Molecular dynamics simulations assisted investigation of phytochemicals as potential lead candidates against anti-apoptotic Bcl-B protein.

Due to the multifarious nature of cancer, finding a single definitive cure for this dreadful disease remains an elusive challenge. The dysregulation of the apoptotic pathway or programmed cell death, governed by the Bcl-2 family of proteins plays a crucial role in cancer development and progression. Bcl-B stands out as a unique anti-apoptotic protein from the Bcl-2 family that selectively binds to Bax which inhibits its pro-apoptotic function. Although several inhibitors are reported for Bcl-2 family proteins, no specific inhibitors are available against the anti-apoptotic Bcl-B protein. This study aims to address this research gap by using virtual screening of an in-house library of phytochemicals from seven anti-cancer medicinal plants to identify lead molecules against Bcl-B protein. Through pharmacokinetic analysis and molecular docking studies, we identified three lead candidates (Enterolactone, Piperine, and Protopine) based on appreciable drug-likeliness, ADME properties, and binding affinity values. The identified molecules also exhibited specific interactions with critical amino acid residues of the binding cleft, highlighting their potential as lead candidates. Finally, molecular dynamics simulations and MM/PBSA based binding free energy analysis revealed that Enterolactone (CID_114739) and Piperine (CID_638024) molecules were on par with Obatoclax (CID_11404337), which is a known inhibitor of the Bcl-2 family proteins.Communicated by Ramaswamy H. Sarma.

Presence of SARS-CoV-2-like coronaviruses in bats from east coast Malaysia.

Most of the public health importance coronaviruses, such as Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2 are likely originated from bats and spread to humans through intermediate hosts; civet cats, dromedary camel and Malayan pangolin, respectively. SARS-CoV-2-like coronaviruses were detected in Thailand, which is neighbouring with Kelantan in East Coast Malaysia. To date, there is no report on the presence of public health concerns (SARS-CoV, SARS-CoV-2 and MERS-CoV) coronaviruses in bats from Malaysia. This study was aimed to elucidate the presence of these coronaviruses in bat samples from East Coast, Malaysia. A total of hundred seventy oropharyngeal swab samples were collected from three states of East Coast Malaysia. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was conducted based on partial 3' Untranslated region (3'UTR) or ORF10 gene and the products were sequenced. The sequences were compared with all coronavirus sequences from the National Center for Biotechnology Information-GenBank (NCBI-GenBank) using NCBI-Basic Local Alignment Search Tool (NCBI-BLAST) software. A phylogenetic tree was constructed to determine the genetic relationship among the detected coronaviruses with the reference coronaviruses from the NCBI-GenBank. Our results showed that SARSCoV-2-like viruses were present in 3% (5/170) of the bats from East Coast Malaysia that have 98-99% sequence identities and are genetically related to SARS-CoV-2 from humans. This finding indicates the presence of SARS-CoV-2-like viruses in bats from East Coast Malaysia that may become a public health concern in the future.

Presence of SARS-CoV-2-like coronaviruses in bats from east coast Malaysia

@#Most of the public health importance coronaviruses, such as Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2 are likely originated from bats and spread to humans through intermediate hosts; civet cats, dromedary camel and Malayan pangolin, respectively. SARS-CoV-2-like coronaviruses were detected in Thailand, which is neighbouring with Kelantan in East Coast Malaysia. To date, there is no report on the presence of public health concerns (SARS-CoV, SARS-CoV-2 and MERS-CoV) coronaviruses in bats from Malaysia. This study was aimed to elucidate the presence of these coronaviruses in bat samples from East Coast, Malaysia. A total of hundred seventy oropharyngeal swab samples were collected from three states of East Coast Malaysia. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was conducted based on partial 3’ Untranslated region (3’UTR) or ORF10 gene and the products were sequenced. The sequences were compared with all coronavirus sequences from the National Center for Biotechnology Information-GenBank (NCBI-GenBank) using NCBI-Basic Local Alignment Search Tool (NCBI-BLAST) software. A phylogenetic tree was constructed to determine the genetic relationship among the detected coronaviruses with the reference coronaviruses from the NCBI-GenBank. Our results showed that SARSCoV-2-like viruses were present in 3% (5/170) of the bats from East Coast Malaysia that have 98-99% sequence identities and are genetically related to SARS-CoV-2 from humans. This finding indicates the presence of SARS-CoV-2-like viruses in bats from East Coast Malaysia that may become a public health concern in the future.

Epidemiology of Intussusception Hospitalizations in Children Under 2 Years of Age Post Rotavirus Vaccine Introduction in Tamil Nadu and Puducherry, India.

OBJECTIVE: High burden of rotavirus associated diarrhea has been documented among Indian children. The phased introduction of an indigenous rotavirus vaccine 'ROTAVAC' in India's national immunization programme began in 2017. Phase-III trial showed the vaccine to have a low-intussusception-risk profile. However, evaluation of post-licensure trends of intussusception is necessary to assess potential vaccine-associated intussusception risk. This study's objective was to describe the epidemiology of intussusception hospitalizations in children under two years of age in Tamil Nadu and Puducherry following ROTAVAC introduction. METHODS: A cross-sectional surveillance was established in six hospitals in Tamil Nadu and Puducherry. Children under two years of age with intussusception fulfilling Brighton Collaboration's criteria for level 1 diagnostic certainty were enrolled. Patient and disease characteristics were captured using a standardized questionnaire. Descriptive and inferential statistical analyses were performed using Stata Version 13. RESULTS: Overall, 287 cases were enrolled and had a median age of seven months. Frequently presenting symptoms were vomiting (78%), abdominal pain (76%), and blood in stool (71%). Abdominal ultrasonography or radiography confirmed diagnosis in 65% of cases and managed by nonoperative measures. Remaining 35% of cases were diagnosed and managed with surgery. Over 98% of the cases had positive treatment outcomes. Age less than five months (OR = 4.36), and hospitalization at a state government health facility (OR = 5.01) were significant predictors for children to receive surgical management. CONCLUSIONS: The present study documents the epidemiology of intussusceptions immediately after the rollout of rotavirus vaccine in Tamil Nadu and Puducherry. No appreciable increase in intussusception hospitalizations was seen in the study hospitals after vaccine introduction.

