A new species of the genus Cirrhimuraena (Anguilliformes: Ophichthidae) from the Bay of Bengal,India

A new species of the genus Cirrhimuraena (Anguilliformes: Ophichthidae), Cirrhimuraena indica sp. nov., is described based on eight specimens collected from the Paradip (Odisha) and Petuaghat harbours (West Bengal) along the Bay of Bengal. The species is distinct in having the upper jaw fringed with 16–17 cirri before posterior nostril and 4–5 in between the anterior and posterior nostrils on the side; dorsal fin originates above the level of gill opening, predorsal length is 9.3–10.9 in total length; the head is relatively large, the length is 9.3–9.8 in total length; no infraorbital pores are observed between the nostrils; teeth are numerous, small, conical and in bands on each jaw; pores are present before the gill opening 10–11 and before anus 47–48; pectoral-fin length is 2.4–2.8 in head length; predorsal vertebrae are 8–10, pre-anal vertebrae 43–47 and total vertebrae 164–169. In the maximum likelihood tree analysis for COI gene, the new species belongs to the same clade as the other congener of Cirrhimuraena chinensis and is separated from the species morphologically and genetically.     

Targeting RET to induce medullary thyroid cancer cell apoptosis: an antagonistic interplay between PI3K/Akt and p38MAPK/caspase-8 pathways

Mutations in REarranged during Transfection (RET) receptor tyrosine, followed by the oncogenic activation of RET kinase is responsible for the development of medullary thyroid carcinoma (MTC) that responds poorly to conventional chemotherapy. Targeting RET, therefore, might be useful in tailoring surveillance of MTC patients. Here we showed that theaflavins, the bioactive components of black tea, successfully induced apoptosis in human MTC cell line, TT, by inversely modulating two molecular pathways: (i) stalling PI3K/Akt/Bad pathway that resulted in mitochondrial transmembrane potential (MTP) loss, cytochrome-c release and activation of the executioner caspases-9 and -3, and (ii) upholding p38MAPK/caspase-8/caspase-3 pathway via inhibition of Ras/Raf/ERK. Over-expression of either constitutively active myristoylated-Akt-cDNA (Myr-Akt-cDNA) or dominant-negative-caspase-8-cDNA (Dn-caspase-8-cDNA) partially blocked theaflavin-induced apoptosis, while co-transfection of Myr-Akt-cDNA and Dn-caspase-8-cDNA completely eradicated the effect of theaflavins thereby negating the possibility of existence of other pathways. A search for the upstream signaling revealed that theaflavin-induced disruption of lipid raft caused interference in anchorage of RET in lipid raft that in turn stalled phosphorylation of Ras and PI3Kinase. In such anti-survival cellular micro-environment, pro-apoptotic signals were triggered to culminate into programmed death of MTC cell. These findings not only unveil a hitherto unexplained mechanism underlying theaflavin-induced MTC death, but also validate RET as a promising and potential target for MTC therapy.     

Abundant Intracellular IgG in Enterocytes and Endoderm Lacking FcRn

FcRn, a non-classical MHCI molecule, transports IgG from mother to young and regulates the rate of IgG degradation throughout life. Brambell proposed a mechanism that unified these two functions, saying that IgG was pinocytosed nonspecifically by the cell into an FcRn-expressing endosome, where, at low pH, it bound to FcRn and was exocytosed. This theory was immediately challenged by claims that FcRn specificity for ligand could be conferred at the cell surface in neonatal jejunum. Assessing Brambell''s hypothesis we found abundant nonspecifically endocytosed IgG present in the cytoplasm of FcRn^−/− enterocytes. Further, IgG was present in the intercellular clefts and the cores of FcRn^+/+ but not FcRn^−/− jejunum. FcRn specificity for ligand could be determined within the cell.     

Role of alpha-melanocyte stimulating hormone (α-MSH) in modulating the molecular mechanism adopted by melanocytes of Bos indicus under UVR stress

Molecular and Cellular Biochemistry - Ultraviolet radiations (UVR) are responsible for a wide variety of acute and chronic effects on the animal skin. However, the effect of UVR-induced oxidative...     

Investigation on the Fusarium induced stress protein (FISP) in wheat: Immunolocalisation in root cells

Abstract

Fusarium induced-stress-protein (FISP) of ～51 kDa molecular mass was detected in seven day old germinated wheat (Triticum aestivum var Sonalika) seedlings infected with F. oxysporum for a period of seven days. This particular stress protein (FISP) of ～51 kDa was over-expressed in the case of Fusarium infected seedlings compared to the untreated seedlings where the presence of this protein was insignificant. Localisation of this ～51 kDa protein in root tissue by anti-CSAP (Cadmium Stress Associated Protein) antiserum showed a significantly higher number of gold particles in the case of Fusarium infected root tissue compared to the untreated control. A unique type of organised localisation of FISP around the plasma membrane and outer vacuolar membrane suggests its defensive role against Fusarium infection that might be a general stress protein against biotic and abiotic stresses.     

