A winged-helix protein from Sulfolobus turreted icosahedral virus points toward stabilizing disulfide bonds in the intracellular proteins of a hyperthermophilic virus

Sulfolobus turreted icosahedral virus (STIV) was the first non-tailed icosahedral virus to be isolated from an archaeal host. Like other archaeal viruses, its 37 open reading frames generally lack sequence similarity to genes with known function. The roles of the gene products in this and other archaeal viruses are thus largely unknown. However, a protein's three-dimensional structure may provide functional and evolutionary insight in cases of minimal sequence similarity. In this vein, the structure of STIV F93 reveals a homodimer with strong similarity to the winged-helix family of DNA-binding proteins. Importantly, an interchain disulfide bond is found at the dimer interface, prompting analysis of the cysteine distribution in the putative intracellular proteins of the viral proteome. The analysis suggests that intracellular disulfide bonds are common in cellular STIV proteins, where they enhance the thermostability of the viral proteome.     

Segmental foot mobility in individuals with and without diabetes and neuropathy

BACKGROUND: Impairment in intrinsic foot mobility has been identified as an important potential contributor to altered foot function in individuals with diabetes mellitus and neuropathy, however the role of limited foot mobility in gait remains poorly understood. The purpose of our study was to examine segmental foot mobility during gait in subjects with and without diabetes and neuropathy. METHODS: Segmental foot mobility during gait was examined using a multi-segment kinematic foot model in subjects with diabetes (n=15) and non-diabetic control subjects (n=15). FINDINGS: Subjects with diabetes showed reduced frontal as well as sagittal plane excursion of the calcaneus relative to the tibia. Decreased excursion of the first metatarsal relative to the calcaneus in the frontal as well as transverse plane was noted in subjects with diabetes. INTERPRETATION: Our findings agree with traditional understanding of foot mechanics and shed new light on patterns and magnitude of motion during gait. Calcaneal pronation, noted in early stance in both groups, was reduced in subjects with diabetes and may have important consequences on joints proximal as well as distal to it. Subjects with diabetes showed reduced foot 'splay' in early stance, indicated by first metatarsal and forefoot eversion. At terminal stance, decreases in calcaneal plantarflexion, first metatarsal and forefoot supination were noted in subjects with diabetes, suggesting that less supination is required in subjects with diabetes to create a rigid lever. In subjects with diabetes, a greater proportion of midfoot stability may be derived from modified/stiffer soft tissue such as the plantar fascia.     

Inhibition of invariant chain expression in dendritic cells presenting endogenous antigens stimulates CD4+ T-cell responses and tumor immunity

Induction of potent and sustained antiviral or antitumor immunity is dependent on the efficient activation of CD8+ and CD4+ T cells. While dendritic cells constitute a powerful platform for stimulating cellular immunity, presentation of endogenous antigens by dendritic cells transfected with nucleic acid-encoded antigens favors the stimulation of CD8+ T cells over that of CD4+ T cells. A short incubation of mRNA-transfected dendritic cells with antisense oligonucleotides directed against the invariant chain enhances the presentation of mRNA-encoded class II epitopes and activation of CD4+ T-cell responses in vitro and in vivo. Immunization of mice with the antisense oligonucleotide-treated dendritic cells stimulates a more potent and longer lasting CD8+ cytotoxic T-cell (CTL) response and enhances the antitumor efficacy of dendritic cell-based tumor vaccination protocols. Transient inhibition of invariant chain expression represents a simple and general method to enhance the stimulation of CD4+ T-cell responses from endogenous antigens.     

Subtype B and subtype C HIV type 1 recombinants in the northeastern state of Manipur, India

The predominant HIV-1 strain circulating in India is subtype C. However, subtype A and B strains of HIV-1 have also been reported in India. In 1999, the first A/C recombinant strain was reported from Pune in India. Intravenous drug users (IVDUs) from the northeastern region of India have a high HIV-1 seroprevalence. Studies carried out in intravenous drug users in the northeastern region of India have shown that HIV-1 subtype C is the predominant strain infecting IVDUs. Fourteen blood samples were collected from HIV-1-infected individuals from the northeastern region of India and screened by env and gag heteroduplex mobility assays (HMA). Where the env and gag HMA results from a sample yielded different subtypes, sequencing of env and gag PCR products was carried out to confirm the presence of HIV-1 recombinants. Of the 14 samples subtyped, nine samples belonged HIV-1 subtype C (gag C/env C), one to HIV-1 subtype B (gag B/env B), and the remaining were B/C recombinants (gag C/env B). This is the first report of HIV-1 B/C recombinants from India.     

