“
“Purpose Hepatobiliary cancers respond poorly to cytotoxic Selleckchem RG7112 chemotherapy. We evaluated the activity and safety

of ixabepilone, an epothilone B analogue which stabilizes microtubules, in a phase II trial in patients with advanced cancers of the gallbladder, bile duct, and liver. Methods Eligible patients had previously-untreated, histologically-proven unresectable hepatobiliary cancer. Ixabepilone, 40 mg/m(2), was administered intravenously over 3 h every 21 days. Results Between January 2002 and April 2005, 54 patients (19 hepatocelluar carcinoma, 13 cholangiocarcinomas, 22 gallbladder carcinomas) were enrolled; 47 patients were evaluable for efficacy. The objective response rate was 8.5%; 51% had stable disease. Median overall survival was 7.0 months (95% CI, 5.0 to 10.8 months) and median progression-free survival was 2.6 months (95% CI,

1.4 to 4.1 months). Grade 3/4 toxicities included neutropenia (39%), fatigue (9%), allergic/hypersensitivity reaction (4%) and sensory neuropathy (4%). Conclusion Single agent ixabepilone has limited activity in advanced hepatobiliary cancers.”
“The current epidemics of type 2 diabetes mellitus (T2DM), non-alcoholic steatohepatitis (NASH), and Alzheimer’s disease (AD) all represent insulin-resistance diseases. Previous studies showed that streptozotocin, a nitrosamine-related compound, causes Entinostat insulin resistance diseases including, T2DM, NASH, and AD-type neurodegeneration. We hypothesize that chronic human exposure to nitrosamine compounds, which are widely present in processed foods, contributes to the pathogenesis of T2DM, NASH, and

AD. Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA) by i.p. (x3) or i.c. (x1) injection, and 2-4 weeks later, they were evaluated for cognitive-motor dysfunction, insulin resistance, and neurodegeneration selleckchem using behavioral, biochemical, and molecular approaches. NDEA treatment caused T2DM, NASH, deficits in motor function and spatial learning, and neurodegeneration characterized by insulin resistance and deficiency, lipid peroxidation, cell loss, increased levels of amyloid-beta protein precursor/amyloid-beta, phospho-tau, and ubiquitin immunoreactivities, and upregulated expression of pro-inflammatory cytokine and pro-ceramide genes, which together promote insulin resistance. In conclusion, environmental and food contaminant exposures to nitrosamines play critical roles in the pathogenesis of major insulin resistance diseases including T2DM, NASH, and AD. Improved detection and prevention of human exposures to nitrosamines will lead to earlier treatments and eventual quelling of these costly and devastating epidemics.”
“Metabolomics, based on ultraperformance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry, was used to explore metabolic signatures of tumor growth in mice.

The objective of the present work was to identify important diagnostic indicators and their accuracy for specific and non-specific conditions underlying NCCP. Methods: A systematic review and meta-analysis were performed. In May 2012, six databases were searched. Hand and bibliography searches were also conducted. Studies evaluating a diagnostic test against a reference test in patients with NCCP

learn more were included. Exclusion criteria were having smaller than 30 patients per group, and evaluating diagnostic tests for acute cardiovascular disease. Diagnostic accuracy is given in likelihood ratios (LR): very good (LR+ bigger than 10, LR- smaller than 0.1); good (LR + 5 to 10, LR- 0.1 to 0.2); fair (LR + 2 to 5, LR- 0.2 to 0.5); or poor (LR + 1 to 2, LR- 0.5 to 1). Joined meta-analysis of the diagnostic test sensitivity and specificity was performed by applying a hierarchical Bayesian model. Results: Out of 6,316 records, 260 were reviewed in full text, and 28 were included: 20 investigating gastroesophageal reflux disorders (GERD), 3 musculoskeletal chest pain, and 5 psychiatric conditions. Study quality was good in 15 studies and moderate in 13. GERD diagnosis was more likely with

selleck chemicals llc typical GERD symptoms (LR + 2.70 and 2.75, LR- 0.42 and 0.78) than atypical GERD symptoms (LR + 0.49, LR- 2.71). GERD was also more likely with a positive response to a proton pump inhibitor (PPI) test (LR + 5.48, 7.13, and 8.56; LR- 0.24, 0.25, and 0.28); the posterior mean sensitivity and specificity of six studies were 0.89 (95% credible interval, 0.28 to 1) and 0.88 (95% credible interval, 0.26 to 1), respectively. Panic and anxiety screening check details scores can identify individuals requiring further testing for anxiety or panic disorders. Clinical findings in musculoskeletal pain either had a fair to moderate LR + and a poor LR- or vice versa. Conclusions: In patients with

