α - synuclein and Parkinson's disease: the first roadblock

α-synuclein gene mutations are major underlying genetic defects known in familial juvenile onset Parkinson's disease (PD), and α-synuclein is a major constituent of Lewy Bodies, the pathological hallmark of PD. The normal cellular function of α-synuclein has been elusive, and its exact etiological mechanism in causing dopaminergic neuronal death in PD is also not clearly understood. Very recent reports now indicate that mutant or simply over-expressed α-synuclein could cause damage by interfering with particular steps of neuronal membrane traffic. α-synuclein selectively blocks endoplamic reticulum-to-Golgi transport, thus causing ER stress. A screen in a yeast revealed that α-synuclein toxicity could be suppressed by over-expression of the small GTPase Ypt1/Rab1, and that over-expression of the latter rescues neuron loss in invertebrate and mammalian models of α-synuclein-induced neurodegeneration. α-synuclein may also serve a chaperone function for the proper folding of synaptic SNAREs that are important for neurotransmitter release. We discuss these recent results and the emerging pathophysiological interaction of α-synuclein with components of neuronal membrane traffic.     

Environmental margin and island evolution in Middle Eastern populations of the Egyptian fruit bat

Here, we present a study of the population genetic architecture and microevolution of the Egyptian fruit bat (Rousettus aegyptiacus) at the environmental margins in the Middle East using mitochondrial sequences and nuclear microsatellites. In contrast to the rather homogenous population structure typical of cave‐dwelling bats in climax tropical ecosystems, a relatively pronounced isolation by distance and population diversification was observed. The evolution of this pattern could be ascribed to the complicated demographic history at higher latitudes related to the range margin fragmentation and complex geomorphology of the studied area. Lineages from East Africa and Arabia show divergent positions. Within the northwestern unit, the most marked pattern of the microsatellite data set is connected with insularity, as demonstrated by the separate status of populations from Saharan oases and Cyprus. These demes also exhibit a reduction in genetic variability, which is presumably connected with founder effects, drift and other potential factors related to island evolution as site‐specific selection. Genetic clustering indicates a semipermeability of the desert barriers in the Sahara and Arabian Peninsula and a corridor role of the Nile Valley. The results emphasize the role of the island environment in restricting the gene flow in megabats, which is also corroborated by biogeographic patterns within the family, and suggests the possibility of nascent island speciation on Cyprus. Demographic analyses suggest that the colonization of the region was connected to the spread of agricultural plants; therefore, the peripatric processes described above might be because of or strengthened by anthropogenic changes in the environment.     

Transport protein synthesis in non-growing yeast cells

Addition of a metabolizable substrate (glucose, ethanol and, to a degree, trehalose) to non-growing baker's yeast cells causes a boost of protein synthesis, reaching maximum rate 20 min after addition of glucose and 40–50 min after ethanol or trehalose addition. The synthesis involves that of transport proteins for various solutes which appear in the following sequence: H⁺, l-proline, sulfate, l-leucine, phosphate, α-methyl-d-glucoside, 2-aminoisobutyrate. With the exception of the phosphate transport system, the K_t of the synthesized systems is the same as before stimulation. Glucose is usually the best stimulant, but ethanol matches it in the case of sulfate and exceeds it in the case of proline. This may be connected with ethanol's stimulating the synthesis of transport proteins both in mitochondria and in the cytosol while glucose acts on cytosolic synthesis alone. The stimulation is often repressed by ammonium ions (leucine, proline, sulfate, H⁺), by antimycin (proline, trehalose, sulfate, H⁺), by iodoacetamide (all systems tested), and by anaerobic preincubation (leucine, proline, trehalose, sulfate). It is practically absent in a respiration-deficient petite mutant, only little depressed in the op₁ mutant lacking ADP/ATP exchange in mitochondria, but totally suppressed (with the exception of transport of phosphate) in a low-phosphorus strain. The addition of glucose causes a drop in intracellular inorganic monophosphate by 30%, diphosphate by 45%, ATP by 70%, in total amino acids by nearly 50%, in transmembrane potential (absolute value) by about 50%, an increase of high-molecular-weight polyphosphate by 65%, of total cAMP by more than 100%, in the endogenous respiration rate by more than 100%, and a change of intracellular pH from 6.80 to 7.05. Ethanol caused practically no change in ATP, total amino acids, endogenous respiration, intracellular pH or transmembrane potential; a slight decrease in inorganic monophosphate and diphosphate and a sizeable increase in high-molecular-weight polyphosphate. The synthesis of the various transport proteins thus appears to draw its energy from different sources and with different susceptibility to inhibitors. It is much more stimulated in facultatively aerobic species (Saccharomyces cerevisiae, Endomyces magnusii) than in strictly aerobic ones (Rhodotorula glutinis, Candida parapsilosis) where an inhibition of transport activity is often observed after preincubation with metabolizable substrates.     

Zweiter Beitrag zur Flora Montenegro's

Ohne Zusammenfassung     

Linking membrane dynamics and trafficking to autophagy and the unfolded protein response

Cellular stressors typically induce two protective counter‐responses—autophagy and the unfolded protein response (UPR). It is conceivable that these two endoplasmic reticulum (ER) membrane‐based processes would intersect/interact somehow with the constitutive housekeeping process of exocytic membrane traffic from the ER. How exactly might this occur? Recent evidence indicates that a conserved Rab protein, Rab1/Ypt1p, has functional roles in UPR and autophagy. This molecular switch and its associated effectors may therefore serve to link up a network of cellular responses to stress through changes in membrane dynamics and protein turnover. The notion provides further explanations as to why elevation of Rab1/Ypt1p levels could counter the cytotoxicity of α‐synuclein, and a similar mode of protection may well be at work against other stresses. J. Cell. Physiol. 228: 1638–1640, 2013. © 2013 Wiley Periodicals, Inc.     

