Polymorphisms of TNFalpha, IL1beta, and IL1RN genes in chronic obstructive pulmonary disease

It is recognized that genetic factors play a role in the susceptibility to COPD. COPD is characterized by airflow limitation. Chronic inflammation causes small airway disease and parenchymal destruction, leading to the airflow limitation. Polymorphisms in pro-inflammatory cytokine genes may confer a risk for the development of COPD. A case-control association study was performed in Japanese population (88 COPD patients and 61 controls) and Egyptian population (106 patients and 72 controls). Genotype and allele frequencies of the TNFalpha -308 G/A and +489 G/A polymorphisms, the IL1beta -511 C/T, -31 T/C, and +3954 C/T polymorphisms, and a VNTR polymorphism in intron 2 of the IL1RN gene were investigated. In addition, pairwise haplotype frequencies were analyzed. When studied independently, none of the polymorphisms were associated with the development of COPD in both populations. However, in the Egyptian population, the distributions of the haplotype (IL1beta -31 T/C : IL1beta +3954 C/T) were significantly different between the COPD patients and the controls (p(corr)=0.0037). Our findings suggest that this haplotype within the IL1beta gene may be involved in the pathogenesis of COPD and that the genetic factors of COPD susceptibility might be different between different populations.     

Molecular Characterization of a Deep-Sea Methanotrophic Mussel Symbiont that Carries a RuBisCO Gene

In our previous investigation on the genes of 1,5-ribulose bisphosphate carboxylase/oxygenase (RuBisCO; EC 4.1.1.39) in deep-sea chemoautotrophic and methanotrophic endosymbioses, the gene encoding the large subunit of RuBisCO form I (cbbL) had been detected in the gill of a mussel belonging to the genus Bathymodiolus from a western Pacific back-arc hydrothermal vent. This study further examined the symbiont source of the RuBisCO cbbL gene along with the genes of 16S ribosomal RNA (16S rDNA) and particulate methane monooxygenase (EC 1.14.13.25; pmoA) and probed for the presence of the ATP sulfurylase gene (EC 2.7.7.4; sopT). The 16S rDNA sequence analysis indicated that the mussel harbors a monospecific methanotrophic Gammaproteobacterium. This was confirmed by amplification and sequencing of the methanotrophic pmoA, while thiotrophic sopT was not amplified from the same symbiotic genome DNA. Fluorescence in situ hybridization demonstrated simultaneous occurrence of the symbiont-specific 16S rDNA, cbbL and pmoA, but not sopT, in the mussel gill. This is the first molecular and visual evidence for a methanotrophic bacterial endosymbiont that bears the RuBisCO cbbL gene relevant to autotrophic CO₂ fixation.     

Conservation genetics of Sinai’s remnant populations of Moringa peregrina, an economically valuable medicinal plant

Moringa peregrina is an economically valuable tree of Egyptian deserts. It is used medicinally, provides a highly nutritious supplement to Bedouin diets, provides fodder for livestock, and is used for fire wood. M. peregrina seeds have been a source of high-quality oil for cosmetics and perfumes since antiquity. Due to unmanaged grazing and over-collection, M. peregrina has become one of the most endangered tree species in the Egyptian desert ecosystem. A long-term conservation program is urgently needed to maintain or increase the number and size of M. peregrina populations. Ten populations harboring a total of 130 adult M. peregrina were sampled from three disjunct Wadis in South Sinai (W. Me’ar, W. Fieran and W. Zaghra). Open-pollinated seedlings were electrophoretically analyzed to address two basic questions: (1) how is genetic diversity distributed within and among populations within these three Wadis; and (2) what is the mating system of this species. M. peregrina has a mixed mating system with a selfing rate up to 16% and has limited genetic diversity within and significant genetic differentiation among its populations, the majority of which occurs among Wadis. Direct protection is urgently needed to decrease genetic deterioration within M. peregrina populations and to improve their ability to maintain or improve their population numbers. The priority of in situ conservation should be to conserve a few large well-distributed populations representing different Wadis. Ex situ germplasm collections should be made across the species’ range to ensure a representative sample of its genetic variation. Seed orchards designed to maximize cross-fertilization among unrelated individuals should be established to generate propagules to supplement natural populations.     

