bluuebunny/crossref_metadata_2025 huggingface dataset:
The BTB-ZF Family of Transcription Factors: Key Regulators of Lineage Commitment and Effector Function Development in the Immune System
Authors: Beaulieu Aimee M. , Sant'Angelo Derek B.
Published: September 2011

Successful immunity depends upon the activity of multiple cell types. Commitment of pluripotent precursor cells to specific lineages, such as T or B cells, is obviously fundamental to this process. However, it is also becoming clear that continued differentiation and specialization of lymphoid cells is equally important for immune system integrity. Several members of the BTB-ZF family have emerged as critical factors that control development of specific lineages and also of specific effector subsets within these lineages. For example, BTB-ZF genes have been shown to control T cell versus B cell commitment and CD4 versus CD8 lineage commitment. Others, such as PLZF for NKT cells and Bcl-6 for T follicular helper cells, are necessary for the acquisition of effector functions. In this review, we summarize current findings concerning the BTB-ZF family members with a reported role in the immune system.
Fiber Tracts Anomalies in APPxPS1 Transgenic Mice Modeling Alzheimer's Disease
Authors: Chen H. , Epelbaum S. , Delatour B.
Published: September 2011

Amyloid beta (A) peptides are known to accumulate in the brain of patients with Alzheimer's disease (AD). However, the link between brain amyloidosis and clinical symptoms has not been elucidated and could be mediated by secondary neuropathological alterations such as fiber tracts anomalies. In the present study, we have investigated the impact of A overproduction in APPxPS1 transgenic mice on the integrity of forebrain axonal bundles (corpus callosum and anterior commissure). We found evidence of fiber tract volume reductions in APPxPS1 mice that were associated with an accelerated age-related loss of axonal neurofilaments and a myelin breakdown. The severity of these defects was neither correlated with the density of amyloid plaques nor associated with cell neurodegeneration. Our data suggest that commissural fiber tract alterations are present in A-overproducing transgenic mice and that intracellular A accumulation preceding extracellular deposits may act as a trigger of such morphological anomalies.
Electrochemical Properties of Silver Nanoparticle Doped Aminosilica Nanocomposite
Authors: Choi Yong-Jae , Luo Tzy-Jiun M.
Published: September 2011

The electrochemical properties of silver nanoparticle (d∼5 nm) synthesized within aminosilica film from spontaneous reduction reaction were examined using cyclic voltammetry and the results show that the nanocomposite film exhibits similar redox property as solution-synthesized silver nanoparticles when measuring in phosphate buffer solution and its redox potentials were found to be sensitive to the presence of chloride ions. It also shows that silver nanoparticles and hydrolyzed aminosilica increase the electron diffusivity of the aminosilica film. Both results confirm that an accurate reference electrode suitable for microfluidic devices can be created simply by treating an aminosilica-coated electrode with a silver nitrate solution. Furthermore, a humidity sensor based on silver-silica nanocomposite film has also been demonstrated.
Use of a Designed Peptide Library to Screen for Binders to a Particular DNA G-Quadruplex Sequence
Authors: Kobayashi Keita , Matsui Noriko , Usui Kenji
Published: September 2011

We demonstrated a method to screen for binders to a particular G-quadruplex sequence using easily designed short peptides consisting of naturally occurring amino acids and mining of binding data using statistical methods such as hierarchical clustering analysis (HCA). Despite the small size of the library used in this study, candidates of specific binders were identified. In addition, a selected peptide stabilized the G-quadruplex structure of a DNA oligonucleotide derived from the promoter region of the protooncogene c-MYC. This study illustrates how a peptide library can be designed and presents a screening guideline for construction of G-quadruplex binders. Such G-quadruplex peptide binders could be functionally modified to enable switching, cellular penetration, and organelle-targeting for cell and tissue engineering.
Circulation of Diverse Genotypes of Tahyna Virus in Xinjiang, People's Republic of China
Authors: Lu Zhi , Fu Shi-Hong , Wang Feng-Tian , Nasci Roger S. , Tang Qing , Liang Guo-Dong
Published: September 2011

Tahyna virus (TAHV) is widely distributed in Europe and Asia. A previous study reported a high level of conservation of the TAHV genome in isolates from Europe. During 2006 and 2007, three Tahyna virus isolates from mosquitoes were obtained from various locations in Xinjiang, People's Republic of China. We analyzed the complete coding sequence of full-length small, medium, and large segments of these isolates. Molecular and phylogenetic analyses of the three complete TAHV genomes showed that sequence identity between isolates from China and Europe was more divergent, and an unexpected level of medium segment diversity was found among isolates from China compared with high levels of sequence conservation for the small and large segments. This study indicated that effects of genotypic diversity on the ecology, transmission, and pathogenicity of TAHV in China should be studied.
Exploratory Study on Pathogenesis of Far-Eastern Spotted Fever
Authors: Duan Changsong , Meng Yanfen , Wang Xile , Xiong Xiaolu , Wen Bohai
Published: September 2011

