Ultrastructural and functional fate of recycled vesicles in hippocampal synapses

Efficient recycling of synaptic vesicles is thought to be critical for sustained information transfer at central terminals. However, the specific contribution that retrieved vesicles make to future transmission events remains unclear. Here we exploit fluorescence and time-stamped electron microscopy to track the functional and positional fate of vesicles endocytosed after readily releasable pool (RRP) stimulation in rat hippocampal synapses. We show that most vesicles are recovered near the active zone but subsequently take up random positions in the cluster, without preferential bias for future use. These vesicles non-selectively queue, advancing towards the release site with further stimulation in an actin-dependent manner. Nonetheless, the small subset of vesicles retrieved recently in the stimulus train persist nearer the active zone and exhibit more privileged use in the next RRP. Our findings reveal heterogeneity in vesicle fate based on nanoscale position and timing rules, providing new insights into the origins of future pool constitution

Prevalence, symptoms and management of uterine fibroids: an international internet-based survey of 21,746 women

<p>Abstract</p> <p>Background</p> <p>In 2009 the Uterine Bleeding and Pain Women's Research Study (UBP-WRS) was conducted interviewing 21,479 women across 8 countries in order to gain patient-based prevalence data on uterine pain and bleeding indications and investigate uterine symptoms and women's treatment experiences. This article shows relevant results of the study for the indication uterine fibroids providing data on self-reported prevalence, symptomatology and management of uterine fibroids.</p> <p>Methods</p> <p>2,500 women (USA: 4,500 women) in each country (Brazil, Canada, France, Germany, Italy, South Korea, the UK, the USA) completed an online survey. Women included were in their reproductive age (age group 15-49 years; USA: 18-49 years) and had ever experienced menstrual bleedings. Quotas were applied for age, region, level of education and household income of respondents. Variables have been analyzed descriptively and exploratory statistical tests have been performed.</p> <p>Results</p> <p>The self-reported prevalence of uterine fibroids ranged from 4.5% (UK) to 9.8% (Italy), reaching 9.4% (UK) to 17.8% (Italy) in the age group of 40-49 years. Women with a diagnosis of uterine fibroids reported significantly more often about bleeding symptoms than women without a diagnosis: heavy bleedings (59.8% vs. 37.4%), prolonged bleedings (37.3% vs. 15.6%), bleeding between periods (33.3% vs. 13.5%), frequent periods (28.4% vs. 15.2%), irregular and predictable periods (36.3% vs. 23.9%). Furthermore women with diagnosed uterine fibroids reported significantly more often about the following pain symptoms: pressure on the bladder (32.6% vs. 15.0%), chronic pelvic pain (14.5% vs. 2.9%), painful sexual intercourse (23.5% vs. 9.1%) and pain occurring mid-cycle, after and during menstrual bleeding (31.3%, 16.7%, 59.7%, vs. 17.1%, 6.4%, 52.0%). 53.7% of women reported that their symptoms had a negative impact on their life in the last 12 month, influencing their sexual life (42.9%), performance at work (27.7%) and relationship & family (27.2%).</p> <p>Conclusions</p> <p>Uterine fibroid is a common concern in women at fertile age causing multiple bleeding and pain symptoms which can have a negative impact on different aspects in women's life.</p

Synapsin- and Actin-Dependent Frequency Enhancement in Mouse Hippocampal Mossy Fiber Synapses

The synapsin proteins have different roles in excitatory and inhibitory synaptic terminals. We demonstrate a differential role between types of excitatory terminals. Structural and functional aspects of the hippocampal mossy fiber (MF) synapses were studied in wild-type (WT) mice and in synapsin double-knockout mice (DKO). A severe reduction in the number of synaptic vesicles situated more than 100 nm away from the presynaptic membrane active zone was found in the synapsin DKO animals. The ultrastructural level gave concomitant reduction in F-actin immunoreactivity observed at the periactive endocytic zone of the MF terminals. Frequency facilitation was normal in synapsin DKO mice at low firing rates (∼0.1 Hz) but was impaired at firing rates within the physiological range (∼2 Hz). Synapses made by associational/commissural fibers showed comparatively small frequency facilitation at the same frequencies. Synapsin-dependent facilitation in MF synapses of WT mice was attenuated by blocking F-actin polymerization with cytochalasin B in hippocampal slices. Synapsin III, selectively seen in MF synapses, is enriched specifically in the area adjacent to the synaptic cleft. This may underlie the ability of synapsin III to promote synaptic depression, contributing to the reduced frequency facilitation observed in the absence of synapsins I and II

