bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmodium vivax
Ookinete Surface Protein Pvs25 Linked to Cholera Toxin B Subunit Induces Potent Transmission-Blocking Immunity by Intranasal as Well as Subcutaneous Immunization
Authors: Miyata Takeshi , Harakuni Tetsuya , Tsuboi Takafumi , Sattabongkot Jetsumon , Kohama Hideyasu , Tachibana Mayumi , Matsuzaki Goro , Torii Motomi , Arakawa Takeshi 
Published: June 2010

ABSTRACT

The nontoxic cholera toxin B subunit (CTB) was evaluated as a potential delivery molecule for the
Plasmodium vivax
ookinete surface protein, Pvs25. Recombinant Pvs25 was expressed as a secreted protein in the yeast
Pichia pastoris
, as a mixture of isoforms including multimers and the A and B monomers. The A isoform with the presumed native protein fold was the most abundant, accounting for more than 40% of all expressed protein. The molecularly uniform A isoform was chemically conjugated to CTB via its primary amines, and the fusion protein, retaining GM1-ganglioside affinity, was administered to BALB/c mice by the subcutaneous (s.c.) or intranasal (i.n.) route. Immunization of mice with conjugated Pvs25 without supplemental adjuvant induced antisera that specifically recognized
P. vivax
ookinetes
in vitro
. Furthermore, the antisera, when mixed with parasitized blood isolated from
P. vivax
patients from Thailand, was found to reduce parasite transmission to mosquitoes, conferring a 93 to 98% (s.c.) or a 73 to 88% (i.n.) decrease in oocyst number. Unconjugated Pvs25 alone conferred only a 23 to 60% (s.c.) or a 0 to 6% (i.n.) decrease in oocyst number. Coadministration of extraneous adjuvants, however, further enhanced the vaccine efficacy up to complete blockade. Taken together, we conclude that a weakly immunogenic Pvs25 by itself, when linked to CTB, transforms into a potent transmission-blocking antigen in both i.n. and s.c. routes. In addition, the present study is, to the best of our knowledge, the first demonstration of the immune potentiating function of CTB for a vaccine antigen delivered by the s.c. route.
T-Cell-Independent Immune Responses Do Not Require Cxc Ligand 13-Mediated B1 Cell Migration
Authors: Colombo Matthew J. , Sun Guizhi , Alugupalli Kishore R. 
Published: June 2010

ABSTRACT

The dynamic movement of B cells increases the probability of encountering specific antigen and facilitates cell-cell interactions required for mounting a rapid antibody response. B1a and B1b cells are enriched in the coelomic cavity, contribute to T-cell-independent (TI) antibody responses, and increase in number upon antigen exposure. B1 cell movement is largely governed by Cxc ligand 13 (Cxcl13), and mice deficient in this chemokine have a severe reduction in peritoneal B1 cells. In this study, we examined the role of Cxcl13-dependent B cell migration using
Borrelia hermsii
infection or intraperitoneal immunization with pneumococcal polysaccharide or 4-hydroxy-3-nitrophenyl-acetyl (NP)-Ficoll, all of which induce robust antibody responses from B1b cells. Surprisingly, we found that antibody responses to
B. hermsii
or to FhbA, an antigenic target of B1b cells, and the resolution of bacteremia were indistinguishable between wild-type and
Cxcl13
−/−
mice. Importantly, we did not observe an expansion of peritoneal B1b cell numbers in
Cxcl13
−/−
mice. Nonetheless, mice that had resolved infection were resistant to reinfection, indicating that the peritoneal B1b cell reservoir is not required for controlling
B. hermsii
. Furthermore, despite a reduced peritoneal B1b compartment, immunization with pneumococcal polysaccharide vaccine yielded comparable antigen-specific antibody responses in wild-type and
Cxcl13
−/−
mice and conferred protection against
Streptococcus pneumoniae
. Likewise, immunization with NP-Ficoll elicited similar antibody responses in wild-type and
Cxcl13
−/−
mice. These data demonstrate that homing of B1 cells into the coelomic cavity is not a requirement for generating protective TI antibody responses, even when antigen is initially localized to this anatomical compartment.
Analyzing the Regulatory Role of the HigA Antitoxin within
Mycobacterium tuberculosis
Authors: Fivian-Hughes Amanda S. , Davis Elaine O. 
Published: June 2010

