Real-time intermembrane force measurements and imaging of lipid domain morphology during hemifusion

Membrane fusion is the core process in membrane trafficking and is essential for cellular transport of proteins and other biomacromolecules. During protein-mediated membrane fusion, membrane proteins are often excluded from the membrane-membrane contact, indicating that local structural transformations in lipid domains play a major role. However, the rearrangements of lipid domains during fusion have not been thoroughly examined. Here using a newly developed Fluorescence Surface Forces Apparatus (FL-SFA), migration of liquid-disordered clusters and depletion of liquid-ordered domains at the membrane-membrane contact are imaged in real time during hemifusion of model lipid membranes, together with simultaneous force-distance and lipid membrane thickness measurements. The load and contact time-dependent hemifusion results show that the domain rearrangements decrease the energy barrier to fusion, illustrating the significance of dynamic domain transformations in membrane fusion processes. Importantly, the FL-SFA can unambiguously correlate interaction forces and in situ imaging in many dynamic interfacial systems.open0

Molecular diversity of anthracnose pathogen populations associated with UK strawberry production suggests multiple introductions of three different Colletotrichum species.

Fragaria × ananassa (common name: strawberry) is a globally cultivated hybrid species belonging to Rosaceae family. Colletotrichum acutatum sensu lato (s.l.) is considered to be the second most economically important pathogen worldwide affecting strawberries. A collection of 148 Colletotrichum spp. isolates including 67 C. acutatum s.l. isolates associated with the phytosanitary history of UK strawberry production were used to characterize multi-locus genetic variation of this pathogen in the UK, relative to additional reference isolates that represent a worldwide sampling of the diversity of the fungus. The evidence indicates that three different species C. nymphaeae, C. godetiae and C. fioriniae are associated with strawberry production in the UK, which correspond to previously designated genetic groups A2, A4 and A3, respectively. Among these species, 12 distinct haplotypes were identified suggesting multiple introductions into the country. A subset of isolates was also used to compare aggressiveness in causing disease on strawberry plants and fruits. Isolates belonging to C. nymphaeae, C. godetiae and C. fioriniae representative of the UK anthracnose pathogen populations showed variation in their aggressiveness. Among the three species, C. nymphaeae and C. fioriniae appeared to be more aggressive compared to C. godetiae. This study highlights the genetic and pathogenic heterogeneity of the C. acutatum s.l. populations introduced into the UK linked to strawberry production

Characterization of seasonal groundwater origin and evolution processes in a geologically heterogeneous catchment using geophysical, isotopic and hydro-chemical techniques (Lough Gur, Ireland)

Lough Gur is a shallow groundwater fed eutrophic lake situated within a small agri-cultural catchment containing volcanic and karst rock features in mid-west Ireland.Seasonally active conduits linking two spring discharge locations from the lake underhigh flow conditions were revealed using dye tracing and a terrestrial geophysicalsurvey, highlighting the architecture of the conduit flow path from Lough Gur to itsdischarge spring. A radon survey combined with a lake geophysical survey identifiedthe locations of in-lake discharge springs and thickness of the lakebed sediments.Falling head hydraulic characterization experiments illustrated the heterogenousnature of lakebed sediments and hydrograph analysis coupled with stable isotopes ofwater (δ18O andδ2H) revealed significant surface water - groundwater interactionduring high flow periods. Significantly,δ18O andδ2H signatures plot above the globalmeteoric water line and local meteoric water line indicating hydration of silicate min-erals and direct isotope exchange ofδ18O between water and rock minerals. Ground-waterδ18O andδ2H signatures during low flow periods indicate that rechargesources are influenced by enriched surface waters and precipitation while a widerrange of signatures during high flow periods indicates a greater variation of sources.D-excess signatures illustrate rapid rainfall infiltration under high flow conditions,thereby demonstrating the vulnerability of the groundwater, while lake water signa-tures confirm widespread surface water-groundwater interaction/mixing. Hydroche-mical analyses confirm both silicate weathering and carbonate dissolution as primarygeochemical processes with Mg/Ca ratios suggesting greater groundwater residencetime during low flow periods. Correlations betweenδ13CDICand dissolved organiccarbon suggest a seasonal switch in the source of DIC to groundwaters between theoxidation of organic matter in summer and dissolution of carbonate minerals in winter. The SI saturation index for calcite (SIC) illustrates calcium carbonate precipitation along with CO2 evasion to be a perennial processes. Finally, the spatial variation for nitrate isotopic signatures (δ18ONO3- and δ15NNO3-) suggests a number of nitrate sources to groundwaters including soil organic nitrogen, manure and/or domestic effluent with indications of denitrification processes under low flow condition

