The impact of CYP2D6*4 and GSTP1 Ile105Val polymorphisms on the susceptibility to develop BCR-ABL1 negative myeloproliferative neoplasms

Molecular Biology Reports - Inter-individual variations in the genes encoding xenobiotic-metabolizing enzymes have been reported to alter susceptibility to various diseases involving hematological...     

A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It has been used in folk medicine for many years in Middle East countries. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine long-term applied 900 MHz emitting mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and, was to investigate the role of CAPE on kidney tissue against the possible electromagnetic radiation (EMR)-induced renal impairment in rats. In particular, the ROS such as superoxide and nitric oxide (NO) may contribute to the pathophysiology of EMR-induced renal impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels, urinary N-acetyl-β-d-glucosaminidase (NAG, a marker of renal tubular injury) and nitric oxide (NO, an oxidant product) levels were used as markers of oxidative stress-induced renal impairment and the success of CAPE treatment. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissue were determined to evaluate the changes of antioxidant status. The rats used in the study were randomly grouped (10 each) as follows: i) Control group (without stress and EMR), ii) Sham-operated rats stayed without exposure to EMR (exposure device off), iii) Rats exposed to 900 MHz EMR (EMR group), and iv) A 900 MHz EMR exposed + CAPE treated group (EMR + CAPE group). In the EMR exposed group, while tissue MDA, NO levels and urinary NAG levels increased (p < 0.0001), the activities of SOD, CAT, and GSH-Px in renal tissue were reduced (p < 0.001). CAPE treatment reversed these effects as well (p < 0.0001, p < 0.001 respectively). In conclusion, the increase in NO and MDA levels of renal tissue, and in urinary NAG with the decrease in renal SOD, CAT, GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced renal tissue damage, and CAPE, via its free radical scavenging and antioxidant properties, ameliorates oxidative renal damage. These results strongly suggest that CAPE exhibits a protective effect on mobile phone-induced and free radical mediated oxidative renal impairment in rats.     

Protein dynamics analysis reveals that missense mutations in cancer-related genes appear frequently on hinge-neighboring residues

Missense mutations have various effects on protein structures, also leading to distorted protein dynamics that plausibly affects the function. We hypothesized that missense mutations in cancer-related genes selectively target hinge-neighboring residues that orchestrate collective structural dynamics. To test our hypothesis, we selected 69 cancer-related genes from the Cancer Gene Census database and their representative protein structures from the Protein Data Bank. We first identified the hinge residues in two global modes of motion by applying the Gaussian Network Model. We then showed that missense mutations are significantly enriched on hinge-neighboring residues in oncogenes and tumor suppressor genes. We observed that several oncogenes (eg, MAP2K1, PTPN11, and KRAS) and tumor suppressor genes (eg, EZH2, CDKN2C, and RHOA) strongly exhibit this phenomenon. This study highlights and rationalizes the functional importance of missense mutations on hinge-neighboring residues in cancer.     

Molecular and biochemical characterization of a novel intronic single point mutation in a Tunisian family with glycogen storage disease type III

Genetic deficiency of the glycogen debranching enzyme causes glycogen storage disease type III, an autosomal recessive inherited disorder. The gene encoding this enzyme is designated as AGL gene. The disease is characterized by fasting hypoglycemia, hepatomegaly, growth retardation, progressive myopathy and cardiomyopathy. In the present study, we present clinical features and molecular characterization of two consanguineous Tunisian siblings suffering from Glycogen storage disease type III. The full coding exons of the AGL gene and their corresponding exon–intron boundaries were amplified for the patients and their parents. Gene sequencing identified a novel single point mutation at the conserved polypyrimidine tract of intron 21 in a homozygous state (IVS21-8A>G). This variant cosegregated with the disease and was absent in 102 control chromosomes. In silico analysis using online resources showed a decreased score of the acceptor splice site of intron 21. RT-PCR analysis of the AGL splicing pattern revealed a 7 bp sequence insertion between exon 21 and exon 22 due to the creation of a new 3′ splice site. The predicted mutant enzyme was truncated by the loss of 637 carboxyl-terminal amino acids as a result of premature termination. This novel mutation is the first mutation identified in the region of Bizerte and the tenth AGL mutation identified in Tunisia. Screening for this mutation can improve the genetic counseling and prenatal diagnosis of GSD III.     

