Which Measure of Abdominal Adiposity Best Relates with Body Mass Index Among Older Bengalee Hindus of Kolkata, India? A Comparison of Three Measures

A cross-sectional study of 410 (210 men and 200 women) older (≥55 years) Bengalee Hindus of Kolkata, India, was undertaken to determine which measure of abdominal adiposity best relates with body mass index (BMI), an indicator of overall adiposity. Three measures of abdominal adiposity were studied: waist circumference (WC), waist–hip ratio (WHR), and conicity index (CI). Results revealed that, in both sexes, WC had the strongest partial (age controlled) correlations with BMI (men = 0.56, women = 0.80). Linear regression analyses demonstrated that BMI had the strongest significant impact on WC in both sexes. BMI alone accounted for 28.2 and 61.8% variation in WC in men and women, respectively. This strongest significant impact remained even after controlling for age. In conclusion, this study provides strong evidence that WC can be preferred over WHR and CI in studies dealing with BMI among older Bengalee Hindus. In particular, BMI and WC can be useful in studies dealing with aging and anthropometric characteristics among older Bengalees.     

Identification of highly potent and selective PI3Kδ inhibitors

Selective PI3Kδ inhibitors have recently been hypothesized to be appropriate immunosuppressive agents for the treatment of immunological disorders such as rheumatoid arthritis. However, few reports have highlighted molecules that are highly selective for PI3Kδ over the other PI3K isoforms. In this letter, isoform and kinome selective PI3Kδ inhibitors are presented. The Structural Activity Relationship leading to such molecules is outlined.     

Post‐flowering night respiration and altered sink activity account for high night temperature‐induced grain yield and quality loss in rice (Oryza sativa L.)

High night temperature (HNT) is a major constraint to sustaining global rice production under future climate. Physiological and biochemical mechanisms were elucidated for HNT‐induced grain yield and quality loss in rice. Contrasting rice cultivars (N22, tolerant; Gharib, susceptible; IR64, high yielding with superior grain quality) were tested under control (23°C) and HNT (29°C) using unique field‐based tents from panicle initiation till physiological maturity. HNT affected 1000 grain weight, grain yield, grain chalk and amylose content in Gharib and IR64. HNT increased night respiration (Rn) accounted for higher carbon losses during post‐flowering phase. Gharib and IR64 recorded 16 and 9% yield reduction with a 63 and 35% increase in average post‐flowering Rn under HNT, respectively. HNT altered sugar accumulation in the rachis and spikelets across the cultivars with Gharib and IR64 recording higher sugar accumulation in the rachis. HNT reduced panicle starch content in Gharib (22%) and IR64 (11%) at physiological maturity, but not in the tolerant N22. At the enzymatic level, HNT reduced sink strength with lower cell wall invertase and sucrose synthase activity in Gharib and IR64, which affected starch accumulation in the developing grain, thereby reducing grain weight and quality. Interestingly, N22 recorded lower Rn‐mediated carbon losses and minimum impact on sink strength under HNT. Mechanistic responses identified will facilitate crop models to precisely estimate HNT‐induced damage under future warming scenarios.     

Differential desensitization and internalization of three different bullfrog gonadotropin-releasing hormone receptors

We previously demonstrated the presence of three distinct types of the gonadotropin-releasing hormone receptor (GnRHR) in a bullfrog (denoted bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3). The bfGnRHRs exhibited differential tissue distribution and ligand selectivity. In the present study, we demonstrated the desensitization and internalization kinetics of these receptors in both transiently-transfected HEK293 cells and retrovirus-mediated stable cells. The time-course accumulation of the inositol phosphate in response to GnRH revealed that bfGnRHR-1 and -2 were rapidly desensitized, whereas bfGnRHR-3 was slowly desensitized. A comparison of the internalization kinetics revealed the most rapid rate and highest extent of internalization of bfGnRHR-2 among the three receptors. Interestingly, the mechanisms that underlie the receptor internalization appear to differ from each other. Internalization of bfGnRHR-1 was dependent on both dynamin and beta-arrestin, whereas those of bfGnRHR-2 and -3 were dependent on dynamin, but not on arrestin. These results, therefore, suggest that differential regulatory mechanisms for desensitization and internalization of the GnRHR are involved in diverse cellular and physiological responses to GnRH stimulation.     

