Molecular Organization of 5S rDNAs in Rajidae (Chondrichthyes): Structural Features and Evolution of Piscine 5S rRNA Genes and Nontranscribed Intergenic Spacers

The genomic and gene organisation of 5S rDNA clusters have been extensively characterized in bony fish and eukaryotes, providing general issues for understanding the molecular evolution of this multigene DNA family. By contrast, the 5S rDNA features have been rarely investigated in cartilaginous fish (only three species). Here, we provide evidence for a dual 5S rDNA gene system in the Rajidae by sequence analysis of the coding region (5S) and adjacent nontranscribed spacer (NTS) in five Mediterranean species of rays (Rajidae), and in a large number of piscine taxa including lampreys and bony fish. As documented in several bony fish, two functional 5S rDNA types were found here also in the rajid genome: a short one (I) and a long one (II), distinguished by distinct 5S and NTS sequences. That the ancestral piscine genome had these two 5S rDNA loci might be argued from the occurrence of homologous dual gene systems that exist in several fish taxa and from 5S phylogenetic relationships. An extensive analysis of NTS-II sequences of Rajidae and Dasyatidae revealed the occurrence of large simple sequence repeat (SSR) regions that are formed by microsatellite arrays. The localization and organization of SSR within the NTS-II are conserved in Rajiformes since the Upper Cretaceous. The direct correlation between the SSRs extension and the NTS length indicated that they might play a role in the maintenance of the larger 5S rDNA clusters in rays. The phylogenetic analysis indicated that NTS-II is a valuable systematic tool limited to distantly related taxa of Rajiformes. Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users. [Reviewing Editor: Dr. Rafael Zardoya]     

Neurocysticercosis,a Persisting Health Problem in Mexico

Background

The ongoing epidemiological transition in Mexico minimizes the relative impact of neurocysticercosis (NC) on public health. However, hard data on the disease frequency are not available.

Methodology

All clinical records from patients admitted in the Instituto Nacional de Neurologia y Neurocirugia (INNN) at Mexico City in 1994 and 2004 were revised. The frequencies of hospitalized NC patients in neurology, neurosurgery and psychiatry services, as well as NC mortality from 1995 through 2009, were retrieved. Statistical analyses were made to evaluate possible significant differences in frequencies of NC patients'' admission between 1994 and 2004, and in yearly frequencies of NC patients'' hospitalization and death between 1995 and 2009.

Principal Findings

NC frequency in INNN is not significantly different in 1994 and 2004. Between these two years, clinical severity of the cases diminished and the proportion of patients living in Mexico City increased. Yearly frequencies of hospitalization in neurology and psychiatry services were stable, while frequencies of hospitalization in neurosurgery service and mortality significantly decreased between 1995 and 2009.

Conclusions

Our findings show a stable tendency of hospital cases during the last decade that should encourage to redouble efforts to control this ancient disease.     

BMI and Waist Circumference as Predictors of Well‐being in Older Adults: Findings From the English Longitudinal Study of Ageing

The aim of this study is to examine the association of BMI and waist circumference (WC), with a quality of life (QoL) indicator designed for older ages (CASP19), and with depressive symptoms (Centre for Epidemiologic Studies Depression Scale). We included 8,688 individuals aged ≥52 years who participants of Wave 2 (2004–2005) and Wave 3 (2006–2007) of the English Longitudinal Study of Ageing (ELSA). To explore cross‐sectional relationships (2004–2005), we fitted regression models for BMI and WC (included simultaneously) as our predictors of QoL and depressive symptoms adjusted for covariates. To explore longitudinal relationships, BMI and waist at baseline (2004–2005) were related to the each outcome variable measured at follow‐up (2006–2007), and adjusted for baseline characteristics (2004–2005). For a given BMI, larger WC was associated with lower QoL and higher risk of depressive symptoms for women in cross‐sectional and longitudinal analyses. By contrast for a given WC increased BMI for women was positively associated with QoL and lower odds of depressive symptoms. In men, for a given BMI, increased WC was related to QoL only cross‐sectionally; neither WC nor BMI at baseline were associated with depressive symptoms (cross‐sectionally or longitudinally). In conclusion among older people, for a given BMI, increased WC was related with higher risk of poor QoL and, for women, of depressive symptoms; whereas for a given WC, increased BMI had a protective effect on QoL for women.     

