bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of calcium in constraining egg synthesis in the Audouin’s Gull (Ichthyaetus audouinii)
Authors: Ramirez F. , Garcia-Tarrasón M. , Rami L. , Genovart M. , Jover L. , Sanpera C.
Published: July 2013

Understanding how resources are allocated to form eggs is crucial to our better understanding of avian reproductive strategies. However, little is currently known about how egg synthesis in wild birds might be constrained by the availability of specific micronutrients. Here, we investigated the potential role of calcium (Ca) in constraining egg synthesis in the Audouin’s Gull (Ichthyaetus audouinii (Payraudeau, 1826)). In particular, we evaluated the relationship between plasma Ca levels (mg/dL) in incubating females (as an indicator of the physiological response of females to increased Ca demand associated with clutch production) and several fitness-related egg traits such as egg size (i.e., egg volume), egg shape, and eggshell thickness from three-egg clutches. Egg size was positively related with incubating female plasma Ca levels, with the slope of this relationship being significantly higher for later-laid eggs. The observational nature of this study and reversed timing precludes causal inferences, but observed relationships supported the constraining role of Ca in egg synthesis and suggested that Ca may also have a role in modulating the intraclutch pattern of egg-size variation typical of this gull species.
INVESTIGATIONS OF THE DENSITY DISTRIBUTIONS OF 208Pb WITH THE THOMAS–FERMI METHOD
Authors: GOKBULUT M. , KOC H. , ESER E. , YIGITOGLU I. , MAMEDOV B. A.
Published: July 2013

In this study, the neutron and proton density distributions of 208 Pb nucleus have been analytically calculated by using a new, simple and physically meaningful analytical expression obtained for the Fermi integral which is situated in the nucleon density distributions. The results obtained for 208 Pb have been compared with those of the other theoretical and experimental data and found in good agreement.
BALANCING STRATEGY USING THE PRINCIPLE OF ENERGY CONSERVATION FOR A HOPPING HUMANOID ROBOT
Authors: CHO BAEK-KYU , KIM JUNG-HOON , OH JUN-HO
Published: July 2013

Even though many humanoid robots have been developed and they have locomotion ability, their balancing ability is not sufficient. In the future, humanoid robots will work and act within the human environment. At that time, the humanoid robot will be exposed to various disturbances. This paper proposes a balancing strategy for hopping humanoid robots against various magnitude of disturbance. The proposed balancing strategy for a hopping humanoid robot consists of two controllers, the posture balance controller and the landing position controller. The posture balance controller is used for small disturbances, and its role is to maintain stability by controlling the ankle torque of the robot. On the other hand, if disturbance is large, the landing position controller, which changes the landing position of the swing foot, works with the posture balance controller simultaneously. In this way, the landing position controller reduces large disturbances, and the posture balance controller controls the remaining disturbances. The landing position controller is derived by the principle of energy conservation. An experiment conducted with a real humanoid robot, HUBO2, verifies the proposed method. HUBO2 made a stable and continuous hopping action with the proposed balancing strategy overcoming various disturbances placed in the way of the robot.
A ZONOTOPE-BASED APPROACH FOR MANIPULABILITY STUDY OF REDUNDANT ROBOT LIMBS
Authors: TONDU BERTRAND
Published: July 2013

Kinematic efficiency of robot limbs can be analyzed by means of the manipulability concept defined by Yoshikawa. However, when it is applied to redundant serial chains, that are the most common case in humanoid robotics, Yoshikawa's manipulability measure is not able to take into account the joint velocity range of each robot joint. In order to overcome this difficulty we propose to substitute in the place of the manipulability ellipsoid a manipulability zonotope resulting from the robot Jacobian transform of the joint velocities parallelotope. The proposed manipulability zonotope notion is similar to the well-known manipulability polytope notion, but its associated volume measure can take benefit of the so-called zonotope theory. By means of a famous and powerful theorem about the cubical dissection of any zonotope, an original formula of manipulability measure is proposed from which is also derived a mean manipulability estimate associated to a given joint space working. The proposed tools are applied to a kinematic analysis of a 4R-regional structure model of the upper limb.
Formations and Formalisms: Charles Tilly and the Paradox of the Actor
Authors: Krinsky John , Mische Ann
Published: July 2013

Charles Tilly (1929–2008) was a pioneer in joining sociology and history. Throughout his career, he was especially concerned with the ways in which ordinary people made political claims, and how this was shaped by transformations in the state and in capitalism. Most often seen as a structuralist, Tilly was nevertheless deeply concerned with how to understand actors. This article traces Tilly's work from early research on French contention through his later, synthetic work on mechanisms and regimes to show how Tilly's understanding of actors, agency, culture, and social construction developed. Further, we show how this development went hand in hand with Tilly's development of distinctive methodological approaches to historical and sociological data.
Housing: Commodity versus Right
Authors: Pattillo Mary
Published: July 2013

The study of housing has a long history in sociology, but since the 1960s, it has been relatively hidden in a number of sociological subfields and scattered across a range of disciplines. The financial crisis of 2008 elevated housing issues to the level of national and international debate and protest, and it offers a framework for organizing the scholarship on housing into that which studies housing as a commodity, on one hand, and as a right, on the other. In the former category, I review the literature on mortgage financing; property values and wealth; and affordable rental housing, foreclosures, and evictions. In the latter category, I discuss the theoretical arguments for a right to housing and review the research on activist demands for that right. The tension between these two aspects of housing is discussed throughout. I conclude by proposing the actual home or apartment as a productive area for new sociological analysis.
Migración Internacional y Cambios Familiares en las Comunidades de Origen. Transformaciones y Resistencias
Authors: Arias Patricia
Published: July 2013

