Hybridization in human evolution: Insights from other organisms

During the late Pleistocene, isolated lineages of hominins exchanged genes thus influencing genomic variation in humans in both the past and present. However, the dynamics of this genetic exchange and associated phenotypic consequences through time remain poorly understood. Gene exchange across divergent lineages can result in myriad outcomes arising from these dynamics and the environmental conditions under which it occurs. Here we draw from our collective research across various organisms, illustrating some of the ways in which gene exchange can structure genomic/phenotypic diversity within/among species. We present a range of examples relevant to questions about the evolution of hominins. These examples are not meant to be exhaustive, but rather illustrative of the diverse evolutionary causes/consequences of hybridization, highlighting potential drivers of human evolution in the context of hybridization including: influences on adaptive evolution, climate change, developmental systems, sex-differences in behavior, Haldane’s rule and the large X-effect, and transgressive phenotypic variation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151330/1/evan21787.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151330/2/evan21787_am.pd

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

EFFICIENCY OF INFLUENZA VACCINATION IN PATIENTS WITH CIRCULATORY SYSTEM DISEASES UNDER DISPENSARY OBSERVATION IN OUTPATIENT CLINICS: PROSPECTIVE FOLLOW-UP MONITORING DATA

Aim. To estimate an efficiency of influenza vaccination in patients with circulatory system diseases diseases (CSD) under 3-year follow-up in outpatient clinics.Methods. The efficiency of influenza vaccination was investigated in CSD patients followed up at 2Ivanovo outpatient clinics and 2Saratov ones. The investigation enrolled 817 people, including 367 patients who consented to Grippol Plus influenza vaccination and 450 who refused.Results. During 36-month follow-up after being included in the study the vaccinated group showed a significantly fewer influenza and acute respiratory viral infections than the non-vaccinated group (28 and 442; р<0.0001). The vaccinated group had fewer CSD worsening cases per patient (p=0.04) and CSD-associated hospitalization rates (p=0.006) than the non-vaccinated group. In the vaccinated group, the total number of cases of cerebral stroke, myocardial infarction, deaths from cardiovascular diseases (CVD) was significantly less (17) compared with non-vaccinated (38), р=0.03. The risk of infectious diseases and acute cardiovascular event (myocardial infarction, stroke, death from CVD) was significantly lower in the group of vaccinated patients: by 36% (p=0.001) and by 59% (p=0.008), respectively.Conclusion. Influenza vaccination, as an essential component of complex medical prevention, leads to reduction in incidence of infectious diseases and of CSD worsening including myocardial infarction, stroke, and death from CVD in patients under 3-year monitoring in outpatient clinic