bluuebunny/crossref_metadata_2025 huggingface dataset:
Head Start Fathers’ Involvement With Their Children
Authors: Gorvine Benjamin J.
Published: October 2009

Until recently, fathers have been underexamined relative to mothers in research on parenting. Fathers in poverty, as well as stepfathers and nonresidential fathers, have been a particularly understudied group. This study explores Head Start fathers’ involvement with their children. Fathers are defined to include stepfathers as well as nonresidential fathers. Seventy-eight mothers have been interviewed about fathers’ involvement with their children. Mothers generally perceive a modest extent of fathers’ involvement but also report high levels of children’s satisfaction with fathers’ emotional support. Mothers generally report a higher extent of involvement for residential fathers than for nonresidential fathers and report higher levels of interaction for stepfathers than for biological fathers. Mothers consistently report that both residential biological fathers and residential stepfathers are more involved than nonresidential biological fathers. The findings suggest the importance of continuing to gather data that looks at both residential and nonresidential fathers as well as biological fathers and stepfathers.
Risk and Protective Factors for Psychological Adjustment Among Low-Income, African American Children
Authors: Gabalda Megan K. , Thompson Martie P. , Kaslow Nadine J.
Published: October 2009

This investigation identifies unique risk and protective factors for internalizing and externalizing problems among 8- to 12-year-old, low-income, African American children and tests cumulative risk and protective models. A total of 152 mother—child dyads complete questionnaires. Receipt of food stamps, mother’s distress, and child maltreatment increase children’s risk for internalizing and externalizing problems and family functioning (adaptability, cohesion), and after-school program participation (externalizing only) are protective against internalizing and externalizing problems. A cumulative risk model reveals that compared with youth with no risk factors, having one risk factor confers three- and fivefold risk for internalizing and externalizing symptoms, respectively. Having two or three risk factors confers 12 and 19 times greater risk for internalizing and externalizing symptoms, respectively. Compared with no protective factors, youth with two protective factors are 4 and 6 times less likely to display internalizing and externalizing problems, respectively. Implications for community-based preventive intervention efforts and future research are discussed.
Evaluation of Subchronic Toxicity of Pet Food Contaminated with Melamine and Cyanuric Acid in Rats
Authors: Chen Kun-Chao , Liao Chen-Wei , Cheng Fen-Pang , Chou Chi-Chung , Chang Shih-Chien , Wu Jhaol-Huei , Zen Jyh-Myng , Chen Yng-Tay , Liao Jiunn-Wang
Published: October 2009

Outbreaks of food-associated renal failure in pets occurred in Asia and the United States of America in 2004 and 2007. They were related to the combined intoxication of cyanuric acid and melamine. Our aims were to investigate cyanuric acid and melamine contamination of pet food and to examine subchronic toxicity in rats. Levels of 10%, 20%, 50%, and 50%–100% (w/w) of contaminated pet food were fed to rats for three months. Analytical results revealed that the tainted food contained significant levels of cyanuric acid and melamine in a ratio of 1:6.8. Rats fed the diet of 50%–100% for three months exhibited elevated serum blood urea nitrogen and creatinine, as well as dose-dependent melamine/cyanuric acid crystal-induced nephrotoxicity. The melamine/cyanuric acid crystals of various sizes were mixed with necrotic cell debris and inflammatory cells, accompanied by tubular dilation and interstitial fibrosis. The immunohistochemistry index of proliferative cellular nuclear antigen and osteopontin in the kidney of the 50%–100% group were elevated, indicating regeneration of renal cells and the formation of crystals. In conclusion, the combination ratio of cyanuric acid to melamine and the acidic urine content were two factors that, upon repeated exposure, determined the severity of the nephrotoxicity.
Post-Keynesian Theories of the Firm under Financialization
Authors: Dallery Thomas
Published: October 2009

Financialization is studied here from a microeconomic viewpoint. Following Stockhammer (2004a), the theory of the firm has been amended by introducing agency problems and class analysis between shareholders and managers. Further to that, I propose two alternative configurations for incorporation into the theory: the first views financialization as a constraint for the managerial firm, while the second discusses shareholders’ interests and integrates them as an end in itself for the finance-dominated firm. My conclusions focus on finance-oppressed accumulation, financial fragility, and potential macroeconomic instability.

JEL classification: D21, E12, G30
A Further Look at the Intergenerational Transmission of Violence: Witnessing Interparental Violence in Emerging Adulthood
Authors: Black David S. , Sussman Steve , Unger Jennifer B.
Published: October 2009

The intergenerational transmission (IGT) of violence has been a main the oretical consideration to explain the link between interparental aggression in the family of origin and intimate partner violence (IPV) in subsequent intimate relationships. Studies have examined this theoretical link based on self reports of interparental violence witnessed during childhood and adolescence. However, no study has examined whether emerging adults who currently witness interparental violence are more likely to exhibit violence in their own intimate relationships. Data were analyzed from undergraduate students ( N = 223) attending an ethnically diverse Southern California uni versity. Multivariate linear regression analyses were used to examine the impact of witnessing interparental violence on the physical and psycho logical IPV experienced in emerging adult relationships. The joint effects of witnessing both forms of interparental violence were also tested. Support for the intergenerational transmission of violence was identified for specific types of violence. Future directions of study and implications for prevention and treatment are offered.
Lost in Transition
Authors: Velikonja Mitja
Published: October 2009

