Role of heavy metals (copper (Cu), arsenic (As), cadmium (Cd), iron (Fe) and lithium (Li)) induced neurotoxicity.

Parkinson's disease (PD) is a neurodegenerative condition characterized by the dopamine (DA) neuronal loss in the substantia nigra. PD impairs motor controls symptoms such as tremor, rigidity, bradykinesia and postural imbalance gradually along with non-motor problems such as olfactory dysfunction, constipation, sleeping disorder. Though surplus of factors and mechanisms have been recognized, the precise PD etiopathogenesis is not yet implied. Reports suggest that various environmental factors play a crucial role in the causality of the PD cases. Epidemiological studies have reported that heavy metals has a role in causing defects in substantia nigra region of brain in PD. Though the reason is unknown, exposure to heavy metals is reported to be an underlying factor in PD development. Metals are classified as either essential or non-essential, and they have a role in physiological processes such protein modification, electron transport, oxygen transport, redox reactions, and cell adhesion. Excessive metal levels cause oxidative stress, protein misfolding, mitochondrial malfunction, autophagy dysregulation, and apoptosis, among other things. In this review, we check out the link between heavy metals like copper (Cu), arsenic (As), cadmium (Cd), iron (Fe), and lithium (Li) in neurodegeneration, and how it impacts the pathological conditions of PD. In conclusion, increase or decrease in heavy metals involve in regulation of neuronal functions that have an impact on neurodegeneration process. Through this review, we suggest that more research is needed in this stream to bring more novel approaches for either disease modelling or therapeutics.

Environmental survival of SARS-CoV-2 - A solid waste perspective.

The advent of COVID-19 has kept the whole world on their toes. Countries are maximizing their efforts to combat the virus and to minimize the infection. Since infectious microorganisms may be transmitted by variety of routes, respiratory and facial protection is required for those that are usually transmitted via droplets/aerosols. Therefore this pandemic has caused a sudden increase in the demand for personal protective equipment (PPE) such as gloves, masks, and many other important items since, the evidence of individual-to-individual transmission (through respiratory droplets/coughing) and secondary infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). But the disposal of these personal protective measures remains a huge question mark towards the environmental impact. Huge waste generation demands proper segregation according to waste types, collection, and recycling to minimize the risk of infection spread through aerosols and attempts to implement measures to monitor infections. Hence, this review focuses on the impact of environment due to improper disposal of these personal protective measures and to investigate the safe disposal methods for these protective measures by using the safe, secure and innovative biological methods such as the use of Artificial Intelligence (AI) and Ultraviolet (UV) lights for killing such deadly viruses.

Ethnobotanical survey of medicinal plants used in the management of cancer and diabetes.

OBJECTIVE: To conduct an ethnobotanical survey and document the traditional anticancer and antidiabetic plants used by the local tribes of Mizoram, Northeast India. METHODS: A systematic survey was conducted in rural and urban areas of Mizoram by interviewing traditional practitioners, and cancer and diabetes patients. A detailed literature search was carried out using MEDLINE and SCOPUS and available literatures were selected and included in the study. The use value (UV) of the selected plants was calculated based on the number of citations per species given by informants. RESULTS: Data was obtained for 201 traditional medicinal plants from Mizoram, Northeast India. These plants were from 72 different families and belonged to 140 genera. Of these, 103 plants were reported for the first time as possessing either anticancer or antidiabetic potential, and 105 plants were identified that were used for the treatment of both diseases. Three plants (Phlogacanthus thysiformis, Solanum gilo and Lobelia angulata) with antidiabetic potential, and six plants (Dillenia scabrella, Circium sinesis, Eupatorium nodiflorum, Pratia begonifolia, Vernonia teres and Plantago erosa) with both as anticancer and antidiabetic potential were documented for the first time. CONCLUSION: In this study, we documented several explored and unexplored medicinal plants that may be useful for the management of cancer and diabetes. This study suggests that there is a broad scope fordeveloping potent anticancer and antidiabetic agent from the flora of Mizoram, Northeast India.

Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India.

