bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Mena+11a Isoform Serves as a Marker of Epithelial Phenotype and Sensitivity to Epidermal Growth Factor Receptor Inhibition in Human Pancreatic Cancer Cell Lines
Authors: Pino Maria S. , Balsamo Michele , Di Modugno Francesca , Mottolese Marcella , Alessio Massimo , Melucci Elisa , Milella Michele , McConkey David J. , Philippar Ulrike , Gertler Frank B. , Natali Pier Giorgio , Nisticò Paola
Published: August 2008

Purpose: hMena, member of the enabled/vasodilator-stimulated phosphoprotein family, is a cytoskeletal protein that is involved in the regulation of cell motility and adhesion. The aim of this study was to determine whether or not the expression of hMena isoforms correlated with sensitivity to EGFR tyrosine kinase inhibitors and could serve as markers with potential clinical use.

Experimental Design: Human pancreatic ductal adenocarcinoma cell lines were characterized for in vitro sensitivity to erlotinib, expression of HER family receptors, markers of epithelial to mesenchymal transition, and expression of hMena and its isoform hMena+11a. The effects of epidermal growth factor (EGF) and erlotinib on hMena expression as well as the effect of hMena knockdown on cell proliferation were also evaluated.

Results: hMena was detected in all of the pancreatic tumor cell lines tested as well as in the majority of the human tumor samples [primary (92%) and metastatic (86%)]. Intriguingly, in vitro hMena+11a isoform was specifically associated with an epithelial phenotype, EGFR dependency, and sensitivity to erlotinib. In epithelial BxPC3 cells, epidermal growth factor up-regulated hMena/hMena+11a and erlotinib down-regulated expression. hMena knockdown reduced cell proliferation and mitogen-activated protein kinase and AKT activation in BxPC3 cells, and promoted the growth inhibitory effects of erlotinib.

Conclusions: Collectively, our data indicate that the hMena+11a isoform is associated with an epithelial phenotype and identifies EGFR-dependent cell lines that are sensitive to the EGFR inhibitor erlotinib. The availability of anti-hMena+11a–specific probes may offer a new tool in pancreatic cancer management if these results can be verified prospectively in cancer patients.
The Genetics of Castration-Resistant Prostate Cancer: What Can the Germline Tell Us?
Authors: Sharifi Nima , Dahut William L. , Figg William D.
Published: August 2008

Androgen deprivation therapy (ADT) is the cornerstone treatment for advanced prostate cancer. Despite frequent responses, the majority of metastatic tumors will progress to castration-resistant prostate cancer. Numerous molecular and genetic perturbations have been described in castration-resistant prostate cancer, which are attributable for gain-of-function changes in the androgen receptor, allowing for cell survival and proliferation with castrate levels of testosterone. The utility of these somatic perturbations, which are selected for in the tumor after ADT, for prognostication of response and response duration in metastatic prostate cancer, is problematic. Here, we discuss recent studies that describe germline polymorphisms that determine the response to ADT. Coding and noncoding germline polymorphisms in genes involved in the androgen pathway affect the response to ADT. These polymorphisms require further study and validation. However, they have the potential to be useful for prognosticating the response to ADT, designing clinical trials for patients who have poor germline prognostic features and designing novel therapies targeted against genes that influence the response to ADT.
T-Cell Coregulatory Molecule Expression in Urothelial Cell Carcinoma: Clinicopathologic Correlations and Association with Survival
Authors: Boorjian Stephen A. , Sheinin Yuri , Crispen Paul L. , Farmer Sara A. , Lohse Christine M. , Kuntz Susan M. , Leibovich Bradley C. , Kwon Eugene D. , Frank Igor
Published: August 2008

Purpose: Aberrant expression of T-cell coregulatory molecules has been investigated as a mechanism by which certain cancers may evade host immune surveillance. We evaluated expression of the T-cell coregulators B7-H1, B7-H3, and PD-1 in urothelial cell carcinoma (UCC) of the bladder.

Experimental Design: Immunohistochemistry for B7-H1, B7-H3, and PD-1 was done on paraffin-embedded sections from 318 consecutive patients with UCC who underwent radical cystectomy. Expression was correlated with clinicopathologic outcomes and postoperative survival.

Results: B7-H3 was widely expressed in UCC, as 222 of 314 (70.7%) tumors showed positive staining. Expression of B7-H3 in UCC was significantly increased compared with adjacent, nontumor urothelium, as a median of 70% of tumor cells expressed B7-H3, compared with 20% of cells in nontumor specimens (P < 0.001). The increase in B7-H3 expression was independent of tumor stage (P = 0.13). Expression of B7-H1 by UCC tumors (P < 0.001) and PD-1 by tumor-infiltrating lymphocytes (P = 0.012) were significantly associated with increased pathologic stage. Patients who had received intravesical bacillus Calmette-Guerin before cystectomy tended to show increased expression of B7-H3 (P = 0.023) and PD-1 (P = 0.071) but were less likely to express B7-H1 (P = 0.027). Moreover, for the subset of patients with organ-confined disease (n = 167), B7-H1 expression independently predicted all-cause mortality after cystectomy (hazard ratio, 3.18; 95% confidence interval, 1.74-5.79; P < 0.001).

