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Prostate cancer is consistently the most frequently diagnosed cancer in American males as well as the second leading cause of cancer-related mortality. This underscores the dire need to understand the healthy prostate and how it can transform into a diseased state. Therefore, I have sought to investigate the heterogeneity and ontogeny of the mouse and human prostate. To do this, I employed single-cell RNA-sequencing, electron microscopy, immunofluorescence, and immunohistochemical analyses to identify specific cell populations, as well as lineage tracing, organoid culture, and tissue recombination assays to assess the function and origin of these populations. I discovered a profound level of heterogeneity uniquely within the luminal epithelial compartment of the prostate, including several novel populations. These luminal populations differ in distribution between mouse prostate lobes and along the proximal-distal axis within each lobe. These populations demonstrated significant differences in progenitor behavior in both organoid culture and tissue recombination assays, as shown by their differential abilities to proliferate, generate patterned structures, and differentiate into distinct cell types. Comparisons of the mouse prostate cell populations to cells from several benign human prostate samples showed that there is also luminal heterogeneity in the human prostate, and that several mouse populations have substantial gene expression overlap with human prostate populations. The observed luminal heterogeneity as well as the functional differences were consistent across several different published studies of the mouse prostate, and cross-species transcriptional similarities between populations were maintained across additional human samples, indicating that these findings are robust. My findings suggest that the luminal compartment of the mouse prostate contains distinct populations of cells that may act as reserve progenitors, and that their distribution across the prostate lobes could be functional. Additionally, if these populations can be cells of origin for prostate cancer, then their differences in progenitor behavior could contribute to the heterogeneity observed in prostate cancer prognosis and treatment response, which could have substantial clinical implications for patients.

Reproduction is an essential feature of all animals and a fundamental step to produce new generations. Study of sperm proteins is crucial for understanding of the sperm-egg recognition. We searched out sperm surface proteins involving in the zona pellucida (ZP) binding and studied whether these proteins are preserved throughout mammalian species. Indirect immunofluorescent technique was used to test a panel of monoclonal antibodies prepared against boar sperm surface proteins on spermatozoa of bull and mice. We found a cross-reactivity of some antibodies against boar sperm with bull ejaculated and mouse epididymal spermatozoa. Further, we isolated sperm proteins from different mammalian species, such as pig, bull, dog, cat, mouse and human. Proteins were separated by SDS- electrophoresis and protein/glycoprotein profiles from epididymal, ejaculated and in vitro capacitated sperm were compared. The interaction of sperm with ZP was studied on electrophoretically-separated sperm surface proteins from pig and bull with biotin-labeled ZP glycoproteins. Antibodies, which reacted with boar sperm surface proteins with ZP- binding activity, therefore could be potential egg-binding receptors, were used for monitoring of the sperm protein origin in reproductive fluids and tissues. (In Czech) Keywords: sperm...