Why is there nostalgia for real socialism? Is it but a logical response to sudden, dramatic transformation? Don’t people remember those days anymore—or do they remember them all too well? In popular opinion, nostalgia for socialism is something fabricated, invented, and then imposed by different groups of people to achieve some goals: to open a new commercial niche, to attain political credit, to win popular support, to get artistic inspiration, and so on. Thus, many academic studies have examined only this instrumental side of the phenomenon, limiting it to the “industry of nostalgia” only. But research shows that nostalgia is in fact a retrospective utopia, a wish and a hope for a safe world, a fair society, true friendships, mutual solidarity, and well-being in general, in short, for a perfect world. As such, it is less a subjective, arbitrary, ideological effort to recall the past as it is, an undetermined, undefined, amorphous wish to transcend the present. So nostalgia for socialism in fact does not relate exclusively and precisely to past times, regimes, values, relations, and so on as such, but it embodies a utopian hope that there must be a society that is better than the current one.
Regional Benchmarking in a Global Context: Knowledge, Competitiveness, and Economic Development
Authors: Huggins Robert , Izushi Hiro
Published: October 2009

Benchmarking exercises have become increasingly popular within the sphere of regional policy making. However, most exercises are restricted to comparing regions within a particular continental bloc or nation.This article introduces the World Knowledge Competitiveness Index (WKCI), which is one of the very few benchmarking exercises established to compare regions across continents.The article discusses the formulation of the WKCI and analyzes the results of the most recent editions.The results suggest that there are significant variations in the knowledge-based regional economic development models at work across the globe. Further analysis also indicates that Silicon Valley, as the highest ranked WKCI region, holds a unique economic position among the globe’s leading regions. However, significant changes in the sources of regional competitiveness are evolving as a result of the emergence of new regional hot spots in Asia. It is concluded that benchmarking is imperative to the learning process of regional policy making.
In for the Long Haul: Knowledge Translation Between Academic and Nonprofit Organizations
Authors: Jansson S. Mikael , Benoit Cecilia , Casey Lauren , Phillips Rachel , Burns David
Published: October 2009

Although scientists are continually refining existing knowledge and producing new evidence to improve health care and health care delivery, far too little scientific output finds its way into the tool kits of practitioners. Likewise, the questions that clinicians would like to be answered all too rarely get taken up by researchers. In this article we focus on knowledge translation challenges accompanying a longitudinal research program with nonprofit organizations providing direct and indirect health and social services to disadvantaged groups in one region of Canada. Three essential factors influencing authentic and reciprocal knowledge transfer and utilization between nonprofit service providers and researchers are discussed: strong institutional partnerships, the use of skilled knowledge brokers, and the meaningful involvement of frontline personnel.
Sensory Experience and Cortical Rewiring
Authors: Barnes Samuel J. , Finnerty Gerald T.
Published: October 2009

Adult primary sensory cortex is not hard wired, but adapts to sensory experience. The cellular basis for cortical plasticity involves a combination of functional and structural changes in cortical neurons and the connections between them. Functional changes such as synaptic strengthening have been the focus of many investigations. However, structural modifications to the connections between neurons play an important role in cortical plasticity. In this review, the authors focus on structural remodeling that leads to rewiring of cortical circuits. Recent work has identified axonal remodeling, growth of new dendritic spines, and synapse turnover as important structural mechanisms for experience-dependent plasticity in mature cortex. These findings have begun to unravel how rewiring occurs in adult neocortex and offer new insights into the cellular mechanisms for learning and memory.
Adopting Direct Democracy
Authors: Lawrence Eric D. , Donovan Todd , Bowler Shaun
Published: October 2009

Why was direct democracy adopted in some U.S. states and not others? In this article, we sort through the various arguments advanced in the predominantly historical literature by using event history analysis. Among other factors we identify the importance of popular support for Populists and Socialists as well as the constraints imposed by state constitutions. We also find that the demographic composition of states was strongly associated with success or failure to adopt the initiative. Furthermore, we identify a number of key cases—highlighted by this approach—that present intriguing anomalies to the general patterns identified in the historical and political science literatures to date.
Do Voters Perceive Negative Campaigns as Informative Campaigns?
Authors: Sides John , Lipsitz Keena , Grossmann Matthew
Published: October 2009

We argue that citizens distinguish the tone of a campaign from the quality of information that it provides and that evaluations on each dimension respond differently to positive and negative political advertising. We test these claims using survey and advertising data from the 2000 presidential campaign and two 1998 gubernatorial races. In each race, citizens separate judgments about the tone of a campaign from judgments about the quality of information they have received. Furthermore, negative campaigning affects the former, but not the latter, set of evaluations. These results have implications for the debate over the impact of negative advertising and for how citizens perceive campaigns as political processes.
Racing Toward Representation
Authors: Shah Paru
Published: October 2009