BACKGROUND: Gastric cancer (GC) is one of the most frequently diagnosed digestive tract cancers and carries a high risk of mortality. Acetaldehyde (AA), a carcinogenic intermediate of ethanol metabolism contributes to the risk of GC. The accumulation of AA largely depends on the activity of the major metabolic enzymes, alcohol dehydrogenase and aldehyde dehydrogenase encoded by the ADH (ADH1 gene cluster: ADH1A, ADH1B and ADH1C) and ALDH2 genes, respectively. This study aimed to evaluate the association between genetic variants in these genes and GC risk in West Bengal, India. METHODS: We enrolled 105 GC patients (cases), and their corresponding sex, age and ethnicity was matched to 108 normal individuals (controls). Genotyping for ADH1A (rs1230025), ADH1B (rs3811802, rs1229982, rs1229984, rs6413413, rs4147536, rs2066702 and rs17033), ADH1C (rs698) and ALDH2 (rs886205, rs968529, rs16941667 and rs671) was performed using DNA sequencing and RFLP. RESULTS: Genotype and allele frequency analysis of these SNPs revealed that G allele of rs17033 is a risk allele (A vs G: OR = 3.67, 95% CI = 1.54-8.75, p = 0.002) for GC. Significant association was also observed between rs671 and incidence of GC (p = 0.003). Moreover, smokers having the Lys allele of rs671 had a 7-fold increased risk of acquiring the disease (OR = 7.58, 95% CI = 1.34-42.78, p = 0.009). CONCLUSION: In conclusion, rs17033 of ADH1B and rs671 of ALDH2 SNPs were associated with GC risk and smoking habit may further modify the effect of rs671. Conversely, rs4147536 of ADH1B might have a protective role in our study population. Additional studies with a larger patient population are needed to confirm our results.

Structural basis to stabilize the domain motion of BARD1-ARD BRCT by CstF50.

BRCA1 associated ring domain protein 1(BARD1) is a tumor suppressor protein having a wide role in cellular processes like cell-cycle checkpoint, DNA damage repair and maintenance of genomic integrity. Germ-line mutation Gln 564 His discovered in linker region of BARD1 leads to loss of binding to Cleavage stimulating factor (CstF50), which in turn instigates the premature mRNA transcript formation and apoptosis. We have studied the dynamics of ARD domain present in the BARD1 wild-type and mutant protein in association with CstF50 using biophysical, biochemical and molecular dynamics simulations. It has been observed that the ARD domain is relatively more flexible than the BRCT domain of BARD1. Further relative orientations of both the ARD and BRCT domains varies due to the highly flexible nature of the connecting linker region present between the domains. It has been observed that mutant ARD domain is more dynamic in nature compared to wild-type protein. Molecular docking studies between BARD1 Gln 564 His mutant and CstF50 shows the loss of interactions. Furthermore, domain motion of ARD present in BARD1 was stabilized when complexed with CstF50.

Characterization and cytotoxic activity of apoptosis-inducing pierisin-5 protein from white cabbage butterfly.

In this study, caspase-dependent apoptosis-inducing pierisin-5 gene was identified and characterized from cabbage white butterfly, Pieris canidia. A thousand-fold increase in expression of pierisin-5 gene was observed from second to third instar larvae, gradually decreasing before pupation. Pierisin-5 was purified from the fifth-instar larvae and was found to exhibit cytotoxicity against HeLa and HepG2 human cancer cell lines. Pierisin-5 showed growth inhibition and several morphological changes such as cell shrinkage, chromatin condensation and apoptotic body formation with programmed cell death in HeLa and HepG2 cells. Moreover, DNA fragmentation was observed after gel electrophoresis analysis. Caspase substrate assay showed further cleavage of Ac-DEVD-pNA, suggesting the activation of Caspase-3. Flow cytometry analysis revealed the cell cycle arrest at G1 phase and increased the percentage of apoptotic cells in cancer cell lines treated with pierisin-5. These findings suggest that pierisin-5 could significantly induce apoptosis in cancer cell lines and is mediated by activation of caspase-3 in the mitochondrial pathway. Phylogenetic analysis using pierisin proteins from Pierid butterflies, ADP-ribosylating toxins from bacteria, human, rat, and mouse indicated the possibility of horizontal transfer of pierisin genes from bacteria to butterflies. The single copy of pierisin gene unlike other insect toxin genes also supports lateral transfer.