Inter-cluster distance dependence of electrical conduction in nanocluster assembled films of silver: a new paradigm for design of nanostructures.

The transport properties of films assembled from metal nanoclusters can be significantly different from the metals in their bulk or thin film forms due to quantum confinement effects and several competing energy and length scales. For a film composed of metal nanoclusters as its building blocks, the cluster size and the inter-cluster separation are parameters that can be varied experimentally. Here we show that the electrical conductivity of a film composed of silver nanoclusters can be changed by 9 orders of magnitude as a function of the average inter-cluster separation while keeping the average cluster size same. For inter-cluster separations of 9 nanometres or more the conductivity is insulating type whereas for lesser inter-cluster separations the conductivity behaviour is metallic type with a positive temperature coefficient of resistance. In the intermediate range between the two regions, a very interesting temperature-independent conductivity is seen. Our work provides a new paradigm for design of artificial solid structures composed of nanoclusters. The properties of these nanostructures could be tuned by varying the inter-cluster distances to get the desired properties in the same material.

Transfer factor of the radionuclides in food crops from high-background radiation area of south west India.

It is necessary to obtain the transfer factor (TF) of long-lived radionuclides because soil type and vegetation can affect TF. We studied the food crops commonly consumed by the general public of Kanyakumari district of south India. The main focus was on rice, fruits, vegetables and tapioca because the consumption of these is high. The soil to rice TF for the radionuclides, (226)Ra, (232)Th, (238)U and (40) K are 8.8×10(-2), 14.2×10(-2), 5.8×10(-2) and 6.3×10(-2), respectively. The TF of tapioca for (226)Ra, (232)Th, (238)U and (40) K are 6.2×10(-2) , 11×10(-2), 1.9×10(-2) and 8.9×10(-2), respectively. For fruits and vegetables, the TFs are low. In the majority of the crops the non-edible parts accumulate more radionuclides than the edible parts.

Measurement of activity concentration of natural radionuclides for the assessment of radiological indices.

The concentration of natural radionuclides ((226)Ra, (232)Th and (40)K) in the soil samples were determined for 28 locations in Kanyakumari district of southwest India by means of gamma spectroscopy with NaI (Tl) detector. The mean activity concentrations for (232)Th and (40)K are greater than the world average values reported by United Nations Scientific Committee on Effects of Atomic Radiation for areas of normal background radiation. Radiological indices were estimated for the radiation of the natural radioactivity of all soil samples. Estimated mean total absorbed dose in air from activity concentration of (226)Ra, (232)Th and (40)K in high background radiation areas (HBRAs) is 200 + or - 30 nGy h(-1) and in low background radiation areas (LBRAs) is 29 + or - 14 nGy h(-1). Annual outdoor effective dose was also calculated for HBRA and LBRA. Also the representative level index, which resulted from the natural radionuclides in the soil samples were also estimated and given.

Structure-function study of the extracellular domain of the human type I interferon receptor (IFNAR)-1 subunit.

Despite accumulating information about the different effector molecules and signaling cascades that are invoked on interferon-alpha (IFN-alpha) binding to the type 1 IFN receptor, little is known about the specifics of the binding interactions between the ligand and the receptor complex. The IFN-alpha/beta receptor (IFNAR)-2 subunit of the IFN receptor is considered the primary binding chain of the receptor, yet it is clear that both receptor subunits, IFNAR-1 and IFNAR-2, cooperate in the high-affinity binding of IFN to the receptor complex. Earlier results from our laboratory suggested that an association of IFNAR-1 with membrane Galalpha1-4Gal-containing glycolipids facilitates receptor-mediated signaling. The data implicated amino acid residues in the SD100 domain of IFNAR-1 in the glycosphingolipid (GSL) modification of the type 1 IFN receptor. Interestingly, the human and murine counterparts of IFNAR-1 exhibit remarkable species specificity despite their considerable amino acid sequence identity. Certainly, those amino acid residues that effect GSL modification of IFNAR-1 are conserved between species, yet specific regions of IFNAR-1 that confer species specificity have not been defined. To delineate further the role of the IFNAR-1 SD100A domain in receptor function, a chimeric cDNA was assembled, in which the SD100A domain of the murine IFNAR-1 chain was replaced with the human sequence. This construct was expressed in IFNAR-1-/- mouse embryonic fibroblasts, and stable transfectants were established. Transfectants are fully sensitive to murine IFN-alpha4 treatment with respect to the induction of IFN-stimulated gene factor 3 (ISGF3) and sis-inducing factor (SIF) signal transducer and activator of transcription factor (Stat) complexes, exhibiting comparable levels of Stat activation to those observed in IFNAR-1-/- cells reconstituted with intact MuIFNAR-1. Similar results were obtained with IFN-induced antiviral and growth inhibitory responses. Viewed together, these data suggest that the SD100A domain of IFNAR-1 does not contribute to species-specific IFN binding.