Reconstruction of Protein-Protein Interaction Network of Insulin Signaling in Homo Sapiens

Diabetes is one of the most prevalent diseases in the world. Type 1 diabetes is characterized by the failure of synthesizing and secreting of insulin because of destroyed pancreatic β-cells. Type 2 diabetes, on the other hand, is described by the decreased synthesis and secretion of insulin because of the defect in pancreatic β-cells as well as by the failure of responding to insulin because of malfunctioning of insulin signaling. In order to understand the signaling mechanisms of responding to insulin, it is necessary to identify all components in the insulin signaling network. Here, an interaction network consisting of proteins that have statistically high probability of being biologically related to insulin signaling in Homo sapiens was reconstructed by integrating Gene Ontology (GO) annotations and interactome data. Furthermore, within this reconstructed network, interacting proteins which mediate the signal from insulin hormone to glucose transportation were identified using linear paths. The identification of key components functioning in insulin action on glucose metabolism is crucial for the efforts of preventing and treating type 2 diabetes mellitus

Perception of discrimination in worklife and a field research in private sector

ÖZET Bu çalışmanın amacı, çalışan kişilerin çalışma yaşamları içerisinde "ayrımcılık" kavramının farkında olup olmadıklarını tespit etmek ve bu doğrultuda ayrımcılık olarak neyi algıladıklarını ve nasıl algıladıklarını tespit etmeye çalışmaktır. (Sayfa: 30)Çalışma iki ana bölümden oluşmaktadır. Bunlar literatür taraması ve saha araştırmasıdır. Literatür taraması çalışmanın teorik altyapısını kapsarken, saha araştırması çalışmada yürütülen araştırmanın uygulanmasını kapsar. Bu bağlamda, literatür taramasında elde edilen veriler ile saha araştırmasında kullanılacak girdilerin elde edilmesi sağlanılmıştır. Saha araştırmasında 22 sorudan oluşan yapılandırılmış anket 100 kişiye uygulanmış, elde edilen veriler SPSS programı kullanılarak incelenmiştir. (Sayfa: 31)İş yaşamı içerisindeki yoğun çalışma saatleri, anket sorularının özel ve gizlilik arz ettiği düşüncesi, çalışma esnasında karşılaşılan kısıtlamaları meydana getirmektedir. (Sayfa: 35)Araştırma sonuçlarına göre, Çifte standart ayrımcılığı (terfi, ücret, iş değerleme, gibi uygulamalarda eşitsizlik), Eğitim ayrımcılığı (okul, branş, ... ayrımcılığı), Yandaşlık ayrımcılığı (hemşehrilik, tanıdık olma, ... ayrımcılığı), Cinsiyet ayrımcılığı ve Sosyal / kültürel çevre ayrımcılığı (sınıf, değer, norm, statü, rol, ... ayrımcılığı) 11(on bir) temel ayrımcılık türü arasında , hem algılanan hem de yaşanan ayrımcılık türleri olarak ilk beşi oluşturduğu görülmektedir. (Sayfa: 40-48)Çalışmada elde edilen bulgulara göre, ayrımcılık ile ilgili uygulama ve olayların azaltılması ve önlenmesi için ayrımcılığın gerek iş yönetmeliklerinde gerekse işyerindeki mevzuata uyum çalışmalarında yer verilerek görünür kılınması sağlanabilir. (Sayfa: 59)Sonuç olarak, bu çalışma hem sivil toplum örgütleri hem de işletmelerde personel yönetmeliklerinin güncellenmesinde, ve bu doğrultudaki stratejilerin geliştirilmesinde kaynak olarak kullanılabilir.SUMMARYThe aim of this study is to try to find out whether working people in Istanbul are aware of discrimination in work life, and if they consider that there is discrimination in work life, to determine what they perceive as discrimination and how they perceive discrimination. (Page: 30)The study consists of two main parts. These are literature survey and field research. The literature survey part includes the theoretical framework of the study where, the field research part includes the application of research. The data gathered from literature survey provided the inputs for field research. A structured questionnaire composed of 22 questions is applied to 100 people. The data collected has been processed and analysed in SPSS. (Page: 31)The dense job programs which create difficulty for employees to participate in questionnaire study, and the thought that the questionnaire is confidential are the limitations faced while the research was undertaken. (Page: 35)Based on the field research findings; stereotype (discrimination in business applications such as promotion, payment and performance appraisal...), educational (school, branch...), relationship (citizenry...), gender (male, female) and social status (status, role, ... ) discrimination are the first five ranked experienced and perceived discrimination types. (Page: 40-48)According to findings, in order to reduce or prevent discriminatory events in work life, discrimination should be visible through compliance applications and work policies in the organisations. (Page: 59)Consequently, the organisations or occupational groups may benefit from this study while developing business strategies and work policies

