Clinical phenotype and the lack of mutations in the CHRNG, CHRND, and CHRNA1 genes in two Indian families with Escobar syndrome

The objective of this study was to report the clinical phenotype and genetic analysis of two Indian families with Escobar syndrome (ES). The diagnosis of ES in both families was made on the basis of published clinical features. Blood samples were collected from members of both families and used in genomic DNA isolation. The entire coding regions and intron-exon junctions of the ES gene CHRNG (cholinergic receptor, nicotinic, gamma), and two other related genes, CHRND and CHRNA1, were amplified and sequenced to search for mutations in both families. Both families show a typical form of ES. Sequencing of the entire coding regions including the intron-exon junctions of the three genes did not yield any mutations in these families. In conclusion, it is possible that the mutations in these genes are located in the promoter or deep intronic regions that we failed to identify or the ES in these families is caused by mutations in a different gene. The lack of mutations in CHRNG has also been reported in several families, suggesting the possibility of at least one more gene for this syndrome. Clin Dysmorphol 22:54-58 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

GYROSONICS: SIGNATURE ANALYSIS AND REDUCED-ORDER MODELS

In this paper, the authors study the structure of a novel binaural sound with a certain phase and amplitude modulation and the response to this excitation when it is applied to natural rewarding circuit of human brain through auditory neural pathways. This novel excitation, also referred to as gyrosonic excitation in this work, has been found to have interesting effects such as stabilization effects on the left and right hemispheric brain signaling as captured by Galvanic Skin Resistance (GSR) measurements, control of cardiac rhythms (observed from ECG signals), mitigation of psychosomatic syndrome, and mitigation of migraine pain. Experimental data collected from human subjects are presented, and these data are examined to categorize the extent of systems disorder and reinforcement reward due to the gyrosonic stimulus. A multi-path reduced-order model has been developed to analyze the GSR signals. The filtered results are indicative of complicated reinforcing reward patterns due to the gyrosonic stimulation when it is used as a control input for patients with psychosomatic and cardiac disorders.

Magnetic skin layer of NiO(100) probed by polarization-dependent spectromicroscopy

Using polarization-dependent x-ray photoemission electron microscopy, we have investigated the surface effects on antiferromagnetic (AFM) domain formation. Depth-resolved information obtained from our study indicates the presence of strain-induced surface AFM domains on some of the cleaved NiO(100) crystals, which are unusually thinner than bulk AFM domain wall widths (similar to 150 nm). Existence of such magnetic skin layer is substantiated by exchange-coupled ferromagnetic Fe domains in Fe/NiO(100), thereby evidencing the influence of this surface AFM domains on interfacial magnetic coupling. Our observations demonstrate a depth evolution of AFM structure in presence of induced surface strain, while the surface symmetry-breaking in absence of induced strain does not modify the bulk AFM domain structure. Realization of such thin surface AFM layer will provide better microscopic understanding of the exchange bias phenomena. (C) 2014 AIP Publishing LLC.

Whole exome sequencing identifies a novel splice-site mutation in ADAMTS17 in an Indian family with Weill-Marchesani syndrome

Purpose: Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder, characterized by short stature, micro-spherophakic lens, and stubby hands and feet (brachydactyly). WMS is caused by mutations in the FBN1, ADAMTS10, and LTBP2 genes. Mutations in the LTBP2 and ADAMTS17 genes cause a WMS-like syndrome, in which the affected individuals show major features of WMS but do not display brachydactyly and joint stiffness. The main purpose of our study was to determine the genetic cause of WMS in an Indian family. Methods: Whole exome sequencing (WES) was used to identify the genetic cause of WMS in the family. The cosegregation of the mutation was determined with Sanger sequencing. Reverse transcription (RT)-PCR analysis was used to assess the effect of a splice-site mutation on splicing of the ADAMTS17 transcript. Results: The WES analysis identified a homozygous novel splice-site mutation c.873+1G>T in a known WMS-like syndrome gene, ADAMTS17, in the family. RT-PCR analysis in the patient showed that exon 5 was skipped, which resulted in the deletion of 28 amino acids in the ADAMTS17 protein. Conclusions: The mutation in the WMS-like syndrome gene ADAMTS17 also causes WMS in an Indian family. The present study will be helpful in genetic diagnosis of this family and increases the number of mutations of this gene to six.

A feasibility study of a post-buckled beam for actuating helicopter trailing edge flap

Active trailing edge flaps (TEFs) are one of the most promising devices for helicopter vibration reduction. Smart actuators such as the piezoelectric stack actuators (PEAs) are used for TEF actuation. PEAs possess high energy density and have large force in dynamic condition but are limited to small displacements. In this investigation, we study a linear to rotary motion amplification mechanism (AM-2) based on a pinned-pinned post-buckled beam to actuate trailing edge flaps. A linear motion amplification mechanism is developed and coupled with AM-2 to amplify angular flap deflections. Experiments are conducted on bench top-test setup, and maximum flap angle deflections of the order of 12A degrees are achieved in the static case. An aeroelastic analysis is performed and 91 % reduction in helicopter vibration is obtained with multiharmonic control inputs.

SIRT6 Promotes COX-2 Expression and Acts as an Oncogene in Skin Cancer

SIRT6 is a SIR2 family member that regulates multiple molecular pathways involved in metabolism, genomic stability, and aging. It has been proposed previously that SIRT6 is a tumor suppressor in cancer. Here, we challenge this concept by presenting evidence that skin-specific deletion of SIRT6 in the mouse inhibits skin tumorigenesis. SIRT6 promoted expression of COX-2 by repressing AMPK signaling, thereby increasing cell proliferation and survival in the skin epidermis. SIRT6 expression in skin keratinocytes was increased by exposure to UVB light through activation of the AKT pathway. Clinically, we found that SIRT6 was upregulated in human skin squamous cell carcinoma. Taken together, our results provide evidence that SIRT6 functions as an oncogene in the epidermis and suggest greater complexity to its role in epithelial carcinogenesis. (C) 2014 AACR.

