Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome

Arterial tortuosity syndrome (ATS) is an autosomal recessive disorder characterized by tortuosity, elongation, stenosis and aneurysm formation in the major arteries owing to disruption of elastic fibers in the medial layer of the arterial wall. Previously, we used homozygosity mapping to map a candidate locus in a 4.1-Mb region on chromosome 20q13.1 (ref. 2). Here, we narrowed the candidate region to 1.2 Mb containing seven genes. Mutations in one of these genes, SLC2A10, encoding the facilitative glucose transporter GLUT10, were identified in six ATS families. GLUT10 deficiency is associated with upregulation of the TGFbeta pathway in the arterial wall, a finding also observed in Loeys-Dietz syndrome, in which aortic aneurysms associate with arterial tortuosity. The identification of a glucose transporter gene responsible for altered arterial morphogenesis is notable in light of the previously suggested link between GLUT10 and type 2 diabetes. Our data could provide new insight on the mechanisms causing microangiopathic changes associated with diabetes and suggest that therapeutic compounds intervening with TGFbeta signaling represent a new treatment strategy.     

Root tip contact with low-phosphate media reprograms plant root architecture

Plant roots are able to sense soil nutrient availability. In order to acquire heterogeneously distributed water and minerals, they optimize their root architecture. One poorly understood plant response to soil phosphate (P(i)) deficiency is a reduction in primary root growth with an increase in the number and length of lateral roots. Here we show that physical contact of the Arabidopsis thaliana primary root tip with low-P(i) medium is necessary and sufficient to arrest root growth. We further show that loss-of-function mutations in Low Phosphate Root1 (LPR1) and its close paralog LPR2 strongly reduce this inhibition. LPR1 was previously mapped as a major quantitative trait locus (QTL); the molecular origin of this QTL is explained by the differential allelic expression of LPR1 in the root cap. These results provide strong evidence for the involvement of the root cap in sensing nutrient deficiency, responding to it, or both. LPR1 and LPR2 encode multicopper oxidases (MCOs), highlighting the essential role of MCOs for plant development.     

Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas

Melatonin is an ancient antioxidant. After its initial development in bacteria, it has been retained throughout evolution such that it may be or may have been present in every species that have existed. Even though it has been maintained throughout evolution during the diversification of species, melatonin’s chemical structure has never changed; thus, the melatonin present in currently living humans is identical to that present in cyanobacteria that have existed on Earth for billions of years. Melatonin in the systemic circulation of mammals quickly disappears from the blood presumably due to its uptake by cells, particularly when they are under high oxidative stress conditions. The measurement of the subcellular distribution of melatonin has shown that the concentration of this indole in the mitochondria greatly exceeds that in the blood. Melatonin presumably enters mitochondria through oligopeptide transporters, PEPT1, and PEPT2. Thus, melatonin is specifically targeted to the mitochondria where it seems to function as an apex antioxidant. In addition to being taken up from the circulation, melatonin may be produced in the mitochondria as well. During evolution, mitochondria likely originated when melatonin-forming bacteria were engulfed as food by ancestral prokaryotes. Over time, engulfed bacteria evolved into mitochondria; this is known as the endosymbiotic theory of the origin of mitochondria. When they did so, the mitochondria retained the ability to synthesize melatonin. Thus, melatonin is not only taken up by mitochondria but these organelles, in addition to many other functions, also probably produce melatonin as well. Melatonin’s high concentrations and multiple actions as an antioxidant provide potent antioxidant protection to these organelles which are exposed to abundant free radicals.     

Prospects for a vaccine against the hepatitis C virus

The recent discovery of natural immunity to the hepatitis C virus and vaccine efficacy in the chimpanzee challenge model has allowed optimism about the development of at least a partly effective vaccine against this heterogeneous pathogen that is responsible for much of the chronic liver disease around the world. The immune systems of some infected individuals can spontaneously clear the virus, whereas other people need treatment with antivirals that work partly by stimulating humoral and cellular immune responses. Therefore, therapeutic vaccine strategies are also being pursued to improve treatment outcome.     

