Virtual high-throughput screening of natural compounds in-search of potential inhibitors for protection of telomeres 1 (POT1)

Communicated by Ramaswamy H. Sarma     

TGFβ mediated LINC00273 upregulation sponges mir200a-3p and promotes invasion and metastasis by activating ZEB1

Transforming growth factor β (TGFβ) is a prominent cytokine that promotes tumor progression by activating epithelial-to-mesenchymal transition (EMT). This study indicated that TGFβ exerted metastasis by inducing zinc finger E-box binding homeobox 1 (ZEB1) and a long noncoding RNA, LINC00273, expressions in A549 cells. Knocking down LINC00273 diminished TGFβ induced ZEB1 expression as well as metastasis. Mechanistically, LINC00273 acted as a molecular sponge of microRNA (miR)-200a-3p which liberate ZEB1 to perform its prometastatic functions. LINC00273 knockdown and miR200a3p mimic transfection of A549 cells were used for validating the link between TGFβ and LINC00273 induced metastasis. RNA pulldown and luciferase assay were performed to establish mir200a-3p-LINC00273 interaction. High expressions of LINC00273, TGFβ, and ZEB1 with concurrent low miR200a-3p expression had been verified in vivo and in patient samples. Overall, LINC00273 promoted TGFβ-induced lung cancer EMT through miR-200a-3p/ZEB1 feedback loop and may serve as a potential target for therapeutic intervention in lung cancer metastasis.     

A survey of die-back disease of neem in Tamil Nadu,India and PCR-based confirmation of the isolates

A survey of die-back disease of neem was done in different agro climatic regions of Tamil Nadu, India using Global Positioning System (GARMIN 12). Twigs of Azadirachta indica (Neem) infected with die-back were collected from different regions of Tamil Nadu, India and they were further analyzed to determine the pathogen. Phomopsis azadirachtae the causal organism was isolated on malt extract agar from die-back infected neem twigs. They were identified by conventional and molecular methods. Phomopsis genus specific primers (5.8S r-DNA) were then used for the confirmation of P. azadirachtae – the causative agent of die-back of neem by Polymerase chain reaction (PCR). Studies revealed the amplification of expected 141bp DNA in P. azadirachtae isolated from the diseased trees of different regions of Tamil Nadu confirming the causal organism of die-back of neem. Studies revealed a very high incidence of die-back in most of the places of Tamil Nadu. Hand held GPS was used in the study which would help in continuous monitoring of the diseased trees.     

Genetic variants associated with breast cancer risk for Ashkenazi Jewish women with strong family histories but no identifiable BRCA1/2 mutation

The ability to establish genetic risk models is critical for early identification and optimal treatment of breast cancer. For such a model to gain clinical utility, more variants must be identified beyond those discovered in previous genome-wide association studies (GWAS). This is especially true for women at high risk because of family history, but without BRCA1/2 mutations. This study incorporates three datasets in a GWAS analysis of women with Ashkenazi Jewish (AJ) homogeneous ancestry. Two independent discovery cohorts comprised 239 and 238 AJ women with invasive breast cancer or preinvasive ductal carcinoma in situ and strong family histories of breast cancer, but lacking the three BRCA1/2 founder mutations, along with 294 and 230 AJ controls, respectively. An independent, third cohort of 203 AJ cases with familial breast cancer history and 263 healthy controls of AJ women was used for validation. A total of 19 SNPs were identified as associated with familial breast cancer risk in AJ women. Among these SNPs, 13 were identified from a panel of 109 discovery SNPs, including an FGFR2 haplotype. In addition, six previously identified breast cancer GWAS SNPs were confirmed in this population. Seven of the 19 markers were significant in a multivariate predictive model of familial breast cancer in AJ women, three novel SNPs [rs17663555(5q13.2), rs566164(6q21), and rs11075884(16q22.2)], the FGFR2 haplotype, and three previously published SNPs [rs13387042(2q35), rs2046210(ESR1), and rs3112612(TOX3)], yielding moderate predictive power with an area under the curve (AUC) of the ROC (receiver-operator characteristic curve) of 0.74. Population-specific genetic variants in addition to variants shared with populations of European ancestry may improve breast cancer risk prediction among AJ women from high-risk families without founder BRCA1/2 mutations.     

Excited state intramolecular proton transfer in 3-hydroxychromone: a DFT-based computational study

Potential energy (PE) curves for intramolecular proton transfer in the ground (GSIPT) and intramolecular proton transfer in the excited (ESIPT) states of 3-hydroxychromone (3HC) have been studied using DFT-B3LYP/6-31G(d,p) and TD-DFT/6-31G(d,p) level of theory, respectively. Our calculations suggest the non-viability of GSIPT in 3HC. Excited states PE calculations show the existence of ESIPT process in 3HC. ESIPT in 3HC has also been explained in terms of HOMO and LUMO electron densities of the enol and keto tautomers of 3HC.     

Mutations in exons 3 and 7 resulting in truncated expression of human ATP6V1B1 gene showing structural variations contributing to poor substrate binding-causative reason for distal renal tubular acidosis with sensorineural deafness

Distal renal tubular acidosis (dRTA) is an autosomal recessive syndrome results defect in either proximal tubule bicarbonate reabsorption or in distal tubule H⁺ secretion and is characterized by severe hyperchloraemic metabolic acidosis in childhood. dRTA is associated with functional variations in the ATP6V1B1 gene encoding β1 subunit of H⁺-ATPase, key membrane transporters for net acid excretion of α-intercalated cells of medullary collecting ducts. In the present study, a 13-year-old male patient suffering with nephropathy and sensorineural deafness was reported in the Department of Nephrology. We predicted improper functioning of ATP6V1B1 gene could be the reason for diseased condition. Therefore, exons 3, 4, and 7 contributing active site of ATP6V1B1 gene was amplified and sequenced (Accession numbers: KF571726, KM222653). The obtained sequences were BLAST searched against the wild type ATP6V1B1 gene which showed novel mutations c.307 A > G, c.308 C > A, c.310 C > G, c.704 T > C, c.705 G > T, c.709 A > G, c.710 A > G, c.714 G > A, c.716 C > A, c.717delC, c.722 C > G, c.728insG, c.741insT, c.753G > C. These mutations resulted in the expression of truncated protein terminating at Lys 209. The mutated ATP6V1B1structure superimposed with wild type showed extensive variations with RMSD 1.336 Å and could not bind to substrate ADP leading to non-functional ATPase. These results conclusively explain these mutations in ATP6V1B1 gene resulted in structural changes causing accumulation of H⁺ ions contributing to dRTA with sensorineural deafness.     

Epigenetic mechanisms of plant stress responses and adaptation

Epigenetics has become one of the hottest topics of research in plant functional genomics since it appears promising in deciphering and imparting stress-adaptive potential in crops and other plant species. Recently, numerous studies have provided new insights into the epigenetic control of stress adaptation. Epigenetic control of stress-induced phenotypic response of plants involves gene regulation. Growing evidence suggest that methylation of DNA in response to stress leads to the variation in phenotype. Transposon mobility, siRNA-mediated methylation and host methyltransferase activation have been implicated in this process. This review presents the current status of epigenetics of plant stress responses with a view to use this knowledge towards engineering plants for stress tolerance.