Administration of autologous platelet rich plasma and the impact on outcomes of assisted reproduction treatment in infertile women

Objective: There are diverse findings concerning the use of platelet-rich plasma (PRP) in assisted reproduction treatment (ART) cycles of infertile women with low ovarian reserve, ovarian failure or implantation failure due to endometrial problems. A debate continues regarding the benefit of this technique because of the low number of evidence-based studies. Mechanism: Different PRP preparation methods have been described in the literature, aiming to obtain the highest number of platelets following centrifugation steps. Findings in brief : Research on the use of PRP in female infertility aims to improve the deteriorated hormonal profile, gamete production and implantation of the embryo into the endometrium. Conclusions: This paper reviewed literature evaluating the impact of PRP on the outcomes of subsequent ART cycles in infertile women. PRP is a safe and easy-to-apply procedure and can be used as an 'add-on' therapy in patients with reduced ovarian reserve, ovarian failure or implantation failure prior to the in vitro fertilization (IVF) cycle, although it is still regarded as an empirical treatment method. Further studies should be conducted to enlighten the subject

Effects o follicular fluid oxidative status on human mural granulosa cells, oocyte competency and ICSI parameters

Purpose: The aim of the present study was to understand the molecular and genetic alterations involved in follicular fluid oxidative process by investigating human mural granulosa cells and to find possible biomarkers for oocyte competency and ICSI outcome measures.Methods: A total of 166 patients were included in the study. Total antioxidant and oxidant levels of follicular fluids were measured on the day of oocyte pick-up and oxidative status were calculated. Expression profiles of three potential target proteins in cases of oxidative stress (Hsp70, Tgf-beta, Notch1), DNA status and chromatin integrity of mural granulosa cells were analyzed.Results: TAS levels were positively correlated with the Hsp70 and Tgf-beta expression patterns of mural granulosa cells. Mature oocyte rate and fertilization rates were affected negatively by the presence of oxidative stress and a significant positive correlation was found with the oxidative status and the fertilization rate, whereas no correlation with the remaining ICSI parameters in the overall group.Conclusions: Oxidative stress detected in follicular fluid adversely affects fertilization rates post-ICSI however no effect on the remaining parameters including embryo quality, pregnancy, and implantation rates. DNA damage, chromatin integrity were increased, whereas Hsp70 and Tgf-ss were decreased in mural granulosa cells in cases of oxidative stress which may indirectly reflect the oocyte competency and may be used as biomarkers for ICSI outcome measures

Effects of human sperm cryopreservation on apoptotic markers in normozoospermic and non-normozoospermic patients