Despite 35 years of empirical research, the question of how electoral structure influences Latino representation continues to be debated. Motivated by the uncertainty surrounding electoral systems, in this article, I argue that the inconsistent and inconclusive results of previous research stem from two limitations—one theoretical and the other methodological—of commonly used models. In the following analysis, I use an alternative theoretical conceptualization and the appropriate methodological approach to shed light on several puzzles encountered in the literature. My findings suggest, for example, that electoral structure and voting strength are key components in determining the likelihood of Latino representation, but specific demographic and institutional contexts determine how these matter: Ceteris paribus, ward elections hurt Latino chances of representation, unless there are high levels of segregation within a district. Moreover, I find that the impact of the Latino population is in great part determined by the likelihood that the populace (a) has voting rights (i.e., U.S. citizenship), (b) is not in direct competition with Blacks for elected seats, and (c) resides in an area of the United States with a long history of Latino incorporation. In short, in the race toward representation, Latinos cannot simply tread the same path as their Black counterparts but must forge new roads to victory.
Deracializing Obama: White Voters and the 2004 Illinois U.S. Senate Race
Authors: Andersen David J. , Junn Jane
Published: October 2009

Using the unique circumstances of the 2004 Illinois U.S. Senate election, we report findings from survey data from a probability sample of White voters conducted in Illinois during the course of the 2004 election. In an experimental manipulation embedded in the survey, we tested four distinctive framings of Barack Obama by systematically altering the degree and content of his racialization as a Black man, and observing the effect of these treatments on evaluations of Obama. We hypothesize that more strongly racialized framings that highlight Obama’s identity and connection with African Americans would push White voters toward more unfavorable evaluations of the candidate in comparison with deracialized framings. In addition, we argue that party identification has an important moderating influence on the relationship between the racialized treatment and respondents’ evaluations of Obama.
Review: Obesity and Alzheimer’s Disease: A Link Between Body Weight and Cognitive Function in Old Age
Authors: Naderali Ebrahim K. , Ratcliffe Stuart H. , Dale Mark C.
Published: October 2009

Obesity is now a global health hazard. It not only predisposes to an array of risk factors leading to increased morbidity and mortality amongst adults but it also has a major negative impact on children’s health. The deleterious effects of obesity on cardiovascular system have now been well acknowledged. It causes insulin resistance that in turn leads to diabetes, hypertension and cardiovascular abnormalities. The vascular effects of obesity may have a role in the development of a rapidly growing disease of late life, Alzheimer’s disease. The precise mechanisms of the association between adiposity and impairment of cognitive performance remain to be elucidated. However, negative impact of obesity on cognitive function may be, at least in part, due to vascular defects, impaired insulin metabolism and signaling pathway or a defect in glucose transport mechanisms in brain. This review examines the available data regarding the impact of obesity on cognitive function.
Sox7-sustained expression alters the balance between proliferation and differentiation of hematopoietic progenitors at the onset of blood specification
Authors: Gandillet Arnaud , Serrano Alicia G. , Pearson Stella , Lie-A-Ling Michael , Lacaud Georges , Kouskoff Valerie
Published: October 2009

The molecular mechanisms that regulate the balance between proliferation and differentiation of precursors at the onset of hematopoiesis specification are poorly understood. By using a global gene expression profiling approach during the course of embryonic stem cell differentiation, we identified Sox7 as a potential candidate gene involved in the regulation of blood lineage formation from the mesoderm germ layer. In the present study, we show that Sox7 is transiently expressed in mesodermal precursors as they undergo specification to the hematopoietic program. Sox7 knockdown in vitro significantly decreases the formation of both primitive erythroid and definitive hematopoietic progenitors as well as endothelial progenitors. In contrast, Sox7-sustained expression in the earliest committed hematopoietic precursors promotes the maintenance of their multipotent and self-renewing status. Removal of this differentiation block driven by Sox7-enforced expression leads to the efficient differentiation of hematopoietic progenitors to all erythroid and myeloid lineages. This study identifies Sox7 as a novel and important player in the molecular regulation of the first committed blood precursors. Furthermore, our data demonstrate that the mere sustained expression of Sox7 is sufficient to completely alter the balance between proliferation and differentiation at the onset of hematopoiesis.
Difference in the regulation of IL-8 expression induced by uropathogenic E. coli between two kinds of urinary tract epithelial cells
Authors: Tsai Kun-Wei , Lai Hong-Thih , Tsai Tzung-Chieh , Wu Yi-Chien , Yang Ya-Ting , Chen Kwei-Yi , Chen Chun-Ming , Li Yi-Shuan J , Chen Cheng-Nan
Published: October 2009

