Arsenic-Induced Cardiovascular Diseases and their Correlation with Mitochondrial DNA Copy Number, Deletion, and Telomere Length in Bangladeshi Population.

Arsenic contamination is a global health concern, primarily through contaminated groundwater and its entry into the food chain. The association between arsenic exposure and cardiovascular diseases (CVDs) is particularly alarming due to CVDs being the leading cause of death worldwide. Arsenic exposure has also been linked to changes in telomere length, mitochondrial DNA copy number (mtDNAcn), and deletion, further increasing the risk of CVDs. We aimed to determine whether arsenic exposure alters telomere length and mtDNAcn and deletion in a total of 50 CVD patients who underwent open heart surgery hailed from known arsenic-affected and unaffected areas in Bangladesh. Amount of arsenic was determined from the collected nails and cardiac tissues. Relative telomere length and mtDNAcn and deletion were quantified by qRT-PCR. The patients from arsenic-contaminated areas had higher average arsenic deposits in their fingers and toenails (P < 0.05) and higher cardiac tissue injury scores (P < 0.05). Moreover, approximately 1.5-fold shorter telomere length (P < 0.05, r = - 0.775), 1.2-fold decreased mtDNAcn (P < 0.05, r = - 0.797), and an 81-fold higher amount of mitochondrial DNA deletion (P < 0.05, r = 0.784) were observed in the patients who had higher arsenic deposition in their nails. Higher levels of arsenic exposure were found to be linked to shorter telomere length, decreased mtDNAcn, and increased mitochondrial DNA deletion in the patients from As-affected areas. It can also be anticipated that the correlation of arsenic exposure with telomere length, mtDNAcn, and deletion can be used as biomarkers for early diagnosis of arsenic-induced cardiovascular diseases.

The Na+/H+ antiporter SALT OVERLY SENSITIVE 1 regulates salt compensation of circadian rhythms by stabilizing GIGANTEA in Arabidopsis.

The circadian clock is a timekeeping, homeostatic system that temporally coordinates all major cellular processes. The function of the circadian clock is compensated in the face of variable environmental conditions ranging from normal to stress-inducing conditions. Salinity is a critical environmental factor affecting plant growth, and plants have evolved the SALT OVERLY SENSITIVE (SOS) pathway to acquire halotolerance. However, the regulatory systems for clock compensation under salinity are unclear. Here, we show that the plasma membrane Na+/H+ antiporter SOS1 specifically functions as a salt-specific circadian clock regulator via GIGANTEA (GI) in Arabidopsis thaliana. SOS1 directly interacts with GI in a salt-dependent manner and stabilizes this protein to sustain a proper clock period under salinity conditions. SOS1 function in circadian clock regulation requires the salt-mediated secondary messengers cytosolic free calcium and reactive oxygen species, pointing to a distinct regulatory role for SOS1 in addition to its function as a transporter to maintain Na+ homeostasis. Our results demonstrate that SOS1 maintains homeostasis of the salt response under high or daily fluctuating salt levels. These findings highlight the genetic capacity of the circadian clock to maintain timekeeping activity over a broad range of salinity levels.

Comparative proteomic analysis to annotate the structural and functional association of the hypothetical proteins of S. maltophilia k279a and predict potential T and B cell targets for vaccination.

Stenotrophomonas maltophilia is a multidrug-resistant bacterium with no precise clinical treatment. This bacterium can be a vital cause for death and different organ failures in immune-compromised, immune-competent, and long-time hospitalized patients. Extensive quorum sensing capability has become a challenge to develop new drugs against this pathogen. Moreover, the organism possesses about 789 proteins which function, structure, and pathogenesis remain obscured. In this piece of work, we tried to enlighten the aforementioned sectors using highly reliable bioinformatics tools validated by the scientific community. At first, the whole proteome sequence of the organism was retrieved and stored. Then we separated the hypothetical proteins and searched for the conserved domain with a high confidence level and multi-server validation, which resulted in 24 such proteins. Furthermore, all of their physical and chemical characterizations were performed, such as theoretical isoelectric point, molecular weight, GRAVY value, and many more. Besides, the subcellular localization, protein-protein interactions, functional motifs, 3D structures, antigenicity, and virulence factors were also evaluated. As an extension of this work, 'RTFAMSSER' and 'PAAPQPSAS' were predicted as potential T and B cell epitopes, respectively. We hope our findings will help in better understating the pathogenesis and smoothen the way to the cure.

