bluuebunny/crossref_metadata_2025 huggingface dataset:
B Cells, Dendritic Cells, and Macrophages Are Required To Induce an Autoreactive CD4 Helper T Cell Response in Experimental Epidermolysis Bullosa Acquisita
Authors: Iwata Hiroaki , Bieber Katja , Tiburzy Benjamin , Chrobok Navina , Kalies Kathrin , Shimizu Atsushi , Leineweber Sarah , Ishiko Akira , Vorobyev Artem , Zillikens Detlef , Köhl Jörg , Westermann Jürgen , Seeger Karsten , Manz Rudolf , Ludwig Ralf J.
Published: August 2013

In autoimmune bullous dermatoses (AIBD), autoantibodies induce blisters on skin or mucous membranes, or both. Mechanisms of continued autoantibody production and blistering have been well characterized using AIBD animal models. Mechanisms leading to the initial autoantibody production, however, have not been investigated in detail. Epidermolysis bullosa acquisita (EBA) is an AIBD associated with autoantibodies to type VII collagen (COL7). The majority of EBA patients’ sera recognize the noncollagenous domain 1, including the von Willebrand factor A–like domain 2 (vWFA2). In experimental EBA induced by immunization with GST-COL7, disease manifestation depended on the genetic background, a Th1 polarization, and the GST-tag. In this model, nude mice neither produced autoantibodies nor blisters. It has remained uncertain which APC and T cell subsets are required for EBA induction. We established a novel EBA model by immunization with vWFA2 fused to intein (lacking the GST-tag). All tested mouse strains developed autoantibodies, but blisters were exclusively observed in mice carrying H2s. In immunized mice, CD4 T cells specific for vWFA2 were detected, and their induction required presence of B cells, dendritic cells, and macrophages. Anti-vWFA2 autoantibodies located at the lamina densa bound to the dermal side of salt-split skin and induced blisters when transferred into healthy mice. Absence of CD8 T cells at time of immunization had no effect, whereas depletion of CD4 T cells during the same time period delayed autoantibody production and blisters. Collectively, we demonstrate the pathogenic relevance of Abs targeting the vWFA2 domain of COL7 and show the requirement of APC-induced CD4 T cells to induce experimental EBA.
The Interdependent, Overlapping, and Differential Roles of Type I and II IFNs in the Pathogenesis of Experimental Autoimmune Encephalomyelitis
Authors: Naves Rodrigo , Singh Simer P. , Cashman Kevin S. , Rowse Amber L. , Axtell Robert C. , Steinman Lawrence , Mountz John D. , Steele Chad , De Sarno Patrizia , Raman Chander
Published: August 2013

Type I IFNs (IFN-α and IFN-β) and type II IFN (IFN-γ) mediate both regulation and inflammation in multiple sclerosis, neuromyelitis optica, and in experimental autoimmune encephalomyelitis (EAE). However, the underlying mechanism for these Janus-like activities of type I and II IFNs in neuroinflammation remains unclear. Although endogenous type I IFN signaling provides a protective response in neuroinflammation, we find that when IFN-γ signaling is ablated, type I IFNs drive inflammation, resulting in exacerbated EAE. IFN-γ has a disease stage–specific opposing function in EAE. Treatment of mice with IFN-γ during the initiation phase of EAE leads to enhanced severity of disease. In contrast, IFN-γ treatment during the effector phase attenuated disease. This immunosuppressive activity of IFN-γ required functional type I IFN signaling. In IFN-α/β receptor–deficient mice, IFN-γ treatment during effector phase of EAE exacerbated disease. Using an adoptive transfer EAE model, we found that T cell–intrinsic type I and II IFN signals are simultaneously required to establish chronic EAE by encephalitogenic Th1 cells. However, in Th17 cells loss of either IFN signals leads to the development of a severe chronic disease. The data imply that type I and II IFN signals have independent but nonredundant roles in restraining encephalitogenic Th17 cells in vivo. Collectively, our data show that type I and II IFNs function in an integrated manner to regulate pathogenesis in EAE.
The Cellular Source and Target of IL-21 in K/BxN Autoimmune Arthritis
Authors: Block Katharine E. , Huang Haochu
Published: August 2013

IL-21 is a pluripotent cytokine that regulates B cell and plasma cell differentiation and is thought be an autocrine factor for follicular helper T cell (TFH) and Th17 differentiation. Although IL-21 has been implicated in autoimmune diseases, its relevant cellular source and target cells have not been well characterized. We investigated this issue in the K/BxN mouse model of autoimmune arthritis. Adoptive transfer of KRN-transgenic CD4+ T cells into appropriate hosts drives germinal center (GC) formation and autoantibody production against glucose-6-phosphate isomerase, leading to joint inflammation and destruction. By comparing transfer of T or B cells deficient in IL-21 or IL-21R, we were able to dissect the contribution of each cell type. T cells deficient in IL-21 did not induce GC formation or autoantibody production, but they went through normal TFH differentiation. However, T cells lacking IL-21R induced Ab titers, GC B cell frequency, and arthritis development similar to wild-type T cells, suggesting that IL-21 is not required for TFH differentiation and function. IL-21 acts on B cells, because IL-21R expression on B cells was required to induce disease. In contrast, Th17 cells, a T cell subset that also produces IL-21 and can provide help to B cells, are not required for the GC response and arthritis. These data have implications in developing effective therapies for rheumatoid arthritis and other Ab-mediated autoimmune diseases.
Renal Medullary Carcinoma Response to Chemotherapy: a Referral Center Experience in Brazil
Authors: Maroja Silvino Marina Cavalcanti , Venchiarutti Moniz Camila Motta , Munhoz Piotto Gustavo Henrique , Siqueira Sheila , Galapo Kann Ariel , Dzik Carlos
Published: August 2013