Whole exome sequencing in an Indian family links Coats plus syndrome and dextrocardia with a homozygous novel CTC1 and a rare HES7 variation

Background: Coats plus syndrome is an autosomal recessive, pleiotropic, multisystem disorder characterized by retinal telangiectasia and exudates, intracranial calcification with leukoencephalopathy and brain cysts, osteopenia with predisposition to fractures, bone marrow suppression, gastrointestinal bleeding and portal hypertension. It is caused by compound heterozygous mutations in the CTC1 gene. Case presentation: We encountered a case of an eight-year old boy from an Indian family with manifestations of Coats plus syndrome along with an unusual occurrence of dextrocardia and situs inversus. Targeted resequencing of the CTC1 gene as well as whole exome sequencing (WES) were conducted in this family to identify the causal variations. The identified candidate variations were screened in ethnicity matched healthy controls. The effect of CTC1 variation on telomere length was assessed using Southern blot. A novel homozygous missense mutation c.1451A > C (p.H484P) in exon 9 of the CTC1 gene and a rare 3'UTR known dbSNP variation (c.*556 T > C) in HES7 were identified as the plausible candidates associated with this complex phenotype of Coats plus and dextrocardia. This CTC1 variation was absent in the controls and we also observed a reduced telomere length in the affected individual's DNA, suggesting its likely pathogenic nature. The reported p.H484P mutation is located in the N-terminal 700 amino acid regionthat is important for the binding of CTC1 to ssDNA through its two OB domains. WES data also showed a rare homozygous missense variation in the TEK gene in the affected individual. Both HES7 and TEK are targets of the Notch signaling pathway. Conclusions: This is the first report of a genetically confirmed case of Coats plus syndrome from India. By means of WES, the genetic variations in this family with unique and rare complex phenotype could be traced effectively. We speculate the important role of Notch signaling in this complex phenotypic presentation of Coats plus syndrome and dextrocardia. The present finding will be useful for genetic diagnosis and carrier detection in the family and for other patients with similar disease manifestations.

Microbial community profiling shows dysbiosis in the lesional skin of Vitiligo subjects

Healthy human skin harbours a diverse array of microbes that comprise the skin microbiome. Commensal bacteria constitute an important component of resident microbiome and are intricately linked to skin health. Recent studies describe an association between altered skin microbial community and epidemiology of diseases, like psoriasis, atopic dermatitis etc. In this study, we compare the differences in bacterial community of lesional and non-lesional skin of vitiligo subjects. Our study reveals dysbiosis in the diversity of microbial community structure in lesional skin of vitiligo subjects. Although individual specific signature is dominant over the vitiligo-specific microbiota, a clear decrease in taxonomic richness and evenness can be noted in lesional patches. Investigation of community specific correlation networks reveals distinctive pattern of interactions between resident bacterial populations of the two sites (lesional and non-lesional). While Actinobacterial species constitute the central regulatory nodes (w.r.t. degree of interaction) in non-lesional skin, species belonging to Firmicutes dominate on lesional sites. We propose that the changes in taxonomic characteristics of vitiligo lesions, as revealed by our study, could play a crucial role in altering the maintenance and severity of disease. Future studies would elucidate mechanistic relevance of these microbial dynamics that can provide new avenues for therapeutic interventions.

Effects of 'sinking in' and 'piling up' on estimating the contact area under load in indentation

The phenomena of the 'piling up' and 'sinking-in' of surface profiles in conical indentation in elastic-plastic solids with work hardening are studied using dimensional and finite-element analysis. The degree of sinking in and piling up is shown to depend on the ratio of the initial yield strength Y to Young's modulus E and on the work-hardening exponent n. The widely used procedure proposed by Oliver and Pharr for estimating contact depth is then evaluated systematically. By comparing the contact depth obtained directly from finite-element calculations with that obtained from the initial unloading slope using the Oliver-Pharr procedure, the applicability of the procedure is discussed.

The effect of an insoluble surfactant on the skin friction of a bubble

In this paper, we develop a novel moving mesh method suitable for solving axisymmetric free-boundary problems, including the Marangoni effect induced by surfactant or temperature variation. This method employs a body-fitted grid system where the gas-liquid interface is one line of the grid system. We model the surfactant equation of state with a non-linear Langmuir law, and, for simplicity, we limit ourselves to the situation of an insoluble surfactant. We solve complicated dynamic boundary conditions accurately on the gas-liquid interface in the framework of finite-volume methods. Our method is used to study the effect of a surfactant on the skin friction of a bubble in a uniaxial flow. For the limiting case where the surface diffusivity is zero, the effect of a tangential stress generated by the surface tension gradient, allows us to explain a new phenomenon in high concentration regimes: larger surface tension, but also larger deformation. Furthermore, this condition leads to the formation of boundary layers and flow separation at high Reynolds numbers. The influence of these complex flow patterns is examined. © 2005 Elsevier SAS. All rights reserved.

Control dynamics of severe acute respiratory syndrome transmission

Severe acute respiratory syndrome (SARS) is a serious disease with many puzzling features. We present a simple, dynamic model to assess the epidemic potential of SARS and the effectiveness of control measures. With this model, we analysed the SARS epidemic data in Beijing. The data fitting gives the basic case reproduction number of 2.16 leading to the outbreak, and the variation of the effective reproduction number reflecting the control effect. Noticeably, our study shows that the response time and the strength of control measures have significant effects on the scale of the outbreak and the lasting time of the epidemic.