bluuebunny/crossref_metadata_2025_split huggingface dataset:
CP-690,550, a therapeutic agent, inhibits cytokine-mediated Jak3 activation and proliferation of T cells from patients with ATL and HAM/TSP
Authors: Ju Wei , Zhang Meili , Jiang Jian-kang , Thomas Craig J. , Oh Unsong , Bryant Bonita R. , Chen Jing , Sato Noriko , Tagaya Yutaka , Morris John C. , Janik John E. , Jacobson Steven , Waldmann Thomas A. 
Published: November 2010

Abstract
The retrovirus, human T-cell–lymphotrophic virus-1 (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL) and the neurological disorder HTLV-I–associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-I–encoded protein tax constitutively activates interleukin-2 (IL-2), IL-9, and IL-15 autocrine/paracrine systems that in turn activate the Jak3 (Janus kinase 3)/STAT5 (signal transducers and activators of transcription 5) pathway, suggesting a therapeutic strategy that involves targeting Jak3. We evaluated the action of the Jak3 inhibitor CP-690,550 on cytokine dependent ex vivo proliferation that is characteristic of peripheral blood mononuclear cells (PBMCs) from select patients with smoldering or chronic subtypes of ATL, or from those with HAM/TSP whose PBMCs are associated with autocrine/paracrine pathways that involve the production of IL-2, IL-9, IL-15, and their receptors. CP-690,550 at 50nM inhibited the 6-day ex vivo spontaneous proliferation of PBMCs from ATL and HAM/TSP patients by 67.1% and 86.4%, respectively. Furthermore, CP-690,550 inhibited STAT5 phosphorylation in isolated ATL T cells ex vivo. Finally, in an in vivo test of biological activity, CP-690,550 treatment of mice with a CD8 T-cell IL-15–transgenic leukemia that manifests an autocrine IL-15/IL-15Rα pathway prolonged the survival duration of these tumor-bearing mice. These studies support further evaluation of the Jak3 inhibitor CP-690,550 in the treatment of select patients with HTLV-I–associated ATL and HAM/TSP.
Size-assortative mating and sexual size dimorphism are predictable from simple mechanics of mate-grasping behavior
Authors: Han Chang S , Jablonski Piotr G , Kim Beobkyun , Park Frank C 
Published: November 2010

Abstract

Background
A major challenge in evolutionary biology is to understand the typically complex interactions between diverse counter-balancing factors of Darwinian selection for size assortative mating and sexual size dimorphism. It appears that rarely a simple mechanism could provide a major explanation of these phenomena. Mechanics of behaviors can predict animal morphology, such like adaptations to locomotion in animals from various of taxa, but its potential to predict size-assortative mating and its evolutionary consequences has been less explored. Mate-grasping by males, using specialized adaptive morphologies of their forelegs, midlegs or even antennae wrapped around female body at specific locations, is a general mating strategy of many animals, but the contribution of the mechanics of this wide-spread behavior to the evolution of mating behavior and sexual size dimorphism has been largely ignored.

Results
Here, we explore the consequences of a simple, and previously ignored, fact that in a grasping posture the position of the male's grasping appendages relative to the female's body is often a function of body size difference between the sexes. Using an approach taken from robot mechanics we model coercive grasping of females by water strider Gerris gracilicornis males during mating initiation struggles. We determine that the male optimal size (relative to the female size), which gives the males the highest grasping force, properly predicts the experimentally measured highest mating success. Through field sampling and simulation modeling of a natural population we determine that the simple mechanical model, which ignores most of the other hypothetical counter-balancing selection pressures on body size, is sufficient to account for size-assortative mating pattern as well as species-specific sexual dimorphism in body size of G. gracilicornis.

Conclusion
The results indicate how a simple and previously overlooked physical mechanism common in many taxa is sufficient to account for, or importantly contribute to, size-assortative mating and its consequences for the evolution of sexual size dimorphism.
Evolution of the Kdo2-lipid A biosynthesis in bacteria
Authors: Opiyo Stephen O , Pardy Rosevelt L , Moriyama Hideaki , Moriyama Etsuko N 
Published: November 2010

Abstract

Background
Lipid A is the highly immunoreactive endotoxic center of lipopolysaccharide (LPS). It anchors the LPS into the outer membrane of most Gram-negative bacteria. Lipid A can be recognized by animal cells, triggers defense-related responses, and causes Gram-negative sepsis. The biosynthesis of Kdo2-lipid A, the LPS substructure, involves with nine enzymatic steps.

