The reduced content of estrogen and progesterone receptors in varicocele sperm may be indicative of the clinical surgery in the testicular varicocele

The enigma of testicular varicocele has always attracted the researcher’s attention as attested by the consistent literature, although conflicting data are reported (1). The detrimental role of varicocele in fertility is supported by the presence of an higher frequency of affected men in the infertile population (2). Varicocele influences male fertility in a variety of ways: spermatogenesis, semen quality and gamete biology. However, the mechanism/s by which the pathology impairs sperm production and activity, are not known yet. In spite of active interest, our knowledge about sperm molecular anatomy is very limited. Instead, it is important to fully elucidate the molecular sperm architecture, in order to clarify clinical cases of idiopathic infertility since not all the apparently normal sperm are able to fertilize. The presence of steroid/steroid receptor systems was demonstrated in human sperm, suggesting that both systemic and local steroids through sperm receptors, may influence male fertility. From our data, it emerged that varicocele causes a damage in the gamete at molecular level which includes a significant reduction of estrogen and progesterone receptors, opening a new chapter in the already multifaceted physiopathology of the disease. By the time of ovulation, estradiol and progesterone are almost everywhere in the egg microenvironment affecting ability of sperm to fertilize the oocyte. Therefore, the reduced responsiveness to these hormones as we observed in varicocele sperm, impedes their goal. Altogether, these studies constrain the need of further researches on the molecular anatomy of human male gamete both in healthy and in pathological conditions related the male genital apparatus, considering the high couple infertility linked to the male. The translation of these new researches in the clinic surgery of testicular varicocele needs to be taken into account since the reduction of steroid receptors in sperm implies a decline in the acquisition of fertilizing ability

Adipocyte-derived extracellular vesicles promote breast cancer cell malignancy through HIF-1α activity.

Abstract Extracellular vesicles (EVs) are emerging key protagonists in intercellular communication between adipocytes and breast cancer (BC) cells. Here, we described a new mechanism by which EVs released by mature adipocytes promoted breast cancer cell malignancy "in vitro" and "in vivo". We found that adipocyte-derived EVs enhanced growth, motility and invasion, stem cell-like properties, as well as specific traits of epithelial-to-mesenchymal transition in both estrogen receptor positive and triple negative BC cells. Of note, adipocyte-derived EVs aid breast tumor cells in lung metastatic colonization after tail-vein injection in mice. These EV-mediated effects occur via the induction of HIF-1α activity, since they were abrogated by the use of the HIF-1α inhibitor KC7F2 or in cells silenced for HIF-1α expression. Moreover, using an "ex vivo" model of obese adipocytes we found that the depletion of EVs counteracted the ability of obese adipocytes to sustain pro-invasive phenotype in BC cells. Interestingly, EVs released by undifferentiated adipocytes failed to induce aggressiveness and HIF-1α expression. These findings shed new light on the role of adipocyte-derived EVs in breast cancer progression, suggesting the possibility to target HIF-1α activity to block the harmful adipocyte-tumor cell dialogue, especially in obese settings

PERFIL TECNOLÓGICO DAS AGROINDUSTRIAS FAMILIARES DE FRANCISCO BELTRÃO – PR

Este artigo tem como objetivo avaliar o perfil tecnológico das agroindústrias que comercializam seus produtos alimentícios junto à Cooperativa de Agricultura Familiar Integrada – COOPAFI, do município de Francisco Beltrão –PR. A avaliação das agroindústrias foi realizada através da aplicação de questionário estruturado e semi-estruturado aplicado nas propriedades rurais no período de 04 de março a 27 de abril de 2009. Tais agroindústrias possuem assessoria técnico-científica do projeto de Extensão “Desenvolvimento de Inovações Tecnológicas dos Produtos Alimentícios e Agroecológicos da Pequena Agroindústria Familiar, UNIOESTE – Campus de Francisco Beltrão, em parceria com a Fundação Araucária”. A pesquisa indicou que, 60 % dos associados da Coopafi atuam no processamento de produtos alimentícios artesanais, 27 % destes, processam produtos de panificação, biscoitos e massas, 21 % produzem queijo colonial, 11 % processam produtos derivados da cana de açúcar, como açúcar mascavo e melado, 11 % trabalham no processamento de embutidos, 6 % no ramo do mel, 6 % cachaça, 6 % trabalham com filetagem de peixe, 6 % no processamento de geleias e 6 % no abate de frango de corte