Association of DNA repair and xenobiotic pathway gene polymorphisms with genetic susceptibility to gastric cancer patients in West Bengal, India.

Gastric cancer is one of the most common malignancies in India. DNA repair gene or xenobiotic pathway gene polymorphisms have recently been shown to affect individual susceptibility to gastric cancer. Here, the possible interaction between common polymorphisms in X-ray repair cross complementing group I (XRCC1) gene and glutathione S-transferase (GST) genes (GSTM1, GSTT1 and GSTP1), smoking and alcohol consumption and overall survival in gastric cancer patients were evaluated. In this population-based case control study, 70 gastric cancer patients and 82 healthy controls were enrolled. The epidemiological data were collected by a standard questionnaire, and blood samples were collected from each individual. XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms were determined by polymerase chain reaction and direct DNA sequencing. GSTM1 and GSTT1 null polymorphisms and GSTP1 Ile105Val polymorphism were identified by multiplex polymerase chain reaction and restriction fragment length polymorphism (RFLP), respectively. The risk of gastric cancer was significantly elevated in individuals with XRCC1 Arg/Gln +Gln/Gln (p = 0.031; odds ratio = 2.32; 95 % confidence interval (CI) 1.07-5.06) and GSTP1 Val/Val genotype (p = 0.009; odds ratio = 8.64; 95 % CI 1.84-40.55). An elevated risk for GC was observed in smokers and alcohol consumers carrying GSTP1 Ile/Val +Val/Val genotype (p = 0.041; odds ratio = 3.71; 95 % CI 0.98-14.12; p = 0.002; odds ratio = 12.31; 95 % CI 1.71-88.59). These findings suggest that XRCC1 rs25487 and GSTP1 rs1695 can be considered as a risk factor associated with gastric cancer and might be used as a molecular marker for evaluating the susceptibility of the disease.

The complete mitochondrial genome of the Indian honey bee, Apis cerena cerana (Hymenoptera: Apidae: Apinae).

The complete mitogenome of Apis cerana cerana (Hymenoptera: Apidae: Apinae) was sequenced using Illumina NextSeq500 platform and found to be 15 831 bp long. The mitogenome contains 37 genes (13 PCGs, 22 tRNAs, and 2 rRNAs) and a control region. The base composition is biased towards A-T (83.9%). The control region is 498 bp long with polyT stretch and poly [TA (A)]n-like stretch. The phylogenetic tree constructed using concatenated PCGs showed that A. cerana cerana clustered with other cavity nesting Apis species.

The near complete mitochondrial genome of the Giant honey bee, Apis dorsata (Hymenoptera: Apidae: Apinae) and its phylogenetic status.

In this report, we sequenced and characterized the near complete mitochondrial genome of Apis dorsata collected from Mizoram, India. For sequencing of the complete mitochondrial genome, Illumina NextSeq500 platform was used. The near complete mitochondrial genome was assembled to be 15 076 bplong and contains the same gene order as the other honey bees. The assembly contains 13 protein coding genes, 21 transfer RNA, 2 ribosomal RNA and a partial control (A + T-rich) region estimated to be 75 bp. This is the first near complete sequenced mitochondrial genome from the giant honeybee A. dorsata which will benefit future genomics studies for understanding the phylogenetic relationship within the bee family.

Illumina based whole mitochondrial genome of Junonia iphita reveals minor intraspecific variation.

In the present study, the near complete mitochondrial genome (mitogenome) of Junonia iphita (Lepidoptera: Nymphalidae: Nymphalinae) was determined to be 14,892 bp. The gene order and orientation are identical to those in other butterfly species. The phylogenetic tree constructed from the whole mitogenomes using the 13 protein coding genes (PCGs) defines the genetic relatedness of the two J. iphita species collected from two different regions. All the Junonia species clustered together, and were further subdivided into clade one consisting of J. almana and J. orithya and clade two comprising of the two J. iphita which were collected from Indo and Indochinese subregions separated by river barrier. Comparison between the two J. iphita sequences revealed minor variations and Single Nucleotide Polymorphisms were identified at 51 sites amounting to 0.4% of the entire mitochondrial genome.