NCCP, thorough clinical evaluation of the patient’s history, symptoms, and clinical findings can indicate the most appropriate diagnostic tests. Treatment response to high-dose PPI treatment provides important information regarding GERD, and should be considered early. Panic and anxiety disorders are often undiagnosed and should be considered in the differential diagnosis of chest pain.”
“The biologic basis of autism is complex and is thought to involve multiple and variable gene-environment interactions. While the logical focus has been on the affected child, the impact of maternal genetics on intrauterine microenvironment during pivotal developmental windows could be substantial. Folate-dependent one carbon metabolism is a highly polymorphic pathway that regulates the distribution of one-carbon derivatives between DNA synthesis (proliferation) and DNA methylation (cell-specific gene expression and differentiation).

\n\nConclusions Our data demonstrate the potential importance of bias in household air pollution studies. This results from failure to address the possibility that those receiving improved stoves are themselves prone to better or worse health outcomes. It suggests the value of data collection and of study design for cookstove interventions and, more generally, for policy interventions within many health

outcomes.”
“Introduction: The aim of this paper was to examine the association between exposure to second-hand smoke (SHS) among non-smokers, in the home and the vehicle, and poor mental health outcomes (mood disorder, anxiety disorder, poor/fair mental health, and high stress).\n\nMethods: Data were drawn from the 2010 Canadian Community Health Survey, a representative sample of 62,909 Canadians 12 years and older. Measures of SHS exposure are BMS-777607 chemical structure drawn from self-reported daily or near daily exposure in the β-Nicotinamide mw home or in the vehicle. Mental health indicators include self-reported diagnosed mood and anxiety disorders, and self-report measures of overall mental health and experiences of stress. Associations between SHS exposure and poor mental health among non-smokers were examined in a series of logistic regression models. Additional analyses stratified on respondent’s smoking status, physical health, and gender.\n\nResults: Analyses

revealed that SHS exposure among non-smokers was associated with increased anxiety disorders, poor/fair mental health, and high stress, with no association to mood disorders. Stratified analyses demonstrated that associations between SHS and poor mental health are contextualized by respondent’s gender, physical health, and smoking status.\n\nConclusions: Beyond changes to physical health, SHS exposure in private spaces was negatively associated with the mental health of non-smokers. Public health efforts to reduce SHS exposure in private spaces are warranted. Findings also reveal additional targets for decreasing and eliminating the societal burden of mental health disorders. Further research is needed to examine causality and to explore associations between SHS exposure and specific mental health outcomes. (C) 2012 Elsevier

Selleckchem Nutlin3a Ltd. All rights reserved.”
“A series of platinum nanoparticles-deposited carbon nitride nanotubes (Pt/C3N4 NTs) was fabricated by a simple one-step solvothermal treatment strategy using graphite carbon nitride (g-C3N4) and chloroplatinic acid (H2PtCl6 center dot 6H(2)O) as precursors. The morphology, porosity, phase and chemical structure, and optical and electronic properties of Pt/C3N4 NTs were well characterized. Compared with bulk g-C3N4, the as-prepared Pt/C3N4 NTs exhibited efficient photocatalytic activity toward hydrogen evolution from water-splitting and aqueous p-chlorophenol degradation under visible-light irradiation (lambda bigger than 420 nm) as a result of their unique tubular nanostructure and the synergic effect of Pt nanoparticles.

