Increased nuclear import characterizes aberrant nucleocytoplasmic transport in neurons from patients with spinocerebellar ataxia type 7.

Introduction: Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disorder characterized by cerebellar and retinal degeneration. SCA7 is caused by a CAG-polyglutamine repeat expansion in the ataxin-7 gene, which encodes a transcription factor protein that is a core component of the STAGA co-activator complex. As ataxin-7 protein regularly shuttles between the nucleus and the cytosol, we sought to test if polyglutamine-expanded ataxin-7 protein results in nuclear membrane abnormalities or defects in nucleocytoplasmic (N/C) transport.

A new high-pressure technique for the measurement of low frequency seismic attenuation using cyclic torsional loading.

We report a new technique for torsional testing of materials under giga-pascal pressures, which uses a shearing module in a large-volume Paris-Edinburgh press in combination with high-resolution fast radiographic x-ray imaging. The measurement of the relative amplitude and phase lag between the cyclic displacement in the sample and a standard material (AlO) provides the effective shear modulus and attenuation factor for the sample. The system can operate in the 0.

Microelectromechanical Transducer to Monitor High-Doses of Nuclear Irradiation.

This paper reports the design, fabrication and measured performance of a passive microelectromechanical transducer for the wireless monitoring of high irradiation doses in nuclear environments. The sensing device is composed of a polymer material (high-density polyethylene) sealed inside a cavity. Subjected to ionizing radiation, this material releases various gases, which increases the pressure inside the cavity and deflects a dielectric membrane.

Acoustofluidic rotational tweezing enables high-speed contactless morphological phenotyping of zebrafish larvae.

Modern biomedical research and preclinical pharmaceutical development rely heavily on the phenotyping of small vertebrate models for various diseases prior to human testing. In this article, we demonstrate an acoustofluidic rotational tweezing platform that enables contactless, high-speed, 3D multispectral imaging and digital reconstruction of zebrafish larvae for quantitative phenotypic analysis. The acoustic-induced polarized vortex streaming achieves contactless and rapid (~1 s/rotation) rotation of zebrafish larvae.

Loss-of-function mutations in MRAP2 are pathogenic in hyperphagic obesity with hyperglycemia and hypertension.

The G-protein-coupled receptor accessory protein MRAP2 is implicated in energy control in rodents, notably via the melanocortin-4 receptor. Although some MRAP2 mutations have been described in people with obesity, their functional consequences on adiposity remain elusive. Using large-scale sequencing of MRAP2 in 9,418 people, we identified 23 rare heterozygous variants associated with increased obesity risk in both adults and children.

Contactless, programmable acoustofluidic manipulation of objects on water.

Contact-free manipulation of small objects (e.g., cells, tissues, and droplets) using acoustic waves eliminates physical contact with structures and undesired surface adsorption.

Polyketide Synthase Plays a Conserved Role in Otolith Formation.

Otoliths (ear stones) are biomineralized complexes essential for the balancing and hearing function of the inner ears in fish. Their formation is controlled by a genetically programmed biological process that is yet to be defined. We have isolated and characterized a spontaneous genetic mutant zebrafish with a complete absence of otoliths, named ().

In-Situ Wireless Pressure Measurement Using Zero-Power Packaged Microwave Sensors.

This paper reports the indoor wireless measurement of pressure from zero-power (or passive) microwave (24 GHz) sensors. The sensors are packaged and allow the remote measurement of overpressure up to 2.1 bars.

Convergent origination of a -like dosage compensation mechanism in a reptile lineage.

Sex chromosomes differentiated from different ancestral autosomes in various vertebrate lineages. Here, we trace the functional evolution of the XY Chromosomes of the green anole lizard (), on the basis of extensive high-throughput genome, transcriptome and histone modification sequencing data and revisit dosage compensation evolution in representative mammals and birds with substantial new expression data. Our analyses show that sex chromosomes represent an ancient XY system that originated at least ≈160 million years ago in the ancestor of Iguania lizards, shortly after the separation from the snake lineage.

[Orthodontics and Alexis Schange in 1841].

Introduction: Alexis Schange was one of the first practitioners able to use accurate casts of the dental arches thanks to the invention of the impression-tray by Delabarre. Consequently, his diagnoses were more precise and his appliances fitted better than those of his predecessors.

Materials And Method: The author will first outline the status of Orthodontics prior to Schange and the advent of the first casts, before describing Schange's contribution to Orthodontics.

A novel NEUROG3 mutation in neonatal diabetes associated with a neuro-intestinal syndrome.

Neonatal diabetes mellitus (NDM) is a rare form of non-autoimmune diabetes usually diagnosed in the first 6 months of life. Various genetic defects have been shown to cause NDM with diverse clinical presentations and variable severity. Among transcriptional factor genes associated with isolated or syndromic NDM, a few cases of homozygous mutations in the NEUROG3 gene have been reported, all mutated patients presenting with congenital malabsorptive diarrhea with or without diabetes at a variable age of onset from early life to childhood.

[Optimization of the final lingual occlusion: an analysis].

