bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound-targeted microbubble destruction mediated herpes simplex virus-thymidine kinase gene treats hepatoma in mice
Authors: Zhou Shiji , Li Shengwei , Liu Zuojin , Tang Yong , Wang Zhigang , Gong Jianping , Liu Changan 
Published: January 2011

AbstractObjectiveThe purpose of the study was to explore the anti-tumor effect of ultrasound -targeted microbubble destruction mediated herpes simplex virus thymidine kinase (HSV-TK) suicide gene system on mice hepatoma.MethodsForty mice were randomly divided into four groups after the models of subcutaneous transplantation tumors were estabilished: (1) PBS; (2) HSV-TK (3) HSV-TK+ ultrasound (HSV-TK+US); (4) HSV-TK+ultrasound+microbubbles (HSV-TK+US+MB). The TK protein expression in liver cancer was detected by western-blot. Applying TUNEL staining detected tumor cell apoptosis. At last, the inhibition rates and survival time of the animals were compared among all groups.ResultsThe TK protein expression of HSV-TK+MB+US group in tumor-bearing mice tissues were significantly higher than those in other groups. The tumor inhibitory effect of ultrasound-targeted microbubble destruction mediated HSV-TK on mice transplantable tumor was significantly higher than those in other groups (p < 0.05), and can significantly improve the survival time of tumor-bearing mice.ConclusionUltrasound-targeted microbubble destruction can effectively transfect HSV-TK gene into target tissues and play a significant inhibition effect on tumors, which provides a new strategy for gene therapy in liver cancer.
Deciphering the pathogenesis of tendinopathy: a three-stages process
Authors: Fu Sai-Chuen , Rolf Christer , Cheuk Yau-Chuk , Lui Pauline PY , Chan Kai-Ming 
Published: January 2011

AbstractOur understanding of the pathogenesis of "tendinopathy" is based on fragmented evidences like pieces of a jigsaw puzzle. We propose a "failed healing theory" to knit these fragments together, which can explain previous observations. We also propose that albeit "overuse injury" and other insidious "micro trauma" may well be primary triggers of the process, "tendinopathy" is not an "overuse injury" per se. The typical clinical, histological and biochemical presentation relates to a localized chronic pain condition which may lead to tendon rupture, the latter attributed to mechanical weakness. Characterization of pathological "tendinotic" tissues revealed coexistence of collagenolytic injuries and an active healing process, focal hypervascularity and tissue metaplasia. These observations suggest a failed healing process as response to a triggering injury. The pathogenesis of tendinopathy can be described as a three stage process: injury, failed healing and clinical presentation. It is likely that some of these "initial injuries" heal well and we speculate that predisposing intrinsic or extrinsic factors may be involved. The injury stage involves a progressive collagenolytic tendon injury. The failed healing stage mainly refers to prolonged activation and failed resolution of the normal healing process. Finally, the matrix disturbances, increased focal vascularity and abnormal cytokine profiles contribute to the clinical presentations of chronic tendon pain or rupture. With this integrative pathogenesis theory, we can relate the known manifestations of tendinopathy and point to the "missing links". This model may guide future research on tendinopathy, until we could ultimately decipher the complete pathogenesis process and provide better treatments.
Six3 demarcates the anterior-most developing brain region in bilaterian animals
Authors: Steinmetz Patrick RH , Urbach Rolf , Posnien Nico , Eriksson Joakim , Kostyuchenko Roman P , Brena Carlo , Guy Keren , Akam Michael , Bucher Gregor , Arendt Detlev 
Published: January 2011

Abstract

Background
The heads of annelids (earthworms, polychaetes, and others) and arthropods (insects, myriapods, spiders, and others) and the arthropod-related onychophorans (velvet worms) show similar brain architecture and for this reason have long been considered homologous. However, this view is challenged by the 'new phylogeny' placing arthropods and annelids into distinct superphyla, Ecdysozoa and Lophotrochozoa, together with many other phyla lacking elaborate heads or brains. To compare the organisation of annelid and arthropod heads and brains at the molecular level, we investigated head regionalisation genes in various groups. Regionalisation genes subdivide developing animals into molecular regions and can be used to align head regions between remote animal phyla.