A three year study on distribution and ecology of Anophelines in Thenzawl, Mizoram, India.

A systematic survey on Anopheline species abundance, bionomics and habitat preference was conducted for three years in Thenzawl, Mizoram. A scoop-net method was employed for larval collection and a local made killing-jar for adults. A total of 10 species Anopheles campestris (25.8%), An. nivipes (24.0%), An. vagus (20.6%), An. jamesii (15.1%), An. jeyporiensis (11.4%), An. maculatus (1.7%), An. philippinensis (0.7%), An. annularis (0.26%), An. sinensis (0.23%) and An. peditaeniatus (0.22%) were collected. The survey site having thick tall grasses, numerous rural-huts as residents, small to relatively larger ponds and very slow running water bodies well shaded from sunlight with floating aquatic plants provided the largest area for Anopheles larvae breeding and accounted for 40% of all Anopheles larva and 25.4% total Anopheles spp. collected. An. campestris (NSK01), maculatus (NSK04), philippinensis (NSK06), nivipes (NSK10) and jeyporiensis (NSK09) were strongly anthropogenic and endophagic while vagus (NSK18) and jamesii (NSK03) were found to be highly zoophilic and exophilic and An. peditaeniatus (NSK02), annularis (NSK07) and sinensis (NSK15) were found to be highly zoophilic. Because of its abundance and bionomics, An. campestris, jeyporiensis and nivipes may have played a role in malarial transmission throughout the year. This is the first study reported on Anopheline distribution and abundance in Thenzawl, Mizoram.

A simple method of genomic DNA extraction from human samples for PCR-RFLP analysis.

Isolation of DNA from blood and buccal swabs in adequate quantities is an integral part of forensic research and analysis. The present study was performed to determine the quality and the quantity of DNA extracted from four commonly available samples and to estimate the time duration of the ensuing PCR amplification. Here, we demonstrate that hair and urine samples can also become an alternate source for reliably obtaining a small quantity of PCR-ready DNA. We developed a rapid, cost-effective, and noninvasive method of sample collection and simple DNA extraction from buccal swabs, urine, and hair using the phenol-chloroform method. Buccal samples were subjected to DNA extraction, immediately or after refrigeration (4-6°C) for 3 days. The purity and the concentration of the extracted DNA were determined spectrophotometerically, and the adequacy of DNA extracts for the PCR-based assay was assessed by amplifying a 1030-bp region of the mitochondrial D-loop. Although DNA from all the samples was suitable for PCR, the blood and hair samples provided a good quality DNA for restriction analysis of the PCR product compared with the buccal swab and urine samples. In the present study, hair samples proved to be a good source of genomic DNA for PCR-based methods. Hence, DNA of hair samples can also be used for the genomic disorder analysis in addition to the forensic analysis as a result of the ease of sample collection in a noninvasive manner, lower sample volume requirements, and good storage capability.

Characterization of Bacillus thuringiensis Cry1 class proteins in relation to their insecticidal action.

Thirty nine Bt Cry1 subgroup protein sequences were retrieved from NCBI and analyzed for physicochemical properties, active site and relationship in relation to their variations in toxicity. Cry1 proteins were found to be hydrophilic and stable. SOSUI server predicted presence of two transmembrane regions in Ag and a single transmembrane region from Aa to Ae. EMBOSS PepWheel tool analysis of the transmembrane regions showed that there were 23 highly conserved residues towards the N terminal which are hydrophobic and more than half of the residues were neutrally charged. No signal peptide was detected which classifies the Cry1 group proteins as non-secretory proteins. Cry1 proteins have very high composition of neutral amino acids and might transform into negative charge after solubilization in alkaline environment (insect midgut). The negatively charged protein might misfold causing difficultly to digest and thereby be toxic to lepidopteran. Active sites of Cry1 proteins with more than 50% neutral amino acids showed wide insecticidal spectrum and further positive correlation (r = 0.7731) was observed between neutral amino acids and insect species affected (Y = -138.21 + 2.907X). Similarity of sequences was found between Cry1 proteins based on their high or low spectrum of insecticidal activity.

