Leukocyte Gene Expression and Plasma Concentration in Multiple Sclerosis: Alteration of Transforming Growth Factor-βs,Claudin-11, and Matrix Metalloproteinase-2

Multiple sclerosis is a neurodegenerative disease characterized by the present of leukocytes in the brain tissue and subsequently the formation of sclerotic plaques. Leukocytes penetration into the blood–brain barrier is related to several factors, such as, the conversion of leukocyte gene expression or plasma characteristics. In this frame, we explore alteration of matrix metalloproteinase-2 (MMP-2), transforming growth factor beta (TGF-β) family, and Claudin-11 (as a main myelin structural protein) in leukocytes and blood plasma of multiple sclerosis patients compared to the normal group. Blood samples were collected from thirteen men affected by MS and fifteen healthy men. Leukocyte gene expression was measured using real-time PCR and plasma parameters were examined by ELISA. The results of this study showed that the gene expression of Claudin-11 was significantly higher in MS group compared with normal. Interestingly, the MMP-2 pattern was similar to Claudin-11 and correlated positively with it. It was observed that, although the expressions of TGF-β1 and TGF-β2 are down-regulated in the leukocytes of subjects with MS, they showed higher levels of these cytokines in blood plasma. The plasma level of TGF-β3 in MS patients was higher than normal and correlated with Claudin-11 concentration. In conclusion, the aberrant pattern of Claudin-11, TGF-βs family, and MMP-2 expression in leukocytes of the MS patients was observed in this study. Moreover, the plasma levels of TGF-βs family increased in the MS group. The findings of this study provide clues for further investigations to assay MS pathogenesis.     

Biogenic Iron Preserves Structures during Fossilization: A Hypothesis

It is hypothesized that iron from biological tissues, liberated during decay, may have played a role in inhibiting loss of anatomical information during fossilization of extinct organisms. Most tissues in the animal kingdom contain iron in different forms. A widely distributed iron-bearing molecule is ferritin, a globular protein that contains iron crystallites in the form of ferrihydrite minerals. Iron concentrations in ferritin are high and ferrihydrites are extremely reactive. When ancient animals are decaying on the sea floor under anoxic environmental conditions, ferrihydrites may initialize the selective replication of some tissues in pyrite FeS₂. This model explains why some labile tissues are preserved, while other more resistant structures decay and are absent in many fossils. A major implication of this hypothesis is that structures described as brains in Cambrian arthropods are not fossilization artifacts, but are instead a source of information on anatomical evolution at the dawn of complex animal life.     

Environmental risk assessment of heavy metals pollution in aquatic ecosystem—A case study: Sediment of Kor River,Iran

A comprehensive investigation of fractionation and environmental risk of nine heavy metals is carried out for 12 sediment samples collected from Kor River, Iran. For this purpose, the 5-stage sequential extraction method, along with individual contamination factor, global contamination factor, and Environmental Risk Index (ERI), is used. Total concentrations of Cr, Hg, Ni, and Zn were found to be beyond the threshold effect level. The results of fractionation patterns indicate that As, Cr, Ni, Pb, and Zn are mostly associated with Fe-Mn oxide fraction, organic fraction, and residual fraction, while Cd and Mo are predominantly associated with carbonate fraction. Cu and Hg are mostly associated with organic and exchangeable fractions. The results of ERI revealed High to Dangerous risks in 40% of Kor River stations. The applied approach in this study is beneficial to other environmental studies that require analysis of complex data.     

MRSA Clonal Complex 22 Strains Harboring Toxic Shock Syndrome Toxin (TSST-1) Are Endemic in the Primary Hospital in Gaza,Palestine

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in both community and healthcare-related settings worldwide. Current knowledge regarding the epidemiology of S. aureus and MRSA in Gaza is based on a single community-based carriage study. Here we describe a cross-sectional analysis of 215 clinical isolates collected from Al-Shifa Hospital in Gaza during 2008 and 2012.

Methods

All isolates were characterized by spa typing, SCCmec typing, and detection of genes encoding Panton-Valentine leukocidin (PVL) and toxic shock syndrome toxin (TSST-1). Representative genotypes were also subjected to multilocus sequence typing (MLST). Antibiotic susceptibility testing was performed using VITEK2 and MicroScan.

Results

MRSA represented 56.3% of all S. aureus strains, and increased in frequency from 2008 (54.8%) to 2012 (58.4%). Aside from beta-lactams, resistance was observed to tetracycline, erythromycin, clindamycin, gentamicin, and fluoroquinolones. Molecular typing identified 35 spa types representing 17 MLST clonal complexes (CC), with spa 998 (Ridom t223, CC22) and spa 70 (Ridom t044, CC80) being the most prevalent. SCCmec types I, III, IV, V and VI were identified among MRSA isolates, while type II was not detected. PVL genes (lukF/S-PV) were detected in 40.0% of all isolates, while the TSST-1 gene (tst) was detected in 27.4% of all isolates, with surprisingly high frequency within CC22 (70.4%). Both PVL and TSST-1 genes were found in several isolates from 2012.

Conclusions

Molecular typing of clinical isolates from Gaza hospitals revealed unusually high prevalence of TSST-1 genes among CC22 MRSA, which is noteworthy given a recent community study describing widespread carriage of a CC22 MRSA clone known as the ‘Gaza strain’. While the latter did not address TSST-1, tst-positive spa 998 (Ridom t223) has been detected in several neighboring countries, and described as endemic in an Italian NICU, suggesting international spread of a ‘Middle Eastern variant’ of pandemic CC22 strain EMRSA-15.     

