Age-related regulation of excitation–contraction coupling in rat heart

Hearts from subjects with different ages have different Ca²⁺ signaling. Release of Ca²⁺ from intracellular stores in response to an action potential initiates cardiac contraction. Both depolarization-stimulated and spontaneous Ca²⁺ releases, Ca²⁺ transients and Ca²⁺ sparks, demonstrate the main events of excitation–contraction coupling (ECC). Global increase in free Ca²⁺ concentration ([Ca²⁺] _i ) consists of summation of Ca²⁺ release events in cardiomyocytes. Since the Ca²⁺ flux induced by Ca²⁺ sparks reports a summation of ryanodine-sensitive Ca²⁺ release channels (RyR2s)’s behavior in a spark cluster, evaluation of the properties of Ca²⁺ sparks and Ca²⁺ transients may provide insight into the role of RyR2s on altered heart function between 3-month-old (young adult) and 6-month-old (mature adult) rats. Basal [Ca²⁺] _i and Ca²⁺ sparks frequency were significantly higher in mature adult rats compared to those of young adults. Moreover, amplitudes of Ca²⁺ sparks and Ca²⁺ transients were significantly smaller in mature adults than those of young adults with longer time courses. A smaller L-type Ca²⁺ current density and decreased SR Ca²⁺ load was observed in mature adult rats. In addition, RyR2s were markedly hyperphosphorylated, and phosphorylation levels of PKA and CaMKII were higher in heart from mature adults compared to those of young adults, whereas their SERCA protein levels were similar. Our data demonstrate that hearts from rats with different ages have different Ca²⁺ signaling including hyperphosphorylation of RyR2s and higher basal [Ca²⁺] _i together with increased oxidized protein-thiols in mature adult rats compared to those of young adults, which play important roles in ECC. Finally, we report that ECC efficiency changes with age during maturation, partially related with an increased cellular oxidation level leading to reduced free protein-thiols in cardiomyocytes.     

Are HIV Epidemics among Men Who Have Sex with Men Emerging in the Middle East and North Africa?: A Systematic Review and Data Synthesis

Background

Men who have sex with men (MSM) bear a disproportionately higher burden of HIV infection than the general population. MSM in the Middle East and North Africa (MENA) are a largely hidden population because of a prevailing stigma towards this type of sexual behavior, thereby limiting the ability to assess infection transmission patterns among them. It is widely perceived that data are virtually nonexistent on MSM and HIV in this region. The objective of this review was to delineate, for the first time, the evidence on the epidemiology of HIV among MSM in MENA.

Methods and Findings

This was a systematic review of all biological, behavioral, and other related data on HIV and MSM in MENA. Sources of data included PubMed (Medline), international organizations'' reports and databases, country-level reports and databases including governmental and nongovernmental organization publications, and various other institutional documents. This review showed that onsiderable data are available on MSM and HIV in MENA. While HIV prevalence continues at low levels among different MSM groups, HIV epidemics appear to be emerging in at least few countries, with a prevalence reaching up to 28% among certain MSM groups. By 2008, the contribution of MSM transmission to the total HIV notified cases increased and exceeded 25% in several countries. The high levels of risk behavior (4–14 partners on average in the last six months among different MSM populations) and of biomarkers of risks (such as herpes simplex virus type 2 at 3%–54%), the overall low rate of consistent condom use (generally below 25%), the relative frequency of male sex work (20%–76%), and the substantial overlap with heterosexual risk behavior and injecting drug use suggest potential for further spread.

Conclusions

This systematic review and data synthesis indicate that HIV epidemics appear to be emerging among MSM in at least a few MENA countries and could already be in a concentrated state among several MSM groups. There is an urgent need to expand HIV surveillance and access to HIV testing, prevention, and treatment services in a rapidly narrowing window of opportunity to prevent the worst of HIV transmission among MSM in the Middle East and North Africa. Please see later in the article for the Editors'' Summary     

Immobilization of nisin producer Lactococcus lactis strains to chitin with surface-displayed chitin-binding domain

In this study, nisin producer Lactococcus lactis strains displaying cell surface chitin-binding domain (ChBD) and capable of immobilizing to chitin flakes were constructed. To obtain ChBD-based cell immobilization, Usp45 signal sequence with ChBD of chitinase A1 enzyme from Bacillus circulans was fused with different lengths of PrtP (153, 344, and 800 aa) or AcmA (242 aa) anchors derived from L. lactis. According to the whole cell ELISA analysis, ChBD was successfully expressed on the surface of L. lactis cells. Scanning electron microscope observations supported the conclusion of the binding analysis that L. lactis cells expressing the ChBD with long PrtP anchor (800 aa) did bind to chitin surfaces more efficiently than cells with the other ChBD anchors. The attained binding affinity of nisin producers for chitin flakes retained them in the fermentation during medium changes and enabled storage for sequential productions. Initial nisin production was stably maintained with many cycles. These results demonstrate that an efficient immobilization of L. lactis cells to chitin is possible for industrial scale repeated cycle or continuous nisin fermentation.     

Examining problem solving skills of physical education and sport students from several factors

In this research, problem solving skills of university students are examined in the factors of sex and class. In this research problem solving inventory that is improved by Heppner and Petersen (1982) is applied to the students that are training 1. and 4. class 58 female 86 male at Selcuk University Konya, Turkey Physical Education and Sport Collage. In statistical analysis of research for the factors sex and class, variance analysis and t test are used. In the research while meaningful difference is found in the above dimension of the factors sex and there is not found meaningful difference in the factors of class. In conclusion, female students have more positive problem solving skills than male students.     