Solution structure and DNA-binding properties of the phosphoesterase domain of DNA ligase D

The phosphoesterase (PE) domain of the bacterial DNA repair enzyme LigD possesses distinctive manganese-dependent 3′-phosphomonoesterase and 3′-phosphodiesterase activities. PE exemplifies a new family of DNA end-healing enzymes found in all phylogenetic domains. Here, we determined the structure of the PE domain of Pseudomonas aeruginosa LigD (PaePE) using solution NMR methodology. PaePE has a disordered N-terminus and a well-folded core that differs in instructive ways from the crystal structure of a PaePE•Mn²⁺• sulfate complex, especially at the active site that is found to be conformationally dynamic. Chemical shift perturbations in the presence of primer-template duplexes with 3′-deoxynucleotide, 3′-deoxynucleotide 3′-phosphate, or 3′ ribonucleotide termini reveal the surface used by PaePE to bind substrate DNA and suggest a more efficient engagement in the presence of a 3′-ribonucleotide. Spectral perturbations measured in the presence of weakly catalytic (Cd²⁺) and inhibitory (Zn²⁺) metals provide evidence for significant conformational changes at and near the active site, compared to the relatively modest changes elicited by Mn²⁺.     

Identification of main effect and epistatic quantitative trait loci for morphological and yield-related traits in peanut (<Emphasis Type="Italic">Arachis hypogaea</Emphasis> L.)

An effort was made in the present study to identify the main effect and epistatic quantitative trait locus (QTL) for the morphological and yield-related traits in peanut. A recombinant inbred line (RIL) population derived from TAG 24 × GPBD 4 was phenotyped in seven environments at two locations. QTL analysis with available genetic map identified 62 main-effect QTLs (M-QTLs) for ten morphological and yield-related traits with the phenotypic variance explained (PVE) of 3.84–15.06%. Six major QTLs (PVE >?10%) were detected for PLHT, PPP, YPP, and SLNG. Stable M-QTLs appearing in at least two environments were detected for PLHT, LLN, YPP, YKGH, and HSW. Five M-QTLs governed two traits each, and 16 genomic regions showed co-localization of two to four M-QTLs. Intriguingly, a major QTL reported to be linked to rust resistance showed pleiotropic effect for yield-attributing traits like YPP (15.06%, PVE) and SLNG (13.40%, PVE). Of the 24 epistatic interactions identified across the traits, five interactions involved six M-QTLs. Three interactions were additive × additive and remaining two involved QTL × environment (QE) interactions. Only one major M-QTL governing PLHT showed epistatic interaction. Overall, this study identified the major M-QTLs for the important productivity traits and also described the lack of epistatic interactions for majority of them so that they can be conveniently employed in peanut breeding.     

Purification and characterization of enterocin FH 99 produced by a faecal isolate <Emphasis Type="Italic">Enterococcus faecium</Emphasis> FH 99

Enterococcus faecium FH 99 was isolated from human faeces and selected because of its broad spectrum of inhibitory activity against several Gram-positive foodborne spoilage and pathogenic bacteria. Ent. faecium FH 99 accumulates enterocin in large number in early stationary phase of the growth. The enterocin FH 99 was stable over a wide pH range (2–10) and recovered activity even after treatment at high temperatures (10 min at 100°C). The enterocin was subjected to different purification techniques viz., gel filteration, cation exchange chromatography and reverse-phase high-performance liquid chromatography. The activity was eluted as one individual active fraction. SDSPAGE revealed a molecular weight of less than 6.5 kDa. Studies carried out to identify the genetic determinants for bacteriocin production showed that this trait may be plasmid encoded as loss in both of the plasmids (size>chromosomal DNA) led to loss in bacteriocin production by Ent. faecium FH 99. Ent. faecium strain FH 99 is a newly discovered high bacteriocin producer with Activity Units 1.8 × 10⁵ AU ml⁻¹ and its characteristics indicate that it may have strong potential for application as a protective agent against pathogens and spoilage bacteria in foods.     

