Age-dependent hepatic lymphoid organization directs successful immunity to hepatitis B

Hepatitis B virus (HBV) is a major human pathogen that causes immune-mediated hepatitis. Successful immunity to HBV is age dependent: viral clearance occurs in most adults, whereas neonates and young children usually develop chronic infection. Using a mouse model of HBV infection, we sought mechanisms underpinning the age-dependent outcome of HBV and demonstrated that hepatic macrophages facilitate lymphoid organization and immune priming within the adult liver and promote successful immunity. In contrast, lymphoid organization and immune priming was greatly diminished in the livers of young mice, and of macrophage-depleted adult mice, leading to abrogated HBV immunity. Furthermore, we found that CXCL13, which is involved in B lymphocyte trafficking and lymphoid architecture and development, is expressed in an age-dependent manner in both adult mouse and human hepatic macrophages and plays an integral role in facilitating an effective immune response against HBV. Taken together, these results identify some of the immunological mechanisms necessary for effective control of HBV.     

Extended delivery of ophthalmic drugs by silicone hydrogel contact lenses

We developed extended wear silicone hydrogel soft contact lenses that deliver ophthalmic drugs for an extended period of time ranging from weeks to months. Silicone hydrogels comprising of N,N-dimethylacrylamide, 3-methacryloxypropyltris(trimethylsiloxy)silane, bis-alpha,omega-(methacryloxypropyl) polydimethylsiloxane, 1-vinyl-2-pyrrolidone, and ethylene glycol dimethacrylate were prepared with varying ratios of monomers and transport of three different ophthalmic drugs, timolol, dexamethasone, and dexamethasone 21-acetate was explored. All the silicone hydrogels of 0.1 mm thickness exhibit diffusion limited transport and extended release varying 20 days up to more than three months depending on the compositions of hydrophobic and hydrophilic components of silicone hydrogels. Also, there are multiple time scales in transport of at least certain molecules, which is perhaps due to the complex microstructure of these gels. The mechanical and physical properties of lenses such as ion permeability, equilibrium water content, transparency, and surface contact angles of some of the gels are suitable for contact lens application.     

BRCA1-methylated sporadic breast cancers are BRCA-like in showing a basal phenotype and absence of ER expression

BRCA1 mutations have been associated with hereditary breast cancer only. Recent studies indicate that a subgroup of sporadic breast cancer might also be associated with reduction in BRCA1 mRNA levels and protein expression. However, the mechanism of reduced mRNA and protein expression is yet not fully elucidated. This study aims to assess BRCA1 protein expression and the role of BRCA1 promoter methylation in sporadic breast cancer in North Indian population and to correlate these with known prognostic factors and molecular profiles of breast cancer. BRCA1 protein expression was normal (>50?% tumour cells) in 41 (43?%) cases, reduced (20-50?% tumour cells) in 33 (35?%) cases and absent/markedly reduced (<20?% tumour cells) in 21 (22.1?%) cases. Cases which were negative for BRCA1 protein were more frequently positive for basal markers (29 versus 5?%) and were more often ER-negative (62 versus 39?%) than BRCA1-positive tumours. Methylation of BRCA1 promoter region was seen in 11/45 cases (24?%). All 11 cases showing BRCA1 methylation had absent (eight cases) or reduced (three cases) BRCA1 protein expression. BRCA1 protein-negative tumours were more frequently basal marker-positive and ER-negative, highlighting the 'BRCAness' of sporadic breast cancer with loss of BRCA1 protein expression through promoter hypermethylation similar to hereditary breast cancer with BRCA1 mutations. Loss of BRCA1 in sporadic breast cancer suggests that therapeutics targeting BRCA1 pathway in hereditary breast cancer like PARP inhibitors might be used as therapeutic targets for sporadic breast tumours.     

WormBot,an open-source robotics platform for survival and behavior analysis in C. elegans

GeroScience - Caenorhabditis elegans is a popular organism for aging research owing to its highly conserved molecular pathways, short lifespan, small size, and extensive genetic and reverse genetic...     

Cartridge based nucleic acid amplification test is superior in diagnosing lymphnode tuberculosis

BackgroundThe role of Cartridge based Nucleic Acid Amplification test (CBNAAT) in the diagnosis of lymphnode TB which helps in reducing the mortality and morbidity by early identification and initiating treatment at the earliest. Also helps in identify the drug resistance among tubercular lymphnodes cases.Patients and methodsA prospective clinical study was performed in 101 suspected lymph node tuberculosis patients. The results of FNAC and/or excision biopsy of lymphnode samples obtained by CBNAAT were compared with direct smear microscopy for AFB bacilli, cytology and their combination considering AFB culture as gold standard.ResultsA total of 101 patients were evaluated of which 74 subjects (73.3%) were CBNAAT positive for TB. Among the CBNAAT positive cases, 57 were aged above 16 years, 38 were females, equal number (37) had single and multiple lymphnodes, 46 had less than 1 cm size lymphnodes, 69 had lymphnode in neck region, 65 had chest X-ray normal. Among CBNAAT positive 74 subjects, 53 subjects (71.6%) were positive for AFB direct smear, 64 subjects (86.48%) were cytology consistent with TB and their combination were positive for TB in 71 subjects (95.94%) and 71 subjects (95.94%) were positive by AFB culture and 3 cases (0.04%) showed Rifampicin resistance.ConclusionCBNAAT is a rapid diagnostic tool having sensitivity of 93.42% with specificity of 86.96% and positive predictive value of 95.95% and having comparable results with AFB culture and more sensitive than other investigation procedures. Thus it can be a rule in test for lymphnode TB.