Evaluation of Vulvar Disorders by Vulvoscopy Index and N-S-P Scheme Using Three Rings Vulvoscopy (TRIV).

Background And Objective: TRIV is a new and promising technique based on the fact that Vulva can be divided into three circular zones based on anatomy, embryology, and histology- Outer, Middle, and Inner ring. The Vulvoscopy Index and N-S-P scheme are objective tools to improve the systematization of vulvoscopy findings and to simplify information management using TRIV.

Methods: Hundred women with vulvar complaints (Cases) and 100 asymptomatic women (Controls) underwent TRIV and findings were documented as per N-S-P Scheme and Vulvoscopy Index.

A multifaceted approach for analyzing complex phenotypic data in rodent models of autism.

Autism (MIM 209850) is a multifactorial disorder with a broad clinical presentation. A number of high-confidence ASD risk genes are known; however, the contribution of non-genetic environmental factors towards ASD remains largely uncertain. Here, we present a bioinformatics resource of genetic and induced models of ASD developed using a shared annotation platform.

The ubiquitin ligase HECTD1 promotes retinoic acid signaling required for development of the aortic arch.

The development of the aortic arch is a complex process that involves remodeling of the bilaterally symmetrical pharyngeal arch arteries (PAAs) into the mature asymmetric aortic arch. Retinoic acid signaling is a key regulator of this process by directing patterning of the second heart field (SHF), formation of the caudal PAAs and subsequent remodeling of the PAAs to form the aortic arch. Here, we identify the HECTD1 ubiquitin ligase as a novel modulator of retinoic acid signaling during this process.

AutDB: a platform to decode the genetic architecture of autism.

AutDB is a deeply annotated resource for exploring the impact of genetic variations associated with autism spectrum disorders (ASD). First released in 2007, AutDB has evolved into a multi-modular resource of diverse types of genetic and functional evidence related to ASD. Current modules include: Human Gene, which annotates all ASD-linked genes and their variants; Animal Model, which catalogs behavioral, anatomical and physiological data from rodent models of ASD; Protein Interaction (PIN), which builds interactomes from direct relationships of protein products of ASD genes; and Copy Number Variant (CNV), which catalogs deletions and duplications of chromosomal loci identified in ASD.

Proteasome regulates turnover of toxic human amylin in pancreatic cells.

Toxic human amylin (hA) oligomers and aggregates are implicated in the pathogenesis of type 2 diabetes mellitus (T2DM). Although recent studies demonstrated a causal connection between hA uptake and toxicity in pancreatic cells, the mechanism of amylin's clearance following its internalization and its relationship to toxicity is yet to be determined, and hence was investigated here. Using pancreatic rat insulinoma β-cells and human islets as model systems, we show that hA, following its internalization, first accumulates in the cytosol followed by its translocation into nucleus, and to a lesser extent lysosomes, keeping the net cytosolic amylin content low.

Abnormal labyrinthine zone in the Hectd1-null placenta.

Introduction: The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta.

Role of Cholesterol and Phospholipids in Amylin Misfolding, Aggregation and Etiology of Islet Amyloidosis.

Amyloidosis is a biological event in which proteins undergo structural transitions from soluble monomers and oligomers to insoluble fibrillar aggregates that are often toxic to cells. Exactly how amyloid proteins, such as the pancreatic hormone amylin, aggregate and kill cells is still unclear. Islet amyloid polypeptide, or amylin, is a recently discovered hormone that is stored and co-released with insulin from pancreatic islet β-cells.

Hectd1 is required for development of the junctional zone of the placenta.

The placenta plays a critical role in the growth and survival of the fetus. Here we demonstrate that the Homologous to the E6-AP Carboxyl Terminus (HECT) domain E3 ubiquitin ligase, Hectd1, is essential for development of the mouse placenta. Hectd1 is widely expressed during placentation with enrichment in trophoblast giant cells (TGCs) and other trophoblast-derived cell subtypes in the junctional and labyrinth zones of the placenta.

An explant assay for assessing cellular behavior of the cranial mesenchyme.

The central nervous system is derived from the neural plate that undergoes a series of complex morphogenetic movements resulting in formation of the neural tube in a process known as neurulation. During neurulation, morphogenesis of the mesenchyme that underlies the neural plate is believed to drive neural fold elevation. The cranial mesenchyme is comprised of the paraxial mesoderm and neural crest cells.

HectD1 E3 ligase modifies adenomatous polyposis coli (APC) with polyubiquitin to promote the APC-axin interaction.

The adenomatous polyposis coli (APC) protein functions as a negative regulator of the Wnt signaling pathway. In this capacity, APC forms a "destruction complex" with Axin, CK1α, and GSK3β to foster phosphorylation of the Wnt effector β-catenin earmarking it for Lys-48-linked polyubiquitylation and proteasomal degradation. APC is conjugated with Lys-63-linked ubiquitin chains when it is bound to Axin, but it is unclear whether this modification promotes the APC-Axin interaction or confers upon APC an alternative function in the destruction complex.

Does the cranial mesenchyme contribute to neural fold elevation during neurulation?