Conclusions: B7-H3 is highly expressed in UCC across tumor stages, whereas B7-H1 and PD-1 expression are associated with advanced disease. B7-H1 expression predicts mortality after cystectomy for patients with organ-confined tumors. These molecules may represent novel diagnostic or prognostic markers, as well as therapeutic targets, for patients with UCC.
Quantitative Analysis of the Transrenal Excretion of Circulating EBV DNA in Nasopharyngeal Carcinoma Patients
Authors: Chan K.C. Allen , Leung Sing F. , Yeung Sze W. , Chan Anthony T.C. , Lo Y.M. Dennis
Published: August 2008

Purpose: The existence of transrenal clearance of circulating cell-free DNA is controversial. In this study, we used NPC as a model to investigate if circulating EBV DNA can be excreted into urine and to quantify the contribution of renal excretion to the clearance of plasma EBV DNA.

Experimental Design: Quantitative analysis of urine EBV DNA was done for 74 NPC patients using real-time PCR with two different amplicon sizes. The urine concentration of EBV DNA was expressed as copies per millimole of creatinine (copies/mmol Cr) to minimize the effects of interindividual variations in hydration status.

Results: EBV DNA was detectable in the urine of 56% NPC patients using a 59-bp real-time PCR assay. The median urine EBV DNA concentrations measured by the 59- and 76-bp assays were 7,040 and 290 copies/mmol Cr, respectively. Patients with detectable urine EBV DNA had significantly higher plasma concentrations, with a positive correlation between the plasma and urine concentrations of EBV DNA. The fraction of plasma EBV DNA excreted into the urine was 0.0026% of that for creatinine.

Conclusions: We have shown that circulating EBV DNA can be excreted transrenally into urine in NPC patient and the fraction of excretion is negatively associated with the size of the DNA molecules. Because there is a positive correlation between plasma and urine EBV DNA concentration, urine EBV DNA analysis may potentially be applicable as an ultra-noninvasive test for the monitoring and prognostication of NPC patients.
Niacin Increases HDL by Reducing Hepatic Expression and Plasma Levels of Cholesteryl Ester Transfer Protein in
APOE*3Leiden.CETP
Mice
Authors: van der Hoorn José W.A. , de Haan Willeke , Berbée Jimmy F.P. , Havekes Louis M. , Jukema J. Wouter , Rensen Patrick C.N. , Princen Hans M.G.
Published: August 2008

Objective—

Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol–increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect.

Methods and Results—

In
APOE*3Leiden
transgenic mice expressing the human CETP transgene, niacin dose-dependently decreased plasma triglycerides (up to −77%,
P
<0.001) and total cholesterol (up to -66%,
P
<0.001). Concomitantly, niacin dose-dependently increased HDL-cholesterol (up to +87%,
P
<0.001), plasma apoAI (up to +72%,
P
<0.001), as well as the HDL particle size. In contrast, in
APOE*3Leiden
mice, not expressing CETP, niacin also decreased total cholesterol and triglycerides but did not increase HDL-cholesterol. In fact, in
APOE*3Leiden.CETP
mice, niacin dose-dependently decreased the hepatic expression of CETP (up to −88%;
P
<0.01) as well as plasma CETP mass (up to −45%,
P
<0.001) and CETP activity (up to −52%,
P
<0.001). Additionally, niacin dose-dependently decreased the clearance of apoAI from plasma and reduced the uptake of apoAI by the kidneys (up to −90%,
P
<0.01).

Conclusion—

Niacin markedly increases HDL-cholesterol in
APOE*3Leiden.CETP
mice by reducing CETP activity, as related to lower hepatic CETP expression and a reduced plasma (V)LDL pool, and increases HDL-apoAI by decreasing the clearance of apoAI from plasma.
The Helix–Loop–Helix Factors Id3 and E47 Are Novel Regulators of Adiponectin
Authors: Doran Amanda C. , Meller Nahum , Cutchins Alexis , Deliri Hamid , Slayton R. Parker , Oldham Stephanie N. , Kim Jae B. , Keller Susanna R. , McNamara Coleen A.
Published: August 2008

Adiponectin is an adipocyte-derived cytokine with beneficial effects on insulin sensitivity and the development of atherosclerosis. Id3 is a helix–loop–helix factor that binds to E-proteins such as E47 and inhibits their binding to DNA. Although the helix–loop–helix factor sterol regulatory element binding protein (SREBP)-1c is a known activator of adiponectin transcription, this study provides the first evidence of a role for Id3 and E47 in adiponectin expression. Decreased Id3 in differentiating adipocytes correlates with increased adiponectin expression and forced expression of Id3 inhibits adiponectin expression. Moreover, Id3-null mice have increased adiponectin expression in visceral fat tissue and in serum. We demonstrate that E47 potentiates SREBP-1c–mediated adiponectin promoter activation and that Id3 can dose-dependently inhibit this action via interaction with E47. Mutation of a consensus E47 binding site results in nearly complete loss of promoter activation. Furthermore, we demonstrate E47 binding to the endogenous adiponectin promoter both in vitro and in vivo by chromatin immunoprecipitation analysis. Binding is not detected in undifferentiated cells which express Id3 but peaks during differentiation in parallel with Id3 decline. This promoter binding can be completely abolished by the overexpression of Id3 and is enhanced in adipose tissue null for Id3. These data establish Id3 and E47 as novel regulators of SREBP-1c–mediated adiponectin expression in differentiating adipocytes and provide evidence that Id3 regulates adiponectin expression in vivo.
RXP-E
Authors: Lewandowski Rebecca , Procida Kristina , Vaidyanathan Ravi , Coombs Wanda , Jalife José , Nielsen Morten S. , Taffet Steven M. , Delmar Mario
Published: August 2008