Follicle-stimulating hormone receptor (FSHR) a promising novel target for cancer diagnosis in seminoma and embryonal carcinoma

Adult testicular germ cell tumors (TGCTs) are the most frequent malignant tumors in male patients aged 15–45 years, their incidence is increasing in recent years. There are two main subclasses of TGCTs: seminomas (SE) and non-seminomatous germ cell tumors (NSGCTs). SE have histological features of primordial germ cells, whereas NSGCTs have varying degrees of differentiation (i.e. embryonal carcinoma, EC), they present distinctive clinical features and differ for therapy and prognosis. NSGCTs tend to be metastatic at presentation, and have a worse prognosis than seminomas at an equivalent stage of disease. Despite general advances in the management of TGCTs, the molecular bases underlying their progression remain almost unknown. The effects of the Follicle-stimulating hormone (FSH), central hormone in mammalian reproductive biology, are mediated by FSHR, which was believed to be expressed primarily in ovary and testis. Recently, FSHR expression has been shown in the blood vessels of different solid tumors, including prostate, urothelial and breast carcinomas, suggesting a role in neoangiogenesis. The expression of FSHR at the periphery of tumors, also suggests that FSHR may be of relevance to the metastatic process. In normal human testis, estrogen physiological actions are mediated by estrogen receptor (ER) β and highly variable ERβ expression has been reported in the different TGCTs. ERβ loss is associated with advanced tumor stage in several cancers and previously, we showed a higher expression of ERβ1 in SE with respect EC. In this study, we evaluated the expression of FSHR in normal and neoplastic human testis tissues. Further, we compared FSHR expression with that of ERβ1 in the same samples. In normal testes, immunohistochemical studies showed the presence of FSHR prevalently in somatic testicular cells, while ERβ1 is expressed both in somatic and germinal testicular cells. Intriguingly, we discovered that FSHR was strongly expressed in EC and absent in SE. Conversely, immunostaining for ERβ1 revealed higher intensity in SE as compared to EC. These data suggest distinct physiopathological roles for the two receptors in TGCTs progression, being ERβ1 protective and FSHR harmful. Our data report for the first time the expression of FSHR in TGCTs, suggesting its possible involvement in testicular carcinogenesis. FSHR may be considered an useful molecular marker to distinguish seminoma from embryonal carcinoma, the most common TGCTs subtypes, and this could be informative in clinical decision making and patient counseling

Mitochondrial DNA involvement in human longevity

AbstractThe main message of this review can be summarized as follows: aging and longevity, as complex traits having a significant genetic component, likely depend on a number of nuclear gene variants interacting with mtDNA variability both inherited and somatic. We reviewed the data available in the literature with particular attention to human longevity, and argued that what we hypothesize for aging and longevity could have a more general relevance and be extended to other age-related complex traits such as Alzheimer's and Parkinson's diseases. The genetics which emerges for complex traits, including aging and longevity, is thus even more complicated than previously thought, as epistatic interactions between nuclear gene polymorphisms and mtDNA variability (both somatic and inherited) as well as between mtDNA somatic mutations (tissue specific) and mtDNA inherited variants (haplogroups and sub-haplogroups) must be considered as additional players capable of explaining a part of the aging and longevity phenotype. To test this hypothesis is one of the main challenge in the genetics of aging and longevity in the next future

The follicle-stimulating hormone receptor (FSHR) is expressed in human sperm and it may be considered as molecular marker of the detrimental effects related to the physiopathology of testicular varicocele