Results
In order to elucidate the evolutionary pathway of Kdo2-lipid A biosynthesis, we examined the distribution of genes encoding the nine enzymes across bacteria. We found that not all Gram-negative bacteria have all nine enzymes. Some Gram-negative bacteria have no genes encoding these enzymes and others have genes only for the first four enzymes (LpxA, LpxC, LpxD, and LpxB). Among the nine enzymes, five appeared to have arisen from three independent gene duplication events. Two of such events happened within the Proteobacteria lineage, followed by functional specialization of the duplicated genes and pathway optimization in these bacteria.

Conclusions
The nine-enzyme pathway, which was established based on the studies mainly in Escherichia coli K12, appears to be the most derived and optimized form. It is found only in E. coli and related Proteobacteria. Simpler and probably less efficient pathways are found in other bacterial groups, with Kdo2-lipid A variants as the likely end products. The Kdo2-lipid A biosynthetic pathway exemplifies extremely plastic evolution of bacterial genomes, especially those of Proteobacteria, and how these mainly pathogenic bacteria have adapted to their environment.
Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI) stress
Authors: Dubey Sonali , Misra Prashant , Dwivedi Sanjay , Chatterjee Sandipan , Bag Sumit K , Mantri Shrikant , Asif Mehar H , Rai Arti , Kumar Smita , Shri Manju , Tripathi Preeti , Tripathi Rudra D , Trivedi Prabodh K , Chakrabarty Debasis , Tuli Rakesh 
Published: November 2010

Abstract

Background
Widespread use of chromium (Cr) contaminated fields due to careless and inappropriate management practices of effluent discharge, mostly from industries related to metallurgy, electroplating, production of paints and pigments, tanning, and wood preservation elevates its concentration in surface soil and eventually into rice plants and grains. In spite of many previous studies having been conducted on the effects of chromium stress, the precise molecular mechanisms related to both the effects of chromium phytotoxicity, the defense reactions of plants against chromium exposure as well as translocation and accumulation in rice remain poorly understood.

Results
Detailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice. To check whether the Cr-specific motifs were indeed significantly over represented in the promoter regions of Cr-responsive genes, occurrence of these motifs in whole genome sequence was carried out. In the background of whole genome, the lift value for these 14 and 13 motifs was significantly high in the test dataset. Though no functional role has been assigned to any of the motifs, but all of these are present as promoter motifs in the Database of orthologus promoters.

Conclusion
These findings clearly suggest that a complex network of regulatory pathways modulates Cr-response of rice. The integrated matrix of both transcriptome and metabolome data after suitable normalization and initial calculations provided us a visual picture of the correlations between components. Predominance of different motifs in the subsets of genes suggests the involvement of motif-specific transcription modulating proteins in Cr stress response of rice.
Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria
Authors: Browne Patrick , Barret Matthieu , O'Gara Fergal , Morrissey John P 
Published: November 2010

Abstract

Background
Catabolite repression control (CRC) is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored.

Results
In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs) such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits.

Conclusions
Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas bacteria integrate nutritional status cues with the regulation of traits that are of ecological, industrial and clinical importance.
DPI-ELISA: a fast and versatile method to specify the binding of plant transcription factors to DNA in vitro
Authors: Brand Luise H , Kirchler Tobias , Hummel Sabine , Chaban Christina , Wanke Dierk 
Published: November 2010

Abstract

Background
About 10% of all genes in eukaryote genomes are predicted to encode transcription factors. The specific binding of transcription factors to short DNA-motifs influences the expression of neighbouring genes. However, little is known about the DNA-protein interaction itself. To date there are only a few suitable methods to characterise DNA-protein-interactions, among which the EMSA is the method most frequently used in laboratories. Besides EMSA, several protocols describe the effective use of an ELISA-based transcription factor binding assay e.g. for the analysis of human NFκB binding to specific DNA sequences.

Results
We provide a unified protocol for this type of ELISA analysis, termed DNA-Protein-Interaction (DPI)-ELISA. Qualitative analyses with His-epitope tagged plant transcription factors expressed in E. coli revealed that EMSA and DPI-ELISA result in comparable and reproducible data. The binding of At bZIP63 to the C-box and At WRKY11 to the W2-box could be reproduced and validated by both methods. We next examined the physical binding of the C-terminal DNA-binding domains of At WRKY33, At WRKY50 and At WRKY75 to the W2-box. Although the DNA-binding domain is highly conserved among the WRKY proteins tested, the use of the DPI-ELISA discloses differences in W2-box binding properties between these proteins. In addition to these well-studied transcription factor families, we applied our protocol to At BPC2, a member of the so far uncharacterised plant specific B asic P entac ysteine transcription factor family. We could demonstrate binding to GA/TC-dinucleotide repeat motifs by our DPI-ELISA protocol. Different buffers and reaction conditions were examined.