Short hairpin RNAs against eotaxin or interleukin‐5 decrease airway eosinophilia and hyper‐responsiveness in a murine model of asthma

Background

Eosinophilia plays the major role in the pathogenesis of asthma and correlates with the up‐regulation of eotaxin, which, together with interleukin (IL)‐5, is important for differentiation, chemo‐attraction, degranulation, and survival of eosinophils in local tissue. In a previous study, we found that administration of lentivirus‐delivered short hairpin RNA (shRNA) to suppress the expression of IL‐5 inhibited airway inflammation. The present study aimed to investigate the role of eotaxin shRNA and the synergistic effect of eotaxin and IL‐5 shRNAs on airway inflammation in an ovalbumin (OVA)‐induced murine model of asthma.

Methods

Lentivirus‐delivered shRNAs were used to suppress the expression of eotaxin and/or IL‐5 in local tissue in an OVA‐induced murine asthma model.

Results

Intra‐tracheal administration of lentivirus containing eotaxin shRNA expressing cassette (eoSEC3.3) efficiently moderated the characteristics of asthma, including airway hyper‐responsiveness, cellular infiltration of lung tissues, and eotaxin and IL‐5 levels in bronchio‐alveolar lavage fluid. Administration of lentiviruses expressing IL‐5 or eotaxin shRNAs (IL5SEC4 + eoSEC3.3) also moderated the symptoms of asthma in a mouse model.

Conclusions

Local delivery of lentiviruses expressing IL‐5 and eotaxin shRNAs provides a potential tool in moderating airway inflammation and also has the potential for developing clinical therapy based on the application of shRNAs of chemokines and cytokines involved in T helper 2 cell inflammation and eosinophilia. Copyright © 2008 John Wiley & Sons, Ltd.     

Insect ecology and veteran trees

Insect and veteran trees are important parts of ecosystems and are usually included in ecological studies of forest management. The loss of veteran trees in woodlands and open landscapes would lead to the loss of saproxylic organisms—an important part of biodiversity. Hence, the persistence of many specialized insects depends on the presence of veteran trees scattered in woodlands (e.g. ancient wood pastures, game parks or protected areas), cities, towns and villages (e.g. avenues, parks or chateau parks) or open landscapes (e.g. fishpond dams, solitary trees or fruit orchards). Veteran tree conditions could be fairly well described by three components—diameter, age and microhabitats present. The problem is that diameter belongs to the most studied characteristics, while age and microhabitats, which can be quite complicated to measure, are much less studied. This paper illustrates that, due to this unbalanced use of indicators of veteran-tree conditions, we are still missing some important information on saproxylic species ecology—and sometimes only large trees might be studied, rather than real veterans. Although we already know that veteran trees are essential habitat for a range of saproxylic organisms, there are still gaps in our knowledge of the specific conditions that veteran trees provide. It is vital that these are quantified and understood so that this information can be used to conserve veteran trees and their associated species.     

Activity pattern, smoking habits, and somatometric variables of the Czechoslovakian population

A total of 3762 subjects of both sexes, natives of Czechoslovakia, ranging in age from 12--55 years, were examined. Both anamnestic data and selected anthropometric variables were evaluated. The proportion of non-smokers for adult males was 47--56%, and for adult females was 54--74% of the population. The proportion of subjects not engaged in any type of physical activity decreases in boys between 12 and 18 years from 28 to 16%, in girls between 12 and 15 years from 25 to 22%; from then on the trend reverses and the percentages rises up to 42% in men and 65% in women. The number of subjects participating in competitive sporting activity reaches its peak at 18 years, when 46% of boys annd 43% of girls compete, but then decreases quickly. 12 year old girls are taller and heavier than boys but at 15 years the relationship is reversed. The LBM at the age of 12 is equal in boys and girls, but from then till 18 years the increase is larger in boys. The LBM weight in adults remains steady, women attaining 77% of the value found in men. The skinfold increases with age similarly in both sexes, except for an interval between 12 and 18 years, when girls show a steeper increase. Adult women attain 121--160% of the values characteristic for men. The grip strength of the right hand equals about 50 kp in adult men and 30 kp in adult women. Within the age range followed, it remains unaffected by age.     

Is unconventional secretion inhibited during cell division by Cdk1 activity?

A process of unconventional secretion that is dependent on the Golgi stacking protein GRASP and multiple components of the autophagy machinery has recently been documented for several cytoplasmic and membrane protein. Classical secretion via the exocytic pathway is inhibited during cell division in animal cells, as key membrane compartments, particularly the Golgi, are disassembled and fragmented. The question as to whether unconventional secretion is likewise inhibited during mitosis has not been explored. This mode of secretion supposedly bypasses the Golgi. However, GRASP and Vps34 (a key autophagy protein) are both substrates of the cell cycle regulating cyclin‐dependent kinase 1 (Cdk1), and their activities are apparently inhibited by Cdk1 phosphorylation. Is unconventional secretion therefore similarly inhibited during cell division like conventional secretion? The story may yet turn out to be more complicated. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.