bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular, Physicochemical and Rheological Characteristics of Introgressive Triticale/Triticum monococcum ssp. monococcum Lines with Wheat 1D/1A Chromosome Substitution
Authors: Salmanowicz Bolesław , Langner Monika , Wiśniewska Halina , Apolinarska Barbara , Kwiatek Michał , Błaszczyk Lidia
Published: July 2013

Three sets of hexaploid introgressive triticale lines, with Triticum monococcum ssp. monococcum (cultivated einkorn wheat) genes and a bread wheat chromosome 1D substituted for chromosome 1A, and one set of secondary triticale lines were evaluated for grain and flour physicochemical and dough rheological characteristics in two generations (F7 and F8). Genomic in situ hybridization (GISH) and fluorescence in situ hybridization (FISH) confirmed the 1D/1A chromosome substitution. The presence or absence of einkorn high-molecular-weight (HMW) glutenin subunits and the wheat Glu-D1d locus encoding the 5 + 10 subunits was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), capillary zone electrophoresis, and allele-specific molecular markers. Significant differences were found among physicochemical properties (with the exception of the Hagberg falling number) of all introgressive Triticale/T. monococcum lines and the secondary triticale lines. The wheat 1D/1A chromosome substitution also affected these properties. The results showed that in all introgressive triticale lines, the protein and gluten content, Zeleny sedimentation value, and water absorption capacity, were increased. The rheological parameters estimated using micro-farinograph, reomixer, and Kieffer dough extensibility systems also showed an appreciable increase in dough-mixing properties, maximum resistance to extension (Rmax), and dough extensibility. Introgressive Triticale/T. monococcum lines with 5 + 10 subunits have particularly favorable rheological parameters. The results obtained in this study suggest that the cultivated einkorn genome Am, in the context of hexaploid secondary triticale lines and with a wheat 1D/1A substitution, has the potential to improve gluten polymer interactions and be a valuable genetic resource for triticale quality improvement.
Experimental Evidence of Persistent Androgen-Receptor-Dependency in Castration-Resistant Prostate Cancer
Authors: Kobayashi Takashi , Inoue Takahiro , Kamba Tomomi , Ogawa Osamu
Published: July 2013

In the majority of castration-resistant prostate cancer (CRPC), prostate-specific antigen (PSA), product of a gene that is almost exclusively regulated by the androgen receptor (AR), still acts as a serum marker reflecting disease burden, indicating that AR signaling is activated even under castrate level of serum androgen. Accumulated evidence shows that transcriptional ability of AR is activated both in ligand-dependent and -independent manners in CRPC cells. Some androgen-independent sublines derived from originally androgen-dependent LNCaP prostate cancer cells overexpress the AR and PSA, for which silencing the AR gene suppresses cellular proliferation. The overexpression of the AR confers androgen-independent growth ability on androgen-dependent prostate cancer cells. Some patient-derived prostate cancer xenograft lines also acquire castration-resistant growth ability secreting PSA. More recent publications have shown that the AR activated in CRPC cells regulates distinct gene sets from that in androgen-dependent status. This concept provides very important insights in the development of novel anti-prostate cancer drugs such as new generation anti-androgens and CYP17 inhibitors.
Resveratrol Sensitizes Tamoxifen in Antiestrogen-Resistant Breast Cancer Cells with Epithelial-Mesenchymal Transition Features
Authors: Shi Xiao-Peng , Miao Shan , Wu Yin , Zhang Wei , Zhang Xiao-Fang , Ma Hua-Zhao , Xin Hai-Li , Feng Juan , Wen Ai-Dong , Li Yan
Published: July 2013

Tamoxifen resistance remains to be a huge obstacle in the treatment of hormone-dependent breast cancer, and this therefore highlights the dire need to explore the underlying mechanisms. The epithelial-mesenchymal transition (EMT) is a molecular process through which an epithelial cell transfers into a mesenchymal phenotype. Roles of EMT in embryo development, cancer invasion and metastasis have been extensively reported. Herein, we established tamoxifen-resistant MCF-7/TR breast cancer cells and showed that MCF-7/TR cells underwent EMT driven by enhanced endogenous TGF-β/Smad signaling. Ectopic supplement of TGF-β promoted in MCF-7 cells a mesenchymal and resistant phenotype. In parallel, we demonstrated that resveratrol was capable of synergizing with tamoxifen and triggering apoptosis in MCF-7/TR cells. Further Western blot analysis indicated that the chemosensitizing effects of resveratrol were conferred with its modulation on endogenous TGF-β production and Smad phosphorylation. In particular, 50 μM resveratrol had minor effects on MCF-7/TR cell proliferation, but could significantly attenuate endogenous TGF-β production and the Smad pathway, ultimately leading to reversion of EMT. Collectively, our study highlighted distinct roles of EMT in tamoxifen resistance and resveratrol as a potential agent to overcome acquired tamoxifen resistance. The molecular mechanism of resveratrol chemosensitizing effects is, at least in part, TGF-β/Smad-dependent.
Impaired Pre-mRNA Processing and Altered Architecture of 3' Untranslated Regions Contribute to the Development of Human Disorders
Authors: Michalova Eva , Vojtesek Borivoj , Hrstka Roman
Published: July 2013

