bluuebunny/crossref_metadata_2025_split huggingface dataset:
IQGAP1 Plays an Important Role in the Invasiveness of Thyroid Cancer
Authors: Liu Zhi , Liu Dingxie , Bojdani Ermal , El-Naggar Adel K. , Vasko Vasily , Xing Mingzhao 
Published: October 2010

Abstract
Purpose: This study was designed to explore the role of IQGAP1 in the invasiveness of thyroid cancer and its potential as a novel prognostic marker and therapeutic target in this cancer.
Experimental Design: We examined IQGAP1 copy gain and its relationship with clinicopathologic outcomes of thyroid cancer and investigated its role in cell invasion and molecules involved in the process.
Results: We found IQGAP1 copy number (CN) gain ≥3 in 1 of 30 (3%), 24 of 74 (32%), 44 of 107 (41%), 8 of 16 (50%), and 27 of 41 (66%) of benign thyroid tumor, follicular variant papillary thyroid cancer (FVPTC), follicular thyroid cancer (FTC), tall cell papillary thyroid cancer (PTC), and anaplastic thyroid cancer, respectively, in the increasing order of invasiveness of these tumors. A similar tumor distribution trend of CN ≥4 was also seen. IQGAP1 copy gain was positively correlated with IQGAP1 protein expression. It was significantly associated with extrathyroidal and vascular invasion of FVPTC and FTC and, remarkably, a 50%–60% rate of multifocality and recurrence of BRAF mutation–positive PTC (P = 0.01 and 0.02, respectively). The siRNA knockdown of IQGAP1 dramatically inhibited thyroid cancer cell invasion and colony formation. Coimmunoprecipitation assay showed direct interaction of IQGAP1 with E-cadherin, a known invasion-suppressing molecule, which was upregulated when IQGAP1 was knocked down. This provided a mechanism for the invasive role of IQGAP1 in thyroid cancer. In contrast, IQGAP3 lacked all these functions.
Conclusions: IQGAP1, through genetic copy gain, plays an important role in the invasiveness of thyroid cancer and may represent a novel prognostic marker and therapeutic target for this cancer. Clin Cancer Res; 16(24); 6009–18. ©2010 AACR.
Diallyl Trisulfide Inhibits Activation of Signal Transducer and Activator of Transcription 3 in Prostate Cancer Cells in Culture and In vivo
Authors: Chandra-Kuntal Kumar , Singh Shivendra V. 
Published: October 2010

Abstract
Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor implicated in prostate carcinogenesis. The present study shows that diallyl trisulfide (DATS), a promising cancer-chemopreventive constituent of processed garlic, inhibits phosphorylation of STAT3 in prostate cancer cells in culture and in vivo. Exposure of DU145 and LNCaP human prostate cancer cells to growth-suppressive and pharmacologically relevant concentrations of DATS (20 and 40 μmol/L) resulted in suppression of constitutive (DU145) as well as interleukin-6 (IL-6)–induced (LNCaP) phosphorylation of STAT3 (Tyr705), which correlated with inhibition of Janus-activated kinase 2 phosphorylation. Constitutive and/or IL-6–induced nuclear translocation of pSTAT3 and STAT3 dimerization was also markedly inhibited on treatment with DATS in both cell lines. Inhibition of prostate cancer development in transgenic adenocarcinoma of mouse prostate mice by gavage of DATS correlated with a visible decrease in the levels of pSTAT3. Interestingly, the IL-6–mediated activation of STAT3 largely failed to confer protection against proapoptotic response to DATS in both cells. Likewise, DATS-mediated inhibition of cell migration was either not affected or minimally reversed by IL-6 treatment or ectopic expression of constitutively active STAT3. In conclusion, the present study indicates that DATS treatment suppresses STAT3 phosphorylation in prostate cancer cells in culture and in vivo, but activation of this oncogenic transcription factor is largely dispensable for cellular responses to DATS. Ability of DATS to overcome STAT3 activation is a therapeutic advantage for this chemopreventive agent. Cancer Prev Res; 3(11); 1473–83. ©2010 AACR.
Synthetic Triterpenoids Prolong Survival in a Transgenic Mouse Model of Pancreatic Cancer
Authors: Liby Karen T. , Royce Darlene B. , Risingsong Renee , Williams Charlotte R. , Maitra Anirban , Hruban Ralph H. , Sporn Michael B. 
Published: October 2010