A Febre Maculosa Brasileira (FMB) é uma doença infecciosa causada por Rickettsia rickettsii, transmitida pelo carrapato-estrela Amblyomma sculptum no interior do estado de São Paulo, onde equinos e capivaras são utilizados como sentinelas para FMB por serem considerados hospedeiros primários deste carrapato. Objetivou-se com este trabalho verificar a ocorrência de anticorpos anti-Rickettsia rickettsii em sentinelas clássicos (equinos) e potenciais (ovinos, bovinos e gambás) para FMB que vivem em diferentes ambientes do Campus \"Luiz de Queiroz\", da Universidade de São Paulo, em Piracicaba-SP. De fevereiro de 2017 a janeiro de 2018 foram amostrados 156 hospedeiros, 48 que habitam áreas urbanas, sem a presença ou trânsito de capivaras (15 equinos e 33 gambás), 60 ovinos que frequentam pastagens sem presença de capivaras, mas adjacentes a matas ciliares ocupadas pelos roedores, e 48 que frequentam pastagens por onde transitam capivaras (31 bovinos e seis equinos) ou matas ciliares ocupadas pelos roedores (11 gambás). Quando possível, a amostragem envolveu a coleta de ectoparasitos. O soro obtido após centrifugação do sangue colhido foi analisado em duas etapas, triagem e titulação, pela reação de imunofluorescência indireta (RIFI). Na triagem todas as amostras foram testadas contra R. rickettsii, e consideradas positivas se apresentassem título de anticorpos >= 64. As amostras positivas foram diluídas na etapa de titulação e testadas contra R. rickettsii, R. parkeri, R. bellii, R. ambyommatis e R. rhipicephali para determinação do título máximo de anticorpos para cada espécie. Das 156 amostras testadas, 15 estavam soropositivas, 1/60 ovinos, 1/31 bovinos, 7/21 equinos e 6/44 gambás; os títulos finais variaram de 64 a 4.096. Foi possível determinar o possível antígeno envolvido em reação homóloga (PAERH) em seis amostras, um equino (R. bellii) e quatro gambás e um ovino (R. rickettsii). Foram registrados os carrapatos Amblyomma ovale, Amblyomma dubitatum, Amblyomma sculptum, Dermacentor nitens e Rhipicephalus microplus, e as pulgas Ctenocephalides felis e Siphonaptera: Rhopalopsyllidae cf. Rhopalopsyllus nos hospedeiros amostrados. Conclui-se que equinos e gambás podem ser utilizados como sentinelas para FMB no Campus \"Luiz de Queiroz\", mas os ovinos não. Não foi possível concluir se os bovinos podem ser utilizados com esta função. R. bellii, ou um microrganismo muito semelhante, ocorre na área urbana do Campus \"Luiz de Queiroz\" e é capaz de infectar cavalos. R. rickettsii, ou um microrganismo muito semelhante, ocorre no Campus \"Luiz de Queiroz\" em áreas de permanência e trânsito de capivaras / Brazilian Spotted Fever (BSF) is an infectious disease caused by Rickettsia rickettsii, transmitted by the tick Amblyomma sculptum outside the metropolitan region in the State of São Paulo, where horses and capybaras are used as sentinels for BSF as they are considered primary hosts for this tick. This survey aimed to verify the occurrence of antibodies against Rickettsia rickettsii in sentinels (horses) and potential sentinels (sheep, cattle and opossums) for BSF that lives in different environments of the \"Luiz de Queiroz\" Campus, University of São Paulo, in Piracicaba, SP, Brazil. A total of 156 host were sampled between February of 2017 and January of 2018; 48 that live in urban areas, with no presence or transit of capybaras (15 horses and 33 opossums), 60 sheep that regularly graze on capybara-free pastures adjacent to a riparian forest occupied by these rodents, and 48 that occupy, cross or regularly graze on pastures (31 cows and six horses) or riparian forests (11 opossums) that are areas used by capybaras. Whenever possible, host sampling included ectoparasites collection. Sera obtained after centrifugation of the collected blood was analyzed in two steps, screening and titration, by the indirect immunofluorescence assay technique (IFA). All samples were tested against R. rickettsii during the screening, and those that presented antibodies titers >= 64 were considered positive. Positive samples were diluted during titration and tested against R. rickettsii, R. parkeri, R. bellii, R. ambyommatis and R. rhipicephali for determination of maximum antibodies titers for each species. Of the 156 tested samples, 15 were seropositive, 1/60 sheep, 1/31 cows, 7/21 horses and 6/44 opossums; antibodies endpoint titers ranged from 64 to 4.096. Possible antigen involved