Oxidants Induce α-Synuclein-Independent Toxicity in a Fission Yeast Model for Parkinson's Disease

Parkinson's disease is a progressive neurodegenerative disease caused by the death of midbrain dopaminergic neurons. The misfolding and aggregation of the protein α-synuclein and accumulation of oxidants is thought to underlie the cell death, but how α-synuclein becomes toxic is unclear. Using fission yeast as a model organism, where α-synuclein expression induces aggregation but not toxicity, we tested the hypothesis that α-synuclein toxicity can result from the combination of protein aggregation and oxidative stress. Surprisingly, we found that both oxidants (hydrogen peroxide and cumene hydroperoxide) tested in our study resulted in α-synuclein-independent toxicity. Nevertheless, this work illustrates the usefulness of yeasts in evaluating genetic factors and environmental factors like oxidative stress to potentially regulate α-synuclein toxicity linked to Parkinson's disease.

Cedrela odorata acts as a Contraceptive in Adult Female Mice

The researchers wanted to find a medicinal plant that could be used in the pharmaceutical world as a contraceptive due to women looking for a safer and more effective one. According to Rainforest Remedies by Dr. Michael Balick and Rosita Arvigo (1998), Mayan women would make Cedrela odorata bark into tea and drink it three times a day for three days in order to cause sterility for one cycle. Hence, the researchers felt that this needed to be researched further to determine if it could become the contraceptive women were looking for. To assess the efficacy of Cedrela odorata as an affective contraceptive, (CD-1) female mice were administered tea made from the bark three times a day for three consecutive days, followed by copulation with male mice. The tea intercepted 92% of the pregnancies in female mice among the three experimental groups when administered orally for three days with three doses of 0.15 milliliters. All of the control group mice became pregnant when administered orally for three days with three doses of 0.15 milliliters of distilled water. No mortality and changes in the behavior were observed from pre-dose days to the postcoitum days in all the control and experimental groups. The two-tailed P value ≤ 0.0001 compared the number of pregnancies of the six experimental groups to the number of pregnancies of the two control groups. Findings demonstrated that there was a significant contraceptive efficacy of the Cedrela odorata bark made into tea at the dose of 0.15 milliliters. More research is needed to determine the length of sterility and the mechanism of the bark. This research will help meet the increasing need for population control due to no clear improvement in the effectiveness in contraceptives between 1995 and 2002 (Kost et al. 2008). Being of plant origin would allow for a relatively cheap and effective contraceptive that could become widely available and accepted.

Attention, Water Consumption, Water Appraisals and Nonconscious Affect

Relatively minimal work has examined the extent to which sad and happy emotional detectors nonconsciously influence executive processes and if these mechanisms affect water appraisal and water consumption behavior. This research studies if and the degrees to which sad and happy emotional detectors affect water appraisal, water consumption and attention. The participants were asked to locate and report an asterisk's location that was superimposed in subliminal pictures of happy or sad people presented on a computer, pour water from a 1000 mL container into a 473 mL cup, consume as much of the 1000 mL of water as desired, and provide ratings of the water on a questionnaire. The one tailed independent samples t-tests revealed that the participants in the "happy" condition detected more (p.05) causal relationships and interactions, respectively, between the experimental conditions and appraisal and behavioral processes regarding water. These findings suggest that humans may be unable to devote their full attention to a task when their "sad" emotional detectors are activated. Also, our "happy" and "sad" emotional detectors may not be able to influence water consumption or appraisals.

