Ataxia with Vitamin E Deficiency: Refinement of Genetic Localization and Analysis of Linkage Disequilibrium by Using New Markers in 14 Families

Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disease characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich ataxia. This disorder has been reported previously as familial isolated vitamin E deficiency. We have mapped recently the AVED locus to a 5-cM confidence interval on chromosome 8q by homozygosity mapping in six Mediterranean families. We have now analyzed six new and two previously described families and demonstrate genetic homogeneity despite important clinical variability and wide geographic origins. Analysis of nine new tightly linked microsatellite markers, including four characterized in this study, revealed a predominant but not unique mutation in northern African populations, where this condition is more frequent. Haplotype analysis but also classical recombinations allowed us to refine the AVED position to a 1-cM interval. A YAC contig over this interval was constructed from marker STSs and YAC fingerprint data, in order to facilitate the search of the AVED gene.     

Molecular monitoring of the Leu-164 mutation of dihydrofolate reductase in a highly sulfadoxine/pyrimethamine-resistant area in Africa

Background

Procalcitonin (PCT) is closely correlated with parasite burden and clinical outcome in falciparum malaria. The role of PCT in tertian malaria has not previously been investigated.

Patients and methods

PCT serum levels in 37 patients with tertian malaria were analysed. Clinical and laboratory parameters were assessed and statistically correlated both to the initial PCT levels and during the course of the disease.

Results

PCT levels rose for one day after commencing treatment and declined thereafter. However, there was no significant correlation with parasite burden, clinical parameters, laboratory values, or the presence of semi-immunity. Before treatment, the majority of patients showed normal or slightly elevated PCT levels (< 2.5 ng/ml), but PCT was markedly elevated (4.8 – 47 ng/ml) in one third of the population. The two groups did not differ by any other of the assessed parameters. Thus, while the post-treatment course of PCT resembles falciparum malaria, the lack of correlation between disease severity and even high PCT levels in a large proportion of patients is intriguing.

Conclusions

There is a fundamental difference in the relationship of PCT with tertian malaria not seen in other infectious diseases in which elevated PCT levels have been observed. This suggests distinct pathophysiological pathways in malaria.     

Spawning Site Selection and Contingent Behavior in Common Snook,Centropomus undecimalis

Reproductive behavior affects spatial population structure and our ability to manage for sustainability in marine and diadromous fishes. In this study, we used fishery independent capture-based sampling to evaluate where Common Snook occurred in Tampa Bay and if it changed with spawning season, and passive acoustic telemetry to assess fine scale behavior at an inlet spawning site (2007–2009). Snook concentrated in three areas during the spawning season only one of which fell within the expected spawning habitat. Although in lower numbers, they remained in these areas throughout the winter months. Acoustically-tagged snook (n = 31) showed two seasonal patterns at the spawning site: Most fish occurred during the spawning season but several fish displayed more extended residency, supporting the capture-based findings that Common Snook exhibit facultative catadromy. Spawning site selection for iteroparous, multiple-batch spawning fishes occurs at the lifetime, annual, or intra-annual temporal scales. In this study we show colonization of a new spawning site, indicating that lifetime spawning site fidelity of Common Snook is not fixed at this fine spatial scale. However, individuals did exhibit annual and intra-seasonal spawning site fidelity to this new site over the three years studied. The number of fish at the spawning site increased in June and July (peak spawning months) and on new and full lunar phases indicating within population variability in spawning and movement patterns. Intra-seasonal patterns of detection also differed significantly with sex. Common Snook exhibited divergent migration tactics and habitat use at the annual and estuarine scales, with contingents using different overwintering habitat. Migration tactics also varied at the spawning site at the intra-seasonal scale and with sex. These results have important implications for understanding how reproductive behavior affects spatio-temporal patterns of fish abundance and their resilience to disturbance events and fishing pressure.     

A synthesis of species interactions,metacommunities, and the conservation of avian diversity in hemiboreal and boreal forests

The rate at which climate is changing in northern latitudes presents a significant threat to bird populations that rely on boreal forests. Alterations in the distributions of trees and other plants as a result of warming will alter the habitat suitability of vast regions of boreal and hemiboreal forests. Climate change associated habitat alterations along with range expansions of bird species are likely to have substantial consequences on avian communities and biodiversity. Identifying factors that contribute to species coexistence and community assembly processes at local and regional scales will facilitate predictions about the impact of climate change on avian communities in these forest ecosystems. This paper provides a comprehensive review of historic and current theories of community ecology dynamics providing a theoretical synthesis that links the evolution of species traits at the individual level, the dynamics of species interactions, and the overall maintenance of biodiversity. Integration of these perspectives is necessary to provide the scientific means to face growing environmental challenges in boreal ecosystems.     