Este artículo revisa los hallazgos y discusiones antropológicas y sociológicas de investigaciones recientes en torno a los impactos que puede haber acarreado la migración internacional en las dinámicas familiares de los hogares—campesinos e indígenas—en las comunidades de origen en México. Como uno de los cambios mayores tiene que ver con la intensificación de la migración femenina pero también con la situación de las mujeres que se quedan, el artículo hace hincapié, aunque no únicamente, en la situación de las mujeres desde una perspectiva de género.
Extracellular matrix composition significantly influences pancreatic stellate cell gene expression pattern: role of transgelin in PSC function
Authors: Apte Minoti V. , Yang Lu , Phillips Phoebe A. , Xu Zhihong , Kaplan Warren , Cowley Mark , Pirola Romano C. , Wilson Jeremy S.
Published: July 2013

Activated pancreatic stellate cells (PSCs) are responsible for the fibrotic matrix of chronic pancreatitis and pancreatic cancer. In vitro protocols examining PSC biology have usually involved PSCs cultured on plastic, a nonphysiological surface. However, PSCs cultured on physiological matrices, e.g., Matrigel (normal basement membrane) and collagen (fibrotic pancreas), may have distinctly different behaviors compared with cells cultured on plastic. Therefore, we aimed to 1) compare PSC gene expression after culture on plastic, Matrigel, and collagen I; 2) validate the gene array data for transgelin, the most highly dysregulated gene in PSCs grown on activating vs. nonactivating matrices, at mRNA and protein levels; 3) examine the role of transgelin in PSC function; and 4) assess transgelin expression in human chronic pancreatitis sections. Culture of PSCs on different matrices significantly affected their gene expression pattern. 146, 619, and 432 genes, respectively, were differentially expressed ( P < 0.001) in PSCs cultured on collagen I vs. Matrigel, Matrigel vs. plastic, and collagen I vs. plastic. The highest fold change (12.5-fold upregulation) in gene expression in cells on collagen I vs. Matrigel was observed for transgelin (an actin stress fiber-associated protein). Transgelin was significantly increased in activated PSCs vs. quiescent PSCs. Silencing transgelin expression decreased PSC proliferation and also reduced platelet-derived growth factor-induced PSC migration. Notably, transgelin was highly expressed in chronic pancreatitis in stromal areas and periacinar spaces but was absent in acinar cells. These findings suggest that transgelin is a potentially useful target protein to modulate PSC function so as to ameliorate pancreatic fibrosis.
Reduced thoracic fluid content in early-stage primary biliary cirrhosis that associates with impaired cardiac inotropy
Authors: Zalewski Paweł , Jones David , Lewis Ieuan , Frith James , Newton Julia L.
Published: July 2013

Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by cholestasis. Recent MRI studies have confirmed the presence of cardiac abnormalities in noncirrhotic PBC patients. However, cardiorespiratory consequences of these abnormalities have not been explored. Thoracic fluid content (TFC) is a noninvasive bioelectrical impedance measure of the electrical conductivity of the chest cavity. We explored TFC and its relationship with cardiac contractility parameters in early-stage PBC patients, compared with chronic liver disease and community controls. TFC was measured in early-stage PBC (noncirrhotic; n = 78), nonalcoholic fatty liver disease ( n = 23), and primary sclerosing cholangitis ( n = 18) and in a community control population ( n = 78). Myocardial contractility was measured as index of contractility, acceleration index, cardiac index, stroke index, left ventricular ejection time, and left ventricular work index. We also measured total arterial compliance and the Heather Index (HI; cardiac inotropy). The PBC group had significantly lower TFC compared with controls and the chronic liver disease groups ( P < 0.0001). There was an association between increasing TFC and markers of cardiac function (cardiac index, stroke index, end-diastolic index, index of contractility, and acceleration index), together with indicators of cardiac inotropy and total arterial compliance. Multivariate analysis confirmed that the only parameter that independently associated with TFC was the marker of cardiac inotropy HI ( P = 0.037; β 0.5). This study has confirmed that TFC is reduced in those with PBC, that this is specific to PBC, and that it associates independently with markers of cardiac inotropy.
Normal pulmonary gas exchange efficiency and absence of exercise-induced arterial hypoxemia in adults with bronchopulmonary dysplasia
Authors: Lovering Andrew T. , Laurie Steven S. , Elliott Jonathan E. , Beasley Kara M. , Yang Ximeng , Gust Caitlyn E. , Mangum Tyler S. , Goodman Randall D. , Hawn Jerold A. , Gladstone Igor M.
Published: July 2013

Cardiopulmonary function is reduced in adults born very preterm, but it is unknown if this results in reduced pulmonary gas exchange efficiency during exercise and, consequently, leads to reduced aerobic capacity in subjects with and without bronchopulmonary dysplasia (BPD). We hypothesized that an excessively large alveolar to arterial oxygen difference (AaDO2) and resulting exercise-induced arterial hypoxemia (EIAH) would contribute to reduced aerobic fitness in adults born very preterm with and without BPD. Measurements of pulmonary function, lung volumes and diffusion capacity for carbon monoxide (DLco) were made at rest. Measurements of maximal oxygen consumption, peak workload, temperature- and tonometry-corrected arterial blood gases, and direct measure of hemoglobin saturation with oxygen (SaO2) were made preexercise and during cycle ergometer exercise in ex-preterm subjects ≤32-wk gestational age, with BPD ( n = 12), without BPD (PRE; n = 12), and full term controls (CONT; n = 12) breathing room air. Both BPD and PRE had reduced pulmonary function and reduced DLco compared with CONT. The AaDO2 was not significantly different between groups, and there was no evidence of EIAH (SaO2 < 95% and/or AaDO2 ≥ 40 Torr) in any subject group preexercise or at any workload. Arterial O2 content was not significantly different between the groups preexercise or during exercise. However, peak power output was decreased in BPD and PRE subjects compared with CONT. We conclude that EIAH in adult subjects born very preterm with and without BPD does not likely contribute to the reduction in aerobic exercise capacity observed in these subjects.
Diminished leptin signaling can alter circadian rhythm of metabolic activity and feeding
Authors: Hsuchou Hung , Wang Yuping , Cornelissen-Guillaume Germaine G. , Kastin Abba J. , Jang Eunjin , Halberg Franz , Pan Weihong
Published: July 2013