Synthetic versions of these mediators have potent bioactions when administered in vivo. In animal experiments, the mediators evoke anti-inflammatory and novel pro-resolving mechanisms, and enhance microbial clearance. Although check details they have been identified in inflammation resolution, specialized pro-resolving mediators are conserved structures that also function in host defence, pain, organ protection and tissue remodelling. This Review covers the mechanisms

of specialized pro-resolving mediators and omega-3 essential fatty acid pathways that could help us to understand their physiological functions.”
“Plant soil specialists contribute greatly to global diversity; however, the ecoevolutionary forces responsible for generating this diversity are poorly understood. We integrate molecular phylogenies with descriptive and experimental ecological data, https://www.selleckchem.com/products/BMS-777607.html creating a powerful framework with which to elucidate forces driving soil specialization. Hypotheses explaining edaphic specialization have historically focused on costs of adaptation to elements (e. g., nickel, calcium/magnesium) and accompanying tradeoffs in

competitive ability in benign soils. We combine in situ microhabitat data for 37 streptanthoid species (Brassicaceae), soil analyses, and competition experiments with their phylogeny to reconstruct selective forces generating serpentine soil endemism, which has four to five independent origins in this group. Coupling ancestral state reconstruction with phylogenetic independent

contrasts, β-Nicotinamide cost we examine the magnitude and timing of changes in soil and habitat attributes relative to inferred shifts to serpentine. We find large changes in soil chemistry at nodes associated with soil shifts, suggesting that elemental changes occurred concomitantly with soil transitions. In contrast, the amount of bare ground surrounding plants in the field (“bareness”), which is greater in serpentine environments, is conserved across soil-type shifts. Thus, occupation of bare environments preceded shifts to serpentine, and may serve as an evolutionary precursor to harsh elemental soils and environments. In greenhouse experiments, taxa from barer environments are poorer competitors, a tradeoff that may contribute to soil endemism. The hypothesis of occupation of bare habitats as a precursor of soil specialization can be tested in other systems with a similar integrative ecophylogenetic approach, thereby providing deeper insights into this rich source of biodiversity.”
“To estimate the 2009-2010 death rates, causes, and patterns of mortality in rural Cambodia, we conducted active, population-based death surveillance in 25 rural villages of Cambodia from March 2009 to August 2010. Among the population of 28 053 under surveillance, 280 deaths were reported and explored by physician-certified verbal autopsies, using the International Classification of Diseases 10, yielding an overall mortality rate (MR) of 6.7/1000 persons-year (95% CI 5.74-7.68).

The expression of CK-8, CK-14, miR-205, and miR-143 was similar between neosquamous epithelium compared to normal squamous epithelium in patients with Barrett’s esophagus. Only miR-143 expression was significantly higher in neosquamous and normal squamous epithelium before and after APC compared to normal squamous epithelium from control subjects (p < 0.004).\n\nThe expression levels of cytokeratins and miRNAs studied in post-ablation neosquamous epithelium and normal squamous epithelium in patients with Barrett’s esophagus are similar. In patients

with Barrett’s esophagus, miR-143 expression is still elevated in both neosquamous mucosa, and the squamous mucosa above the metaplastic segment, suggesting that this mucosa may not be normal; i.e., it is NVP-LDE225 different to that seen in subjects without Barrett’s esophagus. miR-143 could promote a Barrett’s epithelium gene expression pattern, and this could have a role in development of Barrett’s esophagus.”
“The results of adhesion improvement and SET-RESET operation voltage reduction for the GeN buffer layer are presented. It is found that the adhesive strength between the Ge2Sb2Te5(GST) layer and the layer below could be increased

at least 20 times, which is beneficial for solving the phase change material peeling issue in the fabrication process of phase change memory (PCM). Meanwhile, the RESET voltage of the PCM cell with a 3-nm-thick GeN learn more buffer layer can be this website reduced

from 3.5V to 2.2 V. The GeN buffer layer will play an important role in high density and low power consumption PCM applications.”
“Commonsense, logic and clarity provide an ageless quality to Ayurveda knowledge for health care. Ayurvedic institutions along with its teachers, students and practitioners are in despair – a crisis similar to that faced by contemporary Western medicine compatriots. We envision vaidya-scientists, a scholarly group of change agents, who are well versed in the richness of the Ayurveda classics and the details and insights of modern biology. While acknowledging the need to create physician-scientists in India, we portray here a tentative roadmap for creating Vaidya-Scientists as ambassadors to catalyse a much needed Ayurveda renaissance to invigorate and renew its teaching, research and practice.”
“Amyotrophic lateral sclerosis (ALS) is a multisystem disease that overlaps with frontotemporal dementia (FTD). Although FTD patients exhibit prominent deficits in emotion perception and social cognition, these domains have received relatively little attention in ALS. Moreover, direct comparisons between ALS and FTD on emotion processing tasks remain lacking.