Renal medullary carcinoma (RMC) is rare, accounting for less than 1% of all renal neoplasms. Case reports suggest RMC is highly aggressive, poorly responsive to chemotherapy, often metastatic at diagnosis, affects young men with sickle cell trait, and median overall survival (mOS) is less than 12 months. We report the epidemiological characteristics, treatments performed, response rate to each treatment and mOS of five patients with RMC. All patients had sickle cell trait, four were male, three had metastatic disease at diagnosis and mean age at diagnosis was 25 years. Non-metastatic patients were submitted to nephrectomy. Two patients had partial response to first line chemotherapy including cisplatin and gemcitabine. There was no response to sunitinib or second line chemo - therapy; mOS was 6 months. Due to its rarity, case series are the only evidence available to discuss the treatment for RMC. In our experience, only cisplatin and gemcitabine based regimen offered response.
Short Communication: Ruminal pH profile and feeding behaviour of feedlot cattle transitioning from a high-forage to a high-concentrate diet
Authors: Holtshausen L. , Schwartzkopf-Genswein K. S. , Beauchemin K. A.
Published: August 2013

Holtshausen, L., Schwartzkopf-Genswein, K. S. and Beauchemin, K. A. 2013. Short Communication: Ruminal pH profile and feeding behaviour of feedlot cattle transitioning from a high-forage to a high-concentrate diet. Can. J. Anim. Sci. 93: 529–533. Sixteen ruminally cannulated cattle (384±33.9 kg) were transitioned from a high-forage to a finishing diet over 21 d using three steps (+15% concentrate DM wk−1). Following the initiation of each transition step, mean daily ruminal pH declined and DM intake, meal size and meal duration were reduced. Recovery time to baseline feeding behaviour increased with severity of acidosis. Changes in feeding behaviour can be indicative of sub-optimal ruminal pH conditions during dietary transition. Transition protocols such as more steps, smaller grain increments or shorter initial and longer final steps may aid in reducing the incidence of acidosis.
In situ measurement of snowmelt infiltration under various topsoil cap thicknesses on a reclaimed site
Authors: Christensen Andre F. , He Hailong , Dyck Miles F. , Lenore Turner E. , Chanasyk David S. , Naeth M. Anne , Nichol Connie
Published: August 2013

Christensen, A. F., He, H., Dyck, M. F., Turner, L., Chanasyk, D. S., Naeth, M. A. and Nichol, C. 2013. In situ measurement of snowmelt infiltration under various topsoil cap thicknesses on a reclaimed site. Can. J. Soil Sci. 93: 497–510. Understanding the soil and climatic conditions affecting the partitioning of snowmelt to runoff and infiltration during spring snow ablation is a requisite for water resources management and environmental risk assessment in cold semi-arid regions. Soil freezing and thawing processes, snowmelt runoff or infiltration into seasonally frozen soils have been documented for natural, agricultural or forested systems but rarely studied in severely disturbed systems such as reclaimed lands. The objective of this study was to quantify the snowmelt infiltration/runoff on phosphogypsum (PG) tailings piles capped with varying thicknesses of topsoil (0.15, 0.3, and 0.46 m) at a phosphate fertilizer production facility in Alberta. There are currently no environmental regulations specifying topsoil capping thickness or characteristics for these types of tailings piles. Generally, the function of the topsoil cap is to facilitate plant growth and minimize the amount of drainage into the underlying PG. Experimental plots were established in 2006 to better understand the vegetation and water dynamics in this reconstructed soil. In 2011, time domain reflectometry (TDR) probes and temperature sensors were installed at various depths for continuous, simultaneous, and automated measurement of composite dielectric permittivity (ɛeff) and soil temperature, respectively. An on-site meteorological station was used to record routine weather data. Liquid water and ice content were calculated with TDR-measured effective permittivity (ɛeff) and a composite dielectric mixing model. Spatial and temporal change of total water content (ice and liquid) revealed that snowmelt infiltration into the topsoil cap increased with increasing topsoil depth and net soil water flux from the topsoil cap into the PG material was positive during the snowmelt period in the spring of 2011. Given the objective of the capping soil is to reduce drainage of water into the PG material it is recognized that a capping soil with a higher water-holding capacity could reduce the amount of meteoric water entering the tailings.
Anatomy of the Spermatophore in Triatomines (Hemiptera, Reduviidae, Triatominae) and Its Applications to the Study of Chagas Disease Vector Biology
Authors: Pereira-Lourenço Ariane S. , Santos-Mallet Jacenir R. , Freitas Simone P. C.
Published: August 2013

The present study focused on spermatophore structure, transfer, and subsequent destination inside bloodfeeding females of the species Triatoma infestans and Rhodnius neglectus. The morphology of the spermatophore differed between the species studied, such that in T. infestans, the shape was ovaloid, whereas in R. neglectus, the shape resembled a rod. Structures' spine-like cuticulars distributed across the inner surface of the vagina of both species were observed; however, the role of these cuticulars is unknown in Triatominae. In both species, there was an opening in the spermatophore exactly where the common oviduct is connected, thereby making it possible to confirm that the process of spermatozoid migration takes place through this opening. The results obtained show that the spermatophores of T. infestans and R. neglectus differ in size, shape, and structure. Therefore, they can be used as taxonomic markers and may provide information regarding physiology and evolution.
Characterization of Three Novel Adhesins of Leptospira interrogans
Authors: Siqueira Gabriela H. , Atzingen Marina V. , Alves Ivy J. , de Morais Zenaide M. , Vasconcellos Silvio A. , Nascimento Ana L. T. O.
Published: August 2013

