Sex significantly influences transduction of murine liver by recombinant adeno-associated viral vectors through an androgen-dependent pathway.

A systematic evaluation of the influence of sex on transduction by recombinant adeno-associated viral vector (rAAV) indicated that transgene expression after liver-targeted delivery of vector particles was between 5- to 13-fold higher in male mice compared with female mice, irrespective of the proviral promoter or cDNA and mouse strain. Molecular analysis revealed that the rAAV genome was stably retained in male liver at levels that were 7-fold higher than those observed in females. Further, the sex difference in transduction was observed with AAV-2- and AAV-5-based vectors, which use distinct receptor complexes for infection. In concordance with the differences in AAV transduction, gel shift analysis with nuclear extracts derived from the liver of mice and humans revealed substantially higher binding of host nuclear protein to the rep-binding site (RBS) of AAV inverted terminal repeat (ITR) in males compared with females. Transduction efficiency and binding of nuclear protein to RBS was dramatically reduced in male mice by castration. In contrast, although oophorectomy did not significantly influence rAAV transduction, administration of 5alpha dihydrotestosterone, prior to gene transfer, increased stable hepatocyte gene transfer in females to levels observed in male mice, implying that androgens significantly influence hepatocyte gene transfer. Interestingly, sex did not have a significant effect on AAV gene transfer into nonhepatic tissue, indicating that there are distinct tissue- and sex-specific differences in the mechanisms responsible for efficient transduction with this vector. These results have significant implications for gene therapy of autosomal and acquired disorders affecting the liver

Paragangliomas and paraganglioma syndromes

Paragangliomas are rare tumors of neural crest origin. They are benign in the majority of cases and are characterized by a strong vascularisation

Inhibitory postsynaptic actions of taurine, GABA and other amino acids on motoneurons of the isolated frog spinal cord

The actions of glycine, GABA, α-alanine, β-alanine and taurine were studied by intracellular recordings from lumbar motoneurons of the isolated spinal cord of the frog. All amino acids tested produced a reduction in the amplitude of postsynaptic potentials, a blockade of the antidromic action potential and an increase of membrane conductance. Furthermore, membrane polarizations occurred, which were always in the same direction as the IPSP. All these effects indicate a postsynaptic inhibitory action of these amino acids. When the relative strength of different amino acids was compared, taurine had the strongest inhibitory potency, followed by β-alanine, α α-alanine, GABA and glycine. Topically applied strychnine and picrotoxin induced different changes of postsynaptic potentials, indicating that distinct inhibitory systems might be influenced by these two convulsants. Interactions with amino acids showed that picrotoxin selectively diminished the postsynaptic actions of GABA, while strychnine reduced the effects of taurine, glycine, α- and β-alanine. But differences in the susceptibility of these amino acid actions to strychnine could be detected: the action of taurine was more sensitively blocked by strychnine compared with glycine, α- and β-alanine. With regard to these results the importance of taurine and GABA as transmitters of postsynaptic inhibition on motoneurons in the spinal cord of the frog is discussed

Squaring the Circle: The Cultural Relativity of 'Good' Shape

The Gestalt theorists of the early twentieth century proposed a psychological primacy for circles, squares and triangles over other shapes. They described them as 'good' shapes and the Gestalt premise has been widely accepted. Rosch (1973), for example, suggested that shape categories formed around these 'natural' prototypes irrespective of the paucity of shape terms in a language. Rosch found that speakers of a language lacking terms for any geometric shape nevertheless learnt paired-associates to these 'good' shapes more easily than to asymmetric variants. We question these empirical data in the light of the accumulation of recent evidence in other perceptual domains that language affects categorization. A cross-cultural investigation sought to replicate Rosch's findings with the Himba of Northern Namibia who also have no terms in their language for the supposedly basic shapes of circle, square and triangle. A replication of Rosch (1973) found no advantage for these 'good' shapes in the organization of categories. It was concluded that there is no necessary salience for circles, squares and triangles. Indeed, we argue for the opposite because these shapes are rare in nature. The general absence of straight lines and symmetry in the perceptual environment should rather make circles, squares and triangles unusual and, therefore, less likely to be used as prototypes in categorization tasks. We place shape as one of the types of perceptual input (in philosophical terms, 'vague') that is readily susceptible to effects of language variation

Uninsured Americans with Chronic Health Conditions: Key Findings from the National Health Interview Survey

The Robert Wood Johnson Foundation (RWJF) commissioned researchers Amy Davidoff of the Department of Public Policy of the University of Maryland, Baltimore County and Genevieve Kenney, of the Health Policy Center at The Urban Institute, to document the prevalence and impact of selected chronic health conditions among the uninsured.1 Using the most recent data from the National Center for Health Statistics' National Health Interview Survey (NHIS), the researchers quantified the number of uninsured adults with chronic conditions, overall and by race and ethnicity, and examined whether they experience gaps in their access to care. Researchers further examined access problems faced by uninsured adults with different chronic health problems. The results are startling

Maintenance of polar stratospheric clouds in a moist stratosphere

Previous work has shown that polar stratospheric clouds (PSCs) could have acted to substantially warm high latitude regions during past warm climates such as the Eocene (55 Ma). Using a simple model of stratospheric water vapor transport and polar stratospheric cloud (PSC) formation, we investigate the dependence of PSC optical depth on tropopause temperature, cloud microphysical parameters, stratospheric overturning, and tropospheric methane. We show that PSC radiative effects can help slow removal of water from the stratosphere via self-heating. However, we also show that the ability of PSCs to have a substantial impact on climate depends strongly on the PSC particle number density and the strength of the overturning circulation. Thus even a large source of stratospheric water vapor (e.g. from methane oxidation) will not result in substantial PSC radiative effects unless PSC ice crystal number density is high compared to most current observations, and stratospheric overturning (which modulates polar stratospheric temperatures) is low. These results are supported by analysis of a series of runs of the NCAR WACCM model with methane concentrations varying up to one thousand times present levels

Local and global processing. Observations from a remote culture

In Experiment 1, a normal adult population drawn from a remote culture (Himba) in northern Namibia made similarity matches to [Navon, D. (1977). Forest before trees: The precedence of global features in visual perception. Cognitive Psychology, 9, 353–383] hierarchical figures. The Himba showed a local bias stronger than that has been previously observed in any other non-clinical human population. However, in Experiment 2, their recognition of normal or distorted (“Thatcherized”) faces did not appear to have been affected by their attention to detail as has been suggested for autistic populations. The data are consistent with a cultural/experiential origin for population differences in local processing and suggest that attention to the local and global properties of stimuli may differ for hierarchical figures and faces

Cross-species differences in color categorization

International audienceBerlin and Kay (1969) found systematic restrictions in the color terms of the world's languages and were inclined to look to the primate visual system for their origin. Because the visual system does not provide adequate neurophysiological discontinuities to supply natural color category boundaries, and because recent evidence points to a linguistic origin (Davidoff, Davies, & Roberson, 1999), a new approach was used to investigate the controversial issue of the origin of color categories. Baboons and humans were given the same task of matching-to-sample colors that crossed the blue/green boundary. The data and consequent modeling were remarkably clear-cut All human subjects matched our generalization probe stimuli as if to a sharp boundary close to the midpoint between their training items. Despite good color discrimination, none of the baboons showed any inclination to match to a single boundary but rather responded with two boundaries close to the training stimuli. The data give no support to the claim that color categories are explicitly instantiated in the primate color vision system