Far-eastern spotted fever is an emerging disease caused by Rickettsia heilongjiangensis, a tick-borne obligate intracellular bacterium. In this study, R. heilongjiangensis was used to infect BALB/c mice by inoculation of retro-orbital venous plexus to imitate a blood infection caused by tick biting. We found that R. heilongjiangensis rapidly entered the circulation for systemic dissemination and the pathogen existed in liver, spleen, lungs, and brain of the mice at least 9 days post-infection (p.i.). Severe pathological lesions were observed in liver, lungs, and brain at Day 6 p.i. In addition, the elevated levels of inflammatory cytokines, including interferon-γ, tumor necrosis factor, and CC chemokine, were detected in the infected organs at Day 3 p.i. Our results reveal that R. heilongjiangensis may cause an infection in BALB/c mice and the pathological lesions in the infected mice are associated with host inflammatory response induced by R. heilongjiangensis.
Latrine Promotion for Trachoma: Assessment of Mortality from a Cluster-Randomized Trial in Ethiopia
Authors: Gebre Teshome , Ayele Berhan , Zerihun Mulat , House Jenafir I. , Stoller Nicole E. , Zhou Zhaoxia , Ray Kathryn J. , Gaynor Bruce D. , Porco Travis C. , Emerson Paul M. , Lietman Thomas M. , Keenan Jeremy D.
Published: September 2011

Trachoma control strategies, including latrine construction and antibiotic distribution, are directed at reducing ocular chlamydia, but may have additional benefits. In a cluster-randomized clinical trial, 24 subkebeles (administrative geographic units) in Ethiopia were offered a single mass azithromycin treatment, and half were randomized to receive an intensive latrine promotion. At a follow-up census 26 months after the baseline treatment, 320 persons had died. The mortality rate of children 1–5 years of age was 3.87 (95% confidence interval [CI] = 2.19–6.82) per 1,000 person-years in the latrine promotion arm, and 2.72 (95% CI = 1.37–5.42) per 1,000 person-years in the control arm. In a multi-level mixed effects logistic regression model controlling for age, there was no difference in mortality in persons randomized into the latrine or control arms (odds ratio = 1.18, 95% CI = 0.89–1.58). Latrine promotion provided no additional effect on mortality in the context of an azithromycin distribution program (clinicaltrials.gov, #NCT00322972).
Impact of Global Health Residency Training on Medical Knowledge of Immigrant Health
Authors: Bjorklund Ashley Balsam , Cook Bethany A. , Hendel-Paterson Brett R. , Walker Patricia F. , Stauffer William M. , Boulware David R.
Published: September 2011

Lack of global health knowledge places immigrants at risk of iatrogenic morbidity. Although global health education programs have grown in popularity, measurable impact is lacking. We previously surveyed 363 physicians in training across 15 programs in four countries in 2004 regarding basic parasite knowledge and recognition of Strongyloides risk through a theoretical case scenario. In 2005, the University of Minnesota implemented a formal global health training program (GHP). In 2009, the identical survey was repeated. Strongyloidiasis recognition increased from 11.1% (19/171) in 2004 to 39.4% (50/127) in 2009 (P < 0.001). Trainees participating in formal didactic and interactive curriculum had superior recognition (77% versus 29%; P < 0.001). In a multivariate model of GHP training activities, participation in an American Society of Tropical Medicine and Hygiene-accredited global health certificate course increased recognition (odds ratio = 9.5, 95% confidence interval = 2.5–36, P = 0.001), whereas participation in international electives alone did not (P = 0.9). A formal GHP curriculum was associated with improved knowledge regarding common parasitic infections and the risk of iatrogenic morbidity and mortality due to strongyloidiasis.
Genetic Diversity of Thottapalayam Virus, a Hantavirus Harbored by the Asian House Shrew (Suncus murinus) in Nepal
Authors: Kang Hae Ji , Kosoy Michael Y. , Shrestha Sanjaya K. , Shrestha Mrigendra P. , Pavlin Julie A. , Gibbons Robert V. , Yanagihara Richard
Published: September 2011

Despite the recent discovery of genetically divergent hantaviruses in shrews of multiple species in widely separated geographic regions, data are unavailable about the genetic diversity and phylogeography of Thottapalayam virus (TPMV), a hantavirus originally isolated from an Asian house shrew (Suncus murinus) captured in southern India more than four decades ago. To bridge this knowledge gap, the S, M, and L segments of hantavirus RNA were amplified by reverse transcription polymerase chain reaction from archival lung tissues of Asian house shrews captured in Nepal from January to September 1996. Pair-wise alignment and comparison revealed approximately 80% nucleotide and > 94% amino acid sequence similarity to prototype TPMV. Phylogenetic analyses, generated by maximum likelihood and Bayesian methods, showed geographic-specific clustering of TPMV, similar to that observed for rodent- and soricid-borne hantaviruses. These findings confirm that the Asian house shrew is the natural reservoir of TPMV and suggest a long-standing virus–host relationship.
Adipose Tissue-Derived Mesenchymal Stem Cells as a New Host Cell in Latent Leishmaniasis
Authors: Allahverdiyev Adil M. , Bagirova Melahat , Elcicek Serhat , Koc Rabia Cakir , Baydar Serap Yesilkir , Findikli Necati , Oztel Olga N.
Published: September 2011

Some protozoan infections such as Toxoplasma, Cryptosporidium, and Plasmodium can be transmitted through stem cell transplantations. To our knowledge, so far, there is no study about transmission of Leishmania parasites in stem cell transplantation and interactions between parasites and stem cells in vitro. Therefore, the aim of this study was to investigate the interaction between different species of Leishmania parasites and adipose tissue-derived mesenchymal stem cells (ADMSCs). ADMSCs have been isolated, cultured, characterized, and infected with different species of Leishmania parasites (L. donovani, L. major, L. tropica, and L. infantum). Infectivity was examined by Giemsa staining, microculture, and polymerase chain reaction methods. As a result, infectivity of ADMSCs by Leishmania parasites has been determined for the first time in this study. According to our findings, it is very important that donors are screened for Leishmania parasites before stem cell transplantations in regions where leishmaniasis is endemic.
American Tegumentary Leishmaniasis and HIV-AIDS Association in a Tertiary Care Center in the Brazilian Amazon
Authors: Guerra Jorge Augusto O. , Coelho Leíla I. R. C. , Pereira Flávio R. , Siqueira André M. , Ribeiro Rogério L. , Almeida Thiago Miranda L. , Lacerda Marcus Vinícius G. , Barbosa Maria das Graças V. , Talhari Sinésio
Published: September 2011

