Antihypertensive drug Valsartan promotes dendritic spine density by altering AMPA receptor trafficking

Recent studies demonstrated that the antihypertensive drug Valsartan improved spatial and episodic memory in mouse models of Alzheimer’s Disease (AD) and human subjects with hypertension. However, the molecular mechanism by which Valsartan can regulate cognitive function is still unknown. Here, we investigated the effect of Valsartan on dendritic spine formation in primary hippocampal neurons, which is correlated with learning and memory. Interestingly, we found that Valsartan promotes spinogenesis in developing and mature neurons. In addition, we found that Valsartan increases the puncta number of PSD-95 and trends toward an increase in the puncta number of synaptophysin. Moreover, Valsartan increased the cell surface levels of AMPA receptors and selectively altered the levels of spinogenesis-related proteins, including CaMKIIα and phospho-CDK5. These data suggest that Valsartan may promote spinogenesis by enhancing AMPA receptor trafficking and synaptic plasticity signaling.     

Biodiversity and biogeography of the avifauna of the Sierra Madre Occidental,Mexico

The Sierra Madre Occidental (SMOc) is located in the boundary between the Nearctic and Neotropical regions, area which has been considered as a complex transition zone. We analysed biogeographic patterns of its resident avifauna, including species richness, endemism, and biotic regionalization by analysing presence-absence matrices of 148 species of resident-terrestrial birds. We created the species richness maps by overlapping potential distribution maps obtained for each species via species distribution models (SDMs). To depict biogeographic patterns, we used strict consensus cladograms from parsimony analyses of endemicity (PAE) and phenograms from an unweighted pair-group method with arithmetic average clustering algorithm. The Pacific slope of the SMOc contains the highest species richness, decreasing towards the northeast, and reflected in endemic and endangered species richness patterns. The PAE resulted in one area of endemism represented by the whole SMOc, outlining a divided area in its Pacific slope. The cluster analyses divided the area into two. One group towards the Pacific slope, delimited by the mountain ridge and characterized by tropical vegetation types and Mexican-Mesoamerican affinities; the other group is located towards the east and northeast, characterized by arid and temperate types of vegetation and Nearctic affinities. These results evidence a transition from a tropical to a temperate composition of bird species. In this way the location for a boundary between the Nearctic and the transition zone, for birds in this part of Mexico, is restricted to these highest elevations.     

Thermal biology and locomotor performance of the Andean lizard Liolaemus fitzgeraldi (Liolaemidae) in Argentina

Ectotherms thermoregulate to maintain their body temperature within the optimal range needed for performing vital functions. The effect of climate change on lizards has been studied as regards the sensitivity of locomotor performance to environmental temperatures. We studied thermoregulatory efficiency and locomotor performance for Liolaemus fitzgeraldi in the Central Andes of Argentina. We determined body temperature, micro-environmental temperatures and operative temperatures in the field. In the laboratory, we measured preferred temperatures and calculated the index of thermoregulatory efficiency. We estimated the thermal sensitivity of locomotion by measuring sprint speed (initial velocity and long sprint) and endurance at five different body temperatures. Body temperature was not associated with either micro-environmental temperature, nor did it show differences with preferred temperatures. Thermoregulatory efficiency was moderate (0.61). Initial velocity and long sprint trials showed differences at different temperatures; however, endurance did not. Moreover, the optimal temperatures for the performance trials showed no significant differences among themselves. We conclude that Liolaemus fitzgeraldi has thermal sensitivity in locomotor performance with respect to body temperature and that it is an eurythermic lizard that experiences a large variation in body temperature and that has thermal flexibility in the cold.     

DNA sequence data reveal a subfamily-level divergence within Thamnophilidae (Aves: Passeriformes)

The Thamnophilidae is a diverse radiation of insectivorous passerine birds that comprises nearly 220 species and is mostly restricted to the lowlands and lower montane forests of the Neotropics. Current classification within Thamnophilidae relies primarily on morphological variation, but recent incorporation of molecular and vocal data has promoted changes at various taxonomic levels. Here we demonstrate that the genus Terenura is polyphyletic because Terenura callinota, T. humeralis, T. spodioptila, and T. sharpei are phylogenetically distant from the type species of the genus, Terenura maculata. More importantly, the former four species are not particularly closely related to any other thamnophilids and represent a clade that is sister to all other members of the family. Because no genus name is available for this previously undetected lineage in the Thamnophilidae, we describe the genus Euchrepomis for callinota, humeralis, spodioptila, and sharpei, and erect the subfamily Euchrepomidinae. We discuss the taxonomic and evolutionary significance of this divergent lineage. This study highlights the importance of taxonomic coverage and the inclusion of type taxa to redefine classifications to reflect accurately evolutionary relationships.     

Identification of a Major Susceptibility Locus for Restless Legs Syndrome on Chromosome 12q

Restless legs syndrome (RLS) is a neurological disorder characterized by leg paresthesia associated with an irresistible urge to move that often interferes with nocturnal sleep, leading to chronic sleep deprivation. To map genes that may play a role in the vulnerability to RLS, a genomewide scan was conducted in a large French-Canadian family. Significant linkage was established on chromosome 12q, for a series of adjacent microsatellite markers with a maximum two-point LOD score of 3.42 (recombination fraction.05; P=6x10(-4); autosomal recessive mode of inheritance), whereas multipoint linkage calculations yielded a LOD score of 3.59. Haplotype analysis refined the genetic interval, positioning the RLS-predisposing gene in a 14.71-cM region between D12S1044 and D12S78. These findings represent the first mapping of a locus conferring susceptibility to RLS.     