Abstract
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and is nearly always fatal. Whereas early detection offers the most promising approach for reducing the mortality of this disease, there is still a need to develop effective drugs for the prevention and treatment of pancreatic cancer. We tested two promising classes of noncytotoxic drugs, synthetic oleanane triterpenoids and rexinoids, for the prevention of carcinogenesis in the highly relevant LSL-KrasG12D/+;LSL-Trp53R127H/+;Pdx-1-Cre (KPC) mouse model of pancreatic cancer. KPC transgenic mice closely recapitulate the genetic mutations, clinical symptoms, and histopathology found in human pancreatic cancer. Beginning at 4 weeks of age, mice were fed powdered control diet or a diet containing the triterpenoids CDDO-methyl ester (CDDO-Me) or CDDO-ethyl amide, the rexinoid LG100268 (LG268), or the combination, until the mice displayed overt symptoms of pancreatic cancer. CDDO-Me, LG268, the combination of CDDO-Me and LG268, and the combination of CDDO-ethyl amide and LG268, all significantly (P &lt; 0.05) increased survival in the KPC mice by 3 to 4 weeks. Recent studies have shown that gemcitabine, the current standard of care for human pancreatic cancer, does not extend survival in KPC mice. In cell lines developed from the KPC mice, the triterpenoids directly interact with both signal transducer and activator of transcription 3 and IκB kinase (IKK) to decrease constitutive interleukin-6 secretion, inhibit constitutive signal transducer and activator of transcription 3 phosphorylation, and block the degradation of IκBα when challenged with tumor necrosis factor α. These results suggest that oleanane triterpenoids and rexinoids have the potential to prevent pancreatic cancer. Cancer Prev Res; 3(11); 1427–34. ©2010 AACR.
Hebrew Brain vs. English Brain: Language Modulates the Way It Is Processed
Authors: Bick Atira S. , Goelman Gadi , Frost Ram 
Published: October 2010

Abstract
Is language processing universal? How do the specific properties of each language influence the way it is processed? In this study, we compare the neural correlates of morphological processing in Hebrew—a Semitic language with a rich and systematic morphology, to those revealed in English—an Indo-European language with a linear morphology. Using fMRI, we show that while in the bilingual brain both languages involve a common neural circuitry in processing morphological structure, this activation is significantly modulated by the different aspects of language. Whereas in Hebrew, morphological processing is independent of semantics, in English, morphological activation is clearly modulated by semantic overlap. These findings suggest that the processes involved in reading words are not universal, and therefore impose important constraints on current models of visual word recognition.
Selective Cortical Mapping of Biological Motion Processing in Young Infants
Authors: Lloyd-Fox Sarah , Blasi Anna , Everdell Nick , Elwell Clare E. , Johnson Mark H. 
Published: October 2010

Abstract
How specialized is the infant brain for perceiving the facial and manual movements displayed by others? Although there is evidence for a network of regions that process biological motion in adults—including individuated responses to the perception of differing facial and manual movements—how this cortical specialization develops remains unknown. We used functional near-infrared spectroscopy [Lloyd-Fox, S., Blasi, A., & Elwell, C. Illuminating the developing brain: The past, present and future of functional near-infrared spectroscopy. Neuroscience and Biobehavioral Reviews, 34, 269–284, 2010] to investigate the ability of 5-month-old infants to process differing biological movements. Infants watched videos of adult actors moving their hands, their mouth, or their eyes, all in contrast to nonbiological mechanical movements, while hemodynamic responses were recorded over the their frontal and temporal cortices. We observed different regions of the frontal and temporal cortex that responded to these biological movements and different patterns of cortical activation according to the type of movement watched. From an early age, our brains selectively respond to biologically relevant movements, and further, selective patterns of regional specification to different cues occur within what may correspond to a developing “social brain” network. These findings illuminate hitherto undocumented maps of selective cortical activation to biological motion processing in the early postnatal development of the human brain.
Special Issue for GR2P: Africa's Responsibility to Protect Introduction
Authors: Sarkin Jeremy , Paterson Mark 
Published: October 2010

