Middle Pleistocene Steppe Lion Remains from Grotte de la Carrière (Têt Valley,Eastern Pyrenees)

Journal of Mammalian Evolution - Late Pleistocene cave lions are one of the most iconic species of Northern Hemisphere Quaternary taphocoenoses. Despite their often-scarce record in cave...     

Anemia of Inflammation Is Related to Cognitive Impairment among Children in Leyte,The Philippines

Background

Many studies have addressed the relationship between iron deficiency anemia (IDA) and cognitive impairment, but none have evaluated the role of non-iron deficiency anemia (NIDA). One of the main causes of NIDA in developing countries is AI, largely due to infectious diseases, whereby iron is shunted away from bio-available forms to storage forms, making it less accessible for use by host tissues. The objective of this study was to determine the effect of NIDA, due largely to AI in this context, on cognitive function after adjustment for potential confounders.

Methodology

This cross-sectional study was conducted in Leyte, The Philippines among 322 children ages 7–18 years. Blood samples were collected and analyzed at the time of cognition testing. Three stool samples were collected and evaluated by the Kato Katz method for quantitative assessment for Schistosoma japonicum and geo-helminth infection. Socio-economic status (SES) was evaluated by survey. Linear regression models were used to quantify the adjusted relationship between performance in different cognitive domains and both IDA and NIDA.

Principal Findings

After adjusting for age, sex, SES and nutritional status, children in the NIDA had lower scores on the PNIT (P = <0.05) and the WRAML memory domain (P<0.05) compared to children in the non-anemic group. Children in the IDA had lower performance on the PNIT compared to the non-anemic group after controlling for potential confounders (P<0.05).

Conclusions

NIDA, predominantly due to AI in this context, was related to lower performance on two tests of cognitive function. This is likely due to decreased delivery of iron to host tissues in this context, including the CNS.     

Functional Complementation in Yeast Allows Molecular Characterization of Missense Argininosuccinate Lyase Mutations

Deficiency of argininosuccinate lyase (ASL) causes argininosuccinic aciduria, an urea cycle defect that may present with a severe neonatal onset form or with a late onset phenotype. To date phenotype-genotype correlations are still not clear because biochemical assays of ASL activity correlate poorly with clinical severity in patients. We employed a yeast-based functional complementation assay to assess the pathogenicity of 12 missense ASL mutations, to establish genotype-phenotype correlations, and to screen for intragenic complementation. Rather than determining ASL enzyme activity directly, we have measured the growth rate in arginine-free medium of a yeast ASL^null strain transformed with individual mutant ASL alleles. Individual haploid strains were also mated to obtain diploid, “compound heterozygous” yeast. We show that the late onset phenotypes arise in patients because they harbor individual alleles retaining high residual enzymatic activity or because of intragenic complementation among different mutated alleles. In these cases complementation occurs because in the hybrid tetrameric enzyme at least one active site without mutations can be formed or because the differently mutated alleles can stabilize each other, resulting in partial recovery of enzymatic activity. Functional complementation in yeast is simple and reproducible and allows the analysis of large numbers of mutant alleles. Moreover, it can be easily adapted for the analysis of mutations in other genes involved in urea cycle disorders.Argininosuccinic aciduria (ASAuria, MIM 207900)³ is an autosomal recessive disorder of the urea cycle caused by mutations of the ASL gene (hASL, MIM 608310), encoding argininosuccinate lyase (ASL; EC 4.3.2.1.) (1). This enzyme is ubiquitously expressed and catalyzes the reversible breakdown of argininosuccinate to arginine and fumarate. ASL belongs to a superfamily of hydrolases that includes adenylosuccinate lyase and fumarase, which share a homotetrameric structure and a similar catalytic mechanism. The tetrameric structure of ASL accounts for the phenomenon of intragenic complementation. This particular situation occurs when a multimeric protein is formed from subunits produced by differently mutated alleles of the same gene. On complementation, a partially functional hybrid protein is produced from the two distinct types of mutant subunits, neither of which individually has appreciable enzymatic activity (2).ASL participates to the urea cycle, and in humans it is essential for ammonia detoxification, whereas in lower organisms it is required for the biosynthesis of arginine. Saccharomyces cerevisiae strains harboring a deletion of the homolog of human ASL (ARG4) cannot grow on media lacking arginine (3).ASAuria is characterized by accumulation of argininosuccinic acid (ASA) in body fluids, and severe hyperammonaemia. The disease displays clinical heterogeneity with two main clinical phenotypes: the acute/neonatal onset form, with symptoms rapidly progressing to deep coma, apnea, and death (1), and the subacute/late onset type, which is diagnosed in infancy or childhood (4). Such patients may present simply with mental retardation or an epileptic disorder. In both types the diagnosis is established unambiguously by measuring plasma levels of ammonia (not always elevated in the late onset form), ASA, and its anhydrides by plasma amino acids assay (1). Over 40 mutations of the ASL gene have been reported, both amino acid substitutions and truncating variants, which are scattered throughout the gene (5, 6).We have previously reported the identification of novel mutations of the ASL gene in a cohort of Italian patients (7). In this study we employed a yeast model to validate the pathogenicity of missense ASL mutations found in our cohort, to study the effects of different allelic combinations, and to establish possible genotype-phenotype correlations.     