WOS: 000448811000008PubMed ID: 30220260The negative effects of cryopreservation on sperm parameters are well documented but little information is known about molecular basis of the process. The aim of the present study was to investigate the possible effects of sperm cryopreservation on main apoptotic signs including DNA fragmentation and caspase-3 activation and to determine if these effects vary according to sperm parameters. Sperm samples of 72 patients were cryopreserved. The patients were sub-grouped as normozoospermic or non-normozoospermic patients according to their semen parameters. DNA fragmentation rates and caspase-3 activation levels were analyzed before and after cryopreservation in both groups. Mean DNA fragmentation rate was increased significantly from 23.98% in neat semen samples to 27.34% after cryopreservation (P = 0.03). DNA fragmentation rates were slightly higher in non-normozoospermic patients compared with the normozoospermic patients in both the neat semen and after cryopreservation (23.25 and 24.71% vs. 26.32 and 28.36%, respectively) although the difference obtained were not statistically significant. An increasing trend for caspase-3 activations (0.093 vs. 0.116) was observed after cryopreservation but the differences were not statistically significant. Caspase-3 activation was found to be slightly higher in non-normozoospermic patients both in the neat semen and after cryopreservation compared with the normozoospermic patients but the differences were not statistically significant. Caspase-3 expression was also shown using immunocytochemistry in both fresh ejaculated sperm and thawed sperm after cryopreservation but at different localizations. The cryopreservation process had detrimental effects on sperm quality but the quality of the sperm samples was not adversely effective for the apoptotic markers including DNA fragmentation and caspase-3 activation patterns. In fact, it was the cryopreservation process itself that adversely effected the above apoptotic markers and apoptosis. It was concluded therefore that sperm cell cryopreservation triggers apoptosis after thawing and this process adversely affects semen parameters

Fresh versus frozen blastocyst transfer outcomes deriven from the same ICSI cycle in male factor infertility

The aim of this study was to investigate the clinical outcomes of fresh and frozen-thawed blastocyst transfer deriven from the same ICSI cycle because of male infertility. 2372 couples undergoing a total of 5075 ICSI cycles (2372 fresh + 2703 frozen embryo transfer) were enrolled in the study. Female factor infertility cases were excluded to prevent from the contribution of maternal factors that would influence the outcomes dramatically. Only the cycles for which day 5 blastocyst transfer was performed, had at least 1 surplus blastocyst available for freezing, and had at least one frozen embryo transfer (FET) cycle were included in the study. Clinical pregnancy rates and live birth rates were compared between fresh and FET cycles. No statistically significant difference was obtained in clinical pregnancy rates and live birth rates of fresh versus FET cycles of day 5 transfers, regardless of the number of embryos transferred. According to the results of the recent study, frozen embryo cycles appear to be as effective as fresh ICSI cycles provided that the patients' embryos can develop into blastocysts, which is proven by using the same patient as the control group regardless of the result of previous ICSI attempt but further research is required to test the efficacy in terms of cost-effectiveness and the duration for conception

Türkiye'deki üç infertilite kliniğinin erkek infertilitesi, azoospermi ve kriptozoospermi insidansı

