Influence of mild-to-moderate alcohol consumption on cardiovascular diseases in men from the general population

Background and methodsThere is controversy about the association between mild-to-moderate alcohol consumption and a reduced risk of cardiovascular diseases. The relationships between daily alcohol consumption and the incidence of acute myocardial infarction (MI) or ischemic stroke (IS) were examined in men in a community-based, prospective cohort study (n = 8014, age 40–80 years, mean age = 64.1 years). Alcohol consumption was categorized into 3 groups (A1, none or occasional; A2, ≤25 g/day; A3, >25 g/day as ethanol) at baseline.ResultsDuring the mean follow-up of 5.5 years, 53 MIs and 186 ISs occurred. On Cox regression analysis adjusted for age, hypertension, diabetes, dyslipidemia, smoking index, and body mass index (BMI), the hazard ratio (HR) for incident MI was significantly lower in the A2 group than in the A1 group (HR = 0.49, p = 0.043). The HR for incident MI in the A3 group tended to be lower than in the A1 group (HR = 0.53, p = 0.10). In obese subjects, while a significantly lower HR for incident MI in the A2 group was retained (HR = 0.29, p = 0.049), no significant difference in the HR of the A3 group compared with the A1 group was found. No significant differences were found in the IS-free curve among the 3 groups of alcohol consumption.ConclusionsAlcohol consumption may have a protective effect on the onset of MI but not on IS in the general population. A U-shaped relation between alcohol consumption and incident MI was found in obese subjects. An appropriate limit for daily alcohol consumption, depending on the risk of ischemic heart disease, may need to be established.     

Wnt2 accelerates cardiac myocyte differentiation from ES-cell derived mesodermal cells via non-canonical pathway

The efficient induction of cardiomyocyte differentiation from embryonic stem (ES) cells is crucial for cardiac regenerative medicine. Although Wnts play important roles in cardiac development, complex questions remain as to when, how and what types of Wnts are involved in cardiogenesis. We found that Wnt2 was strongly up-regulated during cardiomyocyte differentiation from ES cells. Therefore, we investigated when and how Wnt2 acts in cardiogenesis during ES cell differentiation. Wnt2 was strongly expressed in the early developing murine heart. We applied this embryonic Wnt2 expression pattern to ES cell differentiation, to elucidate Wnt2 function in cardiomyocyte differentiation. Wnt2 knockdown revealed that intrinsic Wnt2 was essential for efficient cardiomyocyte differentiation from ES cells. Moreover, exogenous Wnt2 increased cardiomyocyte differentiation from ES cells. Interestingly, the effects on cardiogenesis of intrinsic Wnt2 knockdown and exogenous Wnt2 addition were temporally restricted. During cardiomyocyte differentiation from ES cells, Wnt2 didn't activate canonical Wnt pathway but utilizes JNK/AP-1 pathway which is required for cardiomyocyte differentiation from ES cells. Therefore we conclude that Wnt2 plays strong positive stage-specific role in cardiogenesis through non-canonical Wnt pathway in murine ES cells.     

Nanoparticle delivery in infant lungs

The lung surface is an ideal pathway to the bloodstream for nanoparticle-based drug delivery. Thus far, research has focused on the lungs of adults, and little is known about nanoparticle behavior in the immature lungs of infants. Here, using nonlinear dynamical systems analysis and in vivo experimentation in developing animals, we show that nanoparticle deposition in postnatally developing lungs peaks at the end of bulk alveolation. This finding suggests a unique paradigm, consistent with the emerging theory that as alveoli form through secondary septation, alveolar flow becomes chaotic and chaotic mixing kicks in, significantly enhancing particle deposition. This finding has significant implications for the application of nanoparticle-based inhalation therapeutics in young children with immature lungs from birth to 2 y of age.     

Coordinated phenotype switching with large-scale chromosome flip-flop inversion observed in bacteria

Genome inversions are ubiquitous in organisms ranging from prokaryotes to eukaryotes. Typical examples can be identified by comparing the genomes of two or more closely related organisms, where genome inversion footprints are clearly visible. Although the evolutionary implications of this phenomenon are huge, little is known about the function and biological meaning of this process. Here, we report our findings on a bacterium that generates a reversible, large-scale inversion of its chromosome (about half of its total genome) at high frequencies of up to once every four generations. This inversion switches on or off bacterial phenotypes, including colony morphology, antibiotic susceptibility, hemolytic activity, and expression of dozens of genes. Quantitative measurements and mathematical analyses indicate that this reversible switching is stochastic but self-organized so as to maintain two forms of stable cell populations (i.e., small colony variant, normal colony variant) as a bet-hedging strategy. Thus, this heritable and reversible genome fluctuation seems to govern the bacterial life cycle; it has a profound impact on the course and outcomes of bacterial infections.