Leptin, a hormone mainly produced by fat cells, shows cell-specific effects to regulate feeding and metabolic activities. We propose that an important feature of metabolic dysregulation resulting in obesity is the loss of the circadian rhythm of biopotentials. This was tested in the pan-leptin receptor knockout (POKO) mice newly generated in our laboratory. In the POKO mice, leptin no longer induced pSTAT-3 signaling after intracerebroventricular injection. Three basic phenotypes were observed: the heterozygotes had similar weight and adiposity as the wild-type (WT) mice (>60% of the mice); the homozygotes were either fatter (∼30%), or rarely leaner (<5%) than the WT mice. By early adulthood, the POKO mice had higher average body weight and adiposity than their respective same-sex WT littermate controls, and this was consistent among different batches. The homozygote fat POKO showed significant reduction of midline estimating statistic of rhythm of circadian parameters, and shifts of ultradian rhythms. The blunted circadian rhythm of these extremely obese POKO mice was also seen in their physical inactivity, longer feeding bouts, and higher food intake. The extent of obesity correlated with the blunted circadian amplitude, accumulative metabolic and locomotor activities, and the severity of hyperphagia. This contrasts with the heterozygote POKO mice which showed little obesity and metabolic disturbance, and only subtle changes of the circadian rhythm of metabolic activity without alterations in feeding behavior. The results provide a novel aspect of leptin resistance, almost manifesting as an “all or none” phenomenon.
Reg3β Deficiency Impairs Pancreatic Tumor Growth by Skewing Macrophage Polarization
Authors: Gironella Meritxell , Calvo Carlos , Fernández Anna , Closa Daniel , Iovanna Juan L. , Rosello-Catafau Joan , Folch-Puy Emma
Published: July 2013

The lectin Reg3β provides crucial protection to various tissues against inflammation, a potential risk factor for pancreatic ductal adenocarcinoma. Reg3β is also overexpressed in serum and pancreatic juice from patients with this cancer, but its function in this context remains to be elucidated. In this study, we investigated the role of Reg3β in tumor development in an orthotopic mouse model of pancreatic cancer. Reg3β deletion in mice drastically impaired pancreatic tumor growth, correlating with decreased angiogenesis and increased apoptosis of tumor cells. Moreover, Reg3β deficiency resulted in an alteration of the tumoral immune microenvironment, reflected by a decrease in the M2/M1 ratio of tumor-associated macrophages and an upregulation of CD3+ cell infiltration. Addition of Reg3β to prestimulated RAW 264.7 or primary macrophages enhanced M2 polarization through the activation of STAT3 signaling pathway. Conditioned media from Reg3β-M2-polarized primary macrophages inhibited apoptosis and prolonged the viability of Panc02 tumor cells. Our studies reveal a novel role for Reg3β as a tumor promoter in pancreatic adenocarcinoma through the regulation of tumor stroma. Thus, inhibition of this protein may be a useful strategy in treatment of pancreatic cancer. Cancer Res; 73(18); 5682–94. ©2013 AACR.
Mammary Tumor Formation and Metastasis Evoked by a HER2 Splice Variant
Authors: Alajati Abdullah , Sausgruber Nina , Aceto Nicola , Duss Stephan , Sarret Sophie , Voshol Hans , Bonenfant Debora , Bentires-Alj Mohamed
Published: July 2013

The HER2 gene is amplified and overexpressed in approximately 20% of invasive breast cancers where it is associated with metastasis and poor prognosis. Here, we describe a constitutively active splice variant of HER2 (Delta-HER2) in human mammary epithelial cells that evokes aggressive breast cancer phenotypes. Delta-HER2 overexpression in mammary epithelial cells was sufficient to reduce apoptosis, increase proliferation, and induce expression of mesenchymal markers, features that were associated with greater invasive potential in three-dimensional cultures in vitro and more aggressive tumorigenicity and metastasis in vivo. In contrast, overexpression of wild-type HER2 was insufficient at evoking such effects. Unbiased protein–tyrosine phosphorylation profiling in Delta-HER2–expressing cells revealed increased phosphorylation of several signaling proteins not previously known to be controlled by the HER2 pathway. Furthermore, microarray expression analysis revealed activation of genes known to be highly expressed in ER-negative, high-grade, and metastatic primary breast tumors. Together, our results provide mechanistic insights into the activity of a highly pathogenic splice variant of HER2. Cancer Res; 73(17); 5320–7. ©2013 AACR.
SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma
Authors: Bareiss Petra M. , Paczulla Anna , Wang Hui , Schairer Rebekka , Wiehr Stefan , Kohlhofer Ursula , Rothfuss Oliver C. , Fischer Anna , Perner Sven , Staebler Annette , Wallwiener Diethelm , Fend Falko , Fehm Tanja , Pichler Bernd , Kanz Lothar , Quintanilla-Martinez Leticia , Schulze-Osthoff Klaus , Essmann Frank , Lengerke Claudia
Published: July 2013

