Structure-based discovery and in vitro validation of inhibitors of chloride intracellular channel 4 protein.

The use of computer-aided methods have continued to propel accelerated drug discovery across various disease models, interestingly allowing the specific inhibition of pathogenic targets. Chloride Intracellular Channel Protein 4 (CLIC4) is a novel class of intracellular ion channel highly implicated in tumor and vascular biology. It regulates cell proliferation, apoptosis and angiogenesis; and is involved in multiple pathologic signaling pathways.

A Zn2+-triggered two-step mechanism of CLIC1 membrane insertion and activation into chloride channels.

The chloride intracellular channel (CLIC) protein family displays the unique feature of altering its structure from a soluble form to a membrane-bound chloride channel. CLIC1, a member of this family, is found in the cytoplasm or in internal and plasma membranes, with membrane relocalisation linked to endothelial disfunction, tumour proliferation and metastasis. The molecular switch promoting CLIC1 activation remains under investigation.

Cyberbullying and School Bullying Are Related to Additive Adverse Effects among Adolescents.

Introduction: The aim of this study was to examine whether (a) cyberbullying has unique associations with mental health problems, risk-taking, and self-harm behavior in victims and perpetrators when compared to school bullying and (b) if cyberbullying is associated with an additional burden for students already involved in school bullying.

Methods: Data were collected from 6,561 students across 23 schools in Germany (grades 5-13). The sample was divided into the following four groups: cyber-only involvement (victims = 1.

A lithium-isotope perspective on the evolution of carbon and silicon cycles.

The evolution of the global carbon and silicon cycles is thought to have contributed to the long-term stability of Earth's climate. Many questions remain, however, regarding the feedback mechanisms at play, and there are limited quantitative constraints on the sources and sinks of these elements in Earth's surface environments. Here we argue that the lithium-isotope record can be used to track the processes controlling the long-term carbon and silicon cycles.

Effects and moderators of the Olweus bullying prevention program (OBPP) in Germany.

Bullying is a common and significant risk factor for mental and physical health problems. The aim of the outlined study was to evaluate the German version of the Olweus Bullying Prevention Program (OBPP) and to investigate potential moderators of its effectiveness. 23 schools started with the implementation and all students were invited to complete the Olweus Bullying Questionnaire annually.

Symptoms of posttraumatic stress disorder among targets of school bullying.

Background: The aim of this study was to investigate whether bullying among students is associated with symptoms of posttraumatic stress disorder (PTSD), and whether associations are comparable to other traumatic events leading to PTSD.

Methods: Data were collected from 219 German children and adolescents: 150 students from grade six to ten and 69 patients from an outpatient clinic for PTSD as a comparison group. Symptoms of PTSD were assessed using the Children's Revised Impact of Event Scale (CRIES) and the Posttraumatic Symptom Scale (PTSS-10).

In vitro bioassessment of the immunomodulatory activity of Saccharomyces cerevisiae components using bovine macrophages and Mycobacterium avium ssp. paratuberculosis.

The yeast Saccharomyces cerevisiae and its components are used for the prevention and treatment of enteric disease in different species; therefore, they may also be useful for preventing Johne's disease, a chronic inflammatory bowel disease of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). The objective of this study was to identify potential immunomodulatory S.

A Review of the Human Sigma-1 Receptor Structure.

The Sigma-1 Receptor (S1R) is a small, ligand-regulated integral membrane protein involved in cell homeostasis and the cellular stress response. The receptor has a multitude of protein and small molecule interaction partners with therapeutic potential. Newly reported structures of the human S1R in ligand-bound states provides essential insights into small molecule binding in the context of the overall protein structure.

Assessment of yeast Saccharomyces cerevisiae component binding to Mycobacterium avium subspecies paratuberculosis using bovine epithelial cells.

Background: Since yeast Saccharomyces cerevisiae and its components are being used for the prevention and treatment of enteric diseases in different species, they may also be useful for preventing Johne's disease, a chronic inflammatory bowel disease of ruminants caused by Mycobacterium avium spp. paratuberculosis (MAP). This study aimed to identify potential yeast derivatives that may be used to help prevent MAP infection.

Live yeasts enhance fibre degradation in the cow rumen through an increase in plant substrate colonization by fibrolytic bacteria and fungi.

Aims: To monitor the effect of a live yeast additive on feedstuff colonization by targeted fibrolytic micro-organisms and fibre degradation in the cow rumen.

Methods And Results: Abundance of adhering fibrolytic bacteria and fungi on feedstuffs incubated in sacco in the cow rumen was quantified by qPCR and neutral detergent fibre (NDF) degradation was measured. Saccharomyces cerevisiae I-1077 (SC) increased the abundance of fibre-associated Fibrobacter succinogenes on wheat bran (WB) and that of Ruminococcus flavefaciens on alfalfa hay (AH) and wheat silage (WS).

Solution NMR studies reveal the location of the second transmembrane domain of the human sigma-1 receptor.

The sigma-1 receptor (S1R) is a ligand-regulated membrane chaperone protein associated with endoplasmic reticulum stress response, and modulation of ion channel activities at the plasma membrane. We report here a solution NMR study of a S1R construct (S1R(Δ35)) in which only the first transmembrane domain and the eight-residue N-terminus have been removed. The second transmembrane helix is found to be composed of residues 91-107, which corresponds to the first steroid binding domain-like region.

[Prevalence and intensity of nightmares in traumatized versus non-traumatized children and adolescents].

Objective: Nightmares may be seen as a symptom of traumatization in both children and adults. Nightmares are assumed to be more frequent and more distressing among traumatized children and adolescents than among those without trauma. A total of 38 traumatized and 40 nontraumatized children and adolescents were surveyed.

Characterization of the human sigma-1 receptor chaperone domain structure and binding immunoglobulin protein (BiP) interactions.

The sigma-1 receptor (S1R) is a ligand-regulated membrane protein chaperone involved in the ER stress response. S1R activity is implicated in diseases of the central nervous system including amnesia, schizophrenia, depression, Alzheimer disease, and addiction. S1R has been shown previously to regulate the Hsp70 binding immunoglobulin protein (BiP) and the inositol triphosphate receptor calcium channel through a C-terminal domain.

Large colonial organisms with coordinated growth in oxygenated environments 2.1 Gyr ago.

The evidence for macroscopic life during the Palaeoproterozoic era (2.5-1.6 Gyr ago) is controversial.

The Myxococcus xanthus Nla4 protein is important for expression of stringent response-associated genes, ppGpp accumulation, and fruiting body development.

Changes in gene expression are important for the landmark morphological events that occur during Myxococcus xanthus fruiting body development. Enhancer binding proteins (EBPs), which are transcriptional activators, play prominent roles in the coordinated expression of developmental genes. A mutation in the EBP gene nla4 affects the timing of fruiting body formation, the morphology of mature fruiting bodies, and the efficiency of sporulation.

Nla18, a key regulatory protein required for normal growth and development of Myxococcus xanthus.

NtrC-like activators regulate the transcription of a wide variety of adaptive genes in bacteria. Previously, we demonstrated that a mutation in the ntrC-like activator gene nla18 causes defects in fruiting body development in Myxococcus xanthus. In this report, we describe the effect that nla18 inactivation has on gene expression patterns during development and vegetative growth.