Antimicrobial evaluation of indole-containing hydrazone derivatives

There has been an increasing importance of drug-resistant pathogens in clinical microbiological and antibacterial research. Indoles and hydrazone-type compounds constitute important classes of compounds in the search for effective agents against multidrug-resistant microbial infections. In this study a series of 1-methylindole-3-carboxaldehyde hydrazone derivatives were evaluated for their in vitro antimicrobial activities using the two-fold serial dilution technique against Staphylococcus aureus, methicillin-resistant S. aureus, methicillin-resistant S. aureus isolate, Escherichia coli, Bacillus subtilis, and Candida albicans. The minimum inhibitory concentration (MIC) of the test compounds and the reference standards sultamicillin, ampicillin, fluconazole, and ciprofloxacin was determined. All compounds possessed a broad spectrum of activity having MIC values of 6.25-100 microg/ml against the tested microorganisms. Aromaticity and disubstitution of the phenyl ring with especially fluorine and chlorine atoms were found to be significant for the antimicrobial activity     

Differential biological role of CD3 chains revealed by human immunodeficiencies

The biological role in vivo of the homologous CD3gamma and delta invariant chains within the human TCR/CD3 complex is a matter of debate, as murine models do not recapitulate human immunodeficiencies. We have characterized, in a Turkish family, two new patients with complete CD3gamma deficiency and SCID symptoms and compared them with three CD3gamma-deficient individuals belonging to two families from Turkey and Spain. All tested patients shared similar immunological features such as a partial TCR/CD3 expression defect, mild alphabeta and gammadelta T lymphocytopenia, poor in vitro proliferative responses to Ags and mitogens at diagnosis, and very low TCR rearrangement excision circles and CD45RA(+) alphabeta T cells. However, intrafamilial and interfamilial clinical variability was observed in patients carrying the same CD3G mutations. Two reached the second or third decade in healthy conditions, whereas the other three showed lethal SCID features with enteropathy early in life. In contrast, all reported human complete CD3delta (or CD3epsilon) deficiencies are in infants with life-threatening SCID and very severe alphabeta and gammadelta T lymphocytopenia. Thus, the peripheral T lymphocyte pool was comparatively well preserved in human CD3gamma deficiencies despite poor thymus output or clinical outcome. We propose a CD3delta > CD3gamma hierarchy for the relative impact of their absence on the signaling for T cell production in humans.     

Synthesis and antimicrobial activity of some novel phenyl and benzimidazole substituted benzyl ethers

In this study, a series of novel phenyl- and benzimidazole-substituted benzyl ethers were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), Escherichia coli, Candida albicans, and Candida krusei. Compound 6g exhibited the most potent antibacterial activity with lowest MIC values of 3.12 and 6.25 microg/mL against S. aureus and MRSA, respectively.     

ATXN2 and Its Neighbouring Gene SH2B3 Are Associated with Increased ALS Risk in the Turkish Population

Expansions of the polyglutamine (polyQ) domain (≥34) in Ataxin-2 (ATXN2) are the primary cause of spinocerebellar ataxia type 2 (SCA2). Recent studies reported that intermediate-length (27–33) expansions increase the risk of Amyotrophic Lateral Sclerosis (ALS) in 1–4% of cases in diverse populations. This study investigates the Turkish population with respect to ALS risk, genotyping 158 sporadic, 78 familial patients and 420 neurologically healthy controls. We re-assessed the effect of ATXN2 expansions and extended the analysis for the first time to cover the ATXN2 locus with 18 Single Nucleotide Polymorphisms (SNPs) and their haplotypes. In accordance with other studies, our results confirmed that 31–32 polyQ repeats in the ATXN2 gene are associated with risk of developing ALS in 1.7% of the Turkish ALS cohort (p = 0.0172). Additionally, a significant association of a 136 kb haplotype block across the ATXN2 and SH2B3 genes was found in 19.4% of a subset of our ALS cohort and in 10.1% of the controls (p = 0.0057, OR: 2.23). ATXN2 and SH2B3 encode proteins that both interact with growth receptor tyrosine kinases. Our novel observations suggest that genotyping of SNPs at this locus may be useful for the study of ALS risk in a high percentage of individuals and that ATXN2 and SH2B3 variants may interact in modulating the disease pathway.     

Effects of capsaicin on nitric oxide synthase isoforms in prepubertal rat ovary

Nitric oxide (NO) has emerged as an important intra-ovarian regulatory factor. We investigated effects of low dose capsaicin (CAP) treatment on the different NOS isoforms in prepubertal rat ovaries. Fifteen 21-day-old female Sprague-Dawley rats were divided randomly into three groups. The first group received no treatment, the second group received 0.5 mg/kg/day CAP dissolved in the vehicle, and the third group was treated with the vehicle only. The animals were euthanized by ether inhalation after 15 days and their ovaries were excised. Ovaries were fixed in 10% neutral buffered formalin and embedded in paraffin. Sections were processed for standard immunohistochemistry using the labeled streptavidin-biotin technique for expression of nNOS, eNOS and iNOS. We demonstrated that CAP induced expression of NOS isotypes including eNOS, iNOS and nNOS in prepubertal rat ovaries. CAP may lead to release of NO either directly from nerves or indirectly by evoking release from other cells via the action of neuropeptides that are released from afferent terminals and are involved in regulating female reproductive function.