Bacterial adherence to epithelial cells is a key virulence trait of pathogenic bacteria. The type 1 fimbriae and the P-fimbriae of uropathogenicEscherichia coli(UPEC) have both been described to be important for the establishment of urinary tract infections (UTI). To explore the interactions between the host and bacterium responsible for the different environments of UPEC invasion, we examined the effect of pH and osmolarity on UPEC strain J96 fimbrial expression, and subsequent J96-induced interleukin-8 (IL-8) expression in different uroepithelial cells. The J96 strain grown in high pH with low osmolarity condition was favorable for the expression of type 1 fimbriae; whereas J96 grown in low pH with high osmolarity condition was beneficial for P fimbriae expression. Type 1 fimbriated J96 specifically invaded bladder 5637 epithelial cells and induced IL-8 expression. On the contrary, P fimbriated J96 invaded renal 786-O epithelial cells and induced IL-8 expression effectively. Type 1 fimbriated J96-induced IL-8 induction involved the p38, as well as ERK, JNK pathways, which leads to AP-1-mediated gene expression. P fimbriated J96-induced augmentation of IL-8 expression mainly involved p38-mediated AP-1 and NF-κB transcriptional activation. These results indicate that different expression of fimbriae in J96 trigger differential IL-8 gene regulation pathways in different uroepithelial cells.
An editor for pathway drawing and data visualization in the Biopathways Workbench
Authors: Byrnes Robert W , Cotter Dawn , Maer Andreia , Li Joshua , Nadeau David , Subramaniam Shankar
Published: October 2009

Background

Pathway models serve as the basis for much of systems biology. They are often built using programs designed for the purpose. Constructing new models generally requires simultaneous access to experimental data of diverse types, to databases of well-characterized biological compounds and molecular intermediates, and to reference model pathways. However, few if any software applications provide all such capabilities within a single user interface.

Results

The Pathway Editor is a program written in the Java programming language that allows de-novo pathway creation and downloading of LIPID MAPS (Lipid Metabolites and Pathways Strategy) and KEGG lipid metabolic pathways, and of measured time-dependent changes to lipid components of metabolism. Accessed through Java Web Start, the program downloads pathways from the LIPID MAPS Pathway database (Pathway) as well as from the LIPID MAPS web server http://www.lipidmaps.org. Data arises from metabolomic (lipidomic), microarray, and protein array experiments performed by the LIPID MAPS consortium of laboratories and is arranged by experiment. Facility is provided to create, connect, and annotate nodes and processes on a drawing panel with reference to database objects and time course data. Node and interaction layout as well as data display may be configured in pathway diagrams as desired. Users may extend diagrams, and may also read and write data and non-lipidomic KEGG pathways to and from files. Pathway diagrams in XML format, containing database identifiers referencing specific compounds and experiments, can be saved to a local file for subsequent use. The program is built upon a library of classes, referred to as the Biopathways Workbench, that convert between different file formats and database objects. An example of this feature is provided in the form of read/construct/write access to models in SBML (Systems Biology Markup Language) contained in the local file system.

Conclusion

Inclusion of access to multiple experimental data types and of pathway diagrams within a single interface, automatic updating through connectivity to an online database, and a focus on annotation, including reference to standardized lipid nomenclature as well as common lipid names, supports the view that the Pathway Editor represents a significant, practicable contribution to current pathway modeling tools.
Early over expression of messenger RNA for multiple genes, including insulin, in the Pancreatic Lymph Nodes of NOD mice is associated with Islet Autoimmunity
Authors: Regnault Béatrice , Osorio y Fortea José , Miao Dongmei , Eisenbarth George , Melanitou Evie
Published: October 2009

Background

Autoimmune diabetes (T1D) onset is preceded by a long inflammatory process directed against the insulin-secreting β cells of the pancreas. Deciphering the early autoimmune mechanisms represents a challenge due to the absence of clinical signs at early disease stages. The aim of this study was to identify genes implicated in the early steps of the autoimmune process, prior to inflammation, in T1D. We have previously established that insulin autoantibodies (E-IAA) predict early diabetes onset delineating an early phenotypic check point (window 1) in disease pathogenesis. We used this sub-phenotype and applied differential gene expression analysis in the pancreatic lymph nodes (PLN) of 5 weeks old Non Obese Diabetic (NOD) mice differing solely upon the presence or absence of E-IAA. Analysis of gene expression profiles has the potential to provide a global understanding of the disease and to generate novel hypothesis concerning the initiation of the autoimmune process.

Methods

Animals have been screened weekly for the presence of E-IAA between 3 and 5 weeks of age. E-IAA positive or negative NOD mice at least twice were selected and RNAs isolated from the PLN were used for microarray analysis. Comparison of transcriptional profiles between positive and negative animals and functional annotations of the resulting differentially expressed genes, using software together with manual literature data mining, have been performed.

Results

The expression of 165 genes was modulated between E-IAA positive and negative PLN. In particular, genes coding for insulin and for proteins known to be implicated in tissue remodelling and Th1 immunity have been found to be highly differentially expressed. Forty one genes showed over 5 fold differences between the two sets of samples and 30 code for extracellular proteins. This class of proteins represents potential diagnostic markers and drug targets for T1D.

