Assessment of knowledge about malaria and LLIN ownership and its use in Bankura, West Bengal, India.

BACKGROUND & OBJECTIVES: Community participation is one of the key factors for implementation and success of a public health programme which depends upon knowledge about that disease. Therefore, understanding the community knowledge about malaria is important for designing sustainable control programmes. This study was conducted to assess the knowledge about malaria, to evaluate long lasting insecticidal nets (LLINs) distribution and their use by LQAS method in endemic areas of Bankura district, West Bengal state, India Methods: It was a community based cross-sectional survey conducted in Bankura during December 2019-March 2020. Structured questionnaire under four categories: socio-demographic variables, knowledge of malaria, owner ship of LLINs and its use were used for the interview. Ownership of LLINs and its use were analysed by LQAS method. Data were analysed by binary logistic regression model and chi-squared test. RESULTS: Out of 456 respondents, 88.59% had good knowledge, 97.37% had good ownership of LLIN and 78.95% used LLINs properly. The knowledge about malaria was significantly associated with education level (p-value<0.0001). Out of 24 lots studied, 3, 2, 4 lots were underperforming with respect to knowledge, ownership of LLIN and its use, respectively. INTERPRETATION & CONCLUSION: The study population had a good knowledge about malaria. In spite of good coverage of LLIN distribution, the use of LLINs was not up to the mark. LQAS analysis showed underperformance in few lots about knowledge, ownership of LLIN and its use. The IEC and BCC activities about LLIN should be done to achieve the impact of this intervention at the community level.

Synthesis and Characterization of Andrographolide Derivatives as Regulators of ßAPP Processing in Human Cells.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder, one of the main characteristics of which is the abnormal accumulation of amyloid peptide (Aß) in the brain. Whereas ß-secretase supports Aß formation along the amyloidogenic processing of the ß-amyloid precursor protein (ßAPP), α-secretase counterbalances this pathway by both preventing Aß production and triggering the release of the neuroprotective sAPPα metabolite. Therefore, stimulating α-secretase and/or inhibiting ß-secretase can be considered a promising anti-AD therapeutic track. In this context, we tested andrographolide, a labdane diterpene derived from the plant Andrographis paniculata, as well as 24 synthesized derivatives, for their ability to induce sAPPα production in cultured SH-SY5Y human neuroblastoma cells. Following several rounds of screening, we identified three hits that were subjected to full characterization. Interestingly, andrographolide (8,17-olefinic) and its close derivative 14α-(5',7'-dichloro-8'-quinolyloxy)-3,19-acetonylidene (compound 9) behave as moderate α-secretase activators, while 14α-(2'-methyl-5',7'-dichloro-8'-quinolyloxy)-8,9-olefinic compounds 31 (3,19-acetonylidene) and 37 (3,19-diol), whose two structures are quite similar although distant from that of andrographolide and 9, stand as ß-secretase inhibitors. Importantly, these results were confirmed in human HEK293 cells and these compounds do not trigger toxicity in either cell line. Altogether, these findings may represent an encouraging starting point for the future development of andrographolide-based compounds aimed at both activating α-secretase and inhibiting ß-secretase that could prove useful in our quest for the therapeutic treatment of AD.

Assessment of heavy metal contamination in two edible fish species Carassius carassius and Triplophysa kashmirensis of Dal Lake, Srinagar, Kashmir, India.

The present study was aimed to examine the concentration of heavy metals in the two edible fish species Carassius carassius and Triplophysa kashmirensis of the Dal Lake (Srinagar, Jammu, and Kashmir, India). Metals cadmium (Cd), manganese (Mn), copper (Cu), zinc (Zn), lead (Pb), and chromium (Cr) were analyzed using atomic absorption spectroscopy (AAS). Differences in the heavy metal accumulation were observed between the two species as well as between different sizes of the same species. Small size fishes exhibited more concentration of heavy metals than the larger size fishes of the same species. Heavy metals were found in the ranking order of Zn > Cr > Pb > Cu > Mn > Cd in both species of fishes and in both sizes as well. Zn, being the most concentrated metal found in both species, can pose a threat in the near future. Since both species are edible and constitute an essential part of human diet, the heavy metals assessed can be bioaccumulated in humans when consumed; hence, an extensive investigation is needed to evaluate the heavy metal concentration of other edible fishes of the Dal Lake in the future. The study will also be helpful in providing baseline data on the heavy metal accumulation of edible fish species in freshwater ecosystems.

Erratum: Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activity.

[This corrects the article DOI: 10.1016/j.omtn.2022.11.008.].