The biological fate of each mRNA and consequently, the protein to be synthesised, is highly dependent on the nature of the 3' untranslated region. Despite its non-coding character, the 3' UTR may affect the final mRNA stability, the localisation, the export from the nucleus and the translation efficiency. The conserved regulatory sequences within 3' UTRs and the specific elements binding to them enable gene expression control at the posttranscriptional level and all these processes reflect the actual state of the cell including proliferation, differentiation, cellular stress or tumourigenesis. Through this article, we briefly outline how the alterations in the establishment and final architecture of 3' UTRs may contribute to the development of various disorders in humans.
Left-Right Asymmetrical Development of the Proepicardium
Authors: Schlueter Jan , Brand Thomas
Published: July 2013

The proepicardium (PE) is a cluster of cells that forms on the cardiac inflow tract and gives rise to the epicardium and connective tissue and largely contributes to the coronary vasculature. In many vertebrates, the PE undergoes left-right asymmetrical development. While PE cells and marker genes can be initially found on both sides, only the right-sided PE will fully develop and ultimately deliver cells to the heart. Several signalling inputs, like FGF and BMP signals, are involved in PE induction in the lateral plate mesoderm, as well as during inflow tract formation and, also, control asymmetric PE development. These signalling events will be put into the context of embryonic left-right asymmetry determination. Finally, it will be discussed whether PE development may serve as a readout for asymmetric inflow tract morphogenesis.
Antidiarrheal Activity of 19-Deoxyicetexone Isolated from Salvia ballotiflora Benth in Mice and Rats
Authors: Pérez-Gutiérrez Salud , Zavala-Mendoza Daniel , Hernández-Munive Abigail , Mendoza-Martínez Ángel , Pérez-González Cuauhtemoc , Sánchez-Mendoza Ernesto
Published: July 2013

The antidiarrheal properties of 19-deoxyicetexone, a diterpenoid isolated from Salvia ballotiflora were evaluated on castor oil-, arachidonic acid (AA)- and prostaglandin (PGE2)-induced diarrhea in rodent models. The structure of 19-deoxyicetexone was determined by X-ray crystallography, mass spectrometry (EI-MS), as well as ultraviolet (UV-Vis), infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopies. This compound significantly and dose-dependently reduced frequency of stooling in castor oil-induced diarrhea, and at dose of 25 mg/kg it also inhibited diarrhea induced with AA, while it had no effect on PGE2-induced diarrhea. This compound at doses of 25 mg/kg also diminished castor oil-induced enteropooling and intestinal motility, and inhibited the contraction of the rats’ ileum induced by carbachol chloride at a concentration of 100 µg/mL. 19-Deoxyicetexone did not present acute toxicity at doses of 625 mg/kg. Its antidiarrheal activity may be due to increased reabsorption of NaCl and water and inhibition of the release of prostaglandins, gastrointestinal motility and fluid accumulation in the intestinal tracts of rats. These findings suggest that 19-deoxyicetexone may be used in the treatment of diarrhea, although more studies must be carried out to confirm this.
Inhibitors of Urokinase Type Plasminogen Activator and Cytostatic Activity from Crude Plants Extracts
Authors: Zha Xueqiang , Diaz Ricardo , Franco Jose , Sanchez Veronica , Fasoli Ezio , Barletta Gabriel , Carvajal Augusto , Bansal Vibha
Published: July 2013

In view of the clear evidence that urokinase type plasminogen activator (uPA) plays an important role in the processes of tumor cell metastasis, aortic aneurysm, and multiple sclerosis, it has become a target of choice for pharmacological intervention. The goal of this study was thus to determine the presence of inhibitors of uPA in plants known traditionally for their anti-tumor properties. Crude methanol extracts were prepared from the leaves of plants (14) collected from the subtropical dry forest (Guanica, Puerto Rico), and tested for the presence of inhibitors of uPA using the fibrin plate assay. The extracts that tested positive (6) were then partitioned with petroleum ether, chloroform, ethyl acetate and n-butanol, in a sequential manner. The resulting fractions were then tested again using the fibrin plate assay. Extracts from leaves of Croton lucidus (C. lucidus) showed the presence of a strong uPA inhibitory activity. Serial dilutions of these C. lucidus partitions were performed to determine the uPA inhibition IC50 values. The chloroform extract showed the lowest IC50 value (3.52 µg/mL) and hence contained the most potent uPA inhibitor. Further investigations revealed that the crude methanol extract and its chloroform and n-butanol partitions did not significantly inhibit closely related proteases such as the tissue type plasminogen activator (tPA) and plasmin, indicating their selectivity for uPA, and hence superior potential for medicinal use with fewer side effects. In a further evaluation of their therapeutic potential for prevention of cancer metastasis, the C. lucidus extracts displayed cytostatic activity against human pancreatic carcinoma (PaCa-2) cells, as determined through an MTS assay. The cytostatic activities recorded for each of the partitions correlated with their relative uPA inhibitory activities. There are no existing reports of uPA inhibitors being present in any of the plants reported in this study.
Kaposi’s Sarcoma-Associated Herpesvirus ORF57 Protein: Exploiting All Stages of Viral mRNA Processing
Authors: Schumann Sophie , Jackson Brian , Baquero-Perez Belinda , Whitehouse Adrian
Published: July 2013

