Case control polysomnographic studies of sleep disorders in Parkinson's disease

Background

The relationship between a number of primary sleep disorders and Parkinson''s disease (PD) is still debated. There are limited case control polysomnographic studies in PD and most of these study sample sizes are small.

Methodology/Findings

We conducted one of the largest case-control studies involving overnight polysomnographic evaluation, with prospective recruitment of unselected Parkinson''s disease patients and healthy controls from an Asian population. The cases were recruited from the specialized movement disorder outpatient clinics in a tertiary referral center, and controls from the same geographical locations. All subjects underwent an overnight polysomnographic study and a multiple sleep latency test.A total of 124 subjects including 56 patients and 68 controls frequency-matched for age and sex were included. Multivariate analysis revealed that patients had significantly shorter total sleep time than controls (p = 0.01), lower sleep efficiency (p = 0.001) and increased REM latency (p = 0.007). In patients, multivariate analysis showed that reduced total sleep time was significantly associated with increased age (p = 0.001) and increased levodopa dose (p = 0.032). The mean Insomnia Severity Index was higher in PD patients (9.0±7.1) compared to controls (3.3±3.9, p<0.001). The mean Epworth Sleepiness Scale score was higher in PD patients (9.3±5.9 vs. 5.7±4.8, p<0.001). Nocturnal arousals, obstructive sleep apnea, periodic leg movements and objective abnormal sleepiness were not increased in our patients.

Conclusions/Significance

Our case-control polysomnographic study, the first-ever performed in an Asian population, revealed altered sleep architecture and reduced sleep in PD patients compared to controls. Reduced total sleep time was associated with increased age and levodopa dose. However, nocturnal arousals, primary sleep disorders and abnormal sleepiness were not increased in our PD patients suggesting that ethnic/genetic differences may be a factor in the pathophysiology of these conditions.     

Complete killing of Caenorhabditis elegans by Burkholderia pseudomallei is dependent on prolonged direct association with the viable pathogen

Background

Burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. Much remains to be known about the contributions of genotypic variations within the bacteria and the host, and environmental factors that lead to the manifestation of the clinical symptoms of melioidosis.

Methodology/Principal Findings

In this study, we showed that different isolates of B. pseudomallei have divergent ability to kill the soil nematode Caenorhabditis elegans. The rate of nematode killing was also dependent on growth media: B. pseudomallei grown on peptone-glucose media killed C. elegans more rapidly than bacteria grown on the nematode growth media. Filter and bacteria cell-free culture filtrate assays demonstrated that the extent of killing observed is significantly less than that observed in the direct killing assay. Additionally, we showed that B. pseudomallei does not persistently accumulate within the C. elegans gut as brief exposure to B. pseudomallei is not sufficient for C. elegans infection.

Conclusions/Significance

A combination of genetic and environmental factors affects virulence. In addition, we have also demonstrated that a Burkholderia-specific mechanism mediating the pathogenic effect in C. elegans requires proliferating B. pseudomallei to continuously produce toxins to mediate complete killing.     

Understanding lignin-degrading reactions of ligninolytic enzymes: binding affinity and interactional profile

Previous works have demonstrated that ligninolytic enzymes mediated effective degradation of lignin wastes. The degrading ability greatly relied on the interactions of ligninolytic enzymes with lignin. Ligninolytic enzymes mainly contain laccase (Lac), lignin peroxidase (LiP) and manganese peroxidase (MnP). In the present study, the binding modes of lignin to Lac, LiP and MnP were systematically determined, respectively. Robustness of these modes was further verified by molecular dynamics (MD) simulations. Residues GLU460, PRO346 and SER113 in Lac, residues ARG43, ALA180 and ASP183 in LiP and residues ARG42, HIS173 and ARG177 in MnP were most crucial in binding of lignin, respectively. Interactional analyses showed hydrophobic contacts were most abundant, playing an important role in the determination of substrate specificity. This information is an important contribution to the details of enzyme-catalyzed reactions in the process of lignin biodegradation, which can be used as references for designing enzyme mutants with a better lignin-degrading activity.     

Systematic study of sequence motifs for RNA trans splicing in Trypanosoma brucei

mRNA maturation in Trypanosoma brucei depends upon trans splicing, and variations in trans-splicing efficiency could be an important step in controlling the levels of individual mRNAs. RNA splicing requires specific sequence elements, including conserved 5' splice sites, branch points, pyrimidine-rich regions [poly(Y) tracts], 3' splice sites (3'SS), and sometimes enhancer elements. To analyze sequence requirements for efficient trans splicing in the poly(Y) tract and around the 3'SS, we constructed a luciferase-beta-galactosidase double-reporter system. By testing approximately 90 sequences, we demonstrated that the optimum poly(Y) tract length is approximately 25 nucleotides. Interspersing a purely uridine-containing poly(Y) tract with cytidine resulted in increased trans-splicing efficiency, whereas purines led to a large decrease. The position of the poly(Y) tract relative to the 3'SS is important, and an AC dinucleotide at positions -3 and -4 can lead to a 20-fold decrease in trans splicing. However, efficient trans splicing can be restored by inserting a second AG dinucleotide downstream, which does not function as a splice site but may aid in recruitment of the splicing machinery. These findings should assist in the development of improved algorithms for computationally identifying a 3'SS and help to discriminate noncoding open reading frames from true genes in current efforts to annotate the T. brucei genome.     