MOSR and NDHA Genes Comprising G-Quadruplex as Promising Therapeutic Targets against Mycobacterium tuberculosis: Molecular Recognition by Mitoxantrone Suppresses Replication and Gene Regulation.

Occurrence of non-canonical G-quadruplex (G4) DNA structures in the genome have been recognized as key factors in gene regulation and several other cellular processes. The mosR and ndhA genes involved in pathways of oxidation sensing regulation and ATP generation, respectively, make Mycobacterium tuberculosis (Mtb) bacteria responsible for oxidative stress inside host macrophage cells. Circular Dichroism spectra demonstrate stable hybrid G4 DNA conformations of mosR/ndhA DNA sequences. Real-time binding of mitoxantrone to G4 DNA with an affinity constant ~105-107 M-1, leads to hypochromism with a red shift of ~18 nm, followed by hyperchromism in the absorption spectra. The corresponding fluorescence is quenched with a red shift ~15 nm followed by an increase in intensity. A change in conformation of the G4 DNA accompanies the formation of multiple stoichiometric complexes with a dual binding mode. The external binding of mitoxantrone with a partial stacking with G-quartets and/or groove binding induces significant thermal stabilization, ~20-29 °C in ndhA/mosR G4 DNA. The interaction leads to a two/four-fold downregulation of transcriptomes of mosR/ndhA genes apart from the suppression of DNA replication by Taq polymerase enzyme, establishing the role of mitoxantrone in targeting G4 DNA, as an alternate strategy for effective anti-tuberculosis action in view of deadly multi-drug resistant tuberculosis disease causing bacterial strains t that arise from existing therapeutic treatments.

Green synthesis and characterization of zinc oxide nanoparticles using leaf extract of Thryallis glauca (Cav.) Kuntze and their role as antioxidant and antibacterial.

The present work has reported a green chemistry-based approach for the synthesis of crystalline metal oxide nanoparticle using plant extract to reduce metal ions. It demonstrated the efficient synthesis of Zinc oxide nanoparticles (ZnO NPs) using aqueous leaf extract of Thryallis glauca (Cav.) Kuntze with a focus on minimizing toxic reactants and byproducts. The physicochemical characterizations by standard methods and the mechanism of action were presented. The UV-Vis absorption peak of the annealed ZnO NPs appeared at a 359 nm wavelength. The calculated direct band-gap energy was 3.6 eV. The peak at 567 nm in the visible region in the photoluminescence spectra indicated surface defects from oxygen vacancy, and the vibrational peak also indicated it at 582 cm-1 in Raman spectra. FTIR spectroscopy showed the possible involvement of proteins, aromatic compounds, and alcohols as reducing agents in the reaction. X-ray diffraction analysis revealed that pure crystalline ZnO NPs have structural properties as hexagonal wurtzite below 50 nm size. Antioxidant analysis by DPPH assay illustrated an excellent free radical scavenging activity. The prepared ZnO NPs tested against pathogenic Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis did not show any antibacterial activity. HIGHLIGHTS: Renewable, eco-friendly plant material was used to synthesize Zinc Oxide nanoparticles (NPs). Synthesis of thermally stable, pure crystalline NPs with good optical properties. The synthesized NPs showed excellent free radical scavenging activity. ZnO NPs exhibited antibacterial resistance at the test concentrations.

Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activity.

G-quadruplex is a non-canonical secondary structure identified in the telomeric region and the promoter of many oncogenes. Anthraquinone derivatives, a well-known inducer of telomere disruption in malignant cells and activate the apoptotic pathway. We used biophysical and biochemical studies to confirm the interaction of synthesized anthraquinone derivatives with the human telomeric G-quadruplex sequence. The binding affinity of N-2DEA and N-1DEA are K b = 4.8 × 106 M-1 and K b = 7.6 × 105 M-1, respectively, leading to hypochroism, fluorescence quenching with minor redshift and ellipticity variations indicating ligand binding in the external groove. We found that sodium ions induced stabilization more rather than potassium ions. Molecular docking of complex demonstrates a molecule's exterior binding to a quadruplex. The investigation of ROS activity indicated that the cell initiates mortality in response to the IC50 concentration. Cellular morphology, nuclear condensation, and fragmentation were altered in the treated cell, impairing cellular function. Finally, the transcriptional regulatory study paves the way for drug design as an anti-cancer agent because of the tremendous possibilities of changing substituent groups on anthraquinones to improve efficacy and selectivity for G-quartet DNA. Our research focused on how ligand binding to telomere sequences induces oxidative stress and inhibits the growth of malignant cells.