The SRY-related HMG-box family of transcription factors member SOX2 regulates stemness and pluripotency in embryonic stem cells and plays important roles during early embryogenesis. More recently, SOX2 expression was documented in several tumor types including ovarian carcinoma, suggesting an involvement of SOX2 in regulation of cancer stem cells (CSC). Intriguingly, however, studies exploring the predictive value of SOX2 protein expression with respect to histopathologic and clinical parameters report contradictory results in individual tumors, indicating that SOX2 may play tumor-specific roles. In this report, we analyze the functional relevance of SOX2 expression in human ovarian carcinoma. We report that in human serous ovarian carcinoma (SOC) cells, SOX2 expression increases the expression of CSC markers, the potential to form tumor spheres, and the in vivo tumor-initiating capacity, while leaving cellular proliferation unaltered. Moreover, SOX2-expressing cells display enhanced apoptosis resistance in response to conventional chemotherapies and TRAIL. Hence, our data show that SOX2 associates with stem cell state in ovarian carcinoma and induction of SOX2 imposes CSC properties on SOC cells. We propose the existence of SOX2-expressing ovarian CSCs as a mechanism of tumor aggressiveness and therapy resistance in human SOC. Cancer Res; 73(17); 5544–55. ©2013 AACR.
Tumor Microenvironmental Conversion of Natural Killer Cells into Myeloid-Derived Suppressor Cells
Authors: Park Young-Jun , Song Boyeong , Kim Yun-Sun , Kim Eun-Kyung , Lee Jung-Mi , Lee Ga-Eun , Kim Jae-Ouk , Kim Yeon-Jeong , Chang Woo-Sung , Kang Chang-Yuil
Published: July 2013

How myeloid-derived suppressor cells (MDSC) emerge in the tumor environment remains unclear. Here, we report that GM-CSF can convert natural killer (NK) cells into MDSCs. When transferred into tumor-bearing mice, adoptively transferred NK cells lost their NK phenotype and were converted into Ly6ChighLy6Ghigh MDSC. This conversion was abolished by exposure to IL-2 either in vitro or in vivo. Notably, we found that of the 4 maturation stages based on CD11b/CD27 expression levels, only the CD11bhighCD27high NK cells could be converted into CD11b+Gr1+ MDSC ex vivo. Transfer of CD27high NK cells from tumor-bearing mice into tumor-bearing recipients was associated with conversion to MDSC in a manner associated with reduced numbers of CD11bhighCD27high and CD11bhighCD27low NK cell populations in the recipients. Our results identify a pathway of MDSC development from immature NK cells in tumor-bearing hosts, providing new insights into how tumor cells modulate their host immune microenvironment to escape immune surveillance. Cancer Res; 73(18); 5669–81. ©2013 AACR.
MUC1 Is a Potential Target for the Treatment of Acute Myeloid Leukemia Stem Cells
Authors: Stroopinsky Dina , Rosenblatt Jacalyn , Ito Keisuke , Mills Heidi , Yin Li , Rajabi Hasan , Vasir Baldev , Kufe Turner , Luptakova Katarina , Arnason Jon , Nardella Caterina , Levine James D. , Joyce Robin M. , Galinsky Ilene , Reiter Yoram , Stone Richard M. , Pandolfi Pier Paolo , Kufe Donald , Avigan David
Published: July 2013

Acute myeloid leukemia (AML) is a malignancy of stem cells with an unlimited capacity for self-renewal. MUC1 is a secreted, oncogenic mucin that is expressed aberrantly in AML blasts, but its potential uses to target AML stem cells have not been explored. Here, we report that MUC1 is highly expressed on AML CD34+/lineage−/CD38− cells as compared with their normal stem cell counterparts. MUC1 expression was not restricted to AML CD34+ populations as similar results were obtained with leukemic cells from patients with CD34− disease. Engraftment of AML stem cell populations that highly express MUC1 (MUC1high) led to development of leukemia in NOD-SCID IL2Rgammanull (NSG) immunodeficient mice. In contrast, MUC1low cell populations established normal hematopoiesis in the NSG model. Functional blockade of the oncogenic MUC1-C subunit with the peptide inhibitor GO-203 depleted established AML in vivo, but did not affect engraftment of normal hematopoietic cells. Our results establish that MUC1 is highly expressed in AML stem cells and they define the MUC1-C subunit as a valid target for their therapeutic eradication. Cancer Res; 73(17); 5569–79. ©2013 AACR.
The Cumulative Risk of False-Positive Fecal Occult Blood Test after 10 Years of Colorectal Cancer Screening
Authors: Hubbard Rebecca A. , Johnson Eric , Hsia Raymond , Rutter Carolyn M.
Published: July 2013

Background: Annual colorectal cancer screening with fecal occult blood test (FOBT) is a noninvasive alternative to screening colonoscopy once every 10 years. If false-positive FOBT results are common, then many patients selecting an FOBT regimen will be exposed to the same invasive testing as those selecting a colonoscopy regimen. The objective of this study was to estimate the probability of experiencing a false-positive after receiving annual FOBT screening for 10 years.

Methods: Medical records for patients aged 50 to 79 years receiving FOBT screening with Hemoccult Sensa between 1997 and 2009 at Group Health of Washington State captured the date and results of each FOBT, along with subsequent colorectal cancer diagnoses. We used logistic regression to analyze associations between patient characteristics and odds of a positive FOBT with no invasive cancer diagnosis within 1 year (FOBT+, CRC−). We estimated the probability of receiving at least one FOBT+, CRC− result after 10 years of screening.