Nuclear mRNA export is a highly complex and regulated process in cells. Cellular transcripts must undergo successful maturation processes, including splicing, 5'-, and 3'-end processing, which are essential for assembly of an export competent ribonucleoprotein particle. Many viruses replicate in the nucleus of the host cell and require cellular mRNA export factors to efficiently export viral transcripts. However, some viral mRNAs undergo aberrant mRNA processing, thus prompting the viruses to express their own specific mRNA export proteins to facilitate efficient export of viral transcripts and allowing translation in the cytoplasm. This review will focus on the Kaposi’s sarcoma-associated herpesvirus ORF57 protein, a multifunctional protein involved in all stages of viral mRNA processing and that is essential for virus replication. Using the example of ORF57, we will describe cellular bulk mRNA export pathways and highlight their distinct features, before exploring how the virus has evolved to exploit these mechanisms.
Preliminary Study on the Effect of Wastewater Storage in Septic Tank on E. coli Concentration in Summer
Authors: Appling Dominique , Habteselassie Mussie , Radcliffe David , Bradshaw James
Published: July 2013

On-site wastewater treatment systems (OWTS) work by first storing the wastewater in a septic tank before releasing it to soils for treatment that is generally effective and sustainable. However, it is not clear how the abundance of E. coli changes during its passage through the tank. In this study, which was conducted under the UGA young Scholar Program in summer of 2010, we examined the change in wastewater quality parameters during the passage of the wastewater through the tank and after its release into soil. We collected wastewater samples at the inlet and outlet of an experimental septic tank in addition to obtaining water samples from lysimeters below trenches where the drainpipes were buried. We report that E. coli concentration was higher by 100-fold in the septic tank effluent than influent wastewater samples, indicating the growth of E. coli inside the tank under typical Georgian summer weather. This is contrary to the assumption that E. coli cells do not grow outside their host and suggests that the microbial load of the wastewater is potentially enhanced during its storage in the tank. Electrical conductivity, pH and nitrogen were similar between the influent and effluent wastewater samples. E. coli and total coliform concentrations were mainly below detection in lysimeter samples, indicating the effectiveness of the soil in treating the wastewater.
Enjeux de sens et enjeux politiques de la notion de dépendance
Authors: Ennuyer Bernard
Published: July 2013

Dans les années 1970, sous l’impulsion des médecins de long séjour, l’adjectif dépendant est devenu le qualificatif pour désigner les personnes âgées atteintes d’incapacité dans les actes essentiels de la vie quotidienne et ayant besoin, de ce fait, d’être aidées pour les effectuer. Le vocable dépendance est ainsi devenu, au fil du temps, le stigmate, c’est-à-dire un attribut péjoratif, des personnes âgées qui vieillissent avec des difficultés de vie quotidienne. Il a conduit à la mise en place d’une politique publique spécifique et ségrégative en direction des « personnes âgées dépendantes ». Récemment, c’est le mot perte d’autonomie qui s’est imposé pour définir cette population ayant besoin d’être aidée dans sa vie quotidienne, entraînant une confusion redoutable entre incapacité fonctionnelle et incapacité décisionnelle. Cet article propose résolument de remplacer ces vocables négatifs par le vocable européen de « besoin d’aide et de soins de longue durée ».
La fin de vie : le point sur les pratiques médicales en France
Authors: Pennec Sophie , Monnier Alain , Pontone Silvia , Aubry Régis , Gaymu Joëlle , Riou Françoise
Published: July 2013

En France, dans les décennies à venir, avec l’arrivée des générations du baby-boom au grand âge et l’augmentation de l’espérance de vie, le nombre de décès, notamment de personnes très âgées, va augmenter. Dans une proportion importante, ces décès seront précédés de maladies chroniques longues et potentiellement invalidantes requérant soins et aides. Actuellement, près de la moitié des décès (48 % en 2010) a été précédée d’une décision médicale ayant pu hâter la mort du patient. Les décisions prises s’appuient dans leur grande majorité sur les dispositions de la loi Leonetti, qui permet, sous certaines conditions, de limiter ou d’arrêter un traitement, ou d’administrer des médicaments pour soulager les souffrances du patient, qui peuvent avoir pour effet d’avancer la survenue de la mort.
Le vieillissement démographique : quelles promesses économiques ?
Authors: Malochet Guillaume
Published: July 2013

Le vieillissement démographique est porteur de promesses économiques. Cet article cherche à en donner quelques illustrations originales tirées d’expériences étrangères. Il ne s’agit pas de dresser un nouveau bilan des perspectives offertes au développement des services à la personne, mais plutôt de montrer, exemples à l’appui, comment l’avancée en âge peut emporter avec elle une dynamique économique positive.
L'assurance dépendance : en « supplémentaire » ou en « complémentaire ? »
Authors: Colvez Alain , Loirat Jean-Louis
Published: July 2013

Quelle part l’assurance doit-elle prendre dans le financement de la « dépendance »? La question est moins de savoir si elle doit y contribuer – elle y est déjà présente – que de définir quelle place et sous quelle forme elle peut y être impliquée. Un point essentiel de la discussion à soumettre à la représentation nationale est de trancher entre la position de « complémentaire » qu’elle occupe pour les problèmes de santé et la position de « supplémentaire » à laquelle le secteur assurantiel se limite actuellement pour la dépendance. Tous les éléments techniques sont disponibles et doivent être utilisés pour conduire un véritable débat sur l’articulation entre la protection sociale et les assurances (individuelles ou mutualistes) pour le financement de cet enjeu national de santé.
Les espaces du commerce alimentaire à Tours au XVIII e siècle
Authors: Villeret Maud
Published: July 2013

L’étude de la distribution spatiale des commerces alimentaires à Tours montre que les villes d’Ancien Régime sont de véritables marchés à ciel ouvert, malgré les tentatives de régulation du XVIII e siècle. Si la localisation des commerces de bouche obéit à des logiques multiples, c’est leur polarisation qui frappe l’observateur. Le secteur alimentaire est plus que tout autre créateur de centralité dans une ville. La maitrise des espaces commerciaux est un enjeu sanitaire, économique, voire identitaire pour les multiples acteurs urbains : commerçants, clients et autorités de la ville. Leurs différentes visions s’affrontent ce qui contribue à modifier le paysage urbain.
La naissance d'une cité ouvrière sous le Second Empire
Authors: Calvarin Claude
Published: July 2013

À proximité de la barrière de la Chopinette, encore habitée par des commis de l’Octroi, Adolphe de Madre (1813-1894), un notaire parisien, achète un premier bâtiment sur ses fonds propres en 1852. Cette mise de fonds devient le gage d’un premier emprunt au Crédit Foncier, d’autres suivront au fur et à mesure de l’achat et du lotissement de terrains, essentiellement des jardins maraîchers, et de l’élévation de constructions pour ouvriers. Il achète ainsi 34 000m 2  de terrain à différents propriétaires, à proximité de l’hôpital Saint-Louis. Il loue pour 18 ans ses terrains à de petits entrepreneurs, à charge pour eux de construire pour leur usage propre et de sous-louer des maisons qui lui reviennent en fin de bail. Entre 1861 et 1863, il construit ses propres bâtiments. Entrepreneurs et locataires appartiennent à un milieu populaire venu en majorité de province. Madre, imprégné des valeurs des catholiques sociaux, concrétise sa volonté d’entreprendre dans une stratégie du charitable qui le conduit à construire une cité pour des ouvriers méritants. Efficace homme d’affaires, rigoureux gestionnaire, habile homme de loi, il développe son projet sans aucune aide du gouvernement. Il est un des rares à avoir gagné de l’argent tout en étant charitable. À l’inverse de la cité Napoléon, les bâtiments de Madre se fondent dans le bâti avoisinant et quelques-uns, transformés au fil des usages, n’ont pas été détruits ; une récente réhabilitation prolonge leur existence.
REDUCING CO2 EMISSIONS IN A TYPICAL 60 YEARS OLD DETACHED HOUSE IN LONDON
Authors: Barbhuiya Saadia , Barbhuiya Salim
Published: July 2013

INTRODUCTION

In this paper an attempt has been made to provide the best options for renewable energy and low carbon technologies to reduce CO2 emissions from a detached house built in 1950 and located in London. The options for energy efficiency measures—photovoltaics, solar thermal, wind turbine, ground source heat pump, Gas CHP—have been evaluated on the basis of energy and CO2 savings and technical viability. The main conclusions derived from this study are summarised in this paper.
FAÇADE DESIGN EFFECT ON CROSS-VENTILATION IN TAIWANESE SCHOOL BUILDINGS
Authors: Chiang W.H. , Hsu H.H. , Huang J.S.
Published: July 2013

This study performed a three-dimensional numerical prediction for the induced airflow patterns and mean age of air (MAGE) around and inside a naturally ventilated school building, while accounting for the wind profile effect. Various fenestrations, hallways, and shading devices on the windward side of building were analyzed to determine how they affected wind velocity, the incident angle of airflow, and MAGE distribution inside classrooms. The numerical scheme is based on a commercial computational fluid dynamics (CFD) code, PHOENICS. The incline of incoming wind was observed on higher floors that decreased the air exchange rate in the simulated room. The inclined airflow could be effectively deflected downward through the breathing zone by hallways, 1.2-m shades as overhangs, and 0.6-m louvers. Based on this research, an appropriate combination of external attachments on the windward side of building façade can be utilized to enhance ventilation in school buildings. (See Appendix 1 for nomenclature.)
La construction sociale de la paranoïa pénitentiaire
Authors: Janicaud Élodie
Published: July 2013

Régulièrement décrite comme un trait décuplant l’imaginaire de la violence en prison ou réactivant les appréhensions des personnes soumises aux effets de la carcéralisation, la « paranoïa pénitentiaire » s’avère peu questionnée par la littérature sociologique. À la croisée du sens commun et du langage psychiatrique, cette notion reste descriptive pour qualifier les mécanismes de défense collectifs ou individuels imbriqués à la peur perçue ou ressentie des protagonistes de l’univers carcéral. À partir d’une analyse constructiviste, cet article met l’accent sur la place prise par l’organisation violente de la prison, structurant un environnement sinistre qui frappe les détenus, les acteurs de terrain. Tous mobilisent leur subjectivité pour résister à cette souffrance. Espace-temps doublement confiné et propice à la suspicion, les UHSI sont une occasion de questionner cet impensé de la paranoïa pénitentiaire en sociologie carcérale. Ces traits caractéristiques sont la résultante d’une sinistrose propre aux surveillants de prison provoquant déliaison sociale et désubjectivation.
Human CRP Defends against the Toxicity of Circulating Histones
Authors: Abrams Simon T. , Zhang Nan , Dart Caroline , Wang Susan Siyu , Thachil Jecko , Guan Yunyan , Wang Guozheng , Toh Cheng-Hock
Published: July 2013

C-reactive protein (CRP) is an acute-phase protein that plays an important defensive role in innate immunity against bacterial infection, but it is also upregulated in many noninfectious diseases. The generic function of this highly conserved molecule in diseases that range from infection, inflammation, trauma, and malignancy is not well understood. In this article, we demonstrate that CRP defends the human body against the toxicity of histones released into the circulation after extensive cell death. In vitro, CRP significantly alleviates histone-induced endothelial cell damage, permeability increase, and platelet aggregation. In vivo, CRP rescues mice challenged with lethal doses of histones by inhibiting endothelial damage, vascular permeability, and coagulation activation, as reflected by significant reductions in lung edema, hemorrhage, and thrombosis. In patients, elevation of CRP significantly increases the capacity to neutralize extracellular histones in the circulation. We have also confirmed that CRP interacts with individual histones in vitro and forms CRP–histone complexes in serum from patients with both elevated CRP and histones. CRP is able to compete with phospholipid-containing liposomes for the binding to histones. This explains how CRP prevents histones from integrating into cell membranes, which would otherwise induce calcium influx as the major mechanism of cytotoxicity caused by extracellular histones. Because histone elevation occurs in the acute phase of numerous critical illnesses associated with extensive cell death, CRP detoxification of circulating histones would be a generic host defense mechanism in humans.
Autophagy-Inducing Protein Beclin-1 in Dendritic Cells Regulates CD4 T Cell Responses and Disease Severity during Respiratory Syncytial Virus Infection
Authors: Reed Michelle , Morris Susan H. , Jang Sihyug , Mukherjee Sumanta , Yue Zhenyu , Lukacs Nicholas W.
Published: July 2013

Recent work demonstrated the importance of macroautophagy in dendritic cell (DC) maturation and innate cytokine production upon viral infection through delivery of cytoplasmic viral components to intracellular TLRs. To study the functional consequences of impaired autophagosome formation during a respiratory syncytial virus (RSV) infection, mice harboring significant autophagy defects due to Beclin-1 haploinsufficiency (Beclin-1+/−) were used. Upon RSV infection in vivo, lungs of Beclin-1+/− mice showed increased Th2 cytokine production, mucus secretion, and lung infiltration of eosinophils and inflammatory DCs. Although isolated airway epithelial cells from Beclin-1+/− mice demonstrated little change compared with wild-type mice, Beclin-1+/− pulmonary and bone marrow–derived DCs showed decreased expression of MHC class II and innate cytokine production upon RSV infection. Further examination indicated that Beclin-1+/− DCs stimulated less IFN-γ and IL-17 production by cocultured CD4+ T cells and increased Th2 cytokine production in comparison with wild-type controls. Finally, adoptive transfer of RSV-infected Beclin-1+/− DCs into the airways of wild-type mice produced severe lung pathology and increased Th2 cytokine production upon subsequent RSV challenge compared with wild-type DC transfer controls. These results indicate a critical role for autophagy in DCs during pulmonary viral infection, facilitating appropriate antiviral adaptive immune responses.
Predator-Prey – An Alternative Model of Stock Market Bubbles and the Business Cycle
Authors: Gracia Eduard
Published: July 2013

For the last quarter of a century, the Real Business Cycle model has dominated the interpretation of business cycles in mainstream economics; yet a number of significant empirical objections to it justify exploring an alternative approach. This paper proposes to base such an approach on a predator-prey mechanism, along the lines of the classical Lotka-Volterra model for ecosystem dynamics, where agency costs play the role of the predatory activity, in a process very similar to the one proposed by the classical Austrian School interpretation of the cycle (Hayek/Schumpeter). The model is consistent with both Rational Expectations and the Efficient Markets Hypothesis, and predicts that stock market valuations will regularly present bubbles and crashes synchronised with the business cycle without this implying any irrational behaviour on the part of the investors.
Projected Population Proximity Indices (30km) for 2005, 2030 & 2050
Authors: Alexander Neil S. , Wint William
Published: July 2013

This data package includes nine population proximity index layers for 2005, 2030 and 2050, for rural, urban and total populations.  The layers are distributed as 1km GeoTIFFs and GeoJPGss at 1km.The aim of these layers is to describe the population which may be likely to visit a specific locality where access is determined by Euclidean distance. By using the layers alongside other geographic datasets relating to disease risk it may help identify where people may come into contact with a disease.  Human population layers are often used in models to identify risk areas where humans and viruses interact, however most pathogens are not restricted to areas of human habitation: many are found in lesser populated areas such as forests.  This dataset will help identify less populated areas that may well still receive high visitor numbers.The layers have been projected to 2030 and 2050 to enable projections of human/disease interfaces in the medium-term which are required to inform policy makers at country and continental level.Urban and rural populations have been separated into individual layers as in some cases it is useful to distinguish between the behaviour and associated risks attributed to the different population segments.  There may be a different risk of contacting diseases in rural habitats for rural workers than for than urban visitors.
Four Rodent and Vole Biodiversity Models for Europe
Authors: Wint William , Morley David , Alexander Neil S.
Published: July 2013

The mechanisms underlying associations between rodent diversity and the spread of rodent borne diseases are still unclear. The number of potential host species may influence a disease by either spreading the pathogen (or vectors) more rapidly or conversely by reducing contact with other hosts through the effects of dilution. In either case the number of potential hosts may impact on the distribution of a disease or its vectors.  Four spatially modelled indices of rodent species richness have been generated to support distribution modelling of rodent borne diseases specifically initially focussing on Hantaviruses and tick borne diseases.
Data from the Multiprofessional Workshop: ‘Paediatric Patient-Reported Outcome and Experience Measures (PROMS and PREMS) in Routine Clinical Practice.’
Authors: Tadic Val , Knowles Rachel L. , Rahi Jugnoo
Published: July 2013

To explore current challenges surrounding the development and application of PROMs/PREMs in paediatric healthcare1, a workshop was held for healthcare professionals and parent representatives from University College London (UCL) Institute of Child Health (ICH) and two clinical partners, Great Ormond Street Hospital and Moorfields Eye Hospital. The workshop aimed to establish an academic-clinical-service user collaborative network to support local development and translation into clinical practice of paediatric PROMs/PREMs. The workshop report summarises invited presentations, small group discussions and key local issues. The report is permanently archived at UCL Discovery and publicly available.
Data: ‘Initial Clinical Referral Standards after Newborn Screening for Congenital Hypothyroidism: Final Report of the UK Newborn Screening Programme Centre Expert Working Group and Systematic Evidence Review 2010-2011’.
Authors: Knowles Rachel L. , Olafsdottir Freyja
Published: July 2013

The multidisciplinary Expert Working Group was tasked with revising the existing standards of the UK NHS National Screening Programme for diagnosis and management of babies in whom congenital hypothyroidism (CHT) is suspected after newborn bloodspot screening. This report includes a systematic evidence review and account of the proceedings of the working group in key areas: screening test performance, referral pathways, diagnostic investigations, treatment and communication with parents. After public consultation, the recommendations were adopted as policy. This final report provides an evidence base for reviewing newborn screening for CHT in other populations and outlines a transparent consensus-based process for agreeing changes to screening standards and policy.
Can substrate in early rearing prevent feather pecking in adult laying hens?
Authors: de Jong IC , Reuvekamp BFJ , Gunnink H
Published: July 2013

In The Netherlands, laying hen chicks are often reared without litter on the raised slatted area of a barn system or confined in the aviary system during the first two to five weeks after hatching, with chick paper or chicken wire on the floor. In the absence of a suitable pecking substrate, chicks may redirect their pecking behaviour to other birds, which possibly increases the risk of developing feather-pecking behaviour. The aim of this study was to determine whether housing on wood-shavings (WS treatment; n = 15 groups) as compared to housing on chicken wire (CW treatment; n = 15 groups) between day 1-20 could reduce feather pecking in adult birds. After day 20, all chickens were allowed wood-shavings as litter. Behavioural observations showed that CW chicks performed significantly less ground-pecking behaviour compared with WS chicks up to day 20. More CW chicks showed gentle feather pecking at day 7 and 14 as compared to WS chicks, and more CW chicks pecked at the feeder or drinker than WS chicks up to day 20. CW chicks showed rebound behaviour: the day after they were introduced to wood-shavings they displayed more ground-pecking behaviour compared to the WS chicks. Later on in the rearing period no noticeable differences between treatments were found in frequency of gentle and severe feather-pecking bouts. During laying, more gentle feather-pecking bouts were observed in CW than in WS groups but no differences in severe feather-pecking bouts were observed, nor in feather damage at the end of the trial. The results indicate that hens can display substantial flexibility in their pecking behaviour and that, despite more gentle feather pecking in CW hens in laying, the absence of substrate in early rearing does not increase the risk of developing severe feather-pecking behaviour when adult.
Die Bedeutung der Mukaiyama‐Aldolreaktion für die Totalsynthese
Authors: Kan S. B. Jennifer , Ng Kenneth K.‐H. , Paterson Ian
Published: July 2013

Im Laufe der vierzig Jahre, die seit Mukaiyamas ersten Berichten zur Verwendung von Silicium‐ und Borenolaten in gezielten Aldolreaktionen vergangen sind, hat sich diese in hohem Maße kontrollierte Kohlenstoff‐Kohlenstoff‐Kupplung aufgrund ihrer Fähigkeit zur simultanen Definition der Stereochemie, Einführung der Komplexität und Aufbau des Kohlenstoffgerüsts mit einem charakteristischen Oxygenierungsmuster als eine leistungsstarke Methode für die Naturstoffsynthese etabliert. Dieser Kurzaufsatz präsentiert repräsentative Totalsynthesen, die die Bedeutung der Mukaiyama‐Aldolreaktion veranschaulichen, und diskutiert die zugrundeliegenden Mechanismen, die für die stereochemische Anordnung entscheidend sind.
Determination of the Diameter‐Dependent Onset Potential for the Oxygenation of SWCNTs
Authors: Sakamoto Shingo , Tominaga Masato
Published: July 2013

The evaluation of the diameter‐dependent onset potential for the oxygenation of a SWCNT (single‐walled carbon nanotube) is an important issue because its chemical and physical properties, such as chemical reactivity, electronic conductance, and optical characteristics, would be changed. We investigated the diameter‐dependent onset potential for the oxygenation of SWCNTs in neutral aqueous solution by using in situ Raman spectroelectrochemical measurements, which was explained quantitatively in terms of the strain energy per carbon atom. These results will be useful for the fabrication of materials in which CNTs are used as a platform for applications such as fuel cells, capacitors, and Li‐ion batteries.
Multiple, consecutive, fully‐extended 2.05‐helix peptide conformation
Authors: Peggion Cristina , Moretto Alessandro , Formaggio Fernando , Crisma Marco , Toniolo Claudio
Published: July 2013

The peptide 2.05‐helix does exist. It has been experimentally authenticated both in the crystalline state (by X‐ray diffraction) and in solution (by several spectroscopic techniques). It is the most common conformation for Cα‐tetrasubstituted α‐amino acids with at least two atoms in each side chain, provided that cyclization on the Cα‐atom is absent. X‐Ray diffraction has allowed a detailed description of its geometrical and three‐dimensional (3D)‐structural features. The infrared absorption and the nuclear magnetic resonance parameters characteristics of this multiple, consecutive, fully‐extended structure have been described. Conformational energy calculations are in agreement with the experimental findings. As the contribution per amino acid residue to the length of this helix is the longest possible, its exploitation as a molecular spacer is quite promising. However, it is a rather fragile 3D‐structure and particularly sensitive to solvent polarity. Interestingly, in such a case, it may reversibly convert to the much shorter 310‐helix, thus generating an attractive molecular spring. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 621–636, 2013.
Effects of lysine methylation on gramicidin A channel folding in lipid membranes
Authors: Wang Fang , Qin Luoheng , Wong Patrick , Gao Jianmin
Published: July 2013

Protein‐membrane interactions underlie numerous biological processes including folding of ion channels and signal transduction across lipid membranes. A detailed understanding of protein–lipid interactions is critical for designing membrane‐active peptides as potential antibiotics, as well. Using gramicidin A (gA) as a model system, we investigated the effects of lysine methylation on peptide folding into transmembrane channels. The results are discussed in terms of the peptides' binding affinity to, translocation across, and structure formation in lipid membranes. The results show that gA mutants with Nɛ‐trimethylated d‐lysines (dMe3K) are capable of folding into wild type‐like channels that are selective for monovalent cations. Surprisingly, Nɛ‐trimethylation in general reduces the peptide's binding affinity to lipid membranes despite the increased hydrophobicity. Further investigation reveals the critical contribution of the hydrogen bonding potential of lysine side chains to peptide‐membrane association, which has previously been underappreciated. Importantly, methylation does give improved therapeutic indices for certain combinations of gA variant and bacterium, indicating that methylation can be an effective strategy to fine tune the performance of peptide antibiotics. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 656–661, 2013.
Dual system for the central nervous system targeting and blood‐brain barrier transport of a selective prolyl oligopeptidase inhibitor
Authors: Teixidó Meritxell , Zurita Esther , Mendieta Laura , Oller‐Salvia Benjamí , Prades Roger , Tarragó Teresa , Giralt Ernest
Published: July 2013

Less than 2% of all potential neurotherapeutics cross the blood‐brain barrier (BBB). Here, we sought to build a construct with the capacity to cross this barrier, to behave as a chemical delivery system, and, once inside the central nervous system, to be transformed and then act as an enzyme inhibitor. With all this in mind, here, we describe the entire process to obtain such a compound, from the initial candidate selection to preparation of the compound library and posterior evaluation and final selection of the most promising candidates in terms of selectivity, serum stability, and BBB‐transport. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 662–674, 2013.
Synthesis of temperature‐dependent elastin‐like peptide‐modified dendrimer for drug delivery
Authors: Kojima Chie , Irie Kotaro
Published: July 2013

Dendrimers are synthetic macromolecules with a unique structure that are potential unimolecular drug carriers and potential scaffolds for peptides. Elastin is one of the main components of the extracellular matrix, as well as a temperature‐sensitive biomacromolecule. Val‐Pro‐Gly‐Val‐Gly repeats, an elastin‐like peptide, have been used for designing artificial elastin molecules. In this study, we have synthesized a novel type of temperature‐dependent drug carrier by conjugating Ac‐Val‐Pro‐Gly‐Val‐Gly to a dendrimer, named elastin‐mimetic dendrimer. The elastin‐mimetic dendrimer formed β‐turn structure by heating. The elastin‐mimetic dendrimer exhibited the inverse phase transition, depending on pH and NaCl concentration in addition to temperature. The elastin‐mimetic dendrimer could encapsulate a model drug, rose bengal, even though the complex stability was similar to the dendrimer without elastin‐like peptide. Therefore, the elastin‐mimetic dendrimer is a potential drug carrier with temperature‐ and pH‐dependent properties. (134 words) © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 714–721, 2013.
Toward the de novo design of antimicrobial peptides: Lack of correlation between peptide permeabilization of lipid vesicles and antimicrobial, cytolytic, or cytotoxic activity in living cells
Authors: He Jing , Krauson Aram J. , Wimley William C.
Published: July 2013

We previously performed a lipid vesicle‐based, high‐throughput screen on a 26‐residue combinatorial peptide library that was designed de novo to yield membrane‐permeabilizing peptides that fold into β‐sheets. The most active and soluble library members that were identified permeabilized lipid vesicles detectably, but not with high potency. Nonetheless, they were broad‐spectrum, membrane‐permeabilizing antibiotics with minimum sterilizing activity at low µM concentrations. In an expansion of that work, we recently performed an iterative screen in which an active consensus sequence from that first‐generation library was used as a template to design a second‐generation library which was then screened against lipid vesicles at very high stringency. Compared to the consensus sequence from the first library, the most active second‐generation peptides are highly potent, equilibrium pore‐formers in synthetic lipid vesicles. Here, we use these first‐ and second‐generation families of peptides to test the hypothesis that a large increase in potency in bacteria‐like lipid vesicles will correlate with a large improvement in antimicrobial activity. The results do not support the hypothesis. Despite a 20‐fold increase in potency against bacteria‐like lipid vesicles, the second‐generation peptides are only slightly more active against bacteria, and at the same time, are also more toxic against mammalian cells. The results suggest that a “pipeline” strategy toward the optimization of antimicrobial peptides could begin with a vesicle‐based screen for identifying families with broad‐spectrum activity, but will also need to include screening or optimization steps that are done under conditions that are more directly relevant to possible therapeutic applications. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 1–6, 2014.
Cell attachment and spreading activity of mixed laminin peptide–chitosan membranes
Authors: Otagiri Dai , Yamada Yuji , Hozumi Kentaro , Katagiri Fumihiko , Kikkawa Yamato , Nomizu Motoyoshi
Published: July 2013

Laminins are a multifunctional molecule with numerous active sites that have been identified in short peptide sequences. Mixed peptide‐conjugated chitosan membranes using laminin‐derived active peptides have been previously demonstrated to be useful as a biomaterial for tissue engineering. In this study, two syndecan‐binding peptides, AG73 (RKRLQVQLSIRT) and C16 (KAFDITYVRLKF), and three integrin‐binding peptides, EF1zz (ATLQLQEGRLHFXFDLGKGR, X: Nle, binding to integrin α2β1), A99a (ALRGDN, binding to integrin αvβ3), and A2G10 (SYWYRIEASRTG, binding to integrin α6β1), were mixed in various combinations, conjugated to chitosan membranes, and evaluated for their cell attachment and spreading activities. The cell attachment and spreading activity of EF1zz, A99a, and A2G10 were enhanced by AG73. In contrast, C16 enhanced only the cell attachment and spreading activity of A99a and did not influence the activity of EF1zz and A2G10. As well as previous study, the AG73–chitosan membrane bound to only syndecan. On the other hand, the C16–chitosan membrane interacted with both syndecan and β1 integrin. These data suggest that interaction of different receptors can cause synergistic effects. Therefore, AG73 is widely applicable as a synergistic agent for mixed peptide–matrices using several types of integrin‐binding peptides. Additionally, the A2G10/AG73–chitosan membrane may be useful to investigate detailed biological functions of α6β1 integrin, which is a major laminin‐binding receptor. Using a combination of tissue‐appropriate laminin‐derived peptides, the mixed peptide–chitosan membranes may serve as functional biomaterials for tissue engineering. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 751–759, 2013.
Self‐assembling peptide nanofibers promoting cell adhesion and differentiation
Authors: Fukunaga Kazuto , Tsutsumi Hiroshi , Mihara Hisakazu
Published: July 2013

There is an increasing need for the development of functional artificial extracellular matrices (ECMs) for tissue engineering. Recently, we have successfully designed a self‐assembling peptide, named E1Y9, to construct functional ECMs. We describe here an enhancement of abilities of E1Y9 materials to promote cell adhesion and differentiation, using functional peptide sequences derived from natural extracellular matrix proteins. We designed functionalized self‐assembling peptides, RGDS‐conjugated E1Y9 (E1Y9‐RGDS) and IKVAV‐conjugated E1Y9 (E1Y9‐IKVAV). E1Y9‐RGDS and E1Y9‐IKVAV formed peptide nanofibers in a similar manner to E1Y9, with β‐sheet secondary structures. Surfaces coated with peptide nanofibers displayed the higher bioactivities of E1Y9‐RGDS for cell adhesion and E1Y9‐IKVAV for cell differentiation than those of E1Y9, with the activities being dependent on the concentrations of the functional peptides. These functionalized peptides will be useful for the construction of functional ECMs in cell and tissue engineering. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 731–737, 2013.
Microsurgical anatomy of the denticulate ligaments and their relationship with the axilla of the spinal nerve roots
Authors: Gürer Bora , Canbay Suat , Bozkurt Melih , Cikla Ulaş , Hananya Tomer , Okut Hayrettin , Başkaya Mustafa K.
Published: July 2013

The denticulate ligaments (DL), 20 or 21 pairs of meningeal extensions, spread from the lateral aspect of the spinal cord to the internal aspect of the spinal dura mater. The aim of this study is to define the specific relationship of the DL with adjacent axilla of the spinal nerve roots and to investigate the anatomical features of the DLs and their variations. The topographical anatomy of the DLs and their relationships with the adjacent axilla of the spinal nerve roots was examined on 16 formalin‐fixed adult cadaveric spinal cords. The distances from the dural attachment of the DL to the axilla of the superior and inferior spinal nerve roots were measured bilaterally at every spinal level. Also the distances from the dural attachment of the DL to the lateral aspect of the spinal cord were measured bilaterally. Cervical DLs showed a triangular shape, while in the thoracic segment the ligament changes the shape to “Y.” Also the most caudal DL was identified to be at the L1–2 level. Our study revealed that the distances from the dural attachment of the DL to the superior and inferior spinal nerve root axilla were different at the cervical, upper thoracic and the lower thoracic segments. Both distances to the superior and inferior spinal nerve root axilla were shown to increase from cervical to lower thoracic segments. This study provides a detailed anatomy of the DLs and their relationship with the adjacent spinal nerve root axilla. Clin. Anat. 27:733–737, 2014. © 2013 Wiley Periodicals, Inc.