Native lagomorphs suppress grass establishment in a shrub‐encroached,semiarid grassland

Shrub encroachment into arid grasslands has been associated with reduced grass abundance, increased soil erosion, and local declines in biodiversity. Livestock overgrazing and the associated reduction of fine fuels has been a primary driver of shrub encroachment in the southwestern United States, but shrublands continue to persist despite livestock removal and grassland restoration efforts. We hypothesized that an herbivory feedback from native mammals may contribute to continued suppression of grasses after the removal of livestock. Our herbivore exclusion experiment in southeastern Arizona included five treatment levels and allowed access to native mammals based on their relative body size, separating the effects of rodents, lagomorphs, and mule deer. We included two control treatments and replicated each treatment 10 times (n = 50). We introduced uniform divisions of lawn sod (Cynodon dactylon) into each exclosure for 24‐hr periods prior to (n = 2) and following (n = 2) the monsoon rains and used motion‐activated cameras to document herbivore visitations. In the pre‐monsoon trials, treatments that allowed lagomorph access had less sod biomass relative to other treatments (p < 0.001), averaging 44% (SD 36%) and 29% (SD 45%) remaining biomass after the 24‐hr trial periods. Following the onset of monsoons, differences in remaining biomass among treatments disappeared. Desert cottontails (Sylvilagus audubonii) were detected more frequently than any of the other 11 herbivore species present at the site, accounting for 83% of detections during the pre‐monsoon trials. Significantly more (p < 0.001) desert cottontails were detected during the pre‐monsoon trials (2,077) compared to the post‐monsoon trials (174), which coincided with biomass removal from lagomorph accessible treatments. We conclude that desert cottontails are significant consumers of herbaceous vegetation in shrub‐encroached arid grasslands and they, along with other native herbivores, may act as a biotic feedback contributing to the competitive advantage and persistence of shrubs.     

Marine Nematode Taxonomy in Africa: Promising Prospects Against Scarcity of Information

From the late 19th century, Africa has faced heavy exploitation of its natural resources with increasing land/water pollution, and several described species have already become extinct or close to extinction. This could also be the case for marine nematodes, which are the most abundant and diverse benthic group in marine sediments, and play major roles in ecosystem functioning. Compared to Europe and North America, only a handful of investigations on marine nematodes have been conducted to date in Africa. This is due to the scarcity of experienced taxonomists, absence of identification guides, as well as local appropriate infrastructures. A pivotal project has started recently between nematologists from Africa (Tunisia), India, and Europe (Italy) to promote taxonomic study and biodiversity estimation of marine nematodes in the African continent. To do this, as a first step, collection of permanent slides of marine nematodes (235 nominal species and 14 new to science but not yet described) was recently established at the Faculty of Sciences of Bizerte (Tunisia). Capacity building of next generation of African taxonomists have been carried out at level of both traditional and molecular taxonomy (DNA barcoding and next-generation sequencing [NGS]), but they need to be implemented. Indeed, the integration of these two approaches appears crucial to overcome lack of information on the taxonomy, ecology, and biodiversity of marine nematodes from African coastal waters.     

Dehydroepiandrosterone ameliorates hepatocellular damage in obstructive jaundice

We aimed to investigate the ameliorating effect of dehydroepiandrosterone (DHEA) on the potential hepatocellular damage in experimental obstructive jaundice. Twenty‐four male rabbits in the study were randomly allocated into three groups. In the sham group, the choledochal canal was identified and explored. In the obstructive jaundice and treatment groups, the choledochal canal was ligated. Placebo and DHEA were administered to the obstructive jaundice and treatment groups, respectively. Blood samples were obtained at baseline, and both blood samples and liver tissue samples were obtained by re‐laparotomy performed on day 8. Biochemical parameters were measured in blood samples, and liver samples were histopathologically evaluated. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP) and bilirubin levels were lower in the treatment group than in obstructive jaundice. Mononuclear inflammation in the portal region and hepatocyte degeneration were milder in the treatment group compared to obstructive jaundice group. Fibrosis and necrosis were also recovered by the DHEA treatment. In conclusion, these findings suggested that DHEA may reduce the obstructive jaundice‐induced hepatocellular damage. Copyright © 2010 John Wiley & Sons, Ltd.     

Lithium-induced renal toxicity in rats: Protection by a novel antioxidant caffeic acid phenethyl ester

Lithium carbonate used in the long-term treatment of manic-depressive illness has been reported to lead to progressive renal impairment in rats and humans. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygene species mediated oxidative stress in ischemia-reperfusion and toxic injuries. The beneficial effect CAPE on lithium-induced nephrotoxicity has not been reported yet. The purpose of this study was to examine a possible renoprotective effect of CAPE against lithium-induced nephrotoxicity in a rat model. Twenty-two adult male rats were randomly divided into three experimental groups, as follows: control group, lithium-treated group (Li), and lithium plus CAPE-treated group (Li+CAPE). Li were treated intraperitoneally (i.p.) with 25 mg/kg Li₂CO₃ solution in 0.9% NaCl twice daily for 4 weeks. CAPE was co-administered i.p. with a dose of 10 μM/kg/day for 4 weeks. Serum Li, blood urea nitrogen and plasma creatinine, urinary N-acetyl-β-D-glucosaminidase (NAG, a marker of renal tubular injury), and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in Li-treated rats. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Serum Li levels were found high in the Li and Li+CAPE groups. In Li-administrated rats, urinary NAG and renal MDA levels were increased according to control and Li+CAPE groups (p < 0.05). CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD, CAT and GSH-Px activities were decreased in Li-administrated animals; CAPE caused a significant increase in the activities of these antioxidant enzymes. In conclusion, CAPE treatment has a protective effect against Li-induced renal tubular damage and oxidative stress in a rat model.