Functionally Important Carboxyls in a Bacterial Homologue of the Vesicular Monoamine Transporter (VMAT)

Transporters essential for neurotransmission in mammalian organisms and bacterial multidrug transporters involved in antibiotic resistance are evolutionarily related. To understand in more detail the evolutionary aspects of the transformation of a bacterial multidrug transporter to a mammalian neurotransporter and to learn about mechanisms in a milieu amenable for structural and biochemical studies, we identified, cloned, and partially characterized bacterial homologues of the rat vesicular monoamine transporter (rVMAT2). We performed preliminary biochemical characterization of one of them, Brevibacillus brevis monoamine transporter (BbMAT), from the bacterium B. brevis. BbMAT shares substrates with rVMAT2 and transports them in exchange with >1H⁺, like the mammalian transporter. Here we present a homology model of BbMAT that has the standard major facilitator superfamily fold; that is, with two domains of six transmembrane helices each, related by 2-fold pseudosymmetry whose axis runs normal to the membrane and between the two halves. The model predicts that four carboxyl residues, a histidine, and an arginine are located in the transmembrane segments. We show here that two of the carboxyls are conserved, equivalent to the corresponding ones in rVMAT2, and are essential for H⁺-coupled transport. We conclude that BbMAT provides an excellent experimental paradigm for the study of its mammalian counterparts and bacterial multidrug transporters.     

May mothers given warfarin breast-feed their infants?

Warfarin was measured with a sensitive and specific method in the plasma and breast milk of 13 mothers. Less than 0-08 micronmol warfarin per litre (25 ng/ml) of breast milk was found in each instance. Seven of the mothers were breast-feeding their infants, in none of whom was warfarin detected in the plasma; furthermore, in three the British corrected ratio of the plasma was appreciably less than that of the mother and was within the expected range. We conclude that nursing mothers given warfarin may safely breast-feed their infants.     

Cellular mechanisms controlling light-stimulated gravitropism: role of calcium

An irradiation with visible light can alter the gravitropic responsiveness of shoots and roots. This indicates that light must affect some biochemical process in plant cells which is the same as, or importantly influences, a biochemical process that regulates gravitropism. In many cases, the light receptor for this effect is the pigment phytochrome, which initiates a variety of important photomorphogenic responses in plants. Recent results suggest that both gravistimulation and phytochrome photoactivation result in altered Ca²⁺ transport into and out of the affected cells. This article reviews the evidence that these Ca²⁺ fluxes may be the common biochemical process which modulates both gravitropism and photomorphogenesis.     

Epidemiologic data and pathogen genome sequences: a powerful synergy for public health

Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of pathogen genomes, together with date, location, clinical manifestation and other relevant data about sample origins, can contribute to describing nearly every aspect of transmission dynamics, including local transmission and global spread. The analyses of these data have implications for all levels of clinical and public health practice, from institutional infection control to policies for surveillance, prevention and treatment. This review highlights the range of epidemiological questions that can be addressed from the combination of genome sequence and traditional ‘line lists’ (tables of epidemiological data where each line includes demographic and clinical features of infected individuals). We identify opportunities for these data to inform interventions that reduce disease incidence and prevalence. By considering current limitations of, and challenges to, interpreting these data, we aim to outline a research agenda to accelerate the genomics-driven transformation in public health microbiology.     

Membrane-Mediated Interaction between Strongly Anisotropic Protein Scaffolds

Specialized proteins serve as scaffolds sculpting strongly curved membranes of intracellular organelles. Effective membrane shaping requires segregation of these proteins into domains and is, therefore, critically dependent on the protein-protein interaction. Interactions mediated by membrane elastic deformations have been extensively analyzed within approximations of large inter-protein distances, small extents of the protein-mediated membrane bending and small deviations of the protein shapes from isotropic spherical segments. At the same time, important classes of the realistic membrane-shaping proteins have strongly elongated shapes with large and highly anisotropic curvature. Here we investigated, computationally, the membrane mediated interaction between proteins or protein oligomers representing membrane scaffolds with strongly anisotropic curvature, and addressed, quantitatively, a specific case of the scaffold geometrical parameters characterizing BAR domains, which are crucial for membrane shaping in endocytosis. In addition to the previously analyzed contributions to the interaction, we considered a repulsive force stemming from the entropy of the scaffold orientation. We computed this interaction to be of the same order of magnitude as the well-known attractive force related to the entropy of membrane undulations. We demonstrated the scaffold shape anisotropy to cause a mutual aligning of the scaffolds and to generate a strong attractive interaction bringing the scaffolds close to each other to equilibrium distances much smaller than the scaffold size. We computed the energy of interaction between scaffolds of a realistic geometry to constitute tens of k_BT, which guarantees a robust segregation of the scaffolds into domains.     