Results: We observed 181,950 FOBTs from 94,637 individuals. Older patients, males, and non-White patients were significantly more likely to receive FOBT+, CRC− results (P < 0.001 for all risk factors). After 10 years of annual FOBT, 23.0% [95% confidence interval (CI), 18.2–27.0] will receive at least one FOBT+, CRC− result.

Conclusions: Most patients participating in annual FOBT screening for 10 years will not have a positive result, reinforcing the potential value of this regimen as a noninvasive alternative to colonoscopy.

Impact: Annual stool-based screening is a screening alternative resulting in substantially fewer colonoscopies than once per decade colonoscopy. Cancer Epidemiol Biomarkers Prev; 22(9); 1612–9. ©2013 AACR.
Molecular Pathways: Coexpression of Immune Checkpoint Molecules: Signaling Pathways and Implications for Cancer Immunotherapy
Authors: Nirschl Christopher J. , Drake Charles G.
Published: July 2013

The expression of immune checkpoint molecules on T cells represents an important mechanism that the immune system uses to regulate responses to self-proteins. Checkpoint molecules include cytotoxic T lymphocyte antigen-4, programmed death-1, lymphocyte activation gene-3, T-cell immunoglobulin and mucin protein-3, and several others. Previous studies have identified individual roles for each of these molecules, but more recent data show that coexpression of checkpoint molecules occurs frequently on cancer-specific T cells as well as on pathogen-specific T cells in chronic infections. As the signaling pathways associated with each checkpoint molecule have not been fully elucidated, blocking multiple checkpoints with specific monoclonal antibodies results in improved outcomes in several chronic viral infections as well as in a wide array of preclinical models of cancer. Recent clinical data suggest similar effects in patients with metastatic melanoma. These findings support the concept that individual immune checkpoint molecules may function through nonoverlapping molecular mechanisms. Here, we review current data regarding immune checkpoint molecule signaling and coexpression, both in cancer and infectious disease, as well as the results of preclinical and clinical manipulations of checkpoint proteins. Clin Cancer Res; 19(18); 4917–24. ©2013 AACR.
Interleukin-6 and Oncostatin-M Synergize with the PI3K/AKT Pathway to Promote Aggressive Prostate Malignancy in Mouse and Human Tissues
Authors: Smith Daniel A. , Kiba Atsushi , Zong Yang , Witte Owen N.
Published: July 2013

Chronic inflammation has been proposed as an etiological and progression factor in prostate cancer. In this study, we used a dissociated prostate tissue recombination system to interrogate the role of interleukin 6 (IL6) and the related cytokine oncostatin-M (OSM) in the initiation and progression of prostate cancer. We identified that prostatic intraepithelial neoplasia (PIN) lesions induced by PTEN loss of function (PTENLOF) progress to invasive adenocarcinoma following paracrine expression of either cytokine. Increased expression of OSM was also able to drive progression of benign human epithelium when combined with constitutively activated AKT. Malignant progression in the mouse was associated with invasion into the surrounding mesenchyme and increased activation of STAT3 in PTENLOF grafts expressing IL6 or OSM. Collectively, our work indicates that pro-inflammatory cytokines such as IL6 or OSM could activate pathways associated with prostate cancer progression and synergize with cell-autonomous oncogenic events to promote aggressive malignancy.

Implications: Increased expression of IL6 or OSM synergizes with loss of PTEN to promote invasive prostate cancer.

Visual Overview: http://mcr.aacrjournals.org/content/early/2013/09/02/1541-7786.MCR-13-0238/F1.large.jpg. Mol Cancer Res; 11(10); 1159–65. ©2013 AACR.
Inflammatory Mediators Alter Interleukin-17 Receptor, Interleukin-12 and -23 Expression in Human Osteoarthritic and Rheumatoid Arthritis Synovial Fibroblasts: Immunomodulation by Vasoactive Intestinal Peptide
Authors: Carrión Mar , Pérez-García Selene , Jimeno Rebeca , Juarranz Yasmina , González-Álvaro Isidoro , Pablos José Luis , Gutiérrez-Cañas Irene , Gomariz Rosa P.
Published: July 2013

Aims: To assess the contribution of fibroblast-like synoviocytes (FLS) to the inflammatory joint microenvironment under different pathogenic stimuli and their potential to respond to interleukin (IL)-17 and to determine whether the neuroimmunomodulatory vasoactive intestinal peptide (VIP) is able to modulate IL-17 receptor (IL-17R) and related cytokines. Methods: The effect of proinflammatory cytokines [tumor necrosis factor α (TNFα) and IL-17] and Toll-like receptor (TLR) ligands [poly(I:C) and lipopolysaccharide (LPS)] on IL-17R expression and IL-12 and IL-23 production was studied in osteoarthritis (OA)- and rheumatoid arthritis (RA)-FLS, involved in Th1/Th17 differentiation. The effect of VIP was also determined. IL-17RA, IL-17RC, IL-12p35 and IL-23p19 expression was measured by real-time polymerase chain reaction. IL-12 and IL-23 protein levels were measured by ELISA in supernatant cultures. Results: TNFα, LPS and poly(I:C) induced an increase in IL-17RA in RA-FLS, whereas TNFα, TNFα plus IL-17 and poly(I:C) enhanced IL-17RC transcripts in FLS. VIP diminished the upregulated expression of IL-17RA in RA-FLS following TNFα and poly(I:C). TNFα, LPS and poly(I:C) increased IL-12 and IL-23 levels in cells derived from patients presenting both pathologies. However, IL-17A decreased IL-12 and augmented IL-23. VIP decreased IL-12p35 mRNA upregulation by poly(I:C) and IL-23p19 transcripts in LPS-treated FLS. Conclusions: Inflammatory cytokines and TLR ligands modulate IL-17R, IL-12 and IL-23 possibly favoring the cross talk between FLS and Th1/Th17 cells. The ability of VIP to counteract the enhancing effect of proinflammatory molecules on IL-17R and the IL-12 family of cytokines corroborates and amplifies the beneficial effect of this endogenous neuroimmunopeptide in rheumatic diseases.
Outcomes of Secondary Self-Expandable Metal Stents versus Surgery after Delayed Initial Palliative Stent Failure in Malignant Colorectal Obstruction
Authors: Yoon Jin Young , Park Soo Jung , Hong Sung Pil , Kim Tae Il , Kim Won Ho , Cheon Jae Hee
Published: July 2013