Abyssinones and related flavonoids as potential steroidogenesis modulators

Abyssinones and related flavonoids were screened against 3 enzymes (3βHSD, 17βHSD and Aromatase) of steroidogenesis pathway. The virtual screening experiment shows high affinity for flavonones than their respective chalcones. A 4'' ­OH blocked prenylated flavonone 2b (2­(2'', 2''­dimethyl chroman­6''­yl)­7­hydroxy chroman­4­one) had consistent binding affinity to all the three enzymes used in this study showing higher binding affinity to aromatase. A good correlation was observed between cytotoxic data (MCF­7, breast cancer cell line) and docking results indicating flavonone as a better steroidogenesis modulator in hormone dependent cancer.     

Renal cell carcinoma tumors induce T cell apoptosis through receptor-dependent and receptor-independent pathways

Tumors can promote their own progressive growth by inducing T cell apoptosis. Though previous studies suggested that tumor-mediated T cell killing is receptor dependent, we recently showed that tumor gangliosides also participate, a notion consistent with reports indicating that, in some cell types, gangliosides can activate the intrinsic apoptotic pathway by stimulating reactive oxygen species production, cytochrome c release, and caspase-9 activation. In this study, we used normal peripheral blood T cells, as well as caspase-8-, caspase-9-, and Fas-associated death domain protein-deficient Jurkat cells, to assess whether the death ligands and gangliosides overexpressed by the renal cell carcinoma (RCC) cell line SK-RC-45 can independently stimulate T cell apoptosis as a mechanism of immune escape. Anti-FasL Abs and the glycosylceramide synthase inhibitor 1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (PPPP) each partially inhibited the ability of SK-RC-45 to kill cocultured activated T cells; together, as purified molecules, RCC gangliosides and rFasL induced a more extensive mitochondrial permeability transition and greater levels of apoptosis than either agent alone, equivalent to that induced by the FasL- and ganglioside-expressing RCC line itself. rFasL-mediated apoptosis was completely inhibited in caspase-8- and Fas-associated death domain protein-negative Jurkat cells, though apoptosis induced by purified gangliosides remained intact, findings that correlate with the observed partial inhibition of SK-RC-45-induced apoptosis in the Jurkat lines with defective death receptor signaling. Western blot analysis performed on lysates made from wild-type and mutant Jurkat cells cocultured with SK-RC-45 revealed caspase activation patterns and other biochemical correlates which additionally supported the concept that tumor-associated gangliosides and FasL independently activate the caspase cascade in T cells through the intrinsic and extrinsic pathways, respectively.     

A study of 7-deaza-2'-deoxyguanosine 2'-deoxycytidine base pairing in DNA

The incorporation of 7-deazaguanine modifications into DNA is frequently used to probe protein recognition of H-bonding information in the major groove of DNA. While it is generally assumed that 7-deazaguanine forms a normal Watson–Crick base pair with cytosine, detailed thermodynamic and structural analyses of this modification have not been reported. The replacement of the 7-N atom on guanine with a C–H, alters the electronic properties of the heterocycle and eliminates a major groove cation-binding site that could affect the organization of salts and water in the major groove. We report herein the characterization of synthetic DNA oligomers containing 7-deazaguanine using a variety of complementary approaches: UV thermal melting, differential scanning calorimetry (DSC), circular dichroism (CD), chemical probing and NMR. The results indicate that the incorporation of a 7-deazaguanine modification has a significant effect on the dynamic structure of the DNA at the flanking residue. This appears to be mediated by changes in hydration and cation organization.