The Movember Global Action Plan 1 (GAP1): Unique Prostate Cancer Tissue Microarray Resource

BackgroundThe need to better understand the molecular underpinnings of the heterogeneous outcomes of patients with prostate cancer is a pressing global problem and a key research priority for Movember. To address this, the Movember Global Action Plan 1 Unique tissue microarray (GAP1-UTMA) project constructed a set of unique and richly annotated tissue microarrays (TMA) from prostate cancer samples obtained from multiple institutions across several global locations.MethodsThree separate TMA sets were built that differ by purpose and disease state.ResultsThe intended use of TMA1 (Primary Matched LN) is to validate biomarkers that help determine which clinically localized prostate cancers with associated lymph node metastasis have a high risk of progression to lethal castration-resistant metastatic disease, and to compare molecular properties of high-risk index lesions within the prostate to regional lymph node metastases resected at the time of prostatectomy. TMA2 (Pre vs. Post ADT) was designed to address questions regarding risk of castration-resistant prostate cancer (CRPC) and response to suppression of the androgen receptor/androgen axis, and characterization of the castration-resistant phenotype. TMA3 (CRPC Met Heterogeneity)'s intended use is to assess the heterogeneity of molecular markers across different anatomic sites in lethal prostate cancer metastases.ConclusionsThe GAP1-UTMA project has succeeded in combining a large set of tissue specimens from 501 patients with prostate cancer with rich clinical annotation.ImpactThis resource is now available to the prostate cancer community as a tool for biomarker validation to address important unanswered clinical questions around disease progression and response to treatment.</p

The Movember Global Action Plan 1 (GAP1) : Unique Prostate Cancer Tissue Microarray Resource

BACKGROUND: The need to better understand the molecular underpinnings of the heterogeneous outcomes of patients with prostate cancer is a pressing global problem and a key research priority for Movember. To address this, the Movember Global Action Plan 1 Unique tissue microarray (GAP1-UTMA) project constructed a set of unique and richly annotated tissue microarrays (TMA) from prostate cancer samples obtained from multiple institutions across several global locations. METHODS: Three separate TMA sets were built that differ by purpose and disease state. RESULTS: The intended use of TMA1 (Primary Matched LN) is to validate biomarkers that help determine which clinically localized prostate cancers with associated lymph node metastasis have a high risk of progression to lethal castration-resistant metastatic disease, and to compare molecular properties of high-risk index lesions within the prostate to regional lymph node metastases resected at the time of prostatectomy. TMA2 (Pre vs. Post ADT) was designed to address questions regarding risk of castration-resistant prostate cancer (CRPC) and response to suppression of the androgen receptor/androgen axis, and characterization of the castration-resistant phenotype. TMA3 (CRPC Met Heterogeneity)'s intended use is to assess the heterogeneity of molecular markers across different anatomic sites in lethal prostate cancer metastases. CONCLUSIONS: The GAP1-UTMA project has succeeded in combining a large set of tissue specimens from 501 patients with prostate cancer with rich clinical annotation. IMPACT: This resource is now available to the prostate cancer community as a tool for biomarker validation to address important unanswered clinical questions around disease progression and response to treatment.publishedVersionPeer reviewe

The androgenic profile of women with non-insulin-dependent diabetes mellitus

WOS: 000224110300010PubMed ID: 15493567OBJECTIVE: To evaluate the androgenic profile of women with non-insulin-dependent diabetes mellitus. STUDY DESIGN: This case-control study evaluated the clinical, hormonal and ultrasonographic characteristics of women of reproductive age with non-insulin-dependent diabetes mellitus and compared them with those of age- and weight-matched controls. Radioimmunoassays were used for total testosterone, estradiol, dehydroepiandrosterone sulfate (DHEAS) and androstenedione. Sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were analyzed by fluoroimmunoassays. Ovarian appearance and volume were assessed by transvaginal or transabdominal ultrasonography. RESULTS: The prevalence of polycystic ovary syndrome was higher in diabetic patients than in the general population as reported earlier. Hirsutism was also more prevalent in diabetic patients (p < 0.05). The serum levels of FSH, LH, estradiol, total testosterone, androstenedione and DHEAS were significantly higher in diabetic patients than in the control group (p < 0.05). In contrast, the levels of SHBG were lower in diabetic patients (p < 0.05). The rates of ultrasonographically apparent polycystic ovaries and greater ovarian volumes were also higher in diabetic patients (p < 0.05). CONCLUSION: Women with non-insulin-dependent diabetes mellitus seem to have biochemical and clinical hyperandrogenism when compared with nondiabetic controls