Background/Aims: When re-intervention is required due to an occluded first colorectal self-expanding metal stent for malignant colorectal obstruction, serious controversies exist regarding whether to use endoscopic re-stenting or surgery. To compare the clinical outcomes in patients who underwent stent re-insertion versus palliative surgery as a second intervention. Methods: A total of 115 patients who received either self-expandable metal stent (SEMS) insertion or palliative surgery for treatment of a second occurrence of malignant colorectal obstruction after the first SEMS placement were retrospectively studied between July 2005 and December 2009. Results: The median overall survival (8.2 vs. 15.5 months) and progression-free survival (4.0 vs. 2.7 months) were not significantly different between the stent and surgery groups (p = 0.895 and 0.650, respectively). The median lumen patency in the stent group was 3.4 months and that in the surgery group was 7.9 months (p = 0.003). The immediate complication rate after second stent insertion was 13.9% and late complication rate was observed in 12 of 79 (15.2%) patients. There was no mortality related to the SEMS procedure. The complication and mortality rates associated with palliative surgery were 3.5% (2/57) and 12.3% (7/57), respectively. Conclusions: Although there is no significant difference in the overall survival between stenting and surgery, a secondary stent insertion had a lower mortality rate despite a shorter duration of temporary colorectal decompression compared to that of palliative surgery.
Using Temporal Modulation Sensitivity to Select Stimulation Sites for Processor MAPs in Cochlear Implant Listeners
Authors: Garadat Soha N. , Zwolan Teresa A. , Pfingst Bryan E.
Published: July 2013

Previous studies in our laboratory showed that temporal acuity as assessed by modulation detection thresholds (MDTs) varied across activation sites and that this site-to-site variability was subject specific. Using two 10-channel MAPs, the previous experiments showed that processor MAPs that had better across-site mean (ASM) MDTs yielded better speech recognition than MAPs with poorer ASM MDTs tested in the same subject. The current study extends our earlier work on developing more optimal-fitting strategies to test the feasibility of using a site-selection approach in the clinical domain. This study examined the hypothesis that revising the clinical speech processor MAP for cochlear implant (CI) recipients by turning off selected sites that have poorer temporal acuity and reallocating frequencies to the remaining electrodes would lead to improved speech recognition. Twelve CI recipients participated in the experiments. We found that site selection procedure based on MDTs in the presence of a masker resulted in improved performance on consonant recognition and recognition of sentences in noise. In contrast, vowel recognition was poorer with the experimental MAP than with the clinical MAP, possibly due to reduced spectral resolution when sites were removed from the experimental MAP. Overall, these results suggest a promising path for improving recipient outcomes using personalized processor-fitting strategies based on a psychophysical measure of temporal acuity.
New-Generation Multifocal Intraocular Lens for Pediatric Cataract
Authors: Abouzeid Hana , Moetteli Leila , Munier Francis L.
Published: July 2013

Background/Aims: To evaluate multifocal intraocular lens (MIOL) implantation in children. Methods: This is a retrospective study evaluating refractive, visual and safety results of MIOL in pediatric cataract surgery. Average follow-up was 25.73 ± 10.5 months. Surgery included 12 o'clock clear corneal incision, anterior capsulorhexis, lens material aspiration and MIOL implantation (SN6AD3; Alcon). Results: We included 34 cataract eyes of 26 pediatric patients aged 2-15 years, of which 14 (54%) were unilateral. Best near visual acuity (BNVA) and best distance visual acuity (BDVA) improved significantly in 100% of eyes (p = 0.0001). BDVA was above 0.8 in 31.25% (5/16) of bilateral cases. Significant stereopsis improvement was observed postoperatively in bilateral cases only (p = 0.01). Conclusion: MIOL implantation is a safe alternative to monofocal pseudophakia for pediatric cataract with a very low complication rate. Significant BNVA, BDVA and stereopsis improvement can be achieved, particularly in bilateral cases. Message: This study shows significant BDVA, BNVA and stereopsis improvement, especially in bilateral cases, after MIOL implantation for pediatric cataracts.
Both Hair Cortisol Levels and Perceived Stress Predict Increased Symptoms of Depression: An Exploratory Study in Young Adults
Authors: Gerber Markus , Kalak Nadeem , Elliot Catherine , Holsboer-Trachsler Edith , Pühse Uwe , Brand Serge
Published: July 2013

