1,639 research outputs found

    Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation

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    Mammalian sperm require to spend a limited period of time in the female reproductive tract to become competent to fertilize in a process called capacitation. It is well established that HCO3 − is essential for capacitation because it activates the atypical soluble adenylate cyclase ADCY10 leading to cAMP production, and promotes alkalinization of cytoplasm, and membrane hyperpolarization. However, how HCO3 − is transported into the sperm is not well understood. There is evidence that CFTR activity is involved in the human sperm capacitation but how this channel is integrated in the complex signaling cascades associated with this process remains largely unknown. In the present work, we have analyzed the extent to which CFTR regulates different events in human sperm capacitation. We observed that inhibition of CFTR affects HCO3 −-entrance dependent events resulting in lower PKA activity. CFTR inhibition also affected cAMP/PKA-downstream events such as the increase in tyrosine phosphorylation, hyperactivated motility, and acrosome reaction. In addition, we demonstrated for the first time, that CFTR and PKA activity are essential for the regulation of intracellular pH, and membrane potential in human sperm. Addition of permeable cAMP partially recovered all the PKA-dependent events altered in the presence of inh-172 which is consistent with a role of CFTR upstream of PKA activation.Fil: Puga Molina, Lis del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pinto, Nicolás Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Torres Rodríguez, Paulina. Universidad Nacional Autónoma de México; MéxicoFil: Romarowski, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vicens Sanchez, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Visconti, Pablo E.. University of Massachussets; Estados UnidosFil: Darszon, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Treviño, Claudia L.. Universidad Nacional Autónoma de México; MéxicoFil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

    The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor

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    Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be orroborated in humans

    Próteses parciais fixas reforçadas por fibras: um estudo clínico retrospectivo preliminar

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    The aim of this study was to evaluate the clinical performance (retention rate) of fiber-reinforced composite fixed partial dentures (FPDs). Polyethylene fiber (Ribbond®) was used combined with restorative composite during FPDs fabrication. FPDs were placed in thirteen patients in a private clinic. Nineteen FPDs were evaluated. The prosthetic space was filled with only one pontic using extracted teeth (2 cases), acrylic resin teeth (11 cases), or with composite resin (6 cases), combined with Polyethylene fiber. The clinical criterion used was based on retention rate of FPDs. If FPDs were in function in the mouth at the time of examination without previous repair they were classified as Complete Survival (CS) restorations. A classification of Survival with Rebonding (SR) was assigned in the event of an adhesive failure, but after rebonding the FPD still remained under evaluation. Treatment was classified as a Failure (F) if the FPD restoration was lost. The time of evaluation was 41.15 months (±15.13). The FPDs evaluated were retained (CS=94.75%), and no failure was found except for in one situation which required rebonding (SR=5.25%). According to the survival estimation method of Kaplan-Meyer the mean survival time was 42.3 months. At the time of evaluation investigated, polyethylene-reinforced FPDs showed a favorable retention rate in preliminary data.O objetivo deste estudo foi avaliar a performance clínica (percentagem de retenção) de próteses parciais fixas reforçadas por fibras. Fibras de polietileno (Ribbond®) foram usadas em combinação com resina composta durante a confecção das próteses. Os tratamentos foram realizadas em 13 pacientes, em uma clínica privada., sendo que 19 próteses foram reavaliadas. O espaço protético era preenchido com um pôntico usando o próprio dente extraído (2 casos), dentes de acrílico (11 casos) ou confeccionados com resina composta (6 casos), em todas as situações eram empregadas fibras de polietileno. Os critérios clínicos usados foram baseados na percentagem de retenção das próteses parciais fixas. As próteses que estavam em função no momento da avaliação, sem nunca necessitar de qualquer reparo prévio, foram classificadas como sobrevivência completa (SC). A classificação de sobrevivência com nova colagem (SR) foi utilizada para os casos de falha adesiva, com posterior cimentação da peça, a qual permanecia em função. O tratamento era classificado como falha (F) quando a restauração era perdida. O tempo médio de avaliação foi de 41,15 meses (±15,13). Nenhum caso de falha foi detectado, em apenas um caso houve falha adesiva com posterior colagem da peça (SR=5,25%) e em 94.75% dos casos as próteses permaneciam em função.. De acordo com o método de sobrevida de Kaplan-Meyer o tempo médio de sobrevida foi de 42,3 meses. As próteses parciais fixas reforçadas por fibras mostraram uma percentagem de retenção favorável neste estudo preliminar

