No Evidence for a Difference in Neuropsychological Profile among Carriers and Noncarriers of the FMR1 Premutation in Adults under the Age of 50

The 5′ untranslated region of the fragile X mental retardation gene, FMR1, contains a polymorphic CGG repeat. Expansions of this repeat are associated with a spectrum of disorders. Full mutation alleles, repeats ≥ 200, are associated with fragile X syndrome. Premutation alleles, repeats of ~55–199, are associated with a tremor-ataxia syndrome most commonly in older males and primary ovarian insufficiency in females. However, the neuropsychological impact of carrying a premutation allele is presently unclear in younger adults. In this study, we analyzed neuropsychological scores for 138 males and 506 females ascertained from the general population and from families with a history of fragile X syndrome. Subjects were age 18–50 years and had varying repeat lengths. Neuropsychological scores were obtained from measures of general intelligence, memory, and executive functioning, including attention. Principal component analysis followed by varimax rotation was used to create independent factors for analysis. These factors were modeled for males and females separately via a general linear model that accounted for correlation among related subjects. All models were adjusted for potential confounders, including age at testing, ethnicity, and household income. Among males, no repeat length associations were detected for any factor. Among females, only a significant association with repeat length and self-report attention (p < 0.01) was detected, with premutation carriers self-reporting significantly more attention-related problems compared to noncarriers. No significant interactions between repeat length and age were detected. Overall, these results indicate the lack of a global neuropsychological impact of carrying a premutation allele among adults under the age of 50.     

Non-enzymatic glycation of type I collagen diminishes collagen-proteoglycan binding and weakens cell adhesion

Non-enzymatic glycation of type I collagen occurs in aging and diabetes, and may affect collagen solubility, charge, polymerization, and intermolecular interactions. Proteoglycans(1) (PGs) bind type I collagen and are proposed to regulate fibril assembly, function, and cell-collagen interactions. Moreover, on the collagen fibril a keratan sulfate (KS) PG binding region overlaps with preferred collagen glycation sites. Thus, we examined the effect of collagen modified by simple glycation on PG-collagen interactions. By affinity coelectrophoresis (ACE), we found reduced affinities of heparin and KSPGs for glycated but not normal collagen, whereas the dermatan sulfate (DS)PGs decorin and biglycan bound similarly to both, and that the affinity of heparin for normal collagen decreased with increasing pH. Circular dichroism (CD) spectroscopy revealed normal and glycated collagens to assume triple helical conformations, but heparin addition caused precipitation and decreased triple helical content-effects that were more marked with glycated collagen. A spectrophotometric assay revealed slower polymerization of glycated collagen. However, ultrastructural analyses indicated that fibrils assembled from normal and glycated collagen exhibited normal periodicity, and had similar structures and comparable diameter distributions. B-cells expressing the cell surface heparan sulfate PG syndecan-1 adhered well to normal but not glycated collagen, and endothelial cell migration was delayed on glycated collagen. We speculate that glycation diminishes the electrostatic interactions between type I collagen and PGs, and may interfere with core protein-collagen associations for KSPGs but not DSPGs. Therefore in vivo, collagen glycation may weaken PG-collagen interactions, thereby disrupting matrix integrity and cell-collagen interactions, adhesion, and migration.     

Leaf structural changes associated with iron deficiency chlorosis in field-grown pear and peach: physiological implications

Plants grown in calcareous, high pH soils develop Fe deficiency chlorosis. While the physiological parameters of Fe-deficient leaves have been often investigated, there is a lack of information regarding structural leaf changes associated with such abiotic stress. Iron-sufficient and Fe-deficient pear and peach leaves have been studied, and differences concerning leaf epidermal and internal structure were found. Iron deficiency caused differences in the aspect of the leaf surface, which appeared less smooth in Fe-deficient than in Fe-sufficient leaves. Iron deficiency reduced the amount of soluble cuticular lipids in peach leaves, whereas it reduced the weight of the abaxial cuticle in pear leaves. In both plant species, epidermal cells were enlarged as compared to healthy leaves, whereas the size of guard cells was reduced. In chlorotic leaves, bundle sheaths were enlarged and appeared disorganized, while the mesophyll was more compacted and less porous than in green leaves. In contrast to healthy leaves, chlorotic leaves of both species showed a significant transient opening of stomata after leaf abscission (Iwanoff effect), which can be ascribed to changes found in epidermal and guard cells. Results indicate that Fe-deficiency may alter the barrier properties of the leaf surface, which can significantly affect leaf water relations, solute permeability and pest and disease resistance.     