“Dynamic” liver retraction at laparoscopy: An easy and effective technique

Liver retraction is an essential step during any laparoscopic upper gastrointestinal operation, especially during dissection at the oesophageal hiatus. However, the generally employed Nathanson retractor may cause significant postoperative liver dysfunction secondary to congestion of the liver.1,2 It may be technically cumbersome to systematize its frequent use intraoperatively and it may not be readily available at large. Furthermore, the unabated pressure it inflicts on the left lobe of the liver, especially during prolonged surgeries, may lead to hepatic ischaemic necrosis, gangrene, or even unexpected mortality.1 While few recently developed innovative liver retraction techniques seem useful in this context, 2-5 they tend to offer a “static” liver retraction. In this paper, we describe an easy-to-use method of laparoscopic liver retraction wherein any 5mm laparoscopic instrument can be used to manipulate the “heavy” liver so as to provide a “dynamic” counter-traction at will.     

NCoR1 fine-tunes type-I IFN response in cDC1 dendritic cells by directly regulating Myd88-IRF7 axis under TLR9

Plasmacytoid dendritic cells (DCs) are reported to induce robust type-I interferon (IFN) response, whereas cDC1 DCs develop moderate type-I IFN response upon TLR9 stimulation. It is very interesting to understand how this signaling under TLR9 is tightly regulated for the induction of type-I IFNs. Here, we report co-repressor protein NCoR1 as the major factor fine-tuning the signaling pathways regulating IFN-β expression under TLR9 in cDC1 DCs. We found that NCoR1 knockdown induced a robust IFN-β-mediated antiviral response upon TLR9 activation in cDC1 DCs. At the molecular level, we showed that NCoR1 directly repressed MyD88-IRF7 signaling axis in cDC1 cells. Therefore, NCoR1 depletion enhanced pIRF7 levels, IFN-β secretion, and downstream pSTAT1-pSTAT2 signaling, leading to sustained induction of IFN stimulatory genes. Integrative genomic analysis depicted strong enrichment of an antiviral gene-module in CpG-activated NCoR1 knockdown DCs upon TLR9 activation. Moreover, we confirmed our findings in primary DCs derived from splenocytes of WT and NCoR1 DC^−/− animals, which showed protection from Sendai and Vesicular Stomatitis viruses upon CpG activation. Ultimately, we identified that NCoR1–HDAC3 complex is involved in repressing the type-I IFN response in cDC1 DCs.     

Study on influence of age,gender and genetic variants on lactose intolerance and its impact on milk intake in adult Asian Indians

Background: Lactase non-persistence (LNP) has been associated with the CC genotype of ?13910C?>?T and GG genotype of ?22018G?>?A polymorphisms present upstream of the lactase gene. Lactose intolerance (LI) is caused when gastrointestinal symptoms develop in individuals with low lactase activity.

Objective: To analyse association of LNP genotype and LI symptoms with milk intake and determine whether factors such as age, gender and genotype affect LI status.

Subjects and methods: Genetic analysis and lactose tolerance test (LTT) were performed on 205 healthy Indian adults. The pattern of milk consumption was recorded using a dietary questionnaire.

Results: LI was strongly associated with ?13910CC genotype (OR?=?10.28, 95% CI?=?2.32–45.55, p?=?0.002). Females were found to be at a higher risk of developing LI (OR?=?2.47, 95% CI?=?1.33–4.59, p?=?0.004). The association of the ≥50 years age group with LI was marginally significant (OR?=?1.86, 95% CI?=?0.995–3.47, p?=?0.05). Frequency and quantity of milk intake were lower in subjects belonging to the LNP genotype and LI groups (p?Conclusions: Subject study suggests that gender and genotype may be associated with development of LI. Association of age with LI was marginal. The data also indicate that LNP genotype and LI may play a role in influencing milk intake in individuals.     

Experience of 100 solid organ transplants over a five‐yr period from the first successful pediatric multi‐organ transplant program in India

To analyze the clinical profile and outcome of pediatric patients who had undergone a liver and/or RT at our center over a five yr period, case records of all the patients who had undergone a liver or RT were analyzed retrospectively. One hundred solid organ transplants were performed at our center between January 2007 and January 2012. These included 50 liver, 44 renal, one sequential liver and renal, and two CLKT. BA was the most common indication for an LT (38%). At a median follow‐up of two yr three months, the patient survival was 88%. The most common indication for an RT was chronic glomerulonephritis (54.5%). At a median follow‐up of three yr, the survival was 91%. The CLKT were performed for hyperoxaluria. Two yr post LT, a sequential RT was performed for ESRD resulting from transplant associated microangiopathy. All patients received a living related graft. The common post‐operative complications were infections, vascular complications, and graft dysfunction. Survival rates for liver and RT at our center are comparable to those in the established centers in the West.