American tegumentary leishmaniasis (ATL) and human immunodeficiency virus (HIV) are both common infectious diseases in the Brazilian Amazon with overlapping expansion areas, which leads to the occurrence of Leishmania/HIV coinfection. Most ATL/HIV–acquired immunodeficiency syndrome (AIDS) association cases have been reported from areas where Leishmania (Viannia) braziliensis is the main pathogen; this finding is in contrast with the Amazon region, where L. (V.) guyanensis is the most implicated agent, implying distinct clinical and therapeutic aspects. We describe 15 cases of ATL/HIV coinfection treated in a tertiary care center in the Brazilian Amazon between 1999 and 2008. Thirteen patients presented with diverse clinical manifestations of cutaneous leishmaniasis, and four of them had disseminated forms; two patients presented with mucosal leishmaniasis (ML). Seven patients required more than one course of treatment. The particularities of ATL/HIV-AIDS association in L. (V.) guyanensis-endemic areas require efforts for an increased understanding of its burden and subsequent improvements in case management.
Paracoccidioidomycosis Epidemiological Features of a 1,000-Cases Series from a Hyperendemic Area on the Southeast of Brazil
Authors: Bellissimo-Rodrigues Fernando , Machado Alcyone Artioli , Martinez Roberto
Published: September 2011

Paracoccidioidomycosis has been known for over 100 years, and until now, there were only few estimates of the disease's incidence. We aim to analyze 1,000 cases treated between 1960 and 1999 at Ribeirão Preto city, São Paulo, Brazil, where the disease's incidence range detected was 1.6 to 3.7 cases per 100,000 habitants per year (mean = 2.7 cases/year). We observed a male to female ratio of 6:1 and an age distribution from 3 to 85 years. The acute/subacute form of the disease accounted for 25.4% of cases. Most of the patients (93.5%) had lived or worked in rural areas before the disease development. Smoking and alcoholism were reported by 64.7% and 37.2% of patients, respectively. Comorbidities identified included tuberculosis (8.3%), Chagas' disease (8.6%), and human immunodeficiency virus/acquired immunodeficiency syndrome (4.2%). The present study revealed an area in Brazil where paracoccidioidomycosis is hyperendemic (has the highest reported incidence of this disease); this endemic area is probably caused by geological and climatic conditions as well as intensive agriculture.
Evaluation of Pichia pastoris–Expressed Recombinant Rhoptry Protein 2 of Toxoplasma gondii for Its Application in Diagnosis of Toxoplasmosis
Authors: Chang Phooi Yee , Fong Mun Yik , Nissapatorn Veeranoot , Lau Yee Ling
Published: September 2011

Rhoptry protein 2 (ROP2) of Toxoplasma gondii is a rhoptry-secreted protein that plays a critical role in parasitophorous vacuole membrane formation during invasion. In previous studies, ROP2 has been shown to be efficient in triggering humoral and cell-mediated responses. High immunogenicity of ROP2 makes it a potential candidate for diagnosis and vaccination against toxoplasmosis. In this study, the ROP2 gene was cloned into pPICZα A expression vector and extracellularly expressed in the yeast Pichia pastoris, which has numerous advantages over other expression systems for eukaryotic proteins expression. The effectiveness of the secreted recombinant ROP2 as a diagnosis agent was assessed by Western Blot with 200 human serum samples. Recombinant ROP2 reacted with toxoplasmosis-positive human serum samples and yielded an overall sensitivity of 90% and specificity of 95%. However, recombinant ROP2 is a better marker for detection of IgG (91.7%) rather than IgM (80%).
Interpreting methane variations in the past two decades using measurements of CH4 mixing ratio and isotopic composition
Authors: Monteil G. , Houweling S. , Dlugockenky E. J. , Maenhout G. , Vaughn B. H. , White J. W. C. , Rockmann T.
Published: September 2011

Abstract. The availability δ13C-CH4 measurements from atmospheric samples has significantly improved in recent years, which allows the construction of time series spanning up to about 2 decades. We have used these measurements to investigate the cause of the methane growth rate decline since 1980, with a special focus on the period 1998–2006 when the methane growth came to a halt. The constraints provided by the CH4 and δ13C-CH4 measurements are used to construct hypothetical source and sink scenarios, which are translated into corresponding atmospheric concentrations using the atmospheric transport model TM3 for evaluation against the measurements. The base scenario, composed of anthropogenic emissions according to EDGAR 4.0, constant emissions from natural sources, and a constant atmospheric lifetime, overestimates the observed global growth rates of CH4 and δ13C-CH4 by, respectively, 10 ppb yr−1 and 0.02‰ yr−1 after the year 2000. It proves difficult to repair this inconsistency by modifying trends in emissions only, notably because a temporary reduction of isotopically light sources, such as natural wetlands, leads to a further increase of δ13C-CH4. Furthermore, our results are difficult to reconcile with the estimated increase of 5 Tg CH4 yr−1 in emissions from fossil fuel use in the period 2000–2005. On the other hand, we find that a moderate (less than 5% per decade) increase in the global OH concentration can bring the model in agreement with the measurements for plausible emission scenarios. This study demonstrates the value of global monitoring of methane isotopes, and calls for further investigation into the role OH and anthropogenic emissions to further improve our understanding of methane variations in recent years.
Diel variations in the carbon isotope composition of respired CO2 and associated carbon sources: a review of dynamics and mechanisms
Authors: Werner C. , Gessler A.
Published: September 2011