Overexpression of extracellular superoxide dismutase has a protective role against hyperoxia-induced brain injury in neonatal mice

There is increasing evidence that hyperoxia, particularly at the time of birth, may result in neurological injury, in particular to the susceptible vasculature of these tissues. This study was aimed at determining whether overexpression of extracellular superoxide dismutase (EC-SOD) is protective against brain injury induced by hyperoxia. Transgenic (TG) mice (with an extra copy of the human extracellular superoxide dismutase gene) and wild-type (WT) neonate mice were exposed to hyperoxia (95% of F(i) o(2) ) for 7 days after birth versus the control group in room air. Brain positron emission tomography (PET) scanning with fludeoxyglucose (FDG) isotope uptake was performed after exposure. To assess apoptosis induced by hyperoxia exposure, caspase 3 ELISA and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed. Quantitative western blot for the following inflammatory markers was performed: glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, macrophage-inhibiting factor, and phospho-AMP-activated protein kinase. PET scanning with FDG isotope uptake showed significantly higher uptake in the WT hyperoxia neonate brain group (0.14 ± 0.03) than in both the TG group (0.09 ± 0.01) and the control group (0.08 ± 0.02) (P< 0.05). Histopathological investigation showed more apoptosis and dead neurons in hippocampus and cerebellum brain sections of WT neonate mice after exposure to hyperoxia than in TG mice; this finding was also confirmed by TUNEL staining. The caspase 3 assay confirmed the finding of more apoptosis in WT hyperoxia neonates (0.814 ± 0.112) than in the TG hyperoxic group (0.579 ± 0.144) (P < 0.05); this finding was also confirmed by TUNEL staining. Quantitative western blotting for the inflammatory and metabolic markers showed significantly higher expression in the WT group than in the TG and control groups. Thus, overexpression of EC-SOD in the neonate brain offers significant protection against hyperoxia-induced brain damage.     

Plasmodium falciparum dolichol phosphate mannose synthase represents a novel clade

Dolichol phosphate mannose synthase (DPM) catalyzes the reaction between dolichol phosphate (Dol-P) and guanosine diphosphate mannose (GDP-Man) to form dolichol-phosphate-mannose (Dol-P-Man). This molecule acts as mannose donor for N-glycosylation and glycosylphosphatidylinositol (GPI) biosynthesis. The Plasmodium falciparum DPM1 (Pfdpm1) possesses a single predicted transmembrane region near the N-, but not the C-terminus. Here we show that the cloned Pfdpm1 gene failed to complement a Saccharomyces cerevisiae mutant indicating that the parasite gene does not belong to the baker’s yeast group, as was previously assumed. Furthermore, Pfdpm1 was unable to complement a mouse mutant deficient in DPM but efficiently complements the Schizosaccharomyces pombe fission yeast mutant, indicating a difference between fission yeast and mammalian DPM genes. Therefore, we reanalyzed the hydrophobicity scales of all known DPMs and consequently reclassify the DPM clade into six major novel subgroups. Furthermore, we show that Pfdpm1 represents a unique enzyme among these subgroups.     

The effect of chronic cadmium exposure on the pharmacokinetics of theophylline and ciprofloxacin in rats

