Check us out at cutiepieandbaby.com.

Epidemiologic studies have shown that aging accounts significantly for the prevalence of erectile dysfunction (ED). The pathophysiology of ED during aging and its underlying molecular mechanisms are largely unknown. We hypothesized that increased RhoA/Rho-kinase signaling is a major factor in the pathogenesis of age-associated ED and the mechanism involves increased penile smooth muscle contractility through inhibition of myosin light chain phosphatase. Male Fischer 344 young (4 month old) and aged (20-22 month old) rats underwent erectile function testing in vivo by measuring intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) upon electrical stimulation of the cavernous nerve. The data demonstrated that erectile function was significantly lower in aged rats than that in young rats at all voltages tested (P<0.05).

Western blot analysis results showed that there were no significant changes in protein expressions of RhoA, Rho-kinase-alpha and -beta isoforms, and myosin light chain phosphatase target subunit (MYPT1); however, membrane-bound RhoA and phosphorylated MYPT1 were increased in aged rat penes by 95 +/- 15 and 56 +/- 8% (P<0.05), respectively, indicating enhanced RhoA and Rho-kinase activity. Inhibition of Rho-kinase with Y27632 maximally increased ICP/MAP to 0.72 +/- 0.05 in aged rats vs. 0.47 +/- 0.06 in young rats (P<0.05).

Gene transfer of adeno-associated virus (AAV) encoding dominant negative RhoA (T19NRhoA) to penes of aged and young rats for 7 days markedly improved erectile function in aged rats when compared with that in young rats (P<0.05). These observations were also supported by Rho-kinase activity assay results showing that basal Rho-kinase activity in aged rat penes receiving AAV vehicle treatment was twofold greater than that in young rat penes receiving AAV vehicle treatment, while it was reduced to a level similar to that in young rat penes after gene therapy of T19NRhoA (P<0.05). Taken together, these data suggest that impaired erectile function during the aging process involves increased RhoA/Rho-kinase signaling, and this pathway may be exploited for the treatment of age-associated ED.

Then our hotel owner Damir drove us across the border to Bihač  in Bosnia. We had to stop for a few minutes at one point to wait for mine sweepers to finish checking a spot by the road. A bit later we drove through a deserted town which Damir told us was an old Serbian village – The townspeople had fled during the 1990s war (it’s very close to Croatia), and now most of them are afraid to come back because there are 12 unexplained Croatian deaths. We took a bus from Bihač to the medieval mountain castle town Jajce, seat of power of the ancient Bosnian kings. One wall of the house we are staying in is a thousand year old stone tower.

Interesting trivia – The medieval Bosnian kings didn’t like Christianity very much, so they converted the entire country to a primitive religion called Bogomil around 600 AD. When the Turks conquered Bosnia in the 1400s, the people didn’t care much about their old-fashioned religion, so thez were easily converted to Islam. Ergo, By the early 1900s, almost the entire country was made up of ethnically European Muslims. Even after being killed in vast numbers in WW1, then again in WW2, and in the mid 1990s, Bosnia and Hercegovina is still the only country in Europe with a Muslim majority.

Forgive the lack of links – it is really tough to make them on this shit keyboard. Wikipedia anything you’re interested in.

Achieving a balance between cortical circuit stability and plasticity allows us to adapt to and learn from novel environmental experiences without forgetting useful information from the past. Children and adolescents have little experience to guide their actions, so new information is very important, and plasticity (learning) is favored over stability (memory). Conversely, the elderly have a wealth of past experiences, so incorporating new information into world models is less likely to be beneficial, and stability is favored over plasticity.

One theory for the pathophysiology of developmental brain disorders like Fragile X syndrome, Rett Syndrome, Angelman syndrome, and MECP2 duplication syndrome is that the link between genetic lesions and certain neuropsychiatric phenotypes is an imbalance between stability and plasticity. If the brain’s synapses are too stable, the brain will have trouble adapting to new experiences; Synaptic rigidity of this sort could lead to the permanent infantilism seen in Angelman syndrome, and has indeed been demonstrated Angelman syndrome mouse model. If the brain’s synapses are too labile, on the other hand, extant memories may be continually overturned by new experiences, or even worse synapses will continue to develop past their normal strengths, generating stereotypic behavior and epileptic circuitry. In either case, the cumulative refinement of neural circuitry that is important for brain development cannot occur.

Results in my lab suggest that MECP2 duplication syndrome is an example may be such a syndrome of too much plasticity. In juvenile mice, this bias toward synapse turnover allows relatively rapid acquisition of both adaptive (enhanced motor learning) and maladaptive (enhanced conditioned fear response) environmental adaptations. As the mice reach adulthood, they have sampled a broader range of world states, but the normal developmental deceleration of cortical plasticity which would shift the continuum to stability in cortical circuits does not occur. Instead, circuits oversaturate, leading to hyperexcitable ensembles which continue to self-strengthen by positive feedback. Activity in these dysfunctional cortical circuits produces compulsive, repetitive, stereotyped behaviors as well as runaway resonant excitation and epileptic seizures. Along these lines, it appears that patients steadily acquire developmental milestones until a critical point in which neurodevelopment stagnates and seizures ensue (Karas & Zoghbi, unpublished observations).

