochemical processes as cofactors and coenzymes, vitamins and minerals have an immunoregulatory function; meanwhile, gut microbiota and its metabolites coordinate directly and indirectly the cell response through the interaction with the host receptors. Malnourishment is a crucial risk factor for several pathologies, and its involvement during the Coronavirus Disease 2019 pandemic has been reported. This pandemic has caused a significant decline in the worldwide population, especially those with chronic diseases, reduced physical activity, and elder age. Diet and gut microbiota composition are probable causes for this susceptibility, and its supplementation can play a role in reestablishing microbial homeostasis and improving immunity response against Coronavirus Disease 2019 infection and recovery. This study reviews the role of micronutrients and microbiomes in the risk of infection, the severity of disease, and the Coronavirus Disease 2019 sequelae.
Repurposing SGLT-2 Inhibitors to Target Aging: Available Evidence and Molecular Mechanisms
Authors: La Grotta Rosalba , Frigé Chiara , Matacchione Giulia , Olivieri Fabiola , de Candia Paola , Ceriello Antonio , Prattichizzo Francesco
Published: October 2022

Caloric restriction promotes longevity in multiple animal models. Compounds modulating nutrient-sensing pathways have been suggested to reproduce part of the beneficial effect of caloric restriction on aging. However, none of the commonly studied caloric restriction mimetics actually produce a decrease in calories. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) are a class of drugs which lower glucose by promoting its elimination through urine, thus inducing a net loss of calories. This effect promotes a metabolic shift at the systemic level, fostering ketones and fatty acids utilization as glucose-alternative substrates, and is accompanied by a modulation of major nutrient-sensing pathways held to drive aging, e.g., mTOR and the inflammasome, overall resembling major features of caloric restriction. In addition, preliminary experimental data suggest that SGLT-2i might also have intrinsic activities independent of their systemic effects, such as the inhibition of cellular senescence. Consistently, evidence from both preclinical and clinical studies have also suggested a marked ability of SGLT-2i to ameliorate low-grade inflammation in humans, a relevant driver of aging commonly referred to as inflammaging. Considering also the amount of data from clinical trials, observational studies, and meta-analyses suggesting a tangible effect on age-related outcomes, such as cardiovascular diseases, heart failure, kidney disease, and all-cause mortality also in patients without diabetes, here we propose a framework where at least part of the benefit provided by SGLT-2i is mediated by their ability to blunt the drivers of aging. To support this postulate, we synthesize available data relative to the effect of this class on: 1- animal models of healthspan and lifespan; 2- selected molecular pillars of aging in preclinical models; 3- biomarkers of aging and especially inflammaging in humans; and 4- COVID-19-related outcomes. The burden of evidence might prompt the design of studies testing the potential employment of this class as anti-aging drugs.