AbstractThe introduction sketches the recent development of the 'responsibility to protect' norm and emphasises its African roots, both in terms of its conceptualisation and implementation and with particular respect to two tragedies—the genocide in Rwanda in 1994 and the crisis in Darfur since 2003—that have lent urgency to the norm's formulation and widespread international adoption. The number and extent of R2P cases in Africa are outlined and the roles of the African Union and Africa's regional organisations in implementing the norm are briefly considered. The introduction acknowledges the importance of examining R2P through African perspectives. Referencing the justifications and primary principles for action upon which the norm is founded, the authors also assess the relative strengths of competing notions of sovereignty in Africa. The essay further considers how R2P has come to be seen as a mechanism that can bolster the capacity of weak states to fulfil their sovereign responsibilities to their own citizens, and how new international obligations imposed upon states, and particularly those adopted in Africa, have made significant inroads into the old concept of sovereignty as territorial integrity and freedom from external interventions.
Breaking the lock: Addressing ‘disproportionate minority confinement’ in the United States using a human rights approach
Authors: Mooradian John K 
Published: October 2010

• Summary: Injustice, oppression, and inequality affect human experience in all contexts. This article describes the problem of ‘disproportionate minority confinement’ in the United States juvenile justice system as one manifestation of such injustice. With specific focus on overrepresentation of African American males, the juvenile justice approach to this problem is contrasted with a critical social work perspective in the form of the human rights approach. • Findings: Available data from all but one of the 50 United States indicate a disproportionate level of incarceration of youth classified as African American in juvenile justice facilities. Although the United States federal government enacted policy reforms in 1988 that require states which receive federal funds to decrease the proportion of minority youth who are incarcerated in secure facilities, few gains have been realized. • Application: The author proposes that social workers employ a human rights approach to supplant the dominant juvenile justice paradigm. Application of human rights practice to disproportionate minority confinement suggests that social workers challenge the juvenile justice/social control discourse with a human rights/social change discourse; deconstruct the constructs of ‘disproportionate minority confinement’, ‘juvenile delinquency’, and ‘race’; challenge the expert/exclusionary problem-solving process with a dialogical/inclusionary process; challenge deficit-oriented activities with strength-based and asset-building activities; and introduce critical reflectivity into professional decision-making.
von Willebrand factor–mediated platelet adhesion is critical for deep vein thrombosis in mouse models
Authors: Brill Alexander , Fuchs Tobias A. , Chauhan Anil K. , Yang Janie J. , De Meyer Simon F. , Köllnberger Maria , Wakefield Thomas W. , Lämmle Bernhard , Massberg Steffen , Wagner Denisa D. 
Published: October 2010

Abstract
Deep vein thrombosis (DVT) and its complication, pulmonary embolism, are frequent causes of disability and mortality. Although blood flow disturbance is considered an important triggering factor, the mechanism of DVT initiation remains elusive. Here we show that 48-hour flow restriction in the inferior vena cava (IVC) results in the development of thrombi structurally similar to human deep vein thrombi. von Willebrand factor (VWF)–deficient mice were protected from thrombosis induced by complete (stasis) or partial (stenosis) flow restriction in the IVC. Mice with half normal VWF levels were also protected in the stenosis model. Besides promoting platelet adhesion, VWF carries Factor VIII. Repeated infusions of recombinant Factor VIII did not rescue thrombosis in VWF−/− mice, indicating that impaired coagulation was not the primary reason for the absence of DVT in VWF−/− mice. Infusion of GPG-290, a mutant glycoprotein Ibα-immunoglobulin chimera that specifically inhibits interaction of the VWF A1 domain with platelets, prevented thrombosis in wild-type mice. Intravital microscopy showed that platelet and leukocyte recruitment in the early stages of DVT was dramatically higher in wild-type than in VWF−/− IVC. Our results demonstrate a pathogenetic role for VWF-platelet interaction in flow disturbance-induced venous thrombosis.
Human functional genetic studies are biased against the medically most relevant primate-specific genes
Authors: Hao Lili , Ge Xiaomeng , Wan Haolei , Hu Songnian , Lercher Martin J , Yu Jun , Chen Wei-Hua 
Published: October 2010

Abstract

Background
Many functional, structural and evolutionary features of human genes have been observed to correlate with expression breadth and/or gene age. Here, we systematically explore these correlations.