Cadmium has been associated with a number of adverse health effects but the impact of those effects on the pharmacokinetics of different drugs has not been investigated. Therefore, the pharmacokinetics of theophylline and ciprofloxacin were studied in cadmium-exposed and control rats (72 rats) following i.p. (6.5mg/kg) and p.o. (10mg/kg) administration, respectively. The third-generation offsprings of rats exposed to 100 microg/mL of cadmium chloride in drinking water were used in this study. Following 8 weeks of exposure, animals received the drugs as a single dose. Blood samples were withdrawn at different time-points and the plasma concentrations of both drugs were analyzed by HPLC. The pharmacokinetic parameters of theophylline and ciprofloxacin were altered significantly in the cadmium-exposed animals. For theophylline, a statistically significant increase (p<0.0001) in C(max) (69%) and AUC(0-)(infinity) (68%) of theophylline in the cadmium-exposed rats as compared to the control were observed. A corresponding significant (p<0.0001) reduction of 41% in clearance (CL/F) of theophylline was detected in the exposed group. Neither the half-life nor the mean residence time (MRT) showed any significant change due to the exposure to cadmium. For ciprofloxacin, no significant difference was seen in the C(max) of the exposed group as compared to the control animals. However, a delay in T(max) was observed in the exposed group (from 0.16(+/-0.003) to 0.37(+/-0.14)h). A small, but significant increase in t(1/2) (p<0.05) was detected (1.74(+/-0.25) vs. 1.45(+/-0.12)h). A significant reduction (p<0.05) of CL/F from 30.54(+/-1.9) to 24.01(+/-3.81)mL/min/kg was seen in the treated group. The current investigation showed that chronic exposure to cadmium could have a very significant impact on altering the pharmacokinetic parameters of various drugs. Therefore, in cadmium-polluted areas, dose adjustments and drug monitoring, especially for drugs with a narrow therapeutic window, should be carried out.     

An essential role for DYF-11/MIP-T3 in assembling functional intraflagellar transport complexes

MIP-T3 is a human protein found previously to associate with microtubules and the kinesin-interacting neuronal protein DISC1 (Disrupted-in-Schizophrenia 1), but whose cellular function(s) remains unknown. Here we demonstrate that the C. elegans MIP-T3 ortholog DYF-11 is an intraflagellar transport (IFT) protein that plays a critical role in assembling functional kinesin motor-IFT particle complexes. We have cloned a loss of function dyf-11 mutant in which several key components of the IFT machinery, including Kinesin-II, as well as IFT subcomplex A and B proteins, fail to enter ciliary axonemes and/or mislocalize, resulting in compromised ciliary structures and sensory functions, and abnormal lipid accumulation. Analyses in different mutant backgrounds further suggest that DYF-11 functions as a novel component of IFT subcomplex B. Consistent with an evolutionarily conserved cilia-associated role, mammalian MIP-T3 localizes to basal bodies and cilia, and zebrafish mipt3 functions synergistically with the Bardet-Biedl syndrome protein Bbs4 to ensure proper gastrulation, a key cilium- and basal body-dependent developmental process. Our findings therefore implicate MIP-T3 in a previously unknown but critical role in cilium biogenesis and further highlight the emerging role of this organelle in vertebrate development.     

The influence of pulsed magnetic fields (PMFs) on nonsynaptic potentials recorded from the central and peripheral nervous systems in vitro

The influence of pulsed magnetic fields (PMFs) on nonsynaptic potentials recorded from the central and peripheral nervous system in vitro has been investigated. The population spikes (PSs) recorded from hippocampal slices during antidromic stimulation and compound action potentials (CAPs) recorded from the segments of the sciatic nerve were used as indicators of neuronal activity. The potentials recorded from both preparations were significantly and permanently enhanced following PMF (0.16 Hz, 15 mT) exposure. The increase in the antidromic PS occurred even in the presence of potassium channel blocker tetraethylammonium (TEA) and was accompanied by multiple spiking. Among all frequencies of PMF tested (0.5, 0.16, 0.07, 0.03, 0.0 Hz), the frequency of 0.5 Hz was the most effective in enhancement of potential amplitude. The influence of PMF on the amplitude of two CAPs evoked by the pair of electrical stimuli applied in rapid succession has also been evaluated. In control conditions the potential triggered by the second stimuli was slightly smaller expressing the phenomenon of short‐term depression (STD). Although PMF exposure amplified the amplitude of both potentials, the increase in the size of the first potential was significantly greater increasing further the magnitude of STD. The blocking of potassium channels reversed STD into facilitation. One of the possible mechanisms involved in PMF action could be the modification of the axonal threshold, which was significantly reduced following exposure to PMF. Bioelectromagnetics 30:621–630, 2009. © 2009 Wiley‐Liss, Inc.