We report cloning, expression, purification, and characterization of three predicted leptospiral membrane proteins (LIC11360, LIC11009, and LIC11975). In silico analysis and proteinase K accessibility data suggest that these proteins might be surface exposed. We show that proteins encoded by LIC11360, LIC11009 and LIC11975 genes interact with laminin in a dose-dependent and saturable manner. The proteins are referred to as leptospiral surface adhesions 23, 26, and 36 (Lsa23, Lsa26, and Lsa36), respectively. These proteins also bind plasminogen and generate active plasmin. Attachment of Lsa23 and Lsa36 to fibronectin occurs through the involvement of the 30-kDa and 70-kDa heparin-binding domains of the ligand. Dose-dependent, specific-binding of Lsa23 to the complement regulator C4BP and to a lesser extent, to factor H, suggests that this protein may interfere with the complement cascade pathways. Leptospira spp. may use these interactions as possible mechanisms during the establishment of infection.
The Complex Relationship between Weather and Dengue Virus Transmission in Thailand
Authors: Campbell Karen M. , Lin C. D. , Iamsirithaworn Sopon , Scott Thomas W.
Published: August 2013

Using a novel analytical approach, weather dynamics and seasonal dengue virus transmission cycles were profiled for each Thailand province, 1983–2001, using monthly assessments of cases, temperature, humidity, and rainfall. We observed systematic differences in the structure of seasonal transmission cycles of different magnitude, the role of weather in regulating seasonal cycles, necessary versus optimal transmission “weather-space,” basis of large epidemics, and predictive indicators that estimate risk. Larger epidemics begin earlier, develop faster, and are predicted at Onset change-point when case counts are low. Temperature defines a viable range for transmission; humidity amplifies the potential within that range. This duality is central to transmission. Eighty percent of 1.2 million severe dengue cases occurred when mean temperature was 27–29.5°C and mean humidity was > 75%. Interventions are most effective when applied early. Most cases occur near Peak, yet small reductions at Onset can substantially reduce epidemic magnitude. Monitoring the Quiet-Phase is fundamental in effectively targeting interventions pre-emptively.
When More Poor Means Less Poverty: On Income Inequality and Purchasing Power
Authors: Bergh Andreas , Nilsson Therese
Published: August 2013

We show theoretically that the poor can benefit from price changes induced by higher income inequality. As the number of poor increases, the market for products aimed toward the poor grows, and such products become more profitable. As a result, there are circumstances where an increase in income inequality associates with higher purchasing power of the poor. Using cross‐country data on the price of one kilogram of rice and the price of a Big Mac hamburger, we confirm a negative association between income inequality and the price of inferior goods, robust to the inclusion of a large set of control variables. Results are also robust to a first difference specification and to a two‐stage instrumental variables approach. Examining economic well‐being, it is thus important to analyze not only the incomes of households, but also the prices of the products and services that they buy.
Droughts in the Czech Lands, 1090–2012 AD
Authors: Brázdil R. , Dobrovolný P. , Trnka M. , Kotyza O. , Řezníčková L. , Valášek H. , Zahradníček P. , Štěpánek P.
Published: August 2013

Abstract. This paper addresses droughts in the Czech Lands in the 1090–2012 AD period, basing its findings on documentary evidence and instrumental records. Various documentary sources were employed for the selection of drought events, which were then interpreted at a monthly level. While the data on droughts before 1500 AD are scarce, the analysis concentrated mainly on droughts after this time. A dry year in 1501–1804 period (i.e. pre-instrumental times) was defined as a calendar year in the course of which dry patterns occurred on at least two consecutive months. Using this definition, 129 dry years were identified (an average of one drought per 2.4 yr). From the 16th to the 18th centuries these figures become 41, 36 and 49 yr respectively, with the prevailing occurrence of dry months from April to September (73.7%). Drought indices – SPEI-1, Z-index and PDSI – calculated for the Czech Lands for April–September describe drought patterns between 1805 and 2012 (the instrumental period). N-year recurrence intervals were calculated for each of the three indices. Using N ≥ 5 yr, SPEI-1 indicates 40 drought years, Z-index 39 yr and PDSI 47 yr. SPEI-1 and Z-index recorded 100 yr drought in 1834, 1842, 1868, 1947 and 2003 (50 yr drought in 1992). PDSI as an indicator of long-term drought disclosed two important drought periods: 1863–1874 and 2004–2012. The first period was related to a lack of precipitation, the other may be attributed to recent temperature increases without significant changes in precipitation. Droughts from the pre-instrumental and instrumental period were used to compile a long-term chronology for the Czech Lands. The number of years with drought has fluctuated between 26 in 1951–2000 and 16 in 1651–1700. Only nine drought years were recorded between 1641 and 1680, while between 1981 and 2012 the figure was 22 yr. A number of past severe droughts are described in detail: in 1540, 1590, 1616, 1718 and 1719. A discussion of the results centres around the uncertainty problem, the spatial variability of droughts, comparison with tree-ring reconstructions from southern Moravia, and the broader central European context.
Can sparse proxy data constrain the strength of the Atlantic meridional overturning circulation?
Authors: Kurahashi-Nakamura T. , Losch M. , Paul A.
Published: August 2013

Abstract. In a feasibility study, the potential of proxy data for the temperature and salinity during the Last Glacial Maximum (LGM, about 19 000 to 23 000 yr before present) in constraining the strength of the Atlantic meridional overturning circulation (AMOC) in a general ocean circulation model was explored. The proxy data were simulated by drawing data from four different model simulations at the ocean sediment core locations of the Multiproxy Approach for the Reconstruction of the Glacial Ocean surface (MARGO) project and perturbing these data with realistic noise estimates. The results suggest that our method has the potential of providing estimates of the past strength of the AMOC even from sparse data, but in general paleo-sea surface temperature data without additional prior knowledge about the ocean state during the LGM is not adequate to constrain the model. On the one hand, additional salinity data in the deep ocean and at the sea surface are shown to be highly important in estimating the LGM circulation and as expected, reducing proxy-data errors improves the solutions. Whereas increasing the amount of surface data alone does not appear to be enough for better estimates. Finally, better initial guesses to start the state estimation procedure from greatly improve the performance of the method. Indeed, with a sufficiently good first guess, just the sea-surface temperature data from the MARGO project appear sufficient for reliable estimates of the strength of the AMOC.
Da revolução à regeneração: crônicas de Machado de Assis e de Olavo Bilac sobre a Argentina
Authors: Rodrigues João Paulo Coelho de Souza
Published: August 2013