Objective: Depressive symptoms are a common mental health problem among young adults, but the physiological mechanisms that mediate between stress and depressive symptoms remain unclear. Accordingly, this exploratory study (1) examined how hair cortisol concentrations were associated with self-perceived stress and depressive symptoms in a sample of young adults and (2) tested whether hair cortisol could explain variance in depressive symptoms beyond perceived stress before and after controlling for levels of vigorous physical activity (VPA). Methods: The sample consisted of 42 exercise and health science university students (20 males, 22 females; mean age = 21.2 years). Cortisol concentrations were extracted from hair strands close to the scalp. Participants completed self-rating questionnaires about depressive symptoms and perceived stress. Results: Students with elevated hair cortisol levels tended to report lower depressive symptoms and lower perceived stress. Increased perceived stress was associated with higher depressive symptoms, and both hair cortisol and perceived stress predicted depressive symptoms after controlling for VPA. Conclusions: The present data suggest that elevated hair cortisol levels do not necessarily constitute a health risk. Hair cortisol measurement can serve as a noninvasive and painless biomarker of chronic stress and mental disorders; however, additional research is needed.
Impulsiveness in Patients with Bulimia Nervosa: Electrophysiological Evidence of Reduced Inhibitory Control
Authors: Merlotti Eleonora , Mucci Armida , Volpe Umberto , Montefusco Valentina , Monteleone Palmiero , Bucci Paola , Galderisi Silvana
Published: July 2013

Objectives: Bulimia nervosa (BN) is associated with a deficit of self-regulatory control and impulsivity. The present study aimed to clarify whether an impaired inhibitory control due to hyperarousal underlies impulsivity in BN subjects. Methods: Event-related potentials (ERPs) were recorded in 17 female patients with BN and 17 healthy controls during a three-tone oddball task. ERP components related to inhibition of irrelevant distractor stimuli, as well as effortful processing, were analyzed. Standardized low-resolution electromagnetic tomography (sLORETA) was used to assess ERP source activity. Results: Compared to healthy controls, BN patients showed reduced amplitude and shorter latency of the N200 (N2), increased amplitude and shorter latency of the target slow wave (SW), and higher amplitude of the P300 for distractor stimuli (P3a) and for targets (P3b). sLORETA showed the following: (1) higher activity of the P3a generators in the left parietal cortex, bilateral precuneus and right frontal and anterior cingulate for distractor stimuli and (2) lower activity of the SW generators in the left medial frontal gyrus, bilateral superior frontal, anterior cingulate and cuneus for target stimuli. The reduction of the N2 latency was associated with the Barratt scores for impulsiveness. Conclusions: The observed electrophysiological abnormalities suggest a condition of hyperarousal, with impaired suppression of irrelevant stimuli due to abnormal cortical activation and reduced signal-to-noise ratio. Our findings point to functional abnormalities within a neural system that subserves attention and self-regulatory control, which may contribute to impulsive behaviors in BN.
Analysis of Risk Factors and Survival in Pediatric High-Grade Spinal Cord Astrocytoma: A Population-Based Study
Authors: Lam Sandi , Lin Yimo , Melkonian Stephanie
Published: July 2013

Background/Aims: Primary pediatric high-grade spinal cord astrocytomas are rare neoplasms with poor prognoses. Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed prognostic factors and survival. Methods: Pediatric patients with histologically confirmed diagnoses of primary high-grade spinal cord astrocytoma (WHO grade III-IV) from 1973 to 2008 in the SEER database were studied. Univariate and multivariate Cox proportional hazards models were used to analyze the relationship between demographic, tumor grade, and treatment factors on survival. Results: Median survival in the 48 patient cohort was 10 months. Increasing age and higher tumor grade were found to be significantly associated with higher mortality. For children aged <7, 7-12, and 13-18 years, median survival was 22, 11, and 8 months, respectively. For children with anaplastic astrocytoma (WHO grade III), median survival was 12 months, compared with 7 months for those with glioblastoma multiforme (WHO grade IV). This study did not find a statistically significant relationship between sex, race, presence of radiation therapy or extent of surgical resection and mortality. Conclusion: Survival in primary pediatric high-grade spinal cord astrocytomas was positively associated with younger age and lower tumor grade. Survival was not associated with other demographic or treatment modality factors.
Seeing the Wood through the Trees: The Current State of Higher Systematics in the Strepsirhini
Authors: Masters J.C. , Silvestro D. , Génin F. , DelPero M.
Published: July 2013

Strepsirhines comprise 10 living or recently extinct families, ≥50% of extant primate families. Their phylogenetic relationships have been intensively studied, but common topologies have only recently emerged; e.g. all recent reconstructions link the Lepilemuridae and Cheirogaleidae. The position of the indriids, however, remains uncertain, and molecular studies have placed them as the sister to every clade except Daubentonia, the preferred sister group of morphologists. The node subtending Afro-Asian lorisids has been similarly elusive. We probed these phylogenetic inconsistencies using a test data set including 20 strepsirhine taxa and 2 outgroups represented by 3,543 mtDNA base pairs, and 43 selected morphological characters, subjecting the data to maximum parsimony, maximum likelihood and Bayesian inference analyses, and reconstructing topology and node ages jointly from the molecular data using relaxed molecular clock analyses. Our permutations yielded compatible but not identical evolutionary histories, and currently popular techniques seem unable to deal adequately with morphological data. We investigated the influence of morphological characters on tree topologies, and examined the effect of taxon sampling in two experiments: (1) we removed the molecular data only for 5 endangered Malagasy taxa to simulate ‘extinction leaving a fossil record'; (2) we removed both the sequence and morphological data for these taxa. Topologies were affected more by the inclusion of morphological data only, indicating that palaeontological studies that involve inserting a partial morphological data set into a combined data matrix of extant species should be interpreted with caution. The gap of approximately 10 million years between the daubentoniid divergence and those of the other Malagasy families deserves more study. The apparently contemporaneous divergence of African and non-daubentoniid Malagasy families 40-30 million years ago may be related to regional plume-induced uplift followed by a global period of cooling and drying.
Split Cord Malformation: Experience from a Tertiary Referral Center
Authors: Börcek Alp Özgün , Öcal Özgür , Emmez Hakan , Zinnuroğlu Murat , Baykaner M. Kemali
Published: July 2013