Gap junctions provide a low-resistance pathway for cardiac electric propagation. The role of GJ regulation in arrhythmia is unclear, partly because of limited availability of pharmacological tools. Recently, we showed that a peptide called “RXP-E” binds to the carboxyl terminal of connexin43 and prevents chemically induced uncoupling in connexin43-expressing N2a cells. Here, pull-down experiments show RXP-E binding to adult cardiac connexin43. Patch-clamp studies revealed that RXP-E prevented heptanol-induced and acidification-induced uncoupling in pairs of neonatal rat ventricular myocytes. Separately, RXP-E was concatenated to a cytoplasmic transduction peptide (CTP) for cytoplasmic translocation (CTP–RXP-E). The effect of RXP-E on action potential propagation was assessed by high-resolution optical mapping in monolayers of neonatal rat ventricular myocytes, containing ≈20% of randomly distributed myofibroblasts. In contrast to control experiments, when heptanol (2 mmol/L) was added to the superfusate of monolayers loaded with CTP–RXP-E, action potential propagation was maintained, albeit at a slower velocity. Similarly, intracellular acidification (pH
i
6.2) caused a loss of action potential propagation in control monolayers; however, propagation was maintained in CTP–RXP-E–treated cells, although at a slower rate. Patch-clamp experiments revealed that RXP-E did not prevent heptanol-induced block of sodium currents, nor did it alter voltage dependence or amplitude of Kir2.1/Kir2.3 currents. RXP-E is the first synthetic molecule known to: (1) bind cardiac connexin43; (2) prevent heptanol and acidification-induced uncoupling of cardiac gap junctions; and (3) preserve action potential propagation among cardiac myocytes. RXP-E can be used to characterize the role of gap junctions in the function of multicellular systems, including the heart.
Use of Ordinal Outcomes in Vascular Prevention Trials
Authors: Bath Philip M.W. , Geeganage Chamila , Gray Laura J. , Collier Timothy , Pocock Stuart
Published: August 2008

Background and Purpose—

Vascular prevention trials mostly count “yes/no” (binary) outcome events, eg, stroke/no stroke. Analysis of ordered categorical vascular events (eg, fatal stroke/nonfatal stroke/no stroke) is clinically relevant and could be more powerful statistically. Although this is not a novel idea in the statistical community, ordinal outcomes have not been applied to stroke prevention trials in the past.

Methods—

Summary data on stroke, myocardial infarction, combined vascular events, and bleeding were obtained by treatment group from published vascular prevention trials. Data were analyzed using 10 statistical approaches which allow comparison of 2 ordinal or binary treatment groups. The results for each statistical test for each trial were then compared using Friedman 2-way analysis of variance with multiple comparison procedures.

Results—

Across 85 trials (335 305 subjects) the test results differed substantially so that approaches which used the ordinal nature of stroke events (fatal/nonfatal/no stroke) were more efficient than those which combined the data to form 2 groups (
P
<0.0001). The most efficient tests were bootstrapping the difference in mean rank, Mann–Whitney
U
test, and ordinal logistic regression; 4- and 5-level data were more efficient still. Similar findings were obtained for myocardial infarction, combined vascular outcomes, and bleeding. The findings were consistent across different types, designs and sizes of trial, and for the different types of intervention.

Conclusions—

When analyzing vascular events from prevention trials, statistical tests which use ordered categorical data are more efficient and are more likely to yield reliable results than binary tests. This approach gives additional information on treatment effects by severity of event and will allow trials to be smaller.
Perfectionism, Depression, Loneliness, and Life Satisfaction
Authors: Wang Kenneth T. , Yuen Mantak , Slaney Robert B.
Published: August 2008

This study investigates the cross-cultural construct validity of perfectionism using the Chinese translation of the Almost Perfect Scale—Revised (APS-R; Slaney, Mobley, Trippi, Ashby, & Johnson, 1996) with 509 Chinese high school students from Hong Kong. The factor structure of the Chinese APS-R and correlations between the APS-R subscales and measures of Depression, Satisfaction with Life, and Loneliness are examined. Participants are grouped into three clusters—adaptive and maladaptive perfectionists and nonperfectionists. A comparison of group means revealed that adaptive perfectionists reported higher Satisfaction with Life scores and lower Depression scores than the other two groups. This sample of Chinese students also reported higher Discrepancy scores compared to U.S. students' scores in previous studies. Similarities and differences in comparison to previous studies using U.S. participants are examined. Finally, the limitations of this study and implications for future research with Chinese participants are discussed.
Mass Media and Governmental Framing of Riots
Authors: Messer Chris M. , Bell Patricia A.
Published: August 2008

This research extends the theoretical concept of framing to the phenomenon of race riots using the Tulsa riot of 1921 as a case study. Media accounts of this riot published during 1921 illustrate both prognostic and diagnostic framing strategies and techniques and demonstrate how these processes affected official responses. Results of this research suggest that framing is a critical process associated with media and organizational representation of riots. Analyses indicate that the riot was officially attributed to an armed group of Black citizens whose goal was to protect one of its community members from a potential lynching. However, Black residents framed the riot differently in statements of their account of the events. A recurrent theme for both races and a number of media reports was that of inept and incompetent law enforcement officials. The authors suggest that prognostic solutions to riots (e.g., police strategies and tactics and reconciliatory attempts) are rooted in diagnostic assessments.
The Misrepresentation of the Black Poor
Authors: King Marvin P.
Published: August 2008

