Discovery of allosteric regulators with clinical potential to stabilize alpha-L-iduronidase in mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal disease caused by lowered activity of the enzyme alpha-L-iduronidase (IDUA). Current therapeutic options show limited efficacy and do not treat some important aspects of the disease. Therefore, it may be advantageous to identify strategies that could improve the efficacy of existing treatments.

Beta-Amyloid (Aβ) Increases the Expression of NKCC1 in the Mouse Hippocampus.

Alzheimer's disease (AD) is a neurodegenerative disorder with an increasing need for developing disease-modifying treatments as current therapies only provide marginal symptomatic relief. Recent evidence suggests the γ-aminobutyric acid (GABA) neurotransmitter system undergoes remodeling in AD, disrupting the excitatory/inhibitory (E/I) balance in the brain. Altered expression levels of K-Cl-2 (KCC2) and N-K-Cl-1 (NKCC1), which are cation-chloride cotransporters (CCCs), have been implicated in disrupting GABAergic activity by regulating GABA receptor signaling polarity in several neurological disorders, but these have not yet been explored in AD.

Small size does not restrain frugivory and seed dispersal across the evolutionary radiation of Galápagos lava lizards.

Frugivory in lizards is often assumed to be constrained by body size; only large individuals are considered capable of consuming fruits, with the potential of acting as seed dispersers. However, only one previous study has tested the correlation of frugivory with body and head size at an archipelago scale across closely related species. All nine lava lizards ( spp.

Potential role of lava lizards as pollinators across the Galápagos Islands.

Lizards have been reported as important pollinators on several oceanic islands. Here we evaluate the potential role of Galápagos lava lizards (Microlophus spp.) as pollinators across their radiation.

Lanolin-Based Synthetic Membranes as Percutaneous Absorption Models for Transdermal Drug Delivery.

Background: The major in vitro permeation studies are currently performed in Franz-type diffusion cells because of their simplicity, cost effectiveness and because the experimental conditions can be easily controlled. Apart from the skin, Franz-type diffusion cells can be used with synthetic membranes. Nevertheless, they do not emulate the nature of the lipidic matrix, which is responsible for the topical barrier function.

Flowers as a reservoir of yeast diversity: description of Wickerhamiella nectarea f.a. sp. nov., and Wickerhamiella natalensis f.a. sp. nov. from South African flowers and pollinators, and transfer of related Candida species to the genus Wickerhamiella as new combinations.

Flowers offer favourable microenvironments for yeast growth, and are increasingly recognised as a rich source of novel yeast species. Independent surveys of yeasts associated with flowers and pollinators in South Africa led to the discovery of 38 strains of two new species. Physiological profiles and analysis of the internal transcribed spacer and the D1/D2 domains of the large subunit rRNA gene showed that they represent two novel species that belong to the Wickerhamiella clade.

Metschnikowia drakensbergensis sp. nov. and Metschnikowia caudata sp. nov., endemic yeasts associated with Protea flowers in South Africa.

In a taxonomic study of yeasts recovered from nectar of flowers and associated insects in South Africa, 11 strains were found to represent two novel species. Morphological and physiological characteristics and sequence analyses of the large-subunit rRNA gene D1/D2 region, as well as the actin, RNA polymerase II and elongation factor 2 genes, showed that the two novel species belonged to the genus Metschnikowia. Metschnikowia drakensbergensis sp.

Phylogenetic analysis of the angiosperm-floricolous insect-yeast association: have yeast and angiosperm lineages co-diversified?

Metschnikowia (Saccharomycetales, Metschnikowiaceae/Metschnikowia clade) is an ascomycetous yeast genus whose species are associated mostly with angiosperms and their insect pollinators over all continents. The wide distribution of the genus, its association with angiosperm flowers, and the fact that it includes some of the best-studied yeasts in terms of biogeography and ecology make Metschnikowia an excellent group to investigate a possible co-radiation with angiosperm lineages. We performed phylogenetic analyses implementing Bayesian inference and likelihood methods, using a concatenated matrix (≈2.

Extensive pollen flow but few pollen donors and high reproductive variance in an extremely fragmented landscape.

Analysing pollen movement is a key to understanding the reproductive system of plant species and how it is influenced by the spatial distribution of potential mating partners in fragmented populations. Here we infer parameters related to levels of pollen movement and diversity of the effective pollen cloud for the wind-pollinated shrub Pistacia lentiscus across a highly disturbed landscape using microsatellite loci. Paternity analysis and the indirect KinDist and Mixed Effect Mating models were used to assess mating patterns, the pollen dispersal kernel, the effective number of males (N(ep)) and their relative individual fertility, as well as the existence of fine-scale spatial genetic structure in adult plants.

Metschnikowia proteae sp. nov., a nectarivorous insect-associated yeast species from Africa.

A collection of yeasts isolated from nectar of flowers of Protea caffra (Proteaceae) and associated scarab beetles (Atrichelaphinis tigrina, Cyrtothyrea marginalis, Trichostetha fascicularis and Heterochelus sp.) and drosophilid flies in South Africa, contained 28 isolates that could not be assigned to known species. Comparisons of the D1/D2 domains of the large subunit rRNA gene demonstrated the existence of three separate phylotypes with an affinity to the genus Metschnikowia and more specifically to the beetle-associated large-spored Metschnikowia clade.