Ao substituir Machado de Assis como principal cronista do jornal carioca Gazeta de Notícias, Olavo Bilac propôs a seus leitores uma mudança de linguagem literária. Todavia, ele manteve uma das características da crônica de outros escritores do século XIX, sobretudo de Machado de Assis, na tematização dos problemas cotidianos da cidade do Rio de Janeiro. A leitura de algumas crônicas destes dois autores permite iluminar duas interpretações distintas sobre a história argentina, sobre a realidade brasileira e sobre as relações entre Argentina e Brasil, entre a crise final do Império e as reformas urbanas do Rio de Janeiro no início do século XX.
A caricatura política na concepção libertária do periódico A Plebe (1947-1949)
Authors: Silva Zélia Lopes
Published: August 2013

Este artigo discute os sentidos das representações imagéticas (desenhos, caricatura) publicadas em A Plebe, de maio de 1947 a maio de 1949, último período da direção de Edgard Leuenroth. Criado em 1917, o jornal, amparado nos princípios libertários, configurou-se em esfera pública própria para o mundo do trabalho ao discutir os problemas que os trabalhadores enfrentavam em seu cotidiano. O periódico imprimiu fustigadas críticas às elites do país e combateu, sem trégua, o sistema capitalista – qualificado de parasitário, violento e expropriador do proletariado –, ajudado pelas encenações mistificadoras e, igualmente violentas de seu braço religioso expresso nas ações da Igreja Católica cujo combate foi sistemático.
Apresentação
Authors: Silveira Célia Regina da
Published: August 2013

Apresentação do dossiê História, Literatura e Literatos
Padre Belchior de Pontes no universo folhetinesco dos jornais campineiros da década de 1870
Authors: Silveira Célia Regina da
Published: August 2013

A associação proeminente que se estabeleceu entre Júlio Ribeiro e A Carne (1888), em parte em razão do cenário conturbado de sua publicação, acabou por obscurecer seu romance anterior – Padre Belchior de Pontes – publicado no rodapé do jornal Gazeta de Campinas, entre 1876 e 1877. Esse romance mobilizou a imprensa paulista e foi assunto do Diário de Campinas e d’A Província de São Paulo, tanto sob a forma de resenhas e comentários, quanto sob a forma de anúncios. Os jornais, portanto, foram fontes valiosas para inserir essa produção literária de Júlio Ribeiro no horizonte de expectativa de sua época, permitindo, assim, uma análise diacrônica e, também, sincrônica. Neste artigo, buscou-se recompor essa experiência literária no momento próprio de sua aparição.
2013 State of the Water Industry: Exploring the water sector's renewed focus
Authors: Mercer Kenneth
Published: August 2013

If water professionals are to overcome the challenges they face, they must better educate the public about the true value of their water services.
Breaking the White‐paper Cycle: Timing Social Media to Positively Influence Your Utility's Online Reputation
Authors: Hinckley Dan , Baker Keri‐Ann C.
Published: August 2013

Social media provides information in a timely manner with limited costs and allows open communication and comments on the information. It also allows utilities to proactively communicate with their customers and the public. Social media engagement offers many benefits, but these benefits can also be mismanaged, exposing water utilities to negative social media attention.
Cloud‐based computing in the forecast
Authors: Combs Larry
Published: August 2013

Moving to the cloud can cut water/ wastewater supervisory control and data acquisition costs by up to 90% while increasing availability and improving security.
What the Water Sector Can Learn From Recent Weather Disasters
Authors: Spence Shannon , Moyer Jack
Published: August 2013

The years 2011 and 2012 were unprecedented in the weather extremes and disasters they presented. Those weather patterns and incidents have provided strong lessons and reminders to the water sector and others about key preparedness actions that should be taken. These recent weather disasters provide an opportunity to review what the water sector can learn from them and underscores the need for disaster preparedness.
Readers Write – August 2013
Authors: Cohen Harvey T.
Published: August 2013

The letters-to-the-editor section
Solve It! Student Thinking: Suit Up!
Authors: Bair Sherry L. , Mooney Edward S.
Published: August 2013

Solutions to a November 2012 Solve It! problem are discussed, and the procedures used with problem solving are explored.
Window on Resources – August 2013
Authors: Smith Nancy
Published: August 2013

This department contains reviews of books, products, and software.
Réflexions sur les figures de l’intellectuel et du savant en milieu francophone minoritaire
Authors: Ali-Khodja Mourad
Published: August 2013

Examinant les figures de l’intellectuel et du savant en milieufrancophone minoritaire, l’auteur en brosse un tableau àla fois critique et constructif. Prenant exemple de la situation quiprévaut dans l’Acadie du Nouveau-Brunswick, etaprès avoir constaté le peu d’intérêtque cette question suscite généralement, il cherche,d’une part, à rendre compte des formes dedépendance scientifique et intellectuelle qui prévalentencore dans les milieux francophones minoritaires et, d’autrepart, à saisir à travers deux figures opposées del’intellectuel et du savant – celle d’hier etcelle d’aujourd’hui – les limites et lespossibilités de celle-ci et de celle-là et leurportée actuelle.
Bilinguisme et métissage identitaire : vers un modèle conceptuel
Authors: Landry Rodrigue , Allard Réal , Deveau Kenneth
Published: August 2013