Results
Gene age and expression breadth are strongly correlated, but contribute independently to the variation of functional, structural and evolutionary features, even when we take account of variation in mRNA expression level. Human genes without orthologs in distant species ('young' genes) tend to be tissue-specific in their expression. As computational inference of gene function often relies on the existence of homologs in other species, and experimental characterization is facilitated by broad and high expression, young, tissue-specific human genes are often the least characterized. At the same time, young genes are most likely to be medically relevant.

Conclusions
Our results indicate that functional characterization of human genes is biased against young, tissue-specific genes that are mostly medically relevant. The biases should not be taken lightly because they may pose serious obstacles to our understanding of the molecular basis of human diseases. Future studies should thus be designed to specifically explore the properties of primate-specific genes.
Gene expression in a paleopolyploid: a transcriptome resource for the ciliate Paramecium tetraurelia
Authors: Arnaiz Olivier , Goût Jean-François , Bétermier Mireille , Bouhouche Khaled , Cohen Jean , Duret Laurent , Kapusta Aurélie , Meyer Eric , Sperling Linda 
Published: October 2010

AbstractBackgroundThe genome ofParamecium tetraurelia, a unicellular model that belongs to the ciliate phylum, has been shaped by at least 3 successive whole genome duplications (WGD). These dramatic events, which have also been documented in plants, animals and fungi, are resolved over evolutionary time by the loss of one duplicate for the majority of genes. Thanks to a low rate of large scale genome rearrangement inParamecium, an unprecedented large number of gene duplicates of different ages have been identified, making this organism an outstanding model to investigate the evolutionary consequences of polyploidization. The most recent WGD, with 51% of pre-duplication genes still in 2 copies, provides a snapshot of a phase of rapid gene loss that is not accessible in more ancient polyploids such as yeast.ResultsWe designed a custom oligonucleotide microarray platform forP. tetraureliagenome-wide expression profiling and used the platform to measure gene expression during 1) the sexual cycle of autogamy, 2) growth of new cilia in response to deciliation and 3) biogenesis of secretory granules after massive exocytosis. Genes that are differentially expressed during these time course experiments have expression patterns consistent with a very low rate of subfunctionalization (partition of ancestral functions between duplicated genes) in particular since the most recent polyploidization event.ConclusionsA public transcriptome resource is now available forParameciumtetraurelia. The resource has been integrated into the ParameciumDB model organism database, providing searchable access to the data. The microarray platform, freely available through NimbleGen Systems, provides a robust, cost-effective approach for genome-wide expression profiling inP. tetraurelia. The expression data support previous studies showing that at short evolutionary times after a whole genome duplication, gene dosage balance constraints and not functional change are the major determinants of gene retention.
Transcriptome changes in grapevine (Vitis viniferaL.) cv. Malbec leaves induced by ultraviolet-B radiation
Authors: Pontin Mariela A , Piccoli Patricia N , Francisco Rita , Bottini Ruben , Martinez-Zapater Jose M , Lijavetzky Diego 
Published: October 2010

Abstract

Background
Ultraviolet-B radiation (UV-B, 280-315 nm) is a natural component of sunlight, which has numerous regulatory effects on plant physiology. The nature of the response to UV-B is dependent on fluence rate, dose, duration and wavelength of the UV-B treatment. Some reports have analyzed the changes in gene expression caused by UV-B light on several plant species using microarray technology. However, there is no information on the transcriptome response triggered by UV-B in grapevine. In this paper we investigate the gene expression responses of leaves from in vitro cultured Vitis vinifera cv. Malbec plants subjected to the same dose of biologically effective UV-B radiation (4.75 kJ m-2 d-1) administered at two different fluence rates (16 h at ≅ 8.25 μW cm-2, 4 h at ≅ 33 μW cm-2) using a new custom made GrapeGen Affymetrix GeneChip®.

Results
The number of genes modulated by high fluence rate UV-B doubled the number of genes modulated by low fluence UV-B. Their functional analyses revealed several functional categories commonly regulated by both UV-B treatments as well as categories more specifically modulated depending on UV-B fluence rate. General protective responses, namely the induction of pathways regulating synthesis of UV-B absorbing compounds such as the Phenylpropanoid pathway, the induction of different antioxidant defense systems and the activation of pathways commonly associated with pathogen defense and abiotic stress responses seem to play critical roles in grapevine responses against UV-B radiation. Furthermore, high fluence rate UV-B seemed to specifically modulate additional pathways and processes in order to protect grapevine plantlets against UV-B-induced oxidative stress, stop the cell cycle progression, and control protein degradation. On the other hand, low fluence rate UV-B regulated the expression of specific responses in the metabolism of auxin and abscisic acid as well as in the modification of cell walls that could be involved in UV-B acclimation-like processes.

