Mitochondrial haplogroup N1a phylogeography,with implication to the origin of European farmers

Background  

Tracing the genetic origin of central European farmer N1a lineages can provide a unique opportunity to assess the patterns of the farming technology spread into central Europe in the human prehistory. Here, we have chosen twelve N1a samples from modern populations which are most similar with the farmer N1a types and performed the complete mitochondrial DNA genome sequencing analysis. To assess the genetic and phylogeographic relationship, we performed a detailed survey of modern published N1a types from Eurasian and African populations.     

From obesity to cancer: a review on proposed mechanisms

Nowadays, obesity is considered as a serious and growing global health problem. It is documented that the overweight and obesity are major risk factors for a series of noncommunicable diseases, and in recent years, the obesity‐cancer link has received much attention. Numerous epidemiological studies have shown that obesity is associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment. We review here the epidemiological and experimental evidences for the association between obesity and cancer. Specifically, we discuss potential mechanisms focusing how dysfunctional angiogenesis, chronic inflammation, interaction of proinflammatory cytokines, endocrine hormones, and adipokines including leptin, adiponectin insulin, growth factors, estrogen, and progesterone and strikingly, cell metabolism alteration in obesity participate in tumor development and progression, resistance to chemotherapy, and targeted therapies such as antiangiogenic and immune therapies.     

Deciphering the Dynamical Origin of Mixed Population during Neural Stem Cell Development

Neural stem cells (NSCs) often give rise to a mixed population of cells during differentiation. However, the dynamical origin of these mixed states is poorly understood. In this article, our mathematical modeling study demonstrates that the bone morphogenetic protein 2 (BMP2) mediated disparate differentiation dynamics of NSCs in central and peripheral nervous systems essentially function through two distinct bistable switches that are mutually interconnected via a mushroom-like bifurcation. Stochastic simulations of the model reveal that the mixed population originates due to the existence of these bistable switching regulations and that the maintenance of such mixed states depends on the level of stochastic fluctuations of the system. It further demonstrates that due to extrinsic variability, cells in an NSC population can dynamically transit from mushroom to a unique isola kind of bifurcation state, which essentially extends the range of the BMP2-driven mixed population state during differentiation. Importantly, the model predicts that by individually altering the expression level of key regulatory proteins, the NSCs can be converted entirely to a preferred phenotype for BMP2 doses that previously resulted in a mixed population. Our findings show that efficient neuronal regeneration can be achieved by systematically maneuvering the differentiation dynamics.     

The importance of leaf surface wax as short-range attractant and oviposition stimulant in a generalist Lepidoptera

Green gram, Vigna radiata (L.) Wilczek, is an important pulse crop of Asia. Severe attack by the larvae of Spilosoma obliqua Walker (Lepidoptera: Arctiidae) causes defoliation of green gram and reduces seed yield. Females lay eggs on the leaf surface, and therefore, surface wax plays an important role as short-range attractant and oviposition stimulant. So, we have attempted to find out whether leaf surface wax compounds (alkanes and free fatty acids) from three green gram cultivars (PDM 54, PUSA BAISAKHI and SAMRAT) could act as short-range attractant and oviposition stimulant in females. The TLC, GC-MS and GC-FID analyses of n-hexane extracts revealed 20 n-alkanes from n-C₁₅ to n-C₃₆ and 13 free fatty acids from C12:0 to C21:0, whilst linoleic acid was unique in SAMRAT. Pentacosane was the predominant amongst n-alkanes in the leaf surface waxes of three cultivars. Heneicosanoic acid and palmitoleic acid were the predominant free fatty acids in the leaf surface waxes of PDM 54, and PUSA BAISAKHI and SAMRAT, respectively. Females were attracted towards one leaf equivalent surface wax of three green gram cultivars against solvent controls (n-hexane) in Y-tube olfactometer bioassays. A synthetic blend of pentacosane, heptacosane, nonacosane, hexatriacontane, palmitoleic acid, linolenic acid and stearic acid, a synthetic blend of pentacosane, hexatriacontane and stearic acid, and a synthetic blend of hexatriacontane, linolenic acid and stearic acid resembling in amounts present in one leaf equivalent surface wax of PDM 54, PUSA BAISAKHI and SAMRAT, respectively, served as short-range attractant and oviposition stimulant in females. Females showed equal preference for egg laying towards the above three synthetic blends when these blends were tested against each other, and hence, these blends could be employed in development of baited traps in pest management strategies.     

A375 melanoma cells are sensitized to cisplatin-induced toxicity by a synthetic nitro-flavone derivative 2-(4-Nitrophenyl)-4H-chromen-4-one through inhibition of PARP1

Background

Cisplatin has been extensively used in therapeutics for its broad-spectrum anticancer activity and frequently used for the treatment of solid tumors. However, it presents several side-effects and several cancers develop resistance. Combination therapy of cisplatin with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors has been effective in increasing its efficacy at lower doses.

Methods and results

In this work, we have shown that the nitro-flavone derivative, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), can improve the sensitivity of cancer cells to cisplatin through inhibition of PARP1. The effect of 4NCO on cisplatin toxicity was studied through combination therapy in both exponential and density inhibited A375 melanoma cells. Combination index (CI) was determined from isobologram analysis. The mechanism of cell killing was assessed by lactate dehydrogenase (LDH) assay. Temporal nicotinamide adenine dinucleotide (NAD⁺) assay was done to show the inhibition of PARP1. We also performed in silico molecular modeling studies to know the binding mode of 4NCO to a modeled PARP1-DNA complex containing cisplatin-crosslinked adduct. The results from both in silico and in cellulo studies confirmed that PARP1 inhibition by 4NCO was most effective in sensitizing A375 melanoma cells to cisplatin. Isobologram analysis revealed that 4NCO reduced cell viability both in exponential and density inhibited A375 cells synergistically. The combination led to cell death through apoptosis.

Conclusion

The synthetic nitro-flavone derivative 4NCO effectively inhibited the important nuclear DNA repair enzyme PARP1 and therefore, could complement the DNA-damaging anticancer drug cisplatin in A375 cells and thus, could act as a potential adjuvant to cisplatin in melanoma therapy.

     

Identification of Novel Allelic Variants of Integrin Beta 2 (ITGB2) Gene and Screening for Bubaline Leukocyte Adhesion Deficiency Syndrome in Indian Water Buffaloes (Bubalus bubalis)

A fragment of 570 bp corresponding to exon 5 and 6 of integrin beta 2 (ITGB2) gene was amplified for screening D128G mutation in one hundred and fifty two buffaloes (Bubalus bubalis) which causes bovine leukocyte adhesion deficiency syndrome (BLAD) in cattle, as well as to ascertain polymorphism. TaqI PCR-RFLP revealed no such mutation thus indicating the absence of bubaline leukocyte adhesion deficiency (BuLAD) allele in animals under study. However, the polymorphism studies using MspI restriction enzyme revealed two genotypic patterns viz. AA pattern (bands of 293, 141, 105, and 31 bp) and BB pattern (bands of 293, 105, 77, 64, and 31 bp). The sequences of A and B alleles were submitted to the GenBank (EU853307 and AY821799).