Abstract. Recent advances have improved our methodological approaches and theoretical understanding of post-photosynthetic carbon isotope fractionation processes. Nevertheless we still lack a clear picture of the origin of short-term variability in δ13C of respired CO2 (δ13Cres) and organic carbon fractions on a diel basis. Closing this knowledge gap is essential for the application of stable isotope approaches for partitioning ecosystem respiration, tracing carbon flow through plants and ecosystems and disentangling key physiological processes in carbon metabolism of plants. In this review we examine the short-term dynamics in δ13Cres and putative substrate pools at the plant, soil and ecosystem scales and discuss mechanisms, which might drive diel δ13Cres dynamics at each scale. Maximum reported variation in diel δ13Cres is 4.0, 5.4 and 14.8 ‰ in trunks, roots and leaves of different species and 12.5 and 8.1 ‰ at the soil and ecosystem scale in different biomes. Temporal variation in post-photosynthetic isotope fractionation related to changes in carbon allocation to different metabolic pathways is the most plausible mechanistic explanation for observed diel dynamics in δ13Cres. In addition, mixing of component fluxes with different temporal dynamics and isotopic compositions add to the δ13Cres variation on the soil and ecosystem level. Understanding short-term variations in δ13Cres is particularly important for ecosystem studies, since δ13Cres contains information on the fate of respiratory substrates, and may, therefore, provide a non-intrusive way to identify changes in carbon allocation patterns.
Spatial and temporal variability of rainfall erosivity factor for Switzerland
Authors: Meusburger K. , Steel A. , Panagos P. , Montanarella L. , Alewell C.
Published: September 2011

Abstract. Rainfall erosivity, considering rainfall amount and intensity, is an important parameter for soil erosion risk assessment under future land use and climate change. Despite its importance, rainfall erosivity is usually implemented in models with a low spatial and temporal resolution. The purpose of this study is to assess the temporal- and spatial distribution of rainfall erosivity (R-factor) in Switzerland. Time series of 22 yr for rainfall (10 min resolution) and temperature (1 h resolution) data were analysed for 71 automatic gauging stations distributed throughout Switzerland. Multiple regression was used to interpolate the erosivity values of single stations and to generate a map for Switzerland. Latitude, longitude, average annual precipitation, biogeographic units (Jura, Midland, etc.), aspect and elevation were used as covariates, of which average annual precipitation, elevation and the biographic unit (Western Alps) were significant predictors. The mean value of long-term rainfall erosivity is 1323 MJ mm ha−1 h−1 yr−1 with a range of lowest values of 124 MJ mm ha−1 h−1 yr−1 at an elevated station in Grisons to highest values of 5611 MJ mm ha−1 h−1 yr−1 in Ticino. All stations have highest erosivity values from July to August and lowest values in the winter month. Swiss-wide the month May to October show significantly increasing trends of erosivity (p<0.005). Only in February a significantly decreasing trend of rainfall erosivity is found (p<0.01). The increasing trends of erosivity in May, September and October when vegetation cover is susceptible are likely to enhance soil erosion risk for certain agricultural crops and alpine grasslands in Switzerland.
Silicon pool dynamics and biogenic silica export in the Southern Ocean inferred from Si-isotopes
Authors: Fripiat F. , Cavagna A.-J. , Dehairs F. , Speich S. , André L. , Cardinal D.
Published: September 2011

Abstract. Silicon isotopic signatures (δ30Si) of water column silicic acid (Si(OH)4) were measured in the Southern Ocean, along a meridional transect from South Africa (Subtropical Zone) down to 57° S (northern Weddell Gyre). This provides the first reported data of a summer transect across the whole Antarctic Circumpolar Current (ACC). δ30Si variations are large in the upper 1000 m, reflecting the effect of the silica pump superimposed upon meridional water transfer across the ACC: the transport of Antarctic surface waters northward by a net Ekman drift and their convergence and mixing with warmer upper-ocean Si-depleted waters to the north. Using Si isotopic signatures, we determine different mixing interfaces: the Antarctic Surface Water (AASW), the Antarctic Intermediate Water (AAIW), and thermoclines in the low latitude areas. The residual silicic acid concentrations of end-members control the δ30Si alteration of the mixing products and with the exception of AASW, all mixing interfaces have a highly Si-depleted mixed layer end-member. These processes deplete the silicic acid AASW concentration northward, across the different interfaces, without significantly changing the AASW δ30Si composition. By comparing our new results with a previous study in the Australian sector we show that during the circumpolar transport of the ACC eastward, the δ30Si composition of the silicic acid pools is getting slightly, but significantly lighter from the Atlantic to the Australian sectors. This results either from the dissolution of biogenic silica in the deeper layers and/or from an isopycnal mixing with the deep water masses in the different oceanic basins: North Atlantic Deep Water in the Atlantic, and Indian Ocean deep water in the Indo-Australian sector. This isotopic trend is further transmitted to the subsurface waters, representing mixing interfaces between the surface and deeper layers. Through the use of δ30Si constraints, net biogenic silica production (representative of annual export), at the Greenwich Meridian is estimated to be 5.2 ± 1.3 and 1.1 ± 0.3 mol Si m−2 for the Antarctic Zone and Polar Front Zone, respectively. This is in good agreement with previous estimations. Furthermore, summertime Si-supply into the mixed layer of both zones, via vertical mixing, is estimated to be 1.6 ± 0.4 and 0.1 ± 0.5 mol Si m−2, respectively.
A study of the hydrographic conditions in the Adriatic Sea from numerical modelling and direct observations (2000–2008)
Authors: Oddo P. , Guarnieri A.
Published: September 2011