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

International variation in oesophageal and gastric cancer survival 2012–2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study)

Objective To provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare. Methods As part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012–2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country. Results Oesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes. Conclusion Survival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future

Comparison of a one-time educational intervention to a teach-to-goal educational intervention for self-management of heart failure: design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Heart failure (HF) is common, costly and associated with significant morbidity and poor quality of life, particularly for patients with low socioeconomic status. Self-management training has been shown to reduce HF related morbidity and hospitalization rates, but there is uncertainty about how best to deliver such training and what patients benefit. This study compares a single session self-management HF training program against a multiple session training intervention and examines whether their effects differ by literacy level.</p> <p>Methods/Design</p> <p>In this randomized controlled multi-site trial, English and Spanish-speaking patients are recruited from university-affiliated General Internal Medicine and Cardiology clinics at 4 sites across the United States. Eligible patients have HF with New York Heart Association class II-IV symptoms and are prescribed a loop diuretic. Baseline data, including literacy level, are collected at enrollment and follow-up surveys are conducted at 1, 6 and 12 months</p> <p>Upon enrollment, both the control and intervention groups receive the same 40 minute, literacy-sensitive, in-person, HF education session covering the 4 key self-management components of daily self assessment and having a plan, salt avoidance, exercise, and medication adherence. All participants also receive a literacy-sensitive workbook and a digital bathroom scale. After the baseline education was completed, patients are randomly allocated to return to usual care or to receive ongoing education and training. The intervention group receives an additional 20 minutes of education on weight and symptom-based diuretic self-adjustment, as well as periodic follow-up phone calls from the educator over the course of 1 year. These phone calls are designed to reinforce the education, assess participant knowledge of the education and address barriers to success.</p> <p>The primary outcome is the combined incidence of all cause hospitalization and death. Secondary outcomes include HF-related quality of life, HF-related hospitalizations, knowledge regarding HF, self-care behavior, and self-efficacy. The effects of each intervention will be stratified by patient literacy, in order to identify any differential effects.</p> <p>Discussion</p> <p>Enrollment of the proposed 660 subjects will continue through the end of 2009. Outcome assessments are projected to be completed by early 2011.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <url>http://www.clinicaltrials.gov/</url> NCT00378950</p

Electrocatalytic performance of SiO2-SWCNT nanocomposites prepared by electroassisted deposition