Use of Psoralen Monoadducts to Compare The Structure of 16S rRNA in Active and Inactive 30S Ribosomal Subunits

Abstract

E. coli 30S ribosomes in the inactive conformation were irradiated at 390 nm in the presence of 4′ -aminomethyl-4,5′,8-trimethylpsoralen (AMT). This produces monoadducts in which AMT is attached to only one strand of an RNA duplex region. After unbound AMT was removed, some ribosomes were activated and then subjected to 360 nm irradiation; others were reirradiated without activation. Electron microscopic examination of 16S rRNA extracted from these two samples showed covalent rRNA loops indicative of rRNA crosslinks. The general pattern of loops closely matched that seen previously after direct psoralen crosslinking of 30S particles. However, the frequency of occurrence of one major class of loops formed by crosslinks between residues near position 500 and the 3′ end was substantially lower for the activated samples, implying that the structure of the 16S rRNA in active and inactive 30S particles is different.     

Enthalpie and Entropie Contributions in the Transesterification of Sucrose: Computational Study of Lipases and Subtilisin

Abstract

Transesterification of sucrose with fatty acids catalyzed by subtilisin Carlsberg occurs with regioselectivity that is different from that in lipases. Thermomyces lanuginosus lipase (TlL) and Candida antarctica lipase B (CALB) catalyze synthesis at positions 6 and 6′, with differing abilities, while subtilisin catalysis leads to the l′-acylated sucrose. The catalytic machinery in lipases is approximately mirrored in subtilisins but different pocket morphologies including size, shape, and rearrangement of the catalytic elements underlies the differing regioselectivities. The thermodynamic consequences of these differences on the above reactions have been explored systematically using computational methods, determining the free energies of interaction of the putative transition-state adducts. Analysis of the conformers with the lowest transition state energies (protein-ligand interactions and vibrational entropy contributions) indicates that enthalpic factors control specificities in lipases while entropic factors are more important in subtilisin.     

Atmospheric pollen in Santiago,Chile

In the city of Santiago (33°27'S70°38'W), Chile, an atmospheric pollen was monitored for three years using a volumetric Hirst-type pollen trap. The aims of the study were: to assess the pollen types present in the atmosphere, their actual concentrations and dynamics (means and maxima); to establish the pollen calendar for Santiago; and to analyze the aerobiologic characteristics distinguishing introduced and native taxa. Results show that atmospheric pollen mainly originates from the following taxa: Platanus , Poaceae, Acer , Cupressus , Chenopodiaceae, Urticaceae, Morus , Plantago and Oleaceae. For the most frequent pollen types graphs of their atmospheric presence constructed and a table with relevant yearly data for the three studied (July-June) is presented. It is concluded, that the airborne pollen is originating mainly from introduced taxa, many of which are considered allergenic. Native taxa showed no high concentrations. The highest aiborne pollen concentrations where observed in September, however, atmospheric pollen thought to be capable of causing pollinosis, where present during the whole year. The highest pollen concentrations are mostly from trees.     

Evaluación del grado de consecución de objetivos de control metabólico en pacientes con diabetes mellitus tipo 2

ObjectiveTo evaluate the extent to which metabolic targets in type 2 diabetes (DM-2) are achieved in the Endocrinology and Clinical Nutrition Unit of the Hospital Puerta del Mar in Cadiz (Spain) from 2005 to 2008.MethodThe database included in the computer application HP-Doctor used for all patients attended in our unit (admissions, consultations and peripheral centers) was analyzed. All patients with a principal or secondary diagnosis of DM-2 were included. Clinical characteristics, chronic complications, drug treatment and the percentage of patients who achieved annual mean targets of glycosylated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDLc) were analyzed.ResultsFrom 2005 to 2008, the number of DM-2 patients with computerized records increased by 108.7%. In 2008, 1,177 patients were evaluated. A total of 10.8% were active smokers, 53% had hypertension, and 51.2% and 12.6% presented with retinopathy and cardiovascular disease, respectively. During the study period, the percentage of patients with a mean HbA1c <7% was similar (2005: 31.7% 2008: 30.4%), those with LDLc <100 mg/dl increased from 19.2% to 25.6% and only 9.2% of patients achieved both targets, HbA1c <7% and LDLc <100 mg/dl.ConclusionsIn 2008, only 30% of DM-2 patients achieved a mean HbA1c < 7% and only 25% had LDLc < 100 mg/dl. Metabolic control in DM-2 patients should be improved.     

Molecular modeling study on potent and selective adenosine A(3) receptor agonists

Adenosine A(3) receptor (A(3)AR) is involved in a variety of key physio-pathological processes and its agonists are potential therapeutic agents for the treatment of rheumatoid arthritis, dry eye disorders, asthma, as anti-inflammatory agents, and in cancer therapy. Recently reported MECA (5'-N-methylcarboxamidoadenosine) derivatives bearing a methyl group in N(6)-position and an arylethynyl substituent in 2-position demonstrated to possess sub-nanomolar affinity and remarkable selectivity for the human A(3)AR, behaving as full agonists of this receptor. In this study, we made an attempt to get a rationalization of the high affinities and selectivities of these molecules for the human A(3)AR, by using adenosine receptor (AR) structural models based on the A(2A)AR crystal structure and molecular docking analysis. Post-docking analysis allowed to evaluate the ability of modeling tools in predicting AA(3)R affinity and in providing interpretation of compound substituents effect on the A(3)AR affinity and selectivity.