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The progressive failure of protein homeostasis is a hallmark of aging and a common feature in neurodegenerative disease. As the enzymes executing the final stages of autophagy, lysosomal proteases (or cathepsins) are key contributors to maintenance of protein homeostasis with age. Here, we identify the cysteine-rich granulin peptides as a new class of regulators of lysosomal aspartyl protease activity. Granulins are produced in an age and stress-dependent manner through cleavage of the neurodegenerative disease protein, progranulin. Once liberated, granulins selectively interact with the aspartyl protease ASP-3/cathepsin D to impair enzymatic activity. Consequently, protein homeostasis and lysosome function is disrupted, prompting cells to activate a compensatory transcriptional program. Our results support a model in which granulin production modulates a critical transition between the normal, physiological regulation of protease activity and the impairment of lysosomal function that can occur with age and disease.

Benzene has been emitted from most industrial chemicals and automobile gasoline, environmental and occupational exposure to a wide range of benzene has been observed. The needle trap device is a novel and inprogress exhaustive extraction trap which fluid can pass through it by pump. In this study, NTD consisted of a needle gauge 21 with 10 cm length that’s packed with Carboxen-1000 for adsorbing benzene. Samples were analyzed by gas chromatography coupled with flame ionization detector and peak verification was examined by gas chromatographymass spectrometry. Linear range concentration was 25-2500 ppb and limit of detection; limit of quantitation and bias were 10, 20 ppb and -0.12 respectively. The agreement of atmospheric standards analyzed by the method of this study and OSHA’s method was examined by the Bland-Altman plot. According to this method, the agreement of two sets of data was established. 20 samples were taken to check the applicability of the developed method in a refinery unit. Benzene concentrations were measured in the range of 0.15 to 1.2 ppm. The results showed that needle trap device carboxen-1000 is a reliable and effective approach and more sensitive and powerful technique for the sampling and analysis of low concentration of benzene in the atmosphere.

Background: Clinical manifestations of Strongyloides stercoralis are variable from asymptomatic to hyperinfection and devastating disseminated infections. Hereby, clinical characteristics of a large series of Iranian strongyloidiasis indigenous cases are described. Methods: The records of people referred to the Helminthological Diagnostic La-boratory of School of Public Health, Tehran University of Medical Sciences and School of Medicine, Gilan University of Medical Sciences, during 2009-2013 were reviewed. For those patients that were infected with S. stercoralis and their clinical manifestations and demographic data were available (70 cases) a checklist was pre-pared and data analyzed. Results: Forty-three patients (61.4%) were male and 27 (38.6%) female. Gastroin-testinal, cutaneous and pulmonary symptoms were present in 71.4%, 25.7%, and 15.7% of patients, respectively. None of them had larva currens eruption. Eosino-philia was the most prevalent reason for suspicious on S. stercoralis, but the mean was lower in elderly patients. Hyperinfection were recorded in 8 patients (11.4%), and 2 cases had disseminated infection. Conclusion: Eosinophilia is common both in asymptomatic and symptomatic cas-es of strongyloidiasis, but the mean tend to lower with increase in age.

© Lemieux and Ashrafi. The abnormal accumulation of fat increases the lifespans of nematodes that lack sex cells.