Abstract. The inter-annual variability of Adriatic Sea hydrographic characteristics is investigated by means of numerical simulation and direct observation. The period under investigation runs from the beginning of 2000 to the end of 2008. The model used to carry out the simulation is derived from the primitive equation component of the Adriatic Forecasting System (AFS). The model is based on the Princeton Ocean Model (POM) adapted in order to reproduce the features of the Adriatic. Both numerical findings and observations agree in depicting a strong inter-annual variability in the entire Adriatic Sea and its sub-basins. Nevertheless, two model deficiencies are identified: an excessive vertical/horizontal mixing and an inaccurate representation of the thermohaline properties of the entering Mediterranean Waters. The dense water formation process has been found to be intermittent. In addition to inter-annual variability, a long-scale signal has been observed in the salinity content of the basin as a consequence of a prolonged period of reduced Po river runoff and high evaporation rates. As a result, the temperature and salinity of the northern Adriatic dense water vary considerably between the beginning and the end of the period investigated.
Triple Therapy for Corneal Neovascularization: A Case Report
Authors: Veritti Daniele , Vergallo Stefano , Lanzetta Paolo
Published: September 2011

Purpose

To investigate the effect of the combination of photodynamic therapy with verteporfin and subconjunctival bevacizumab and triamcinolone acetonide on corneal neovascularization secondary to corneal graft failure.

Methods

A patient with extensive deep and superficial corneal neovascularization underwent same day triple therapy with subconjunctival bevacizumab (1.25 mg), subconjunctival triamcinolone acetonide (40 mg), and photodynamic therapy with verteporfin (fluence 50 J/cm2, irradiance 300 mW/cm2).

Results

A complete angiographic new vessel regression was obtained and was discernible starting 7 days after combination therapy. Three months after treatment, an initial new-vessel sprout was noted. Triple therapy was then repeated. No angiographic evidence of corneal neovascularization was detectable for the entire 6-month follow-up duration.

Conclusions

Triple therapy may offer a promising tool in the treatment of corneal neovascularization.
Organo‐ and Hydrogelators Based on Luminescent Monocationic Terpyridyl Platinum(II) Complexes with Biphenylacetylide Ligands
Authors: Wang Jia , Chen Yong , Law Yuen‐Chi , Li Meiyi , Zhu Ming‐Xin , Lu Wei , Chui Stephen Sin‐Yin , Zhu Nianyong , Che Chi‐Ming
Published: September 2011

A series of phosphorescent terpyridyl platinum(II) complexes with ancillary biphenylacetylide ligands, namely, [(R3tpy)PtC≡C(biphenyl)]X (R=tBu, H, or Et2N; tpy=2,2′;6′,2′′‐terpyridyl; X is an anion) were synthesized and structurally characterized by various spectroscopic techniques and X‐ray diffraction methods. Despite a lack of long alkyl chain(s) or hydrogen‐bonding motif(s), complexes [(tpy)PtC≡C(biphenyl)]Cl and [(tBu3tpy)PtC≡C(biphenyl)]X (X=Cl, ClO4, PF6, or BF4) were found to gelate water and organic solvents, respectively. The self‐aggregation of these complexes in solutions and the resulting gels were investigated with variable‐temperature (VT) 1H NMR spectroscopy, polarized optical microscopy, and absorption/emission spectroscopy. SEM micrographs on dry gels revealed entangled nanofibers with diameters of 20–40 nm and lengths of tens of micrometers. Powder X‐ray diffraction (PXRD) study revealed various degrees of crystallinity of these fibrillar nanostructures. The substituents on both the terpyridyl and acetylide ligands and counterion of these complexes play a profound but concerted role in tuning the intermolecular metal⋅⋅⋅metal and/or π–π interactions, and hence the gelation properties.
Structure and pH‐induced alterations of recombinant and natural spider silk proteins in solution
Authors: Leclerc Jérémie , Lefèvre Thierry , Pottier Fabien , Morency Louis‐Philippe , Lapointe‐Verreault Camille , Gagné Stéphane M. , Auger Michèle
Published: September 2011

The spinning process of spiders can modulate the mechanical properties of their silk fibers. It is therefore of primary importance to understand what are the key elements of the spider spinning process to develop efficient industrial spinning processes. We have exhaustively investigated the native conformation of major ampullate silk (MaS) proteins by comparing the content of the major ampullate gland of Nephila clavipes, solubilized MaS (SolMaS) fibers and the recombinant proteins rMaSpI and rMaSpII using 1H solution NMR spectroscopy. The results indicate that the protein secondary structure is basically identical for the recombinant protein rMaSpI, SolMaS proteins, and the proteins in the dope, and corresponds to a disordered protein rich in 31‐helices. The data also show that glycine proton chemical shifts of rMaSpI and SolMaS are affected by pH, but that this change is not due to a modification of the secondary structure. Using a combination of NMR and dynamic light scattering, we have found that the spectral alteration of glycine is concomitant to a modification of the hydrodynamical diameter of recombinant and solubilized MaS. This led us to suggest new potential roles for the pH acidification in the spinning process of MaS proteins. © 2011 Wiley Periodicals, Inc. Biopolymers 97: 337–346, 2012.
Fluorinert, an oxygen carrier, improves cell culture performance in deep square 96‐well plates by facilitating oxygen transfer
Authors: Meyer Aaron , Condon Russell G. G. , Keil Gregory , Jhaveri Nikita , Liu Zhong , Tsao Yung‐Shyeng
Published: September 2011