Aim: To present clinical, radiological, and follow-up features of 34 cases with spinal split cord malformation (SCM) treated in a tertiary referral center between April 2000 and March 2012. Methods: A total of 59 patients were treated due to SCM between April 2000 and March 2012 at the Gazi University Faculty of Medicine, Division of Pediatric Neurosurgery. Data for each patient were evaluated retrospectively, and age, sex, clinical findings, radiological findings, complications, and surgical results were recorded. Patients with a follow-up period of less than 6 months, patients harboring an open spinal dysraphism, and patients who had had their index surgery in another clinic were excluded, thus leaving a total of 34 patients for further analysis. Results: There were 19 females and 15 males ranging in age from 2 months to 15 years (mean 5.04 years). In this cohort, skin stigma was the most common reason (76.5%) to seek medical care. Of the cases, 22 (64.7%) had lumbar SCM and 12 (35.3%) had thoracic SCM. There were no cervical SCM. Twenty-one (61.8%) of the cases had type 1 SCM and 13 (38.2%) had Type 2 SCM. Of the patients, 21 (61.8%) had a detectable neurological deficit at initial evaluation. There were no differences between patients with and without a neurological deficit regarding age, sex, type, and level of SCM. Overall evaluation of patients regarding their final neurological status revealed that 16 (47.1%) patients improved, 4 (11.8%) deteriorated, and 14 (41.2%) remained stable. Conclusions: In our opinion, all patients diagnosed with either type of SCM should be surgically treated to prevent further neurological deterioration. The results of this study, together with previously published data, confirm the effectiveness and safety of surgical intervention in SCM.
Baseline IGF-I Levels Determine Insulin Secretion and Insulin Sensitivity during the First Year on Growth Hormone Therapy in Children Born Small for Gestational Age. Results from a North European Multicentre Study (NESGAS)
Authors: Jensen Rikke Beck , Thankamony Ajay , O'Connell Susan M. , Salgin Burak , Kirk Jeremy , Donaldson Malcolm , Ivarsson Sten-A. , Söder Olle , Roche Edna , Hoey Hilary , Dunger David B. , Juul Anders ,   on behalf of the NESGAS group
Published: July 2013

Objective: Developmental programming alters growth and metabolic outcome in children born small for gestational age (SGA). We explored insulin and glucose metabolism in SGA children treated with a fixed GH dose over 1 year. Methods: In the North European Small for Gestational Age Study (NESGAS), 110 short SGA children received GH at 67 µg/kg/day for 1 year. Insulin secretion was assessed by acute insulin response (AIR), insulin sensitivity (IS) by HOMA and disposition index (DI) by insulin secretion adjusted for IS. Results: First-year GH therapy led to increases in height and IGF-I standard deviation score (SDS), and reductions in IS (p < 0.0001). Compensatory increases in AIR (p < 0.0001) were insufficient and resulted in reduced DI (p = 0.032). Children in the highest IGF-I SDS tertile at baseline were the least insulin sensitive at baseline (p = 0.024) and 1 year (p = 0.006). IGF-I responses after 1 year were positively related to AIR (r = 0.30, p = 0.007) and DI (r = 0.29, p = 0.005). Conclusion: In SGA children treated with a high GH dose for 1 year, baseline IGF-I levels were related to IS whilst gains in height and IGF-I responses were associated with insulin secretion. Defining heterogeneity in IGF-I in SGA children may be useful in predicting growth and metabolic response.
Delineation of a de novo 7q21.3q31.1 Deletion by CGH-SNP Arrays in a Girl with Multiple Congenital Anomalies Including Severe Glaucoma
Authors: Martínez-Jacobo L. , Córdova-Fletes C. , Ortiz-López R. , Rivas F. , Saucedo-Carrasco C. , Rojas-Martínez A.
Published: July 2013

In this study, we present a female patient with a constitutional de novo deletion in 7q21.3q31.1 as determined by G-banding and CGH-SNP arrays. She exhibited, among other features, psychomotor retardation, congenital severe bilateral glaucoma, a cleft palate, and heart defect. Microarray assay disclosed a deleted 12.5-Mb region roughly 88 kb downstream the ectrodactyly critical region; thus, the patient's final karyotype was 46,XX.arr 7q21.3q31.1(96,742,140- 109,246,085)×1 dn. This girl represents the fourth patient described so far with congenital glaucoma and a deletion encompassing or overlapping the 7q21.3q31.1 region, and confirms the presence of a locus or loci related to such a clinical feature. According to our results, the proneness to ocular defects secondary to 7q intermediate deletions could be caused by co-deletion of TAC1, HBP1, and a small cluster of cytochrome P450 genes (subfamily 3A). This conclusion is supported by their functional roles and expression locations as well as because TAC1 is related to the functional pathway of the MYOC gene whose mutations are linked to glaucoma. Moreover, given that this girl is clinically reminiscent of several phenotypes related to diverse deletions within 7q21q32, our results and observations offer a general overview of the gene content of deletions/phenotypes overlapping 7q21.3q31.1 and confirm that loci distal to DLX genes including the CUX1 gene and potential regulatory elements downstream from DLX5 are unrelated to ectrodactyly.