Individual metazoan transcription factors (TFs) regulate distinct sets of genes depending on cell type and developmental or physiological context. The precise mechanisms by which regulatory information from ligands, genomic sequence elements, co-factors, and post-translational modifications are integrated by TFs remain challenging questions. Here, we examine how a single regulatory input, sumoylation, differentially modulates the activity of a conserved C. elegans nuclear hormone receptor, NHR-25, in different cell types. Through a combination of yeast two-hybrid analysis and in vitro biochemistry we identified the single C. elegans SUMO (SMO-1) as an NHR-25 interacting protein, and showed that NHR-25 is sumoylated on at least four lysines. Some of the sumoylation acceptor sites are in common with those of the NHR-25 mammalian orthologs SF-1 and LRH-1, demonstrating that sumoylation has been strongly conserved within the NR5A family. We showed that NHR-25 bound canonical SF-1 binding sequences to regulate transcription, and that NHR-25 activity was enhanced in vivo upon loss of sumoylation. Knockdown of smo-1 mimicked NHR-25 overexpression with respect to maintenance of the 3° cell fate in vulval precursor cells (VPCs) during development. Importantly, however, overexpression of unsumoylatable alleles of NHR-25 revealed that NHR-25 sumoylation is critical for maintaining 3° cell fate. Moreover, SUMO also conferred formation of a developmental time-dependent NHR-25 concentration gradient across the VPCs. That is, accumulation of GFP-tagged NHR-25 was uniform across VPCs at the beginning of development, but as cells began dividing, a smo-1-dependent NHR-25 gradient formed with highest levels in 1° fated VPCs, intermediate levels in 2° fated VPCs, and low levels in 3° fated VPCs. We conclude that sumoylation operates at multiple levels to affect NHR-25 activity in a highly coordinated spatial and temporal manner. © 2013 Ward et al.

Background: The protozoan parasites Cryptosporidium spp. and Giardia are known to occur widely in both raw and drinking waters. They are two of the causative agents of waterborne out-breaks of gastroenteritis throughout the world. In the present study, a PCR assay and FA were developed for detection of Cryptosporidium oocysts and Giardia cyst in environmental samples. Methods: We have detected Cryptosporidium spp. oocysts and Giardia cysts in seeded and un-seeded environmental water samples by PCR method. Water samples were spiked with oocysts (50, 100,300,500) and filtrated with a 1.2-µm pore size cellulose nitrate and follow by DNA extrac¬tion and purification by QIAamp DNA mini kit. Nested-PCR assay amplified an 850 bp fragment of 18s rRNA gene specific for Cryptosporidium and 435 bp fragment of glutamate dehydrogenase (GDH) target gene for Giardia. Also many river water from north of Iran, be checked by these methods. Results: Cryptosporidium and Giardia DNAs were detected in seeded water sample and Giardia was detected in all 5 water samples from river in north of Iran by nested- PCR and FA. Also in one river water sample, Cryptosporidium was detected. Conclusion: This protocol is effective for detection of these waterborne parasites in treated and untreated water samples. This study can also serve as a platform for further investigations and research water source in Iran.

Background: Human fascioliasis is an important health problem in the province of Gilan, at the Caspian Sea, Iran. There is the overlapping of both fasciolid species, Fasciola hepatica and F. gigantica. Recent studies on both domestic animal and lym­naeid infection furnished evidence suggesting that F. gigantica and Radix gedrosiana may be the main fasciolid and lym­naeid involved in the disease in that province, controversy still being there concerning the presence and importance of F. hepatica and other lymnaeid species. The present paper includes the results of studies on Galba truncatula and the first find­ing of natural infection by F. hepatica in Gilan proved by molecular studies. Methods: Snail collections were carried out in summer, when their populations present the highest densities. Surveys on lym­naeids furnished the finding of a lymnaeid snail infected by trematode rediae and cercariae in the mountains of Talesh, in the Asalem district, western Gilan. Results: Nuclear ribosomal DNA ITS-2 sequences proved that they were F. hepatica and G. truncatula. The liver fluke ITS-2 sequence was identical to that of F. hepatica from Spain and the Northern Bolivian Altiplano and that of G. trunca­tula to the haplotype H-2 known in Portugal, Spain, France and The Netherlands. Conclusion: This genetic characterization sug­gests that both may be also involved in human fascioliasis infection in Gilan.&nbsp

