C9orf72 poly(PR) mediated neurodegeneration is associated with nucleolar stress.

The ALS/FTD-linked intronic hexanucleotide repeat expansion in the C9orf72 gene is aberrantly translated in the sense and antisense directions into dipeptide repeat proteins, among which poly proline-arginine (PR) displays the most aggressive neurotoxicity in-vitro and in-vivo. PR partitions to the nucleus when heterologously expressed in neurons and other cell types. We show that by lessening the nuclear accumulation of PR, we can drastically reduce its neurotoxicity. PR strongly accumulates in the nucleolus, a nuclear structure critical in regulating the cell stress response. We determined that, in neurons, PR caused nucleolar stress and increased levels of the transcription factor p53. Downregulating p53 levels also prevented PR-mediated neurotoxicity both in in-vitro and in-vivo models. We investigated if PR could induce the senescence phenotype in neurons. However, we did not observe any indications of such an effect. Instead, we found evidence for the induction of programmed cell death via caspase-3 activation.

C9orf72 poly(PR) mediated neurodegeneration is associated with nucleolar stress.

The ALS/FTD-linked intronic hexanucleotide repeat expansion in the C9orf72 gene is translated into dipeptide repeat proteins, among which poly-proline-arginine (PR) displays the most aggressive neurotoxicity in-vitro and in-vivo . PR partitions to the nucleus when expressed in neurons and other cell types. Using drosophila and primary rat cortical neurons as model systems, we show that by lessening the nuclear accumulation of PR, we can drastically reduce its neurotoxicity. PR accumulates in the nucleolus, a site of ribosome biogenesis that regulates the cell stress response. We examined the effect of nucleolar PR accumulation and its impact on nucleolar function and determined that PR caused nucleolar stress and increased levels of the transcription factor p53. Downregulating p53 levels, either genetically or by increasing its degradation, also prevented PR-mediated neurotoxic phenotypes both in in-vitro and in-vivo models. We also investigated whether PR could cause the senescence phenotype in neurons but observed none. Instead, we found induction of apoptosis via caspase-3 activation. In summary, we uncovered the central role of nucleolar dysfunction upon PR expression in the context of C9-ALS/FTD.

Why is humoral medicine so popular?

The hot/cold system is perhaps the most widely known medical belief system in the world. I propose that the wide acceptance of hot/cold ideas is due to the fact that they provide a particularly simple, economic coding for common human experience, such as hypothermia, heatstroke, and fevers. Coding of foods as heating or cooling can be understood in terms of a system of sensory cues that make the foods appear hot or cold. This paper deals primarily with data from Chinese culture.

Pathways of decision making among Yucatan Mayan traditional birth attendants.

In rural, developing world communities, women are often isolated from biomedical services. Frequently, traditional birth attendants (TBAs) are the only caregivers during childbirth, both normal and complicated. Women trust their TBAs to manage their births. Globally, government and non-governmental organizations (NGOs) have sought to upgrade TBAs' skills and to encourage them to refer complications. However, most training programs have failed to change TBAs' practice substantially. Logistical barriers in reaching biomedical services in a timely manner are a key issue. Another is the difference between biomedical and traditional practitioners in the cognitive frameworks that shape decision making and management behaviors. The purpose of this study, conducted in Quintana Roo State, Mexico, was to listen to the voices of practicing Yucatec Maya TBAs (parteras) as they described decision making and management of complicated births. In-depth interviews with six practicing parteras in rural, isolated communities revealed that the parteras used traditional Maya ethnomedicine while valuing biomedical approaches. We isolated themes in decision making and mapped management of birth complications. Integrating TBAs' traditional knowledge into biomedical training programs is one way to honor their knowledge and make training relevant.

Environmental backgrounds of young Chinese nasopharyngeal carcinoma patients.

Twenty-four Chinese NPC patients under 25 years of age at the time of diagnosis were interviewed. The interviews were carried out in the presence of their families in 22 cases and concentrated on the environmental background of the subject's infancy and early childhood. An analysis of the results eliminated household inhalants, aerial contaminants, medicines, food therapy, spices, fresh foods and soya sauce as likely factors in carcinogenesis. The only remaining foods eaten by all subjects and worthy of consideration were laap cheung, salted fish and tau si. Salted fish was the most commonly eaten and the only one fed to babies. In childhood, the subjects had rarely or never been fed vegetables or fruits. Most had, since childhood, been characteristically sickly, inactive, withdrawn and choosy about their food. It would appear that consumption of salted fish and vitamin C-deficiency in early childhood are important environmental factors and that a certain personality type may be associated with an increased risk.