WOS: 000427076700003PubMed ID: 29511578Objective: Semen parameters are directly correlated with the infertility of the male. Incidence rates of male factor infertility, azoospermia and cryptozoospermia differ according to many factors such as geographic region, age, occupation and body weight. The aim of the present study is to determine the incidence of male factor infertility, azoospermia and cryptozoospermia among patients who have been admitted to three separate infertility clinics in Turkey for infertility investigation and analyze the outcomes of these patients. Material and methods: A total of 9733 men, who have been admitted to 3 infertility clinics in Turkey due to infertility between March 2011 and October 2016, were included in the study. Male infertility, azoozpermia and cryptozoospermia incidence were calculated according to WHO criteria. Results: Male factor infertility was determined in 3114 (32%) of the patients including cases with azoospermia and cryptozoospermia. Azoospermia cases were observed in 570 (5.85%) and cryptozoospermia in 850 (8.73%) men. Azoospermic, and cryptozoospermic patients constitute 18.3%, and 27.2% of the male infertility cases. Sperm retrieval rates in diagnostic or oocyte pick-up plus testicular sperm extraction groups were found to be comparable (16.39%, and 41.3%, respectively). Conclusion: The data obtained may help to estimate the number of in vitro fertilization cycles and testicular sperm extraction cases, to determine social security policies, and reproductive potential, and in the light of these data to establish social insurance policies. These data will help patients to decide on treatment alternatives, and guide the urologists about the issue.Amaç: Semen parametreleri erkek infertilitesi ile direkt ilişkilidir. Erkek faktörlü infertilite, azoospermi vekriptozoospermi insidansı coğrafi bölge, yaş, meslek ve vücut ağırlığı gibi birçok faktöre göre değişmektedir. Bu çalışmanın amacı, Türkiye’de 3 farklı infertilite kliniğine infertilite nedeniyle başvuran hastalararasında erkek faktörlü infertilite, azoospermi ve kriptozoospermi oranlarını belirlemek ve bu hastalarınsonuçlarını analiz etmektir.Gereç ve yöntemler: Mart 2011 ve Ekim 2016 tarihleri arasında, Türkiye’de 3 farklı infertilite kliniğineinfertilite nedeniyle başvuran 9733 erkek çalışmaya alınmıştır.Bulgular: Hastaların 3114’ünde (%32) erkek faktörlü infertilite (azoospermi ve kriptospermi vakaları dahil)belirlenmiştir. Hastaların 570’inde (%5,85) azoospermi, 850’sinde (%8,73) kriptozoospermi belirlenmiştir.Azoospermi vakaları erkek infertilite vakalarının %18,3’ünü, kriptozoospermi vakaları ise %27,2’sini oluşturmaktadır. Azoospermik ve kriptozoospermik hastalarda tanısal ya da oosit toplama işlemi ile eşleniktestiküler sperm ekstraksiyonu gruplarının sperm bulma oranları benzer (%16,39-%41,3 sırasıyla) bulunmuştur.Sonuç: Elde edilen sonuçlar in vitro fertilizasyon siklusu ve TESE vakalarını tahmin etmede ve bu verilerışığında sosyal güvenlik politikalarının belirlenmesine, üreme potansiyelinin belirlenmesi ve bu veriler ışığında ulusal sağlık politikaları belirlenmesine yardımcı olacaktır. Veriler aynı zamanda hastalara tedavi seçenekleri arasında karar vermelerine ve ürologlara konu ile ilgili yönlendirme yaparken fayda sağlayacaktır

Factors related to follicular oxidative stress in intracytoplasmic sperm injection cycles and its effects on granulosa cells

The aim of the present study was to investigate several common conditions that may potentially be correlated with follicular oxidative status during an intracytoplasmic sperm injection (ICSI) cycle and that include the serum oestrogen level on the day of oocyte pick-up, maternal age and pregnancy outcome. Patients that were enrolled in the study were classified randomly into three groups using their numerical order. The first group were classified based on maternal age (= 35 years) (n = 398), the second group on the serum oestradiol (E2) level on the day of human chorionic gonadotropin (hCG) administration (levels >90th percentile and <= 90th percentile) (n = 491) and the third group on pregnancy outcome (positive/negative) (n = 376). The groups were matched for the other variables (stimulation protocol, dose of gonadotropin, duration of stimulation, antral follicle count, body mass index, basal follicle stimulating hormone (FSH), and E2 levels and day of hCG trigger) to prevent the possible contribution of those parameters to the results. Each group was matched for other variables (stimulation protocol, dose of gonadotrophin, duration of stimulation, antral follicle count, body mass index, basal FSH and E2 levels and day of hCG trigger) that may have affected the outcome, except for the parameter under investigation. Maternal age (P = 0.044,168 r = 0.418), oestrogen level on day of hCG administration (P = 0.001, r = 0.436) and pregnancy outcome (AUC = 0.65, P = 0.071) were found to be correlated with follicular oxidative status. The results obtained will help us to shield patients from possible situations that may cause oxidative stress and therefore adverse outcomes of an ICSI cycle