Molecular rec§ognition of telomere DNA sequence by 2, 6 anthraquinone derivatives leads to thermal stabilization and induces apoptosis in cancer cells.

According to current research, anti-cancer anthraquinones impact telomere disruption and may interact with G-quadruplex DNA that triggers signaling to apoptosis. The present study represents the biophysical investigation of oxidative stress, late apoptosis, and induced senescence among cancer cells after binding laboratory synthesized piperidine-based anthraquinone derivatives, 2, 6- Bis [(3-piperidino)acetamido)]anthracene-9,10-dione (N1P) and 2, 6-Bis [piperidino)propionamido]anthracene-9,10-dione (N2P), with G-quadruplex DNA. We employed biophysical approaches to explore the interaction of synthetic anthraquinone derivatives with quadruplex DNA sequences to influence biological activities in the presence of K+ and Na+ cations. The binding affinity for N2P and N1P are Kb = 5.8 × 106 M-1 and Kb = 1.0 × 106 M-1, respectively, leading to hypo-/hyper-chromism with 5-7 nm red shift and significant fluorescence quenching and changes in ellipticity resulting in external binding of both the ligands to G-quadruplex DNA. Ligand binding induced enhancement of thermostability of G4 DNA is greater in Na+ environment (ΔTm = 34 °C) as compared to that in K+ environment (ΔTm = 21 °C), thereby restricting telomerase binding access to telomeres. Microscopic images of treated cells indicated cellular shape, nuclear condensation, and fragmentation alterations. The findings pave the path for therapeutic research, given the great potential of modifying anthraquinone substituent groups towards improved efficacy, ROS generation, and G-quadruplex DNA selectivity.

On the Observation of Wild Zebrafish (Danio rerio) in India.

Zebrafish is one of the world's most widely used laboratory species, and it is utilized to answer important research questions in disparate fields such as biomedicine, genetics, developmental biology, pharmacology, toxicology, physiology, and evolution. Despite their popularity, very little is known about the biology of zebrafish in their natural habitat. This may, in part, be due to the difficulties associated with undertaking field trips to the remote areas of northern India, Nepal, and Bangladesh, which is the natural distribution range of zebrafish. Here, we present a field report describing a recent trip where we, together with local collaborators, visited several rivers in West Bengal, India, to observe wild zebrafish and their habitat. We present an overview of our observations on the biology of wild zebrafish, and the great variability of the different environments where they were found. We also include data collected on water chemistry parameters at 12 zebrafish sites, and weight data and photos of fish from these sites. We present extensive underwater videos of wild zebrafish and photographs of the sites, including video footage of courtship behavior. We show that the breeding period of wild zebrafish can be extended from the previous record of April-August to April-October. In addition, we provide practical advice for future zebrafish expeditions to this rural and inaccessible area. The goals of this article are to shed some light on the ecology of wild zebrafish, and to facilitate scientists in their future research trips. We hope that by observing zebrafish in the wild, we can increase our understanding of the natural ecology of this important model organism.

Are model organisms representative for climate change research? Testing thermal tolerance in wild and laboratory zebrafish populations.

Model organisms can be useful for studying climate change impacts, but it is unclear whether domestication to laboratory conditions has altered their thermal tolerance and therefore how representative of wild populations they are. Zebrafish in the wild live in fluctuating thermal environments that potentially reach harmful temperatures. In the laboratory, zebrafish have gone through four decades of domestication and adaptation to stable optimal temperatures with few thermal extremes. If maintaining thermal tolerance is costly or if genetic traits promoting laboratory fitness at optimal temperature differ from genetic traits for high thermal tolerance, the thermal tolerance of laboratory zebrafish could be hypothesized to be lower than that of wild zebrafish. Furthermore, very little is known about the thermal environment of wild zebrafish and how close to their thermal limits they live. Here, we compared the acute upper thermal tolerance (critical thermal maxima; CTmax) of wild zebrafish measured on-site in West Bengal, India, to zebrafish at three laboratory acclimation/domestication levels: wild-caught, F1 generation wild-caught and domesticated laboratory AB-WT line. We found that in the wild, CTmax increased with increasing site temperature. Yet at the warmest site, zebrafish lived very close to their thermal limit, suggesting that they may currently encounter lethal temperatures. In the laboratory, acclimation temperature appeared to have a stronger effect on CTmax than it did in the wild. The fish in the wild also had a 0.85-1.01°C lower CTmax compared to all laboratory populations. This difference between laboratory-held and wild populations shows that environmental conditions can affect zebrafish's thermal tolerance. However, there was no difference in CTmax between the laboratory-held populations regardless of the domestication duration. This suggests that thermal tolerance is maintained during domestication and highlights that experiments using domesticated laboratory-reared model species can be appropriate for addressing certain questions on thermal tolerance and global warming impacts.