7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to 1.23; P = 0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of 399), as compared with 4.4% signaling pathway of survivors in the lower-intensity group (18 of 411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI, 0.86 to 2.92; P = 0.14). Hypophosphatemia was more common in the higher-intensity group than in the lower-intensity group (65% vs. 54%, P< 0.001).\n\nConclusions\n\nIn critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality

at 90 days. (ClinicalTrials.gov number, NCT00221013.)”
“RAR1, SGT1, and HSP90 are important components of effector-triggered immunity (ETI) ON-01910 in diverse plants, where RAR1 and SGT1 are thought to serve as HSP90 co-chaperones. We show that ETI in soybean requires RAR1 and SGT1 but

not HSP90. Rsv1-mediated extreme resistance to Soybean mosaic virus (SMV) and Rpg-1b-mediated resistance to Pseudomonas syringae were compromised in plants silenced for GmRAR1 and GmSGT1-2 but not GmHSP90. This suggests that RAR1- or SGT1-dependant signaling is not always associated with a dependence on HSP90. Unlike in Arabidopsis, SGT1 in soybean also mediates ETI against the bacterial pathogen P. syringae. Similar to Arabidopsis, soybean RAR1 and SGT1 proteins interact with each other and two related

HSP90 proteins. Plants silenced for GmHSP90 genes or GmRAR1 exhibited altered morphology, suggesting that these proteins also contribute to developmental processes. Silencing GmRAR1 and GmSGT1-2 impaired resistance to virulent bacteria and systemic acquired resistance (SAR) in soybean as well. Because the Arabidopsis rar1 mutant also showed a defect in SAR, we conclude that RAR1 and SGT1 serve as a point of convergence for basal resistance, ETI, and SAR. We demonstrate that, although soybean defense signaling pathways recruit structurally conserved components, they have distinct requirements for specific proteins.”
“Objectives The aim of the study is to evaluate the safety and effectiveness of treating femoropopliteal in-stent restenosis (ISR) with debulking with excimer laser followed by implantation of a VIABAHN endoprosthesis. Background The optimal Ilomastat chemical structure treatment strategy for femoropopliteal ISR is unclear. Methods The SALVAGE study is a multicenter prospective registry involving nine US centers. Patients with femoropopliteal ISR with moderate to severe intermittent claudication or critical limb ischemia (Rutherford categories 25) and an ankle-brachial index (ABI) =0.8 were treated with excimer laser and the VIABAHN endoprosthesis. The primary efficacy endpoint is primary patency at 12 months as measured by duplex ultrasonography. The primary safety endpoint is the major adverse event (MAE) rate at 30 days.

\n\nResults: Using surface plasmon resonance imaging (SPRI), the deposition of protein by vascular smooth muscle cells (vSMC) cultured on fibronectin was quantified as a function of cell density and distance from the cell periphery. We observed that as much as KPT-8602 in vitro 120 ng/cm(2) of protein was deposited by cells in 24 h.\n\nConclusion: SPRI is a real-time, low-light-level, label-free imaging technique that allows the simultaneous

observation and quantification of protein layers and cellular features. This technique is compatible with live cells such that it is possible to monitor cellular modifications to the extracellular matrix in real-time.”
“This report defines the role of Apophysomyces as an aggressive fungal pathogen seen after a tornado injury. Clinical and laboratory manifestations of infections after environmentally contaminated wounds incurred during a tornado are outlined, emphasizing mechanism of injury, comorbidities, and diagnostic and treatment challenges. Therapy selleck chemicals llc with systemic antifungal therapy and aggressive serial tissue debridement was successful in achieving cure.”
“A taxonomic re-evaluation

of the Carcharhinus sealei-dussumieri group using meristic and morphological data revealed that this group consists of 5 species. Two species, Carcharhinus coatesi (Whitley, 1939) from northern Australia and probably New Guinea and C. tjutjot (Bleeker, 1852) from Indonesian to Taiwan, are resurrected as valid species and together

