The Central Theme of Parkinson’s Disease: α-Synuclein

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, defined by the presence of resting tremor, muscular rigidity, bradykinesia, and postural instability. PD is characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta of the midbrain. The neuropathological hallmark of the disease is the presence of intracytoplasmic inclusions, called Lewy bodies (LBs) and Lewy neurites (LNs), containing α-synuclein, a small protein which is widely expressed in the brain. The α-synuclein gene, SNCA, is located on chromosome 4q22.1; SNCA-linked PD shows an autosomal dominant inheritance pattern with a relatively early onset age, and it usually progresses rapidly. Three missense mutations, A53T, A30P, and E46K, in addition to gene multiplications of the SNCA have been described so far. Although it is clear that LBs and LNs contain mainly the α-synuclein protein, the mechanism(s) which leads α-synuclein to accumulate needs to be elucidated. The primary question in the molecular pathology of PD is how wild-type α-synuclein aggregates in PD, and which interacting partner(s) plays role(s) in the aggregation process. It is known that dopamine synthesis is a stressfull event, and α-synuclein expression somehow affects the dopamine synthesis. The aberrant interactions of α-synuclein with the proteins in the dopamine synthesis pathway may cause disturbances in cellular mechanisms. The normal physiological folding state of α-synuclein is also important for the understanding of pathological aggregates. Recent studies on the α-synuclein protein and genome-wide association studies of the α-synuclein gene show that PD has a strong genetic component, and both familial and idiopathic PD have a common denominator, α-synuclein, at the molecular level. It is clear that the disease process in Parkinson’s disease, as in other neurodegenerative disorders, is very complicated; there can be several different molecular pathways which are responsible for diverse and possibly also unrelated functions inside the neuron, playing roles in PD pathogenesis.     

Lipid rafts control human melanoma cell migration by regulating focal adhesion disassembly

Tumor cell migration is a crucial step in the metastatic cascade, and interruption of this step is considered to be logically effective in preventing tumor metastasis. Lipid rafts, distinct liquid ordered plasma membrane microdomains, have been shown to influence cancer cell migration, but the underlying mechanisms are still not well understood. Here, we report that lipid rafts regulate the dynamics of actin cytoskeleton and focal adhesion in human melanoma cell migration. Disrupting the integrity of lipid rafts with methyl-β cyclodextrin enhances actin stress fiber formation and inhibits focal adhesion disassembly, accompanied with alterations in cell morphology. Furthermore, actin cytoskeleton, rather than microtubules, mediates the lipid raft-dependent focal adhesion disassembly by regulating the dephosphorylation of focal adhesion proteins and the internalization of β3 integrin. We also show that Src–RhoA–Rho kinase signaling pathway is responsible for lipid raft disruption-induced stress fiber formation. Taken together, these observations provide a new mechanism to further explain how lipid rafts regulate the migration of melanoma cell and suggest that lipid rafts may be novel and attractive targets for cancer therapy.     

Length–weight relationships of freshwater fishes from the western part of Anatolia,Turkey

Length–weight relationships were calculated for nine freshwater fish species belonging to two families using 1020 specimens from 15 water sources in the western part of Anatolia, Turkey. This study is the first reference on length–parameters for these species, eight of which are endemic, and with new maximum length records for three of the species.     

Large-scale biomedical ontology matching with ServOMap

The proliferation of biomedical applications, which rely on different knowledge organization systems, such as ontologies and thesauri raises the issue of the automated identification of the correspondences between these models, in particular for the data integration need. A significant effort has been conducted for tackling this issue of ontology alignment. However, few systems are able to deal with ontologies containing tens of thousands of entities, as it may be the case in the biomedical domain where resources such as SNOMED-CT, the FMA or the NCI thesaurus are commonly used. We present in this paper ServOMap, an efficient system for large-scale ontology alignment. It relies on an Ontology Server (ServO) and uses Information Retrieval techniques for computing similarity between entities. The system participated with two configurations in the 2012 Ontology Alignment Evaluation Initiative campaign. We report the very promising results obtained by the system for large biomedical ontologies alignment. ServOMap is freely available for download at http://code.google.com/p/servo/.     