In bioprocess development, the 96‐well plate format has been widely used for high‐throughput screening of production cell line or culture conditions. However, suspension cell cultures in conventional 96‐well plates often fail to reach high cell density under normal agitation presumably due to constraints in oxygen transfer. Although more vigorous agitation can improve gas transfer in 96‐well plate format, it often requires specialized instruments. In this report, we employed Fluorinert, a biologically inert perfluorocarbon, to improve oxygen transfer in 96‐well plate and to enable the growth of a Chinese Hamster Ovary cell line expressing a recombinant monoclonal antibody. When different amounts of Fluorinert were added to the cell culture medium, a dose‐dependent improvement in cell growth was observed in both conventional and deep square 96‐well plates. When sufficient Fluorinert was present in the culture, the cell growth rate, the peak cell density, and recombinant protein production levels achieved in deep square 96‐wells were comparable to cultures in ventilated shake flasks. Although Fluorinert is known to dissolve gases such as oxygen and CO2, it does not dissolve nor extract medium components, such as glucose, lactate, or amino acids. We conclude that mixing Fluorinert with culture media is a suitable model for miniaturization of cell line development and process optimization. Proper cell growth and cellular productivity can be obtained with a standard shaker without the need for any additional aeration or vigorous agitation. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2012
In Search of Oligo(2‐thienyl)‐Substituted Pyridine Derivatives: A Modular Approach to Di‐, Tri‐ and Tetra(2‐thienyl)pyridines
Authors: Bera Mrinal K. , Hommes Paul , Reissig Hans‐Ulrich
Published: September 2011

Herein, we describe our attempts to systematically prepare a series of oligo(2‐thienyl)‐substituted pyridine derivatives. The crucial starting material, a β‐alkoxy‐β‐ketoenamide, is easily available on a large scale by the reaction of lithiated methoxyallene with thiophene‐2‐carbonitrile and thiophene‐2‐carboxylic acid. This three‐component reaction is followed by intramolecular cyclization to yield the suitably functionalized 2,6‐di(2‐thienyl)‐substituted pyridine derivates. The two oxygen atoms allow the programmed activation of positions C‐3, C‐4, or C‐5 of the pyridine ring to perform palladium‐catalyzed coupling reactions with thiophene‐2‐boronic acid or 2‐(tributylstannyl)thiophene, and alternatively, reductive removal of groups. With this concept, we were able to prepare five pyridine derivatives with 2‐thienyl substituents in the 2,6‐, 2,3,6‐, 2,4,6‐, 2,3,4,6‐, and 2,3,5,6‐positions. 2,3,4,5,6‐Penta(2‐thienyl)pyridine was not available with our methods. The UV/Vis and fluorescence spectra of all pyridines were recorded and showed a dependence on the substitution pattern and protonation state. For the protonated 2,3,5,6‐tetra(2‐thienyl)‐substituted pyridine, a Stokes shift of about 180 nm with an emission at 515 nm was observed.
Phase 1 trial of everolimus plus sunitinib in patients with metastatic renal cell carcinoma
Authors: Molina Ana M. , Feldman Darren R. , Voss Martin H. , Ginsberg Michelle S. , Baum Michael S. , Brocks Dion R. , Fischer Patricia M. , Trinos Michael J. , Patil Sujata , Motzer Robert J.
Published: September 2011

BACKGROUND:

Simultaneous inhibition of the vascular epithelial growth factor (VEGF) and the mammalian target of rapamycin (mTOR) pathway may improve treatment response in advanced renal cell carcinoma (RCC). Everolimus, an oral mTOR inhibitor, and sunitinib, an oral tyrosine kinase inhibitor targeting VEGF, are standard agents in the management of metastatic RCC.

METHODS:

Sequential cohorts of 3 to 6 patients with advanced RCC received dose‐escalated combinations of sunitinib (37.5 or 50 mg daily, 4 weeks on/2 weeks off) with everolimus (2.5‐5 mg daily or 20‐30 mg weekly). Dose‐limiting toxicities (DLTs) were assessed in the first 6‐week cycle to determine maximum tolerated dose (MTD). Pharmacokinetic profiles were obtained.

RESULTS:

Twenty patients (13 clear cell and 7 nonclear cell RCC) were enrolled in 5 cohorts. Daily everolimus was not tolerated when combined with sunitinib; the first 2 patients on the second cohort suffered DLTs. With weekly everolimus, the MTD was 30 mg everolimus on days 7, 14, 21, and 28, plus 37.5 mg sunitinib on days 1 to 28 of a 42‐day cycle; however, chronic treatment was associated with grade 3 and 4 toxicities. A schedule of 20 mg everolimus weekly/37.5 mg sunitinib was tolerated as chronic therapy. Five patients (25%) had confirmed partial responses, and 3 had nonclear cell RCC. No unexpected accumulation of everolimus, sunitinib, or N‐desethyl sunitinib was observed.

CONCLUSIONS:

The combination of everolimus and sunitinib is associated with significant acute and chronic toxicities and is only tolerated at attenuated doses. Responses were observed in nonclear cell and clear cell RCC. Cancer 2012. © 2011 American Cancer Society.
Phase II trial of continuous once‐daily dosing of sunitinib as first‐line treatment in patients with metastatic renal cell carcinoma
Authors: Barrios Carlos H. , Hernandez‐Barajas David , Brown Michael P. , Lee Se‐Hoon , Fein Luis , Liu Jin‐Hwang , Hariharan Subramanian , Martell Bridget A. , Yuan Jinyu , Bello Akintunde , Wang Zhixiao , Mundayat Rajiv , Rha Sun‐Young
Published: September 2011

BACKGROUND:

Sunitinib at 50 mg/day on the 4‐weeks‐on‐2‐weeks‐off schedule is the current approved regimen for advanced/metastatic renal cell carcinoma (mRCC). Escudier et al reported that continuous, once‐daily dosing with sunitinib 37.5 mg had a manageable safety profile and significant antitumor activity as second‐line mRCC therapy. In this prospective, multicenter, phase II study, we evaluated the activity of continuous once‐daily dosing with sunitinib 37.5 mg as first‐line mRCC treatment.