Conclusion

Our data strongly suggest that the immune related mechanisms taking place at this early age in the PLN, correlate with homeostatic changes influencing tissue integrity of the adjacent pancreatic tissue. Functional analysis of the identified genes suggested that similar mechanisms might be operating during pre-inflammatory processes deployed in tissues i) hosting parasitic microorganisms and ii) experiencing unrestricted invasion by tumour cells.
Plasma cytokine profiles in systemic sclerosis: associations with autoantibody subsets and clinical manifestations
Authors: Gourh Pravitt , Arnett Frank C , Assassi Shervin , Tan Filemon K , Huang Mei , Diekman Laura , Mayes Maureen D , Reveille John D , Agarwal Sandeep K
Published: October 2009

Introduction

Systemic sclerosis (SSc) (scleroderma) is a complex autoimmune disease that clinically manifests as progressive fibrosis of the skin and internal organs. Anti-centromere antibodies (ACAs), anti-topoisomerase antibodies (ATAs), and anti-RNA polymerase III antibodies (ARAs) are three mutually exclusive SSc-associated autoantibodies that correlate with distinct clinical subsets characterized by extent of cutaneous involvement and pattern of organ involvement. The current report sought to determine whether plasma cytokine profiles differ in SSc patients grouped according to these SSc-associated autoantibody subsets.

Methods

Plasma from 444 SSc patients and 216 healthy controls was obtained from the Scleroderma Family Registry and University of Texas Rheumatology Division. Patients were classified according to the presence of ACAs, ATAs, ARAs, or none of the above (antibody-negative). Levels of 13 cytokines were determined using multiplex assays.

Results

Compared with females, healthy control males had higher plasma levels of IL-2 (P = 0.008), IL-5 (P = 0.01) and IL-8 (P = 0.01). In addition, in controls, IL-6 (P = 0.02) and IL-17 (P = 0.01) levels increased with advancing age. After adjusting for age and gender, SSc patients had higher circulating levels of TNFα (P < 0.0001), IL-6 (P < 0.0001), and IFNγ (P = 0.05) and lower IL-17 (P = 0.0005) and IL-23 (P = 0.014). Additional analyses demonstrated that disease duration also influenced these cytokine profiles. IL-6 was elevated in ATA-positive and ARA-positive patients, but not in ACA-positive patients. IL-8 was uniquely increased in the ATA-positive subset while both ATA-positive and ACA-positive subsets had elevated IFNγ and IL-10. IL-5 was only significantly increased in the ACA-positive subset. Lastly, patients with interstitial lung disease had elevated IL-6 and patients with pulmonary hypertension had elevated IL-6 and IL-13.

Conclusions

Plasma cytokine profiles differ in SSc patients based on the presence of SSc-associated autoantibodies. Plasma cytokine profiles in SSc patients may also be affected by disease duration and the pattern of internal organ involvement.
Hypertrophy is induced during the in vitrochondrogenic differentiation of human mesenchymal stem cells by bone morphogenetic protein-2 and bone morphogenetic protein-4 gene transfer
Authors: Steinert Andre F , Proffen Benedikt , Kunz Manuela , Hendrich Christian , Ghivizzani Steven C , Nöth Ulrich , Rethwilm Axel , Eulert Jochen , Evans Christopher H
Published: October 2009

Introduction

The present study compares bone morphogenetic protein (BMP)-4 and BMP-2 gene transfer as agents of chondrogenesis and hypertrophy in human primary mesenchymal stem cells (MSCs) maintained as pellet cultures.

Methods

Adenoviral vectors carrying cDNA encoding human BMP-4 (Ad.BMP-4) were constructed by cre-lox combination and compared to previously generated adenoviral vectors for BMP-2 (Ad.BMP-2), green fluorescent protein (Ad.GFP), or firefly luciferase (Ad.Luc). Cultures of human bone-marrow derived MSCs were infected with 5 × 102 viral particles/cell of Ad.BMP-2, or Ad.BMP-4, seeded into aggregates and cultured for three weeks in a defined, serum-free medium. Untransduced cells or cultures transduced with marker genes served as controls. Expression of BMP-2 and BMP-4 was determined by ELISA, and aggregates were analyzed histologically, immunohistochemically, biochemically and by RT-PCR for chondrogenesis and hypertrophy.

Results

Levels of BMP-2 and BMP-4 in the media were initially 30 to 60 ng/mL and declined thereafter. BMP-4 and BMP-2 genes were equipotent inducers of chondrogenesis in primary MSCs as judged by lacuna formation, strong staining for proteoglycans and collagen type II, increased levels of GAG synthesis, and expression of mRNAs associated with the chondrocyte phenotype. However, BMP-4 modified aggregates showed a lower tendency to progress towards hypertrophy, as judged by expression of alkaline phosphatase, annexin 5, immunohistochemical staining for type X collagen protein, and lacunar size.

