Effect of Deletion of Ghrelin-O-Acyltransferase on the Pulsatile Release of Growth Hormone in Mice.

Ghrelin, a gut hormone originating from the post-translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT), conferring selective binding to the GHS-R1a receptor via acylated ghrelin. Complete loss of preproghrelin-derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl-ghrelin to pulsatile GH release remains to be established.

Infants born large-for-gestational-age display slower growth in early infancy, but no epigenetic changes at birth.

We evaluated the growth patterns of infants born large-for-gestational-age (LGA) from birth to age 1 year compared to those born appropriate-for-gestational-age (AGA). In addition, we investigated possible epigenetic changes associated with being born LGA. Seventy-one newborns were classified by birth weight as AGA (10(th)-90(th) percentile; n = 42) or LGA (>90(th) percentile; n = 29).

Mechanism of MenE inhibition by acyl-adenylate analogues and discovery of novel antibacterial agents.

MenE is an o-succinylbenzoyl-CoA (OSB-CoA) synthetase in the bacterial menaquinone biosynthesis pathway and is a promising target for the development of novel antibacterial agents. The enzyme catalyzes CoA ligation via an acyl-adenylate intermediate, and we have previously reported tight-binding inhibitors of MenE based on stable acyl-sulfonyladenosine analogues of this intermediate, including OSB-AMS (1), which has an IC50 value of ≤25 nM for Escherichia coli MenE. Herein, we show that OSB-AMS reduces menaquinone levels in Staphylococcus aureus, consistent with its proposed mechanism of action, despite the observation that the antibacterial activity of OSB-AMS is ∼1000-fold lower than the IC50 for enzyme inhibition.

The interplay between metabolic homeostasis and neurodegeneration: insights into the neurometabolic nature of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease that is characterized by the selective degeneration of upper motor neurons and lower spinal motor neurons, resulting in the progressive paralysis of all voluntary muscles. Approximately 10 % of ALS cases are linked to known genetic mutations, with the remaining 90 % of cases being sporadic. While the primary pathology in ALS is the selective death of upper and lower motor neurons, numerous studies indicate that an imbalance in whole body and/or cellular metabolism influences the rate of progression of disease.

[Which place for direct oral anticoagulants in routine hospital medical practice?].

Purpose: More than one million patients received an oral anticoagulant treatment in France. This medication is the first aetiology of iatrogenic events. Recently, direct oral anticoagulant (DOA) provided efficacy and safety in the treatment of atrial fibrillation and venous thromboembolic events.

When Is It Safe to Return to Driving After Spinal Surgery?

Study Design Prospective study. Objective Surgeons' recommendations for a safe return to driving following cervical and lumbar surgery vary and are based on empirical data. Driver reaction time (DRT) is an objective measure of the ability to drive safely.

Altered expression of metabolic proteins and adipokines in patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by the loss of upper cortical and lower motor neurons. ALS causes death within 2-5years of diagnosis. Diet and body mass index influence the clinical course of disease, however there is limited information about the expression of metabolic proteins and fat-derived cytokines (adipokines) in ALS.

[Agranulocytosis related to fluindione: A case report].

Introduction: While in most countries warfarin is the preferred anti-vitamin K, fluindione, a molecule with a prolonged half-life remains largely prescribed in France. Some of its side effects, including immuno-allergic complications, remain poorly understood.

Case Report: A 77-year-old woman presented with a febrile severe neutropenia of immunoallergic mechanism with a favourable outcome associated with fluindione, introduced 25 days earlier for the treatment of atrial fibrillation.

The diversity and host interactions of Propionibacterium acnes bacteriophages on human skin.

The viral population, including bacteriophages, is an important component of the human microbiota, yet is poorly understood. We aim to determine whether bacteriophages modulate the composition of the bacterial populations, thus potentially playing a role in health or disease. We investigated the diversity and host interactions of the bacteriophages of Propionibacterium acnes, a major human skin commensal implicated in acne pathogenesis.

A metabolic switch toward lipid use in glycolytic muscle is an early pathologic event in a mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common fatal motor neuron disease in adults. Numerous studies indicate that ALS is a systemic disease that affects whole body physiology and metabolic homeostasis. Using a mouse model of the disease (SOD1(G86R)), we investigated muscle physiology and motor behavior with respect to muscle metabolic capacity.

Estimation of the Binding Free Energy of AC1NX476 to HIV-1 Protease Wild Type and Mutations Using Free Energy Perturbation Method.

The binding mechanism of AC1NX476 to HIV-1 protease wild type and mutations was studied by the docking and molecular dynamics simulations. The binding free energy was calculated using the double-annihilation binding free energy method. It is shown that the binding affinity of AC1NX476 to wild type is higher than not only ritonavir but also darunavir, making AC1NX476 become attractive candidate for HIV treatment.

Evolution in obesity and chronic disease prevention practice in California public health departments, 2010.