ABSTRACT

Bacterial chromosomally encoded type II toxin-antitoxin (TA) loci may be involved in survival upon exposure to stress and have been linked to persistence and dormancy. Therefore, understanding the role of the numerous predicted TA loci within the human pathogen
Mycobacterium tuberculosis
has become a topic of great interest. Antitoxin proteins are known to autoregulate TA expression under normal growth conditions, but it is unknown whether they have a more global role in transcriptional regulation. This study focuses on analyzing the regulatory role of the
M. tuberculosis
HigA antitoxin. We first show that the
M. tuberculosis higBA
locus is functional within its native organism, as
higB
,
higA
, and Rv1957 were successfully deleted from the genome together while the deletion of
higA
alone was not possible. The effects of
higB
-Rv1957 deletion on
M. tuberculosis
global gene expression were investigated, and a number of potential HigA-regulated genes were identified. Transcriptional fusion and protein-DNA-binding assays were utilized to confirm the direct role of HigA in Rv1954A-Rv1957 repression, and the
M. tuberculosis
HigA DNA-binding motif was defined as ATATAGG(N
6
)CCTATAT. As HigA failed to bind to the next-most-closely related motif within the
M. tuberculosis
genome, HigA may not directly regulate any other genes in addition to its own operon.
Sense of effort and other unpleasant sensations during exercise: clarifying concepts and mechanisms
Authors: Smirmaul Bruno de Paula Caraça 
Published: June 2010

IntroductionThe sense of effort is an essential component of all forms of exercise. Although extensively studied, exercise physiologists have failed to reach consensus about whether this sensation is based on afferent sensory feedback or is centrally generated and independent of such feedback. This confusion has led to misunderstandings regarding the neurological mechanisms responsible for the sense of effort as opposed to other specific sensations such as pain and temperature.DiscussionA mechanism in which the sense of effort is centrally generated and independent of feedback had been proposed more than 150 years ago. However, a more recent concept of sense of effort as a subjective rating of exercise intensity based on various sensations experienced during exercise given by Borg may have caused confusion, especially among exercise physiologists. Many began to use and understand the sense of effort as a sensation that is generated by afferent sensory feedback. The information reviewed in this article, together with the examples given, constitutes a body of evidence in favour of a centrally generated sense of effort. Afferent sensory feedback is important for the conscious awareness of different sensations such as pain and temperature, and plays important roles in the control of homeostasis. However, peripheral sensory feedback does not seem to be important for the generation of the sense of effort.ConclusionThe sense of effort and other specific sensations such as temperature, pain and other muscular sensations present two separate neurological mechanisms. While the former is centrally generated, the latter is based on afferent sensory feedback. An interaction of these sensations is likely the ultimate regulator of exercise performance. However, further investigation is required to fully understand these phenomena.
Quantifying the effects of promoting smokeless tobacco as a harm reduction strategy in the USA
Authors: Mejia Adrienne B , Ling Pamela M , Glantz Stanton A 
Published: June 2010

BackgroundSnus (a form of smokeless tobacco) is less dangerous than cigarettes. Some health professionals argue that snus should be promoted as a component of a harm reduction strategy, while others oppose this approach. Major US tobacco companies (RJ Reynolds and Philip Morris) are marketing snus products as cigarette brand line extensions. The population effects of smokeless tobacco promotion will depend on the combined effects of changes in individual risk with population changes in tobacco use patterns.ObjectiveTo quantitatively evaluate the health impact of smokeless tobacco promotion as part of a harm reduction strategy in the US.MethodsA Monte Carlo simulation of a decision tree model of tobacco initiation and use was used to estimate the health effects associated with five different patterns of increased smokeless tobacco use.ResultsWith cigarette smoking having a health effect of 100, the base case scenario (based on current US prevalence rates) yields a total health effect of 24.2 (5% to 95% interval 21.7 to 26.5) and the aggressive smokeless promotion (less cigarette use and increased smokeless, health-concerned smokers switching to snus, smokers in smokefree environments switching to snus) was associated with a health effect of 30.4 (5% to 95%interval25.9 to 35.2). The anticipated health effects for additional scenarios with lower rates of smokeless uptake also overlapped with the base case.ConclusionsPromoting smokeless tobacco as a safer alternative to cigarettes is unlikely to result in substantial health benefits at a population level.
Toward high-performance polynomial system solvers based on triangular decompositions
Authors: Li Xin 
Published: June 2010

