Draft Genome Sequence of Staphylococcus aureus ST672, an Emerging Disease Clone from India

We report the draft genome sequence of methicillin-resistant Staphylococcus aureus (MRSA) strain ST672, an emerging disease clone in India, from a septicemia patient. The genome size is about 2.82 Mb with 2,485 open reading frames (ORFs). The staphylococcal cassette chromosome mec (SCCmec) element (type V) and immune evasion cluster appear to be different from those of strain ST772 on preliminary examination.     

Resource partitioning and interspecific interactions among sympatric rain forest arboreal mammals of the Western Ghats, India

Resource partitioning in a community of diurnal arboreal mammalsconsisting of the lion-tailed macaque Macaca silenus, bonnetmacaque (BM) Macaca radiata, Nilgiri langur Semnopithecus johnii,and the Indian giant squirrel Ratufa indica of the Western Ghats,southern India, was studied. Differences in their diet, verticalstratification, food resource niche breadth, niche overlap,and behavioral interactions were examined. Resource partitioningwas through differential habitat use, resource use, and verticalstratification. Of the four species, the BM was not a residentspecies and made frequent forays into evergreen forest fromthe adjacent deciduous forest during the flowering season ofCullenia exarillata and fruiting season of Ficus microcarpa.The macaques had narrower niches, and the langur and the squirrelhad wider niches. Niche overlap was highest between the twomacaques. Overlap among the study species was particularly pronouncedduring the flowering of C. exarillata. There was significantcorrelation between niche overlap and intolerance among thestudy species. Certain species pairs showed little or no mutualintolerance despite high overlap. Cooperative interactions suchas alarm calls occurred more frequently among the resident species.Interaction matrices revealed an underlying pattern of interspecificdominance hierarchy, with the BM dominating over the other threespecies. Our study suggests that the BM do not coexist withthe other three because of high overlap with its congener andlow occurrence of cooperative interactions.     

Genome Sequencing Unveils a Novel Sea Enterotoxin-Carrying PVL Phage in Staphylococcus aureus ST772 from India

Staphylococcus aureus is a major human pathogen, first recognized as a leading cause of hospital-acquired infections. Community-associated S. aureus (CA-SA) pose a greater threat due to increase in severity of infection and disease among children and healthy adults. CA-SA strains in India are genetically diverse, among which is the sequence type (ST) 772, which has now spread to Australia, Europe and Japan. Towards understanding the genetic characteristics of ST772, we obtained draft genome sequences of five relevant clinical isolates and studied the properties of their PVL-carrying prophages, whose presence is a defining hallmark of CA-SA. We show that this is a novel prophage, which carries the structural genes of the hlb-carrying prophage and includes the sea enterotoxin. This architecture probably emerged early within the ST772 lineage, at least in India. The sea gene, unique to ST772 PVL, despite having promoter sequence characteristics typical of low expression, appears to be highly expressed during early phase of growth in laboratory conditions. We speculate that this might be a consequence of its novel sequence context. The crippled nature of the hlb-converting prophage in ST772 suggests that widespread mobility of the sea enterotoxin might be a selective force behind its ‘transfer’ to the PVL prophage. Wild type ST772 strains induced strong proliferative responses as well as high cytotoxic activity against neutrophils, likely mediated by superantigen SEA and the PVL toxin respectively. Both proliferation and cytotoxicity were markedly reduced in a cured ST772 strain indicating the impact of the phage on virulence. The presence of SEA alongside the genes for the immune system-modulating PVL toxin may contribute to the success and virulence of ST772.     

Identification of GR and TrxR systems in Setaria cervi: Purification and characterization of glutathione reductase

The glutathione reductase (GR) and thioredoxin reductase (TrxR) are important enzymes of the redox system that aid parasites to maintain an adequate intracellular redox environment. In the present study, the enzyme activity of GR and TrxR was investigated in Setaria cervi (S. cervi). Significant activity of both enzymes was detected in the somatic extract of adult and microfilariae stages of S. cervi. Both GR and TrxR were separated by partial purification using ammonium sulfate fractionation and DEAE ion exchange chromatography suggesting the presence of both glutathione and thioredoxin systems in S. cervi. The enzyme glutathione reductase (ScGR) was purified to homogeneity using affinity and ion exchange chromatography that resulted in 90 fold purification with a yield of 11.54%. The specific activity of the ScGR was 643 U/mg that migrated as a single band on SDS-PAGE. The subunit molecular mass was determined to be ~ 50 kDa while the optimum pH and temperature were found to be 7.0 and 35 °C respectively. The activation energy (Ea) was calculated from the slope of Arrhenius plot as 16.29 ± 1.40 kcal/mol. The Km and Vmax were determined to be 0.27 ± 0.045 mM; 30.30 ± 1.30 U/ml with NADPH and 0.59 ± 0.060 mM; 4.16 ± 0.095 U/ml with GSSG respectively. DHBA, a specific inhibitor for GR has completely inhibited the enzyme activity at 1 μM concentration. The inhibition of ScGR activity with NAI (IC₅₀ 0.71 mM), NEM (IC₅₀ 0.50 mM) and DEPC (IC₅₀ 0.27 mM) suggested the presence of tyrosine, cysteine and histidine residues at its active site. Further studies on characterization and understanding of these antioxidant enzymes may lead to designing of an effective drug against lymphatic filariasis.     

