Epigenetics modifications and Subclinical Atherosclerosis in Obstructive Sleep Apnea: The EPIOSA study.

Background Obstructive sleep apnea (OSA) is associated with increased risk for cardiovascular morbidity and mortality. Epidemiological and animal models studies generate hypotheses for innovative strategies in OSA management by interferig intermediates mechanisms associated with cardiovascular complications. We have thus initiated the Epigenetics modification in Obstructive Sleep Apnea (EPIOSA) study (ClinicalTrials.gov identifier: NCT02131610). Methods/design EPIOSA is a prospective cohort study aiming to recruit 350 participants of caucasian ethnicity and free of other chronic or inflammatory diseases: 300 patients with prevalent OSA and 50 non-OSA subjects. All of them will be follow-up for at least 5 years. Recruitment and study visits are performed in single University-based sleep clinic using standard operating procedures. At baseline and at each one year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized questionnaire and physical examination to determine incident comorbidities and health resources utilization, with a primary focus on cardiovascular events. Confirmatory outcomes information is requested from patient records and the regional Department of Health Services. Every year, OSA status will be assessed by full sleep study and blood samples will be obtained for immediate standard biochemistry, hematology, inflammatory cytokines and cytometry analysis. For biobanking, aliquots of serum, plasma, urine, mRNA and DNA are also obtained. Bilateral carotid echography will be performed to assess subclinical atherosclerosis and atherosclerosis progression. OSA patients are treated according with national guidelines. Discussion EPIOSA will enable the prospective evaluation of inflammatory and epigenetics mechanism involved in cardiovascular complication of treated and non-treated patients with OSA compared with non OSA subjects

Morphological Variation of the Forelimb and Claw in Neotropical Sigmodontine Rodents (Rodentia: Cricetidae)

The limbs of mammals exhibit a variety of morphologies that reflect the diversity of their habitats and their functional needs, including subtle structural differences in their distal limb integumentary appendages (hooks, claws, adhesive pads). Little is known about structure and function of claws of sigmodontine rodents. Here, we analyze claw shape and forelimb skeleton morphology of 25 species of sigmodontine rodents with different locomotory types (ambulatory, fossorial, natatorial, quadrupedal saltatorial, and scansorial), taking into account their phylogenetic affinities. Qualitative differences in claw shape were examined using digital photographs, and quantitative measurements were made for length, height, and curvature of the claws of all digits, and dimensions of other forelimb skeletal elements. Our results show that both phylogeny and ecological categories explain substantial components of the morphological variation in sigmodontine rodents. Qualitative analysis reveals that non-specialized forms (ambulatory, quadrupedal saltatorial, and scansorial) tend to have high and strongly curved claws, whereas highly specialized forms (fossorial and natatorial) tend to have elongate and smoothly curved claws. However, the quantitative analysis differentiated the fossorial and scansorial by variables related to claw, and natatorial by variables related to bones of the forelimb. No variables that could differentiate ambulatory or quadrupedal saltatorial forms were found, demonstrating that these forms show a generalized morphological pattern. This study indicates that both historical and ecological factors contribute to the evolution of claw length in these groups.Fil: Tulli, María José. Fundación Miguel Lillo. Dirección de Zoología. Instituto de Herpetología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carrizo, Luz Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; Argentina. Universidad Nacional de Misiones; ArgentinaFil: Samuels, J. X.. John Day Fossil Beds National Monument; Estados Unido

Na+/K+-ATPase stabilization by Hsp70 in the outer stripe of the outer medulla in rats during recovery from a low-protein diet

A low-protein (LP) diet induces injury from energy depletion in renal epithelial cells. Overexpression of heat-shock proteins has been implicated in the restoration of the cytoskeletal anchorage of Na+/K+-ATPase. We tested if Hsp70 stabilizes renal Na+/K+-ATPase attachment to the cytoskeleton from the cortex and the outer stripe of the outer medulla (OSOM) in rats during recovery from a LP diet. Rats were fed with a LP diet (8% protein) for 14 days, and then the rats were recovered with a 24% protein (RP) diet. The control group received a 24% protein (NP) diet. Increased Na+/K+-ATPase dissociation was demonstrated in soluble fraction from OSOM with lower ATP content as a result of LP diet vs NP. Meanwhile, decreased Hsp70 levels in the same fraction were shown. Translocation of Hsp70 to the cytoskeletal injured fraction associated with stabilization of Na+/K+-ATPase was shown in OSOM from LP after in vitro co-incubation of the cytoskeletal fraction of LP and non-cytoskeletal fraction of RP. These effects were abolished by the addition of the anti-Hsp70 antibody. Absence of Na+/K+-ATPase detachment from its cytoskeletal anchorage was demonstrated in proximal duct segments from cortex in LP. Co-immunoprecipitation showed that the amount of Na+/K+-ATPase co-precipitating with Hsp70 increased in the OSOM as a result of the LP diet. In the cortex tissues from rats fed the LP and the RP diet, the interaction of both proteins were similar to the control groups. Our results indicate that Hsp70 has a critical role in protecting the integrity of the cytoskeletal anchorage of Na+/K+-ATPase during recovery from ATP-depleted injury resulting from LP in OSOM