Results
We find that in the marine annelid Platynereis dumerilii, expression of the homeobox gene six3 defines the apical region of the larval body, peripherally overlapping the equatorial otx+ expression. The six3+ and otx+ regions thus define the developing head in anterior-to-posterior sequence. In another annelid, the earthworm Pristina, as well as in the onychophoran Euperipatoides, the centipede Strigamia and the insects Tribolium and Drosophila, a six3/optix+ region likewise demarcates the tip of the developing animal, followed by a more posterior otx/otd+ region. Identification of six3+ head neuroectoderm in Drosophila reveals that this region gives rise to median neurosecretory brain parts, as is also the case in annelids. In insects, onychophorans and Platynereis, the otx+ region instead harbours the eye anlagen, which thus occupy a more posterior position.

Conclusions
These observations indicate that the annelid, onychophoran and arthropod head develops from a conserved anterior-posterior sequence of six3+ and otx+ regions. The six3+ anterior pole of the arthropod head and brain accordingly lies in an anterior-median embryonic region and, in consequence, the optic lobes do not represent the tip of the neuraxis. These results support the hypothesis that the last common ancestor of annelids and arthropods already possessed neurosecretory centres in the most anterior region of the brain. In light of its broad evolutionary conservation in protostomes and, as previously shown, in deuterostomes, the six3-otx head patterning system may be universal to bilaterian animals.
PERK Activation at Low Glucose Concentration Is Mediated by SERCA Pump Inhibition and Confers Preemptive Cytoprotection to Pancreatic β-Cells
Authors: Moore Claire E. , Omikorede Omotola , Gomez Edith , Willars Gary B. , Herbert Terence P. 
Published: December 2010

AbstractProtein kinase R-like ER kinase (PERK) is activated at physiologically low glucose concentrations in pancreatic β-cells. However, the molecular mechanisms by which PERK is activated under these conditions and its role in β-cell function are poorly understood. In this report, we investigated, in dispersed rat islets of Langerhans and mouse insulinoma-6 (MIN6) cells, the relationship between extracellular glucose concentration, the free endoplasmic reticulum (ER) calcium concentration ([Ca2+]ER) measured directly using an ER targeted fluorescence resonance energy transfer-based calcium sensor, and the activation of PERK. We found that a decrease in glucose concentration leads to a concentration-dependent reduction in [Ca2+]ER that parallels the activation of PERK and the phosphorylation of its substrate eukaryotic initiation factor-2α. We provide evidence that this decrease in [Ca2+]ER is caused by a decrease in sarcoplasmic/ER Ca2+-ATPase pump activity mediated by a reduction in the energy status of the cell. Importantly, we also report that PERK-dependent eukaryotic initiation factor-2α phosphorylation at low glucose concentration plays a significant role in 1) the regulation of both proinsulin and global protein synthesis, 2) cell viability, and 3) conferring preemptive cytoprotection against ER stress. Taken together, these results provide evidence that a decrease in the ATP/energy status of the cell in response to a decrease in glucose concentration results in sarcoplasmic/ER Ca2+-ATPase pump inhibition, the efflux of Ca2+ from the ER, and the activation of PERK, which plays an important role in both pancreatic β-cell function and survival.
A Pituitary-Specific Enhancer of the POMC Gene with Preferential Activity in Corticotrope Cells
Authors: Langlais David , Couture Catherine , Sylvain-Drolet Guillaume , Drouin Jacques 
Published: December 2010

Abstract
Cell-specific expression of the pituitary proopiomelanocortin (POMC) gene depends on the combination of tissue- and cell-restricted transcription factors such as Pitx1 and Tpit. These factors act on the proximal POMC promoter together with transcription factors that integrate inputs from signaling pathways. We now report the identification of an upstream enhancer in the POMC locus that is targeted by the same subset of transcription factors, except Pitx1. This enhancer located at −7 kb in the mouse POMC gene is highly dependent on Tpit for activity. Whereas Tpit requires Pitx1 for action on the promoter, it acts on the −7-kb enhancer as homodimers binding to a palindromic Tpit response element (TpitRE). Both half-sites of the TpitRE palindrome and Tpit homodimerization are required for activity. In vivo, the enhancer exhibits preferential activity in corticotrope cells of the anterior lobe whereas the promoter exhibits preference for intermediate lobe melanotropes. The enhancer is conserved among different species with the TpitRE palindrome localized at the center of conserved sequences. However, the mouse and human −7-kb enhancers do not exhibit conservation of hormone responsiveness and may differ in their relative importance for POMC expression. In summary, pituitary expression of the POMC gene relies on an upstream enhancer that complements the activity of the proximal promoter with Tpit as the major regulator of both regulatory regions.
Cytoplasmic Accumulation of Incompletely Glycosylated SHBG Enhances Androgen Action in Proximal Tubule Epithelial Cells
Authors: Hong Eui-Ju , Sahu Biswajyoti , Jänne Olli A. , Hammond Geoffrey L. 
Published: December 2010

