The binding of progesterone in different parts of the rabbit uterus during implantation

Progesterone receptors, both nuclear and cytosolic, were determined in the embryonic and inter-embryonic segments of the rabbit uterus at 6, 7 and 8 daypost-coitum. At day6 postcoitum a higher concentration of nuclear receptor in the embryonic segment was observed compared with that in the inter-embryonic segment. A reverse situation was observed in the case of cytoplasmic receptors. On the 7th daypost-coitum, no significant alteration in the concentration of either kind of the receptors was observed. However, on day 8, a higher concentration of both nuclear and cytosolic receptors at the embryonic site was observed compared to that in inter-embryonic segment. Since receptors are influenced only in the immediate vicinity of the blastocyst, it can be suggested that the blastocyst plays a role in the induction of its own implantation. Further, at day 8 increase in receptor concentration at the embryonic site may be related to the presence of decidual tissue at this site. CDRI Communication no. 2741.     

Assessment of epigenetic alterations and in silico analysis of mutation affecting PTEN expression among Indian cervical cancer patients

Genetic and epigenetic anomalies accountable for genetic dysregulation are the most common aberrations that determine the underlying heterogeneity of the tumor cells. Currently, phosphatase and tensin homolog (PTEN) incongruity has emerged as potent and persuasive malfunctioning in varied human malignancies. In this study, we have analysed the promoter hypermethylation and expression status of PTEN. We identified different mutations in the exonic region of PTEN. Functional consequences of these mutations were explored using in silico techniques. Promoter hypermethylation of PTEN was detected using methylation-specific polymerase chain reaction (MS-PCR), expression analysis was performed with immunohistochemistry (IHC) and mutation by direct sequencing in a total of 168 uterine cervix tumor cases. The findings were statistically correlated with the clinical parameters. In addition, the effect of nonsynonymous mutations was studied with molecular dynamics simulations. PTEN promoter hypermethylation (45.8%) was found to be significantly associated with the of PTEN loss (57.14%, P < 0.0001). Tumor stages, tumor size, lymph node (LN) were found to be significantly correlated with both PTEN promoter hypermethylation and PTEN loss. Histological grade, however, showed a significant association with only PTEN loss. In total, 11.76% of tumors exhibited mutations in exon 5 and 7, out of which E150K of exon 5 showed the highest deviations in the crystal structure of PTEN by in silico analysis. This study provides valuable insights into oncology and paves the path in the development of efficient biomarker and/or imperative therapeutic tool for cervical cancer treatment.     

Correction to: Opportunistic spongivore fishes in a reef of Gulf of Mannar,India

Environmental Biology of Fishes -     

Effect of APOE and a polygenic risk score on incident dementia and cognitive decline in a healthy older population

Few studies have measured the effect of genetic factors on dementia and cognitive decline in healthy older individuals followed prospectively. We studied cumulative incidence of dementia and cognitive decline, stratified by APOE genotypes and polygenic risk score (PRS) tertiles, in 12,978 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrolment, participants had no history of diagnosed dementia, cardiovascular disease, physical disability or cognitive impairment. Dementia (adjudicated trial endpoint) and cognitive decline, defined as a >1.5 standard deviation decline in test score for either global cognition, episodic memory, language/executive function or psychomotor speed, versus baseline scores. Cumulative incidence for all‐cause dementia and cognitive decline was calculated with mortality as a competing event, stratified by APOE genotypes and tertiles of a PRS based on 23 common non‐APOE variants. During a median 4.5 years of follow‐up, 324 participants developed dementia, 503 died. Cumulative incidence of dementia to age 85 years was 7.4% in all participants, 12.6% in APOE ε3/ε4 and 26.6% in ε4/ε4. APOE ε4 heterozygosity/homozygosity was associated with a 2.5/6.3‐fold increased dementia risk and 1.4/1.8‐fold cognitive decline risk, versus ε3/ε3 (p < 0.001 for both). High PRS tertile was associated with a 1.4‐fold dementia risk versus low (CI 1.04–1.76, p = 0.02), but was not associated with cognitive decline (CI 0.96–1.22, p = 0.18). Incidence of dementia among healthy older individuals is low across all genotypes; however, APOE ε4 and high PRS increase relative risk. APOE ε4 is associated with cognitive decline, but PRS is not.     

Development of a sequence-tagged site (STS) marker for sex identification in the dioecious rattan species Calamus guruba Buch.-Ham.

Molecular Breeding - With the decrease of cost in genotyping, single nucleotide polymorphisms (SNPs) have gained wide acceptance because of their abundance, even distribution throughout the maize...     

Cloning, expression, and characterization of an aldehyde dehydrogenase from Escherichia coli K-12 that utilizes 3-Hydroxypropionaldehyde as a substrate

For efficient production of isoflavone aglycones from soybean isoflavones, we isolated three novel types of β-glucosidase (BGL1, BGL3, and BGL5) from the filamentous fungi Aspergillus oryzae. Three enzymes were independently displayed on the cell surface of a yeast Saccharomyces cerevisiae as a fusion protein with α-agglutinin. Three β-glucosidase-displaying yeast strains hydrolyzed isoflavone glycosides efficiently but exhibited different substrate specificities. Among these β-glucosidases, BGL1 exhibited the highest activity and also broad substrate specificity to isoflavone glycosides. Although glucose released from isoflavone glycosides are generally known to inhibit β-glucosidase, the residual ratio of isoflavone glycosides in the reaction mixture with BGL1-displaying yeast strain (Sc-BGL1) reached approximately 6.2%, and the glucose concentration in the reaction mixture was maintained at lower level. This result indicated that Sc-BGL1 assimilated the glucose before they inhibited the hydrolysis reaction, and efficient production of isoflavone aglycones was achieved by engineered yeast cells displaying β-glucosidase.     

Identification of potential drug target in malarial disease using molecular docking analysis

Malaria caused by genus Plasmodium, is a parasite which is the main health issue for humans and about half of the population were suffered. An every year, approximately 1.2–2.7 million people died due to malaria globally. Therefore to prevent the spreading of malaria from the glob novel active drugs with specific activities are necessary. The present study aimed to identify novel drug molecule together with the bioinformatic tools for the development of active malarial drugs. As the search for latest anti malarial compound was developed, this work determined six active blends from various drug databases which possess drug-like characteristics and presents a significant anti malarial actions in in-silico level. Compound ID 300238, 889, 76569, 87324, 45678, and Z185397112are a few of the ligands were got from the Toss lab, Maybridge, Cambridge, Life chem, Bitter, and Examine drug databases and docked against hexokinase 1 protein (PDB: 1CZA) with high throughput practical screening (HTVS) using Glide v6.6. Amid the 6 compounds, compound no: 300238 from Toss lab has the greatest docking score of −9.889 kcal/mol targeting 1CZA protein. The active sites of Hexokinase I of protein were determine by using superimposition of the destination and template structure showed similar structural folds and active sites which were decidedly conserved. The quality of hexokinase I protein was considered to be sterically stable where the protein was prepared by utilizing the software protein preparation execute in the Schrodinger suite. Prepared proteins were evaluated using SAVES and the studies of molecular dynamics of the hexokinase, and the GROMACS were performed for protein–ligand complex. The low HOMO-LUMO energy gaps of the compound verified the greater stability of the molecule. Here, the tested drug candidates have good absorption, distribution, metabolism, and excretion (ADME) properties which were established by using QikProp, version 3.4 of Schrodinger.