Conclusions

BMP-2 and BMP-4 were equally effective in provoking chondrogenesis by primary human MSCs in pellet culture. However, chondrogenesis triggered by BMP-2 and BMP-4 gene transfer showed considerable evidence of hypertrophic differentiation, with, the cells resembling growth plate chondrocytes both morphologically and functionally. This suggests caution when using these candidate genes in cartilage repair.
Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metalloproteinases-1 blood levels as biomarkers of severity and mortality in sepsis
Authors: Lorente Leonardo , Martín María M , Labarta Lorenzo , Díaz César , Solé-Violán Jordi , Blanquer José , Orbe Josune , Rodríguez José A , Jiménez Alejandro , Borreguero-León Juan M , Belmonte Felipe , Medina Juan C , LLimiñana Maria C , Ferrer-Agüero José M , Ferreres José , Mora María L , Lubillo Santiago , Sánchez Manuel , Barrios Ysamar , Sierra Antonio , Páramo José A
Published: October 2009

Introduction

Matrix metalloproteinases (MMPs) play a role in infectious diseases through extracellular matrix (ECM) degradation, which favors the migration of immune cells from the bloodstream to sites of inflammation. Although higher levels of MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) have been found in small series of patients with sepsis, MMP-10 levels have not been studied in this setting. The objective of this study was to determine the predictive value of MMP-9, MMP-10, and TIMP-1 on clinical severity and mortality in a large series of patients with severe sepsis.

Methods

This was a multicenter, observational, and prospective study carried out in six Spanish Intensive Care Units. We included 192 (125 surviving and 67 nonsurviving) patients with severe sepsis and 50 age- and sex-matched healthy controls in the study. Serum levels of MMP-9, MMP-10, TIMP-1, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10 were measured in patients with severe sepsis at the time of diagnosis and in healthy controls.

Results

Sepsis patients had higher levels of MMP-10 and TIMP-1, higher MMP-10/TIMP-1 ratios, and lower MMP-9/TIMP-1 ratios than did healthy controls (P < 0.001). An association was found between MMP-9, MMP-10, TIMP-1, and MMP-9/TIMP-1 ratios and parameters of sepsis severity, assessed by the SOFA score, the APACHE-II score, lactic acid, platelet count, and markers of coagulopathy. Nonsurviving sepsis patients had lower levels of MMP-9 (P = 0.037), higher levels of TIMP-1 (P < 0.001), lower MMP-9/TIMP-1 ratio (P = 0.003), higher levels of IL-10 (P < 0.001), and lower TNF-α/IL-10 ratio than did surviving patients. An association was found between MMP-9, MMP-10, and TIMP-1 levels, and TNF-α and IL-10 levels. The risk of death in sepsis patients with TIMP-1 values greater than 531 ng/ml was 80% higher than that in patients with lower values (RR = 1.80; 95% CI = 1.13 to 2.87;P = 0.01; sensitivity = 0.73; specificity = 0.45).

Conclusions

The novel findings of our study on patients with severe sepsis (to our knowledge, the largest series reporting data about MMP levels in sepsis) are that reduced MMP-9/TIMP-1 ratios and increased MMP-10 levels may be of great pathophysiologic significance in terms of severity and mortality, and that TIMP-1 levels may represent a biomarker to predict the clinical outcome of patients with sepsis.
Oxidative stress can alter the antigenicity of immunodominant peptides
Authors: Weiskopf Daniela , Schwanninger Angelika , Weinberger Birgit , Almanzar Giovanni , Parson Walther , Buus Soren , Lindner Herbert , Grubeck-Loebenstein Beatrix
Published: October 2009

Oxidative modification of the CMVpp65495–503 peptide influences binding to the T-cell receptor and results in lower proliferation and IFNγ production of CMV-specific CD8+ T cells.

APCs operate frequently under oxidative stress induced by aging, tissue damage, pathogens, or inflammatory responses. Phagocytic cells produce peroxides and free-radical species that facilitate pathogen clearance and can in the case of APCs, also lead to oxidative modifications of antigenic proteins and peptides. Little information is available presently about the consequences of such modifications on the immune response. To model oxidative modification of an immunodominant antigenic peptide, we oxidized the methionine residue of the human CMV pp65495–503 (NLVPMVATV) peptide. Such modifications of an antigenic peptide can affect MHC binding or TCR recognition. Using binding and dissociation assays, we demonstrate that oxidative modification of the CMVpp65495–503 peptide leads to a decreased binding of the pMHC complex to the TCR, whereas binding of the peptide to the MHC class I molecule is not impaired. Additionally, we show that CD8+ T cells have a decreased proliferation and IFN-γ production when stimulated with oxidized CMVpp65495–503 peptide. Spectratyping the antigen-binding site of the TCR of responding T cells demonstrates that the CMVpp65495–503 and the CMVoxpp65495–503 peptides preferentially stimulate BV8 T cells. Sequencing of this dominant BV family reveals a highly conserved CDR3 amino acid motif, independent of the mode of stimulation, demonstrating the recruitment of the same T cell clonotypes. Our results suggest that oxidative modification of antigenic peptides may affect T cell responses severely by binding T cell clones with different affinity. This may lead to an altered immune response against infectious agents as well as against tumor or autoantigens under oxidative stress conditions.
Macrophage differentiation of myeloid progenitor cells in response to M-CSF is regulated by the dual-specificity phosphatase DUSP5
Authors: Grasset Marie-France , Gobert-Gosse Stéphanie , Mouchiroud Guy , Bourette Roland P
Published: October 2009

ERK phosphatase DUSP5 is transiently induced by M-CSF and its expression increases proliferation and favors granulocytic versus macrophage differentiation in myeloid progenitor cells lines.

