Huntington’s Disease and Mitochondrial DNA Deletions: Event or Regular Mechanism for Mutant Huntingtin Protein and CAG Repeats Expansion?!

The mitochondrial DNA (mtDNA) may play an essential role in the pathogenesis of the respiratory chain complex activities in neurodegenerative disorders such as Huntington's disease (HD). Research studies were conducted to determine the possible levels of mitochondrial defect (deletion) in HD patients and consideration of interaction between the expanded Huntingtin gene as a nuclear gene and mitochondria as a cytoplasmic organelle. To determine mtDNA damage, we investigated deletions based in four areas of mitochondrial DNA, in a group of 60 Iranian patients clinically diagnosed with HD and 70 healthy controls. A total of 41 patients out of 60 had CAG expansion (group A). About 19 patients did not show expansion but had the clinical symptoms of HD (group B). MtDNA deletions were classified into four groups according to size; 9 kb, 7.5 kb, 7 kb, and 5 kb. We found one of the four-mtDNA deletions in at least 90% of samples. Multiple deletions have also been observed in 63% of HD patients. None of the normal control (group C) showed mtDNA deletions. The sizes or locations of the deletions did not show a clear correlation with expanded CAG repeat and age in our samples. The study presented evidence that HD patients had higher frequencies of mtDNA deletions in lymphocytes in comparison to the controls. It is thus proposed that CAG repeats instability and mutant Htt are causative factor in mtDNA damage.     

Frequencies of apolipoprotein E polymorphism in a healthy Kurdish population from Kermanshah, Iran

The molecular polymorphism displayed by apolipoprotein E (APOE) has been listed as a risk factor for susceptibility to various disorders, such as those associated with lipid metabolism, arteriosclerosis, coronary artery disease (CAD), and Alzheimer disease. To evaluate the role of APOE genotypes as risk factors for Alzheimer disease, CAD, and atherosclerosis in the Kurdish population of Kermanshah, Iran, we studied the frequencies of APOE alleles *2, *3, and *4 and genotypes in 914 healthy Kurdish subjects (514 men and 400 women). The highest frequency of APOE in the Kurdish population was found for APOE*3 (87.87%). The APOE*2 and APOE*4 allele frequencies were 6.66% and 5.45%, respectively. Distribution of APOE genotypes and alleles was not significantly different between male and female subjects (p > 0.05). Interestingly, the order of the frequency of APOE alleles (*3-->*2-->*4) in the Kurdish population was quite different from that reported for most populations in the world (*3-->*4-->*2). The findings of the present study can be used to identify individuals with high risk of CAD and atherosclerosis and suggest a preventive measure to reduce their susceptibility.     

The role of time of food intake on upcoming liver disease in male Wistar rat

Interventions against obesity, are mainly around changing calorie intake and energy expenditure. Recently, some studies focused on the influence of circadian time of food intake on metabolic status. Here, we compare the role of calorie restriction and time restricted feeding followed by high-fat diet started post weaning, First, 52 male Wistarrats (3 weeks old) were divided into two groups: the high-fat diet (HFD, n = 42) and the control group (CON1, n = 11). After 17 weeks, five rats were randomly selected from each group for sample preparation. In the second phase, the animals in HFD group were assigned into four groups (n = 9): (1) 30% calorie restriction (CR), (2) day intermittent fasting (DIF), (3) night intermittent fasting (NIF), (4) adlibitum food intake (AL), (5) remained animal from the first phase control (CON2). Seventeen weeks of HFD started post-weaning did not cause fatty liver but it caused a significant difference in the body and the adipose tissue weight (P0.05). The results showed that longtime HFD did not lead to liver steatosis while the incorrect time of food intake predisposes the animal to the upcoming liver disease. This data indicate a significant role of timing of food intake rather than nutrition composition itself.     