Psychometric properties of the Spence Child Anxiety Scale with adolescents from five European countries.

This study examined the factor structure, reliability, and validity of the original Spence Child Anxiety Scale (SCAS) and its four translations (German, Cypriot Greek, Swedish, Italian). A total of 2558 adolescents from five European countries (Germany = 495; Cyprus = 611; UK = 469; Sweden = 484; Italy = 499), ages 12-17 years, participated in the study. In addition to the SCAS, all participants completed the Strengths and Difficulties Questionnaire, a measure of general difficulties and positive attributes.

Adaptive radiation in mediterranean cistus (cistaceae).

Background: Adaptive radiation in Mediterranean plants is poorly understood. The white-flowered Cistus lineage consists of 12 species primarily distributed in Mediterranean habitats and is herein subject to analysis.

Methodology/principal Findings: We conducted a "total evidence" analysis combining nuclear (ncpGS, ITS) and plastid (trnL-trnF, trnK-matK, trnS-trnG, rbcL) DNA sequences and using MP and BI to test the hypothesis of radiation as suggested by previous phylogenetic results.

[Early markers for atherosclerosis and metabolic syndrome in children].

Background: The high prevalence of obesity in children favors the appearance of metabolic syndrome (MS), increasing their cardiovascular risk.

Aim: To evaluate components of MS in children and to correlate them with surrogate markers of atherosclerosis and subclinical inflammation.

Material And Methods: We studied 209 children aged 11.

Delta6-desaturase sequence evidence for explosive Pliocene radiations within the adaptive radiation of Macaronesian Echium (Boraginaceae).

The oceanic islands of Macaronesia provide an ideal temporal and spatial context to test hypotheses of plant evolution using a novel set of phylogenetic markers, Delta(6)-desaturase sequences. In contrast to the limited resolution of standard molecular markers (nrDNA and plastid sequences), the Delta(6)-desaturase sequence phylogeny of Echium unequivocally reconstructs its active colonization across islands and archipelagos (Madeira, the Canary Islands, and Cape Verde), as well as its subsequent geographical and ecological speciation. Molecular-clock estimates using penalized likelihood and Bayesian inference reveal two radiation processes coincident with two dramatic climatic changes recorded in the region: the advent of the cold Canarian sea current (ca.

Adiponectin levels, cardiometabolic risk factors and markers of subclinical atherosclerosis in children.

Background: Low levels of adiponectin have been associated with metabolic risk factors (RF) and cardiac disease. Minimal data is available about the relationship between adiponectin and subclinical atherosclerosis.

Objectives: To determine the relationship of adiponectin to cardiometabolic RF, C-reactive protein (CRP), anthropometric parameters of obesity, and subclinical atherosclerosis in children.

[Relationship of C-reactive protein to adiposity, cardiovascular risk factors and subclinical atherosclerosis in healthy children].

Introduction And Objectives: In adults, C-reactive protein is a marker of cardiovascular risk. It is associated with both classical and metabolic risk factors and is a predictor of cardiovascular events. The aim was to investigate the relationship of the C-reactive protein concentration to classical cardiovascular risk factors, measures of adiposity subclinical atherosclerosis in children.

Systematics, character evolution, and biogeography of Cistus L. (Cistaceae) based on ITS, trnL-trnF, and matK sequences.

This paper presents the first phylogenetic hypotheses for the 20 species of Cistus based on plastid (trnL-trnF, matK) and nuclear (ITS) DNA sequence data. Phylogenetic relationships reveal that: (1) Halimium and Cistus form a cohesive, natural group; (2) two major lineages of purple-flowered and white-flowered species are defined, except for the purple-flowered C. parviflorus; (3) monophyly of conspecific populations is congruent with the circumscription of species.

[Cost-effectiveness of health promotion in Chile. Experience with "Mirame!" program].

Background: "Mirame!" program was launched in Chile in 1993, to promote a healthy life style at school age.

Aim: To evaluate cost-effectiveness of this program.

Material And Methods: Fifth and sixth grade school children, from 5 selected municipalities of the Metropolitan Region were studied.

Post-streptococcal acute glomerulonephritis in Chile--20 years of experience.

In order to characterize the epidemiological and clinical picture of post-streptococcal acute glomerulonephritis (PSAGN), a prospective study was designed to investigate all admissions to a general hospital of a local health service in Chile. The protocol included the investigation of previous streptococcal infections (SI), clinical symptoms and signs, socioeconomic situation (SES), throat and skin swabs for the isolation of group A beta-hemolytic streptococci, sequential determination of serum antistreptolysin O (ASO) titer, anti-DNAase B antibodies, and C3. During the 20 years studied, 926 cases were admitted (56% males).

Immunological approach in the evaluation of regional lymph nodes of patients with squamous cell carcinoma of the head and neck.

In cancer, regional lymph node (LN) cells are one of the first components of the immune system to have contact with tumor cells or their products. Therefore, the phenotype and functional properties of hematopoietic cells present within the tumor-draining LN are important to understanding their role in the control of malignant cells. Based on the locoregional metastatic behavior of squamous cell carcinoma of the head and neck (SCCH&N) region, we analyzed tumor-draining lymph nodes from SCCH&N patients to obtain insights into regional tumor immunity.