Association of arsenic-induced cardiovascular disease susceptibility with genetic polymorphisms.

Inorganic arsenic (iAs) exposure has been reported to have an impact on cardiovascular diseases (CVD). However, there is not much known about the cardiac tissue injury of CVD patients in relation to iAs exposure and potential role of single nucleotide polymorphisms (SNPs) of genes related to iAs metabolism, oxidative stress, endothelial dysfunction and inflammation which may play important roles in such CVD cases. In this dual center cross-sectional study, based on the exclusion and inclusion criteria, we have recruited 50 patients out of 270, who came from known arsenic-affected and- unaffected areas of mainly Chittagong, Dhaka and Rajshahi divisions of Bangladesh and underwent open-heart surgery at the selected centers during July 2017 to June 2018. We found that the patients from arsenic affected areas contained significantly higher average iAs concentrations in their urine (6.72 ± 0.54 ppb, P = 0.028), nail (529.29 ± 38.76 ppb, P < 0.05) and cardiac tissue (4.83 ± 0.50 ppb, P < 0.05) samples. Patients' age, sex, BMI, hypertension and diabetes status adjusted analysis showed that patients from arsenic-affected areas had significantly higher iAs concentration in cardiac tissue (2.854, 95%CI 1.017-8.012, P = 0.046) reflecting higher cardiac tissue injury among them (1.831, 95%CI 1.032-3.249, P = 0.039), which in turn allowed the analysis to assume that the iAs exposure have played a vital role in patients' disease condition. Adjusted analysis showed significant association between urinary iAs concentration with AA (P = 0.012) and AG (P = 0.034) genotypes and cardiac iAs concentration with AA (P = 0.017) genotype of AS3MT rs10748835. The AG genotype of AS3MT rs10748835 (13.333 95%CI 1.280-138.845, P = 0.013), AA genotype of NOS3 rs3918181 (25.333 95%CI 2.065-310.757, P = 0.002), GG genotype of ICAM1 rs281432 (12.000 95%CI 1.325-108.674, P = 0.010) and AA genotype of SOD2 rs2758331 (13.333 95%CI 1.280-138.845, P = 0.013) were found significantly associated with CVD patients from arsenic-affected areas. Again, adjusted analysis showed significant association of AA genotype of AS3MT rs10748835 with CVD patients from arsenic affected areas. In comparison to the reference genotypes of the selected SNPs, AA of AS3MT 10748835, AG of NOS3 rs3918181 and AC of rs3918188, GG of ICAM1 rs281432, TT of VCAM1 rs3176867, AA of SOD2 rs2758331 and GT of APOE rs405509 significantly increased odds of cardiac tissue injury of CVD patients from arsenic affected areas. The results showed that the selected SNPs played a susceptibility role towards cardiac tissue iAs concentration and injury among CVD patients from iAs affected areas.

Protective effects of Corchorus olitorius and Butea monosperma against Arsenic induced aberrant methylation and mitochondrial DNA damage in wistar rat model.

Millions of people around the world are chronically exposed to Arsenic (As) through food and drinking water. Studies revealed that Arsenic is genotoxic and causes damage to DNA. In this study, we evaluated Corchorus olitorius and Butea monosperma for their alleviative properties against Arsenic induced genotoxicity in vivo using Wistar Rat model. Arsenic exposed rats were given C. olitorius leaf powder and B. monosperma flower powder as supplementation with normal food. Methylation status of p53 promoter was measured using Methylation Sensitive Restriction Endonuclease PCR (MSRE-PCR) assay and mitochondrial DNA (mtDNA) copy number as well as occurrence of a common deletion in mtDNA in liver and kidney tissue was determined through quantitative realtime PCR (qPCR). Arsenic exposed rats after supplementation showed relatively less severe effects of toxicity evident by significantly higher amount of (p<0.05) mtDNA copy number and reduced occurrence of deletion containing mtDNA as well as lower levels of methylation in p53 gene promoter. Histopathological analysis revealed less severe histopathological changes of liver and kidney and normal liver and kidney function parameters in supplemented rats. So, the protective properties of B. monosperma and C. olitorius against Arsenic toxicity is evident in molecular level.