Early Miocene reef- and mudflat-associated gastropods from Makran (SE-Iran)

A new gastropod fauna of Burdigalian (early Miocene) age is described from the Iranian part of Makran. The fauna comprises 19 species and represents three distinct assemblages from turbid water coral reef, shallow subtidal soft-bottom and mangrove-fringed mudflat environments in the northern Indian Ocean. Especially the reef-associated assemblage comprises largely new species. This is explained by the rare occurrence of reefs along the northern margin of the Miocene Indian Ocean and the low number of scientific studies dealing with the region. In terms of paleobiogeography, the fauna corresponds well to coeval faunas from the Pakistani Balochistan and Sindh provinces and the Indian Kathiawar, Kutch and Kerala provinces. During the early Miocene, these constituted a discrete biogeographic unit, the Western Indian Province, which documents the near complete biogeographic isolation from the Proto-Mediterranean Sea. Some mudflat taxa might represent examples of vicariance following the Tethys closure. The fauna also displays little connection with coeval faunas from Indonesia, documenting a strong provincialism within the Indo-West Pacific Region during early Miocene times. Neritopsis gedrosiana sp. nov., Calliostoma irerense sp. nov., Calliostoma mohtatae sp. nov. and Trivellona makranica sp. nov. are described as new species.     

Physiology of Hibernating Larvae of the Pistachio Twig Borer, <Emphasis Type="Italic">Kermania pistaciella</Emphasis> Amsel (Lepidoptera: Tineidae), Collected from Akbari Cultivar of <Emphasis Type="Italic">Pistacia vera</Emphasis> L.

The pistachio twig borer, Kermania pistaciella Amsel (Lepidoptera: Tineidae), a key pest of pistachio trees, is a monovoltine pest living inside the feeding tunnel of pistachio twigs for almost 10 months in a year and overwinters there as last instar larvae. In this study, we measured some physiological parameters of overwintering field collected larvae of the pest. There were no changes in trehalose, glucose, and myo-inositol contents, but there were differences in the levels of total simple sugar and glycogen during overwintering. Total sugar content at the beginning of overwintering (October) was at the lowest level (24.13 mg/g body weight) and reached to the highest level (55.22 mg/g fresh body weight) in November whereas glycogen content was at the highest level (44.05 mg/g fresh body weight) in October and decreased to 18.42 mg/g fresh body weight in November. Decrease in lipid content during the overwintering period was not significant. The highest and lowest levels of protein content were recorded in January and February, respectively. Supercooling points (SCP) of the overwintering larvae were stable and low (ranged between ?17.80 and ?25.10°C) throughout the cold season and no larva survived after SCP determination. The lowest cold hardiness (60 and 0.0% survival following exposure to ?10 and ?20°C/24 h, respectively) was observed for in November-collected larvae. Overwintering larvae of the pistachio twig borer rely mostly on maintaining the high supercooling capacity throughout the overwintering to avoid freezing of their body fluid.     

Matrix metalloproteinase-1 takes advantage of the induced fit mechanism to cleave the triple-helical type I collagen molecule

The collagenases are members of the matrix metalloproteinase family (MMP) that degrade native triple-helical type I collagen. To understand the mechanism by which these enzymes recognize and cleave this substrate, we studied the substrate specificity of a modified form of MMP-1 (FC) in which its active site region (amino acids 212-254) had been replaced with that of MMP-9 (amino acids 395-437). Although this substitution increased the activity of the enzyme toward gelatin and the peptide substrate Mca-PLGL(Dpa)AR-NH2 by approximately 3- and approximately 11-fold, respectively, it decreased the type I collagenolytic activity of the enzyme to 0.13%. The replacement of Gly233, the only amino acid in this region of FC that is conserved in all collagenase family members, with the corresponding Glu residue in MMP-9 resulted in a substantial decrease in the type I collagenolytic activity of the enzyme without affecting its general proteolytic activities. The kinetic parameters of the FC/G233E mutant for the collagen substrate were similar to those of the chimeric enzyme. In addition, substituting Gly233 for Glu in the chimera increased the collagenolytic activity of the enzyme by 12-fold. Interestingly, replacing Glu415 in MMP-9 with Gly, its corresponding residue in FC, endowed the enzyme with type I collagenolytic activity. The catalytic activity of the MMP-9 mutant toward triple-helical type I collagen was 2-fold higher than that of the collagenase chimera. These data in conjunction with the X-ray crystal structure of FC indicate that Gly233 provides the flexibility necessary for the enzyme active site to change conformation upon substrate binding. The flexibility provided by the Gly residue is essential for type I collagenolytic activity.     