“The final publication is available at Springer via http://dx.doi.org/10.1007/s12678-013-0144-3”Composite materials made of porous SiO2 matrices filled with single-walled carbon nanotubes (SWCNTs) were deposited on electrodes by an electroassisted deposition method. The synthesized materials were characterized by several techniques, showing that porous silica prevents the aggregation of SWCNT on the electrodes, as could be observed by transmission electron microscopy and Raman spectroscopy. Different redox probes were employed to test their electrochemical sensing properties. The silica layer allows the permeation of the redox probes to the electrode surface and improves the electrochemical reversibility indicating an electrocatalytic effect by the incorporation of dispersed SWCNT into the silica films.This work was financed by the following research projects: MAT2010-15273 of the Spanish Ministerio de Economia y Competitividad and FEDER, PROMETEO/2013/038 of the GV, and CIVP16A1821 of the Fundacion Ramon Areces. Alonso Gamero-Quijano and David Salinas-Torres acknowledge Generalitat Valenciana (Santiago Grisolia Program) and Ministerio de Economia y Competitividad, respectively, for the funding of their research fellowships.Gamero-Quijano, A.; Huerta, F.; Salinas-Torres, D.; Morallón, E.; Montilla, F. (2013). Electrocatalytic performance of SiO2-SWCNT nanocomposites prepared by electroassisted deposition. Electrocatalysis. 4(4):259-266. https://doi.org/10.1007/s12678-013-0144-3S25926644P. Alivisatos, Nat. Biotechnol. 22, 47 (2004)S. Stankovich, D.A. Dikin, G.H. Dommett, K.M. Kohlhaas, E.J. Zimney, E.A. Stach, R.D. Piner, S.T. Nguyen, R.S. Ruoff, Nature 442, 282 (2006)D.W. Schaefer, R.S. Justice, Macromolecules 40, 8501 (2007)M. Endo, M.S. Strano, P.M. Ajayan, Carbon Nanotubes 111, 13 (2008)C.E. Banks, R.G. Compton, Analyst 131, 15 (2006)R.H. Baughman, A.A. Zakhidov, W.A. de Heer, Science 297, 787 (2002)Y.H. Lin, F. Lu, Y. Tu, Z.F. Ren, Nano Letters 4, 191 (2004)B.R. Azamian, J.J. Davis, K.S. Coleman, C.B. Bagshaw, M.L.H. Green, J. Am. Chem. Soc. 124, 12664 (2002)W. Yang, K. Ratinac, S. Ringer, P. Thordarson, J.G. Gooding, F. Braet, Angew. Chem. Int. Ed. 49, 2114 (2010)C.E. Banks, R.G. Compton, Analyst 130, 1232 (2005)L. Mazurenko, M. Etienne, O. Tananaiko, V. Zaitsev, A. Walcarius, Electrochim. Acta 83, 359 (2012)J.M.P. Paloma Yáñez-Sedeño, J. Riu, F.X. Rius, TrAC Trends in Analytical Chemistry 29, 939 (2010)Z.J. Wang, M. Etienne, S. Poller, W. Schuhmann, G.W. Kohring, V. Mamane, A. Walcarius, Electroanalysis 24, 376 (2012)R. Bandyopadhyaya, E. Nativ-Roth, O. Regev, R. Yerushalmi-Rozen, Nano Letters 2, 25 (2002)C. Park, Z. Ounaies, K.A. Watson, R.E. Crooks, J. Smith, S.E. Lowther, J.W. Connell, E.J. Siochi, J.S. Harrison, T.L.S. Clair, Chem. Phys. Lett. 364, 303 (2002)O. Matarredona, H. Rhoads, Z.R. Li, J.H. Harwell, L. Balzano, D.E. Resasco, Journal of Physical Chemistry B 107, 13357 (2003)L. Vaisman, H. Wagner, G. Marom, Advances in Colloid and Interface Science 128, 37 (2006)Y.C. Xing, Journal of Physical Chemistry B 108, 19255 (2004)J.J. Liang, Y. Huang, L. Zhang, Y. Wang, Y.F. Ma, T.Y. Guo, Y.S. Chen, Adv. Funct. Mater. 19, 2297 (2009)D. Salinas-Torres, F. Huerta, F. Montilla, E. Morallón, Electrochim. Acta 56, 2464 (2011)Z.F. Ren, Z.P. Huang, J.W. Xu, J.H. Wang, P. Bush, M.P. Siegal, P.N. Provencio, Science 282, 1105 (1998)W.Z. Li, S.S. Xie, L.X. Qian, B.H. Chang, B.S. Zou, W.Y. Zhou, R.A. Zhao, G. Wang, Science 274, 1701 (1996)M. Terrones, N. Grobert, J. Olivares, J.P. Zhang, H. Terrones, K. Kordatos, W.K. Hsu, J.P. Hare, P.D. Townsend, K. Prassides, A.K. Cheetham, H.W. Kroto, D.R.M. Walton, Nature 388, 52 (1997)R. Toledano, D. Mandler, Chem. Mater. 22, 3943 (2010)J.H. Rouse, Langmuir 21, 1055 (2005)X.B. Yan, B.K. Tay, Y. Yang, Journal of Physical Chemistry B 110, 25844 (2006)J. Lim, P. Malati, F. Bonet, B. Dunn, J. Electrochem. Soc. 154, A140 (2007)L.D. Zhu, C.Y. Tian, J.L. Zhai, R.L. Yang, Sensors and Actuators B-Chemical 125, 254 (2007)F. Montilla, M.A. Cotarelo, E. Morallón, J. Mater. Chem. 19, 305 (2009)D. Salinas-Torres, F. Montilla, F. Huerta, E. Morallón, Electrochim. Acta 56, 3620 (2011)T. Dobbins, R. Chevious, Y. Lvov, Polymers 3, 942 (2011)R. Esquembre, J.A. Poveda, C.R. Mateo, Journal of Physical Chemistry B 113, 7534 (2009)M.L. Ferrer, R. Esquembre, I. Ortega, C.R. Mateo, F. del Monte, Chem. Mater. 18, 554 (2006)M.J. O'Connell, S. Sivaram, S.K. Doorn, Physical Review B 69, 235415 (2004)C. Domingo, G. Santoro, Opt. Pura Apl 40, 175 (2007)M.S. Dresselhaus, G. Dresselhaus, R. Saito, A. Jorio, Physics Reports 409, 47 (2005)R.L. McCreery, Chem. Rev. 108, 2646 (2008)C.G. Zoski, in Handbook of Electrochemistry, 1st ed (Elsevier, Amsterdam, 2007