M-CSF regulates the production, survival, and function of monocytes and macrophages. The MAPKs ERK1/2 are key elements for signal integration downstream of the M-CSFR, and their sustained activation is essential for macrophage differentiation. In this study, we sought to isolate genes whose induction by M-CSF is dependent on persistent MAPK activation, thereby being possibly involved in the commitment of myeloid progenitors to macrophage differentiation. Following SSH between cDNA libraries from FD-Fms cells stimulated by M-CSF for 8 h in the presence or the absence of the MEK inhibitor U0126, we isolated DUSP5. DUSP5 expression is induced by M-CSF in various myeloid cells and acts as a specific negative-feedback regulator of ERK1/2. In FD-Fms cells that proliferate and differentiate toward macrophages in response to M-CSF, overexpression of DUSP5 increased M-CSF-dependent proliferation and strongly decreased differentiation. Similarly, overexpression of DUSP5 in the multipotent EGER-Fms cells not only significantly increased M-CSF-induced proliferation and prevented macrophage differentiation but also favored granulocytic differentiation. Altogether, experiments demonstrated that DUSP5 is implicated in M-CSF signaling and suggested that it may influence myeloid cell fate.
MMP-8 promotes polymorphonuclear cell migration through collagen barriers in obliterative bronchiolitis
Authors: Khatwa Umakanth A , Kleibrink Bjoern E , Shapiro Steven D , Subramaniam Meera
Published: October 2009

MMP-8 promotes migration of polymorphonuclear cells through collagen-rich matrices and protection is seen in MMP-8−/− mice in a heterotopic airway transplant model of OB.

Increased levels of MMP-8 (neutrophil collagenase) have been reported in OB, but the biological role of MMP-8 in OB is not known. MMP-8 is an interstitial collagenase highly expressed by polymorphonuclear leukocytes, which are prominent in early OB. Here, we show that MMP-8 promotes migration of PMNs through the collagen-rich matrix in a mouse heterotopic airway transplant model of OB. Overall, MMP-8−/− mice had significantly fewer PMNs in the airway lumen 2 and 14 days post-transplantation, and the percentage of PMNs traversing the matrix to the lumen was decreased markedly in the MMP-8−/− compared with WT mice at 14 days. There were significantly more PMNs outside of the lumen in the ECM in the MMP-8−/− mice compared with WT mice. In vitro, significantly fewer MMP-8−/− PMNs migrated through 3D cross-linked collagen gels than WT PMNs. MMP inhibitor GM6001 was also able to impede migration of WT PMNs through collagen gels. The decreased migration was likely a result of pericollagenase activity of MMP-8, as WT PMNs expressing MMP-8 were not able to migrate effectively through collagen that was resistant to the collagenase. Protection from OB was seen in the MMP-8−/− mice, as the airway lumen had significantly less obliteration and collagen deposition, suggesting that MMP-8 plays an important role in the pathogenesis of OB.
The role of experience in flight behaviour ofDrosophila
Authors: Hesselberg Thomas , Lehmann Fritz-Olaf
Published: October 2009

Experience plays a key role in the acquisition of complex motor skills in running and flight of many vertebrates. To evaluate the significance of previous experience for the efficiency of motor behaviour in an insect, we investigated the flight behaviour of the fruit fly Drosophila. We reared flies in chambers in which the animals could freely walk and extend their wings, but could not gain any flight experience. These naive animals were compared with control flies under both open- and closed-loop tethered flight conditions in a flight simulator as well as in a free-flight arena. The data suggest that the overall flight behaviour in Drosophila seems to be predetermined because both groups exhibited similar mean stroke amplitude and stroke frequency, similar open-loop responses to visual stimulation and the immediate ability to track visual objects under closed-loop feedback conditions. In short free flight bouts, peak saccadic turning rate, angular acceleration, peak horizontal speed and flight altitude were also similar in naive and control flies. However, we found significant changes in other key parameters in naive animals such as a reduction in mean horizontal speed(–23%) and subtle changes in mean turning rate (–48%). Naive flies produced 25% less yaw torque-equivalent stroke amplitudes than the controls in response to a visual stripe rotating in open loop around the tethered animal,potentially suggesting a flight-dependent adaptation of the visuo-motor gain in the control group. This change ceased after the animals experienced visual closed-loop feedback. During closed-loop flight conditions, naive flies had 53% larger differences in left and right stroke amplitude when fixating a visual object, thus steering control was less precise. We discuss two alternative hypotheses to explain our results: the `neuronal experience'hypothesis, suggesting that there are some elements of learning and fine-tuning involved during the first flight experiences in Drosophila and the `muscular exercise' hypothesis. Our experiments support the first hypothesis because maximum locomotor capacity seems not to be significantly impaired in the naive group. Although this study primarily confirms the genetic pre-disposition for flight in Drosophila,previous experience may apparently adjust locomotor fine control and aerial performance, although this effect seems to be small compared with vertebrates.
Cavitation in the embryonic tracheal system ofManduca sexta
Authors: Woods H. Arthur , Sprague Jonathan C. , Smith Jennifer N.
Published: October 2009