A convincing physiological link between the symptoms of MECP2 duplication syndrome and its underlying genetic lesion has yet to be established, but work in mouse models and neuronal culture indicates that deranged dendritic/synaptic structure and plasticity may be an important locus of disease. The MECP2 duplication mice have a dramatically increased density of excitatory synapses in the hippocampus which is most prominent at young ages. Overexpression of MECP2 in primary slice cultures (to make a primary slice culture – a brain is harvested, sliced into slabs, and placed in a petri dish with oxygen and nutrients. They can survive for weeks and months with appropriate care)  causes a range of structural abnormalities in dendritic arbors and dendritic spines (the small protrusions from dendrites at which most excitatory synapses form). Detailed neuropathology with postmortem MECP2 duplication syndrome patient samples has yet to be performed.

In our lab, we are studying the formation, development, and pruning of these dendritic spines in MECP2 duplication mice. We cross the MECP2-duplication mice to the thy1-GFP (Green Fluorescent Protein form jellyfish) transgenic mice, which have been engineered to express bright fluorescence in a small number of layer  pyramidal neurons. These glow-in-the-dark neurons allows us to image apical dendrite and dendritic spine morphology in intact animals over days, weeks, and months, using two-photon microscopy (basically, a laser scans through the brain tissue identifying points of fluorescence in 3 dimensions). We are imaging the synaptic development from presymptomatic (4 weeks) stages to severe symptomatic (40 weeks) stages.

Our key finding so far is that the process of dendritic spine turnover (formation and pruning of synapses over time) does not undergo the normal developmental deceleration with age, but rather stays abnormally high well into adulthood, and that this elevated spine turnover is correlated with a net decrease in dendritic spine densities.

In this study, we investigate gender differences and menstrual cycle effects in first-price and second-price sealed-bid auctions with independent private values in a laboratory setting. We find that women bid significantly higher and earn significantly less than men do in the first-price auction, while we find no evidence of a gender difference in bidding in the second-price auction. At a biological level, we find a sine-like pattern of bidding in the first-price auction throughout the menstrual cycle, with higher bidding in the follicular phase and lower bidding in the luteal phase. Further analysis shows almost all of the variation is driven by contraceptive pill users.

SSRN link: http://papers.ssrn.com/sol3/papers.cfm?abstract_id=881748

Many sociological theories positing a deterrent effect of religion on crime are empirically examined using ordinary least-squares (OLS) regressions of crime measures on measures of religiosity. Most previous studies have found a negative effect of religion on crime using OLS, a result I am able to replicate using county-level data on religious membership and crime rates. If crime affects religious participation, however, OLS coefficients in this context suffer from endogeneity bias. Using historic religiosity as an instrument for current religious participation, I find a negligible effect of religion on crime and a negative effect of crime on religion. To further explore the relationship between religion and crime, I examine variation in crime incidence before and after Easter. Consistent with the IV results, I find no evidence of a decrease in crime following Easter.

Link: http://www.jstor.org/stable/10.1086/501087

In this paper we employ the 1979 Child-Young Adult National Longitudinal Survey of Youth and the 1997 National Longitudinal Survey of Youth to estimate the effects of television fast-food restaurant advertising on children and adolescents with respect to being overweight. A ban on these advertisements would reduce the number of overweight children ages 3-11 in a fixed population by 18 percent and would reduce the number of overweight adolescents ages 12-18 by 14 percent. The elimination of the tax deductibility of this type of advertising would produce smaller declines of between 5 and 7 percent in these outcomes but would impose lower costs on children and adults who consume fast food in moderation because positive information about restaurants that supply this type of food would not be completely banned from television.

Full text: http://democrats.edworkforce.house.gov/documents/111/pdf/publications/20100701hearingarticle3.pdf

Reduced-form regressions of STD rates on state alcohol taxes for the years 1981–95 (with controls for state and year) indicate that a $1 increase in the per-gallon liquor tax reduces gonorrhea rates by 2.1 percent, and a beer tax increase of $.20 per six-pack reduces gonorrhea rates by 8.9 percent, with similar though more pronounced effects on syphilis rates.

Full text link: http://dinhvutrangngan.com/teaching/Social_Economics/Sexual_Behaviors/Chesson%20et%20al_2000.pdf

The Black Death visited unprecedented mortality rates on Europe, realigning relative values of factors of production, and in consequence the costs and benefits of defining and enforcing property rights. . . . [T]he marginal value of labor and human capital rose, which placed insupportable stress on feudal institutions. The predictable evolution of workers’ rights to their own labor accelerated the erosion of serfdom.

Full text available here.