Prevalence of known mutations in the MEFV gene in a population screening with high rate of carriers

The Familial Mediterranean Fever (FMF) shows an autosomal recessive pattern of inheritance and affects certain ethnic groups. Disease is caused by mutations in MEFV gene and more than 180 mutations have been defined in affected individuals. Current study aimed to determine the frequency-type of the mutations for MEFV gene in Sivas??middle Anatolian city. The cohort was composed of 3340 patients. MEFV gene mutations were studied by multiplex PCR based reverse hybridization stripAssay method. Patients?? clinical features were; family history: 68%, erysipelas-like erythema: 17.6%, fever: 89.9%, abdominal pain: 84.2%, peritonitis: 90.2%, arthritis: 33%, pleuritis: 14.2%, parental consanguinity: 21.2%. Current results revealed that M694V is the most frequent mutation (43.12%), followed by E148Q (20.18), M680I(G/C) (15.00%) and V726A (11.32%). The study population has a high rate of carriers and the E148Q mutation frequency was found to be highest when compared to the other regions of Turkey and other Mediterranean groups.     

Association of deep venous thrombosis with prothrombotic gene polymorphism identified in lung cancer cases

Venous thrombosis is a significant cause of morbidity and mortality in patients with malignancies. We aimed to investigate the association between prothrombotic gene polymorphisms detected in lung cancer cases and deep venous thrombosis (DVT). Totally 66 patients with an established diagnosis of lung cancer, of which 33 developed DVT, were enrolled. Multiplex PCR technique and reverse hybridization strip assay were performed on DNA extracted from peripheral blood, in order to analyze prothrombin G20210A, factor V G1691A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, angiotensin converting enzyme (ACE), plasminogen activator inhibitor-1 (PAI-1), and glycoprotein IIIa (Gp IIIa) gene mutations. Among prothrombotic gene polymorphisms investigated in this study, the commonest ones were PAI-1 4G/5G (56% heterozygous, 39% homozygous) and ACE gene mutations (58% heterozygous, 17% homozygous). The presence of homozygous MTHFR A1298C mutation was significantly associated with DVT (P = 0.020). Comparing the lung cancer patients with and without DVT, only MTHFR A1298C gene polymorphism differed significantly (P = 0.040). We determined a higher rate of prothrombotic gene mutations in lung cancer patients who developed DVT. However, statistical significance was achieved only for MTHFR A1298C gene mutation. Therefore, nongenetic factors for disturbance of hemostatic metabolism should also be considered in lung cancer patients.     

Time-dependent changes in the serum levels of prolactin, nesfatin-1 and ghrelin as a marker of epileptic attacks young male patients

A relationship between hormones and seizures has been reported in animals and humans. Therefore, the purpose of this study was to investigate the association between serum levels of prolactin, nesfatin-1 and ghrelin measured different times after a seizure or non-epileptic event and compared with controls. The study included a total of 70 subjects, and of whom 18 patients had secondary generalized epilepsy (SGE), 16 patients had primary generalized epilepsy (PGE), 16 patients exhibited paroxysmal event (psychogenic) and 20 healthy males were control subjects. The first sample was taken within 5 min of a seizure, with further samples taken after 1, 24, and 48 h so long as the patient did not exhibit further clinically observable seizures; blood samples were taken once from control subjects. Prolactin was measured immediately using TOSOH Bioscience hormone assays. Nesfatin-1 and ghrelin peptides were measured using a commercial immunoassay kit. Patients suffering from focal epilepsy with secondary generalization and primary generalized epilepsy presented with significantly higher levels of serum prolactin and nesfatin-1 and lower ghrelin levels 5 min, 1 and 24 h after a seizure than patients presenting with paroxysmal events (psychogenic) and control subjects; the data were similar but not statistically significant after 48 h. The present study suggests that increased serum prolactin and nesfatin-1 concentrations, decreased ghrelin concentrations could be used as markers to identify patients that have suffered a recent epileptic seizure or other paroxysmal event (psychogenic).     

Quorum quenching is an antivirulence strategy employed by endophytic bacteria

Bacteria predominantly use quorum sensing to regulate a plethora of physiological activities such as cell-cell crosstalk, mutualism, virulence, competence, biofilm formation, and antibiotic resistance. In this study, we investigated how certain potent endophytic bacteria harbored in Cannabis sativa L. plants use quorum quenching as an antivirulence strategy to disrupt the cell-to-cell quorum sensing signals in the biosensor strain, Chromobacterium violaceum. We used a combination of high-performance liquid chromatography high-resolution mass spectrometry (HPLC-ESI-HRMSⁿ) and matrix-assisted laser desorption ionization imaging high-resolution mass spectrometry (MALDI-imaging-HRMS) to first quantify and visualize the spatial distribution of the quorum sensing molecules in the biosensor strain, C. violaceum. We then showed, both quantitatively and visually in high spatial resolution, how selected endophytic bacteria of C. sativa can selectively and differentially quench the quorum sensing molecules of C. violaceum. This study provides fundamental insights into the antivirulence strategies used by endophytes in order to survive in their ecological niches. Such defense mechanisms are evolved in order to thwart the plethora of pathogens invading associated host plants in a manner that prevents the pathogens from developing resistance against the plant/endophyte bioactive secondary metabolites. This work also provides evidence towards utilizing endophytes as tools for biological control of bacterial phytopathogens. In continuation, such insights would even afford new concepts and strategies in the future for combating drug resistant bacteria by quorum-inhibiting clinical therapies.     