The author examined the effect, if any, of membership in various Black income groups on members’ political power, conceptualized as the ability to elect ideologically preferred representatives to Congress. The findings indicate that large numbers of Black poor actually mitigate quality representation in Congress. This happens despite large concentrations of Black poor into relatively few congressional districts.
Explanatory Pluralism and Complementarity
Authors: Marchionni Caterina
Published: August 2008

Philosophers of the social sciences are increasingly convinced that macro-and micro-explanations are complementary. Whereas macro-explanations are broad, micro-explanations are deep. I distinguish between weak and strong complementarity: Strongly complementary explanations improve one another when integrated, weakly complementary explanations do not. To demonstrate the explanatory autonomy of different levels of explanation, explanatory pluralists mostly presuppose the weak form of complementarity. By scrutinizing the notions of explanatory depth and breadth, I argue that macro- and micro-accounts of the same phenomenon are more often strongly complementary. This invites a revision of the pluralist position in which integration promotes explanatory progress.
Review Essay: A Future for (Analytical) Marxism?
Authors: Veneziani Roberto
Published: August 2008

Andrew Levine analyses the theoretical legacy of recent Marxist schools, focusing in particular on analytical Marxism (AM). He argues that AM is uniquely suited to provide the foundations for a revival of Marxist theory. In this paper, Levine's reconstruction of the core of Marxism and his analysis of the trajectory of AM are critically discussed. Although the theoretical contribution of AM should not be overlooked, some objectionable methodological and theoretical tenets of AM, and in particular of Rational Choice Marxism, are discussed, which may help to explain the demise of the school. Various directions for further research are suggested, which emphasise the importance of structural constraints and endogenous preferences.
Load Dependence of Dynamic Viscoelasticity of Epoxy Resin and its Composites
Authors: Chenghong HE , Zhang Zuoguang  , Li Yubin  , Sun Zhijie
Published: August 2008

The load dependences of dynamic viscoelasticity of casting novolac epoxy 648 and its composites, reinforced by glass fiber (GFRP) or carbon fiber (CFRP), were investigated by dynamic mechanical thermal analysis under high loads. The fiber property and load pattern were considered to analyze the complicated variations in storage modulus and loss tangent with the change of loads. The load effects are comprehensively addressed by a phenomenological theory about suppression effect of static load on the motion of microstructure units, combined with the influence of shear stress and interface properties between fiber and resin.
Investigation of Relaxation Properties and Potentiality of the Thermoformability of HDPE Charged by Wood Flours
Authors: Erchiqui F. , Godard F. , Koubba A. , Vincent M. , Kaddami H.
Published: August 2008

The processability of the composites made up of wood and a matrix of thermoplastic materials was experimentally and numerically investigated for six different proportions of wood flours. To take account of the enclosed gas volume responsible for inflation of the thermoplastic composite membrane, which contributes significantly to the strength and stiffness of a thermoplastic composite structure, we considered a thermodynamical approach to express external work in terms of a closed volume. The pressure load is thus deduced from the thermodynamic law of the Redlich-Kwong real gas. The viscoelastic behavior of the Lodge model is considered. The Lagrangian formulation together with the assumption of the membrane theory is used in the finite element implementation. Moreover, the air flow influence on the inflation of bubble is analyzed for six different proportions of wood flours in the HDPE material.
Role of Type and Amount of Resin on Performance Behavior of Non-asbestos Organic (NAO) Friction Materials
Authors: Dureja N. , Bijwe J. , Gurunath P.V.
Published: August 2008

The role of phenol formaldehyde or phenolic resin as a binder in friction composites assumes paramount significance because the structural integrity of the composites depends on it. The resin properties as well as its content are critical parameters that strongly influence the overall performance of friction composites. In the present paper the influence of alkyl benzene modified phenolic resin on fade and recovery behavior of friction composites is reported and compared with straight phenolic resin. Six non—asbestos friction composites were developed in the laboratory by varying the content of modified resin and unmodified resin viz., 10, 12.5, and 15% by weight compensating this variation by inert filler BaSO4 to keep concentration at 40%. The concentration of other ingredients was kept constant. Compared to unmodified phenolic resin, modified phenolic resin improved the physical and mechanical properties of composites not friction and wear performance. A scanning electron microscope was used to analyze the wear mechanisms.
Flexural, Compressive, and Interlaminar Shear Strength Properties of Kapok/Glass Composites
Authors: Venkata Reddy G. , Shobha Rani T. , Chowdoji Rao K. , Venkata Naidu S.
Published: August 2008

The unsaturated polyester-based hybrid composites were developed by combining the kapok and glass fabrics into polyester matrix. This study describes the flexural, compressive, and interlaminar shear resistance properties of kapok/glass polyester composites with and without alkali treatment of fabrics. These properties increase with increasing glass fabric content in composite. The mechanical performance of kapok/glass composites is excellent. The kapok/glass hybrid composites exhibited higher flexural and compressive values than sisal/glass and kapok/sisal composites.
Effect of Chemical Surface Modifications on the Properties of Woven Banana-Reinforced Unsaturated Polyester Composites
Authors: Jannah M. , Mariatti M. , Abu Bakar A. , Abdul Khalil H.P.S.
Published: August 2008