This thesis is devoted to the design and implementation of polynomial system solvers based on symbolic computation. Solving systems of non-linear, algebraic or differential equations, is a fundamental problem in mathematical sciences. It has been studied for centuries and still stimulates many research developments, in particular on the front of high-performance computing.
Triangular decompositions are a highly promising technique with the potential to produce high-performance polynomial system solvers. This thesis makes several contributions to this effort.
We propose asymptotically fast algorithms for the core operations on which triangular decompositions rely. Complexity results and comparative implementation show that these new algorithms provide substantial performance improvements.
We present a fundamental software library for polynomial arithmetic in order to support the implementation of high-performance solvers based on triangular decompositions. We investigate strategies for the integration of this library in high-level programming environments where triangular decompositions are usually implemented.
We obtain a high performance library combining highly optimized C routines and solving procedures written in the Maple computer algebra system. The experimental result shows that our approaches are very effective, since our code often outperforms pre-existing solvers in a significant manner.
Witchcraft
Authors: Vanashree  
Published: June 2010

Witchcraft accusation is an issue beyond historical recollection and yet it does not figure in the public sphere. Branding a woman Daayan or Chodail has been a common practice in rural India. This article’s engagement with Mahasweta Devi’s play, Bayen, intends to provide a searching analysis of the mechanism of witchcraft accusations in India. How the accused is seen in possession of an uncanny gaze by which she bewitches her unfortunate victim, how the mob violence condemning her is seen in terms of popular justice, how literate or illiterate people seek a scapegoat in the accused; someone they could blame for their misfortune. The fact that it also gets the sanction of women along with men belonging to the same community does not rule out that it is gendered since most accused are women. Invoking several narratives of violence and torture upon the body of women accused of practicing witchcraft and in closely analysing Bayen, the article probes the way spectacle of torture and exclusion is performed as the ceremony of punishment recalling Arendt’s and Foucault’s understanding of the psychology of crowd power and the relationship between power and surveillance. In this context, it also goes on to debate the identity categories in which subaltern and gendered subjectivity are assumed to speak and discovers in the postcolonial feminist frame of reference the psychic identity of the gendered subaltern as varied, contingent, and capable of showing modes of resistance. In spite of deranged illusions, and dehumanisation, Mahasweta Devi’s Chandidasi survives emotional and physical devastation and renders claims of power and control, discipline and punishment doubtful.
Enhanced c-Met activity promotes G-CSF–induced mobilization of hematopoietic progenitor cells via ROS signaling
Authors: Tesio Melania , Golan Karin , Corso Simona , Giordano Silvia , Schajnovitz Amir , Vagima Yaron , Shivtiel Shoham , Kalinkovich Alexander , Caione Luisa , Gammaitoni Loretta , Laurenti Elisa , Buss Eike C. , Shezen Elias , Itkin Tomer , Kollet Orit , Petit Isabelle , Trumpp Andreas , Christensen James , Aglietta Massimo , Piacibello Wanda , Lapidot Tsvee 
Published: June 2010

Abstract
Mechanisms governing stress-induced hematopoietic progenitor cell mobilization are not fully deciphered. We report that during granulocyte colony-stimulating factor–induced mobilization c-Met expression and signaling are up-regulated on immature bone marrow progenitors. Interestingly, stromal cell–derived factor 1/CXC chemokine receptor-4 signaling induced hepatocyte growth factor production and c-Met activation. We found that c-Met inhibition reduced mobilization of both immature progenitors and the more primitive Sca-1+/c-Kit+/Lin− cells and interfered with their enhanced chemotactic migration to stromal cell–derived factor 1. c-Met activation resulted in cellular accumulation of reactive oxygen species by mammalian target of rapamycin inhibition of Forkhead Box, subclass O3a. Blockage of mammalian target of rapamycin inhibition or reactive oxygen species signaling impaired c-Met–mediated mobilization. Our data show dynamic c-Met expression and function in the bone marrow and show that enhanced c-Met signaling is crucial to facilitate stress-induced mobilization of progenitor cells as part of host defense and repair mechanisms.
Tropomodulin 1-null mice have a mild spherocytic elliptocytosis with appearance of Tropomodulin 3 in red blood cells and disruption of the membrane skeleton
Authors: Moyer Jeannette D. , Nowak Roberta B. , Kim Nancy E. , Larkin Sandra K. , Peters Luanne L. , Hartwig John , Kuypers Frans A. , Fowler Velia M. 
Published: June 2010