Signs of deferasirox genotoxicity

Iron overload is a major health problem for patients who have to have continuous blood transfusions. It brings some metabolic problems together. Various iron chelating agents are being used for treatment of hemochromatosis which arises from excess iron accumulation. This study was conducted with the aim of determining whether deferasirox used as an iron chelator in patients with hemochromatosis has genotoxic effects. Commercial form of deferasirox, Exjade was used as test material. Test material showed a general mutagen character in mutant strains of Salmonella typhimurium. Deferasirox has also led to an increase in mutagenity-related polymorphic band count in random amplification of polymorphic DNA test done with bone marrow cells of rats. Similarly, test material has increased micronucleus formation in cultured in vitro human peripheral lymphocytes particularly in 48 h period. Consistently with the abovementioned findings, deferasirox reduced nuclear division index (NDI) compared to controls and some part of these reductions are statistically significant. NDI reductions were found at positive control levels at high concentrations.     

β‐Hydroxyamide‐Based Ligands and Their Use in the Enantioselective Borane Reduction of Prochiral Ketones

Hydroxyamide‐based ligands have occupied a considerable place in asymmetric synthesis. Here we report the synthesis of seven β‐hydroxyamide‐based ligands from the reaction of 2‐hydroxynicotinic acid with chiral amino alcohols and test their effect on the enantioselective reduction of aromatic prochiral ketones with borane in tetrahydofuran (THF). They produce the corresponding secondary alcohols with up to 76% enantiomeric excess (ee) and good to excellent yields (86‐99%). Chirality 26:21–26, 2013. © 2013 Wiley Periodicals, Inc.     

Cryptic habitats and cryptic diversity: unexpected patterns of connectivity and phylogeographical breaks in a Mediterranean endemic marine cave mysid

The marine cave‐dwelling mysid Hemimysis margalefi is distributed over the whole Mediterranean Sea, which contrasts with the poor dispersal capabilities of this brooding species. In addition, underwater marine caves are a highly fragmented habitat which further promotes strong genetic structuring, therefore providing highly informative data on the levels of marine population connectivity across biogeographical regions. This study investigates how habitat and geography have shaped the connectivity network of this poor disperser over the entire Mediterranean Sea through the use of several mitochondrial and nuclear markers. Five deeply divergent lineages were observed among H. margalefi populations resulting from deep phylogeographical breaks, some dating back to the Oligo‐Miocene. Whether looking at the intralineage or interlineage levels, H. margalefi populations present a high genetic diversity and population structuring. This study suggests that the five distinct lineages observed in H. margalefi actually correspond to as many separate cryptic taxa. The nominal species, H. margalefi sensu stricto, corresponds to the westernmost lineage here surveyed from the Alboran Sea to southeastern Italy. Typical genetic breaks such as the Almeria‐Oran Front or the Siculo‐Tunisian Strait do not appear to be influential on the studied loci in H. margalefi sensu stricto. Instead, population structuring appears more complex and subtle than usually found for model species with a pelagic dispersal phase. The remaining four cryptic taxa are all found in the eastern basin, but incomplete lineage sorting is suspected and speciation might still be in process. Present‐day population structure of the different H. margalefi cryptic species appears to result from past vicariance events started in the Oligo‐Miocene and maintained by present‐day coastal topography, water circulation and habitat fragmentation.     

The inhibitory effect of boric acid on hypoxia-regulated tumour-associated carbonic anhydrase IX

Carbonic anhydrases (EC 4.2.1.1) catalyse the reversible hydration of CO₂ into bicarbonate and protons. As a hypoxia-sensitive and tumour-associated isoform, isoform CA IX, is significantly overexpressed in various malignancies, being a validated target for new anticancer/antimetastatic drugs. A multitude of studies has shown that CA IX inhibition decreases cancer cell proliferation and metastasis through pHe/pHi modulation and enhancement of ferroptosis among others. Numerous studies demonstrated increased efficacy of cytotoxic drugs combined with CA inhibitors (CAIs) in various cancer types. We tested the inhibitory effect of boric acid (BA), an inorganic Lewis acid, on CA IX as well as other isoforms (CA I, II, and XII). BA acted as a millimolar in vitro CAI, decreased proliferation of two cancer cell lines, although not strong correlations between the in vitro inhibition and in vivo effects were observed. The mechanism of antiproliferative action of BA should be investigated in more detail.