with C. dussumieri and C. sealei are redescribed. Garrick’s lectotype designation of C. dussumieri and C. tjutjot are retained. A neotype for C. sealei, collected from the same locality as the holotype which was destroyed during World War II, is designated. A fifth, possibly undescribed species (Carcharhinus sp.) is also noted from the Western Indian Ocean and its affinities briefly discussed. The four redescribed species are very similarly morphologically but can be distinguished by a combination of meristic, morphological, dental and colour characters. The most important GSK1838705A characters for distinguishing these species are: vertebral counts, tooth counts, tooth morphology, shape of first dorsal and pectoral fins, second dorsal fin colouration, and mouth width. Two independent molecular studies have produced results which closely correlate with and support the findings of this study.”
“A series of stilbazolium salts based on donor-it-acceptor (D-it-A) structure have been synthesized and fully characterized. Photophysical properties including linear absorption, one-photon excited fluorescence (OPEF), two-photon absorption (2PA) properties were systematically investigated. The results suggest that increasing electron-releasing character of the terminal group leads to a more pronounced donor-to-acceptor intramolecular charge transfer (ICT).

These findings are new and innovative

as they enlarge the knowledge about basic physiologic and neuroplastic processes in tinnitus.”
“An increased use of bio fuels would contribute to sustainable development by reducing greenhouse-gas emissions and the use of non-renewable resources. Lignocellulosic biomass, including agricultural Selleck APR-246 and forestry residues instead of traditional feedstock (starch crops), could prove to be an ideally inexpensive and abundantly available source of sugar for fermentation into transportation fuels. Cellulose, accessible surface area, protection by lignin, and sheathing by hemicelluloses all contribute to the resistance of cellulose in biomass to hydrolysis for the conversion to fuels. Our research had as objective the reduction of lignin by supercritical fluid extraction process by choosing optimal parameters of extractant, extraction time, pressure and temperature adapted on plant material used. Tests of lignin extraction with supercritical CO2 in laboratory facilities

were performed on cobs and corn stalks. Parameters were followed biomass size ( smaller than 2.35 mm, 2.35 to 3.5 mm), the influence of the type of solvent (methanol and butanol) and co solvent concentration (50-100%). The best results were obtained in extraction with methanol / water 50% v / v. Research is part learn more of the ERA IB 6001, international project.”
“The present study was designed to determine ANG peptide content [ANG I, ANG II, ANG( 1-7)], ACE2 mRNA, and the immunocytochemical

distribution of ANG-(1-7) and ACE2 in the uteroembryonic unit during early and late gestation in Sprague-Dawley rats and in a rat model of pregnancy-induced hypertension, the reduced uterine perfusion pressure (RUPP) model. At early pregnancy ANG-(1-7) and ACE2 staining were localized in the primary and secondary decidual zone and luminal and glandular epithelial cells. During late gestation, ANG-(1-7) and ACE2 staining was visualized in the labyrinth placenta and amniotic and yolk sac epithelium. Uterine ANG C188-9 solubility dmso II concentration at early pregnancy was significantly decreased by 21-55% in the implantation and interimplantation sites compared with virgin rats, whereas ANG-(1-7) levels were maintained at prepregnancy levels. At late gestation, uterine concentrations of ANG I and ANG II were significantly increased (30% and 25%, respectively). In RUPP animals, ANG-(1-7) concentration is significantly reduced in the uterus (181 +/- 16 vs. 372 +/- 74 fmol/g of tissue) and placenta (143 +/- 26 vs. 197 +/- 20 fmol/g of tissue). ACE2 mRNA increased in the uterus of early pregnant compared with virgin rats, yet within the implantation site it was downregulated. At late pregnancy, ACE2 mRNA is elevated by 58% in the uterus and decreased by 59% in RUPP animals.

