Hepatocyte-macrophage crosstalk via the PGRN-EGFR axis modulates ADAR1-mediated immunity in the liver.

ADAR1-mediated RNA editing establishes immune tolerance to endogenous double-stranded RNA (dsRNA) by preventing its sensing, primarily by MDA5. Although deleting Ifih1 (encoding MDA5) rescues embryonic lethality in ADAR1-deficient mice, they still experience early postnatal death, and removing other MDA5 signaling proteins does not yield the same rescue. Here, we show that ablation of MDA5 in a liver-specific Adar knockout (KO) murine model fails to rescue hepatic abnormalities caused by ADAR1 loss.

The High Mutational Sensitivity of ccdA Antitoxin Is Linked to Codon Optimality.

Deep mutational scanning studies suggest that synonymous mutations are typically silent and that most exposed, nonactive-site residues are tolerant to mutations. Here, we show that the ccdA antitoxin component of the Escherichia coli ccdAB toxin-antitoxin system is unusually sensitive to mutations when studied in the operonic context. A large fraction (∼80%) of single-codon mutations, including many synonymous mutations in the ccdA gene shows inactive phenotype, but they retain native-like binding affinity towards cognate toxin, CcdB.

Protein model discrimination attempts using mutational sensitivity, predicted secondary structure, and model quality information.

Structure prediction methods often generate a large number of models for a target sequence. Even if the correct fold for the target sequence is sampled in this dataset, it is difficult to distinguish it from other decoy structures. An attempt to solve this problem using experimental mutational sensitivity data for the CcdB protein was described previously by exploiting the correlation of residue depth with mutational sensitivity (r ~ 0.

Isolation and purification of antibacterial compound from Streptomyces levis collected from soil sample of north India.

During the screening programme for microbial cultures producing antimicrobial agents, an active microbial strain of Streptomyces was isolated from the agricultural soil of Narnaul, Haryana India. Physiological, biochemical characteristics and 16S ribosomal RNA sequence homology studies revealed that it was similar to Streptomyces levis (sequence similarity 100%). The microbial strain was submitted to Genomebio Technologies Pvt.

Rapid Mapping of Protein Binding Sites and Conformational Epitopes by Coupling Yeast Surface Display to Chemical Labeling and Deep Sequencing.

Delineating the precise regions on an antigen that are targeted by antibodies is important for the development of vaccines and antibody therapeutics. X-ray crystallography and NMR are considered the gold standard for providing precise information about these binding sites at atomic resolution. However, these are labor-intensive and require purified protein at high concentration.

Long-term cardiac (valvulopathy) safety of cabergoline in prolactinoma.

Background: Clinical relevance of association of cabergoline use for hyperprolactinemia and cardiac valvulopathy remains unclear.

Objective: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking cabergoline for the treatment of prolactinoma and to explore any associations with the cumulative dose of drug used.

Design: A cross-sectional echocardiographic study was performed in patients who were receiving cabergoline therapy for prolactinoma.

Mapping Protein Binding Sites and Conformational Epitopes Using Cysteine Labeling and Yeast Surface Display.

We describe a facile method for mapping protein:ligand binding sites and conformational epitopes. The method uses a combination of Cys scanning mutagenesis, chemical labeling, and yeast surface display. While Ala scanning is widely used for similar purposes, often mutation to Ala (or other amino acids) has little effect on binding, except at hotspot residues.

Molecular Determinants of Mutant Phenotypes, Inferred from Saturation Mutagenesis Data.

Understanding how mutations affect protein activity and organismal fitness is a major challenge. We used saturation mutagenesis combined with deep sequencing to determine mutational sensitivity scores for 1,664 single-site mutants of the 101 residue Escherichia coli cytotoxin, CcdB at seven different expression levels. Active-site residues could be distinguished from buried ones, based on their differential tolerance to aliphatic and charged amino acid substitutions.

Germline mutations and genotype-phenotype correlation in Asian Indian patients with pheochromocytoma and paraganglioma.

Background: Genetic aetiology of pheochromocytoma (PCC) and paraganglioma (PGL) is increasingly being studied; however, Asian Indian data on this aspect are scarce.

Objective: To study the prevalence of germline mutations and genotype-phenotype correlation in Asian Indian PCC/PGL patients.

Design: In this study, 150 index patients (M:F, 73:77) with PCC/PGL were evaluated.

Multiple endocrine neoplasia type 1 syndrome: single centre experience from western India.