in a homologous reaction (PAIHR) was determined for six samples, one horse (R. bellii), four opossums and one sheep (R. rickettsii). The ticks Amblyomma ovale, Amblyomma dubitatum, Amblyomma sculptum, Dermacentor nitens and Rhipicephalus microplus, and the fleas Ctenocephalides felis and Siphonaptera: Rhopalopsyllidae cf. Rhopalopsyllus were collected from the sampled hosts. Results showed that horses and opossums may be used as sentinels for BSF in the \"Luiz de Queiroz\" Campus, but the sheep do not. It wasn\'t possible to determine if the cows may be used as sentinels. R. bellii, or a very closely related microorganism, occurs in the urban area of the \"Luiz de Queiroz\" Campus and is capable to infect horses. R. rickettsii, or a very closely related microorganism, occurs in capybara-transit areas of the \"Luiz de Queiroz\" Campus

Introdução: A bronquiolite aguda é a principal causa de internação de lactentes menores de um ano de idade e tem como principal agente etiológico o vírus sincicial respiratório (VSR). O diagnóstico baseia-se na apresentação clínica e epidemiologia. A maioria das medidas terapêuticas é controversa e apesar da etiologia viral, a prescrição de antibióticos sistêmicos é freqüente. Não está claro se a pesquisa etiológica viral pode influenciar na conduta nesses lactentes. Objetivo: Analisar o impacto da realização de pesquisa etiológica viral sobre a conduta terapêutica, em lactentes internados com bronquiolite aguda. Casuística e métodos: Foi realizado estudo de coorte histórica que incluiu lactentes menores de 12 meses, internados no Hospital Universitário da USP durante dois anos, com diagnóstico de alta de bronquiolite aguda e que tiveram coletado aspirado de nasofaringe, para pesquisa viral, por imunofluorescência indireta (IFI), à admissão. Foram excluídos os lactentes com fatores de risco conhecidos para desenvolver doença grave. As informações foram coletadas dos prontuários. As alterações de condutas realizadas até 24 horas após a divulgação do diagnóstico etiológico foram consideradas associadas ao resultado da IFI. Resultados: Dentre 1199 lactentes, menores de 12 meses hospitalizados, 71% apresentaram diagnóstico de doença aguda do aparelho respiratório, sendo que 33% apresentaram bronquiolite. Desses, 33 foram excluídos e 20 não puderam ter a análise concluída. A idade média, dos 230 lactentes estudados, foi de 4 meses (± 2,7) e 56% foram do sexo masculino. Broncodilatadores, corticosteróides e antibióticos foram prescritos, à admissão em 80%, 52% e 55% dos casos, respectivamente. A pesquisa viral foi positiva para algum vírus em 165 casos e negativa em 65. O VSR foi identificado em 146 casos e outros vírus em 19. Os grupos com pesquisa viral negativa e positiva foram semelhantes com relação à prescrição de antibióticos (52% x 56%, respectivamente, p = 0,636), corticosteróide (42% x 56% -p = 0,052) e broncodilatadores (74% x 83%, p = 0,114) à admissão. A suspensão de antibióticos predominou nos pacientes com pesquisa viral positiva (35,6% x 9,2%, p < 0,001). Não houve alteração significante quanto as prescrições de corticosteróides e broncodilatadores. Também na comparação entre pacientes VSR (+) e com resultado negativo para pesquisa viral, o padrão de alterações de conduta foi semelhante. Houve suspensão de antibióticos em 32,2% e 9,2%, respectivamente (p < 0,001). O resultado positivo da pesquisa viral foi o único fator independentemente associado à suspensão de antibióticos, tanto no grupo com pesquisa viral positiva para qualquer vírus (RR = 3,37, p = 0,005) como no grupo VSR(+) (RR = 3,33, p = 0,006) Conclusão: Em lactentes hospitalizados com BA, o resultado positivo da pesquisa viral por IFI, foi determinante da suspensão de antibióticos sistêmicos, prescritos à admissão. / Background: Acute bronchiolitis is the leading cause of infant hospitalization, and it is most commonly caused by respiratory syncytial virus (RSV). Etiological tests are not required for its diagnosis, which can be made clinically. The most prescribed therapeutic measures are controversial, and in spite of the viral etiology, the prescription of systemic antibiotics is frequent. It remains unclear whether viral screening could contribute to therapy adjustment. Objective: To analyze the impact of viral screening on the therapeutic management of hospitalized infants with acute bronchiolitis. Patients and methods: A retrospective cohort was performed