Structural and functional diversification in the teleost S100 family of calcium-binding proteins

<p>Abstract</p> <p>Background</p> <p>Among the EF-Hand calcium-binding proteins the subgroup of S100 proteins constitute a large family with numerous and diverse functions in calcium-mediated signaling. The evolutionary origin of this family is still uncertain and most studies have examined mammalian family members.</p> <p>Results</p> <p>We have performed an extensive search in several teleost genomes to establish the <it>s100 </it>gene family in fish. We report that the teleost S100 repertoire comprises fourteen different subfamilies which show remarkable similarity across six divergent teleost species. Individual species feature distinctive subsets of thirteen to fourteen genes that result from local gene duplications and gene losses. Eight of the fourteen S100 subfamilies are unique for teleosts, while six are shared with mammalian species and three of those even with cartilaginous fish. Several S100 family members are found in jawless fish already, but none of them are clear orthologs of cartilaginous or bony fish <it>s100 </it>genes. All teleost <it>s100 </it>genes show the expected structural features and are subject to strong negative selection. Many aspects of the genomic arrangement and location of mammalian <it>s100 </it>genes are retained in the teleost <it>s100 </it>gene family, including a completely conserved intron/exon border between the two EF hands. Zebrafish <it>s100 </it>genes exhibit highly specific and characteristic expression patterns, showing both redundancy and divergence in their cellular expression. In larval tissue expression is often restricted to specific cell types like keratinocytes, hair cells, ionocytes and olfactory receptor neurons as demonstrated by <it>in situ </it>hybridization.</p> <p>Conclusion</p> <p>The origin of the S100 family predates at least the segregation of jawed from jawless fish and some extant family members predate the divergence of bony from cartilaginous fish. Despite a complex pattern of gene gains and losses the total repertoire size is remarkably constant between species. On the expression level the teleost S100 proteins can serve as precise markers for several different cell types. At least some of their functions may be related to those of their counterparts in mammals. Accordingly, our findings provide an excellent basis for future studies of the functions and interaction partners of <it>s100 </it>genes and finally their role in diseases, using the zebrafish as a model organism.</p

Políticas sociais: focalização versus universalização

Neste ensaio, pretende-se analisar brevemente o importante dilema atual das políticas públicas referente à redução das desigualdades e à promoção do desenvolvimento: a dicotomia “focalização” versus “universalização”.Número padronizado: v. 55, n. 3 (2004) Revista do Serviço Público - RSP, ano 55, n. 3, p. 91-95Políticas Públicas e SociaisISSN Impresso: 0034-9240ISSN Eletrônico: 2357-8017O presente documento trata-se de um Ensaio apresentado durante o curso de formação de Especialistas em Políticas Públicas e Gestão Governamental, realizado na ENAP em 2004

Crypt neurons express a single V1R-related ora gene

Abstract Both ciliated and microvillous olfactory sensory neuron populations express large families of olfactory receptor genes. However, individual neurons generally express only a single receptor gene according to the &apos;&apos;one neuron-one receptor&apos;&apos; rule. We report here that crypt neurons, the third type of olfactory neurons in fish species, use an even more restricted mode of expression. We recently identified a novel olfactory receptor family of 6 highly conserved G protein-coupled receptors, the v1r-like ora genes. We show now that a single member of this family, ora4 is expressed in nearly all crypt neurons, whereas the other 5 ora genes are not found in this cell type. Consistent with these findings, ora4 is never coexpressed with any of the remaining 5 ora genes. Furthermore, several lines of evidence indicate the absence of any other olfactory receptor families in crypt neurons. These results suggest that the vast majority of the crypt neuron population may select one and the same olfactory receptor gene, a &apos;&apos;one cell type-one receptor&apos;&apos; mode of expression. Such an expression pattern is familiar in the visual system, with rhodopsin as the sole light receptor of rod photoreceptor cells, but unexpected in the sense of smell

Odor blocking of stress hormone responses

Scents have been employed for millennia to allay stress, but whether or how they might do so is largely unknown. Fear and stress induce increases in blood stress hormones controlled by hypothalamic corticotropin releasing hormone neurons (CRHNs). Here, we report that two common odorants block mouse stress hormone responses to three potent stressors: physical restraint, predator odor, and male-male social confrontation. One odorant inhibits restraint and predator odor activation of excitatory neurons upstream of CRHNs in the bed nucleus of the stria terminalis (BNSTa). In addition, both activate inhibitory neurons upstream of CRHNs in the hypothalamic ventromedial nucleus (VMH) and silencing of VMH inhibitory neurons hinders odor blocking of stress. Together, these findings indicate that odor blocking can occur via two mechanisms: (1) Inhibition of excitatory neurons that transmit stress signals to CRHNs and (2) activation of inhibitory neurons that act directly or indirectly to inhibit stressor activation of CRHNs

A CULTURA DO BRINCAR E O TEA

O presente vídeo etnográfico tem como propósito apresentar características sobre o brincar de crianças com TEA (Transtorno do Espectro Autista). Ele é resultado das vivências de pais e mães de crianças autista em diálogo com o espaço de pesquisa Laboratório de Inclusão (UFPA/campus Bragança). Apresentar a ludicidade de crianças que estão no espectro autista representa uma dimensão de discussão sobre a temática TEA. O brincar faz parte da subjetividade infantil, e é utilizado como principal ferramenta de desenvolvimento e aprendizagem da criança nos espaços educacionais, terapêuticos e familiares. O filme trás características sobre o brincar de crianças autista e sua importância para a infância, com relatos de pais e professora que vivenciam essas experiências. Assista aqui

The quality of energy- and macronutrient-balanced diets regulates host susceptibility to influenza in mice

Modulation of individual macronutrients or caloric density is known to regulate host resistance to infection in mice. However, the impact of diet composition, independent of macronutrient and energy content, on infection susceptibility is unclear. We show that two laboratory rodent diets, widely used as standard animal feeds and experimental controls, display distinct abilities in supporting mice during influenza infection. Mice placed on the highly processed AIN93G showed increased mortality to infection compared with those on a grain-based chow diet, suggesting a detrimental role for highly processed food in host defense. We further demonstrate that the heightened susceptibility of AIN93G-fed mice was associated with the failure in homeostasis restoration mediated by the cytokine interferon (IFN)-γ. Our findings show that diet composition calibrates host survival threshold by regulating adaptive homeostasis and highlights a pivotal role for extrinsic signals in host phenotype and outcome of host-pathogen interaction

A transcriptomic atlas of mammalian olfactory mucosae reveals an evolutionary influence on food odor detection in humans.

The mammalian olfactory system displays species-specific adaptations to different ecological niches. To investigate the evolutionary dynamics of olfactory sensory neuron (OSN) subtypes across mammalian evolution, we applied RNA sequencing of whole olfactory mucosa samples from mouse, rat, dog, marmoset, macaque, and human. We find that OSN subtypes, representative of all known mouse chemosensory receptor gene families, are present in all analyzed species. Further, we show that OSN subtypes expressing canonical olfactory receptors are distributed across a large dynamic range and that homologous subtypes can be either highly abundant across all species or species/order specific. Highly abundant mouse and human OSN subtypes detect odorants with similar sensory profiles and sense ecologically relevant odorants, such as mouse semiochemicals or human key food odorants. Together, our results allow for a better understanding of the evolution of mammalian olfaction in mammals and provide insights into the possible functions of highly abundant OSN subtypes

Baseline characteristics of patients with heart failure and preserved ejection fraction in the PARAGON-HF trial

Background: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. Methods and Results: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464–1610), and structural heart disease. Conclusions: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711