METHODS:

One hundred nineteen treatment‐naive patients with measurable mRCC received sunitinib. The primary endpoint was objective response; secondary endpoints included progression‐free survival (PFS), safety, pharmacokinetic measurements, exploration of response biomarkers, and patient reported outcomes (PRO).

RESULTS:

Objective response rate (ORR) was 35.3%; median response duration was 10.4 months; 36% of patients had stable disease ≥12 weeks. Median PFS at 1 year was 9 months, and 1‐year survival probability was 67.8%. The most common any‐grade treatment‐related adverse events (AEs) were diarrhea (50%) and hand‐foot syndrome (43%); the most common grade 3‐4 treatment‐related AEs were hand‐foot syndrome (13%), neutropenia (11%), and diarrhea (9%). Steady‐state pharmacokinetics were reached within 3 weeks, with no disproportionate accumulation of sunitinib or its active metabolite throughout the study. No significant correlations between trough drug, active metabolite, or soluble protein levels and clinical response were observed. PRO was largely maintained, although fatigue appeared to worsen after treatment started, with improvement over time.

CONCLUSIONS:

Continuous once‐daily dosing with sunitinib 37.5 mg was active with a manageable safety profile as first‐line mRCC therapy, making this a feasible alternative dosing regimen. Cancer 2012. © 2011 American Cancer Society.
Improvement of racial disparities with respect to the utilization of minimally invasive radical prostatectomy in the United States
Authors: Trinh Quoc‐Dien , Schmitges Jan , Sun Maxine , Sukumar Shyam , Sammon Jesse , Shariat Shahrokh F. , Jeldres Claudio , Bianchi Marco , Tian Zhe , Perrotte Paul , Rogers Craig G. , Graefen Markus , Peabody James O. , Menon Mani , Karakiewicz Pierre I.
Published: September 2011

BACKGROUND:

Race represents an established barrier to health care access in the United States and elsewhere. We examined whether race affects the utilization rate of minimally invasive radical prostatectomy (MIRP) in a population‐based sample of individuals from the United States.

METHODS:

Within the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS), we focused on patients in whom MIRP and open radical prostatectomy (ORP) were performed between 2001 and 2007. We assessed the proportions and temporal trends in race distributions between MIRP and ORP. Multivariable logistic regression analyses further adjusted for age, year of surgery, baseline Charlson Comorbidity Index, annual hospital caseload tertiles, hospital region, insurance status, and median zip code income.

RESULTS:

Of 65,148 radical prostatectomies, 3581 (5.5%) were MIRPs. African Americans accounted for 11.4% of patients versus 78.8% for Caucasians versus 9.9% for others. Between 2001 and 2007, the annual proportions of Caucasian patients treated with MIRP were 2.2%, 0.9%, 2.6%, 7.2%, 4.7%, 9.3%, and 11.6%, respectively (chi‐square trend p<0.001). For the same years in African American patients, the proportions were 0.8, 0.3, 1.4, 4.4, 3.5, 9.0 and 8.4% (chi‐square trend P < .001). In multivariable analyses relative to Caucasian patients, African American patients were 14% less likely to undergo MIRP (P = .01). After period stratification between years 2001‐2005 versus 2006‐2007, African Americans were 22% less likely to undergo a MIRP in the early period (P = .007) versus 11% less likely to have a MIRP in the contemporary period (P = .1).

CONCLUSIONS:

The racial discrepancies in MIRP utilization rates are gradually improving. Cancer 2012;. © 2011 American Cancer Society.
Rare‐Earth Cobalt Gallides RE4Co3Ga16 (RE = Gd–Er, Y): Self‐Interstitial Derivatives of RE2CoGa8A Tale of Two Polymorphs – Growth and Characterization of α‐LnNiGa4 (Ln = Y, Gd–Yb) and β‐LnNi1–xGa4 (Ln = Tb–Er)Solution Chemistry Synthesis of Intermetallic Gold–Lithium NanoparticlesMetal Anions in Metal‐Rich Compounds and Polar IntermetallicsRevisiting the Zintl–Klemm Concept: A2AuBi (A = Li or Na)Crystal Structure and Properties of Yb5Ni4Ge10Magnetism in Giant Unit Cells – Crystal Structure and Magnetic Properties of R117Co52+δSn112+γ (R = Sm, Tb, Dy) (Eur. J. Inorg. Chem. 26/2011)
Authors: Mar Arthur , Chan Julia Y. , Schaak Raymond E. , Whangbo Myung‐Hwan , Miller Gordon J. , Kanatzidis Mercouri G. , Shatruk Michael
Published: September 2011