Variations in enzyme activity in stomach and pancreatic tissue and digesta in piglets around weaning

A study was performed to investigate the effect of weaning at 4 weeks of age on the activity of digestive enzymes in the stomach and pancreatic tissue and in digesta from 3 days prior to weaning to 9 days postweaning in 64 piglets. In stomach tissue the activity of pepsin and gastric lipase was determined. Pepsin activity declined abruptly after weaning but 5 days postweaning the weaning level was regained and in the gastric contents no change in pepsin activity was observed. Weaning did not influence the activity of gastric lipase. The activity of eight enzymes and a cofactor was measured in pancreatic tissue. The effect of weaning on the enzyme activity was highly significant for all enzymes except elastase. The activity of all enzymes remained at the weaning level during day 1–2 postweaning followed by a reduction of the activity. The activity of trypsin, carboxypeptidase A, amylase and lipase exhibited minimum activity 5 days postweaning. Trypsin activity increased to the preweaning level on day 7–9 whereas the activity of the others increased but did not reach the preweaning level. The activity of chymotrypsin, carboxypeptidase B and carboxyl ester hydrolase decreased during the entire experimental period. In digesta no effect of weaning was observed on the activity of amylase and trypsin. The activity of chymotrypsin was reduced after weaning in the proximal third of the small intestine and lipase and carboxyl ester hydrolase activity was reduced in the middle and distal parts of the small intestine after weaning. The present study shows that the activities of the digestive enzymes in the pancreatic tissue are affected by weaning. Even though the pancreatic secretion cannot be judged from these results they show that the enzymes respond differently to weaning. In general the activity of the digestive enzymes in pancreatic tissue is low on day 5 postweaning which in interaction with other factors may increase the risk of developing postweaning diarrhoea.     

Perceptual Learning of Interrupted Speech

The intelligibility of periodically interrupted speech improves once the silent gaps are filled with noise bursts. This improvement has been attributed to phonemic restoration, a top-down repair mechanism that helps intelligibility of degraded speech in daily life. Two hypotheses were investigated using perceptual learning of interrupted speech. If different cognitive processes played a role in restoring interrupted speech with and without filler noise, the two forms of speech would be learned at different rates and with different perceived mental effort. If the restoration benefit were an artificial outcome of using the ecologically invalid stimulus of speech with silent gaps, this benefit would diminish with training. Two groups of normal-hearing listeners were trained, one with interrupted sentences with the filler noise, and the other without. Feedback was provided with the auditory playback of the unprocessed and processed sentences, as well as the visual display of the sentence text. Training increased the overall performance significantly, however restoration benefit did not diminish. The increase in intelligibility and the decrease in perceived mental effort were relatively similar between the groups, implying similar cognitive mechanisms for the restoration of the two types of interruptions. Training effects were generalizable, as both groups improved their performance also with the other form of speech than that they were trained with, and retainable. Due to null results and relatively small number of participants (10 per group), further research is needed to more confidently draw conclusions. Nevertheless, training with interrupted speech seems to be effective, stimulating participants to more actively and efficiently use the top-down restoration. This finding further implies the potential of this training approach as a rehabilitative tool for hearing-impaired/elderly populations.     

Cardioprotective Effects of a Novel Hydrogen Sulfide Agent–Controlled Release Formulation of S-Propargyl-Cysteine on Heart Failure Rats and Molecular Mechanisms

Objective

Heart failure (HF) is one of the most serious diseases worldwide. S-propargyl-cysteine (SPRC), a novel modulator of endogenous hydrogen sulfide, is proved to be able to protect against acute myocardial ischemia. In order to produce more stable and sustainable hydrogen sulfide, we used controlled release formulation of SPRC (CR-SPRC) to elucidate possible cardioprotective effects on HF rats and investigate involved mechanisms on apoptosis and oxidation.

Methods

Left coronary artery was occluded to induce HF model of rat. The survival rats were randomly divided into 7 groups after 24 hours and treated with drugs for 6 weeks. Echocardiographic indexes were recorded to determine cardiac function. TTC staining was performed to determine infarct size. Plasmatic level of hydrogen sulfide was detected by modified sulfide electrode. Activity of enzyme and expression of protein were determined by colorimetry and Western blot, respectively.