Contradictory Behavioral Biases Result from the Influence of Past Stimuli on Perception

Biases such as the preference of a particular response for no obvious reason, are an integral part of psychophysics. Such biases have been reported in the common two-alternative forced choice (2AFC) experiments, where participants are instructed to compare two consecutively presented stimuli. However, the principles underlying these biases are largely unknown and previous studies have typically used ad-hoc explanations to account for them. Here we consider human performance in the 2AFC tone frequency discrimination task, utilizing two standard protocols. In both protocols, each trial contains a reference stimulus. In one (Reference-Lower protocol), the frequency of the reference stimulus is always lower than that of the comparison stimulus, whereas in the other (Reference protocol), the frequency of the reference stimulus is either lower or higher than that of the comparison stimulus. We find substantial interval biases. Namely, participants perform better when the reference is in a specific interval. Surprisingly, the biases in the two experiments are opposite: performance is better when the reference is in the first interval in the Reference protocol, but is better when the reference is second in the Reference-Lower protocol. This inconsistency refutes previous accounts of the interval bias, and is resolved when experiments statistics is considered. Viewing perception as incorporation of sensory input with prior knowledge accumulated during the experiment accounts for the seemingly contradictory biases both qualitatively and quantitatively. The success of this account implies that even simple discriminations reflect a combination of sensory limitations, memory limitations, and the ability to utilize stimuli statistics.     

SUN-domain proteins: 'Velcro' that links the nucleoskeleton to the cytoskeleton

The novel SUN-domain family of nuclear envelope proteins interacts with various KASH-domain partners to form SUN-domain-dependent 'bridges' across the inner and outer nuclear membranes. These bridges physically connect the nucleus to every major component of the cytoskeleton. SUN-domain proteins have diverse roles in nuclear positioning, centrosome localization, germ-cell development, telomere positioning and apoptosis. By serving both as mechanical adaptors and nuclear envelope receptors, we propose that SUN-domain proteins connect cytoplasmic and nucleoplasmic activities.     

Assessment of Knowledge and Practice towards Hepatitis B among Medical and Health Science Students in Haramaya University,Ethiopia

Introduction

Hepatitis B (HB) is a serious infection that affects liver and caused by hepatitis B virus (HBV). HB is a serious global public health problem and the health professionals are most at risk. It is contagious and easy to be transmitted from one infected individual to another by blood to blood contact, mother to child, unprotected sexual intercourse, sharing of eating utensils and other barber shop and beauty salon equipment. The aim of this study was to assess knowledge and practices about transmissions and prevention of hepatitis B among medical and health science students on clinical attachment in Haramaya University.

Methods and Findings

A cross sectional study was conducted among 322 health science and medical students who are starting clinical attachment (year II, III, IV, V and IV) from February 1–15, 2013. Self-administered structured questionnaire was used to collect information. Out of 322 distributed questionnaires, 322 were returned with a response rate of 100.0%. Majority of the students (91%) were in the age group 20–24 and 232 (72%) of the respondents were male. Majorities (95.3%) of students were not fully vaccinated against Hepatitis B and 48.4% of the students were not aware about the availability of post exposure prophylaxis for HB. Mean scores for knowledge and practice were 11.52±2.37 and 2.76±1.1 respectively. Significant and positive linear correlations between knowledge-practice (r = 0.173, p = 0.002) was observed. Study department was significantly associated with mean knowledge and practice of study respondents.

Conclusion

This study indicates that lack of awareness about Hepatitis B, its route of transmission and modes of prevention among the medical students entering into the profession. Similarly, 95.3% the students were not fully vaccinated against Hepatitis B, which makes them vulnerable to the disease.