AbstractThe short actin filaments in the red blood cell (RBC) membrane skeleton are capped at their pointed ends by tropomodulin 1 (Tmod1) and coated with tropomyosin (TM) along their length. Tmod1-TM control of actin filament length is hypothesized to regulate spectrin-actin lattice organization and membrane stability. We used a Tmod1 knockout mouse to investigate the in vivo role of Tmod1 in the RBC membrane skeleton. Western blots of Tmod1-null RBCs confirm the absence of Tmod1 and show the presence of Tmod3, which is normally not present in RBCs. Tmod3 is present at only one-fifth levels of Tmod1 present on wild-type membranes, but levels of actin, TMs, adducins, and other membrane skeleton proteins remain unchanged. Electron microscopy shows that actin filament lengths are more variable with spectrin-actin lattices displaying abnormally large and more variable pore sizes. Tmod1-null mice display a mild anemia with features resembling hereditary spherocytic elliptocytosis, including decreased RBC mean corpuscular volume, cellular dehydration, increased osmotic fragility, reduced deformability, and heterogeneity in osmotic ektacytometry. Insufficient capping of actin filaments by Tmod3 may allow greater actin dynamics at pointed ends, resulting in filament length redistribution, leading to irregular and attenuated spectrin-actin lattice connectivity, and concomitant RBC membrane instability.
Embryonic vascular endothelial cells are malleable to reprogramming via Prox1 to a lymphatic gene signature
Authors: Kim Harold , Nguyen Vicky PKH , Petrova Tatiana V , Cruz Maribelle , Alitalo Kari , Dumont Daniel J 
Published: June 2010

Abstract

Background

In vivo studies demonstrate that the Prox1 transcription factor plays a critical role in the development of the early lymphatic system. Upon Prox1 expression, early lymphatic endothelial cells differentiate from the cardinal vein and begin to express lymphatic markers such as VEGFR-3, LYVE-1 and Podoplanin. Subsequent in vitro studies have found that differentiated vascular endothelial cells can be reprogrammed by Prox1 to express a lymphatic gene profile, suggesting that Prox1 can initiate the expression of a unique gene signature during lymphangiogenesis. While the in vitro data suggest that gene reprogramming occurs upon Prox1 expression, it is not clear if this is a direct result of Prox1 in vascular endothelial cells in vivo.

Results
Overexpression of Prox1 in vascular endothelial cells during embryonic development results in the reprogramming of genes to that of a more lymphatic signature. Consequent to this overexpression, embryos suffer from gross edema that results in embryonic lethality at E13.5. Furthermore, hemorrhaging and anemia is apparent along with clear defects in lymph sac development. Alterations in junctional proteins resulting in an increase in vascular permeability upon Prox1 overexpression may contribute to the complications found during embryonic development.

Conclusion
We present a novel mouse model that addresses the importance of Prox1 in early embryonic lymphangiogenesis. It is clear that there needs to be a measured pattern of expression of Prox1 during embryonic development. Furthermore, Prox1 reprograms vascular endothelial cells in vivo by creating a molecular signature to that of a lymphatic endothelial cell.
Microarray analysis of a salamander hopeful monster reveals transcriptional signatures of paedomorphic brain development
Authors: Page Robert B , Boley Meredith A , Smith Jeramiah J , Putta Srikrishna , Voss Stephen R 
Published: June 2010