The front cover picture shows the clock tower, the “Campanile”, of Iowa State University where John Corbett did the ground‐breaking research in polar intermetallics that forms the basis of his Viewpoint in this cluster issue. Superimposed on this background are structures and data to visualize the broad scope of topic. The complexity of structure is displayed by the ternary rare‐earth cobalt gallides that contain interstitial atoms (top left, A. Mar et al.), a calcium‐poor intermetallic phase of the Ca/Ni/Ge system (top right from the lab of T. Fässler), and a single crystal of a polymorph of thallium nickel gallide (bottom right, J. Chan et al.). The potentially general synthesis of colloidal nanoparticles – Au3Li from the lab of R. E. Schaak – is outlined mid left. The groups of M. H. Whangbo and G. Miller devote their contributions to the theoretical aspects of bonding (depicted top centre, the plots showing Au–Au bonding and antibonding interactions in Dy2Au2In and mid right, the effects of ionic interactions on the structural properties of isoelectronic intermetallic compounds, respectively). Representative of the range of properties discussed is the magnetic susceptibility of Yb5Ni4Ge10 (bottom left, M. G. Kanatzidis et al.). We thank the authors for the use of the graphics from their papers on the cover.
A Selective Voltammetric Method for Detecting Dopamine at Quercetin Modified Electrode Incorporating Graphene
Authors: Wang Zonghua , Xia Jianfei , Zhu Lingyan , Chen Xiaoyin , Zhang Feifei , Yao Shuyan , Li Yanhui , Xia Yanzhi
Published: September 2011

The development of a quercetin‐graphene composite‐modified glassy carbon electrode (Qu/GH/GCE) for the selective and sensitive detection of dopamine (DA) is described in this paper. To fabricate the Qu/GH/GCE, graphene (GH) was first coated onto the surface of a glassy carbon electrode (GCE) and then quercetin (Qu) was electrodeposited on the GH matrix. Transmission electron microscopy (TEM) was used to characterize the morphology of the obtained GH and Qu/GH, and the electrochemical properties of the modified electrode were studied using electrochemical techniques. The as‐prepared Qu/GH/GCE occupied a synthetic property between GH and Qu. The common overlapped electrochemical oxidation peaks of DA and AA were completely separated and a remarkable increasing electron‐oxidation current of DA occurred on the Qu/GH/GCE, which enabled the sensitive and selective electrochemical detection of DA in the presence of ascorbic acid (AA) with peak difference of ca. 452 mV between DA and AA. The peak current obtained at 0.174 V (vs. saturated calomel electrode, SCE) from differential pulse voltammetry (DPV) is linearly dependent on the DA concentration in the range from 3.0×10−8 to 4.0×10−4 mol/L with a detection limit of 1.0×10−8 mol/L. Furthermore, the Qu/GH/GCE exhibits good reproducibility and stability, and has been used for the determination of DA in samples of rat’s striatum tissue with satisfactory results.
Hedgehog signaling and osteoblast gene expression are regulated by purmorphamine in human mesenchymal stem cells
Authors: Oliveira F.S. , Bellesini L.S. , Defino H.L.A. , da Silva Herrero C.F. , Beloti M.M. , Rosa A.L.
Published: September 2011

Several biological events are controlled by Hedgehog (Hh) signaling, including osteoblast phenotype development. This study aimed at evaluating the gene expression profile of human mesenchymal stem cells (hMSCs) treated with the Hh agonist, purmorphamine, focusing on Hh signaling and osteoblast differentiation. hMSCs from bone marrow were cultured in non‐osteogenic medium with or without purmorphamine (2 µM) for periods of up to 14 days. Purmorphamine up‐regulated gene expression of the mediators of Hh pathway, SMO, PTCH1, GLI1, and GLI2. The activation of Hh pathway by purmorphamine increased the expression of several genes (e.g., RUNX2 and BMPs) related to osteogenesis. Our results indicated that purmorphamine triggers Hh signaling pathway in hMSCs, inducing an increase in the expression of a set of genes involved in the osteoblast differentiation program. Thus, we conclude that Hh is a crucial pathway in the commitment of undifferentiated cells to the osteoblast lineage. J. Cell. Biochem. 113: 204–208, 2012. © 2011 Wiley Periodicals, Inc.
CD133 and CD44 Cell surface markers do not identify cancer stem cells in primary human gastric tumors
Authors: Rocco Alba , Liguori Eleonora , Pirozzi Giuseppe , Tirino Virginia , Compare Debora , Franco Renato , Tatangelo Fabiana , Palaia Raffaele , D'Armiento Francesco Paolo , Pollastrone Giorgia , Affuso Andrea , Bottazzi Enrico Coppola , Masone Stefania , Persico Giovanni , Nardone Gerardo
Published: September 2011

Emerging evidence suggests that tumors contain and are driven by a cellular component that displays stem cell properties, the so‐called cancer stem cells (CSCs). CSCs have been identified in several solid human cancers; however, there are no data about CSCs in primary human gastric cancer (GC). By using CD133 and CD44 cell surface markers we investigated whether primary human GCs contain a cell subset expressing stem‐like properties and whether this subpopulation has tumor‐initiating properties in xenograft transplantation experiments. We examined tissues from 44 patients who underwent gastrectomy for primary GC. The tumorigenicity of the cells separated by flow cytometry using CD133 and CD44 surface markers was tested by subcutaneous or intraperitoneum injection in NOD/SCID and nude mice. GCs included in the study were intestinal in 34 cases and diffuse in 10 cases. All samples contained surface marker‐positive cells: CD133+ mean percentage 10.6% and CD133+/CD44+ mean percentage 27.7%, irrespective of cancer phenotype or grade of differentiation. Purified CD133+ and CD133+/CD44+ cells, obtained in sufficient number only in 12 intestinal type GC cases, failed to reproduce cancer in two mice models. However, the unseparated cells produced glandular‐like structures in 70% of the mice inoculated. In conclusion, although CD133+ and CD133+/CD44+ were detectable in human primary GCs, they neither expressed stem‐like properties nor exhibited tumor‐initiating properties in xenograft transplantation experiments. J. Cell. Physiol. 227: 2686–2693, 2012. © 2011 Wiley Periodicals, Inc.