Plusieurs recherches montrent la forte présence d’une identité bilingue chez les jeunes francophones du Canada à l’extérieur du Québec. La présente étude propose un modèle conceptuel visant une explication de ce phénomène et présente les résultats d’une étude empirique pancanadienne. L’étude montre que lorsque la concentration territoriale des francophones (CTF) est forte, le métissage identitaire est surtout lié à l’attraction de la langue anglaise et reflète surtout des sentiments de compétence dans cette langue (bilinguisme d’attraction). Lorsque la CTF est faible, ce sont les sentiments d’appartenance à la communauté francophone qui constituent le principal marqueur de l’identité bilingue (bilinguisme de résistance).
Endocytosis gets in tune with action potential bursts
Authors: Herman Melissa A , Rosenmund Christian
Published: August 2013

Neurons use a calcium-dependent mechanism to optimize the rate at which synaptic vesicles are recycled.
Controlling Photons in a Box and Exploring the Quantum to Classical Boundary (Nobel Lecture)
Authors: Haroche Serge
Published: August 2013

Microwave photons trapped in a superconducting cavity constitute an ideal system to realize some of the thought experiments imagined by the founding fathers of quantum physics. The interaction of these trapped photons with Rydberg atoms crossing the cavity illustrates fundamental aspects of measurement theory. The experiments performed with this “photon box” at Ecole Normale Supérieure (ENS) belong to the domain of quantum optics called “Cavity Quantum Electrodynamics”. We have realized the non‐destructive counting of photons, the recording of field quantum jumps, the preparation and reconstruction of “Schrödinger cat” states of radiation and the study of their decoherence, which provides a striking illustration of the transition from the quantum to the classical world. These experiments have also led to the demonstration of basic steps in quantum information processing, including the deterministic entanglement of atoms and the realization of quantum gates using atoms and photons as quantum bits. This lecture starts by an introduction stressing the connection between the ENS photon box and the ion trap experiments of David Wineland, whose accompanying lecture recalls his own contribution to the field of single particle control. I give then a personal account of the early days of Cavity Quantum Electrodynamics before describing the main experiments performed at ENS during the last twenty years and concluding by a discussion comparing our work to other researches dealing with the control of single quantum particles.
Humidity switching properties of sensors based on multiwalled carbon nanotubes/polyvinyl alcohol composite films
Authors: Fei Teng , Jiang Kai , Jiang Fan , Mu Ren , Zhang Tong
Published: August 2013

Multiwalled carbon nanotubes (CNTs) were used as the conductive filler of composites for switching type humidity sensor. The CNTs were oxidized by mixed acids (H2SO4 : HNO3) at a mild temperature to modify carboxylic acid (COOH) groups on the surface of the nanotubes. The dispersibility of acid treated CNTs (CNTs‐COOH) in water is much improved, which is beneficial for dispersing CNTs in the polyvinyl alcohol (PVA) matrix without external additives. The obtained CNTs‐COOH/PVA sensors show nonlinear response to relative humidity (RH), that is, switching properties. The resistances of the sensors remain constant before 80% relative humidity (RH) and then increase sharply with RH, indicating excellent switching characteristic of the sensors. The 10 wt % CNTs‐COOH/PVA sensor shows a sensitivity (ΔR/Ro) of 32.3 at 100% RH. The humidity switching properties of CNTs‐COOH/PVA are much better than that of pristine CNTs/PVA. The improvements are attributed to the improved balance between the dispersibility of CNTs‐COOH and electrical conductivity of the composite films. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39726.
Differential recognition of syk‐binding sites by each of the two phosphotyrosine‐binding pockets of the Vav SH2 domain
Authors: Chen Chih‐Hong , Piraner Dan , Gorenstein Nina M. , Geahlen Robert L. , Beth Post Carol
Published: August 2013

The association of spleen tyrosine kinase (Syk), a central tyrosine kinase in B cell signaling, with Vav SH2 domain is controlled by phosphorylation of two closely spaced tyrosines in Syk linker B: Y342 and Y346. Previous studies established both singly phosphorylated and doubly phosphorylated forms play a role in signaling. The structure of the doubly phosphorylated form identified a new recognition of phosphotyrosine whereby two phosphotyrosines bind simultaneously to the Vav SH2 domain, one in the canonical pTyr pocket and one in the specificity pocket on the opposite side of the central β‐sheet. It is unknown if the specificity pocket can bind phosphotyrosine independent of phosphotyrosine binding the pTyr pocket. To address this gap in knowledge, we determined the structure of the complex between Vav1 SH2 and a peptide (SykLB‐YpY) modeling the singly phosphorylated‐Y346 form of Syk with unphosphorylated Y342. The nuclear magnetic resonance (NMR) data conclusively establish that recognition of phosphotyrosine is swapped between the two pockets; phosphorylated pY346 binds the specificity pocket of Vav1 SH2, and unphosphorylated Y342 occupies what is normally the pTyr binding pocket. Nearly identical changes in chemical shifts occurred upon binding all three forms of singly and doubly phosphorylated peptides; however, somewhat smaller shift perturbations for SykLB‐YpY from residues in regions of high internal mobility suggest that internal motions are coupled to binding affinity. The differential recognition that includes this swapped binding of phosphotyrosine to the specificity pocket of Vav SH2 increases the repertoire of possible phosphotyrosine binding by SH2 domains in regulating protein‐protein interactions in cellular signaling. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 897–907, 2013.
Particle tracking microrheology of purified gastrointestinal mucins
Authors: Georgiades Pantelis , Pudney Paul D. A. , Thornton David J. , Waigh Thomas A.
Published: August 2013