AbstractBackgroundThe Mexican axolotl (Ambystoma mexicanum) is considered a hopeful monster because it exhibits an adaptive and derived mode of development - paedomorphosis - that has evolved rapidly and independently among tiger salamanders. Unlike related tiger salamanders that undergo metamorphosis, axolotls retain larval morphological traits into adulthood and thus present an adult body plan that differs dramatically from the ancestral (metamorphic) form. The basis of paedomorphic development was investigated by comparing temporal patterns of gene transcription between axolotl and tiger salamander larvae (Ambystoma tigrinum tigrinum) that typically undergo a metamorphosis.ResultsTranscript abundances from whole brain and pituitary were estimated via microarray analysis on four different days post hatching (42, 56, 70, 84 dph) and regression modeling was used to independently identify genes that were differentially expressed as a function of time in both species. Collectively, more differentially expressed genes (DEGs) were identified as unique to the axolotl (n= 76) and tiger salamander (n= 292) than were identified as shared (n= 108). All but two of the shared DEGs exhibited the same temporal pattern of expression and the unique genes tended to show greater changes later in the larval period when tiger salamander larvae were undergoing anatomical metamorphosis. A second, complementary analysis that directly compared the expression of 1320 genes between the species identified 409 genes that differed as a function of species or the interaction between time and species. Of these 409 DEGs, 84% exhibited higher abundances in tiger salamander larvae at all sampling times.ConclusionsMany of the unique tiger salamander transcriptional responses are probably associated with metamorphic biological processes. However, the axolotl also showed unique patterns of transcription early in development. In particular, the axolotl showed a genome-wide reduction in mRNA abundance across loci, including genes that regulate hypothalamic-pituitary activities. This suggests that an axolotls failure to undergo anatomical metamorphosis late in the larval period is indirectly associated with a mechanism(s) that acts earlier in development to broadly program transcription. The axolotl hopeful monster provides a model to identify mechanisms of early brain development that proximally and ultimately affect the expression of adult phenotypes.
Serum CD26 is related to histopathological polyp traits and behaves as a marker for colorectal cancer and advanced adenomas
Authors: De Chiara Loretta , Rodríguez-Piñeiro Ana M , Rodríguez-Berrocal Francisco J , Cordero Oscar J , Martínez-Ares David , Páez de la Cadena María 
Published: June 2010

Abstract

Background
Serum CD26 (sCD26) levels were previously found diminished in colorectal cancer (CRC) patients compared to healthy donors, suggesting its potential utility for early diagnosis. Therefore we aimed to estimate the utility of the sCD26 as a biomarker for CRC and advanced adenomas in a high-risk group of patients. The relationship of this molecule with polyp characteristics was also addressed.

Methods
sCD26 levels were measured by ELISA in 299 symptomatic and asymptomatic patients who had undergone a colonoscopy. Patients were diagnosed as having no colorectal pathology, non-inflammatory or inflammatory bowel disease, polyps (hyperplastic, non-advanced and advanced adenomas) or CRC.

Results
At a 460 ng/mL cut-off, the sCD26 has a sensitivity and specificity of 81.8% (95% CI, 64.5-93.0%) and 72.3% (95% CI, 65.0-77.2%) for CRC regarding no or benign colorectal pathology. Clinicopathological analysis of polyps showed a relationship between the sCD26 and the grade of dysplasia and the presence of advanced adenomas. Hence, a 58.0% (95% CI, 46.5-68.9%) sensitivity detecting CRC and advanced adenomas was obtained, with a specificity of 75.5% (95% CI, 68.5-81.0%).

Conclusions
Our preliminary results show that measurement of the sCD26 is a non-invasive and reasonably sensitive assay, which could be combined with others such as the faecal occult blood test for the early diagnosis and screening of CRC and advanced adenomas. Additional comparative studies in average-risk populations are necessary.
Elevated MED28 expression predicts poor outcome in women with breast cancer
Authors: Yoon Nam K , Maresh Erin L , Elshimali Yahya , Li Ai , Horvath Steve , Seligson David B , Chia David , Goodglick Lee 
Published: June 2010

Abstract

Background
MED28 (also known as EG-1 and magicin) has been implicated in transcriptional control, signal regulation, and cell proliferation. MED28 has also been associated with tumor progression in in
vitro and in vivo models. Here we examined the association of MED28 expression with human breast cancer progression.

Methods
Expression of MED28 protein was determined on a population basis using a high-density tissue microarray consisting of 210 breast cancer patients. The association and validation of MED28 expression with histopathological subtypes, clinicopathological variables, and disease outcome was assessed.

Results
MED28 protein expression levels were increased in ductal carcinoma in situ and invasive ductal carcinoma of the breast compared to non-malignant glandular and ductal epithelium. Moreover, MED28 was a predictor of disease outcome in both univariate and multivariate analyses with higher expression predicting a greater risk of disease-related death.

Conclusions
We have demonstrated that MED28 expression is increased in breast cancer. In addition, although the patient size was limited (88 individuals with survival information) MED28 is a novel and strong independent prognostic indicator of survival for breast cancer.