Angiotensin-converting enzyme insertion/deletion (rs106180) and angiotensin type 1 receptor A1166C (rs106165) genotypes and psoriasis: Correlation with cellular immunity,lipid profile,and oxidative stress markers

Psoriasis is a chronic inflammatory skin condition and angiotensin-converting enzyme (ACE) is a key circulating enzyme converting angiotensin (Ang) I to the vasoactive peptide Ang II. The exact role of ACE insertion (I)/deletion (D) polymorphism (rs106180) in psoriasis is not clear. We aimed to examine whether the ACE I/D and Ang II type 1 receptor (AT1R) A₁₁₆₆C-polymorphisms (rs106165), lipid profile, and stress oxidative are associated with susceptibility to psoriasis. One hundred patients with psoriasis and 100 sex- and age-matched unrelated healthy controls were recruited for this case-control study. ACE I/D and AT1R A₁₁₆₆C polymorphisms were identified by the polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively, malondialdehyde (MDA) was detected by the high-performance liquid chromatography, serum arylesterase (ARE) activity of paraoxonase and catalase activities were detected by the spectrophotometry, superoxide dismutase (SOD) activity and vascular adhesion protein (VAP)-1 were measured by ELISA. The presence of C allele of AT1R A₁₁₆₆C and I allele of ACE considerably increased the risk of psoriasis by 6.42-fold (P < 0.001). The distribution of II-genotype of ACE was significantly higher in psoriasis patients than in control group and increased the risk of disease by 3.11-times (P = 0.023). The higher levels of MDA in patients and the higher activity of SOD, ARE, and CAT was observed in healthy controls with I/D+I/I-genotype of ACE I/D. This study for the first time demonstrated that the ACE I/D and AT1R A ₁₁₆₆C genes polymorphisms robustly increases the risk of developing psoriasis in population from west of Iran. In addition, these individuals had significantly higher VAP-1 and MDA concentration and lower enzymatic and nonenzymatic antioxidant-status, suggesting that psoriatic patients carrying C allele of AT1R₁₁₆₆ polymorphism may be more susceptible to cardiovascular disease and myocardial infarction compared with A allele.     

In Silico Designing of Peptidomimetics Enhancing Endoribonucleolytic Activities of Acinetobacter MazF Toxin as the Novel Anti-bacterial Candidates

International Journal of Peptide Research and Therapeutics - Acinetobacter infection is one of the main causes of mortality in the patients admitted to the intensive care units (ICUs). Activation...     

Epithelial cytologic atypia in a fine needle aspirate of an invasive thymoma. A case report.

Fine needle aspiration of a superior-anterior mediastinal mass in a 35-year-old man revealed sheets and clusters of epithelial cells intermingled with a few lymphocytes, characteristic of a thymoma. The presence of atypical cytologic features, such as nuclear pleomorphism, large and vesicular nuclei, prominent nucleoli and frequent mitotic figures, in the epithelial cells caused diagnostic confusion with a thymic carcinoma. However, the subsequent clinical and histologic findings were consistent with an invasive epithelial thymoma. The cytologic features in the present case showed that thymoma with intermediate cytology between that of an ordinary thymoma and thymic carcinoma may be encountered in fine needle aspirates of mediastinal tumors. The cytologic differentiation from a carcinoma may be difficult when the degree of epithelial atypia is high. Histologic confirmation is necessary for a definitive diagnosis.