Haptoglobin Polymorphism: A Novel Genetic Risk Factor for Celiac Disease Development and Its Clinical Manifestations

Background: Haptoglobin (Hp) α-chain alleles 1 and 2 account for 3 phenotypes that may influence the course of inflammatory diseases via biologically important differences in their antioxidant, scavenging, and immunomodulatory properties. Hp1-1 genotype results in the production of small dimeric, Hp2-1 linear, and Hp2-2 cyclic polymeric haptoglobin molecules. We investigated the haptoglobin polymorphism in patients with celiac disease and its possible association to the presenting symptoms. Methods: We studied 712 unrelated, biopsy-proven Hungarian celiac patients (357 children, 355 adults; severe malabsorption 32.9%, minor gastrointestinal symptoms 22.8%, iron deficiency anemia 9.4%, dermatitis herpetiformis 15.6%, silent disease 7.2%, other 12.1%) and 384 healthy subjects. We determined haptoglobin phenotypes by gel electrophoresis and assigned corresponding genotypes. Results: Hp2-1 was associated with a significant risk for celiac disease (P = 0.0006, odds ratio [OR] 1.54, 95% CI 1.20–1.98; prevalence 56.9% in patients vs 46.1% in controls). It was also overrepresented among patients with mild symptoms (69.2%) or silent disease (72.5%). Hp2-2 was less frequent in patients than in controls (P = 0.0023), but patients having this phenotype were at an increased risk for severe malabsorption (OR 2.21, 95% CI 1.60–3.07) and accounted for 45.3% of all malabsorption cases. Celiac and dermatitis herpetiformis patients showed similar haptoglobin phenotype distributions. Conclusions: The haptoglobin polymorphism is associated with susceptibility to celiac disease and its clinical presentations. The predominant genotype in the celiac population was Hp2-1, but Hp2-2 predisposed to a more severe clinical course. The phenotype-dependent effect of haptoglobin may result from the molecule’s structural and functional properties

Systemic inflammatory response syndrome (SIRS) induced by carbon tetrachloride in rats

We have observed the symptoms of systemic inflammatory response syndrome (SIRS) in male rats intoxicated by carbon tetrachloride (CCl(4)). Severe hypothermia, tachypnoea and increase in the heart beat min were diagnosed. These symptoms developed in the first hour of intoxication. The hepatic dysfunction was characterized by elevated bilirubin levels. In the sera we have measured increases in the activity of secretable (group II) phospholipase A(2) sPLA(2) (2,8x) and 6-ketoprostaglandin F(1α) (KPGF) (1,44x). Supposedly the free radicals derived from CCl(4)—mainly trichloromethyl—could induce the prompt reaction of SIRS and the release of sPLA(2) as well as the formation of KPGF. Our findings show that in the early phase of CCl(4) intoxication the symptoms of SIRS can be related to elevation of sPLA(2) and the products of cyclooxygenase II

ACE and ACTN3 genes polymorphisms among female Hungarian athletes in the aspect of sport disciplines

The aim of the study was to determine the importance of two sport-associated gene polymorphisms, alpha-actinin-3 R577X (ACTN3) and angiotensin-converting enzyme I/D (ACE), among Hungarian athletes in different sports. The examination was carried out only on women (n = 100). Sport-specific groups were formed in order to guarantee the most homogeneous clusters. Human genomic DNA was isolated from blood, and genotyping was performed by polymerase chain reaction. To measure the differences between the participating groups, Chi-squared test was performed using Statistica 9.0 for Windows® (significance level: p 0.05) were compared. A similarity was detectable in the I allele frequencies of the water polo (61.11%) and kayaking/rowing (56.67%) groups. The ACTN3 R/X polymorphism showed no differences in comparison with the sport groups. R allele frequencies were higher in every group compared to the X allele. The potential significance of the ACE I allele in sports of an aerobic nature was not clearly confirmed among Hungarian athletes

Spatial variation of PM2.5, PM10, PM2.5 absorbance and PMcoarse concentrations between and within 20 European study areas and the relationship with NO2 - Results of the ESCAPE project

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The MCT1 gene Glu490Asp polymorphism (rs1049434) is associated with endurance athlete status, lower blood lactate accumulation and higher maximum oxygen uptake

The purpose of this study was to explore the association of the MCT1 gene Glu490Asp polymorphism (rs1049434) with athletic status and performance of endurance athletes. A total of 1,208 Brazilians (318 endurance athletes and 890 non-athletes) and 867 Europeans (315 endurance athletes and 552 non-athletes) were evaluated in a case–control approach. Brazilian participants were classified based on self-declared ethnicity to test whether the polymorphism was different between Caucasians and Afro-descendants. Moreover, 66 Hungarian athletes underwent an incremental test until exhaustion to assess blood lactate levels, while 46 Russian athletes had their maximum oxygen uptake ( O2max) compared between genotypes. In the Brazilian cohort, the major T-allele was more frequent in Caucasian top-level competitors compared to their counterparts of lower competitive level (P = 0.039), and in Afro-descendant athletes compared to non-athletes (P = 0.015). Similarly, the T-allele was more frequent in European athletes (P = 0.029). Meta-analysis of the Brazilian and European cohorts confirmed that the T-allele is over-represented in endurance athletes (OR: 1.48, P = 0.03), especially when Afro-descendant athletes were included in the meta-analysis (OR: 1.58, P = 0.005). Furthermore, carriers of the T/T genotype accumulated less blood lactate in response to intense effort (P< 0.01) and exhibited higher O2max (P = 0.04). In conclusion, the Glu490Asp polymorphism was associated with endurance athletic status and performance. Our findings suggest that, although ethnic differences may exist, the presence of the major T-allele (i.e., the Glu-490 allele) favours endurance performance more than the mutant A-allele (i.e., the 490-Asp allele)