AbstractHuman sex hormone-binding globulin (SHBG) accumulates within the cytoplasm of epithelial cells lining the proximal convoluted tubules of mice expressing human SHBG transgenes. The main ligands of SHBG, testosterone and its metabolite, 5α-dihydrotestosterone (DHT), alter expression of androgen-responsive genes in the kidney. To determine how intracellular SHBG might influence androgen action, we used a mouse proximal convoluted tubule (PCT) cell line with characteristics of S1/S2 epithelial cells in which human SHBG accumulates. Western blotting revealed that SHBG extracted from PCT cells expressing a human SHBG cDNA (PCT-SHBG) is 5–8 kDa smaller than the SHBG secreted by these cells, due to incomplete N-glycosylation and absence of O-linked oligosaccharides. PCT-SHBG cells sequester [3H]DHT more effectively from culture medium than parental PCT cells, and the presence of SHBG accentuates androgen-dependent activation of a luciferase reporter gene, as well as the endogenous kidney androgen-regulated protein (Kap) gene. After androgen withdrawal, androgen-induced Kap mRNA levels in PCT-SHBG cells are maintained for more than 2 wk vs 2 d in parental PCT cells. Transcriptome profiling after testosterone or DHT pretreatments, followed by 3 d of steroid withdrawal, also demonstrated that intracellular SHBG enhances androgen-dependent stimulation (e.g.Adh7, Vcam1, Areg, Tnfaip2) or repression (e.g.Cldn2 and Osr2) of many other genes in PCT cells. In addition, nuclear localization of the androgen receptor is enhanced and retained longer after steroid withdrawal in PCT cells containing functional SHBG. Thus, intracellular SHBG accentuates the uptake of androgens and sustains androgens access to the androgen receptor, especially under conditions of limited androgen supply.
Intravenous N-Acetylcysteine in the Prevention of Contrast Media-Induced Nephropathy
Authors: Anderson Spencer M , Park Zoon H , Patel Ramesh V 
Published: January 2011

Objective Ti define the clinical role of intravenous N-acetylcysteine for prophylaxis of contrast-induced nephropathy (CIN). Data Sources: Randomized controlled clinical trials were identified using a search of MEDLINE (1990-September 2010) with the search terms acetylcysteine, N-acetylcysteine, NAC, intravenous, IV, nephropathy, nephrotoxic, radiocontrast, contrast, and media. The search was limited to studies published in English. Additional pertinent literature was retrieved by reviewing references of the articles obtained in the initial search. Data Synthesis: N-Acetylcysteine is a vasodilator and antioxidant that has been investigated for the prevention of CIN. In the majority of clinical trials, neither oral nor intravenous N-acetyIcysteine has demonstrated clinical benefits at preventing CIN. The pharmacodynamic and pharmacokinetic profiles of intravenous N-acetylcysteine are significantly different from those of the oral product in that intravenous administration bypasses extensive first-pass metabolism. Studies have suggested that N-acetylcysteine directly affects serum creatinine levels in a way that is not associated with improvement of kidney function. Only intravenous N-acetylcysteine doses that were higher than the oral doses showed potential benefits, but they were associated with significant adverse events. Furthermore, the study populations were heterogeneous, including patients with various levels of kidney function and other risk factors, and the clinical definition of CIN was not well established. Conclusions: NO conclusive evidence has shown that intravenous N-acetyl-cysteine is safe and effective in preventing CIN. Further clinical trials to define its role are warranted.
Preoperative Statins and Acute Kidney Injury After Cardiac Surgery: Utilization of a Consensus Definition of Acute Kidney Injury
Authors: Bolesta Scott , Uhrin Lindsey M , Guzek John R 
Published: January 2011