Conclusions
We successfully applied our DPI-ELISA protocol to investigate the DNA-binding specificities of three different classes of transcription factors from Arabidopsis thaliana. However, the analysis of the binding affinity of any DNA-binding protein to any given DNA sequence can be performed via this method. The DPI-ELISA is cost efficient, less time-consuming than other methods and provides a qualitative and quantitative readout. The presented DPI-ELISA protocol is accompanied by advice on trouble-shooting, which will enable scientists to rapidly establish this versatile and easy to use method in their laboratories.
Follistatin Regulates Germ Cell Nest Breakdown and Primordial Follicle Formation
Authors: Kimura Fuminori , Bonomi Lara M. , Schneyer Alan L. 
Published: November 2010

AbstractFollistatin (FST) is an antagonist of activin and related TGFβ superfamily members that has important reproductive actions as well as critical regulatory functions in other tissues and systems. FST is produced as three protein isoforms that differ in their biochemical properties and in their localization within the body. We created FST288-only mice that only express the short FST288 isoform and previously reported that females are subfertile, but have an excess of primordial follicles on postnatal day (PND) 8.5 that undergo accelerated demise in adults. We have now examined germ cell nest breakdown and primordial follicle formation in the critical PND 0.5–8.5 period to test the hypothesis that the excess primordial follicles derive from increased proliferation and decreased apoptosis during germ cell nest breakdown. Using double immunofluorescence microscopy we found that there is virtually no germ cell proliferation after birth in wild-type or FST288-only females. However, the entire process of germ cell nest breakdown was extended in time (through at least PND 8.5) and apoptosis was significantly reduced in FST288-only females. In addition, FST288-only females are born with more germ cells within the nests. Thus, the excess primordial follicles in FST288-only mice derive from a greater number of germ cells at birth as well as a reduced rate of apoptosis during nest breakdown. These results also demonstrate that FST is critical for normal regulation of germ cell nest breakdown and that loss of the FST303 and/or FST315 isoforms leads to excess primordial follicles with accelerated demise, resulting in premature cessation of ovarian function.
Skeletal Muscle Mitochondria in Insulin Resistance: Differences in Intermyofibrillar Versus Subsarcolemmal Subpopulations and Relationship to Metabolic Flexibility
Authors: Chomentowski Peter , Coen Paul M. , Radiková Zofia , Goodpaster Bret H. , Toledo Frederico G. S. 
Published: November 2010

abstract

Context:
Insulin resistance is accompanied by lower lipid oxidation during fasting and metabolic inflexibility. Whether these abnormalities correlate with mitochondrial content in skeletal muscle is unknown.

Objective:
The objective of the study was to investigate whether decreased fasting lipid oxidation, metabolic inflexibility, and impaired glucose disposal correlate with reduced mitochondrial content in intermyofibrillar vs. subsarcolemmal (SS) subpopulations.

Design:
Forty sedentary adults with a wide spectrum of insulin sensitivity were studied: insulin-sensitive lean subjects, insulin-resistant nondiabetic subjects, and subjects with type 2 diabetes mellitus. Glucose disposal was measured by euglycemic clamp and [6,6-D2]-glucose methodology. Fuel oxidation and metabolic flexibility (during clamps) were assessed by indirect calorimetry. Maximum aerobic capacity was assessed by treadmill testing. Intermyofibrillar and SS mitochondrial content were measured by quantitative electron microscopy of muscle biopsy samples.

Results:
Intermyofibrillar mitochondrial content was lower in the insulin-resistant nondiabetic subjects and type 2 diabetes mellitus groups, significantly correlating with glucose disposal in both men (R = 0.72, P &lt; 0.01) and women (R = 0.53, P &lt; 0.01). In contrast, SS mitochondrial content was similar among groups. Lower intermyofibrillar mitochondrial content was not explained by mitochondrial size, altered fiber-type distribution, or differences in maximum aerobic capacity. Intermyofibrillar mitochondrial content was significantly correlated with fasting respiratory quotient (R = −0.46, P = 0.003) and metabolic flexibility (R = 0.38, P = 0.02).

Conclusions:
In obese-insulin-resistant subjects with or without diabetes, intermyofibrillar mitochondrial content is decreased. This is not entirely explained by fitness status or fiber-type composition. SS mitochondrial content is unaffected, suggesting independent mitochondrial pool regulation. Lower mitochondrial content correlates with lower fasting lipid oxidation and metabolic inflexibility, suggesting it may be intrinsically linked to abnormal fuel utilization patterns of obesity-associated insulin resistance.
Preparation of Pore-fill-type Palladium–Porous Alumina Composite Membrane for Hydrogen Separation
Authors: Nagata Kensuke , Miyamoto Manabu , Watabe Tsuyoshi , Fujioka Yuichi , Yogo Katsunori 
Published: November 2010

