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Uneven distribution of cobamide biosynthesis and dependence in bacteria predicted by comparative genomics.
The vitamin B12 family of cofactors known as cobamides are essential for a variety of microbial metabolisms. We used comparative genomics of 11,000 bacterial species to analyze the extent and distribution of cobamide production and use across bacteria. We find that 86% of bacteria in this data set have at least one of 15 cobamide-dependent enzyme families, but only 37% are predicted to synthesize cobamides de novo. The distribution of cobamide biosynthesis and use vary at the phylum level. While 57% of Actinobacteria are predicted to biosynthesize cobamides, only 0.6% of Bacteroidetes have the complete pathway, yet 96% of species in this phylum have cobamide-dependent enzymes. The form of cobamide produced by the bacteria could be predicted for 58% of cobamide-producing species, based on the presence of signature lower ligand biosynthesis and attachment genes. Our predictions also revealed that 17% of bacteria have partial biosynthetic pathways, yet have the potential to salvage cobamide precursors. Bacteria with a partial cobamide biosynthesis pathway include those in a newly defined, experimentally verified category of bacteria lacking the first step in the biosynthesis pathway. These predictions highlight the importance of cobamide and cobamide precursor salvaging as examples of nutritional dependencies in bacteria
Role of Human-Induced Pluripotent Stem Cell-Derived Spinal Cord Astrocytes in the Functional Maturation of Motor Neurons in a Multielectrode Array System
The ability to generate human-induced pluripotent stem cell (hiPSC)-derived neural cells displaying region-specific phenotypes is of particular interest for modeling central nervous system biology in vitro. We describe a unique method by which spinal cord hiPSC-derived astrocytes (hiPSC-A) are cultured with spinal cord hiPSC-derived motor neurons (hiPSC-MN) in a multielectrode array (MEA) system to record electrophysiological activity over time. We show that hiPSC-A enhance hiPSC-MN electrophysiological maturation in a time-dependent fashion. The sequence of plating, density, and age in which hiPSC-A are cocultured with MN, but not their respective hiPSC line origin, are factors that influence neuronal electrophysiology. When compared to coculture with mouse primary spinal cord astrocytes, we observe an earlier and more robust electrophysiological maturation in the fully human cultures, suggesting that the human origin is relevant to the recapitulation of astrocyte/motor neuron crosstalk. Finally, we test pharmacological compounds on our MEA platform and observe changes in electrophysiological activity, which confirm hiPSC-MN maturation. These findings are supported by immunocytochemistry and real-time PCR studies in parallel cultures demonstrating human astrocyte mediated changes in the structural maturation and protein expression profiles of the neurons. Interestingly, this relationship is reciprocal and coculture with neurons influences astrocyte maturation as well. Taken together, these data indicate that in a human in vitro spinal cord culture system, astrocytes support hiPSC-MN maturation in a time-dependent and species-specific manner and suggest a closer approximation of in vivo conditions
Training proposal for community health agents in hearing health
TEMA: capacitação de agentes comunitários de saúde na área de saúde auditiva. OBJETIVO: verificar a efetividade de um programa de capacitação de agentes comunitários de saúde do Programa de Saúde da Família, na área de saúde auditiva infantil. MÉTODO: a casuística constou de dois grupos: grupo A foi constituído por 31 agentes comunitários de saúde da cidade de Bauru e, grupo B, formado por 75 agentes comunitários de saúde de Sorocaba, ambos municípios do Estado de São Paulo. A capacitação foi realizada por meio de aulas expositivas para os dois grupos, contudo para o grupo A foi utilizado uma apostila adaptada da World Health Organization (2006), para que os agentes comunitários de saúde pudessem acompanhar as atividades realizadas de forma interativa. A capacitação abordou os temas: audição e deficiência auditiva, tipos, prevenção e causas da deficiência auditiva, técnicas de identificação e diagnóstico da deficiência auditiva e aspectos gerais da deficiência auditiva. Para validar a capacitação foi aplicado um questionário pré e pós-capacitação com perguntas sobre os assuntos que foram abordados no decorrer do curso, a fim de analisar a assimilação do conteúdo ministrado. RESULTADOS: a capacitação foi efetiva, com aumento no escore total obtido nos questionários pré e pós-capacitação. CONCLUSÕES: os resultados comprovam a eficácia do programa de capacitação com utilização de material e abordagem interativa proposto para os agentes comunitários de saúde dos Programas de Saúde da Família.BACKGROUND: training of community health agents in hearing health. AIM: to verify the effectiveness of a training program regarding the hearing health of children for Community Health Agents of a Family Health Program. METHOD: research sample consisted of two groups: Group A, constituted by 31 community health agents, from Bauru, SP, and Group B, constituted by 75 community health agents, from Sorocaba, SP. Training was provided through classes for both groups. For Group A, a text adapted from the material organized by the World Health Organization (2006) was used so that the community health agents could follow the activities in an interactive way. Training focused on the following topics: normal and impaired hearing; types, prevention and causes of hearing loss; procedures to identify and diagnose the hearing impairment and rehabilitation. Pre and post training questionnaires were used to assess the assimilation of the presented content. RESULTS: training demonstrated to be effective, since there was an increase in the overall score when comparing the scores obtained in the pre and post training questionnaires CONCLUSION: the results indicate the effectiveness of the training program for community health agents of a Family Health Program with the use of texts and with an interactive approach.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq
Role of the Small GTPase Rho3 in Golgi/Endosome Trafficking through Functional Interaction with Adaptin in Fission Yeast