Background Previous trials investigating preoperative statin use for prevention of acute kidney injury following cardiovascular surgery were limited to patients undergoing a specific procedure and many used nonconsensus definitions of acute kidney injury. Objective To use a consensus definition of acute kidney injury for evaluating the association of preoperative statin use with the development of acute kidney injury following cardiac surgery utilizing cardiopulmonary bypass. Methods We retrospectively evaluated a cohort of 667 patients ≥18 years who underwent any cardiac surgery on cardiopulmonary bypass between April 2007 and May 2009 at Mercy Hospital in Scranton, PA. Patients were excluded if they were receiving preoperative renal replacement therapy, had stage 5 chronic kidney disease, or did not have a postoperative serum creatinine level assessed. The primary outcome was the odds of developing acute kidney injury given the use of preoperative statins. Acute kidney injury was defined based on the Acute Kidney Injury Network criteria as either an absolute increase in serum creatinine of ≥0.3 mg/dL or 1.5 times baseline, or the need for postoperative renal replacement therapy. Results: The final analysis included 563 patients; 356 were receiving preoperative statins. The incidence of acute kidney injury was 35.1% in the statin group and 26.1% in the non-statin group. On univariate analysis statins were associated with an increase in the odds of acute kidney injury (OR 1.53; 95% CI 1.05 to 2.24). Multivariate logistic regression did not demonstrate an association of statins with acute kidney injury (OR 1.36; 95% CI 0.904 to 2.05). Repeating the analysis using 312 propensity score–matched patients also showed no association of statins with acute kidney injury (OR 1.17; 95% CI 0.715 to 1.93). Conclusions: Our findings do not support the hypothesis that preoperative statin use is associated with a decrease in the incidence of acute kidney injury following cardiac surgery utilizing cardiopulmonary bypass.
Anacetrapib and Dalcetrapib: Two Novel Cholesteryl Ester Transfer Protein Inhibitors
Authors: Miyares Marta A 
Published: January 2011

Objective To evaluate the role of cholesteryl ester transfer protein (CETP) in the cholesterol transport system and review the pharmacology, pharmacokinetic properties, efficacy, and adverse effects of the CETP inhibitors, anacetrapib and dalcetrapib, for the treatment of dyslipidemia. Data Sources: A literature search was conducted in Ovid/MEDLINE (1950 to week 4 December 2010), PubMed/MEDLINE (up to December 2010). EMBASE (2000 to December 2010), and International Pharmaceutical Abstracts (1970 to December 2010) using the MeSH terms and key words anacetrapib, MK 0859, dalcetrapib, and JTT 705. The search was limited to publications in English. Study Selection And Data Extraction: Studies evaluating the pharmacology, pharmacokinetics, safety, and efficacy of anacetrapib and dalcetrapib for the treatment of dyslipidemia were included. Clinical reviews evaluating the characterization of CETP and its inhibition as a mechanism for reducing cardiovascular risk were also included. Data Synthesis: Anacetrapib and dalcetrapib represent a novel treatment option for patients who have dyslipidemia and low levels of high-density lipoprotein cholesterol (HDL-C). Anacetrapib and dalcetrapib increase HDL-C by inhibiting CETP-mediated transfer of cholesteryl ester and triglyceride. Studies evaluating the safety and efficacy of anacetrapib and dalcetrapib concluded that both agents safely and effectively augment HDL-C. Their mechanism of action, potential for significant raising of HDL-C, once-daily dosing regimen, and favorable lipid-altering effects when added to hydroxymethylglutaryl-CoA reductase inhibitors are key elements, Anacetrapib and dalcetrapib are well tolerated, with mild gastrointestinal complaints reported more than with placebo, Although another CETP inhibitor, torcetrapib, was withdrawn from clinical development secondary to increased morbidity and mortality, neither anacetrapib nor dalcetrapib has demonstrated the adverse off-target effects portrayed with torcetrapib. Conclusions: Inhibition of CETP by anacetrapib and dalcetrapib represents an encouraging development in the management of dyslipidemia, particularly in patients with low HDL-C levels. Results of future trials are much anticipated, as these will clarify the role of anacetrapib and dalcetrapib in reduction of cardiovascular disease.
Brain Bases for Auditory Stimulus-Driven Figure–Ground Segregation
Authors: Teki Sundeep , Chait Maria , Kumar Sukhbinder , von Kriegstein Katharina , Griffiths Timothy D. 
Published: January 2011