Conclusion
Our results show the UV-B radiation effects on the leaf transcriptome of grapevine (Vitis vinifera cv. Malbec) plantlets. Functional categories commonly modulated under both UV-B treatments as well as transcripts specifically regulated in an UV-B-intensity dependent way were identified. While high fluence rate UV-B had regulatory effects mainly on defense or general multiple-stress responses pathways, low fluence rate UV-B promoted the expression of genes that could be involved in UV-B protection or the amelioration of the UV-B-induced damage. This study also provides an extensive list of genes regulating multiple metabolic pathways involved in the response of grapevine to UV-B that can be used for future researches.
Hepatitis B virus core protein with hot-spot mutations inhibit MxA gene transcription but has no effect on inhibition of virus replication by interferon α
Authors: Zhijian Yu , Zhen Huang , Fan Zhang , Jin Yang , Qiwen Deng , Zhongming Zeng 
Published: October 2010

Abstract
It has been reported that hepatitis B virus (HBV) core protein (HBc) can inhibit the transcription of human interferon-induced MxA gene. In this study, we investigated whether HBc protein mutations at hot spots (L60V, S87G and I97L) could still inhibit MxA transcription and the potential significance of this inhibition in virus replication in vitro. Our data indicated that the IFN-induced MxA mRNA expression level and MxA promoter activity was significantly down-regulated by mutant protein of HBc(I97L), compared to WT and the other two mutated HBc proteins(L60V or S87G). However, in Huh7 cells stably expressing WT or the mutated HBc proteins (L60V, S87G or I97L), IFN-α could inhibit the extra- and intracellular HBV DNA level and HBsAg secretion to a similar level compared to that in cells transfected with control plasmids. In conclusion, HBc protein with I97L mutation may play an especial role in suppressing the transcription of MxA gene. Moreover, the inhibitory effect on MxA gene transcription by the WT or mutated HBc proteins (L60V, S87G and I97L) has no impact on inhibition of HBV replication by IFN-α in Huh7 cells. The clinical significance of the inhibitory effect of MxA gene transcription by HBc protein requires further study.
Hypercalcemia and huge splenomegaly presenting in an elderly patient with B-cell non-Hodgkin's lymphoma: a case report
Authors: Ghazi Ali AM , Attarian Hamid , Attarian Shirin , Abasahl Abolghasem , Daryani Ebrahim , Farasat Ebrahim , Pourafkari Marina , Tirgari Farrokh , Ghazi Siavash M , Kovacs Kalman 
Published: October 2010

Abstract

Introduction
Hypercalcemia is the major electrolyte abnormality in patients with malignant tumors. It can be due to localized osteolytic hypercalcemia or elaboration of humoral substances such as parathyroid hormone-related protein from tumoral cells. In hematological malignancies, a third mechanism of uncontrolled synthesis and secretion of 1-25(OH)2D3 from tumoral cells or neighboring macrophages may contribute to the problem. However, hypercalcemia is quite unusual in patients with B-cell non-Hodgkin's lymphoma.

Case presentation
An 85-year-old Caucasian woman presented with low grade fever, anorexia, abdominal discomfort and fullness in her left abdomen for the last six months. She was mildly anemic and complained of fatigability. She had huge splenomegaly and was hypercalcemic. After correction of her hypercalcemia, she had a splenectomy. Microscopic evaluation revealed a malignant lymphoma. Her immunohistochemistry was positive for leukocyte common antigen, CD20 and parathyroid hormone-related peptide.

Conclusion
Immunopositivity for parathyroid hormone-related peptide clearly demonstrates that hypersecretion of a parathyroid hormone-like substance from the tumor had led to hypercalcemia in this case. High serum calcium is seen in only seven to eight percent of patients with B-cell non-Hodgkin's lymphoma, apparently due to different mechanisms. Evaluation of serum parathyroid hormone-related protein and 1-25(OH)2D3 can be helpful in diagnosis and management. It should be noted that presentation with hypercalcemia has a serious impact on prognosis and survival.