Insect tracheae form during embryonic development and initially contain liquid, which impedes transport of oxygen and carbon dioxide. Only later do tracheae fill with gas and come to support high rates of gas flux. This liquid-to-gas transition is poorly understood. Using eggs of the sphingid moth Manduca sexta, we show that longitudinal tracheae in embryos fill with gas in less than 5 s, without invasion of external air, by a process of cavitation. Cavitation requires that tracheal liquids be under tension, and we propose two complementary processes for generating it. One likely, classical mechanism is tracheolar fluid absorption, first proposed by Wigglesworth. Our data support this mechanism in Manduca: after cavitation, liquids are progressively drawn out of finer tracheal branches. The second, previously unknown, mechanism is evaporative water loss across the eggshell, which leads both to declining egg volume and to a larger negative pressure potential of water. The pressure potential helps to drive rapid expansion of small bubbles nucleated near spiracles. Once bubbles are large enough to have displaced liquid across the diameter of a trachea, negative capillary pressure reinforces subsequent expansion of the bubble. Together with predictions from modern cavitation theory, our observations substantiate Wigglesworth's contention that gas filling is promoted by increasing hydrophobicity associated with tanning of the spiracles and major tracheal branches.
Daily and seasonal rhythms in the respiratory sensitivity of red-eared sliders (Trachemys scripta elegans)
Authors: Reyes Catalina , Milsom William K.
Published: October 2009

The purpose of the present study was to determine whether the daily and seasonal changes in ventilation and breathing pattern previously documented in red-eared sliders resulted solely from daily and seasonal oscillations in metabolism or also from changes in chemoreflex sensitivity. Turtles were exposed to natural environmental conditions over a one year period. In each season, oxygen consumption, ventilation and breathing pattern were measured continuously for 24 h while turtles were breathing air and for 24 h while they were breathing a hypoxic–hypercapnic gas mixture (H–H). We found that oxygen consumption was reduced equally during the day and night under H–H in all seasons except spring. Ventilation was stimulated by H–H but the magnitude of the response was always less at night. On average, it was also less in the winter and greater in the reproductive season. The data indicate that the day–night differences in ventilation and breathing pattern seen previously resulted from daily changes in chemoreflex sensitivity whereas the seasonal changes were strictly due to changes in metabolism. Regardless of mechanism, the changes resulted in longer apneas at night and in the winter at any given level of total ventilation,facilitating longer submergence at times of the day and year when turtles are most vulnerable.
Aphid watery saliva counteracts sieve-tube occlusion: a universal phenomenon?
Authors: Will Torsten , Kornemann Sarah R. , Furch Alexandra C. U. , Tjallingii W. Fred , van Bel Aart J. E.
Published: October 2009

Ca2+-binding proteins in the watery saliva of Megoura viciae counteract Ca2+-dependent occlusion of sieve plates in Vicia faba and so prevent the shut-down of food supply in response to stylet penetration. The question arises whether this interaction between aphid saliva and sieve-element proteins is a universal phenomenon as inferred by the coincidence between sieve-tube occlusion and salivation. For this purpose,leaf tips were burnt in a number of plant species from four different families to induce remote sieve-plate occlusion. Resultant sieve-plate occlusion in these plant species was counteracted by an abrupt switch of aphid behaviour. Each of the seven aphid species tested interrupted its feeding behaviour and started secreting watery saliva. The protein composition of watery saliva appeared strikingly different between aphid species with less than 50%overlap. Secretion of watery saliva seems to be a universal means to suppress sieve-plate occlusion, although the protein composition of watery saliva seems to diverge between species.
Characterization of a blood-meal-responsive proton-dependent amino acid transporter in the disease vector, Aedes aegypti
Authors: Evans Amy M. , Aimanova Karlygash G. , Gill Sarjeet S.
Published: October 2009

After anautogenous mosquitoes ingest the required blood meal, proteins in it are rapidly cleaved, yielding a large pool of amino acids. Transport of these amino acids into gut epithelial cells and their subsequent translocation into other tissues is critical for oogenesis and other physiological processes. We have identified a proton amino acid transporter (PAT) in Aedes aegypti (AaePAT1, AAEL007191) which facilitates this transport and is expressed in epithelial cell membranes of larval caecae and the adult midgut. AaePAT1 encodes a 475 amino acid protein showing high similarity to Anopheles gambiae AGAP009896, Culex pipiensCPIJ011438 and Drosophila melanogaster CG7888. When expressed in Xenopus oocytes the transport kinetics showed AaePAT1 is a low affinity transporter with low substrate specificity, having Km and Vmax values of about 7.2 mmol l–1 and 69 pmol oocyte–1min–1, respectively, for glutamine. A number of other amino acids are also transported by this PAT. In female adult midgut, AaePAT1 transcript levels were induced after ingestion of a blood meal.