Extra virgin olive oil improves synaptic activity,short‐term plasticity,memory, and neuropathology in a tauopathy model

In recent years, increasing evidence has accumulated supporting the health benefits of extra virgin olive oil (EVOO). Previous studies showed that EVOO supplementation improves Alzheimer's disease (AD)‐like amyloidotic phenotype of transgenic mice. However, while much attention has been focused on EVOO‐mediated modulation of Aβ processing, its direct influence on tau metabolism in vivo and synaptic function is still poorly characterized. In this study, we investigated the effect of chronic supplementation of EVOO on the phenotype of a relevant mouse model of tauopathy, human transgenic tau mice (hTau). Starting at 6 months of age, hTau mice were fed chow diet supplemented with EVOO or vehicle for additional 6 months, and then the effect on their phenotype was assessed. At the end of the treatment, compared with control mice receiving EVOO displayed improved memory and cognition which was associated with increased basal synaptic activity and short‐term plasticity. This effect was accompanied by an upregulation of complexin 1, a key presynaptic protein. Moreover, EVOO treatment resulted in a significant reduction of tau oligomers and phosphorylated tau at specific epitopes. Our findings demonstrate that EVOO directly improves synaptic activity, short‐term plasticity, and memory while decreasing tau neuropathology in the hTau mice. These results strengthen the healthy benefits of EVOO and further support the therapeutic potential of this natural product not only for AD but also for primary tauopathies.     

Correlation between SERT polymorphisms and Venlafaxine response in major depression patients

Major depression (MD) has a complex multifactorial aetiology with genetic and environmental factors contributing to this disorder. As with all antidepressant treatments, there is variability in drug response because of heredity, and this leads us to focus on the genetic polymorphism of the drug’s metabolising transporter genes. The serotonin transporter (5-HTT) gene is a particularly important candidate for genetic involvement in MD disorders owing to its key role in the regulation of serotonergic transmission and is therefore considered an interesting candidate in the mechanism of antidepressant drugs. Here, we studied the associations between genetic polymorphisms in two regions of the 5-HTT gene (5-HTTLPR and VNTR) to understand venlafaxine response. Venlafaxine was found to be effective in MD patients based on their HAM-D and CGI scores (p<0.05). Although the results did not yield a significant difference between the frequencies of the SS, LS, LL, 9/9, 10/10, 12/12 and 10/12 genotypes and venlafaxine response, venlafaxine dose was increased in patients with Stin2.12 and S alleles. These alleles might have a predisposition to mood disorders. Further studies with more patients are required to confirm this clinical association.     

High mobility group box-1 levels in schizophrenia: Potential biomarker of remission phase

Background: Schizophrenia is a chronic mental disorder, characterized byacute exacerbation and remission phases. Immune system has a role in the pathophysiology of schizophrenia. High mobility group box-1 (HMGB-1) is a macrophage secreted protein activating immune cells to produce cytokines. The aim of this study was to evaluate HMGB-1 levels among patients with schizophrenia both in acute exacerbation and remission phases. Methods: Consecutive schizophrenia patients in acute exacerbation and remission phases were enrolled and compared with each other and with age-sex matched healthy subjects. Patients were assessed with the Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression Scale (CGI). Results: Mean HMGB-1 levels were not significantly different in acute exacerbation phase versus remission phase schizophrenia patients (2.139±0.564 g/L vs. 2.326± 0.471 g/L, p=0.335) and both were individually higher than the control group (1.791±0.444 g/L, p=0.05 for acute exacerbation vs control, p=0.002 for remission vs control). In remission phase schizophrenic patients, HMGB-1 levels were positively correlated with Scale For The Assessment of Positive Symptoms (r=0.447, p=0.015) and BPRS (r=0.397, p=0.033) scores and HMGB-1 levels were independently associated with BPRS. Conclusions: Serum HMGB-1 levels were shown to be increased in patients with schizophrenia patients irrespective of phase, there were no differences between patients in acute exacerbation and remission phase in terms of biomarker and HMGB-1 levels were related to symptom severity according to psychiatric scales among patients in remission phase of schizophrenia.     

Time course of hemorheological alterations after heavy anaerobic exercise in untrained human subjects.

The time course of hemorheological alterations was investigated after heavy anaerobic exercise in untrained male human subjects. The Wingate protocol was performed by each subject, and blood lactate, red blood cell (RBC) deformability and aggregation, white blood cell (WBC) activation, and several hematological parameters were investigated during 24 h after the exercise and compared with preexercise values. Compared with the preexercise value, blood lactate level was found to be approximately 10-fold higher immediately after the exercise. There was a transient, significant increment of RBC and WBC counts immediately after exercise that was followed by a decrement of RBC count. There was a second increase of WBC count, accompanied with increased percentages of granulocytes and granulocyte activation, starting 45 min after exercise. RBC deformability was found to be impaired immediately after exercise and remained reduced for at least 12 h; RBC aggregation was also found to be decreased after exercise, with the onset of this decrease delayed by 30 min. The results of this study indicate that a single bout of heavy anaerobic exercise may induce significant hemorheological deterioration lasting for up to 12 h and thus suggest the need to consider such effects in individuals with impaired cardiovascular function.     