The rheological characteristics of gastric and duodenal mucin solutions, the building blocks of the mucus layer that covers the epithelia of the two organs, were investigated using particle tracking microrheology. We used biochemically well characterized purified porcine mucins (MUC5AC and MUC2) as models for human mucins, to probe their viscoelasticity as a function of mucin concentration and pH. Furthermore, we used both reducing (dithiothreitol, DTT) and chaotropic agents (guanidinium chloride and urea) to probe the mesoscopic forces that mediate the integrity of the polymer network. At neutral pH both gastric and duodenal mucins formed self‐assembled semi‐dilute networks above a certain critical mucin concentration (c*) with the viscosity (η) scaling as
for MUC5AC and
for MUC2, where c is the mucin concentration. Above an even higher mucin concentration threshold (ce, the entanglement concentration) reptation occurs and there is a dramatic increase in the viscosity scaling,
for MUC5AC and
for MUC2. The dynamics of the self‐assembled comb polymers is examined in terms of a scaling model for flexible polyelectrolyte combs. Both duodenum and gastric mucin are found to be pH switchable gels, gelation occurring at low pHs. There is a hundred‐fold increase in the elastic shear modulus once the pH is decreased. The addition of DTT, guanidinium chloride and urea disassembles both the semi‐dilute and gel structures causing a large increase in the compliance (decrease in their shear moduli). Addition of the polyphenol EGCG has a reverse effect on mucin viscoelasticity, that is, it triggers a sol–gel transition in semi‐dilute mucin solutions at neutral pH. © 2013 The Authors. Biopolymers published by Wiley Periodicals, Inc. Biopolymers 101: 366–377, 2014.
Characterization and assembly of a GFP‐tagged cylindriform silk into hexameric complexes
Authors: Öster Carl , Bonde Johan Svensson , Bülow Leif , Dicko Cedric
Published: August 2013

Spider silk has been studied extensively for its attractive mechanical properties and potential applications in medicine and industry. The production of spider silk, however, has been lagging behind for lack of suitable systems. Our approach focuses on solving the production of spider silk by designing, expressing, purifying and characterizing the silk from cylindriform glands. We show that the cylindriform silk protein, in contrast to the commonly used dragline silk protein, is fully folded and stable in solution. With the help of GFP as a fusion tag we enhanced the expression of the silk protein in Escherichia coli and could optimize the downstream processing. Secondary structures analysis by circular dichroism and FTIR shows that the GFP‐silk fusion protein is predominantly α‐helical, and that pH can trigger a α‐ to β‐transition resulting in aggregation. Structural analysis by small angle X‐ray scattering suggests that the GFP‐Silk exists in the form of a hexamer in solution. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 378–390, 2014.
A high‐throughput screen for antibiotic drug discovery
Authors: Scanlon Thomas C. , Dostal Sarah M. , Griswold Karl E.
Published: August 2013

We describe an ultra‐high‐throughput screening platform enabling discovery and/or engineering of natural product antibiotics. The methodology involves creation of hydrogel‐in‐oil emulsions in which recombinant microorganisms are co‐emulsified with bacterial pathogens; antibiotic activity is assayed by use of a fluorescent viability dye. We have successfully utilized both bulk emulsification and microfluidic technology for the generation of hydrogel microdroplets that are size‐compatible with conventional flow cytometry. Hydrogel droplets are ∼25 pL in volume, and can be synthesized and sorted at rates exceeding 3,000 drops/s. Using this technique, we have achieved screening throughputs exceeding 5 million clones/day. Proof‐of‐concept experiments demonstrate efficient selection of antibiotic‐secreting yeast from a vast excess of negative controls. In addition, we have successfully used this technique to screen a metagenomic library for secreted antibiotics that kill the human pathogen Staphylococcus aureus. Our results establish the practical utility of the screening platform, and we anticipate that the accessible nature of our methods will enable others seeking to identify and engineer the next generation of antibacterial biomolecules. Biotechnol. Bioeng. 2014;111: 232–243. © 2013 Wiley Periodicals, Inc.
Superior mesenteric artery syndrome and its associated gastrointestinal implications
Authors: Mathenge Njambi , Osiro Stephen , Rodriguez Iliana I. , Salib Christian , Tubbs R. Shane , Loukas Marios
Published: August 2013

The superior mesenteric artery (SMA) syndrome is a rare but potentially life‐threatening gastrointestinal condition. Over the years, it has been referenced by several names, the most common of which is Wilkie's syndrome. These numerous terminologies have made it difficult to estimate its true frequency in the general population. Common symptoms associated with this syndrome include intermittent postprandial abdominal pain, nausea, and bilious vomiting. Our review revealed that although it is currently well‐defined in the literature, the diagnosis of SMA syndrome remains challenging as other disorders can mimic its presentation. However, CT angiography is currently favored in the literature for diagnosis as it can not only show the narrowed aorto‐mesenteric angle and distance, but also the extent of duodenal obstruction. In addition, we found no consensus on the preferred mode of therapy once SMA syndrome is diagnosed. The agreement among authors is that the treatment options should be based on severity of the disease, using conservative measures as the first line of therapy in mild SMA syndrome. Duodenojejunostomy is the preferred surgical approach when conservative management fails, or in severe cases. Clin. Anat. 27:1244–1252, 2014. © 2013 Wiley Periodicals, Inc.
Vitrification of immaturemouse oocytes by the modified‐cut standard straw method
Authors: Jang Woo‐In , Lee Seung‐Eun , Choi Hyun‐Yong , Lim Joon‐Gyo , Heo Young‐Tae , Cui Xiang‐Shun , Kim Nam‐Hyung
Published: August 2013