Histopathological changes of cervical tissue in women with systemic sclerosis

PubMedID: 15482565Systemic sclerosis is a connective tissue disease that can affect almost any organ of the body. The clinical aspects of systemic sclerosis on the reproductive system have been studied in large series, and an increased rate of cesarean section has been reported. For this reason, in the present study the histopathological features of cervical specimens of hysterectomyzed women with systemic sclerosis were evaluated. An increased frequency of vascular and stromal abnormalities in cervical specimens of women with systemic sclerosis were observed. Vascular medial hypertrophy, intimal thickening, and fibrosis were more often encountered in the cervical specimens of the patients with systemic sclerosis. Some of the histopathological features also showed correlation with the clinical profile of the disease. The patients with vascular medial hypertrophy in their cervical specimens were older, had a higher Rodnan score, and had longer duration of the disease. In contrast to vascular medial hypertrophy, periadventitial edema was found in the cervical specimens of the patients who were younger, had a lower Rodnan score, and had shorter duration of the disease. It was concluded that the problems that are seen in common obstetric and gynecological practices in patients with systemic sclerosis may be explained by these tissue abnormalities

The effect of carbohydrate intolerance on neonatal birth weight in pregnant women without gestational diabetes mellitus

Background: There is still no consensus on screening, threshold levels and treatment of gestational diabetes mellitus. Furthermore, the importance of a positive 50-g glucose screening test in patients who had a negative 100-g oral glucose tolerance test remains controversial. We investigated the impact of the 50-g glucose screening test results on neonatal outcome in pregnant women with uncomplicated pregnancies, who had no risk factors according to ACOG criteria. Patients and Methods: Three hundred eighty-six pregnant women with singleton pregnancies were prospectively screened with 50-g glucose challenge test between 24 and 28 weeks. If the test result was >140 mg/dl, a 100-g 3-hour oral glucose tolerance test was performed. Patients with a positive screening test, but not diagnosed as gestational diabetes mellitus constituted the study group, and patients with a negative screening test constituted the control group. Cesarean rates, neonatal birth weights and complications were compared between these groups. Results: The cesarean delivery rates were not statistically different between the study and control groups (8.3% vs. 6.4%, P>0.05). The rates of macrosomic births were 10.0% in the study group, and 6.4% in the control group (P>0.05), but the mean birth weight (3451.67 ± 355.70 g) in the study group was significantly higher than the mean birth weight (3296.29 ± 365.14 g) in the control group (P=0.003). Neonatal hypoglycemia and hyperbilirubinemia was also encountered more often in babies of pregnant women with a positive 50-g glucose challenge test but negative 100-g glucose tolerance test. Conclusion: Because of similarities with gestational diabetes mellitus on the basis of perinatal outcomes, the non-diabetic pregnant women with 50-g glucose screen test result over 140 mg/dl but a negative 100-g OGTT should be followed closely

Identification of different phytoplasmas infecting grapevine in Turkey

Grapevines with severe redness and inward curling of leaves were collected from the main viticulture production areas, Aegean, Central Anatolia and Western Anatolian regions of Turkey. Collected samples were subjected to nucleic acid extraction followed by nested PCR/RFLP analyses that allow to identify different phytoplasmas in symptomatic grapevines. The majority of samples were infected with phytoplasmas belonging to 16SrXII group and referable to the \u2018bois noir\u2019 phytoplasmas, while in some sam-ples 16SrIX or 16SrI-B phytoplasmas were identified. The 16SrIX phytoplasmas are firstly reported in grapevine

Fast Synaptic Vesicle Reuse Slows The Rate Of Synaptic Depression In The Ca1 Region Of Hippocampus

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