Deregulation of poly(A) polymerase I in Escherichia coli inhibits protein synthesis and leads to cell death

Polyadenylation plays important roles in RNA metabolism in both prokaryotes and eukaryotes. Surprisingly, deregulation of polyadenylation by poly(A) polymerase I (PAP I) in Escherichia coli leads to toxicity and cell death. We show here that mature tRNAs, which are normally not substrates for PAP I in wild-type cells, are rapidly polyadenylated as PAP I levels increase, leading to dramatic reductions in the fraction of aminoacylated tRNAs, cessation of protein synthesis and cell death. The toxicity associated with PAP I is exacerbated by the absence of either RNase T and/or RNase PH, the two major 3′ → 5′ exonucleases involved in the final step of tRNA 3′-end maturation, confirming their role in the regulation of tRNA polyadenylation. Furthermore, our data demonstrate that regulation of PAP I is critical not for preventing the decay of mRNAs, but rather for maintaining normal levels of functional tRNAs and protein synthesis in E. coli, a function for polyadenylation that has not been observed previously in any organism.     

The Relaxin Receptor (RXFP1) Utilizes Hydrophobic Moieties on a Signaling Surface of Its N-terminal Low Density Lipoprotein Class A Module to Mediate Receptor Activation

The peptide hormone relaxin is showing potential as a treatment for acute heart failure. Although it is known that relaxin mediates its actions through the G protein-coupled receptor relaxin family peptide receptor 1 (RXFP1), little is known about the molecular mechanisms by which relaxin binding results in receptor activation. Previous studies have highlighted that the unique N-terminal low density lipoprotein class A (LDLa) module of RXFP1 is essential for receptor activation, and it has been hypothesized that this module is the true “ligand” of the receptor that directs the conformational changes necessary for G protein coupling. In this study, we confirmed that an RXFP1 receptor lacking the LDLa module binds ligand normally but cannot signal through any characterized G protein-coupled receptor signaling pathway. Furthermore, we comprehensively examined the contributions of amino acids in the LDLa module to RXFP1 activity using both gain-of-function and loss-of-function mutational analysis together with NMR structural analysis of recombinant LDLa modules. Gain-of-function studies with an inactive RXFP1 chimera containing the LDLa module of the human LDL receptor (LB2) demonstrated two key N-terminal regions of the module that were able to rescue receptor signaling. Loss-of-function mutations of residues in these regions demonstrated that Leu-7, Tyr-9, and Lys-17 all contributed to the ability of the LDLa module to drive receptor activation, and judicious amino acid substitutions suggested this involves hydrophobic interactions. Our results demonstrate that these key residues contribute to interactions driving the active receptor conformation, providing further evidence of a unique mode of G protein-coupled receptor activation.     

Secondary amines containing one aromatic nitro group: Preparation,nitrosation, sustained nitric oxide release,and the synergistic effects of released nitric oxide and an arginase inhibitor on vascular smooth muscle cell proliferation

Atherosclerosis, a leading cause of death worldwide, is associated with the excessive proliferation of vascular smooth muscle cells. Nitrogen monoxide, more commonly known as nitric oxide, inhibits this uncontrolled proliferation. Herein we report the preparation of two families of nitric oxide donors; beginning with the syntheses of secondary amine precursors, obtained through the reaction between 2 equiv of various monoamines with 2,4 or 2,6-difluoronitrobenzene. The purified secondary amines were nitrosated then subjected to a Griess reagent test to examine the slow and sustained nitric oxide release rate for each compound in both the absence and presence of reduced glutathione. The release rate profiles of these two isomeric families of NO-donors were strongly dependent on the number of side chain methylene units and the relative orientations of the nitro groups with respect to the N-nitroso moieties. The nitrosated compounds were then added to human aortic smooth muscle cell cultures, individually and in tandem with S-2-amino-6-boronic acid (ABH), a potent arginase inhibitor. Cell viability studies indicated a lack of toxicity of the amine precursors, in addition to anti-proliferative effects exhibited by the nitrosated compounds, which were enhanced in the presence of ABH.     

Detecting Dysglycemia Using the 2015 United States Preventive Services Task Force Screening Criteria: A Cohort Analysis of Community Health Center Patients

BackgroundIn 2015, the United States Preventive Services Task Force (USPSTF) recommended targeted screening for prediabetes and diabetes (dysglycemia) in adults who are aged 40 to 70 y old and overweight or obese. Given increasing prevalence of dysglycemia at younger ages and lower body weight, particularly among racial/ethnic minorities, we sought to determine whether the current screening criteria may fail to identify some high-risk population subgroups.ConclusionsTargeted diabetes screening based on new USPSTF criteria may detect approximately half of adult community health center patients with undiagnosed dysglycemia and proportionately fewer racial/ethnic minorities than whites. Future research is needed to estimate the performance of these screening criteria in population-based samples.