A Naturally Occurring Canine Model of Autosomal Recessive Congenital Stationary Night Blindness

Congenital stationary night blindness (CSNB) is a non-progressive, clinically and genetically heterogeneous disease of impaired night vision. We report a naturally-occurring, stationary, autosomal recessive phenotype in beagle dogs with normal daylight vision but absent night vision. Affected dogs had normal retinas on clinical examination, but showed no detectable rod responses. They had “negative-type” mixed rod and cone responses in full-field ERGs. Their photopic long-flash ERGs had normal OFF-responses associated with severely reduced ON-responses. The phenotype is similar to the Schubert-Bornschein form of complete CSNB in humans. Homozygosity mapping ruled out most known CSNB candidates as well as CACNA2D4 and GNB3. Three remaining genes were excluded based on sequencing the open reading frame and intron-exon boundaries (RHO, NYX), causal to a different form of CSNB (RHO) or X-chromosome (NYX, CACNA1F) location. Among the genes expressed in the photoreceptors and their synaptic terminals, and mGluR6 cascade and modulators, reduced expression of GNAT1, CACNA2D4 and NYX was observed by qRT-PCR in both carrier (n = 2) and affected (n = 2) retinas whereas CACNA1F was down-regulated only in the affecteds. Retinal morphology revealed normal cellular layers and structure, and electron microscopy showed normal rod spherules and synaptic ribbons. No difference from normal was observed by immunohistochemistry (IHC) for antibodies labeling rods, cones and their presynaptic terminals. None of the retinas showed any sign of stress. Selected proteins of mGluR6 cascade and its modulators were examined by IHC and showed that PKCα weakly labeled the rod bipolar somata in the affected, but intensely labeled axonal terminals that appeared thickened and irregular. Dendritic terminals of ON-bipolar cells showed increased Goα labeling. Both PKCα and Goα labeled the more prominent bipolar dendrites that extended into the OPL in affected but not normal retinas. Interestingly, RGS11 showed no labeling in the affected retina. Our results indicate involvement of a yet unknown gene in this canine model of complete CSNB.     

Evolution of selenium utilization traits

Background

The essential trace element selenium is used in a wide variety of biological processes. Selenocysteine (Sec), the 21st amino acid, is co-translationally incorporated into a restricted set of proteins. It is encoded by an UGA codon with the help of tRNA^Sec (SelC), Sec-specific elongation factor (SelB) and a cis-acting mRNA structure (SECIS element). In addition, Sec synthase (SelA) and selenophosphate synthetase (SelD) are involved in the biosynthesis of Sec on the tRNA^Sec. Selenium is also found in the form of 2-selenouridine, a modified base present in the wobble position of certain tRNAs, whose synthesis is catalyzed by YbbB using selenophosphate as a precursor.

Results

We analyzed completely sequenced genomes for occurrence of the selA, B, C, D and ybbB genes. We found that selB and selC are gene signatures for the Sec-decoding trait. However, selD is also present in organisms that do not utilize Sec, and shows association with either selA, B, C and/or ybbB. Thus, selD defines the overall selenium utilization. A global species map of Sec-decoding and 2-selenouridine synthesis traits is provided based on the presence/absence pattern of selenium-utilization genes. The phylogenies of these genes were inferred and compared to organismal phylogenies, which identified horizontal gene transfer (HGT) events involving both traits.

Conclusion

These results provide evidence for the ancient origin of these traits, their independent maintenance, and a highly dynamic evolutionary process that can be explained as the result of speciation, differential gene loss and HGT. The latter demonstrated that the loss of these traits is not irreversible as previously thought.     

Application of the automated spatial surveillance program to birth defects surveillance data

BACKGROUND: Although many birth defects surveillance programs incorporate georeferenced records into their databases, practical methods for routine spatial surveillance are lacking. We present a macroprogram written for the software package R designed for routine exploratory spatial analysis of birth defects data, the Automated Spatial Surveillance Program (ASSP), and present an application of this program using spina bifida prevalence data for metropolitan Atlanta. METHODS: Birth defects surveillance data were collected by the Metropolitan Atlanta Congenital Defects Program. We generated ASSP maps for two groups of years that correspond roughly to the periods before (1994-1998) and after (1999-2002) folic acid fortification of flour. ASSP maps display census tract-specific spina bifida prevalence, smoothed prevalence contours, and locations of statistically elevated prevalence. We used these maps to identify areas of elevated prevalence for spina bifida. RESULTS: We identified a large area of potential concern in the years following fortification of grains and cereals with folic acid. This area overlapped census tracts containing large numbers of Hispanic residents. CONCLUSIONS: The potential utility of ASSP for spatial disease monitoring was demonstrated by the identification of areas of high prevalence of spina bifida and may warrant further study and monitoring. We intend to further develop ASSP so that it becomes practical for routine spatial monitoring of birth defects.     

Biogeographical patterns of the avifaunas of the Caribbean Basin Islands: a parsimony perspective

We analyzed the avifaunas of the Caribbean islands and nearby continental areas and their relationships using Parsimony Analysis of Endemicity (PAE), in order to assess biogeographical patterns and their concordance with geological and phylogenetic evidence. Using distributional information of birds obtained from published literature, a presence/absence matrix for 695 genera and 2026 species of land and freshwater birds was constructed and analyzed. Three different analyses were performed: for species, for genera, and for species and genera combined. In the combined analysis, the Lesser Antilles appear paraphyletic at the base of the cladogram. Then, two major clades are identified: South America (Andes, Venezuelan lowlands, Dutch West Indies and Trinidad and Tobago) and North America, including the Greater Antilles in a clade that is the sister area to Yucatan and the Central American countries nested from north to south. PAE results support Caribbean vicariant models and cladistic biogeographical hypotheses on area relationships, and show relative congruence with available phylogenetic data. Bird biogeography on the Caribbean islands appears to have been caused by both vicariance and dispersal processes. © The Willi Hennig Society 2007.