    Benefitting from the Grey Literature in Software Engineering Research

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    Researchers generally place the most trust in peer-reviewed, published information, such as journals and conference papers. By contrast, software engineering (SE) practitioners typically do not have the time, access or expertise to review and benefit from such publications. As a result, practitioners are more likely to turn to other sources of information that they trust, e.g., trade magazines, online blog-posts, survey results or technical reports, collectively referred to as Grey Literature (GL). Furthermore, practitioners also share their ideas and experiences as GL, which can serve as a valuable data source for research. While GL itself is not a new topic in SE, using, benefitting and synthesizing knowledge from the GL in SE is a contemporary topic in empirical SE research and we are seeing that researchers are increasingly benefitting from the knowledge available within GL. The goal of this chapter is to provide an overview to GL in SE, together with insights on how SE researchers can effectively use and benefit from the knowledge and evidence available in the vast amount of GL

    Association of physical function with predialysis blood pressure in patients on hemodialysis

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    BACKGROUND: New information from various clinical settings suggests that tight blood pressure control may not reduce mortality and may be associated with more side effects. METHODS: We performed cross-sectional multivariable ordered logistic regression to examine the association between predialysis blood pressure and the short physical performance battery (SPPB) in a cohort of 749 prevalent hemodialysis patients in the San Francisco and Atlanta areas recruited from July 2009 to August 2011 to study the relationship between systolic blood pressure and objective measures of physical function. Mean blood pressure for three hemodialysis sessions was analyzed in the following categories: <110 mmHg, 110-129 mmHg (reference), 130-159 mmHg, and ≥160 mmHg. SPPB includes three components: timed repeated chair stands, timed 15-ft walk, and balance tests. SPPB was categorized into ordinal groups (≤6, 7-9, 10-12) based on prior literature. RESULTS: Patients with blood pressure 130-159 mmHg had lower odds (OR 0.57, 95% CI 0.35-0.93) of scoring in a lower SPPB category than those whose blood pressure was between 110 and 129 mmHg, while those with blood pressure ≥160 mmHg had 0.56 times odds (95% CI 0.33-0.94) of scoring in a lower category when compared with blood pressure 110-129 mmHg. When individual components were examined, blood pressure was significantly associated with chair stand (130-159 mmHg: OR 0.59, 95% CI 0.38-0.92) and gait speed (≥160 mmHg: OR 0.59, 95% CI 0.35-0.98). Blood pressure ≥160 mmHg was not associated with substantially higher SPPB score compared with 130-159 mmHg. CONCLUSIONS: Patients with systolic blood pressure at or above 130 mmHg had better physical performance than patients with lower blood pressure in the normotensive range. The risk-benefit tradeoff of aggressive blood pressure control, particularly in low-functioning patients, should be reexamined

    The effects of low and high glycemic index foods on exercise performance and beta-endorphin responses

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    Τhe aim of this study was to examine the effects of the consumption of foods of various glycemic index values on performance, β-endorphin levels and substrate (fat and carbohydrate) utilization during prolonged exercise. Eight untrained healthy males underwent, in a randomized counterbalanced design, three experimental conditions under which they received carbohydrates (1.5 gr. kg-1 of body weight) of low glycemic index (LGI), high glycemic index (HGI) or placebo. Food was administered 30 min prior to exercise. Subjects cycled for 60 min at an intensity corresponding to 65% of VO2max, which was increased to 90% of VO2max, then they cycled until exhaustion and the time to exhaustion was recorded. Blood was collected prior to food consumption, 15 min prior to exercise, 0, 20, 40, and 60 min into exercise as well as at exhaustion. Blood was analyzed for β-endorphin, glucose, insulin, and lactate. The mean time to exhaustion did not differ between the three conditions (LGI = 3.2 ± 0.9 min; HGI = 2.9 ± 0.9 min; placebo = 2.7 ± 0.7 min). There was a significant interaction in glucose and insulin response (P < 0.05) with HGI exhibiting higher values before exercise. β-endorphin increased significantly (P < 0.05) at the end of exercise without, however, a significant interaction between the three conditions. Rate of perceived exertion, heart rate, ventilation, lactate, respiratory quotient and substrate oxidation rate did not differ between the three conditions. The present study indicates that ingestion of foods of different glycemic index 30 min prior to one hour cycling exercise does not result in significant changes in exercise performance, β-endorphin levels as well as carbohydrate and fat oxidation during exercise
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