Humic Acid Confers HIGH-AFFINITY K+ TRANSPORTER 1-Mediated Salinity Stress Tolerance in Arabidopsis.

Excessive salt disrupts intracellular ion homeostasis and inhibits plant growth, which poses a serious threat to global food security. Plants have adapted various strategies to survive in unfavorable saline soil conditions. Here, we show that humic acid (HA) is a good soil amendment that can be used to help overcome salinity stress because it markedly reduces the adverse effects of salinity on Arabidopsis thaliana seedlings. To identify the molecular mechanisms of HA-induced salt stress tolerance in Arabidopsis, we examined possible roles of a sodium influx transporter HIGH-AFFINITY K+ TRANSPORTER 1 (HKT1). Salt-induced root growth inhibition in HKT1 overexpressor transgenic plants (HKT1-OX) was rescued by application of HA, but not in wild-type and other plants. Moreover, salt-induced degradation of HKT1 protein was blocked by HA treatment. In addition, the application of HA to HKT1-OX seedlings led to increased distribution of Na+ in roots up to the elongation zone and caused the reabsorption of Na+ by xylem and parenchyma cells. Both the influx of the secondary messenger calcium and its cytosolic release appear to function in the destabilization of HKT1 protein under salt stress. Taken together, these results suggest that HA could be applied to the field to enhance plant growth and salt stress tolerance via post-transcriptional control of the HKT1 transporter gene under saline conditions.

A chaperone surveillance system in plant circadian rhythms.

The circadian clock is an internal system that is synchronized by external stimuli, such as light and temperature, and influences various physiological and developmental processes in living organisms. In the model plant Arabidopsis, transcriptional, translational and post-translational processes are interlocked by feedback loops among morning- and eveningphased genes. In a post-translational loop, plant-specific singlegene encoded GIGANTEA (GI) stabilize the F-box protein ZEITLUPE (ZTL), driving the targeted-proteasomal degradation of TIMING OF CAB EXPRESSION 1 (TOC1) and PSEUDORESPONSE REGULATOR 5 (PRR5). Inherent to this, we demonstrate the novel biochemical function of GI as a chaperone and/or co-chaperone of Heat-Shock Protein 90 (HSP90). GI prevents ZTL degradation as a chaperone and facilitates ZTL maturation together with HSP90/HSP70, enhancing ZTL activity in vitro and in planta. GI is known to be involved in a wide range of physiology and development as well as abiotic stress responses in plants, but it could also interact with diverse client proteins to increase protein maturation. Our results provide evidence that GI helps proteostasis of ZTL by acting as a chaperone and a co-chaperone of HSP90 for proper functioning of the Arabidopsis circadian clock. [BMB Reports 2017; 50(5): 235-236].

Fungal Laccase-Catalyzed Oxidation of Naturally Occurring Phenols for Enhanced Germination and Salt Tolerance of Arabidopsis thaliana: A Green Route for Synthesizing Humic-like Fertilizers.

Fungal laccases have been highlighted as a catalytic tool for transforming phenols. Here we demonstrate that fungal laccase-catalyzed oxidations can transform naturally occurring phenols into plant fertilizers with properties very similar to those of commercial humic acids. Treatments of Arabidopsis thaliana with highly cross-linked polyphenolic products obtained from a mixture of catechol and vanillic acid were able to enhance the germination and salt tolerance of this plant. These results revealed that humic-like organic fertilizers can be produced via in vitro enzymatic oxidation reactions. In particular, the root elongation pattern resulting from the laccase products was comparable to that resulting from an auxin-like compound. A detailed structural comparison of the phenol variants and commercial humic acids revealed their similarities and differences. Analyses based on SEM, EFM, ERP, and zeta-potential measurement showed that they both formed globular granules bearing various hydrophilic/polar groups in aqueous and solid conditions. Solid-phase 13C NMR, FT-IR-ATR, and elemental analyses showed that more nitrogen-based functional and aliphatic groups were present in the commercial humic acids. Significant differences were also identifiable with respect to particle size and specific surface area. High-resolution (15 T) FT-ICR mass spectrometry-based van Krevelen diagrams showed the compositional features of the variants to be a subset of those of the humic acids. Overall, our study unraveled essential structural features of polyaromatics that affect the growth of plants, and also provided novel bottom-up ecofriendly and finely tunable pathways for synthesizing humic-like fertilizers.