Analysis of aminoacids pattern in receptor tyrosine kinase using Boolean association rule.

Cancers are characterized by unrestricted cell division and independency of growth factor and other external signal responsiveness. Eukaryotic parental cells of tumors, on the other hand, constitute tissues and other higher structures like organs and systems and are capable of performing various functions in a highly co-ordinated fashion. Hence, cancer cells may be considered as entities capable of incessant growth and cell division but lacking any evolutionarily advanced intracellular or intercellular regulation. Since receptor tyrosine kinases are highly altered and exist in deregulated/constitutively active forms in cancer cells - achieved through various epigenetic mechanisms - we hypothesize the functional RTKs in cancer cells to resemble their counterparts in more primitive species. Analysis of RTK sequences of various species and of cancer is, therefore, expected to prove this hypothesis. Association rule in data mining can reveal the hidden biological information. This study utilizes the Boolean association rule to mine the occurrence pattern of glycine, arginine and alanine in receptor tyrosine kinases (RTKs) of invertebrates, vertebrates and cancer related vertebrate RTKs based on protein sequence informations. The results reveal that vertebrate cancer RTKs resembles prokaryotes and invertebrate RTKs showing an increasing trend of glycine, alanine and decreasing trend in arginine composition. The aminoacid compositions of vertebrates: invertebrates: prokaryotes: vertebrate cancer with respect to Glycine (>=6.1) were 42.86: 50.0: 85.71: 100%, Alanine (>=6.2) were 10.72: 66.67: 85.71: 100%, whereas Arginine (>=5.9) were 21.43: 16.67: 14.29: 0%, respectively. In conclusion, results from this study supports our hypothesis that cancer cells may resemble lower organisms since functionally cancer cells are unresponsive to external signals and various regulatory mechanisms typically found in higher eukaryotes are largely absent.

Insecticidal and repellent activity of Hiptage benghalensis L. Kruz (Malpighiaceae) against mosquito vectors.

Plant-based insecticides for vector control are urgently needed for Anopheles barbirostris, Culex quinquefasciatus, and Aedes albopictus which are the primary vectors of malaria, lymphatic filariasis, and dengue, respectively, in India and other South East Asian countries. In the present study, larvicidal, adulticidal, and repellent activities of acetone root bark extract of Hiptage benghalensis were tested against the larvae and adults of the three mosquito vectors. The acetone root bark extracts of H. benghalensis was more effective as larvicides with low LC(50) (11.15-16.78 ppm) and LT50 (1.25-4.84 h at 200 and 400 ppm) values. Results of log probit analysis (at 95 % confidence level) and regression analysis of crude acetone root bark extract of H. benghalensis revealed that lethal concentration (LC(50)) values gradually decreased with the exposure periods; lethal time (LT(50)) decreased with the concentration, and the mortality is positively correlated with the concentration. The order of susceptibility of the three mosquito species was as follows: A. albopictus > A. barbirostris > C. quinquefascitus. Biochemical changes were also evidenced in third instar larvae of three mosquito species following a sublethal exposure for 24 h. The level of sugar, glycogen, lipids, and proteins was significantly (P < 0.05) reduced in larvae treated with H. benghalensis. The acetone root bark extracts of H. benghalensis is less toxic to adults and repelled laboratory-reared female A. barbirostris, A. albopictus, and C. quinquefascitus with the short median protection times of 57.66-135, 72.41-134.16, and 47.66-93 min, respectively. The present investigation proves it as a potent larvicide against A. albopictus, A. barbirostris, and C. quinquefascitus, which can be recommended to control these mosquito species on its breeding site. However, further investigations are needed to confirm the lethal effects of H. benghalensis in field conditions and its impact on the nontarget organisms.