Weakly Circadian Cells Improve Resynchrony

The mammalian suprachiasmatic nuclei (SCN) contain thousands of neurons capable of generating near 24-h rhythms. When isolated from their network, SCN neurons exhibit a range of oscillatory phenotypes: sustained or damping oscillations, or arrhythmic patterns. The implications of this variability are unknown. Experimentally, we found that cells within SCN explants recover from pharmacologically-induced desynchrony by re-establishing rhythmicity and synchrony in waves, independent of their intrinsic circadian period We therefore hypothesized that a cell''s location within the network may also critically determine its resynchronization. To test this, we employed a deterministic, mechanistic model of circadian oscillators where we could independently control cell-intrinsic and network-connectivity parameters. We found that small changes in key parameters produced the full range of oscillatory phenotypes seen in biological cells, including similar distributions of period, amplitude and ability to cycle. The model also predicted that weaker oscillators could adjust their phase more readily than stronger oscillators. Using these model cells we explored potential biological consequences of their number and placement within the network. We found that the population synchronized to a higher degree when weak oscillators were at highly connected nodes within the network. A mathematically independent phase-amplitude model reproduced these findings. Thus, small differences in cell-intrinsic parameters contribute to large changes in the oscillatory ability of a cell, but the location of weak oscillators within the network also critically shapes the degree of synchronization for the population.     

Generation of specific Ca(2+) signals from Ca(2+) stores and endocytosis by differential coupling to messengers

It remains unclear how different intracellular stores could interact and be recruited by Ca(2+)-releasing messengers to generate agonist-specific Ca(2+) signatures. In addition, refilling of acidic stores such as lysosomes and secretory granules occurs through endocytosis, but this has never been investigated with regard to specific Ca(2+) signatures. In pancreatic acinar cells, acetylcholine (ACh), cholecystokinin (CCK), and the messengers cyclic ADP-ribose (cADPR), nicotinic acid adenine dinucleotide phosphate (NAADP), and inositol 1,4,5-trisphosphate (IP(3)) evoke repetitive local Ca(2+) spikes in the apical pole. Our work reveals that local Ca(2+) spikes evoked by different agonists all require interaction of acid Ca(2+) stores and the endoplasmic reticulum (ER), but in different proportions. CCK and ACh recruit Ca(2+) from lysosomes and from zymogen granules through different mechanisms; CCK uses NAADP and cADPR, respectively, and ACh uses Ca(2+) and IP(3), respectively. Here, we provide pharmacological evidence demonstrating that endocytosis is crucial for the generation of repetitive local Ca(2+) spikes evoked by the agonists and by NAADP and IP(3). We find that cADPR-evoked repetitive local Ca(2+) spikes are particularly dependent on the ER. We propose that multiple Ca(2+)-releasing messengers determine specific agonist-elicited Ca(2+) signatures by controlling the balance among different acidic Ca(2+) stores, endocytosis, and the ER.     

Association between ecological factors and the presence of Rhipicephalus (Boophilus) microplus larvae in Puerto Rico

A prevalence study was conducted to survey tick larvae populations in Puerto Rico (PR), compare the number of infested sites with Rhipicephalus (Boophilus) microplus larvae between the wet and dry season, and assess the associations of ecologic factors on the presence of R. microplus larvae. Ninety-six sites were selected using a GIS-based sampling method. Each site was sampled twice; the first sampling was performed during the dry season (March 4-18, 2007) and the second sampling during the wet season (August 13-26, 2007). Sites were sampled using a tick drag with a 1-m(2) white flannel cloth along a 50-m straight course. Only 2 tick species were identified. In the dry season, 15 sites (0.16, 95?% CI?=?0.09-0.24) were identified with R. microplus larvae (n?=?606) and 9 sites (0.09, 95?% CI?=?0.04-0.17) with Dermacentor (Anocentor) nitens larvae (n?=?779), whereas in the wet season 5 sites (0.05, 95?% CI?=?0.02-0.12) were identified with R. microplus (n?=?94), and 5 sites (0.05?%, 95?% CI = 0.02-0.12) with D. nitens (n?=?275). Difference in the number of infested sites with R. microplus was significant (P =?0.031) between the 2 seasons. Factors associated with the presence of R. microplus larvae in PR were wind speed of >4.0?km/h (OR?=?0.07, 95?% CI?=?0.01-0.63), more than 25?% bushes and shrubs on the site (OR?=?11, 95?% CI?=?1.6-71), and presence of cattle on the site (OR?=?26, 95?% CI?=?3.4-188).