The feasibility of using the modified‐cut standard straw (M‐CSS) method for the vitrification of immature mouse oocytes has been tested. The effects of different vitrification methods on oocyte survival, cytoskeletal organization, the distribution of cortical granules (CGs), and apoptosis have also been compared. Immature mouse oocytes were vitrified–thawed using electron microscope grid or M‐CSS method, and cultured to meiosis II (MII) stage. Oocyte development, cytoskeletal organization, CG distribution, and the expression of apoptosis‐related genes were evaluated. Rates of recovery (91.7 vs. 74.9%) and survival (89.0 vs. 62.6%) were significantly higher in M‐CSS group than in EM grid group. The number of oocytes with normal chromosome alignment at the spindle and spindle morphology were similar in both groups. However, the actin cap was significantly degraded in EM grid groups (52.6 vs. 35.1%, respectively). Abnormal release of CGs also frequently occurred in EM grid groups (42.6 vs. 32.7%, respectively). Pro‐apoptosis‐related gene expression levels of Bax, caspase 3 were expressed lower than control in MII stage oocytes derived from M‐CSS group; anti apoptosis‐related genes, survivin and heat shock factor‐1 (Hsf‐1) were slightly increased. However, all genes expression was significantly increased in MII stage oocytes derived from EM grid groups. Vitrification reduces the survival rate of immature mouse oocytes, alters cytoskeletal organization and CG distribution, and promotes apoptosis. However, these effects are less pronounced in vitrified oocytes generated by M‐CSS than in those generated by EM grid method. Therefore, the novel M‐CSS is a feasible approach for the cryopreservation of immature mouse oocytes.
Overexpression of vasostatin‐1 protects hypoxia/reoxygenation injuries in cardiomyocytes–endothelial cells transwell co‐culture system
Authors: Liu Jian , Yang Dicheng , Shi Sheng , Lin Lei , Xiao Mingdi , Yuan Zhongxiang , Yu Min
Published: August 2013

Vasostatin‐1 (VS‐1) plays important roles in myocardial ischemia/reperfusion injury. We have explored the protective effects of VS‐1 on cardiomyocytes using cardiomyocyte–endothelial cells Transwell Co‐culture System. Cardiomyocytes and rat aortic endothelial cells (RAECs) were prepared from ventricles and thoraco‐abdominal aorta of Sprague–Dawley rats. The experiment used cardiomyocytes alone culture group (C) and cardiomyocytes‐RAECs co‐culture group (T), each with three subgroups: C‐Ad‐Null, C‐Ad‐VS‐1, C‐Hb (Ad‐VS‐1 + NO scavenger Hb), or T‐Ad‐Null, T‐Ad‐VS‐1 transfection, T‐Hb. After 48 h incubation, all groups were treated with hypoxia for 60 min and then reoxygenated for 120 min. We also investigated endothelial cells‐mediated cardiomyocytes protection. RAECs were treated with hypoxia for 30 min and reoxygenated with normal cardiomyocytes for 120 min. The cardiomyocytes apoptosis rate, aspartate aminotransferase (AST) and creatine kinase isozyme MB (CK‐MB) were recorded. As expected, cardiomyocytes apoptosis, AST and CK‐MB were significantly increased in the T‐Ad‐Null group than in the C‐Ad‐Null group. VS transfection significantly reduced these levels. However, apoptosis, AST and CK‐MB levels were increased again after Hb treatment, returning to the similar level of the C‐Ad‐null group in the C‐Hb group, but still significantly lower in the T‐Hb group compared with the T‐Ad‐null group. RAEC injury caused cardiomyocyte injury, and VS‐1 transfection of the RAEC decreased apoptosis and the levels of AST and CK‐MB. The findings suggest that VS‐1 exerts protective effects on the cardiomyocytes directly or indirectly by cardiomyocyte–endothelial cells interaction.
Folate decorated magnetite nanoparticles: Synthesis and targeted therapy against ovarian cancer
Authors: Fazilati Mohammad
Published: August 2013

Doxorubicin (DOX) loaded folate‐coated magnetic Fe3O4 nanoparticles (MNPs) were prepared by co‐precipitation and emulsification cross‐linking method and uniform NPs with an average particle size of 15 (bare) and 35 nm (FA‐MNPs), with high encapsulation efficiencies (EE), were obtained. The release profiles of conjugated DOX showed that pH 6.0 provided suitable conditions for proper drug release. IC50 analysis of C30 and CP70 cell lines after 96 h (4 days) exposure to DOX‐FA‐MNPs showed that the most significant IC50 were at 5.4 ± 0.6 and 11.2 ± 2.7 mM DOX loaded onto the FA‐MNPs. Thus CP70 cells are more resistant to lower concentrations of drug compared to C30 cells (P < 0.05). C30 and CP70 cells reached 91 and 81.8% apoptosis after administration of DOX‐FA‐MNPs (5 mg/mL) compared to 49.2 and 46.6% after administration of the free drug, respectively (P < 0.05). this study indicates that FA modified MNPs enhances the DOX‐induced apoptosis in both of the human ovarian cancer cell lines with sharp decreases in the levels of bcl‐2 and surviving, and increased expression of caspase‐3.
Effects of PTHrP on expression of MMP9 and MMP13 in sika deer antler chondrocytes
Authors: Wang Shou‐Tang , Gao Ying‐Jie , Duan Cui‐Cui , Li Dang‐Dang , Tian Xue‐Chao , Zhang Qiao‐Ling , Guo Bin , Yue Zhan‐Peng
Published: August 2013