Effect of rapid ventricular pacing on cerebral oxygenation in transcatheter aortic valve implantation (Tavi): Role of routine near-infrared spectroscopy monitoring

Objective: Transcatheter aortic valve implantation has become an important treatment modality in patients with high risk comorbidities for surgical aortic valve replacement. The objective of this study is to evaluate the cerebral perfusion status using near infrared spectroscopy method especially during the rapid ventricular pacing phase of the transcatheter aortic valve implantation procedure. Methods: 20 consecutive patients undergoing trans-femoral aortic valve implantation procedure between May 2015 and March 2016 in our institute were retrospectively evaluated. The periprocedural cerebral oxygenation was measured with a near infrared spectroscopy sensor (INVOSTM-5100 C, Medtronic Inc., Minneapolis, MI, USA) located on the forehead of the patients. All hemodynamic data and cerebral near infrared spectroscopy values were recorded before, during and after the procedure with constant time intervals, especially at the time of rapid ventricular pacing and device deployment. Results: The mean age was 74.4 ± 9.2 years. Male female ratio was 1.8 to 1 (13 males, 7 females). Mean procedure time was 70.2 ± 14.3 minutes. The rapid ventricular pacing included two episodes with a total time for pacing of 22.6 ± 5.1 seconds. There was a statistically significant difference with regard to the heart rate and the cerebral near infrared spectroscopy values (p=0.006 and p=0.02; respectively) in all patients during the rapid ventricular pacing period. The cerebral near infrared spectroscopy values were statistically lower than baseline levels (p<0.001). Conclusion: This observational study presents the significant decrease of cerebral near infrared spectroscopy values during the rapid ventricular pacing phase of the transcatheter aortic valve implantation procedure. Further studies may reveal cut-off values both for near infrared spectroscopy values and rapid ventricular pacing duration in order to determine a critical cut-off level

The role of TNF-α and its target HSP-70 in triggering apoptosis in normozoospermic and non-normozoospermic samples

Objective: Semen analysis is performed as one of the screening tests for infertility, including motility, morphology, and concentration observation. We aimed to investigate the expression rates of tumor necrosis factor-α (TNF-α) and heat shock protein (HSP)-70 as two opposite affectors of apoptosis in men with normal semen parameters and abnormal parameters to find the possible effect of this pathway on sperm parameters. We also aimed to investigate the apoptotic markers (DNA fragmentation and Caspase-3 expression) to observe the correlation of this pathway with apoptosis. Materials and Methods: A total of 32 men who applied for infertility evaluation were included in the study. Semen analysis was performed according to WHO criteria. Liquefaction time, appearance, volume, pH, viscosity, sperm concentration, total motility rate, sperm motility, and percentage of spermatozoa with normal morphology were determined. TNF-α, HSP-70, and Caspase-3 immunolocalization were scored histologically. A sperm chromatin dispersion test was used to observe DNA fragmentation. Results: There was no significant difference in TNF-α protein expression rate (mild level). The HSP-70 expression rate was lower, especially in the head region of normo. Caspase-3 was higher totally in non-normo. DNA fragmentation levels were similar in both the groups. Conclusion: From TNF-α protein expression at the mild level in both the groups, it may be hypothesized that the apoptotic pathway might not be triggered by the extrinsic pathway. We found a negative correlation between HSP-70 and Caspase-3 expressions, providing further evidence that HSP-70 works as an inhibitor to apoptosis. This, particularly on specific points, made us think the communication might begin in the anterior chamber, then flow through the cell body to the tail. HSP-70 expression was lower in normo than in non-normo, indicating the possible role of HSP-70 as an answer to any type of stressor in non-normozoospermic patients. Correspondingly, it may be concluded that HSP has an antiapoptotic effect, causing inhibition in the elimination of abnormal sperm cells impairing sperm parameters