Effects of postexercise supplementation of chicken essence on the elimination of exercise-induced plasma lactate and ammonia

We investigated the effects of chicken essence (CE) supplementation on exercise-induced changes of lactate and ammonia during recovery. In this randomized, double blind, crossover study, twelve healthy subjects performed a single bout of exercise to exhaustion, and then consumed either a placebo or CE within 5-min of the exercise cessation. Blood samples were collected before exercise, at exhaustion (0 minute), and 20, 40, 60, and 120 minutes, respectively during the recovery period. There were no differences in plasma glucose, creatine kinase, or heart rate responses between treatments. The exercise exhaustion significantly increased the levels of lactate and ammonia, and both measured values gradually declined during the recovery period. Ammonia levels at 40, 60, and 120 min. of the recovery period were observed lower significantly in the CE group, as compared to those in the placebo group. Additionally, lactate concentrations at 60 and 120 min were lower in the CE group, as compared to those in the placebo group. In conclusion, the main finding of this study was that CE supplementation after exercise reduces plasma lactate and ammonia levels. The results indicated that CE supplementation after an exhaustive exercise could enhance physiological recovery in humans.     

Identification and characterization of the mouse nuclear export factor (Nxf) family members

TAP/hNXF1 is a key factor that mediates general cellular mRNA export from the nucleus, and its orthologs are structurally and functionally conserved from yeast to humans. Metazoans encode additional proteins that share homology and domain organization with TAP/hNXF1, suggesting their participation in mRNA metabolism; however, the precise role(s) of these proteins is not well understood. Here, we found that the human mRNA export factor hNXF2 is specifically expressed in the brain, suggesting a brain-specific role in mRNA metabolism. To address the roles of additional NXF factors, we have identified and characterized the two Nxf genes, Nxf2 and Nxf7, which together with the TAP/hNXF1's ortholog Nxf1 comprise the murine Nxf family. Both mNXF2 and mNXF7 have a domain structure typical of the NXF family. We found that mNXF2 protein is expressed during mouse brain development. Similar to TAP/hNXF1, the mNXF2 protein is found in the nucleus, the nuclear envelope and cytoplasm, and is an active mRNA export receptor. In contrast, mNXF7 localizes exclusively to cytoplasmic granules and, despite its overall conserved sequence, lacks mRNA export activity. We concluded that mNXF2 is an active mRNA export receptor similar to the prototype TAP/hNXF1, whereas mNXF7 may have a more specialized role in the cytoplasm.     

17beta-estradiol downregulates tissue angiotensin-converting enzyme and ANG II type 1 receptor in female rats

Estrogens have been implicated in both worsening and protecting from cardiovascular disease. The effects of 17beta-estradiol (E2) on the cardiovascular system may be mediated, at least in part, by its modulation of local tissue renin-angiotensin systems (RAS). We assessed two critical components, angiotensin-converting enzyme (ACE) and ANG II type 1 receptor (AT(1)R), in the heart, lung, abdominal aorta, adrenal, kidney, and brain in four groups of female Wistar rats (n = 5-6/group): 1) sham ovariectomized, 2) ovariectomized (OVX) treated with subcutaneous vehicle, 3) OVX treated with 25 mug/day (regular) E2 subcutaneously, and 4) OVX treated with 250 mug/day (high) subcutaneous E2 for 2 or 5 wk. After 2 wk, plasma ACE activity was not altered by OVX, but it was 34-38% lower in OVX + regular E2 and OVX + high E2 rats compared with sham OVX rats, and these decreases were no longer present after 5 wk. After 5 wk, OVX alone increased ACE activity and binding densities, and AT(1)R binding densities by 15-100% in right ventricle, left ventricle (LV), kidney, lung, abdominal aorta, adrenal and several cardiovascular regulatory nuclei in the brain. These effects were, for the most part, prevented by regular E2 replacement and were reversed to decreases by high E2 treatment. This regulation of tissue ACE and AT(1)R is significant as the activity of these tissue RAS contributes to the pathogenesis and/or progression of hypertension, atherosclerosis, and LV remodeling after myocardial infarction.