Abstract
A method for formation of the palladium layer in a thermally stable porous substrate was studied. A composite membrane with Pd layer encapsulated in a porous α-alumina substrate (Pd/Al2O3(PF)) was successfully prepared by a new seeding technique and electroless plating. From SEM–EDX, the Pd layer was observed only in the porous substrate at a depth of 10 µm from the top surface. This membrane showed extremely high H2 permselectivity (α H_2/N_2 &gt; 10000) at 773 K and good stability.
Comparison of Vibrational Circular Dichroism between the Langmuir–Blodgett Films and Gels of 12-Hydroxyoctadecanoic Acid
Authors: Sato Hisako , Sakurai Takara , Yamagishi Akihiko 
Published: November 2010

Abstract
Vibrational circular dichroism spectroscopy is applied to the gels and Langmuir–Blodgett (LB) films of R- and S-12-HOA deposited on glass substrates (50 X-type layers) in the wavenumber region of 2700–3400 cm−1, revealing that no long sequence of intermolecular hydrogen bonding was formed in the LB films at C12 position in contrast with the gels of the same compounds.
Expansion of Intertubular Mesopores of Imogolite Nanotubes by Thermal Decomposition of an Imogolite–Poly(sodium 4-styrenesulfonate) Composite
Authors: Kuroda Yoshiyuki , Kuroda Kazuyuki 
Published: November 2010

Abstract
Intertubular mesopores of imogolite nanotubes were enlarged by using poly(sodium 4-styrenesulfonate) as an expander. The polyanion was bound electrostatically on the positively charged imogolite nanotubes to form an intertwined composite, which provided expanded intertubular mesopores after heat treatment. The expanded intertubular mesopores are expected to contribute to efficient diffusion.
The patient's burden of chronic venous disorders: construction of a questionnaire
Authors: Guex J-J , Rahhali N , Taïeb C 
Published: November 2010

Aims On the one hand, the survey aims at the development and validation of an auto-administered questionnaire designed to measure the everyday burden caused by chronic venous disorders (CVDs). On the other hand, it aims at reporting initial epidemiological and demographic data in CVD patients and their correlations. Materials and methods After identification of 66 possible items, the elimination of redundant and less relevant questions left a questionnaire of 36 simple items, the Assessment of Burden in Chronic–Venous Disease (ABC-V) that has been applied prospectively and consecutively to a population of 328 actual chronic venous disorder (CVD) patients in eight vein-specialized centres in France. Questionnaires were completed by patients at home and returned by mail (free return envelopes). Results Significant correlation has been found between ABC-V, the Specific Quality of life & Outcomes Response – Venous (SQOR-V) and the Centre for Epidemiologic Studies Depression Scale (CES-D), demonstrating the validity of the concept. ABC-V has been found increased by age ( P = 0.0127) and body mass index ( P < 0.001), not by gender ( P = 0.8758). Conclusion ABC-V is a first tool to assess the burden of CVDs, it provides with individual data and will help, for instance, determining the weight of the coefficient used in the disability-adjusted life year and quality-adjusted life year formulas, thus ensuring an accurate evaluation of the Global Burden of Chronic Venous Disorders.
Estimating the Operational Impact of Container Inspections at International Ports
Authors: Bakshi Nitin , Flynn Stephen E. , Gans Noah 
Published: November 2010

A U.S. law mandating nonintrusive imaging and radiation detection for 100% of U.S.-bound containers at international ports has provoked widespread concern that the resulting congestion would hinder trade significantly. Using detailed data on container movements, gathered from two large international terminals, we simulate the impact of the two most important inspection policies that are being considered. We find that the current inspection regime being advanced by the U.S. Department of Homeland Security can only handle a small percentage of the total load. An alternate inspection protocol that emphasizes screening—a rapid primary scan of all containers, followed by a more careful secondary scan of only a few containers that fail the primary test—holds promise as a feasible solution for meeting the 100% scanning requirement. This paper was accepted by Yossi Aviv, operations management.
Dynamic Characteristics of a Recoil System When Firing Projectiles with Mach 4.4 Muzzle Velocity from a 105 mm Cannon
Authors: Wu Y. C. , Chang H. , Tsung T. T. 
Published: November 2010

Abstract
This paper discusses the dynamic characteristics of a recoil system when firing armour-piercing fin-stabilized discarding sabot projectiles. They are fired with a muzzle velocity of Mach 4.4 from a 105 mm caliber cannon either equipped with a multi-perforated muzzle brake (MPMB) or with a bare muzzle. In the recoil system, the MPMB moderates the recoil velocity and prolongs the time of resistance to the propellant gases’ force, thereby reducing the inner pressure of the cradle, which possesses both functions of the recoil cylinder and the elevating center, and attenuating the recoil force on the trunnions. The reasons for the formation of each of the dynamic characteristics are discussed. All measurements in this study can be a significant reference for developing guns, tanks, or the chassis of fighting vehicles.