Introduction: Local health departments (LHDs) are dedicating resources and attention to preventing obesity and associated chronic diseases, thus expanding their work beyond traditional public health activities such as surveillance. This study investigated practices of local health departments in California to prevent obesity and chronic disease.

Methods: We conducted a web-based survey in 2010 with leaders in California's LHDs to obtain diverse perspectives on LHDs' practices to prevent obesity and chronic disease.

The role of DNA methylation: a challenge for the DOHaD paradigm in going beyond the historical debate.

A heritage of considerable research into such phenomena as parental imprinting and carcinogenesis is an almost axiomatic association of the DNA methylation epigenetic mark with the silencing of gene expression. However, the increasing technical resolution afforded by burgeoning -omics technologies reveals that a more elaborate interaction may exist between DNA methylation, within sub-regions of gene structure and/or specific dinucleotide sites, and levels of gene activity. Furthermore, seminal observations from the field of DOHaD, which clearly define the alignment of sequential epigenetic modifications and gene activity appear not to support a strictly causal relationship between DNA methylation and gene silencing.

Identification and characterization of yak (Bos grunniens) b-Boule gene and its alternative splice variants.

Boule is responsible for meiotic arrest of sperms and male sterility during mammalian spermatogenesis. In the present study, we first identified yak b-Boule gene and its two alternative splice variants. The full length coding region of yak b-Boule is 888bp and encodes a 295-amino acid protein with a typical RNA-recognition motif (RRM) and a Deleted in Azoospermia (DAZ) repetitive sequence motif.

Antiparallel triple-strand architecture for prefibrillar Aβ42 oligomers.

Aβ42 oligomers play key roles in the pathogenesis of Alzheimer disease, but their structures remain elusive partly due to their transient nature. Here, we show that Aβ42 in a fusion construct can be trapped in a stable oligomer state, which recapitulates characteristics of prefibrillar Aβ42 oligomers and enables us to establish their detailed structures. Site-directed spin labeling and electron paramagnetic resonance studies provide structural restraints in terms of side chain mobility and intermolecular distances at all 42 residue positions.

[Facial diplegia as the presenting feature of Lyme disease].

Introduction: Diagnosis of neuroborreliosis may be difficult. Neuroborreliosis mainly results in lymphocytic meningitis and in meningoradiculitis (67-83% of cases).

Case Report: We report the case of a patient who developed a sudden facial diplegia, revealing neuroborreliosis proved by positive blood and cerebrospinal fluid serology.

Homodyne digital interferometry for a sensitive fiber frequency reference.

Digitally enhanced homodyne interferometry enables robust interferometric sensitivity to be achieved in an optically simple configuration by shifting optical complexity into the digital signal processing regime. We use digitally enhanced homodyne interferometry in a simple, all-fiber Michelson interferometer to achieve a frequency reference stability of better than 20 Hz/√Hz from 10 mHz to 1 Hz, satisfying, for the first time in an all fiber system, the stability requirements for the Gravity Recovery and Climate Experiment Follow On mission. In addition, we have demonstrated stability that satisfies the future mission objectives at frequencies down to 1 mHz.

Large-scale chaos and fluctuations in active nematics.

We show that dry active nematics, e.g., collections of shaken elongated granular particles, exhibit large-scale spatiotemporal chaos made of interacting dense, ordered, bandlike structures in a parameter region including the linear onset of nematic order.

[Complement deficiencies and human diseases].

The complement system is a complex system involving serum and membrane proteins interacting in a regulated manner. The complement system plays a major role in antibacterial immunity, in inflammation, and in immune complex processing. Therefore, deficiencies in complement proteins are associated with increased susceptibility to bacterial infections and autoimmune diseases.

Gender differences in autoimmune disease.

Autoimmune diseases are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Autoimmune diseases can be systemic or can affect specific organs or body systems. For most autoimmune diseases there is a clear sex difference in prevalence, whereby females are generally more frequently affected than males.

Digitally enhanced optical fiber frequency reference.

We use digitally enhanced heterodyne interferometry to measure the stability of optical fiber laser frequency references. Suppression of laser frequency noise by over four orders of magnitude is achieved using post processing time delay interferometry, allowing us to measure the mechanical stability for frequencies as low as 100 μHz. The performance of the digitally enhanced heterodyne interferometer platform used here is not practically limited by the dynamic range or bandwidth issues that can occur in feedback stabilization systems.

Body mass index and dietary intervention: implications for prognosis of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an adult onset, neurodegenerative disease that is characterized by the loss of upper (corticospinal) and lower motor neurons. ALS is a multifactorial disease whereby a combination of genetic and environmental factors may contribute to disease pathogenesis. While the majority of studies indicate that the underlying causes for ALS pathology may be due to multiple defects at the cellular level, factors that have recently been identified to be associated with survival could lead to the development of beneficial interventions.