Background: We aimed to determine the status of strongyloidiasis in mentally disabled population in the institutional places in Rasht City, the capital of Guilan Province, northern Iran. Methods: This cross-sectional study was conducted in 8 institutions for mentally retarded population in Rasht in 2013. Before collecting the samples, a questionnaire was filled out for each participant by an expert person. A single stool sample was obtained from each of the 173 subjects and examined using direct wet mount, formalin-ether concentration technique and agar plate culture method. Results: A total of 173 mentally disabled individuals aged 2-57 (25.69±11.56) yr old were studied. Stool examination showed that 51 (29.5%) cases were infected with at least one parasite. Of 173 studied cases only 10 (5.8%) individuals were infected with pathogenic parasites, of which 2 (1.2%) cases were infected with Strongyloides stercoralis and 8 (4.6%) with Giardia lamblia. On the other hand, 42 (24.3%) of the studied population were infected with non-pathogenic intestinal protozoa such as Blastocystis hominis (n=29, 16.8%), Entamoeba coli (n=16, 9.2%) and Endolimax nana (n=4, 2.3%). Mixed protozoal infections were observed in 8 (4.6%) individuals. Conclusion: The prevalence rate of S. stercoralis in mentally disabled individuals in Rasht was somewhat higher than those of normal population of the province. The same picture was seen when the prevalence of G. lamblia and non-pathogenic protozoa in normal and mentally disabled populations were compared.

Following the occurrence of two large outbreaks in Gilan province, northern Iran, the public health importance of human fascioliasis has increased significantly. The mixed infections of Fasciola gigantica and F. hepatica within a given domestic animal individual suggest a very complicate picture of possible circulation ways of the parasite and the possibility for humans to be infected with both species. Elucidating these circulation ways is very critical for understanding the epidemiology and transmission of the disease and being ascertain how animals and humans enter the different liver fluke circulations in this endemic zone. The main objective of the present study was to investigate the distribution and natural infections of local lymnaeids, environmental characteristics related to the disease transmission and determining the most prevalent fasciolids and definitive hosts in human endemic areas of Gilan province. Bandar-Anzali and Rasht are the most important endemic areas with most of the cases of human disease during the epidemics and inter-epidemic periods. Sheep raising is not normal in these regions, while cattle is the most common definitive host. According to the data obtained from slaughterhouse observations in Bandar-Anzali and Rasht, the main fasciolid in local cattle is F. gigantica. Of 928 adult liver flukes collected from 13 infected livers of cattle, in Rasht and Bandar-Anzali slaughterhouses, 91.1% were diagnosed as F. gigantica and 8.9% as F. hepatica. L. gedrosiana and L. palustris were the most prevalent lymnaeid snails in this endemic zone. It appears that L. truncatula is not prevalent in Bandar-Anzali and Rasht and surroundings of these endemic cities. Of 4830 different snails studied, only seven L. gedrosiana were found to be infected with larval stages (rediae and cercariae) of Fasciola sp. Experimental infections of 15 common laboratory mice by metacercariae, obtained from those naturally infected snails, were carried out and all trematodes recovered at necropsy, 8 weeks post-exposure, appeared to be F. gigantica based on morphology. The high temperature, moisture and rainfall during the year, especially in Bandar-Anzali, support the establishment and transmission of the disease in the zone. Although the species involved in human infections in endemic areas of Gilan has been usually referred to as F. hepatica, the results of this study as well as some interesting epidemiological evidences related to the disease, support that Fasciola gigantica might be the main causal agent of fascioliasis in this important endemic zone.

BACKGROUND AND OBJECTIVE: Allium latifolium has polyphenolic compounds with power antioxidant properties which reduce serum lipids. Phosphatidate phosphohydrolase (PAP) is a key enzyme in controlling the synthesis of glycerophospholipids. The aim of this study was to determine the effect of the hydroalcoholic extract of Allium latifolium on the liver PAP and serum lipid profile in hyperlipidemic rats.METHODS: In this experimental study, 40 male rats were randomly divided into 5 groups (8 in each group). Group I (normal) received standard diet, group II received cholesterol and oil diet (without treatment group), and groups III and IV were the rats which received cholesterol (Chol) and oil plus 150 and 300 mg/kg bw Allium latifolium extract, respectively. Group V were the rats which received cholesterol and oil diet plus 30 mg/kg bw gemfibrozyl. At the end of the study, liver PAP activity, liver triglycerides (TG) and cholesterol, and serum lipoprotein levels were determined and compared. FINDINGS: In group II, liver PAP activity showed a significant reduction (p