Renal oxalosis in free-ranging green turtles Chelonia mydas

Eighteen green turtles Chelonia mydas recovered from the Atlantic and Gulf coasts of Florida and Tortuguero National Park, Costa Rica, were diagnosed with renal oxalosis by histopathological examination. Affected sea turtles included 14 adults and 4 immature animals, which comprised 26% (18/69) of green turtle necropsy cases available for review. Calcium oxalate deposition ranged from small to moderate amounts and was associated with granuloma formation and destruction of renal tubules. All affected turtles died from traumatic events or health problems unrelated to renal oxalosis; however, 1 immature turtle had notable associated renal injury. Crystal composition was confirmed by infrared and scanning electron microscopy and energy dispersive X-ray analysis. The source of calcium oxalate is unknown and is presumed to be of dietary origin.     

Nuclear behavior of the mycelium and the phylogeny of Polypores (Basidiomycota)

This is a review of the available knowledge on nuclear behavior of the mycelium within polypore genera (Agaricomycetes, Basidiomycota). Information on 68 genera showed that nuclear behavior is a distinct and consistent feature at genus level and can be coupled with phylogenetic differentiation. The sole exception was found in Polyporus, where different species with normal, heterocytic and astatocoenocytic nuclear behaviors were found. Of the 68 genera treated 41 (60.3%) displayed a normal nuclear behavior, nine (13.2%) were heterocytic, nine (13.2%) were astatocoenocytic and another eight (11.8%) were holocoenocytic. In 95% of the genera a unique compatibility system was found, with the exceptions of Antrodia, which includes both homothallic and bipolar species all associated with a normal nuclear behavior, and Spongipellis, in which bipolar and tetrapolar species are found, all displaying an astatocoenocytic nuclear behavior. Normal and heterocytic nuclear behaviors were associated mostly with tetrapolarity, astatocoenocity was associated mostly with bipolarity, and holocoenocity was associated with either bipolarity or purported homothallism. The combination of nuclear behavior with mating system and brown or white rot capability appeared as a strong feature characterizing and distinguishing the genera of polypores, each combination being valuable to differentiate between apparently related genera, as is supported by phylogenetic studies. Several examples are presented to support this idea, as well as the cases of species that are problematic to this concept. Poroid genera of Hymenochaetaceae were treated apart because of the lack of knowledge regarding their nuclear behavior. In addition new information on the sexuality and/or nuclear behavior of 15 polyporoid taxa is given.     

ESS++: a C++ objected-oriented algorithm for Bayesian stochastic search model exploration

SUMMARY: ESS++ is a C++ implementation of a fully Bayesian variable selection approach for single and multiple response linear regression. ESS++ works well both when the number of observations is larger than the number of predictors and in the 'large p, small n' case. In the current version, ESS++ can handle several hundred observations, thousands of predictors and a few responses simultaneously. The core engine of ESS++ for the selection of relevant predictors is based on Evolutionary Monte Carlo. Our implementation is open source, allowing community-based alterations and improvements. AVAILABILITY: C++ source code and documentation including compilation instructions are available under GNU licence at http://bgx.org.uk/software/ESS.html.