to assess the impact of RSV screening on medication prescription. The study included infants up to 1 year of age who were hospitalized at the University Hospital USP for 2 years, with bronchiolitis as discharge diagnosis and who had nasopharyngeal samples collected on admission for virus screening, by indirect immunofluorescence assay (IFA). Infants were excluded if they had a known risk factors for developing severe disease. Clinical information was obtained from the patients medical records. Therapeutic changes were considered to be associated with viral screening when made within 24 hours of the release of IFA results. Result: Among 1199 hospitalized infants younger than 12 months, 71% were diagnosed with acute lower respiratory disease, of which 33% had bronchiolitis. Of these, 33 were excluded and 20 could not have the analysis completed. The average age of the 230 infants studied was 4 months (+/- 2.7) and 56% were male. Bronchodilators, steroids and antibiotics were prescribed on admission for 80%, 52%, and 55% of cases, respectively. The viral test was positive for some virus in 165 cases and negative in 65. RSV was identified in 146 cases and other viruses in the 19. At admission, the groups with negative or positive viral test were similar regarding the prescription of antibiotics (52% vs 56% respectively, p=0.636), corticosteroids (42% vs 56%, p=0.052) and bronchodilators (74% vs 83%, p=0.114). The discontinuation of antibiotics predominated in patients who tested positive for virus (35.6% vs 9.2%, p<0.001). There were no significant changes regarding the prescription of corticosteroids and bronchodilators. Also, when comparing patients with viral test positive for RSV or negative for any virus the patterns were similar. There was discontinuation of antibiotics in 32.2 % and 9.2%, respectively (p=0.001). The positive result of viral test was the only independent factor associated with the discontinuation of antibiotics, both in the group with positive viral test for any virus (RR=3.37, p=0.005) and in the RVS (+) group (RR=3.33, p=0.006). Conclusion: In hospitalized infants with acute bronchiolitis, the positive result for virus screening, by IFA was an independent factor associated to the discontinuation of systemic antibiotics prescribed at admission.

O núcleo pré-mamilar dorsal (PMd), de crucial importância para expressão do comportamento de defesa exibido por roedores durante o confronto com predador natural, odor ou contexto associado, representa o sítio hipotalâmico com maior aumento no número de células imunorreativas a proteína Fos após o confronto predatório. Estudos mostram que a mediação noradrenérgica central é crítica para a expressão das respostas de medo e que tanto as respostas incondicionadas como as contextuais ao odor do gato dependem de sua ação central, mediada pelo PMd. Dada a importância da modulação noradrenérgica no PMd para a expressão das respostas anti-predatórias, investigamos quais grupamentos catecolaminérgicos aferentam o núcleo empregando técnicas de rastreamento retrógrado somado a técnica de imunofluorescência (dupla-marcação). Nossos resultados revelaram que a única fonte de aferência catecolaminérgica para o PMd é oriunda do locus ceruleus, onde encontramos um número conspícuo de células duplamente marcadas, indicando ser este o responsável pelo suporte noradrenérgico ao PMd. / Evidence suggests the medial hypothalamic defensive system plays a pivotal role in processing of predator-derived and contextual-related cues. Fear responses to predatory threats rely heavily on the PMd beta adrenergic neurotransmission. Thus, it has been shown that propranolol significantly reduced PMdFos expression in response to cat odor, and that beta adrenoceptor blockade, in the PMd, reduced defensive responses to both cat odor exposure and cat odor-related context. Given the importance of the noradrenergic innervation of the PMd to the expression of unconditioned and learned fear responses, we have presently investigated the putative noradrenergic source of inputs to the nucleus. To this end, we have combined Fluoro-Gold retrograde tract-tracing and catecholamine immunostaining, and found that the locus ceruleus is seemingly the only source of catecholaminergic source of inputs to the PMd. In addition, the present findings are particularly interesting given the well-documented roles of the locus ceruleus roles in attentional processes.