BACKGROUND: We had previously identified the mutant allele of apm1(+) that encodes a homolog of the mammalian µ1A subunit of the clathrin-associated adaptor protein-1 (AP-1) complex, and we demonstrated the role of Apm1 in Golgi/endosome trafficking, secretion, and vacuole fusion in fission yeast. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we isolated rho3(+), which encodes a Rho-family small GTPase, an important regulator of exocystosis, as a multicopy-suppressor of the temperature-sensitive growth of the apm1-1 mutant cells. Overexpression of Rho3 suppressed the Cl(-) sensitivity and immunosuppressant sensitivity of the apm1-1 mutant cells. Overexpression of Rho3 also suppressed the fragmentation of vacuoles, and the accumulation of v-SNARE Syb1 in Golgi/endosomes and partially suppressed the defective secretion associated with apm1-deletion cells. Notably, electron microscopic observation of the rho3-deletion cells revealed the accumulation of abnormal Golgi-like structures, vacuole fragmentation, and accumulation of secretory vesicles; these phenotypes were very similar to those of the apm1-deletion cells. Furthermore, the rho3-deletion cells and apm1-deletion cells showed very similar phenotypic characteristics, including the sensitivity to the immunosuppressant FK506, the cell wall-damaging agent micafungin, Cl(-), and valproic acid. Green fluorescent protein (GFP)-Rho3 was localized at Golgi/endosomes as well as the plasma membrane and division site. Finally, Rho3 was shown to form a complex with Apm1 as well as with other subunits of the clathrin-associated AP-1 complex in a GTP- and effector domain-dependent manner. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings reveal a novel role of Rho3 in the regulation of Golgi/endosome trafficking and suggest that clathrin-associated adaptor protein-1 and Rho3 co-ordinate in intracellular transport in fission yeast. To the best of our knowledge, this study provides the first evidence of a direct link between the small GTPase Rho and the clathrin-associated adaptor protein-1 in membrane trafficking
Color Categorization Independent of Color Naming
Color is continuous, yet we group colors into discrete categories associated with color names (e.g., yellow, blue). Color categorization is a case in point in the debate on how language shapes human cognition. Evidence suggests that color categorization depends on top-down input from the language system to the visual cortex. We directly tested this hypothesis by assessing color categorization in a stroke patient, RDS, with a rare, selective deficit in naming visually presented chromatic colors, and relatively preserved achromatic color naming. Multimodal MRI revealed a left occipito-temporal lesion that directly damaged left color-biased regions, and functionally disconnected their right-hemisphere homologs from the language system. The lesion had a greater effect on RDS’s chromatic color naming than on color categorization, which was relatively preserved on a nonverbal task. Color categorization and naming can thus be independent in the human brain, challenging the mandatory involvement of language in adult human cognition
Speeding Up the Internet: Regulation and Investment in European Fiber Optic Infrastructure
Novel regulators of human gonadal development
The production of viable germ cells during human embryonic development
determines adult reproductive success. This is particularly true for females, as
development of germ cells (GCs) into primordial follicles before birth is imperative
for future fertility. During fetal development GCs migrate to the genital ridge to
form the gonad, after which several tightly regulated events, including proliferation,
differentiation, and association with somatic cells, must occur to form a functional
gonad. In the ovary these processes also include the initiation and subsequent arrest
of meiosis. These developmental processes are orchestrated by local autocrine and
paracrine factors, many of which remain to be identified in the human.
In order to decipher further the pathways by which the gonad and GCs develop,
potential regulators including prostaglandin (PG) E2, the interleukin (IL)6-type
cytokines, and the prokinetecins (PROKs), were examined in the human fetal ovary
and PROKs in the human fetal testis. Patterns of gene expression, protein
localisation, function, and interaction of the potential mediators throughout human
development (8-20 weeks gestation) were determined. Primary fetal tissue was
investigated, in addition to immortalized GCs (T-Cam2 cells) and a murine model of
fetal ovarian development.
PGE2 interacts with known regulators of GC development in non-reproductive
organs. It was postulated PGE2 may regulate GC progression by modulating these
factors. Examination of PGE2 receptors and precursor enzymes in the fetal ovary
revealed that all were present and some were developmentally regulated, with
mRNA expression increasing with gestation. These developmentally regulated
components were localised to the GCs. The PGE2 receptors were among those
differentially expressed, with one localised solely to mature GCs. Culture of human
fetal ovary confirmed that PGE2 regulates known regulators of GC development,
increasing expression of survival and anti-apoptotic factors. To test the hypothesis
that PGE2 is necessary for female GC development, paracetamol, an inhibitor of
PGE2 precursor enzymes, was utilised in a murine model of fetal exposure. Fetal
ovaries from this experiment displayed disruption of normal development. The IL6-type cytokines are also postulated to be involved in early gonad
development, and are known to regulate proliferation and differentiation of mouse
embryonic stem and GCs in vitro. A significant increase in transcript levels of the
shared receptor components was determined in second trimester human ovaries, as
well as developmental increases of several of the IL6-type ligands. Both common
receptor components were located specifically in the GCs identifying them as the
target of IL6 action in the human fetal ovary.
The PROKs regulate cell migration, proliferation and differentiation, and modulate
secretion of PGE2 and expression of some IL6-type cytokines. To-date, PROKs have
not been examined in the human fetal gonad. Transcript levels were higher in the
fetal testis compared to the ovary, with receptor and ligand components increasing
with gestation. Most components also increased with gestation in the ovary.
However, location of PROK components was strikingly different between the two
tissues, with GCs being the primary target of PROK action in the fetal ovary, and
Leydig and interstitial cells being the target in the testis. PROKs interaction with
other regulators of gonad development was examined utilising a GC line in the case
of the ovary and primary interstitial cell cultures in the case of the testis.
These studies have identified new factors involved in human fetal gonad
development, and how they interact with known regulatory pathways of
development
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Standalone vertex finding in the ATLAS muon spectrometer
A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011
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