The central nervous system is derived from the neural plate, which undergoes a series of complex morphogenetic events resulting in formation of the neural tube in a process known as neurulation. The cellular behaviors driving neurulation in the cranial region involve forces generated by the neural tissue itself as well as the surrounding epithelium and mesenchyme. Of interest, the cranial mesenchyme underlying the neural plate undergoes stereotypical rearrangements hypothesized to drive elevation of the neural folds.

Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme.

Hectd1 mutant mouse embryos exhibit the neural tube defect exencephaly associated with abnormal cranial mesenchyme. Cellular rearrangements in cranial mesenchyme are essential during neurulation for elevation of the neural folds. Here we investigate the molecular basis of the abnormal behavior of Hectd1 mutant cranial mesenchyme.

The visceral yolk sac endoderm provides for absorption of nutrients to the embryo during neurulation.

Neural tube defects (NTDs) represent some of the most common congenital malformations in humans. The causes of NTDs are complex with both genetic and environmental contributing factors. Periconception nutrition is an important environmental factor influencing the penetrance of NTDs.

Modeling neural tube defects in the mouse.

Neural tube defects (NTDs) are among the most common structural birth defects observed in humans. Mouse models provide an excellent experimental system to study the underlying causes of NTDs. These models not only allow for identification of the genes required for neurulation, they provide tractable systems for uncovering the developmental, pathological and molecular mechanisms underlying NTDs.

Polymerase chain reaction-based search for two alpha-globin gene mutations in India.

We have used restriction site-dependent polymerase chain reaction (PCR)-based methodology for detection of the alpha-globin polyadenylation (poly A) signal mutation, AATAAA>AATA- - and Hb Sun Prairie [alpha 130(H13)Ala-->Pro, GCT>CCT (alpha2)] mutation. The former mutation produces Hb H disease in the homozygous state and occurs frequently in the Indian population. It was detected in nine of 77 putative alpha-thalassemia (alpha-thal) patients and in three of 13 beta-thal intermedia patients tested.

Expression of Hand2 is sufficient for neurogenesis and cell type-specific gene expression in the enteric nervous system.

The basic helix-loop-helix DNA binding protein Hand2 is expressed in neural crest-derived precursors of enteric neurons and has been shown to affect both neurogenesis and neurotransmitter specification of noradrenergic sympathetic ganglion neurons. In the current study, our goal was to determine whether Hand2 affects neurogenesis and/or expression of vasoactive intestinal polypeptide and choline acetyltransferase in developing enteric neurons. Gain-of-function of Hand2 in HNK-1(+) immmunoselected precursor cells resulted in increased neurogenesis.

Perspectives on integration of cell extrinsic and cell intrinsic pathways of signaling required for differentiation of noradrenergic sympathetic ganglion neurons.

This review presents an analysis of current research aimed at deciphering the interplay of cell extrinsic and intrinsic signals required for specification and differentiation of noradrenergic sympathetic ganglion neurons. The development of noradrenergic sympathetic ganglion neurons depends upon expression of a core set of DNA regulatory molecules, including the Phox2 homeodomain proteins and the basic helix-loop-helix proteins, HAND2 and MASH1 whose expression is dependent upon cell extrinsic cues. Both bone morphogenetic protein(s) and cAMP have an integral role in the specification/differentiation of noradrenergic sympathetic ganglion neurons but how signaling downstream of these molecules is integrated and identification of their particular functions is just beginning to be elucidated.

A novel 33.3 kb deletion (- -KOL) in the alpha-globin gene cluster: a brief report on deletional alpha-thalassaemia in the heterogeneous eastern Indian population.

We have detected, in three unrelated eastern Indian individuals, a hitherto unreported alpha zero deletion, - -KOL, in the heterozygous state, encompassing the embryonic zeta2-globin and the duplicated alpha-globin genes extending from c. 1150 bp upstream of the zeta2 globin gene to c. 960 bp downstream of the theta1 gene.

Co-inheritance of the Hb Sun Prairie mutation with a point mutation at 5'-UTR in the eastern Indian population.

Haemoglobin (Hb) Sun Prairie (alpha2-globin cd130, GCT-->CCT, Ala-->Pro) is detected in three unrelated chromosomes, in association with a C-->T transition in the 5'-untranslated region (UTR), two bases upstream from the translation start site. Reported inversion of alpha/beta-mRNA ratio observed in Hb Sun Prairie mutants might stem from the second mutation and should be investigated. Molecular modelling studies indicate that the 130th residue of alpha-globin faces primarily the central cavity of the molecule and is not in contact with any beta-chain residue; further, no significant disruption of the Hb structure because of the Sun Prairie mutation is discernible.

Profile of beta-thalassemia in eastern India and its prenatal diagnosis.

Objective: To control the birth of thalassemic children in India.

Methods: Mutations present in the population of eastern India and in carrier parents seeking prenatal diagnosis were detected by the PCR-based technique of ARMS (amplification refractory mutation system) or gap-PCR. To screen for maternal tissue contamination in CVS, haplotypes associated with the beta-globin gene clusters were constructed using six polymorphic restriction sites.