Paired box genes, PAX-2 and PAX-8, are not frequently mutated in Wilms tumor

To determine whether PAX-2 and PAX-8 are involved in Wilms tumor (WT) pathogenesis, we sought mutations in these two genes in 99 Wilms tumors of favorable histology. We screened the entire protein coding sequences as well as the intronic regions adjacent to exons, using denaturing HPLC followed by sequencing of samples displaying abnormal chromatograms. In PAX-2, a silent polymorphism was found within exon 2 and exon 8 in 1% and 21% of cases, respectively. Three apparently silent polymorphisms were also found in PAX-8, two in exon 5 (2 of 99 cases or 2%) and one in exon 6 (22 of 99 cases or 22%), all of which were located 3' to the exons. In conclusion, no evidence for disease causing mutation was found using this technique, and so the direct involvement of either of these two genes in WT is unlikely.     

Comparison of the anti-influenza virus activity of cyclopentane derivatives with oseltamivir and zanamivir in vivo

Cyclopentane derivatives, designated as BCX-1812, BCX-1827, BCX-1898, and BCX-1923, were tested in parallel with oseltamivir carboxylate and zanamivir for the in vivo activity in mice infected with A/Turkey/Mas/76 X A/Beijing/32/92 (H6N2) influenza virus. The compounds were tested orally and intranasally at different dose levels. BCX-1812, BCX-1827, and BCX-1923 showed more than 50% protection at 1mg/kg/day dose level on oral treatment. The intranasal treatment was 100% effective even at 0.01 mg/kg/day for all four compounds. On comparison with oseltamivir carboxylate and zanamivir, these four cyclopentane derivatives have shown equal or better efficacies. The synthesis of two new compounds, BCX-1898 and BCX-1923, is also described.     

Microbial larvicides for mosquito control: Impact of long lasting formulations of Bacillus thuringiensis var. israelensis and Bacillus sphaericus on non‐target organisms in western Kenya highlands

The microbial larvicides Bacillus thuringiensis var. israelensis and Bacillus sphaericus have been used extensively for mosquito control and have been found to be effective and safe to non‐target organisms cohabiting with mosquito larvae. Recently developed long lasting microbial larvicides (LLML), although evading the previous challenge of short duration of activity, increase the risk of persistence of toxins in the treated larval habitats. This study monitored the impact of LLML FourStar^® and LL3 on non‐target organisms cohabiting with mosquito larvae in an operational study to control malaria vectors in western Kenya highlands. A total of 300 larval habitats were selected in three highland villages. The habitats were first monitored for 5 weeks to collect baseline data on non‐target organisms cohabiting with mosquito larvae and then randomized into two treatment arms (respective FourStar^® and LL3) and one control arm. Non‐target organisms were sampled weekly for 5 months after treatment to assess the impact of LLML intervention. Before treatment, the mean density of all non‐target organisms combined in the control, LL3 and FourStar^® treated habitats was 1.42, 1.39 and 1.49 individuals per habitat per sampling occasion, respectively. Following treatment, this density remained fairly unchanged for 21 weeks at which time it was 1.82, 2.11, and 2.05 for the respective control, LL3 and FourStar^® treated habitats. Statistical analysis revealed that LL3 and FourStar^® did not significantly alter abundance, richness or diversity of the 11 taxa studied, when comparing the intervention and control larval habitats. However, both FourStar^® and LL3 significantly reduced the density of malaria vectors. In conclusion, one round of label rate application of FourStar^® or LL3 in natural larval habitats did not alter richness, abundance or diversity of the monitored aquatic non‐target organisms cohabiting with mosquito larvae to an ecologically significant level.     

Human mitochondrial variants influence on oxygen consumption

This work investigates if human mitochondrial variants influence on maximal oxygen consumption (VO(2max)). With this purpose we recruited, as a uniform population in term of nutritional habits and life style, 114 healthy male Spanish subjects that practiced fitness exercises 3-4 times a week. Once mtDNA haplogroups were determined, we found that J presents with lower VO(2max) (P=0.02) than nonJ variants. J has been related with a lower efficiency of electron transport chain (ETC), diminished ATP and ROS production. Thus, the difficult to compensate the mitochondrial energetic deficiency could explain the accumulation of J haplogroup in LHON and multiple sclerosis. Furthermore, the lower ROS production associated to J could also account for the accrual of this variant in elderly people consequent to a decreased oxidative damage.     

The SWI/SNF complex acts to constrain distribution of the centromeric histone variant Cse4

In order to gain insight into the function of the Saccharomyces cerevisiae SWI/SNF complex, we have identified DNA sequences to which it is bound genomewide. One surprising observation is that the complex is enriched at the centromeres of each chromosome. Deletion of the gene encoding the Snf2 subunit of the complex was found to cause partial redistribution of the centromeric histone variant Cse4 to sites on chromosome arms. Cultures of snf2Δ yeast were found to progress through mitosis slowly. This was dependent on the mitotic checkpoint protein Mad2. In the absence of Mad2, defects in chromosome segregation were observed. In the absence of Snf2, chromatin organisation at centromeres is less distinct. In particular, hypersensitive sites flanking the Cse4 containing nucleosomes are less pronounced. Furthermore, SWI/SNF complex was found to be especially effective in the dissociation of Cse4 containing chromatin in vitro. This suggests a role for Snf2 in the maintenance of point centromeres involving the removal of Cse4 from ectopic sites.     

Interaction Between Selenium and Mercury in Biological Samples of Pakistani Myocardial Infarction Patients at Different Stages as Related to Controls

It has been speculated that trace elements may a play role in the pathogenesis of heart diseases. In the present study, we aimed to assess the levels of selenium (Se) and mercury (Hg) in biological samples (whole blood, urine, and scalp hair) of myocardial infarction (MI) patients of both genders (age range 45–60 years) at the first, second, and third heart attack (n?=?130), hospitalized in a cardiac ward of a civil hospital of Hyderabad City (Pakistan). For comparison, healthy age-matched referent subjects (n?=?61) of both genders were also selected. Se and Hg in biological samples were measured by electrothermal atomic absorption spectrometry and cold vapor atomic absorption spectrometry, prior to microwave acid digestion, respectively. The validity of the methodology was checked by biological certified reference materials. During this study, 78 % of the 32 registered patients of third MI attack (aged >50 years) died. The concentration of Se was decreased in scalp hair and blood samples of MI patients, while Hg was higher in all biological samples as compared to referent subjects. Se concentration was inversely associated with the risk of MI attacks in both genders. These results add to an increasing body of evidence that Se is a protective element for cardiovascular health.