Introduction: The objectives of orthodontic treatment are to achieve a functional, aesthetic and sustainable occlusion. However, its analysis is often limited to the study of its buccal side, easy to check in mouth. Yet, the lingual occlusion is also of paramount importance.

A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis.

Background: Hydranencephaly is a congenital anomaly leading to replacement of the cerebral hemispheres with a fluid-filled cyst. The goals of this work are to describe a novel autosomal-recessive syndrome that includes hydranencephaly (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly (MARCH)); to identify its genetic cause(s) and to provide functional insight into pathomechanism.

Methods: We used homozygosity mapping and exome sequencing to identify recessive mutations in a single family with three affected fetuses.

[The birth of Edgewise or the last and best Angle's mechanisms].

Introduction: Mechanical forces applied to the teeth constitute a not-insignificant feature of orthodontic treatment. Edgewise, the most commonly used type of mechanics, was introduced 88 years ago and has become a standard worldwide. The invention of Edgewise by E.

The complete local genotype-phenotype landscape for the alternative splicing of a human exon.

The properties of genotype-phenotype landscapes are crucial for understanding evolution but are not characterized for most traits. Here, we present a >95% complete local landscape for a defined molecular function-the alternative splicing of a human exon (FAS/CD95 exon 6, involved in the control of apoptosis). The landscape provides important mechanistic insights, revealing that regulatory information is dispersed throughout nearly every nucleotide in an exon, that the exon is more robust to the effects of mutations than its immediate neighbours in genotype space, and that high mutation sensitivity (evolvability) will drive the rapid divergence of alternative splicing between species unless it is constrained by selection.

What Is the Best NGS Enrichment Method for the Molecular Diagnosis of Monogenic Diabetes and Obesity?

Molecular diagnosis of monogenic diabetes and obesity is of paramount importance for both the patient and society, as it can result in personalized medicine associated with a better life and it eventually saves health care spending. Genetic clinical laboratories are currently switching from Sanger sequencing to next-generation sequencing (NGS) approaches but choosing the optimal protocols is not easy. Here, we compared the sequencing coverage of 43 genes involved in monogenic forms of diabetes and obesity, and variant detection rates, resulting from four enrichment methods based on the sonication of DNA (Agilent SureSelect, RainDance technologies), or using enzymes for DNA fragmentation (Illumina Nextera, Agilent HaloPlex).

[The prehistory of orthodontics].

Orthodontics came into being in 1728. Previously, practitioners were at a loss when confronted with crooked teeth. A Latin philosopher had an ingenious flash of orthodontic inspiration.

Genetic variants in LEP, LEPR, and MC4R explain 30% of severe obesity in children from a consanguineous population.

Objective: Single gene mutations leading to severe obesity have so far been identified in 3-5% cases in European populations. However, prevalence of these pathogenic mutations has not systematically been examined in specific consanguineous populations. Here we describe the incidence of obesity-associated mutations through a step-wise sequence analysis, in a cohort of 73 Pakistani children with severe obesity from consanguineous families.

[What makes a pleasing face].

Regular faces are beautiful because they are expressive and arouse an interest in the observer due to the variations in their shape, their surface appearance and their movements. The sensitivity of the eye of the beholder is correlated to the expressivity of the face and of the dentition. Better, however, to avoid any indication of aggression that could foreshadow the senescence of the face.

Novel LEPR mutations in obese Pakistani children identified by PCR-based enrichment and next generation sequencing.

Objective: Mutations in leptin receptor gene (LEPR) result in early onset extreme adiposity. However, their prevalence in different populations is not known. Indeed, LEPR screening by gold standard Sanger sequencing has been limited by its large size and the cost.

[New developments in cephalometrics].

Recently l recalled the error in the principle which makes cephalometric analysis unsuitable for orthodontic diagnosis. Now, three methods of analysis have been published precisely conceived in order to avoid this error. Will cephalometric analysis succeed in its search for the truth?

Highly sensitive diagnosis of 43 monogenic forms of diabetes or obesity through one-step PCR-based enrichment in combination with next-generation sequencing.

Objective: Accurate etiological diagnosis of monogenic forms of diabetes and obesity is useful as it can lead to marked improvements in patient care and genetic counseling. Currently, molecular diagnosis based on Sanger sequencing is restricted to only a few genes, as this technology is expensive, time-consuming, and labor-intensive. High-throughput next-generation sequencing (NGS) provides an opportunity to develop innovative cost-efficient methods for sensitive diabetes and obesity multigene screening.

Familial early-onset diabetes is not a typical MODY in several Tunisian patients.

Background: MODY (Maturity-onset diabetes of the young), a dominantly inherited form of early-onset diabetes, is clinically and genetically heterogeneous with more than ten genetic subtypes described worldwide.

Aim: To evaluate the possible existence of MODY in 12 young diabetic Tunisian patients by searching for mutations in the most prevalent MODY genes.

Methods: Twelve patients with diabetes in 2-to-3 generations, all diagnosed before age 31, were screened for mutations and deletions in HNF1A, HNF4A, INS, IPF1, NEUROD1 and GCK genes by Sanger sequencing and by Multiplex ligation-dependent probe amplification assay.