Twin anchors of the soybean isoflavonoid metabolon: evidence for tethering of the complex to the endoplasmic reticulum by IFS and C4H

Isoflavonoids are specialized plant metabolites, almost exclusive to legumes, and their biosynthesis forms a branch of the diverse phenylpropanoid pathway. Plant metabolism may be coordinated at many levels, including formation of protein complexes, or ‘metabolons’, which represent the molecular level of organization. Here, we have confirmed the existence of the long‐postulated isoflavonoid metabolon by identifying elements of the complex, their subcellular localizations and their interactions. Isoflavone synthase (IFS) and cinnamate 4–hydroxylase (C4H) have been shown to be tandem P450 enzymes that are anchored in the ER, interacting with soluble enzymes of the phenylpropanoid and isoflavonoid pathways (chalcone synthase, chalcone reductase and chalcone isomerase). The soluble enzymes of these pathways, whether localized to the cytoplasm or nucleus, are tethered to the ER through interaction with these P450s. The complex is also held together by interactions between the soluble elements. We provide evidence for IFS interaction with upstream and non‐consecutive enzymes. The existence of such a protein complex suggests a possible mechanism for flux of metabolites into the isoflavonoid pathway. Further, through interaction studies, we identified several candidates that are associated with GmIFS2, an isoform of IFS, in soybean hairy roots. This list provides additional candidates for various biosynthetic and structural elements that are involved in isoflavonoid production. Our interaction studies provide valuable information about isoform specificity among isoflavonoid enzymes, which may guide future engineering of the pathway in legumes or help overcome bottlenecks in heterologous expression.     

Validation of GNE:p.M712T identification by melting curve analysis

Hereditary inclusion body myopathy/distal myopathy with rimmed vacuoles is an adult onset autosomal recessive muscle-wasting disease common in people of Iranian-Jewish descent, due to the founder allelic variant GNE:p.M712T. High correlation of disease susceptibility with GNE:p.M712T allows its use as a molecular marker for diagnosis. In this study, we applied and validated the use of melting curve analysis using SimpleProbe technology for detection of this mutation using specimens obtained by mouthwash, buccal swab, and whole blood. The assay was then applied to 43 clinical specimens, and results were validated by additional methods. A probe spanning this mutation in exon 12 accurately discerns two Tm corresponding to its hybridization to wild-type and M712T-derived amplicons. A 10 degrees C divergence in Tm allowed rapid single-tube genotyping of reference and patient samples with 100% accuracy. Distal myopathy constitutes a large heterogeneous group of pathologies with similar physiological manifestations and little molecular markers for distinguishing subtypes. Application of SimpleProbes for detection of GNE:p.M712T on genomic DNA obtained from buccal epithelial cells allows accurate, rapid, and cost-effective identification of this allele in individuals at risk. This procedure is amenable to automated high-throughput applications and can be extended to both clinical and research applications.     

Feeding ecology of the vulnerable aoudad (Ammotragus lervia) in north-western Sahara

The feeding ecology of the aoudad (Ammotragus lervia) was investigated for the first time in north-western Sahara, Djebel Antar (Bechar province, Algeria), from autumn 2015 to summer 2016. Microhistological analyses of faeces revealed an annual diet composed of 23 identified taxa belonging to 16 plant families. The highest species diversity was recorded in spring and summer (23 species), despite a marked consumption of two species: Vachellia tortilis (17.7%) and Avena sterilis (14.0%); diet diversity was lower in autumn and winter (16 species), including mainly Teucrium polium (14.7%, 21.0%) and Gymnocarpos decander (19.7%, 10.0%). The main plant parts consumed during these seasons were stems (77.7%, 65.3%), while leaves and inflorescences were mostly consumed during spring and summer (54.7%, 52.3%). Forbs dominated the aoudad's diet, with 46.3% average relative abundance, including mainly T. polium, Limoniastrum feei, and Chrysanthemum macrocarpum. Woody plants including mainly V. tortilis and G. decander accounted for 33.3% (50.0% in autumn), and grasses including A. sterilis and H. murinum for 20.4% (32.0% in summer). Based on this diet, A. lervia can be classified as a “generalist mixed-feeder.”     

Inbreeding under a cyclical mating system

Summary General recursion formulae for the coefficient of inbreeding under a cyclical mating system were derived in which one male and one female are selected from each of the n families per generation (population size N = 2 n). Each male is given the family number of his sire in each generation, while his mate comes from another family, varying systematically in different generations. Males of the r-th family in generations 1, 2, 3,..., t = n–1 within each cycle mate with females from families r+1, r+2, r+3,..., r+t to produce generations 2, 3, 4,..., t+1=1, respectively. The change in heterozygosity shows a cyclical pattern of rises and falls, repeating in cycles of n–1 generations. The rate of inbreeding oscillates between <-3% to >6% in different generations within each cycle, irrespective of the population size. The average rate of inbreeding per generation is approximately 1/[4 N-(Log₂N+1)], which is the rate for the maximum avoidance of inbreeding. The average inbreeding effective population size is approximately 2 N–2.     

Therapeutic potency of Wnt signaling antagonists in the pathogenesis of prostate cancer,current status and perspectives

Prostate cancer is a major cause of cancer-related death in males. Wnt/β-catenin signaling plays a critical role in the pathogenesis of this disease by regulating angiogenesis, drug resistance, cell proliferation, and apoptosis. Suppression of Wnt canonical or noncanonical signaling pathways via Wnt biological or pharmacological antagonists is a potentially novel therapeutic approach for patients with prostate cancer. This review summarizes the role of Wnt signaling inhibitors in the pathogenesis of prostate cancer for a better understanding and hence a better management of this disease.