SNP Haplotype Mapping in a Small ALS Family

The identification of genes for monogenic disorders has proven to be highly effective for understanding disease mechanisms, pathways and gene function in humans. Nevertheless, while thousands of Mendelian disorders have not yet been mapped there has been a trend away from studying single-gene disorders. In part, this is due to the fact that many of the remaining single-gene families are not large enough to map the disease locus to a single site in the genome. New tools and approaches are needed to allow researchers to effectively tap into this genetic gold-mine. Towards this goal, we have used haploid cell lines to experimentally validate the use of high-density single nucleotide polymorphism (SNP) arrays to define genome-wide haplotypes and candidate regions, using a small amyotrophic lateral sclerosis (ALS) family as a prototype. Specifically, we used haploid-cell lines to determine if high-density SNP arrays accurately predict haplotypes across entire chromosomes and show that haplotype information significantly enhances the genetic information in small families. Panels of haploid-cell lines were generated and a 5 centimorgan (cM) short tandem repeat polymorphism (STRP) genome scan was performed. Experimentally derived haplotypes for entire chromosomes were used to directly identify regions of the genome identical-by-descent in 5 affected individuals. Comparisons between experimentally determined and in silico haplotypes predicted from SNP arrays demonstrate that SNP analysis of diploid DNA accurately predicted chromosomal haplotypes. These methods precisely identified 12 candidate intervals, which are shared by all 5 affected individuals. Our study illustrates how genetic information can be maximized using readily available tools as a first step in mapping single-gene disorders in small families

Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1

<p>Abstract</p> <p>Background</p> <p>Steroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC) in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive.</p> <p>Methods</p> <p>Flat panel detector-based cone beam computed tomography (FPDCT) was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT). Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1) protein expression.</p> <p>Results</p> <p>Mice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071) and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.). Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients.</p> <p>Conclusion</p> <p>FPDCT allows longitudinal monitoring of exophytic tumor growth in the UPII-SV40T model of BC that bypasses need for chemical carcinogens, which confound analysis of androgen effects. Androgens increase tumor cell growth <it>in vitro </it>and <it>in vivo </it>and decrease TSP1 expression, possibly explaining the therapeutic effect of castration. This effect may, in part, explain gender differences in BC incidence and implies anti-androgenic therapies may be effective in preventing and treating BC.</p