Computer Generation of Three Dimensional Human Cerebral Vasculature Models

Recent clinical findings suggest changes in vasculature compliance may be responsible for abnormal brain dynamics in diseases like hydrocephalus. Understanding and treating pathological brain dynamics requires a quantitative understanding of the complex interaction between pulsating vasculature, cerebrospinal fluid, and brain tissue. Models addressing anatomically correct geometry, physiological haemodynamics and complete interactions of vasculature and brain tissue are required for this purpose. In this article, a geometrical model of the cerebral vasculature is presented as a first step in the development of a fully distributed mathematical model for quantitative analysis of intracranial dynamics. We present two- and three- dimensional models of the human cerebral vasculature network. The model was generated in two phases. First, the major extracerebral arteries were reconstructed using patient-specific MRI images. Then in step two a special modified algorithm of Beard & Bassingthwaighte generated the microvasculature, starting from the major arteries of step one. This fractal-based growth algorithm incorporates vessel and complex domain boundary avoidance to create the vasculature. Significant findings are: (1) MRI imaging was successful in generating patient specific geometry of the brain cerebral arteries including carotid artery, basilar artery, Circle of Willis and vertebral arteries; (2) a microvasculature below the medical imaging resolution was successfully created by the computer algorithm; (3) vessels consistently remained inside the domain boundary and avoided overlap; (4) model capillary density agrees qualitatively with actual human capillary density. However, there were some limitations to the model. The model is not completely consistent with the cerebral vasculature anatomy due to limited MRI resolution and the absence of physiological driving forces for the vessel growth in the algorithm. Future work will focus on acquiring quantitatively accurate capillary density in the model by incorporating growth factors in the algorithm. Work is being done toward incorporating blood vessel branching factors and constrained optimization techniques into the algorithm. Moreover, in the next step blood flow simulations need to be performed to predict blood flow and vessel dilations.

Letter to the Editor: Evidence-Based Medicine, Some Epistemological Dissents

To the Editor: Because physicians deal daily with human suffering, they should be aware about taking the best clinical decisions to mitigate their misery. This premise generates a crucial question: on what should clinicians’ decisions be based to achieve this goal? Lately, as discussed by Rosenberg et al. (1995), there is strong academic consensus that scientific evidence should be the platform that supports medical decisions; and it is precisely in this scenario where Evidence Based Medicine (EBM) is considered a new paradigm for medical practice.

Immunopathogenesis of Dengue Hemorrhagic Fever

The dengue virus (DENV) with its four unique serotypes is transmitted by the Aedes mosquito vector in tropical countries worldwide. All serotypes can cause illness ranging from asymptomatic, self-limiting flu, Dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). DHF and DSS are characterized by a sudden increase in vascular permeability due to a unique set of cytokines released by DENV-infected monocytes. The method by which DHF/DSS arises is largely accepted to be due to Antibody Dependent Enhancement (ADE) whereby upon secondary infection with a different serotype, the immune system generates non-neutralizing antibody-antigen complexes that permit a greater number of viruses to enter monocytes via Fc-receptors than DENV alone. These DENV-infected monocytes release cytokines resulting in DHF/DSS, the severe and life-threatening forms of the disease. Although the number of people that develop potentially fatal DHF/DSS is relatively small, the effect of all symptomatic DENV infections on Dengue endemic areas is impetus for the large-scale prevention of viral transmission. Given the serotype specific immunity to DENV infections and the possibility of ADE-induced DHF/DSS, prevention of DF is critical. There is currently no Dengue vaccine for the estimated 2.5 billion people at risk of infection; however vaccines under development are being designed to provide protective immunity against all four DENV serotypes to minimize the devastating consequences of ADE-induced DHF/DSS.

The Missing Women Phenomenon in India: Causes and Effects

For decades, India's demography has featured an unnaturally low child sex ratio. Much fewer girls than boys have been born, which has given rise to the so-called missing women phenomenon. Most plausibly, this bias can be assumed to be caused by the rational discriminatory behavior of parents who prefer sons over daughters. The present demographic development is not only morally reprehensible; it may also have undesirable socio-economic consequences such as criminal violence and social disorder. This paper provides both theoretical and empirical evidence regarding the causes and effects of the missing women phenomenon. It offers a socio-economic theory of son preference based on gender-specific cost and revenues as well as parents' opportunity of choice. The unwaning importance of dowry payments and the proliferation and affordability of modern preconceptual and prenatal sex selection techniques are suggested to be the key drivers of the skewed sex ratio. Three hypotheses derived from this theory are tested by means of a district-level multiple regression analysis based on 2001 census data. The regression results confirm that the overall economic status is negatively correlated with the child sex ratio. Regarding the relative economic value of females as compared to males, empirical evidence is mixed. As expected, conservative, anti-female socio-cultural attitudes, as proxied by religion, cast, and political party affiliation, are correlated with lower child sex ratios.