Deer antlers are the only mammalian appendages to display an annual cycle of full regeneration. However, little is known about the molecular mechanisms of antler regeneration. Our previous study has demonstrated that parathyroid hormone‐related peptide (PTHrP) can promote proliferation of antler chondrocytes and inhibit its differentiation, but the mechanism underlying such regulation is not fully understood. We have determined the role of PTHrP on the mRNA expression of matrix metalloproteinase‐9 (MMP9) and MMP13 in the antler chondrocytes. The possible pathways that transduce PTHrP effects were examined. In situ hybridization showed that MMP9 and MMP13 were mainly localized in the dermal fibroblasts, perichondrium, and cartilage in the sika deer antler, of which MMP9 and MMP13 were highly expressed in the chondrocytes. Exogenous PTHrP could inhibit the expression of MMP9 and MMP13 in the antler chondrocytes. The inhibitory effect of PTHrP on MMP9 was abolished by JNK inhibitor, SP600125, while P38MAPK inhibitor SB203850 and PKC inhibitor GF109203X could rescue the inhibitory effect of PTHrP on MMP13. The results suggest that PTHrP can inhibit MMP9 expression by JNK signaling pathway and MMP13 expression by p38MAPK and PKC signaling pathways in the antler chondrocytes. Thus PTHrP is involved in the control of antler chondrocytes maturation and cartilage matrix degradation.
PEITC reverse multi‐drug resistance of human gastric cancer SGC7901/DDP cell line
Authors: Tang Tao , Song Xin , Liu Yu‐Fen , Wang Wen‐Yue
Published: August 2013

Gastric cancer is one of the leading causes of cancer death in the world and nearly all patients who respond initially to cisplatin later develop drug resistance, indicating multi‐drug resistance is an essential aspect of the failure of treatment. Phenethyl isothiocyanate (PEITC) has been implicated in inhibiting metastasis of several types of human cancer. However, the effect and potential mechanism of PEITC reversed multi‐drug resistance of human gastric cancer is not fully clear. We have identified the role of PEITC in multi‐drug resistance reversal of human gastric cancer SGC7901/DDP cell line. PEITC inhibited cisplatin‐resistant human SGC7901/DDP cell growth in a dose‐dependent manner, causing increased apoptosis, ROS generation, glutathione depletion, accumulation of Rhodamine‐123, decreased expression of P‐glycoprotein and cell cycle arrest. mRNA and protein expression of the multi‐drug resistance gene (MDR1), multi‐drug resistance‐associated protein (MRP1), excision repair cross‐complementing gene 1 (ERCC1), survivin, and Mad2 was decreased, and phosphorylation of Akt and transcriptional activation of NF‐κB were suppressed. PEITC may be useful as the therapeutic strategy for overcoming multi‐drug resistance through suppressing the PI3K‐Akt pathway in human gastric cancer.
Hypoxia induces adipocyte differentiation of adipose‐derived stem cells by triggering reactive oxygen species generation
Authors: Kim Ji Hye , Kim Seok‐Ho , Song Seung Yong , Kim Won‐Serk , Song Sun U. , Yi TacGhee , Jeon Myung‐Shin , Chung Hyung‐Min , Xia Ying , Sung Jong‐Hyuk
Published: August 2013

Generation of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4) induces the proliferation and migration of adipose‐derived stem cells (ASCs). However, the functional role of mitochondrial ROS (mtROS) generation in ASCs is unknown. Therefore, we have investigated whether hypoxia induces the differentiation of ASCs via ROS generation. We also have tried to identify the cellular mechanisms of ROS generation underlying adipocyte differentiation. Hypoxia (2%) and ROS generators, such as antimycin and rotenone, induced adipocyte differentiation, which was attenuated by an ROS scavenger. Although Nox4 generates ROS and regulates proliferation of ASCs, Nox4 inhibition or Nox4 silencing did not inhibit adipocyte differentiation; indeed fluorescence intensity of mito‐SOX increased in hypoxia, and treatment with mito‐CP, a mtROS scavenger, significantly reduced hypoxia‐induced adipocyte differentiation. Phosphorylation of Akt and mTOR was induced by hypoxia, while inhibition of these molecules prevented adipocyte differentiation. Thus hypoxia induces adipocyte differentiation by mtROS generation, and the PI3K/Akt/mTOR pathway is involved.
Arsenite Resistance, Accumulation, and Volatilization Properties of Trichoderma asperellumSM‐12F1, Penicillium janthinellumSM‐12F4, and Fusarium oxysporum CZ‐8F1
Authors: Feng Qiufen , Su Shiming , Zeng Xibai , Zhang Yangzhu , Li Lianfang , Bai Lingyu , Duan Ran , Lin Zhiling
Published: August 2013

It is expected that microorganisms capable of arsenic (As) accumulation and volatilization can be used to remediate As‐contaminated environments. In this paper, the arsenite [As(III)] resistance, accumulation, and volatilization properties of Trichoderma asperellum SM‐12F1, Penicillium janthinellum SM‐12F4, and Fusarium oxysporum CZ‐8F1 were investigated. The results indicated that all three fungal strains exhibited significant As(III)‐resistance. After being exposed to 40 and 80 mg/L As(III) for five days, the dry mycelium weights of P. janthinellum SM‐12F4 and F. oxysporum CZ‐8F1 were significantly increased compared to the controls. The spiked As(III) initially inhibited and subsequently promoted fungal growth (mainly in the logarithmic growth phase). The maximal biomasses of 0.25, 0.29, and 0.29 g for T. asperellum SM‐12F1, P. janthinellum SM‐12F4, and F. oxysporum CZ‐8F1 after exposure to As(III), respectively, were all higher than their corresponding controls without As(III). When exposed to 40 mg/L As(III) for five days, the efficiencies of As(III) accumulation for T. asperellum SM‐12F1, P. janthinellum SM‐12F4, and F. oxysporum CZ‐8F1 were 53.02, 13.67, and 13.65 µg/g/day, respectively, and the efficiencies of As(III) volatilization were 51.87, 54.34, and 46.35 µg/g/day, respectively. It seems that these fungal strains can be used in the future to tackle As‐contaminated environments.