Chemical surface modifications involving 1% sodium hydroxide (NaOH) and 1% acrylic acid (AA) treatments are applied to woven banana fabric and it is used as reinforcement in an unsaturated polyester matrix. Vacuum bagging technique was used to prepare the woven banana fiber-reinforced unsaturated polyester composites with four different volume percentages of fibers (5, 10, 15, and 20%). The effects of fiber-loading and fiber surface treatments on the flexural, impact and water absorption properties of the composites were investigated. The acrylic acid treatment results in improved mechanical and water absorption properties of the composites compared to the alkali treatment and untreated fiber composites. The treatment effects on the banana fibers have been characterized by means of infrared spectroscopy (FTIR) and microscopy analysis (SEM). The moisture absorption test showed that acrylic acid-treated woven banana fabric composites exhibit less water absorption than both alkali-treated and untreated woven banana fabric composites.
The Effect of Curing Conditions and Fiber End Shapes on the Mechanical Properties of Composites
Authors: Ataş Akin , Arslan Nurettin , Türkbaş Elim , Özdemir Zafer
Published: August 2008

The study consists of two main experimental parts. The aim of the first part of the study is to investigate the effects of the straight-short steel fibers and different curing conditions on the mechanical properties of the selected composite specimens. For this purpose, unreinforced (no fiber) specimens cured at room temperature (∼20°C) and the straight-short steel fiber reinforced polyester—calcite composite specimens cured at room temperature and at different curing conditions of 40, 80, and 120°C for 4, 8, and 12 h, have been subjected to tensile tests. In the second part of the study, unreinforced specimens and polyester—calcite composite specimens with straight-short, woven, and three different end shaped fibers cured at room temperature have been tested according to the four-point bending test procedure so as to obtain the effects of the end shapes on the mechanical properties of the composite specimens.
Fatigue Crack Growth Behavior of Filament Wound Composite Pipes in Corrosive Environment
Authors: Sahin Ömer Sinan , Akdemir Ahmet , Avci Ahmet , Gemi Lokman
Published: August 2008

The stress corrosion crack growth behavior of ±45°, ±55°, and ±75° filament wound composite pipes with surface crack subjected to 0.6 M HCl acid under alternating internal pressure was investigated. E-glass/epoxy pipes consist of six layers with stacking sequences of (+45/-45) 3, (+55/-55)3, and (+75/-75)3. Dilute (0.6M) HCl acid was applied to the surface crack region by a corrosion cell mounted on the outer surface of the pipe. The specimens were tested at room temperature and exposed to open-ended fatigue tests in which the pipes can deform freely in the axial direction. The tests were performed in accordance with the ASTM D-2992 standard. The surface notches with different a/t and a/c forms were cut on the outer surface of the pipe parallel to the pipe axis. The internal pressure was generated by conventional hydraulic oil for fatigue loading. The low cycle tests were applied with 0.42 Hz frequency and R = 0.05 stress ratio. After the corrosion fatigue test, the fracture surfaces were examined and observed damage mechanisms discussed.
One Foot Wet and One Foot Dry
Authors: Klingberg-Allvin Marie , Binh Nguyen , Johansson Annika , Berggren Vanja
Published: August 2008

This study explores married Vietnamese adolescents' perceptions and experiences related to transition into motherhood and their encounter with health care service. In-depth interviews were conducted with 22 women younger than 20 who were either pregnant or had newly delivered. It emerged from the narratives that young women experienced ambivalence in the transition to motherhood in that they felt too young but also happy to be able to please their husband and the extended family. Patterns were shown indicating that the participants experienced lacking power with regard to decisions in relation to pregnancy, delivery, and contraceptive usage. Feelings of being patronized and ignored in the encounter with health care providers were seen in the narratives. Findings might be used for reproductive health care providers, social workers, and educators in their contact with young mothers to empower them to make their own decisions with regard to marriage, childbearing, and contraception.
ADHD Symptomatology and Its Relationship to Factors Associated With College Adjustment
Authors: Norwalk Kate , Norvilitis Jill M. , MacLean Michael G.
Published: August 2008

Objective: The present study assessed the relationship between self-reported ADHD symptomatology in college students and various factors that are associated with persistence in college. Method: A total of 321 students completed questionnaires examining ADHD symptoms, academic and social adjustment to college, career decision-making self-efficacy, study skills, and GPA. Results: Analyses indicated that higher levels of ADHD symptoms were significantly related to lower levels of career decision-making self-efficacy, academic adjustment, study skills, and GPA. Regression analyses revealed that only the inattentive cluster of symptoms was a significant predictor of career decision-making self-efficacy, study skills, and academic adjustment. Conclusion: These results suggest that the inattentive symptoms of ADHD may have a particularly negative effect on success in college. (J. of Att. Dis. 2009; 13(3) 251-258)
The Moral Legitimacy of Anger
Authors: Muldoon Paul
Published: August 2008