Auditory figure–ground segregation, listeners' ability to selectively hear out a sound of interest from a background of competing sounds, is a fundamental aspect of scene analysis. In contrast to the disordered acoustic environment we experience during everyday listening, most studies of auditory segregation have used relatively simple, temporally regular signals. We developed a new figure–ground stimulus that incorporates stochastic variation of the figure and background that captures the rich spectrotemporal complexity of natural acoustic scenes. Figure and background signals overlap in spectrotemporal space, but vary in the statistics of fluctuation, such that the only way to extract the figure is by integrating the patterns over time and frequency. Our behavioral results demonstrate that human listeners are remarkably sensitive to the appearance of such figures.In a functional magnetic resonance imaging experiment, aimed at investigating preattentive, stimulus-driven, auditory segregation mechanisms, naive subjects listened to these stimuli while performing an irrelevant task. Results demonstrate significant activations in the intraparietal sulcus (IPS) and the superior temporal sulcus related to bottom-up, stimulus-driven figure–ground decomposition. We did not observe any significant activation in the primary auditory cortex. Our results support a role for automatic, bottom-up mechanisms in the IPS in mediating stimulus-driven, auditory figure–ground segregation, which is consistent with accumulating evidence implicating the IPS in structuring sensory input and perceptual organization.
Mutual Subject-Discovery in Syrian Encounters
Authors: Borneman John 
Published: January 2011

Abstract
For anthropologists who engage in encounter-based fieldwork, contact zones have a peculiar phenomenal quality that is often neglected by scholars from other disciplines who have taken up the fieldwork paradigm initially developed by ethnographers. In this paper, I want to elaborate how, in my most recent fieldwork in Syria, I experienced such zones, and I want to reflect on this experience and its relation to concepts and writing as it becomes knowledge. I define fieldwork as the registering of sensory impressions in a (temporal) process of mutual subject-discovery and critique, and anthropology as a mode of engagement in generating knowledge and social and political action that enables ongoing relationships (Borneman/Hammoudi 2009: 19). This picture of fieldwork and ethnography, in its stress on the author being in a zone of contact with the world he is depicting (Bakhtin 1981: 30), is at odds with understandings that focus on anthropology as a cultural critique of the West (Marcus/Fischer 1986), creative and usable mappings (Gupta/Ferguson 1997: 56), comparison of embedded concepts between societies (Asad 2003: 17), or interpretation of another culture (Geertz 1973).
Kontaktzonen im Museum. Kindergruppen in der Ausstellung Indianer Nordamerikas
Authors: Wagner Bernd 
Published: January 2011

Abstract
European ethnological museums usually administer not only exhibitions but also large archives. Visitors of the exhibitions generally do not get to know that the archived objects exist. As these objects are omitted and difficult to access they leave a blank position as Deborah Poole remarks. Decisions as to why objects are displayed or archived are an important matter in museum studies. James Clifford is challenging museums to integrate contact zones in their exhibitions. Ethnological museums contribute to intercultural encounter by allowing contact to their archives, opening exhibition spaces for performative play of children and reflecting collections and collectors in terms of postcolonial theory.
New structural constraints on the southern Provence thrust belt (France): evidences for an Eocene shortening event linked to the Corsica-Sardinia subduction
Authors: Andreani Louis , Loget Nicolas , Rangin Claude , Le Pichon Xavier 
Published: January 2011

AbstractThe Eocene shortening directions along the Southern Provence fold-and-thrust belt are commonly assumed to be N-S. We present here new observations and data that allow reinterpreting the structure of the La Nerthe range as a right-lateral transpressive flower structure. Structural data collected along the range argue for an Eocene N145o shortening event. The age of this shortening event is constrained by the fact that faulting and folding affect the Late Cretaceous-Paleocene continental deposits along the northern flank of the La Nerthe range and is sealed by the Miocene marine deposits. Moreover striated fault planes display both horizontal and vertical striae suggesting that they were reactivated during the Oligocene extensional event. We question here the shortening directions along the Southern Provence thrust belt. Structural data suggest both N-S and NNW-SSE shortening directions during the Eocene. During the Eocene the Provence area was in the foreland of a complex orogenic belt that extended from the Betic Cordillera to the Corsica-Sardinia block. This orogenic belt developed along the subduction linked to the convergence between Africa and Eurasia. Although the convergence vector was nearly N-S the NE-SW orientation of the trench may have led to a complex deformation pattern along the orogenic belt with NW-SE and N-S shortening directions that reflected both the along-trench compression and the regional convergence.