Localization of the follicle-stimulating hormone receptor (FSHR), has been always closely related to the testis and ovary. FSH/FSHR role in Sertoli cell, has been known, however, the sites of FSH action within the male reproductive system are not resolved yet. Few studies have raised the intriguing possibility that germ cells may exhibit FSHR, all the reports point to Sertoli cells as the exclusive FSH target cells in testis. Besides, the attention has been always paid on the FSHR several polymorphisms which affect receptor sensitivity and expression. The presence of FSHR in germinal cells from spermatogonia to spermatocytes, including round spermatids is controversial or excluded. The mechanisms by which testicular varicocele affects fertility remain undetermined. Recently, our studies showed that the disease causes damage in sperm at the molecular level opening a new chapter in the already multifaceted physiopathology of varicocele. Samples used in this study were from normozoospermic and from diagnosed varicocele of grade III on the left testis patients. To date four FSHR isoforms were discovered, FSHR1, FSHR2, FSHR3 and FSHR4. The activity of FSHR1 is mediated by G proteins, which activate adenylate cyclase. FSHR2 and FSHR3 also bind FSH, but this does not result in activation of adenylate cyclase. FSHR4 does not bind FSH. By western blot analysis, we showed that healthy sperm express FSHR1, FSHR2 and FSHR3 while FSHR4 is almost absent. Varicocele does not express FSHR2. Immunofluorescence assay evidences FSHR localization prevalently at the midpiece level, which was strongly reduced in varicocele sperm. Responses to different FSH concentrations on motility and survival were significantly reduced in varicocele respect to the normal sperm, probably due to the lower FSHR1 expression and FSHR2 absence. The FSHR significance in human male gamete also emerged from the acrosome reaction histochemical studies, during FSH treatment which significantly induced the process. Our data showed for the first time that human sperm express the FSHR and constrain the need of further studies on the molecular anatomy of human male gamete both in healthy and in pathological conditions related to the male genital apparatus, considering the high couple infertility linked to the male. The translation of these new researches in the clinic surgery of testicular varicocele needs to be taken into account since molecular alterations in sperm imply a decline in the acquisition of fertilizing ability, and to date controversies exist on the opportunity to intervene surgically

Situações de jogo como fonte de "stress" em modalidades esportivas coletivas

O "stress" competitivo é um assunto muito explorado nas pesquisas da área da psicologia esportiva. Nessas pesquisas, o jogo é um dos fatores que produzem a grande maioria das situações de "stress". Este artigo teve como principal objetivo identificar quais as principais situações de "stress" em jogo, de acordo com a opinião de atletas juvenis praticantes de modalidades esportivas coletivas, analisando e comparando essas situações em função de gênero e modalidade esportiva. Participaram 417 atletas na faixa de 14 a 19 anos praticantes de basquetebol, handebol e voleibol. Foi utilizado o Formulário para Identificação de Situações de "Stress" em Jogo e os resultados mostraram que as situações mais freq üentes apontadas como causadoras de "stress" pelos atletas foram: errar em momentos decisivos, perder jogo praticamente ganho, repetir os mesmos erros, arbitragem prejudicial e cometer erros que causem a derrota da equipe. Verificou-se uma alta correlação entre a classificação das situações em função do gênero (rs = 0,89; p < 0,01), o mesmo acontecendo entre as modalidades estudadas (c2 = 35,52; p < 0,01). As situações relacionadas com as competências individuais e coletivas foram as mais citadas pelos atletas. As situações relacionadas a pessoas importantes (técnicos, arbitragem e companheiros de equipe) também foram identificadas como importantes pelos atletas.Competitive stress is constantly explored in sport psychology researches. On these researches the game is the factor that produces the majority of the stressful situations. The main purpose of this study was to identify the stressful situations related to the game in team sports, according to the opinion of youth athletes, comparing the situations according to gender and type of sport. 417 athletes with age from 14 to 19 took part on the study. They were basketball, handball and volleyball players. It was used the Formulary for Identification of Stressful Situations in Game and the results showed that the most frequent situations identified by the athletes were: to make mistakes in decisive moments of the game, to lose a game that was almost won, to repeat the same mistakes, bad referees and to make mistakes that lead to the team defeat. There was a high correlation between the situations rank according to the gender (rs = 0.89; p < 0.01). The same result was observed among the situations rank according to the sports (c2 = 35.52; p < 0.01). Situations related to individual and collective competence were the most frequent according to the athlete's opinion. The situations related to important people (coaches, referees and team mates) were also frequently identified by the athletes

