Regulation of polarised growth in fungi

Polarised growth in fungi occurs through the delivery of secretory vesicles along tracks formed by cytoskeletal elements to specific sites on the cell surface where they dock with a multiprotein structure called the exocyst before fusing with the plasmamembrane. The budding yeast, Saccharomyces cerevisiae has provided a useful model to investigate the mechanisms involved and their control. Cortical markers, provided by bud site selection pathways during budding, the septin ring during cytokinesis or the stimulation of the pheromone response receptors during mating, act through upstream signalling pathways to localise Cdc24, the GEF for the rho family GTPase, Cdc42. Cdc42 in its GTP-bound activates a multiprotein protein complex called the polarisome which nucleates actin cables along which the secretory vesicles are transported to the cell surface. Hyphae can elongate at a rate orders of magnitude faster than the extension of a yeast bud, so understanding hyphal growth will require substantial modification of the yeast paradigm. The rapid rate of hyphal growth is driven by a structure called the Spitzenkörper, located just behind the growing tip and which is rich in secretory vesicles. It is thought that secretory vesicles are delivered to the apical region where they accumulate in the Spitzenkörper. The Spitzenkörper then acts as vesicle supply centre in which vesicles exit the Spitzenkörper in all directions, but because of its proximity, the tip receives a greater concentration of vesicles per unit area than subapical regions. There are no obvious equivalents to the bud site selection pathway to provide a spatial landmark for polarised growth in hyphae. However, an emerging model is the way that the site of polarised growth in the fission yeast, Schizosaccharomyces pombe, is marked by delivery of the kelch repeat protein, Tea1, along microtubules. The relationship of the Spitzenkörper to the polarisome and the mechanisms that promote its formation are key questions that form the focus of current research

Condition of the excretory function of pancreas and microbiocenosis of a large intestine in patients with chronic pancreatitis in the dependence of severity of the course of the disease

The aim of the research is the analysis of the excretory function of pancreas and microbiocenosis of a large intestine in patients with alcoholic and biliary chronic pancreatitis in the dependence of severity of the course of the disease. 96 patients were examined during the research work. Traditional clinical laboratory methods were used, and the excretory function and the microbiocenosis of the intestine were studied. According of the M-ANNHEIM mark scale, patients with alcoholic chronic pancreatitis had a moderate and medium severity degree of the disease, patients with biliary chronic pancreatitis had a minimal severity. The decrease of the level of elastase-1 in the feces and the amylase in the urine were in patients with severe course of the disease. The invert moderate correlation was set between the severity degree and the level of elastase-1 and the moderate direct connection was established between the severity degree and the level of the amylase in the urine. Disbiotic disorders were revealed in 92,3 % of patients. The results of bacteriologic research coincided with the data of gas-liquid chromatography test. Disbiotic disorders were more apparent in patients with the severe course of the disease.Цель исследования - анализ экскреторной функции поджелудочной железы и микробиоценоза толстой кишки у больных алкогольным и билиарнозависимым хроническим панкреатитом в зависимости от степени тяжести заболевания. Проведено комплексное обследование 96 больных. Использованы традиционные клинико-лабораторные методы, изучена также экскреторная функция и микробиоценоз кишечника. В соответствии с бальной шкалой оценки M-ANNHEIM у больных алкогольным хроническим панкреатитом преобладали умеренная и средняя степени тяжести заболевания, с билиарнозависимым - минимальная. Снижение уровня эластазы-1 в кале и повышение - амилазы в моче чаще наблюдали при тяжелом течении. Дисбиотические нарушения выявили в 92,3% случаев. Результаты бактериологического обследования как правило совпадали с данными газожидкостной хроматографии. Алкогольная форма хронического панкреатита отличалась более тяжелым течением. Между степенью тяжести и уровнем эластазы-1 установлена обратная умеренная коррелятивная связь, - амилазы в моче - умеренная прямая. Дисбиотические нарушения более выражены на фоне тяжелого течения

Glutamine Acts as a Neuroprotectant against DNA Damage, Beta-Amyloid and H2O2-Induced Stress

Glutamine is the most abundant free amino acid in the human blood stream and is ‘conditionally essential’ to cells. Its intracellular levels are regulated both by the uptake of extracellular glutamine via specific transport systems and by its intracellular synthesis by glutamine synthetase (GS). Adding to the regulatory complexity, when extracellular glutamine is reduced GS protein levels rise. Unfortunately, this excess GS can be maladaptive. GS overexpression is neurotoxic especially if the cells are in a low-glutamine medium. Similarly, in low glutamine, the levels of multiple stress response proteins are reduced rendering cells hypersensitive to H2O2, zinc salts and DNA damage. These altered responses may have particular relevance to neurodegenerative diseases of aging. GS activity and glutamine levels are lower in the Alzheimer's disease (AD) brain, and a fraction of AD hippocampal neurons have dramatically increased GS levels compared with control subjects. We validated the importance of these observations by showing that raising glutamine levels in the medium protects cultured neuronal cells against the amyloid peptide, Aβ. Further, a 10-day course of dietary glutamine supplementation reduced inflammation-induced neuronal cell cycle activation, tau phosphorylation and ATM-activation in two different mouse models of familial AD while raising the levels of two synaptic proteins, VAMP2 and synaptophysin. Together, our observations suggest that healthy neuronal cells require both intracellular and extracellular glutamine, and that the neuroprotective effects of glutamine supplementation may prove beneficial in the treatment of AD

The Tomato yellow leaf curl virus V2 protein forms aggregates depending on the cytoskeleton integrity and binds viral genomic DNA

International audienc

Design and synthesis of novel non-nucleoside anti-HCMV agents [Abstract]

Bicyclic furanopyrimidines are potent and selective inhibitors of Varicella Zoster Virus (VZV) (McGuigan et al., 1999). SAR studies have shown 2′,3′-dideoxynucleoside derivatives to be poorly VZV-active but exhibit activity against human cytomegalovirus (HCMV) (McGuigan et al., 2004). Phosphorylation was shown not to be a requisite for activity presenting the possibility to introduce non-sugar moieties. Many long chain N- and O-alkylated derivatives have been presented, some showing comparable activity to ganciclovir (GCV) supporting a non-nucleoside meachanism of action (Kelleher et al., 2005 and Adak et al., 2007). The target structures were prepared by the Pd-catalysed coupling of various alkynes with 5-iodouracil (Scheme 1), to give intermediate 5-alkynyl nucleosides which were subsequently cyclised in the presence of CuI to give the bicyclic systems. The corresponding bases were then reacted with a selection of alkylating agents to form N- and O-alkylated products. The synthesis, biological evaluation and cytotoxicity of novel long chain N- and O-alkylated derivatives will be presented