Discovery and characterization of endogenous cannabinoids.

The characterization of cannabinoid receptors and signal transduction mechanisms provided the impetus for the searching for endogenous ligands for this system. The result was a family of fatty acid derivatives that interact with cannabinoid receptors to varying degrees. The two ligands that have received the most attention are anandamide (AN) and 2-arachidonolyl-glycerol (Ara-Gl). They are both present in central as well as peripheral tissues. Mechanisms for the synthesis and metabolism of AN have been described. Presently, the physiological stimuli for production and release of AN are unknown. As a result, elucidation of its physiological role remains elusive. However, it seems reasonable to conclude that both AN and 2-Ara-Gl interact with cannabinoid receptors in both peripheral and central tissue to produce a wide range of effects. Administration of these ligands to laboratory animals produce effects that are quite similar to those elicited by delta9-tetrahydrocannabinol (THC), the psychoactive constituent in marijuana. Nevertheless, there are some pharmacological differences between the plant-derived THC and the endogenous cannabinoids that could be due to either pharmadynamic or pharmacokinetics dissimilarities. Extensive structure-activity relationship studies have provided some vital insights into the actions of the endogenous ligands. First and foremost, systematic structural alterations in AN have additional support that it is acting at the cannabinoid receptors in a fashion similar to that of THC. Development of metabolically stable analogs of AN, as well as those with greater receptor affinity, have helped substantiate AN and THC similarities. Nevertheless, pharmacological differences remain between the endogenous and exogenous ligands. Whether these differences are due to the nature of their interaction with the cannabinoid receptors, activation of unique signaling pathways, interactions with non-cannabinoid receptors, or pharmacokinetic considerations remain to be resolved.     

Stn1 is critical for telomere maintenance and long‐term viability of somatic human cells

Disruption of telomere maintenance pathways leads to accelerated entry into cellular senescence, a stable proliferative arrest that promotes aging‐associated disorders in some mammals. The budding yeast CST complex, comprising Cdc13, Stn1, and Ctc1, is critical for telomere replication, length regulation, and end protection. Although mammalian homologues of CST have been identified recently, their role and function for telomere maintenance in normal somatic human cells are still incompletely understood. Here, we characterize the function of human Stn1 in cultured human fibroblasts and demonstrate its critical role in telomere replication, length regulation, and function. In the absence of high telomerase activity, shRNA‐mediated knockdown of hStn1 resulted in aberrant and fragile telomeric structures, stochastic telomere attrition, increased telomere erosion rates, telomere dysfunction, and consequently accelerated entry into cellular senescence. Oxidative stress augmented the defects caused by Stn1 knockdown leading to almost immediate cessation of cell proliferation. In contrast, overexpression of hTERT suppressed some of the defects caused by hStn1 knockdown suggesting that telomerase can partially compensate for hStn1 loss. Our findings reveal a critical role for human Stn1 in telomere length maintenance and function, supporting the model that efficient replication of telomeric repeats is critical for long‐term viability of normal somatic mammalian cells.     

An efficient orange–red‐emitting LiNa3P2O7:Sm3+ pyrophosphate: Structural and optical analysis for solid‐state lighting

A trivalent rare‐earth ion (Sm³⁺)‐doped LiNa₃P₂O₇ (LNPO) phosphor was synthesized using a conventional high‐temperature solid‐state reaction route. A predominant orthorhombic phase of LNPO was observed in all X‐ray diffraction patterns. The surface states of the LNPO:Sm phosphor were confirmed by X‐ray photoelectron spectroscopy. Under 401 nm excitation, the Sm‐doped LNPO phosphors showed sharp emission peaks at 563, 600 and 647 nm that are related to the f–f transition of Sm³⁺ ions. The optimum concentration of Sm³⁺ (9 mol%) produced Commission Internationale de l'Eclairage chromaticity coordinates, color rendering index and correlated color temperature of (0.564, 0.434), 42 and 1843 K, respectively.