Association of interleukin 1beta gene (+3953) polymorphism and severity of endometriosis in Turkish women

Endometriosis is regarded as a complex trait, in which genetic and environmental factors contribute to the disease phenotype. We investigated whether the interleukin (IL) 1beta (+3953) polymorphism is associated with the severity of endometriosis. Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. 118 women were enrolled in the study. 78 women didnot have endometriosis, 6 women had stage I, 3 had stage II, 13 had stage III and 18 had stage IV endometriosis. Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the IL 1beta (+3953) genotype. Frequencies of the IL-1beta (+3953) genotypes in the control group were: CC, 0.397; TT, 0.115; CT, 0.487. Frequencies of the IL-1beta (+3953) genotypes in cases were: CC, 0.375; TT, 0.225; CT, 0.400. We found a 2.22 fold increase in TT genotype in the endometriosis group. However, the difference was not statistically significant (P > 0.05). We also observed an increase in the frequency of IL-1beta (+3953) T allele in the endometriosis group. However, the difference was not statistically significant. We also investigated the association between IL-1beta (+3953) polymorphism and the severity of endometriosis. The frequencies of CC+CT genotypes in stage I, III and IV endometriosis patients were 83.3, 84/6 and 72.2%, respectively; and TT genotypes were 16.7, 15.4 and 27.8%, respectively. We observed a statistically insignificant increase in TT genotype in stage IV endometriosis (P > 0.05). We suggest that IL-1beta (+3953) polymorphism is not associated with endometriosis in Turkish women.     

Comparing interfacial dynamics in protein-protein complexes: an elastic network approach

Background  

The transient, or permanent, association of proteins to form organized complexes is one of the most common mechanisms of regulation of biological processes. Systematic physico-chemical studies of the binding interfaces have previously shown that a key mechanism for the formation/stabilization of dimers is the steric and chemical complementarity of the two semi-interfaces. The role of the fluctuation dynamics at the interface of the interacting subunits, although expectedly important, proved more elusive to characterize. The aim of the present computational study is to gain insight into salient dynamics-based aspects of protein-protein interfaces.     

Antioxidant responses in Phanerochaete chrysosporium exposed to Astrazone Red FBL textile dye

Interest in environmental‐pollutant‐induced oxidative stress and knowledge of the interactions between reactive oxygen species and cellular systems have increased in toxicology and microbial ecology considerably in recent decades. These reactive oxidants are produced by a variety of environmental sources: ionizing radiations, ultraviolet light, redox cycling drugs, hyperoxia, ischemia and redox‐active xenobiotics or during metabolism of environmental pollutants, such as heavy metals in mining industries, dyes in wastewater of textile industries, pesticides and polycyclic hydrocarbons, i.e. foreign materials. In this study, the effect of dye on the antioxidative defence system of Phanerochaete chrysosporium was investigated, and we showed the ability of Phanerochaete chrysosporium to antioxidative response and defence system exposed to Astrazone Red FBL. Catalase, glutathione reductase, glutathione s‐transferase activities and level of glutathione decreased, depending on the period of growth in each exposure to low and high concentration group (20 and 50 ppm) compared with the control group. Copyright © 2012 John Wiley & Sons, Ltd.     

Structural and functional analysis of perforin mutations in association with clinical data of familial hemophagocytic lymphohistiocytosis type 2 (FHL2) patients

Perforin plays a key role in the immune system via pore formation at the target cell membrane in the elimination of virus‐infected and transformed cells. A vast number of observed mutations in perforin impair this mechanism resulting in a rare but fatal disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL2). Here we report a comprehensive in silico structural analysis of a collection of 76 missense perforin mutations based on a proposed pore model. In our model, perforin monomers oligomerize having cyclic symmetry in consistent with previously found experimental constraints yet having flexibility in the size of the pore and the number of monomers involved. Clusters of the mutations on the model map to three distinct functional regions of the perforin. Calculated stability (free energy) changes show that the mutations mainly destabilize the protein structure, interestingly however, A91V polymorphism, leads to a more stable one. Structural characteristics of mutations help explain the severe functional consequences on perforin deficient patients. Our study provides a structural approach to the mutation effects on the perforin oligomerization and impaired cytotoxic function in FHL2 patients.     

Synthesis of alginate‐silica hybrid hydrogel for biocatalytic conversion by β‐glucosidase in microreactor

The organic–inorganic hybrid materials have been used in different fields to immobilize biomolecules since they offer many advantages. The aim of this study was to optimize and characterize the alginate‐silica hybrid hydrogel as a stable and injectable form for microfluidic systems using internal gelation method and increase the stability and activity of immobilized enzyme for biocatalytic conversions as well. Characterization was carried out by scanning electron microscopy, energy dispersive spectroscopy/mapping, Brunauer–Emmett–Teller, Barrett–Joyner–Halenda, and Fourier‐transform infrared spectroscopy analyses, and the shrinkages of monoliths were evaluated. Subsequent to optimizing the enzyme concentration (40 μg), hydrolytic conversion of 4‐nitrophenyl β‐d ‐glucopyranoside (pNPG) was performed to understand the behavior of the bioconversion in the microfluidic system. The yield was 94% which reached the equilibrium at 24 h indicating that the alginate‐silica gel derived microsystem overcome some drawbacks of monolithic systems. Additionally, bioconversion of Ruscus aculeatus saponins was carried out at the same setup in order to obtain aglycon part, which has pharmaceutical significance. Although pure aglycon could not be achieved, an intermediate compound was obtained based on the HPLC analysis. The developed formulation can be utilized for various life science applications.