Multiple endocrine neoplasia type 1 syndrome (MEN1) is a rare autosomal dominant familial cancer syndrome affecting multiple endocrine glands. Published literature on MEN1 from Indian subcontinent is scarce. We report here a case series of MEN1 patients (n = 18) from 14 unrelated families.

Residue proximity information and protein model discrimination using saturation-suppressor mutagenesis.

Identification of residue-residue contacts from primary sequence can be used to guide protein structure prediction. Using Escherichia coli CcdB as the test case, we describe an experimental method termed saturation-suppressor mutagenesis to acquire residue contact information. In this methodology, for each of five inactive CcdB mutants, exhaustive screens for suppressors were performed.

Gender differences in macroprolactinomas: a single centre experience.

Macroprolactinomas are the most common functional pituitary tumours. Hypotheses proposed to explain predominance of large tumours in males are: i) diagnostic delay, as hyperprolactinaemia remains under recognised in males and ii) gender-specific difference in tumour proliferation indices. Our study objectives are to compare gender differences in clinical, biochemical, radiological features, management outcomes and cabergoline responsiveness in macroprolactinomas.

HIGH-PRECISION CONFORMAL FRACTIONATED RADIOTHERAPY IS EFFECTIVE IN ACHIEVING REMISSION IN PATIENTS WITH ACROMEGALY AFTER FAILED TRANSSPHENOIDAL SURGERY.

Objective: Variable efficacy of pituitary radiotherapy in acromegaly is reported. Here we sought to assess the efficacy of high-precision conformal fractionated radiotherapy (CRT) in patients with acromegaly after failed TSS.

Methods: A retrospective analysis was conducted a in tertiary care referral center between 1999 to 2013 on 36 acromegaly patients (M: 16, F: 20; median age: 36.

Is it worthwhile to screen patients with type 2 diabetes mellitus for subclinical Cushing's syndrome?

Variable prevalence of subclinical Cushing's syndrome (SCS) has been reported in patients with type 2 diabetes mellitus (T2DM), making the need for screening in this population uncertain. It is unknown if this variability is solely due to study-related methodological differences or a reflection of true differences in ethnic predisposition. The objective of this study is to explore the prevalence of SCS in Asian Indian patients with T2DM.

Radiofrequency ablation, an effective modality of treatment in tumor-induced osteomalacia: a case series of three patients.

Context: Tumor-induced osteomalacia is curable if the tumors can be totally excised. However, when the tumors are present in locations that make surgery disproportionately risky, the need for less invasive strategies like radiofrequency ablation (RFA) is realized.

Patients And Methods: We describe three patients with suspected tumor-induced osteomalacia who were treated in our department between 2006 and 2013 with tumors in surgically difficult locations and were subjected to single or multiple sessions of RFA.

TSpred: a web server for the rational design of temperature-sensitive mutants.

Temperature sensitive (Ts) mutants of proteins provide experimentalists with a powerful and reversible way of conditionally expressing genes. The technique has been widely used in determining the role of gene and gene products in several cellular processes. Traditionally, Ts mutants are generated by random mutagenesis and then selected though laborious large-scale screening.

Wolcott Rallison syndrome: a rare inherited diabetes mellitus.

A 9-y-old boy was referred to authors' institute for the management of insulin dependent diabetes mellitus. He was the product of third degree consanguineous marriage and was delivered by full term vaginal delivery with a birth weight of 2.75 kg.

Clinical, biochemical and imaging characteristics of Cushing's macroadenomas and their long-term treatment outcome.

Objective: Cushing's macroadenoma as a cause of Cushing's disease is less common than microadenoma. The data on nature and behaviour of Cushing's macroadenoma are limited to a few case series. We studied clinical, biochemical and imaging characteristics of macroadenoma and their long-term treatment outcomes.

Primary (autoimmune) hypophysitis: a single centre experience.

Background: Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disorder of pituitary gland.

Objective: To analyse clinical, hormonal, radiological features and management outcomes of AH.

Design: Retrospective analysis of patients with primary hypophysitis (where secondary causes of hypophysitis were ruled out) was carried out from 2006 to 2012.

Ectopic ACTH-secreting syndrome: a single-center experience.

Objective: Ectopic adrenocorticotropic hormone (ACTH)-secreting syndrome (EAS) is a rare cause of ACTH-dependent endogenous hypercortisolism. The objective of this study was to analyze clinical, biochemical, and imaging characteristics; management strategies; and outcomes of EAS patients.

Method: We screened the records (1993-2012) of ACTH-dependent endogenous hypercortisolism cases managed at a tertiary care center.