In Central Obesity,Weight Loss Restores Platelet Sensitivity to Nitric Oxide and Prostacyclin

Central obesity shows impaired platelet responses to the antiaggregating effects of nitric oxide (NO), prostacyclin, and their effectors—guanosine 3′,5′‐cyclic monophosphate (cGMP) and adenosine 3′,5′‐cyclic monophosphate (cAMP). The influence of weight loss on these alterations is not known. To evaluate whether a diet‐induced body‐weight reduction restores platelet sensitivity to the physiological antiaggregating agents and reduces platelet activation in subjects affected by central obesity, we studied 20 centrally obese subjects before and after a 6‐month diet intervention aiming at reducing body weight by 10%, by measuring (i) insulin sensitivity (homeostasis model assessment of insulin resistance (HOMA_IR)); (ii) plasma lipids; (iii) circulating markers of inflammation of adipose tissue and endothelial dysfunction, and of platelet activation (i.e., soluble CD‐40 ligand (sCD‐40L) and soluble P‐selectin (sP‐selectin)); (iv) ability of the NO donor sodium nitroprusside (SNP), the prostacyclin analog Iloprost and the cyclic nucleotide analogs 8‐bromoguanosine 3′,5′‐cyclic monophosphate (8‐Br‐cGMP) and 8‐bromoadenosine 3′,5′‐cyclic monophosphate (8‐Br‐cAMP) to reduce platelet aggregation in response to adenosine‐5‐diphosphate (ADP); and (v) ability of SNP and Iloprost to increase cGMP and cAMP. The 10 subjects who reached the body‐weight target showed significant reductions of insulin resistance, adipose tissue, endothelial dysfunction, and platelet activation, and a significant increase of the ability of SNP, Iloprost, 8‐Br‐cGMP, and 8‐Br‐cAMP to reduce ADP‐induced platelet aggregation and of the ability of SNP and Iloprost to increase cyclic nucleotide concentrations. No change was observed in the 10 subjects who did not reach the body‐weight target. Changes of platelet function correlated with changes of HOMA_IR. Thus, in central obesity, diet‐induced weight loss reduces platelet activation and restores the sensitivity to the physiological antiaggregating agents, with a correlation with improvements in insulin sensitivity.     

Cell-cycle inhibition by Helicobacter pylori L-asparaginase

Helicobacter pylori (H. pylori) is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. One of the mechanisms whereby it induces damage depends on its interference with proliferation of host tissues. We here describe the discovery of a novel bacterial factor able to inhibit the cell-cycle of exposed cells, both of gastric and non-gastric origin. An integrated approach was adopted to isolate and characterise the molecule from the bacterial culture filtrate produced in a protein-free medium: size-exclusion chromatography, non-reducing gel electrophoresis, mass spectrometry, mutant analysis, recombinant protein expression and enzymatic assays. L-asparaginase was identified as the factor responsible for cell-cycle inhibition of fibroblasts and gastric cell lines. Its effect on cell-cycle was confirmed by inhibitors, a knockout strain and the action of recombinant L-asparaginase on cell lines. Interference with cell-cycle in vitro depended on cell genotype and was related to the expression levels of the concurrent enzyme asparagine synthetase. Bacterial subcellular distribution of L-asparaginase was also analysed along with its immunogenicity. H. pylori L-asparaginase is a novel antigen that functions as a cell-cycle inhibitor of fibroblasts and gastric cell lines. We give evidence supporting a role in the pathogenesis of H. pylori-related diseases and discuss its potential diagnostic application.