Only male fin whales sing loud songs

The low-frequency vocalizations of fin and blue whales are the most powerful and ubiquitous biological sounds in the ocean. Here we combine acoustic localization and molecular techniques to show that, in fin whales, only males produce these vocalizations. This finding indicates that they may function as male breeding displays, and will help to focus concern on the impact of human-generated low-frequency sounds on recovering whale populations.     

Conservation status of the threatened, insular San Jose brush rabbit ( Sylvilagus mansuetus )

The conservation status and distribution of the insular endemic San Jose brush rabbit ( Sylvilagus mansuetus ), as well as threats to its population viability, were determined through surveys undertaken since 1995 on San José Island in the Gulf of California, Mexico. Sylvilagus mansuetus is restricted to a specific desert habitat found in the southwestern coastal plains of the island. Vegetation in this habitat is composed primarily of 7 plant species. The extent of rabbit occurrence is only 20 km 2 , and the population density estimate in the most optimal habitat is 25–35 individuals · km –2 . To our knowledge, the San Jose brush rabbit possesses the smallest distribution among all lagomorph species. Sylvilagus mansuetus is threatened by a population of feral cats and by human activities, including illegal hunting, development of a tourist area, and a salt mine. Human activities, even over a short time frame, could severely impact this restricted area and endanger the survival of this species. Recommended management includes removing cats and conducting additional research on the rabbit’s life history and ecology. Se determinó el estado de conservación y la distribución del conejo de San José ( Sylvilagus mansuetus ), una especie insular endémica, mediante muestreos que se han llevado a cabo desde 1995 en la isla de San José en el Mar de Cortés, México. Sylvilagus mansuetus quedó restringido a un tipo específico de hábitat desértico en la llanura costera suroccidental de la isla, donde predominan 7 especies de plantas. La extensión de la especie es de sólo 20 km 2 , y la densidad de la población en el hábitat óptimo se estimó entre 25 y 35 individuos · km –2 . Hasta donde conocemos, el conejo de San José tiene el área de distribución más pequeña de todas las especies de lagomorfos. Sylvilagus mansuetus se ve amenazado por una población de gatos ferales y por actividades humanas tales como la caza ilegal, el turismo y la operación de una mina de sal. Las actividades humanas podrían tener un impacto severo en esta área restringida y podrían poner en peligro la supervivencia de esta especie dentro de poco tiempo. Algunas acciones recomendables para el manejo de la especie incluyen el eliminar los gatos y llevar a cabo estudios adicionales para obtener más detalles sobre la biología y ecología del conejo a fin de mejorar su conservación.     

Status of an invading mainland jackrabbit on Cerralvo island, Gulf of California

We report the first observations of the black-tailed jackrabbit ( Lepus californicus ) on Cerralvo Island, Baja California Sur, Mexico. Evidence suggests a self-sustaining population. Analysis of available records indicates no previous record of Lepus on the island. Introduction of the jackrabbit to the island appears to have occurred between 1960 and 1991.     

Causal implications: The linkage between time series and econometric modelling

Construction of causally and structurally adequate simultaneous equations models can be accomplished by determining causal relations between potential variables and balancing these statistically derived inferences with economic theory to relate behavioural or technological forces among the variables. An appropriate lag structure for each of the equations can be determined by a two step multiple transfer function approach involving reduced form equations. Testing the specification of already existing simultaneous equations models is done by constructing multiple transfer function models of the reduced form equations of the simultaneous equations models which permit incorporation of lead cross correlations.     

人类与机器感知：交流、相互作用与集成

本书是第六届人类与机器感知国际专题研讨会的论文集，该会议于2004年9月6—9日在意大利的Santa　Caterina　di　Pittinuri举行。这次会议除了8位特邀的讲演者及技术委员会成员之外，参与者人数限制在70人。本书共收集了12个讲座的演讲稿，内容涉及交流、相互作用与集成。对每一个基本主题都有相对应的自然及机器的方法的特邀讲座及技术委员会的讨论，介绍了最新的科技发展水平，概括了公开的问题，并强调了与感知相关的学科之问最佳协同作用，进一步激励了新方法的产生。