Regulation of atypical MAP kinases ERK3 and ERK4 by the phosphatase DUSP2

The atypical MAP kinases ERK3 and ERK4 are activated by phosphorylation of a serine residue lying within the activation loop signature sequence S-E-G. However, the regulation of ERK3 and ERK4 phosphorylation and activity is poorly understood. Here we report that the inducible nuclear dual-specificity MAP kinase phosphatase (MKP) DUSP2, a known regulator of the ERK and p38 MAPKs, is unique amongst the MKP family in being able to bind to both ERK3 and ERK4. This interaction is mediated by a conserved common docking (CD) domain within the carboxyl-terminal domains of ERK3 and ERK4 and the conserved kinase interaction motif (KIM) located within the non-catalytic amino terminus of DUSP2. This interaction is direct and results in the dephosphorylation of ERK3 and ERK4 and the stabilization of DUSP2. In the case of ERK4 its ability to stabilize DUSP2 requires its kinase activity. Finally, we demonstrate that expression of DUSP2 inhibits ERK3 and ERK4-mediated activation of its downstream substrate MK5. We conclude that the activity of DUSP2 is not restricted to the classical MAPK pathways and that DUSP2 can also regulate the atypical ERK3/4-MK5 signalling pathway in mammalian cells

Metabolic syndrome and carotid intima-media thickness in chronic obstructive pulmonary disease

BACKGROUND: The aim of this study is to investigate the prevalence of metabolic syndrome (MetS), carotid intima media thickness (IMT), and serum C-reactive protein (CRP) levels in patients with chronic obstructive pulmonary disease (COPD), and the possible relationships among them. METHODS: Fifty stable COPD patients and 40 healthy controls were included in the study. The participants were further divided into four groups according to their smoking status. Pulmonary function tests were performed in COPD patients. Anthropometric measurements and blood chemistry analysis, serum CRP levels and carotid intima-media thickness (IMT) measurements were performed in all the study population. RESULTS: Prevalence of metabolic syndrome was 43% in COPD patients and 30% in the control group (p = 0.173). FEV(1)% and FEV(1)/FVC were higher in COPD patients with MetS (p = 0.001 and p = 0.014, respectively) compared to those without MetS. Prevalence of MetS was significantly different among the COPD patients with different stages (p = 0.017) with the highest value in stage 2 (59%). Carotid IMT was significantly higher in COPD patients than in control group (1.07 ± 0.25 mm and 0.86 ± 0.18 mm, respectively; p < 0.001). Serum CRP levels were not different in COPD patients and controls, however they were higher in individuals with MetS compared to those without MetS regardless of COPD presence (p = 0.02). CONCLUSIONS: Early markers of atherogenesis, in terms of carotid IMT, were found to be higher in COPD patients than in healthy controls. MetS prevalence was observed to decrease as the severity of airflow obstruction increased. Therefore, screening COPD patients for these cardiovascular risk factors would be a novel approach even in absence of symptoms

Sexual behavior and drug consumption among young adults in a shantytown in Lima, Peru

<p>Abstract</p> <p>Background</p> <p>Risky sexual behaviors of young adults have received increasing attention during the last decades. However, few studies have focused on the sexual behavior of young adults in shantytowns of Latin America. Specifically, studies on the association between sexual behaviors and other risk factors for sexually transmitted infections (STI) and HIV/AIDS transmission, such as the consumption of illicit drugs or alcohol are scarce in this specific context.</p> <p>Methods</p> <p>The study participants were 393 men and 400 women between 18 and 30 years of age, from a shantytown in Lima, Peru. Data were obtained via survey: one section applied by a trained research assistant, and a self-reporting section. Logistic regression was used to estimate associations between use of any illicit drug, high-risk sexual behaviors and reported STI symptoms, adjusting for alcohol consumption level and various socio-demographic characteristics.</p> <p>Results</p> <p>Among men, age of sexual debut was lower, number of lifetime sexual partners was higher, and there were higher risk types of sexual partners, compared to women. Though consistent condom use with casual partners was low in both groups, reported condom use at last intercourse was higher among men than women. Also, a lifetime history of illicit drug consumption decreased the probability of condom use at last sexual intercourse by half. Among men, the use of illicit drugs doubled the probability of intercourse with a casual partner during the last year and tripled the probability of reported STI symptoms.</p> <p>Conclusion</p> <p>Drug consumption is associated with high-risk sexual behaviors and reported STI symptoms in a Lima shantytown after controlling for alcohol consumption level. Development of prevention programs for risky sexual behaviors, considering gender differences, is discussed.</p