This article seeks to contest the frequently repeated assertion that anger poses the greatest threat to transitional societies moving from authoritarianism to democracy. Against suggestions that victims of past injustices should forswear their `negative emotions' lest they spark a renewed cycle of violence, it argues that it is important to recognize the moral legitimacy of their anger. While anger is notoriously (though contestably) vulnerable to excess and needs to be moderated in reference to shared norms of reasonableness, it represents an appropriate response to wilful harm and needs to be afforded a central role in any conception of justice.
Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence
Authors: Lataillade Jean-Jacques , Pierre-Louis Olivier , Hasselbalch Hans Carl , Uzan Georges , Jasmin Claude , Martyré Marie-Claire , Le Bousse-Kerdilès Marie-Caroline
Published: August 2008

Primary myelofibrosis (PMF) is the rarest and the most severe Philadelphia-negative chronic myeloproliferative syndrome. By associating a clonal proliferation and a mobilization of hematopoietic stem cells from bone marrow to spleen with profound alterations of the stroma, PMF is a remarkable model in which deregulation of the stem cell niche is of utmost importance for the disease development. This paper reviews key data suggesting that an imbalance between endosteal and vascular niches participates in the development of clonal stem cell proliferation. Mechanisms by which bone marrow niches are altered with ensuing mobilization and homing of neoplastic hematopoietic stem cells in new or reinitialized niches in the spleen and liver are examined. Differences between signals delivered by both endosteal and vascular niches in the bone marrow and spleen of patients as well as the responsiveness of PMF stem cells to their specific signals are discussed. A proposal for integrating a potential role for the JAK2 mutation in their altered sensitivity is made. A better understanding of the cross talk between stem cells and their niche should imply new therapeutic strategies targeting not only intrinsic defects in stem cell signaling but also regulatory hematopoietic niche–derived signals and, consequently, stem cell proliferation.
Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease
Authors: Barlogie Bart , van Rhee Frits , Shaughnessy John D. , Epstein Joshua , Yaccoby Shmuel , Pineda-Roman Mauricio , Hollmig Klaus , Alsayed Yazan , Hoering Antje , Szymonifka Jackie , Anaissie Elias , Petty Nathan , Kumar Naveen S. , Srivastava Geetika , Jenkins Bonnie , Crowley John , Zeldis Jerome B.
Published: August 2008

Smoldering multiple myeloma (SMM) is usually followed expectantly without therapy. We conducted a phase 2 trial in 76 eligible patients with SMM, combining thalidomide (THAL, 200 mg/d) with monthly pamidronate. In the first 2 years, THAL dose reduction was required in 86% and drug was discontinued in 50%. Within 4 years, 63% improved, including 25% qualifying for partial response (PR); by then, 34 patients had progressed and 17 required salvage therapy. Unexpectedly, attaining PR status was associated with a shorter time to salvage therapy for disease progression (P < .001), perhaps reflecting greater drug sensitivity of more aggressive disease. Low beta-2-microglobulin levels less than 2 mg/L were independently associated with superior overall and event-free survival. Four-year survival and event-free survival estimates of 91% and 60%, respectively, together with a median postsalvage therapy survival of more than 5 years justify the conduct of a prospective randomized clinical trial to determine the clinical value of preemptive therapy in SMM. Trial registered at http://www.clinicaltrials.gov under identifier NCT00083382.
Identification and characterization of novel human tissue-specific RFX transcription factors
Authors: Aftab Syed , Semenec Lucie , Chu Jeffrey Shih-Chieh , Chen Nansheng
Published: August 2008

Background

Five regulatory factor X (RFX) transcription factors (TFs)–RFX1-5–have been previously characterized in the human genome, which have been demonstrated to be critical for development and are associated with an expanding list of serious human disease conditions including major histocompatibility (MHC) class II deficiency and ciliaophathies.

Results

In this study, we have identified two additional RFX genes–RFX6 and RFX7–in the current human genome sequences. Both RFX6 and RFX7 are demonstrated to be winged-helix TFs and have well conserved RFX DNA binding domains (DBDs), which are also found in winged-helix TFs RFX1-5. Phylogenetic analysis suggests that the RFX family in the human genome has undergone at least three gene duplications in evolution and the seven human RFX genes can be clearly categorized into three subgroups: (1) RFX1-3, (2) RFX4 and RFX6, and (3) RFX5 and RFX7. Our functional genomics analysis suggests that RFX6 and RFX7 have distinct expression profiles. RFX6 is expressed almost exclusively in the pancreatic islets, while RFX7 has high ubiquitous expression in nearly all tissues examined, particularly in various brain tissues.

Conclusion

The identification and further characterization of these two novel RFX genes hold promise for gaining critical insight into development and many disease conditions in mammals, potentially leading to identification of disease genes and biomarkers.
Trait correlated expression combined with expression QTL analysis reveals biological pathways and candidate genes affecting water holding capacity of muscle
Authors: Ponsuksili Siriluck , Jonas Elisabeth , Murani Eduard , Phatsara Chirawath , Srikanchai Tiranun , Walz Christina , Schwerin Manfred , Schellander Karl , Wimmers Klaus
Published: August 2008

Background

Leakage of water and ions and soluble proteins from muscle cells occurs during prolonged exercise due to ischemia causing muscle damage. Alsopost mortemanoxia during conversion of muscle to meat is marked by loss of water and soluble components from the muscle cell. There is considerable variation in the water holding capacity of meat affecting economy of meat production. Water holding capacity depends on numerous genetic and environmental factors relevant to structural and biochemical muscle fibre properties a well asanteandpostslaughter metabolic processes.