Movement and orientation of the fin rays relative to the body axis were calculated throughout the duration of the C-start. We found that:

(1) timing and magnitude of angular displacement varied among fin rays based on position within the fin and (2) kinematic patterns support the prediction that fin rays are actively resisting hydrodynamic forces and transmitting momentum into the water. We suggest that regions within the fins have different roles. Anterior regions of the fins are rapidly elevated to increase the volume of water that the fish may interact with and transmit force into, thus generating greater total momentum. The movement pattern of all the fin rays creates traveling waves selleck compound that move posteriorly along the length Pevonedistat order of the fin, moving water as they do so. Flexible posterior regions ultimately act to accelerate this water towards the tail, potentially interacting with vortices generated by the caudal fin during the C-start. Despite their simple appearance, median fins are highly complex and versatile control surfaces that modulate

locomotor performance.”
“Chronic lymphocytic leukemia (CLL) is the most common lymphoid neoplasia in Western societies and is currently incurable. Multiple treatment options are practiced, but the available small molecule drugs suffer from dose-limiting toxicity and undesirable side effects. The need for new, less toxic treatments is a pressing concern. Here, we demonstrate that (-)-agelastatin A (1a), a pyrrole-imidazole alkaloid obtained from a marine GSK1210151A sponge, exhibits potent in vitro activity against primary cell lines of CLL

and disclose the synthesis of several analogues that are equipotent or exceed the potency of the natural product. The novel synthetic analogue, 13-debromo-13-trifluoromethyl agelastatin A (1j), showed higher activity than the natural product when tested against the same cell lines and is the most potent agelastatin derivative reported to date. A detailed in vitro structure-activity relationship of la in CLL compared to that of 22 synthetic analogues is described along with preliminary in vivo pharmacokinetic and metabolism studies on the most potent compounds.”
“Disturbances in parvalbumin- and somatostatin-containing neurons, including deficits in the gamma-aminobutyric acid (GABA)-synthesizing enzyme GAD67 in the prefrontal cortex (PFC) in schizophrenia, may be related to disrupted pre- and/or postnatal development. Deficits in the transcription factor Lhx6, which regulates parvalbumin and somatostatin neuron development, are associated with GAD67 deficits in schizophrenia.

\n\nFor each decade of life, odds increase strikingly that

smoking decreases %FEV(1)/FEV(6) and %FEV(1)/FVC. At least for these three ethnicities, Delta lung age can be easily calculated as the product of (predicted-actual) %FEV(1)/FEV(6) find more x 4 or (predicted-actual) %FEV(1)/FVC x 3. Through the sixth decade of life, smokers’ Delta lung age increase rapidly but little thereafter, presumably due to the inabilities of older smokers to participate in the survey or their deaths.\n\nUsing odds and Delta lung ages rather than traditional 95%confidence limits might better persuade smokers to quit.”
“High-fidelity chromosome segregation during mitosis requires kinetochores, protein complexes that assemble on centromeric DNA and mediate chromosome attachment to spindle microtubules. In budding yeast, phosphoinositide-specific Bcl-2 inhibitor phospholipase C (Plc1p encoded by PLC1 gene) is important for function of kinetochores. Deletion of PLC1 results in alterations in chromatin structure of centromeres, reduced binding of microtubules to minichromosomes, and a higher frequency of chromosome loss. The mechanism of Plc1p’s involvement in kinetochore activity was not initially obvious; however, a testable hypothesis emerged with the discovery of the role of inositol polyphosphates (InsPs), produced by a Plc1p-dependent pathway, in the regulation

of chromatin-remodeling complexes. In addition, the remodels structure of chromatin (RSC) chromatin-remodeling complex was found to associate with kinetochores and to affect centromeric chromatin structure. We report here that Plc1p and InsPs are required for recruitment of the RSC complex to kinetochores, which is important for establishing proper chromatin structure of centromeres and centromere proximal regions. Mutations in PLC1 and components of the RSC complex exhibit strong genetic interactions and display synthetic growth defect, altered nuclear morphology, and higher frequency of minichromosome loss. The results thus provide a mechanistic explanation for the previously

elusive Salubrinal cost role of Plc1p and InsPs in kinetochore function.”
“Rab3A is a synaptic vesicle-associated protein found throughout the nervous system, but its precise function is unknown. Genetic knock-out studies show that Rab3A is not necessary for vesicular release or replenishment at conventional synapses in the brain. Here we explore the function of Rab3A at ribbon synapses in the retina of the tiger salamander (Ambystoma tigrinum). Fluorescently labeled Rab3A, delivered into rods and cones through a patch pipette, binds to and dissociates from synaptic ribbons. Experiments using nonphosphorylatable GDP analogs and a GTPase-deficient Rab3A mutant indicate that ribbon binding and dissociation are governed by a GTP hydrolysis cycle.