Intracellular survival of Streptococcus pneumoniae in human alveolar macrophages is augmented with HIV infection

People Living with HIV (PLHIV) are at an increased risk of pneumococcal pneumonia than HIV-uninfected adults, but the reasons for this are still not well understood. We investigated whether alveolar macrophages (AM) mediated control of pneumococcal infection is impaired in PLHIV compared to HIV-uninfected adults. We assessed anti-bactericidal activity against Streptococcus pneumoniae of primary human AM obtained from PLHIV and HIV-uninfected adults. We found that pneumococcus survived intracellularly in AMs at least 24 hours post ex vivo infection, and this was more frequent in PLHIV than HIV-uninfected adults. Corroborating these findings, in vivo evidence showed that PLHIV had a higher propensity for harboring S. pneumoniae within their AMs than HIV-uninfected adults. Moreover, bacterial intracellular survival in AMs was associated with extracellular propagation of pneumococcal infection. Our data suggest that failure of AMs to eliminate S. pneumoniae intracellularly could contribute to the increased risk of pneumococcal pneumonia in PLHIV

Intracellular survival of Streptococcus pneumoniae in human alveolar macrophages is augmented with HIV infection

People Living with HIV (PLHIV) are at an increased risk of pneumococcal pneumonia than HIV-uninfected adults, but the reasons for this are still not well understood. We investigated whether alveolar macrophages (AM) mediated control of pneumococcal infection is impaired in PLHIV compared to HIV-uninfected adults. We assessed anti-bactericidal activity against Streptococcus pneumoniae of primary human AM obtained from PLHIV and HIV-uninfected adults. We found that pneumococcus survived intracellularly in AMs at least 24 hours post ex vivo infection, and this was more frequent in PLHIV than HIV-uninfected adults. Corroborating these findings, in vivo evidence showed that PLHIV had a higher propensity for harboring S. pneumoniae within their AMs than HIV-uninfected adults. Moreover, bacterial intracellular survival in AMs was associated with extracellular propagation of pneumococcal infection. Our data suggest that failure of AMs to eliminate S. pneumoniae intracellularly could contribute to the increased risk of pneumococcal pneumonia in PLHIV

Hierarchical spectral clustering reveals brain size and shape changes in asymptomatic carriers of C9orf72

Traditional methods for detecting asymptomatic brain changes in neurodegenerative diseases such as Alzheimer\u27s disease or frontotemporal degeneration typically evaluate changes in volume at a predefined level of granularity, e.g. voxel-wise or in a priori defined cortical volumes of interest. Here, we apply a method based on hierarchical spectral clustering, a graph-based partitioning technique. Our method uses multiple levels of segmentation for detecting changes in a data-driven, unbiased, comprehensive manner within a standard statistical framework. Furthermore, spectral clustering allows for detection of changes in shape along with changes in size. We performed tensor-based morphometry to detect changes in the Genetic Frontotemporal dementia Initiative asymptomatic and symptomatic frontotemporal degeneration mutation carriers using hierarchical spectral clustering and compared the outcome to that obtained with a more conventional voxel-wise tensor- and voxel-based morphometric analysis. In the symptomatic groups, the hierarchical spectral clustering-based method yielded results that were largely in line with those obtained with the voxel-wise approach. In asymptomatic C9orf72 expansion carriers, spectral clustering detected changes in size in medial temporal cortex that voxel-wise methods could only detect in the symptomatic phase. Furthermore, in the asymptomatic and the symptomatic phases, the spectral clustering approach detected changes in shape in the premotor cortex in C9orf72. In summary, the present study shows the merit of hierarchical spectral clustering for data-driven segmentation and detection of structural changes in the symptomatic and asymptomatic stages of monogenic frontotemporal degeneration