Application of Computational Techniques to Unravel Structure-Function Relationship and their Role in Therapeutic Development.

Application of computational tools and techniques has emerged as an invincible instrument to unravel the structure-function relationship and offered better mechanistic insights in the designing and development of new drugs along with the treatment regime. The use of in silico tools equipped modern chemist with armamentarium of extensive methods to meticulously comprehend the structural tenacity of receptor-ligand interactions and their dynamics. In silico methods offers a striking property of being less resource intensive and economically viable as compared to experimental evaluation. These techniques have proved their mettle in the designing of potential lead compounds to combat life-threatening diseases such as AIDS, cancer, tuberculosis, malaria, etc. In the present scenario, computer-aided drug designing has ascertained an essential and indispensable gizmo in therapeutic development. This review will present a brief outline of computational methods used at different facets of drug designing and its latest advancements. The aim of this review article is to briefly highlight the methodologies and techniques used in structure-based/ ligand-based drug designing viz., molecular docking, pharmacophore modeling, density functional theory, protein-hydration and molecular dynamics simulation which helps in better understanding of macromolecular events and complexities.

Biased paternal transmission of TRH variant to female Down syndrome probands: possible correlation with low breast cancer frequency.

Thyroid malfunction is more common in individuals with Down syndrome (DS) than in the general population. It has been hypothesized that thyroid may influence cancer risk. Individuals with DS are at greater risk of developing leukemia than the general population, while solid tumors especially breast cancer (BC) are rare. BC patients have higher levels of circulating thyroid-stimulating hormone (TSH) and prolactin (PRL), both regulated by the thyrotropin-releasing hormone (TRH), a hypothalamic tripeptide. This study was aimed at investigating the status of TRH functional polymorphisms in subjects with DS and BC. Unrelated families with DS probands (n=180), individuals with BC (n=99) and ethnically matched controls (n=216) were recruited. Genomic DNA isolated from peripheral blood was subjected to PCR amplification followed by DNA sequence analysis. Data obtained were analyzed by population- and family-based statistical analysis. Among 30 studied sites, only 2 (rs7645772 and rs13097335) were polymorphic. Case-control analysis showed a lack of any significant association with DS, while the rs13097335 GG and GT genotype frequency was significantly different in the BC samples. A paternal-biased transmission of the G allele was observed in female DS probands. It may be concluded that rs13097335 may have a protective role toward the development of BC.

Down Syndrome Related Muscle Hypotonia: Association with COL6A3 Functional SNP rs2270669.

Down syndrome (DS), the principal cause for intellectual disability, is also associated with hormonal, immunological, and gastrointestinal abnormalities. Muscle hypotonia (MH) and congenital heart diseases (CHD) are also frequently observed. Collagen molecules are essential components for maintaining muscle integrity and are formed by the assembly of three chains, alpha 1-3. The type VI collagen is crucial for cardiac as well as skeletal muscles. The COL α1 (VI) and α2 (VI) chains are encoded by genes located at the 21st chromosome and are expected to have higher dosage in individuals with DS. The α 3 (VI) chain is encoded by the COL6A3 located at the chromosome 2. We hypothesized that apart from COL6A1 and COL6A2, COL6A3 may also have some role in the MH of subjects with DS. To find out the relevance of COL6A3 in DS associated MH and CHD, we genotyped two SNPs in COL6A3, rs2270669 and rs2270668, in individuals with DS. Subjects with DS were recruited based on the Diagnostic and Statistical Manual for Mental Disorders-IV and having trisomy of the 21st chromosome. Parents of individuals with DS and ethnically matched controls were enrolled for comparison. Informed written consent was obtained for participation. Peripheral blood was used for isolation of genomic DNA. Target genetic loci were studied by DNA sequence analysis. Data obtained was subjected to population - as well as family-based statistical analysis. rs2270668 was found to be non-polymorphic in the studied population. rs2270669 showed significant association of the "C" allele and "CC" genotype with DS probands having MH (P = 0.02). Computational analysis showed that rs2270669 may induce structural and functional alterations in the COL α3 (VI). Interaction of COLα3 (VI) with different proteins, crucial for muscle integrity, was also noticed by computational methods. This pioneering study on COL6A3 with DS related MH thus indicates that rs2270669 "C" could be considered as a risk factor for DS related MH.