Results

Expression microarray analysis of M.longissimus dorsiRNAs of 74 F2 animals of a resource population showed 1,279 transcripts with trait correlated expression to water holding capacity. Negatively correlated transcripts were enriched in functional categories and pathways like extracellular matrix receptor interaction and calcium signalling. Transcripts with positive correlation dominantly represented biochemical processes including oxidative phosphorylation, mitochondrial pathways, as well as transporter activity. A linkage analysis of abundance of trait correlated transcripts revealed 897 expression QTL (eQTL) with 104 eQTL coinciding with QTL regions for water holding capacity; 96 transcripts hadtransacting and 8 hadcisacting regulation.

Conclusion

The complex relationships between biological processes taking place in live skeletal muscle and meat quality are driven on the one hand by the energy reserves and their utilisation in the muscle and on the other hand by the muscle structure itself and calcium signalling. Holistic expression profiling was integrated with QTL analysis for the trait of interest and for gene expression levels for creation of a priority list of genes out of the orchestra of genes of biological networks relevant to the liability to develop elevated drip loss.
Mutation study of Spanish patients with Hereditary Hemorrhagic Telangiectasia
Authors: Fontalba Ana , Fernandez-L Africa , García-Alegria Eva , Albiñana Virginia , Garrido-Martin Eva M , Blanco Francisco J , Zarrabeitia Roberto , Perez-Molino Alfonso , Bernabeu-Herrero Maria E , Ojeda Maria-Luisa , Fernandez-Luna Jose L , Bernabeu Carmelo , Botella Luisa M
Published: August 2008

Background

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant and age-dependent vascular disorder characterised mainly by mutations in the Endoglin (ENG) or activin receptor-like kinase-1 (ALK1, ACVRL1) genes.

Methods

Here, we have identified 22 ALK1 mutations and 15 ENG mutations, many of which had not previously been reported, in independent Spanish families afflicted with HHT.

Results

We identified mutations in thirty-seven unrelated families. A detailed analysis of clinical symptoms was recorded for each patient analyzed, with a higher significant presence of pulmonary arteriovenous malformations (PAVM) in HHT1 patients over HHT2. Twenty-two mutations in ALK1 and fifteen in ENG genes were identified. Many of them, almost half, represented new mutations in ALK1 and in ENG. Missense mutations in ENG and ALK1 were localized in a tridimensional protein structure model.

Conclusion

Overall, ALK1 mutations (HHT2) were predominant over ENG mutations (HHT1) in our Spanish population, in agreement with previous data from our country and other Mediterranean countries (France, Italy), but different to Northern Europe or North America. There was a significant increase of PAVM associated with HHT1 over HHT2 in these families.
Influenza vaccination coverage rates in five European countries during season 2006/07 and trends over six consecutive seasons
Authors: Blank Patricia R , Schwenkglenks Matthias , Szucs Thomas D
Published: August 2008

Background

The objectives of the survey were to identify the level of influenza vaccination coverage in five European countries between 2001 and 2007, to understand the drivers and barriers to vaccination, to assess vaccination intentions for the winter 2007/08 as well as major encouraging factors for vaccination.

Methods

Between 2001 and 2007, representative household surveys were performed with telephone or mailed (France) interviews of individuals aged 14 and above. The questionnaire used in the UK, Germany, Italy, France and Spain was essentially the same in all seasons. The data were subsequently pooled. Four target groups were defined for the analysis: 1) persons aged 65 years and over; 2) persons working in the medical field; 3) chronically ill persons and 4) combined target group composed of individuals belonging to one or more of the previous groups 1, 2 or 3.

Results

In 2006/07, vaccination coverage was, 25.0% in UK, 27.4% in Germany, 21.8% in Spain, 24.2% in France and 24.4% in Italy. During six influenza seasons (2001–2007), vaccination coverage showed a slight positive trend in the five countries (p ≤ 0.0001). In the elderly (≥ 65 years), across all countries, no significant trend was seen; the vaccination rate decreased non-significantly from a peak of 64.2% in season 2005/06 to 61.1% in season 2006/07. The most frequent reason for getting vaccinated was a recommendation by the family doctor or nurse (51%), and this was also perceived as the major encouraging factor for vaccination (61%). The main reason for not getting vaccinated was feeling unlikely to catch the flu (36%).

Conclusion

In the UK, Germany and Spain, influenza vaccination coverage rates in season 2006/07 dropped slightly compared to the previous season. However, a trend of increasing vaccination coverage was observed from 2001/02 to 2006/07 across Europe. The family doctor is the major source of encouragement for individuals getting vaccinated. Efforts to overcome the barriers to vaccination need to be put in place to reach the WHO objective of 75% coverage in the elderly by 2010. This is a major challenge to be faced by governments, healthcare workers and healthcare organisations.
HLA-C increases HIV-1 infectivity and is associated with gp120
Authors: Matucci Andrea , Rossolillo Paola , Baroni Miriam , Siccardi Antonio G , Beretta Alberto , Zipeto Donato
Published: August 2008

Background

A recently identified genetic polymorphism located in the 5' region of the HLA-C gene is associated with individual variations in HIV-1 viral load and with differences in HLA-C expression levels. HLA-C has the potential to restrict HIV-1 by presenting epitopes to cytotoxic T cells but it is also a potent inhibitor of NK cells. In addition, HLA-C molecules incorporated within the HIV-1 envelope have been shown to bind to the envelope glycoprotein gp120 and enhance viral infectivity. We investigated this last property in cell fusion assays where the expression of HLA-C was silenced by small interfering RNA sequences. Syncytia formation was analyzed by co-cultivating cell lines expressing HIV-1 gp120/gp41 from different laboratory and primary isolates with target cells expressing different HIV-1 co-receptors. Virus infectivity was analyzed using pseudoviruses. Molecular complexes generated during cell fusion (fusion complexes) were purified and analyzed for their HLA-C content.