Bacterial Acquisition in Juveniles of Several Broadcast Spawning Coral Species

Coral animals harbor diverse microorganisms in their tissues, including archaea, bacteria, viruses, and zooxanthellae. The extent to which coral-bacterial associations are specific and the mechanisms for their maintenance across generations in the environment are unknown. The high diversity of bacteria in adult coral colonies has made it challenging to identify species-specific patterns. Localization of bacteria in gametes and larvae of corals presents an opportunity for determining when bacterial-coral associations are initiated and whether they are dynamic throughout early development. This study focuses on the early onset of bacterial associations in the mass spawning corals Montastraea annularis, M. franksi, M. faveolata, Acropora palmata, A. cervicornis, Diploria strigosa, and A. humilis. The presence of bacteria and timing of bacterial colonization was evaluated in gametes, swimming planulae, and newly settled polyps by fluorescence in situ hybridization (FISH) using general eubacterial probes and laser-scanning confocal microscopy. The coral species investigated in this study do not appear to transmit bacteria via their gametes, and bacteria are not detectable in or on the corals until after settlement and metamorphosis. This study suggests that mass-spawning corals do not acquire, or are not colonized by, detectable numbers of bacteria until after larval settlement and development of the juvenile polyp. This timing lays the groundwork for developing and testing new hypotheses regarding general regulatory mechanisms that control bacterial colonization and infection of corals, and how interactions among bacteria and juvenile polyps influence the structure of bacterial assemblages in corals

Toxicity and cellular uptake of gold nanoparticles: what we have learned so far?

Gold nanoparticles have attracted enormous scientific and technological interest due to their ease of synthesis, chemical stability, and unique optical properties. Proof-of-concept studies demonstrate their biomedical applications in chemical sensing, biological imaging, drug delivery, and cancer treatment. Knowledge about their potential toxicity and health impact is essential before these nanomaterials can be used in real clinical settings. Furthermore, the underlying interactions of these nanomaterials with physiological fluids is a key feature of understanding their biological impact, and these interactions can perhaps be exploited to mitigate unwanted toxic effects. In this Perspective we discuss recent results that address the toxicity of gold nanoparticles both in vitro and in vivo, and we provide some experimental recommendations for future research at the interface of nanotechnology and biological systems

Insects as Stem Engineers: Interactions Mediated by the Twig-Girdler Oncideres albomarginata chamela Enhance Arthropod Diversity

Background: Ecosystem engineering may influence community structure and biodiversity by controlling the availability of resources and/or habitats used by other organisms. Insect herbivores may act as ecosystem engineers but there is still poor understanding of the role of these insects structuring arthropod communities. Methodology/Principal Findings: We evaluated the effect of ecosystem engineering by the stem-borer Oncideres albomarginata chamela on the arthropod community of a tropical dry forest for three consecutive years. The results showed that ecosystem engineering by O. albomarginata chamela had strong positive effects on the colonization, abundance, species richness and composition of the associated arthropod community, and it occurred mainly through the creation of a habitat with high availability of oviposition sites for secondary colonizers. These effects cascade upward to higher trophic levels. Overall, ecosystem engineering by O. albomarginata chamela was responsible for nearly 95 % of the abundance of secondary colonizers and 82 % of the species richness. Conclusions/Significance: Our results suggest that ecosystem engineering by O. albomarginata chamela is a keystone process structuring an arthropod community composed by xylovores, predators and parasitoids. This study is the first to empirically demonstrate the effect of the ecosystem engineering by stem-boring insects on important attributes o

Regulation of BRCA1 expression and its relationship to sporadic breast cancer

Germ-line mutations in the BRCA1 tumour suppressor gene contribute to familial breast tumour formation, but there is no evidence for direct mutation of the BRCA1 gene in the sporadic form of the disease. In contrast, decreased expression of the BRCA1 gene has been shown to be common in sporadic tumours, and the magnitude of the decrease correlates with disease progression. BRCA1 expression is also tightly regulated during normal breast development. Determining how these developmental regulators of BRCA1 expression are co-opted during breast tumourigenesis could lead to a better understanding of sporadic breast cancer aetiology and the generation of novel therapeutic strategies aimed at preventing sporadic breast tumour progression

Towards the Development of an Empirical Model for Islamic Corporate Social Responsibility: Evidence from the Middle East

Academic research suggests that variances in contextual dynamics, and more specifically religion, may lead to disparate perceptions and practices of corporate social responsibility (CSR). Driven by the increased geopolitical and economic importance of the Middle East and identified gaps in knowledge, the study aims to examine if indeed there is a divergent form of CSR exercised in the region. The study identifies unique CSR dimensions and constructs presented through an empirical framework in order to outline the practice and perception of CSR in a context with strong Islamic beliefs. The framework goes beyond the platform of mere Islamic philanthropy and is based on CSR-stakeholder management practices. Following an exploratory research design and collecting interview data from representatives of 63 organisations from Saudi Arabia, the United Arab Emirates and Oman, the study offers a snapshot of the CSR reality from the perspective of those living the phenomenon. The results suggest that the practice and perception of CSR in the examined context are largely grounded in the areas of social and altruistic actions but they cannot be examined in isolation from the religious context of CSR operation. This focus is mainly attributed to the dominant role of Islam in the examined sample, which leads to forms of non-structured or semi-structured approaches to CSR. Apart from the theoretical advancements offered to the CSR literature, the study also provides contributions for practitioners and policy makers.</p

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain