bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of immune response in Yersinia pestis infection
Authors: Amedei Amedeo , Niccolai Elena , Marino Luigi , D'Elios Mario Milco
Published: September 2011

Yersinia pestis (Y. Pestis) is an infamous pathogen causing plague pandemics throughout history and is a selected agent of bioterrorism threatening public health. Y. pestis was first isolated by Alexandre Yersin in 1894 in Hong Kong and in the years to follow from all continents. Plague is enzootic in different rodents and their fleas in Africa, North and South America, and Asia such as Middle/Far East and ex-USSR countries.

Comprehending the multifaceted interaction between Y. pestis and the host immune system will enable us design more effective vaccines.

Innate immune response and both component (humoral and cellular) of adaptive immune response contribute to host defense against Y.pestis infection, but the bacterium possess different mechanisms to counteract the immune response.

The aims of this review are to analyze the role of immune response versus Yersinia pestis infection and to highlight the various stratagems adopted by Y. pestis to escape the immunological defenses.
La question territoriale dans les relations internationales en Asie du Nord-Est
Authors: Li Jin-Mieung
Published: September 2011

Trois groupes d’îles autour de l’archipel japonais font l’objet de dispute territoriale entre le Japon et ses pays voisins, la Russie, la Chine et la Corée du Sud, créant des tensions récurrentes depuis la fin de la Seconde Guerre mondiale. Ce sont les quatre îles Kouriles du Sud, occupées et administrées par la Russie, mais revendiquées par le Japon sous le nom de « territoires du Nord » ; les îles Senkaku (Diaoyutai), contrôlées et administrées par le Japon, mais revendiquées par la Chine ; l’île Dokdo (Takeshima, Rochers Liancourt), occupée et administrée par la Corée du Sud, mais revendiquée par le Japon. Le but de cet article n’est pas d’analyser le bien-fondé des arguments avancés par les pays protagonistes, mais d’observer l’origine, l’évolution et en particulier les conséquences des conflits territoriaux liés à la souveraineté sur ces îles.
rabid fans that take [Twilight] much too seriously": The construction and rejection of excess in Twilight antifandom
Authors: Pinkowitz Jacqueline Marie
Published: September 2011

The group of Twilight antifans known as the Anti-Twilight Movement has constructed themselves as a safe "us" in relation to the threatening and inappropriate Other that they have defined through their characterization of "rabid" Twilight fans and antifans' "them." Fearful of a low ranking on the cultural hierarchy, they have created their own internal fan hierarchy that, according to cultural notions about the superiority of class, education, and the elite over the uneducated and the popular, as well as of the dismissability of girl culture, ensures the dominance and safety of their own affected rationality over the characterized emotional and excessive behavior of rabid Twilight fans and antifans. Part of the performance of such scholarly affectation involves appropriating discourses of academia into their literary criticism of Twilight, so as to overcome any negative connotations of excess or susceptibility to the mass media. Their often feminine-gendered constructions of rabid emotionality and irrationality, while also perhaps revealing some element of self-hatred, showcases a group of antifans attempting to assign the same policing and consequential narratives and discourses that have traditionally been assigned to fanatics by the dominant culture to certain "threatening" fans and antifans within their own community, the ultimate means of identity construction and self-preservation.
Editorial policies, "public domain," and acafandom
Authors: Musiani Francesca
Published: September 2011

Transformative Works and Cultures' editorial policies are transformative in their own right, putting fans first and acknowledging the dual nature of acafans.
TLR Agonists Downregulate H2-O in CD8α− Dendritic Cells
Authors: Porter Gavin W. , Yi Woelsung , Denzin Lisa K.
Published: September 2011

Peptide loading of MHC class II (MHCII) molecules is catalyzed by the nonclassical MHCII-related molecule H2-M. H2-O, another MHCII-like molecule, associates with H2-M and modulates H2-M function. The MHCII presentation pathway is tightly regulated in dendritic cells (DCs), yet how the key modulators of MHCII presentation, H2-M and H2-O, are affected in different DC subsets in response to maturation is unknown. In this study, we show that H2-O is markedly downregulated in vivo in mouse CD8α− DCs in response to a broad array of TLR agonists. In contrast, CD8α+ DCs only modestly downregulated H2-O in response to TLR agonists. H2-M levels were slightly downmodulated in both CD8α− and CD8α+ DCs. As a consequence, H2-M/H2-O ratios significantly increased for CD8α− but not for CD8α+ DCs. The TLR-mediated downregulation was DC specific, as B cells did not show significant H2-O and H2-M downregulation. TLR4 signaling was required to mediate DC H2-O downregulation in response to LPS. Finally, our studies showed that the mechanism of H2-O downregulation was likely due to direct protein degradation of H2-O as well as downregulation of H2-O mRNA levels. The differential H2-O and H2-M modulation after DC maturation supports the proposed roles of CD8α− DCs in initiating CD4-restricted immune responses by optimal MHCII presentation and of CD8α+ DCs in promoting immune tolerance via presentation of low levels of MHCII–peptide.
Wnt5a Skews Dendritic Cell Differentiation to an Unconventional Phenotype with Tolerogenic Features
Authors: Valencia Jaris , Hernández-López Carmen , Martínez Víctor G. , Hidalgo Laura , Zapata Agustín G. , Vicente Ángeles , Varas Alberto , Sacedón Rosa
Published: September 2011

Dendritic cells (DCs) are critical regulators of immune responses that integrate signals from the innate and adaptive immune system and orchestrate T cell responses toward either immunity or tolerance. Growing evidence points to the Wnt signaling pathway as a pivotal piece in the immune balance and focuses on DCs as a direct target for their immunoregulatory role. Our results show that the increase in Wnt5a signaling during the differentiation of human DCs from monocytes alters their phenotype and compromises their subsequent capacity to mature in response to TLR-dependent stimuli. These Wnt5a-DCs produce scant amounts of IL-12p70 and TNF-α but increased levels of IL-10. Consequently, these Wnt5a-DCs have a reduced capacity to induce Th1 responses that promote IL-10 secretion by CD4 T cells. Changes in the transcriptional profile of Wnt5a-DCs correlate with their unconventional phenotype caused presumably by increased IL-6/IL-10 signaling during the process of DC differentiation. The effect of Wnt5a is not a consequence of β-catenin accumulation but is dependent on noncanonical Ca2+/calmodulin-dependent protein kinase II/NF-κB signaling. Our results therefore suggest that under high levels of Wnt5a, typical of the inflammatory state and sepsis, monocytes could differentiate into unconventional DCs with tolerogenic features.
A New Look at Immune Privilege of the Eye: Dual Role for the Vision-Related Molecule Retinoic Acid
Authors: Zhou Ru , Horai Reiko , Mattapallil Mary J. , Caspi Rachel R.
Published: September 2011

The eye is an immunologically privileged and profoundly immunosuppressive environment. Early studies reported inhibition of T cell proliferation, IFN-γ production, and generation of regulatory T cells (Tregs) by aqueous humor (AH) and identified TGF-β as a critical factor. However, T cell subsets including Foxp3+ Treg and Th17 were unknown at that time, as was the role of retinoic acid (RA) in Treg induction. Consequently, the effect of the ocular microenvironment on T cell lineage commitment and function, and the role of RA in this process, had not been explored. We now use gene-manipulated mice and highly purified T cell populations to demonstrate that AH suppresses lineage commitment and acquisition of Th1 and Th17 effector function of naive T cells, manifested as reduction of lineage-specific transcription factors and cytokines. Instead, AH promoted its massive conversion to Foxp3+ Tregs that expressed CD25, GITR, CTLA-4, and CD103 and were functionally suppressive. TGF-β and RA were both needed and synergized for Treg conversion by AH, with TGF-β–enhancing T cell expression of RA receptor α. Newly converted Foxp3+ Tregs were unstable, but were stabilized upon continued exposure to AH or by the DNA demethylating agent 5-aza-2′-deoxycytidine. In contrast, T cells already committed to effector function were resistant to the suppressive and Treg-inducing effects of AH. We conclude that RA in the eye plays a dual role: in vision and in immune privilege. Nevertheless, primed effector T cells are relatively insensitive to AH, helping to explain their ability to induce uveitis despite an inhibitory ocular microenvironment.
Virulence Plasmid (pYV)-Associated Expression of Phenotypic Virulent Determinants in PathogenicYersiniaSpecies: A Convenient Method for Monitoring the Presence of pYV under Culture Conditions and Its Application for Isolation/Detection ofYersinia pestisin Food
Authors: Bhaduri Saumya , Smith James L.
Published: September 2011

InYersinia pestis,Y. pseudotuberculosis, andY. enterocolitica, phenotypic expression of virulence plasmid (pYV: 70-kb)-associated genetic determinants may include low-calcium response (Lcr, pinpoint colony, size = 0.36 mm), colony morphology (size = 1.13 mm), crystal violet (CV) binding (dark-violet colony), Congo Red (CR) uptake (red pinpoint colony, size = 0.36 mm), autoagglutination (AA = cells agglutinate), and hydrophobicity (HP = clumping of cells).Y. pseudotuberculosisis chromosomally closely related toY. pestis;whereas,Y. enterocoliticais chromosomally more distantly related toY. pestisandY. pseudotuberculosis. All three species demonstrate Lcr, CV binding, and CR uptake. The colony morphology/size, AA, and HP characteristics are expressed in bothY. pseudotuberculosisandY. enterocoliticabut not inY. pestis. Congo red uptake inY. pestiswas demonstrated only on calcium-deficient CR magnesium oxalate tryptic soy agar (CR-MOX), whereas this phenotype was expressed on both CR-MOX and low-calcium agarose media inY. pseudotuberculosisandY. enterocolitica. These phenotypes were detectable at 37°C within 24 h inY. enterocoliticaandY. pseudotuberculosisbut did not appear until 48 h inY. pestisdue to its slower growth rate at 37°C. The pYV is unstable (i.e., easily lost under a variety of culture conditions) in all three species but is more unstable inY. pestis. The specific CR uptake byY. pestisin CR-MOX and the delayed time interval to express Lcr and CR uptake provide a means to differentiateY. pestisfromY. enterocoliticaandY. pseudotuberculosis. These differences in pYV expression inY. pestiscan be used for its isolation and detection in food.
Retrieval of tropospheric water vapour by using spectra of a 22 GHz radiometer
Authors: Bleisch R. , Kämpfer N. , Haefele A.
Published: September 2011

Abstract. In this paper, we present an approach to retrieve tropospheric water vapour profiles from pressure broadened emission spectra at 22 GHz, measured by a ground based microwave radiometer installed in the south of Bern at 905 m. Classical microwave instruments concentrating on the troposphere observe several channels in the center and the wings of the water vapour line (20–30 Ghz), whereas our retrieval approach uses spectra with a bandwidth of 1 GHz and a high resolution around the center of the 22 GHz water vapour line. The retrieval is sensitive up to 7 km with a vertical resolution of 3–5 km. Comparisons with profiles from operational balloon soundings, performed at Payerne, 40 km away from the radiometer location, showed a good agreement up to 7 km with a correlation of above 0.8. The retrievals shows a wet bias of 10–20% compared to the sounding.
Hodgkin lymphoma: 2011 update on diagnosis, risk‐stratification, and management
Authors: Ansell Stephen M.
Published: September 2011

Disease overview:

Hodgkin lymphoma (HL) is an uncommon B‐cell lymphoid malignancy affecting 8,500 new patients annually and representing ∼11% of all lymphomas in the United States.

Diagnosis:

HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte‐rich HL are subgroups under the designation of classical HL.

Risk stratification:

An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence are used to optimize therapy for patients with limited or advanced stage disease.

Risk‐adapted therapy:

Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved‐field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy.

Management of relapsed/refractory disease:

High‐dose chemotherapy (HDCT) followed by an autologous stem‐cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, palliative chemotherapy, nonmyeloablative allogeneic transplant, or participation in a clinical trial should be considered. Am. J. Hematol. 86:852–858, 2011. © 2011 Wiley‐Liss, Inc.
Citric acid used as a crosslinking agent for the grafting of chitosan onto woolen fabric
Authors: Gawish S. M. , Abo El‐Ola S. M. , Ramadan A. M. , Abou El‐Kheir A. A.
Published: September 2011

Modification of woolen fabrics was done by the grafting of low‐molecular‐weight deacetylated chitosan in the presence of citric acid as a crosslinking agent with the pad–dry cure method at different conditions (times and temperatures). The add‐on of chitosan and the optimum conditions were determined. The improved properties of modified wool by chitosan were evaluated with the urea bisulfite solubility test, crease recovery angle, yellowness index, and scanning electron microscopy. The dyeing properties of modified wool fabrics were studied with acid and reactive dyes. The biocidal activities of the modified and unmodified wool samples were evaluated and compared against some species of microorganisms, including Escherichia coli (Gram negative), Staphylococcus aureus (Gram positive), Candida albicans, and Aspergillus flavus. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Is There an Entrance Complex for the F+NH3 Reaction?
Authors: Feng Hao , Sun Weiguo , Xie Yaoming , Schaefer Henry F.
Published: September 2011

Challenges associated with the theoretical and experimental kinetics of the F+NH3→HF+NH2 reaction suggest the need for a more‐precise potential surface. We have investigated the reactants and the products of the reaction, as well as the transition state and two complexes, with rather rigorous ab initio methods. The F••••NH3 complex existing in the entrance valley is predicted to lie 13.7 kcal mol−1 below the reactants. A small classical barrier of 2.0 kcal mol−1 separates this entrance well from products HF+NH2. These results explain the observation by Persky of unprecedented inverse temperature dependence for the F+NH3 rate constants. The strong hydrogen‐bonded complex FH••••NH2 exists in the exit valley, and with a binding energy of 9.9 kcal mol−1 relative to separated products. The vibrational frequencies of all stationary points are predicted with the CCSD(T)/aug‐cc‐pVQZ method.
Assessment of immunization against recombinant human bone morphogenetic protein‐2 (dibotermin alpha) on reproduction and development in rabbits
Authors: Wright David J. , Minck Daniel R. , Nowak John , Warner Garvin , Cukierski Mark
Published: September 2011

BACKGROUND: To determine if the fetus was affected by maternal antibodies to BMP‐2, the antibody response and developmental effects in fetuses from does immunized against recombinant human BMP‐2 were evaluated. METHODS: Female New Zealand White rabbits received four intramuscular injections (on premating days 1, 8, 22, and 43 [3 days before mating]) of saline and adjuvant (TiterMax® Gold [control]) or recombinant human BMP‐2 (2 mg/dose) and adjuvant (treated). On GD 29, fetuses were examined, and maternal and fetal anti‐BMP‐2 titer levels and neutralizing activity were assessed. RESULTS: Anti‐BMP‐2 antibodies were detected in 17 of 18 treated does (127 of 151 fetuses), and low levels were detected in 2 of 16 control does (no fetal exposure observed). In general, levels of fetal anti‐BMP‐2 antibodies were similar to those in the does, and pregnancy did not boost the immune response to BMP‐2. There were no effects of immunization or anti‐BMP‐2 antibody titer levels on embryo–fetal viability, fetal weight, or fetal external, visceral, or skeletal development. Only a small number of fetuses (n = 4) displayed detectable neutralizing anti‐BMP‐2 antibodies, but there were no treatment‐related effects in those fetuses. CONCLUSIONS: The lack of embryo–fetal effects may be due to dosage effects of neutralizing anti‐BMP‐2 antibodies, timing of exposure (stage and duration) to neutralizing anti‐BMP‐2 antibodies, and/or redundancy of effects of the various BMPs. Birth Defects Res (Part B) 92:543–552, 2011. © 2011 Wiley Periodicals, Inc.
Synthesis of Skeletal Analogues of Saxitoxin Derivatives and Evaluation of Their Inhibitory Activity on Sodium Ion Channels NaV1.4 and NaV1.5
Authors: Shinohara Ryoko , Akimoto Takafumi , Iwamoto Osamu , Hirokawa Takatsugu , Yotsu‐Yamashita Mari , Yamaoka Kaoru , Nagasawa Kazuo
Published: September 2011

Skeletal analogues of saxitoxin (STX) that possess a fused‐type tricyclic ring system, designated FD‐STX, were synthesized as candidate sodium ion channel modulators. Three kinds of FD‐STX derivatives4 a–cwith different substitution at C13 were synthesized, and their inhibitory activity on sodium ion channels was examined by means of cell‐based assay. (−)‐FD‐STX (4 a) and (−)‐FD‐dcSTX (4 b), which showed moderate inhibitory activity, were further evaluated by the use of the patch‐clamp method in cells that expressed NaV1.4 (a tetrodotoxin‐sensitive sodium channel subtype) and NaV1.5 (a tetrodotoxin‐resistant sodium channel subtype). These compounds showed moderate inhibitory activity towards NaV1.4, and weaker inhibitory activity towards NaV1.5. Uniquely, however, the inhibition of NaV1.5 by (−)‐FD‐dcSTX (4 b) was “irreversible”.
Pipe Service Age Effect on Chlorine Decay in Drinking‐Water Transmission and Distribution Systems
Authors: Al‐Jasser A. O.
Published: September 2011

Maintaining acceptable quality of water transported in the transmission and distribution system requires the chlorination of water beyond the treatment plant. While flowing through pipes, the chlorine concentration decreases for different reasons. Reaction with the pipe material itself and the reaction with both the biofilm and tubercles formed on the pipe wall are known as pipe wall demand. This varies with pipe parameters. The aim of this paper was to assess the impact of the service age of pipes on the chlorine wall decay constant. One hundred and fifty three pipe sections of different sizes and four different pipe materials were collected and tested for their chlorine first‐order wall decay constants. The results showed that pipe service age was an important factor that must not be ignored. For the range of the 55 years of pipe service age used in this study, the change in the wall decay ranged from 8 to 531% of the corresponding values in the recently installed pipes. The effect of service age on the wall decay constants was most evident in steel pipes. Other important findings were reached.
Tailoring Metal–Organic Frameworks for CO2 Capture: The Amino Effect
Authors: Vitillo Jenny G. , Savonnet Marie , Ricchiardi Gabriele , Bordiga Silvia
Published: September 2011

Carbon dioxide capture from processes is one of the strategies adopted to decrease anthropogenic greenhouse gas emissions. To lower the cost associated with the regeneration of amine‐based scrubber systems, one of the envisaged strategies is the grafting of amines onto high‐surface‐area supports and, in particular, onto metal–organic frameworks (MOFs). In this study, the interaction between CO2 and aliphatic and aromatic amines has been characterized by quantum mechanical methods (MP2), focusing attention both on species already reported in MOFs and on new amine‐based linkers, to inspire the rational synthesis of new high‐capacity MOFs. The calculations highlight binding‐site requisites and indicate that CO2 vibrations are independent of the adsorption energy and monitoring them in probe‐molecule experiments is not a suitable marker of efficient adsorption.
N‐Heterocyclic Carbene‐Catalyzed Oxidative Esterification Reaction of Aldehydes with Alkyl Halides under Aerobic Conditions
Authors: Xin Yang‐Chun , Shi Shi‐Hui , Xie Dong‐Dong , Hui Xin‐Ping , Xu Peng‐Fei
Published: September 2011

An efficient N‐heterocyclic carbene‐catalyzed oxidative esterification reaction of aldehydes with alkyl halides or alkyl 4‐methylbenzenesulfonate is reported. It was worth noting that (1) the configuration of alkyl halides or alkyl 4‐methylbenzenesulfonates was inverted completely, and (2) the presence of oxygen was crucial for this transformation. The reaction proceeded smoothly under mild conditions and various esters were afforded in moderate to good yields. In addition, we have developed an efficient tandem oxidation/esterification reaction of alcohols. This methodology provides a rare example of a reaction of the Breslow intermediate to sp3‐carbon centered electrophiles.
The hypermethylation of the O6‐methylguanine‐DNA methyltransferase gene promoter in gliomas—correlation with array comparative genome hybridization results and IDH1 mutation
Authors: Tuononen Katja , Tynninen Olli , Sarhadi Virinder Kaur , Tyybäkinoja Anne , Lindlöf Mikael , Antikainen Miia , Näpänkangas Juha , Hirvonen Ari , Mäenpää Hanna , Paetau Anders , Knuutila Sakari
Published: September 2011

The use of molecular markers in the diagnostics of gliomas aids histopathological diagnosis and allows their further classification into clinically significant subgroups. The aim of this study was to characterize the methylation pattern of the O6‐methylguanine‐DNA methyltransferase (MGMT) promoter, gene copy number aberrations, and isocitrate dehydrogenase I (IDH1) mutation in gliomas. We studied 51 gliomas (15 oligodendrogliomas, 18 oligoastrocytomas, 3 astrocytomas, and 15 glioblastomas) by pyrosequencing, array comparative genome hybridization (CGH), and immunohistochemistry. MGMT hypermethylation was observed in 100% of oligoastrocytomas, 93% of oligodendrogliomas, and 47% of glioblastomas. The most frequently altered chromosomal regions were deletions of 1p31.1/21.1‐22.2 and 19q13.3qter in oligodendroglial tumors, and losses of 9p21.3, 10q25.3qter, and 10q26.13‐26.2 in glioblastomas. Deletions on 9p and 10q, and gain of 7p were associated with the unmethylated MGMT phenotype, whereas deletion of 19q and oligodendroglial morphology was associated with MGMT hypermethylation. IDH1 mutation showed positive correlation with MGMT hypermethylation and loss of 1p/19q. Our results suggest that MGMT promoter methylation, analyzed by pyrosequencing, is a frequent event in oligodendroglial tumors, and it correlates with IDH1 mutation and 19q loss in gliomas. Pyrosequencing proved a good method for assessing the degree of MGMT methylation in formalin‐fixed paraffin‐embedded glioma samples. However, further studies are needed to confirm a clinically relevant cut‐off point for MGMT methylation in gliomas. © 2011 Wiley Periodicals, Inc.
Different duration of at‐risk mental state associated with neurofunctional abnormalities. A multimodal imaging study
Authors: Smieskova Renata , Allen Paul , Simon Andor , Aston Jacqueline , Bendfeldt Kerstin , Drewe Jürgen , Gruber Kerstin , Gschwandtner Ute , Klarhoefer Markus , Lenz Claudia , Scheffler Klaus , Stieglitz Rolf‐Dieter , Radue Ernst‐Wilhelm , McGuire Philip , Riecher‐Rössler Anita , Borgwardt Stefan J.
Published: September 2011

Objectives: Neurofunctional alterations are correlates of vulnerability to psychosis, as well as of the disorder itself. How these abnormalities relate to different probabilities for later transition to psychosis is unclear. We investigated vulnerability‐ versus disease‐related versus resilience biomarkers of psychosis during working memory (WM) processing in individuals with an at‐risk mental state (ARMS). Experimental design: Patients with “first‐episode psychosis” (FEP, n = 21), short‐term ARMS (ARMS‐ST, n = 17), long‐term ARMS (ARMS‐LT, n = 16), and healthy controls (HC, n = 20) were investigated with an n‐back WM task. We examined functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging (sMRI) data in conjunction using biological parametric mapping (BPM) toolbox. Principal observations: There were no differences in accuracy, but the FEP and the ARMS‐ST group had longer reaction times compared with the HC and the ARMS‐LT group. With the 2‐back > 0‐back contrast, we found reduced functional activation in ARMS‐ST and FEP compared with the HC group in parietal and middle frontal regions. Relative to ARMS‐LT individuals, FEP patients showed decreased activation in the bilateral inferior frontal gyrus and insula, and in the left prefrontal cortex. Compared with the ARMS‐LT, the ARMS‐ST subjects showed reduced activation in the right inferior frontal gyrus and insula. Reduced insular and prefrontal activation was associated with gray matter volume reduction in the same area in the ARMS‐LT group. Conclusions: These findings suggest that vulnerability to psychosis was associated with neurofunctional alterations in fronto‐temporo‐parietal networks in a WM task. Neurofunctional differences within the ARMS were related to different duration of the prodromal state and resilience factors. Hum Brain Mapp 33:2281–2294, 2012. © 2011 Wiley Periodicals, Inc.
The relationship between regional and inter‐regional functional connectivity deficits in schizophrenia
Authors: Zalesky Andrew , Fornito Alex , Egan Gary F. , Pantelis Christos , Bullmore Edward T.
Published: September 2011

While schizophrenia is frequently characterized as a disorder of disturbed functional connectivity, the causes and pathophysiological origins of such disturbances remain unclear. The aim of this study was to better elucidate the mechanistic causes of abnormal functional connectivity in schizophrenia, measured as the extent of temporal correlation between endogenous fluctuations recorded at anatomically discrete brain regions during resting‐state functional MRI. An approach was developed to perform whole‐brain connectivity mapping at the resolution of individual pairs of voxels, without the need for arbitrary parcellation of the cerebrum. Between‐group connectivity reductions in 12 people diagnosed with schizophrenia and 15 age‐, IQ‐, and gender‐matched healthy volunteers were localized to a distributed network including frontoparietal and occipitoparietal connections. The gray‐matter regions comprising this disturbed network showed evidence of local reductions in both intra‐regional homogeneity (29%–33% reduction) and signal power (40%–60% reduction). The extent to which inter‐regional correlation was reduced between a pair of gray matter regions was found to be strongly correlated with the extent of local decoherence evident within the gray matter regions per se. This suggests measurement of aberrant functional connectivity in schizophrenia is both a measurement of altered coupling between regions as well as a measurement of local decoherence within regions. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Chemical Synthesis of Integral Membrane Proteins: Methods and Applications
Authors: Shen Fei , Huang Yi‐Chao , Tang Shan , Chen Yong‐Xiang , Liu Lei
Published: September 2011

The development of efficient chemical methods for total synthesis or semisynthesis of integral membrane proteins is an important challenge at the interface between chemistry and biology. This review outlines the recent advances in the synthesis of integral membrane proteins, with particular focus on the methods for difficult peptide synthesis, purification, and enhancement of peptide solubility under the ligation conditions. The applications of these methods to the synthesis of integral membrane proteins with one or multiple transmembrane domains are also described.
A battery of genotoxicity studies with an allergy vaccine adjuvanted with monophosphoryl lipid A (MPL®) for the treatment of grass pollen allergy
Authors: Reeve Lesley , Baldrick Paul , Hewings Simon , Skinner Murray
Published: September 2011

The allergy vaccine Pollinex® Quattro Grass, developed for the prevention/relief of allergic symptoms caused by grass pollen in adults and children, contains extracts of 12 grass pollens and rye cereal (all chemically modified by glutaraldehyde), adsorbed onto l‐tyrosine with addition of the immunostimulatory adjuvant monophosphoryl lipid A (MPL®). This paper represents the first publication on genetic toxicology data for such a vaccine. An Ames test using five strains of Salmonella typhimurium at concentrations up to 2000 standardized units (SU) per plate in the absence (−) and presence (+) of metabolic activation (rat liver S9) showed negative results, as did treatment − S9 in the mouse lymphoma assay (MLA). However, a reproducible positive response was noted in the MLA + S9, which could not be attributed to extreme culture conditions, but may have been an artefact of the exogenous metabolizing system. Up to 60% false positive results are reported for the MLA with noncarcinogens. Hence, in vivo genotoxicity studies were conducted. These further assessments comprised a rat bone marrow micronucleus test following subcutaneous (s.c.) doses of 10 000, 20 000 or 40 000 SU kg−1 per day for 2 days, and a comet assay in liver and kidney cells from rats treated with Pollinex® Quattro Grass at 20 000 or 40 000 SU kg−1 per day s.c. for 2 days. Plasma analysis showed evidence of systemic antibodies to Pollinex® Quattro Grass immunogens, but the exposure levels could not be quantified. No evidence of genotoxicity was observed in either of the in vivo studies. Overall, the genotoxicity test results supported safe clinical use of Pollinex® Quattro Grass. Copyright © 2011 John Wiley & Sons, Ltd.
The Wnt antagonist Wif‐1 interacts with CTGF and inhibits CTGF activity
Authors: Surmann‐Schmitt Cordula , Sasaki Takako , Hattori Takako , Eitzinger Nicole , Schett Georg , von der Mark Klaus , Stock Michael
Published: September 2011

Wnt inhibitory factor 1 (Wif‐1) is a secreted antagonist of Wnt signalling. We recently demonstrated that this molecule is expressed predominantly in superficial layers of epiphyseal cartilage but also in bone and tendon. Moreover, we showed that Wif‐1 is capable of binding to several cartilage‐related Wnt ligands and interferes with Wnt3a‐dependent Wnt signalling in chondrogenic cells. Here we provide evidence that the biological function of Wif‐1 may not be confined to the modulation of Wnt signalling but appears to include the regulation of other signalling pathways. Thus, we show that Wif‐1 physically binds to connective tissue growth factor (CTGF/CCN2) in vitro, predominantly by interaction with the C‐terminal cysteine knot domain of CTGF. In vivo such an interaction appears also likely since the expression patterns of these two secreted proteins overlap in peripheral zones of epiphyseal cartilage. In chondrocytes CTGF has been shown to induce the expression of cartilage matrix genes such as aggrecan (Acan) and collagen2a1 (Col2a1). In this study we demonstrate that Wif‐1 is capable to interfere with CTGF‐dependent induction of Acan and Col2a1 gene expression in primary murine chondrocytes. Conversely, CTGF does not interfere with Wif‐1‐dependent inhibition of Wnt signalling. These results indicate that Wif‐1 may be a multifunctional modulator of signalling pathways in the cartilage compartment. J. Cell. Physiol. 227: 2207–2216, 2012. © 2011 Wiley Periodicals, Inc.
Tracking the 2009 H1N1 influenza virus in the Italian region Campania
Authors: Esposito Ciro , Di Spirito Antimo , Cuomo Nunzia , Di Nicuolo Giuseppe , Flaminio Giovanni , Altamura Fabiana , Ambrosino Daniele , Cantalupo Federich , Costa Caterina , Pentimalli Francesca , Tarro Giulio
Published: September 2011

A novel swine‐origin influenza A (H1N1) virus affecting humans was detected in April 2009 in Mexico, Canada, and USA. The S‐OIV infection caused a mild to severe febrile respiratory disease throughout the world. Here, we briefly review the main features of influenza A viruses, which caused also other pandemics in the past, and focus in particular on the epidemiology data of the H1N1 influenza in the Italian region Campania, which resulted the most affected by the S‐OIV and the one with more lethal cases. In Campania, the peak of influenza preceded of about 2 weeks the incidence peak at the national level. Moreover, the percentage of H1N1‐positive patients was much higher in the main town Naples, compared to the other Campania provinces. The age group from 7 months to 17 years was the most affected by the H1N1 infection (43.45%), similarly to what reported at the national level. Here, we discuss the possible reasons of the high H1N1 incidence in Campania and the implications that these findings could have on the future prevention campaigns. J. Cell. Physiol. 227: 2813–2817, 2012. © 2011 Wiley Periodicals, Inc.
Simplified and automatic one‐pot synthesis of 16α‐[18F]fluoroestradiol without high‐performance liquid chromatography purification
Authors: Knott K. E. , Grätz D. , Hübner S. , Jüttler S. , Zankl C. , Müller M.
Published: September 2011

16α‐[18F]Fluoroestradiol (16α‐[18F]FES, 1) is known as a valuable tracer in molecular imaging as estrogen receptor (ER) ligand for investigation of primary and metastatic breast cancer. ER concentration in human breast tumor cells is a significant indicator for the degree of disease and is often monitored by immunoassays or in vitro ligand binding of a tumor biopsy sample. More preferable non‐invasive diagnosis is accessible using 16α‐[18F]FES (1) as PET tracer. Our aim was to develop a reliable, easy‐to‐use, remotely controlled synthesis for non carrier added (n.c.a.) 16α‐[18F]FES (1) by nucleophilic substitution using a disposable cassette for GE TRACERlab® MXFDG. Purification of the crude product using solid phase extraction (SPE) cartridges, Oasis® WAX, HLB Plus, Sep‐Pak® C18 and Light Alumina N, allows abandonment of an HPLC purifying system. Formulation of the final product is included in the automatic synthesis. The experimental conditions for this easy‐to‐use synthesis for routine production of 16α‐[18F]FES (1) are given in detail. Within 75 min 16α‐[18F]FES (1) is produced in typically 20% n.c.a., radiochemical yield (non decay corrected). Chemical and radiochemical purity is >95% and >99%, respectively. Copyright © 2011 John Wiley & Sons, Ltd.
Inhibition of inflammation and oxidative stress by Angelica dahuricae radix extract decreases apoptotic cell death and improves functional recovery after spinal cord injury
Authors: Moon Youn Joo , Lee Jee Youn , Oh Myung Sook , Pak Youngmi Kim , Park Kang‐Sik , Oh Tae Hwan , Yune Tae Young
Published: September 2011

Inflammation and oxidative stress play major roles in the pathogenesis after spinal cord injury (SCI). Here, we examined the neuroprotective effects of Angelica dahuricae radix (ADR) extract after SCI. ADR extract significantly decreased the levels of proinflammatory factors such as tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), inducible nitric oxide synthase (iNOS), and cyclooxygenase‐2 (COX‐2) in a lipopolysaccharide (LPS)‐activated microglial cell line, BV2 cells. ADR extract also significantly alleviated the level of reactive oxygen species in LPS‐activated BV2 cells. To examine the neuroprotective effect of ADR extract after SCI, spinally injured rats were administered ADR extract orally at a dose of 100 mg/kg for 14 days. ADR extract treatment significantly reduced the levels of TNF‐α, IL‐1β, IL‐6, iNOS, and COX‐2. The levels of superoxide anion (O2·–) and protein nitration were also significantly decreased by ADR extract. In addition, ADR extract inhibited p38 mitogen‐activated protein kinase activation and pronerve growth factor expression in microglia after SCI. Furthermore, ADR extract significantly inhibited caspase‐3 activation following apoptotic cell death of neurons and oligodendrocytes, thereby improving functional recovery after injury. Thus, our data suggest that ADR extract provides neuroprotection by alleviating inflammation and oxidative stress and can be used as an orally administered therapeutic agent for acute SCI. © 2011 Wiley Periodicals, Inc.
Human peripheral blood derived mesenchymal stem cells demonstrate similar characteristics and chondrogenic differentiation potential to bone marrow derived mesenchymal stem cells
Authors: Chong Pan‐Pan , Selvaratnam Lakshmi , Abbas Azlina A. , Kamarul Tunku
Published: September 2011

The use of mesenchymal stem cells (MSCs) for cartilage repair has generated much interest owing to their multipotentiality. However, their significant presence in peripheral blood (PB) has been a matter of much debate. The objectives of this study are to isolate and characterize MSCs derived from PB and, compare their chondrogenic potential to MSC derived from bone marrow (BM). PB and BM derived MSCs from 20 patients were isolated and characterized. From 2 ml of PB and BM, 5.4 ± 0.6 million and 10.5 ± 0.8 million adherent cells, respectively, were obtained by cell cultures at passage 2. Both PB and BM derived MSCs were able to undergo tri‐lineage differentiation and showed negative expression of CD34 and CD45, but positively expressed CD105, CD166, and CD29. Qualitative and quantitative examinations on the chondrogenic potential of PB and BM derived MSCs expressed similar cartilage specific gene (COMP) and proteoglycan levels, respectively. Furthermore, the s‐GAG levels expressed by chondrogenic MSCs in cultures were similar to that of native chondrocytes. In conclusion, this study demonstrates that MSCs from PB maintain similar characteristics and have similar chondrogenic differentiation potential to those derived from BM, while producing comparable s‐GAG expressions to chondrocytes. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:634–642, 2012
Spending degrees of freedom in a poor economy: A case study of building a sightability model for moose in northeastern Minnesota
Authors: Giudice John H. , Fieberg John R. , Lenarz Mark S.
Published: September 2011

Sightability models are binary logistic‐regression models used to estimate and adjust for visibility bias in wildlife‐population surveys. Like many models in wildlife and ecology, sightability models are typically developed from small observational datasets with many candidate predictors. Aggressive model‐selection methods are often employed to choose a best model for prediction and effect estimation, despite evidence that such methods can lead to overfitting (i.e., selected models may describe random error or noise rather than true predictor–response curves) and poor predictive ability. We used moose (Alces alces) sightability data from northeastern Minnesota (2005–2007) as a case study to illustrate an alternative approach, which we refer to as degrees‐of‐freedom (df) spending: sample‐size guidelines are used to determine an acceptable level of model complexity and then a pre‐specified model is fit to the data and used for inference. For comparison, we also constructed sightability models using Akaike's Information Criterion (AIC) step‐down procedures and model averaging (based on a small set of models developed using df‐spending guidelines). We used bootstrap procedures to mimic the process of model fitting and prediction, and to compute an index of overfitting, expected predictive accuracy, and model‐selection uncertainty. The index of overfitting increased 13% when the number of candidate predictors was increased from three to eight and a best model was selected using step‐down procedures. Likewise, model‐selection uncertainty increased when the number of candidate predictors increased. Model averaging (based onR = 30 models with 1–3 predictors) effectively shrunk regression coefficients toward zero and produced similar estimates of precision to our 3‐df pre‐specified model. As such, model averaging may help to guard against overfitting when too many predictors are considered (relative to available sample size). The set of candidate models will influence the extent to which coefficients are shrunk toward zero, which has implications for how one might apply model averaging to problems traditionally approached using variable‐selection methods. We often recommend the df‐spending approach in our consulting work because it is easy to implement and it naturally forces investigators to think carefully about their models and predictors. Nonetheless, similar concepts should apply whether one is fitting 1 model or using multi‐model inference. For example, model‐building decisions should consider the effective sample size, and potential predictors should be screened (without looking at their relationship to the response) for missing data, narrow distributions, collinearity, potentially overly influential observations, and measurement errors (e.g., via logical error checks). © 2011 The Wildlife Society.
Self‐Driven Gel Conveyer: Effect of Interactions Between Loaded Cargo and Self‐Oscillating Gel Surface
Authors: Murase Yoko , Takeshima Reiji , Yoshida Ryo
Published: September 2011

A “self‐oscillating” gel that swells and deswells periodically under constant conditions is developed as a novel biomimetic gel differing from conventional stimuli‐responsive polymer gels. By utilizing the peristaltic motion of the self‐oscillating gel, autonomous mass‐transport systems can be realized. With the propagation of the chemical wave, the loaded gel cargo is autonomously transported by rotating on the surface. To apply the self‐driven gel conveyer to a wider range of uses, it is important to investigate the influence of the physical interaction between the self‐oscillating gel and the loaded cargo on its transporting ability. Here, the effect of the interaction is evaluated by using several kinds of gel cargo with varying charge states, hydrophilicities, and surface roughnesses.

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Completely independent spanning trees in torus networks
Authors: Hasunuma Toru , Morisaka Chie
Published: September 2011

Let T1, T2, …, Tk be spanning trees in a graph G. If for any two vertices u, v in G, the paths from u to v in T1, T2, …, Tk are pairwise internally disjoint, then T1, T2, …, Tk are completely independent spanning trees in G. Completely independent spanning trees can be applied to fault‐tolerant communication problems in interconnection networks. In this article, we show that there are two completely independent spanning trees in any torus network. Besides, we generalize the result for the Cartesian product. In particular, we show that there are two completely independent spanning trees in the Cartesian product of any 2‐connected graphs. © 2011 Wiley Periodicals, Inc. NETWORKS, 2012
Constructing optimal subnetworks for the crossed cube network
Authors: Wang Dajin
Published: September 2011

We present an algorithm that constructs subnetworks from an n‐dimensional crossed cube, denoted CQn, so that for any given κ, 2 ≤ κ ≤ n − 1, the algorithm can generate a κ‐connected subnetwork that contains all 2n original nodes of CQn and preserves the symmetrical structure. The κ‐connected subnetworks constructed are all optimal in the sense that they use the minimum number of links to maintain the required connectivity. Being able to construct κ‐connected, all‐node subnetworks are important in many applications, such as computing in the presence of faulty links, or diagnosing the system with a lower fault bound. Links that are not used by the induced subnetworks could be used in parallel by some other computing tasks, improving the overall resource utilization of the system. © 2011 Wiley Periodicals, Inc. NETWORKS, 2012
Sensitivity and specificity of the Distress Thermometer and a two‐item depression screen (Patient Health Questionnaire‐2) with a ‘help’ question for psychological distress and psychiatric morbidity in patients with advanced cancer
Authors: Ryan Dermot Anthony , Gallagher Pamela , Wright Shelagh , Cassidy Eugene M.
Published: September 2011

Objectives

Brief screening tools may help clinicians in busy settings detect patients who are experiencing severe psychological distress. This study examined the performance of the Distress Thermometer (DT) and a two‐item depression screen [the Patient Health Questionnaire‐2 (PHQ‐2)] with a ‘help’ question in screening for distress and psychiatric morbidity among patients with advanced cancer.

Methods

Two hundred and five patients with advanced cancer completed the DT, the PHQ‐2 and ‘help’ question and the Hospital Anxiety and Depression Scale and were interviewed using the Structured Clinical Interview for DSM‐IV (SCID). The performance of the screening tools was examined against the Hospital Anxiety and Depression Scale and the SCID.

Results

Overall, discrimination levels were comparable for the DT [area under the curve (AUC) 0.80–0.81] and the PHQ‐2 (AUC 0.73–0.85). The DT performed best in detecting cases of distress and mood, anxiety or adjustment disorders (sensitivity 100%), but it had poor specificity (49–60%). The best performance in terms of combined sensitivity and specificity was the PHQ depression item versus the SCID (sensitivity 88%, specificity 73%). The inclusion of the ‘help’ question with the PHQ‐2 resulted in high levels of specificity (≥89%), but there was a significant drop in sensitivity (≤54%).

Conclusion

Ultra‐brief screening tools offer an efficient means of identifying patients with advanced cancer with severe distress or psychiatric morbidity but are less effective at identifying non‐distressed individuals. Used in conjunction with a ‘help’ question, these tools can help clinicians identify patients who are both distressed and likely to accept professional support. Copyright © 2011 John Wiley & Sons, Ltd.
Evaluation of flammability and toxicity hazards using infinite points
Authors: Prugh Richard W.
Published: September 2011

For many novel or unusual chemicals, there may be only one pressure/temperature point that is available for estimating flammability and/or toxicity hazards. This may be the atmospheric‐pressure boiling point, the vapor pressure at room temperature, or the vapor‐pressure/temperature point that corresponds to both the flash point and the lower flammable limit (LFL). It is shown here how an equation for the vapor‐pressure/temperature relationship above and below that point can be developed through use of a second “infinite point.” Thus, the liquid temperature that corresponds to a given toxic concentration can be estimated, and the flash point and LFL can also be estimated with only one set of T and P.

An infinite point for hydrocarbons was first noted in 1923, and this concept was “rediscovered” and extended to a wide variety of other chemicals in 1949. This article summarizes the previous work and provides a rearrangement of the Antoine equation so that an infinite point can be easily used to estimate vapor pressure (and thereby concentration) at any given temperature.

The primary purpose of this article is to provide guidance concerning the use of an infinite point to aid in establishing hazardous concentrations of flammable and/or toxic vapors, particularly in poorly ventilated enclosures, where a range of vapor‐pressure data is not readily available. © 2011 American Institute of Chemical Engineers Process Saf Prog, 2011