Topoisomerase IIβ Activates a Subset of Neuronal Genes that Are Repressed in AT-Rich Genomic Environment

DNA topoisomerase II (topo II) catalyzes a strand passage reaction in that one duplex is passed through a transient brake or gate in another. Completion of late stages of neuronal development depends on the presence of active β isoform (topo IIβ). The enzyme appears to aid the transcriptional induction of a limited number of genes essential for neuronal maturation. However, this selectivity and underlying molecular mechanism remains unknown. Here we show a strong correlation between the genomic location of topo IIβ action sites and the genes it regulates. These genes, termed group A1, are functionally biased towards membrane proteins with ion channel, transporter, or receptor activities. Significant proportions of them encode long transcripts and are juxtaposed to a long AT-rich intergenic region (termed LAIR). We mapped genomic sites directly targeted by topo IIβ using a functional immunoprecipitation strategy. These sites can be classified into two distinct classes with discrete local GC contents. One of the classes, termed c2, appears to involve a strand passage event between distant segments of genomic DNA. The c2 sites are concentrated both in A1 gene boundaries and the adjacent LAIR, suggesting a direct link between the action sites and the transcriptional activation. A higher-order chromatin structure associated with AT richness and gene poorness is likely to serve as a silencer of gene expression, which is abrogated by topo IIβ releasing nearby genes from repression. Positioning of these genes and their control machinery may have developed recently in vertebrate evolution to support higher functions of central nervous system

Climate and mating systems as drivers of global diversity of parental care in frogs

Aim Amphibians exhibit unusually diverse reproductive modes, including a wide array of parental care strategies. The evolutionary drivers of this diversity, however, remain unclear. Here, we investigate three major factors that might predict interspecific variation in parental care strategies: climate, intrasexual selection and social environment. We hypothesize that some forms of care evolved to cope with harsh conditions, such as dry or unpredictable habitats. We contrast this prediction with the hypothesis that parental roles have co‐evolved with the social environment and mating systems. Location Global. Major taxa studied Frogs and toads (Amphibia: Anura). Time period Extant taxa that represent c . 220 Myr of evolutionary history. Methods Using geographical and behavioural data for 971 species of frogs and toads that represent 45 anuran families, we quantified the global distribution of four forms of parenting separately for males and females: nest building, nest and/or tadpole attendance, carrying and nourishment. We used phylogenetic comparative analyses to investigate whether climate, social environment and mating systems predicted interspecific variation in parental care. Results Our results showed that climatic effects contribute to parental care diversity: in cool and humid climates the males provide offspring attendance, whereas in predictable temperatures endotrophy occurs, whereby the female provides all nutrients for the offspring until metamorphosis. In addition, we found other associations between mating systems and forms of parental care: uniparental clutch attendance by males is present in species with territorial defence, whereas cooperative nest building co‐occurs with sperm competition. The type of parental care is not associated with adult sex ratios. Main conclusions No specific form of care is associated with hostile environments; in fact, some forms of care occur in beneficial conditions, whereas others are used independently from the climate. Instead, parenting diversity has co‐evolved closely with mating systems in frogs

Species Richness and Range Size of the Terrestrial Mammals of the World: Biological Signal within Mathematical Constraints

We explore global spatial diversity patterns for terrestrial mammals using as a tool range-diversity plots. These plots display simultaneously information about the number of species in localities and their spatial covariance in composition. These are highly informative, as we show by linking range-diversity plots with maps and by highlighting the correspondences between well defined regions of the plots with geographical regions or with taxonomic groups. Range-diversity plots are mathematically constrained by the lines of maximum and minimum mean covariance in species composition. We show how regions in the range-diversity plot corresponding to the line of maximum covariance correspond to large continental masses, and regions near the lower limit of the range-diversity plot correspond to archipelagos and mountain ranges. We show how curves of constant covariance correspond to nested faunas. Finally, we show that the observed distribution of the covariance range has significantly longer tails than random, with clear geographic correspondences. At the scale of our data we found that range-diversity plots reveal biodiversity patterns that cannot be replicated by null models, and correspond to conspicuous terrain features and taxonomic groupings

The FUN30 Chromatin Remodeler, Fft3, Protects Centromeric and Subtelomeric Domains from Euchromatin Formation

The chromosomes of eukaryotes are organized into structurally and functionally discrete domains. This implies the presence of insulator elements that separate adjacent domains, allowing them to maintain different chromatin structures. We show that the Fun30 chromatin remodeler, Fft3, is essential for maintaining a proper chromatin structure at centromeres and subtelomeres. Fft3 is localized to insulator elements and inhibits euchromatin assembly in silent chromatin domains. In its absence, euchromatic histone modifications and histone variants invade centromeres and subtelomeres, causing a mis-regulation of gene expression and severe chromosome segregation defects. Our data strongly suggest that Fft3 controls the identity of chromatin domains by protecting these regions from euchromatin assembly