Results

HLA-C positive cells co-expressing HIV-1 gp120/gp41 fused more rapidly and produced larger syncytia than HLA-C negative cells. Transient transfection of gp120/gp41 from different primary isolates in HLA-C positive cells resulted in a significant cell fusion increase. Fusion efficiency was reduced in HLA-C silenced cells compared to non-silenced cells when co-cultivated with different target cell lines expressing HIV-1 co-receptors. Similarly, pseudoviruses produced from HLA-C silenced cells were significantly less infectious. HLA-C was co-purified with gp120 from cells before and after fusion and was associated with the fusion complex.

Conclusion

Virionic HLA-C molecules associate to Env and increase the infectivity of both R5 and X4 viruses. Genetic polymorphisms associated to variations in HLA-C expression levels may therefore influence the individual viral set point not only by means of a regulation of the virus-specific immune response but also via a direct effect on the virus replicative capacity. These findings have implications for the understanding of the HIV-1 entry mechanism and of the role of Env conformational modifications induced by virion-associated host proteins.
The Glucagon-Like Peptide-1 Receptor Agonist Oxyntomodulin Enhances β-Cell Function but Does Not Inhibit Gastric Emptying in Mice
Authors: Maida Adriano , Lovshin Julie A. , Baggio Laurie L. , Drucker Daniel J.
Published: August 2008

The proglucagon gene gives rise to multiple peptides that play diverse roles in the control of energy intake, gut motility, and nutrient disposal. Glucagon-like peptide-1 (GLP-1), a 30-amino-acid peptide regulates glucose homeostasis via control of insulin and glucagon secretion and by inhibition of gastric emptying and food intake. Oxyntomodulin (OXM) a 37-amino-acid peptide also derived from the proglucagon gene, binds to both the glucagon and GLP-1 receptor (GLP-1R); however, a separate OXM receptor has not yet been identified. Here we show that OXM, like other GLP-1R agonists, stimulates cAMP formation and lowers blood glucose after both oral and ip glucose administration, actions that require a functional GLP-1R. OXM also directly stimulates insulin secretion from murine islets and INS-1 cells in a glucose- and GLP-1R-dependent manner. Moreover, OXM ameliorates hyperglycemia and significantly reduces apoptosis in murine β-cells after streptozotocin administration and directly reduces apoptosis in thapsigargin-treated INS-1 cells. Unexpectedly, OXM, but not the GLP-1R agonist exendin-4, increased plasma levels of insulin after oral glucose administration. Moreover, OXM administered at doses that potently lower blood glucose had no effect on inhibition of gastric emptying but reduced food intake in WT mice. Taken together, these findings illustrate that although structurally distinct proglucagon-derived peptides such as GLP-1 and OXM engage the GLP-1R, OXM mimics some but not all of the actions of GLP-1R agonists in vivo. These findings may have implications for therapeutic efforts using OXM as a long-acting GLP-1R agonist for the treatment of metabolic disorders.
Amylin-Mediated Restoration of Leptin Responsiveness in Diet-Induced Obesity: Magnitude and Mechanisms
Authors: Trevaskis James L. , Coffey Todd , Cole Rebecca , Lei Chunli , Wittmer Carrie , Walsh Brandon , Weyer Christian , Koda Joy , Baron Alain D. , Parkes David G. , Roth Jonathan D.
Published: August 2008

Previously, we reported that combination treatment with rat amylin (100 μg/kg·d) and murine leptin (500 μg/kg·d) elicited greater inhibition of food intake and greater body weight loss in diet-induced obese rats than predicted by the sum of the monotherapy conditions, a finding consistent with amylin-induced restoration of leptin responsiveness. In the present study, a 3 × 4 factorial design was used to formally test for a synergistic interaction, using lower dose ranges of amylin (0, 10, and 50 μg/kg·d) and leptin (0, 5, 25, and 125 μg/kg·d), on food intake and body weight after 4 wk continuous infusion. Response surface methodology analysis revealed significant synergistic anorexigenic (P < 0.05) and body weight-lowering (P < 0.05) effects of amylin/leptin combination treatment, with up to 15% weight loss at doses considerably lower than previously reported. Pair-feeding (PF) experiments demonstrated that reduction of food intake was the predominant mechanism for amylin/leptin-mediated weight loss. However, fat loss was 2-fold greater in amylin/leptin-treated rats than PF controls. Furthermore, amylin/leptin-mediated weight loss was not accompanied by the counterregulatory decrease in energy expenditure and chronic shift toward carbohydrate (rather than fat) utilization observed with PF. Hepatic gene expression analyses revealed that 28 d treatment with amylin/leptin (but not PF) was associated with reduced expression of genes involved in hepatic lipogenesis (Scd1 and Fasn mRNA) and increased expression of genes involved in lipid utilization (Pck1 mRNA). We conclude that amylin/leptin interact synergistically to reduce body weight and adiposity in diet-induced obese rodents through a number of anorexigenic and metabolic effects.