Results

The cardioprotective effects of CR-SPRC on HF rats were confirmed by significant reduction of infarct size and improvement of cardiac function, with better effects compared to normal SPRC. CR-SPRC modulated antioxidant defenses by preserving levels of GSH, CAT and SOD and reducing CK leakage. In addition, CR-SPRC elevated ratio of Bcl-2/Bax and inhibited activity of caspases to protect against myocardial apoptosis. The cardioprotective effects of CR-SPRC were mediated by hydrogen sulfide.

Conclusions

All experiment data indicated cardioprotective effects of CR-SPRC on HF rats. More importantly, CR-SPRC exerted better effects than normal SPRC in all respects, providing a new perspective on hydrogen sulfide-mediated drug therapy.     

Chemical Composition and Biological Activity of Centaurea baseri: New Species from Turkey

The genus Centaurea L. is one of the largest and important genera of Asteraceae family. Centaurea species have been widely used as herbal remedies in folk medicine for their antidandruff, antidiarrheic, antirheumatic, anti‐inflammatory, choleretic, diuretic, digestive, stomachic, astringent, antipyretic, cytotoxic, and antibacterial properties. Centaurea baseri Kose & Alan is a recently described local endemic species in Turkey and this is the first study on the chemical composition and bioactivity of its hydrodistilled essential oil and the crude extract. According to chromatospectral analysis, hexadecanoic acid (42.3%), nonacosane (8.2%), and heptacosane (8.0%) were the main compounds of the essential oil, while 16 compounds were determined in the MeOH extract using LC/MS. Furthermore, antimicrobial, antioxidant, and cytotoxic effects of the essential oil and the extract were evaluated in comparison with the standard agents. The extract showed strong antifungal effect against Candida utilis at the concentration of 60 μg/ml (MIC) where the EO showed growth inhibition at the concentration of 47.00 μg/ml (MIC) against pathogen Bacillus cereus. Both the essential oil and the extract did not show any selective antioxidant properties. The extract showed remarkably selective cytotoxic properties against MCF‐7, PANC‐1, A549, and C6 glioma cells.     

Molecular and iridescent feather reflectance data reveal recent genetic diversification and phenotypic differentiation in a cloud forest hummingbird

The present day distribution and spatial genetic diversity of Mesoamerican biota reflects a long history of responses to habitat change. The hummingbird Lampornis amethystinus is distributed in northern Mesoamerica, with geographically disjunct populations. Based on sampling across the species range using mitochondrial DNA (mtDNA) sequences and nuclear microsatellites jointly analysed with phenotypic and climatic data, we (1) test whether the fragmented distribution is correlated with main evolutionary lineages, (2) assess body size and plumage color differentiation of populations in geographic isolation, and (3) evaluate a set of divergence scenarios and demographic patterns of the hummingbird populations. Analysis of genetic variation revealed four main groups: blue‐throated populations (Sierra Madre del Sur); two groups of amethyst‐throated populations (Trans‐Mexican Volcanic Belt and Sierra Madre Oriental); and populations east of the Isthmus of Tehuantepec (IT) with males showing an amethyst throat. The most basal split is estimated to have originated in the Pleistocene, 2.39–0.57 million years ago (MYA), and corresponded to groups of populations separated by the IT. However, the estimated recent divergence time between blue‐ and amethyst‐throated populations does not correspond to the 2‐MY needed to be in isolation for substantial plumage divergence, likely because structurally iridescent colors are more malleable than others. Results of species distribution modeling and Approximate Bayesian Computation analysis fit a model of lineage divergence west of the Isthmus after the Last Glacial Maximum (LGM), and that the species’ suitable habitat was disjunct during past and current conditions. These results challenge the generality of the contraction/expansion glacial model to cloud forest‐interior species and urges management of cloud forest, a highly vulnerable ecosystem to climate change and currently facing destruction, to prevent further loss of genetic diversity or extinction.