bluuebunny/crossref_metadata_2025 huggingface dataset:
The Ecohydrology of a pioneer wetland species and a drastically altered landscape
Authors: McLaughlin Daniel L. , Brown Mark T. , Cohen Matthew J.
Published: September 2011

Vegetation plays a central role in forming and maintaining an ecosystem's physical conditions, which in turn strongly influence vegetation function. These bidirectional feedbacks may be particularly evident during an ecosystem succession following large‐scale disturbances. Clay settling areas (CSAs) are large elevated impoundments that receive clay slurry as a by‐product of phosphate mining in Florida. As CSAs mature, a limited seed source arrests ecological succession, resulting in the dominance of Salix caroliniana, which is likely further supported by altered abiotic conditions. The dominance of this wetland pioneer species and its interactions with soil and hydrology may largely determine the future ecosystem state. To identify how interactions between groundwater levels, soil water availability, and vegetation response regulate the succession of CSA ecosystems, we measured groundwater levels, vertical soil moisture profiles, soil water potentials, and root biomass allocation and transpiration of S. caroliniana at two sites. Fine soil texture in the CSAs resulted in capillary fringe heights greater than 1 m, which maintained soil moisture near saturation well above the water table. Rooting depths over 1 m in the clay soils provided sufficient water availability, which, along with high residual phosphorus concentrations, explained the dominance and high transpiration rates of S. caroliniana across CSAs. Capillary rise‐induced water availability created wetland soil conditions far upgradient from inundated areas, underscoring the role of soil texture in determining wetland extent. The strong coupling between water table and S. caroliniana transpiration, however, suggests that beyond soil development, this pioneer phreatophyte may also drive succession through systematic dewatering. Copyright © 2011 John Wiley & Sons, Ltd.
IL‐7 determines the homeostatic fitness of T cells by distinct mechanisms at different signalling thresholds in vivo
Authors: Pearson Claire , Silva Ana , Saini Manoj , Seddon Benedict
Published: September 2011

The cytokine interleukin (IL)‐7 is essential for Treg‐cell homeostasis. It remains unclear, however, whether IL‐7 regulates the homeostatic fitness of T cells quantitatively and, if so, by what mechanisms. We addressed this question by analysing T cells exposed to different levels of IL‐7 signalling in vivo. Using TCR transgenic mice that conditionally express IL‐7Rα, we show that T‐cell longevity in the absence of survival cues is not a cell‐intrinsic property but rather a dynamic process of which IL‐7 signalling is a key regulator. Naïve T cells deficient in IL‐7Rα expression underwent rapid cell death within hours of in vitro culture. In contrast, the same T cells from lymphopenic hosts, in which IL‐7 is non‐limiting, were able to survive in culture independently of growth factors for many days. Surprisingly, different levels of IL‐7 signalling in vivo evoked distinct molecular mechanisms to regulate homeostatic fitness. When IL‐7 was non‐limiting, increased survival was associated with up‐regulation of anti‐apoptotic Bcl2 family members. In contrast, in T‐cell replete conditions i.e. when IL‐7 is limiting, we found evidence that IL‐7 regulated T‐cell fitness by distinct non‐transcriptional mechanisms. Together, these data demonstrate a quantitative aspect to IL‐7 signalling dependent on distinct molecular mechanisms.
Pre‐differentiated human committed T‐lymphoid progenitors promote peripheral T‐cell re‐constitution after stem cell transplantation in immunodeficient mice
Authors: Eyrich Matthias , Schreiber Susanne C. , Wollny Gernot , Ziegler Hendrik , Schlenker Ramona , Koch‐Büttner Katharina , Wölfl Matthias , Schlegel Paul G. , Schilbach Karin
Published: September 2011

T‐cell re‐constitution after allogeneic stem cell transplantation (alloSCT) is often dampened by the slow differentiation of human peripheral blood CD34+ (huCD34+) hematopoietic stem cells (HSCs) into mature T cells. This process may be accelerated by the co‐transfer of in vitro‐pre‐differentiated committed T/NK‐lymphoid progenitors (CTLPs). Here, we analysed the developmental potential of huCD34+ HSCs compared with CTLPs from a third‐party donor in a murine NOD‐scid IL2Rγnull model of humanised chimeric haematopoiesis. CTLPs (CD34+lin−CD45RA+CD7+) could be generated in vitro within 10 days upon co‐culture of huCD34+ or cord blood CD34+ (CB‐CD34) HSCs on murine OP9/N‐DLL‐1 stroma cells but not in a novel 3‐D cell‐culture matrix with DLL‐1low human stroma cells. In both in vitro systems, huCD34+ and CB‐CD34+ HSCs did not give rise to mature T cells. Upon transfer into 6‐wk‐old immune‐deficient mice, CTLPs alone did not engraft. However, transplantation of CTLPs together with huCD34+ HSCs resulted in rapid T‐cell engraftment in spleen, bone marrow and thymus at day 28. Strikingly, at this early time point mature T cells originated exclusively from CTLPs, whereas descendants of huCD34+ HSCs still expressed a T‐cell‐precursor phenotype (CD7+CD5+CD1a+/−). This strategy to enhance early T‐cell re‐constitution with ex vivo‐pre‐differentiated T‐lymphoid progenitors could bridge the gap until full T‐cell recovery in severely immunocompromised patients after allogeneic stem cell transplantation.
A novel cationic triblock copolymer as noncovalent coating for the separation of proteins by CE
Authors: Cao Fuhu , Zhu Xiaoxi , Luo Zhaofeng , Xing Jinxing , Shi Xiaohua , Wang Yanmei , Cheradame Hervé
Published: September 2011

A novel noncovalent adsorbed coating for CE has been prepared and explored. This coating was based on quaternized poly(2‐(dimethylamino)ethyl methacrylate)‐block‐poly(ethylene oxide)‐block‐poly(2‐(dimethylamino)ethyl methacrylate) (QDED) triblock copolymer which was synthesized by atomic transfer radical polymerization (ATRP) in our laboratory. The polycationic polymer and the negatively charged fused‐silica surface attracted each other through electrostatic interactions and hydrogen bonds. It was demonstrated that the coated capillaries provided an electroosmotic flow with reverse direction, and the magnitude of the electroosmotic flow can be modulated by varying the molecular mass of poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) block and pH value of the buffer. The effects of the molecular mass of PDMAEMA block in QDED triblock copolymer and pH value of the buffer on the separation of basic proteins were investigated in detail. The triblock copolymer coatings showed higher separation efficiency, better migration time repeatability and would apply to wider range of pH than bare fused‐silica capillary when used in separating proteins. Proteins from egg white were also separated through this QDED triblock copolymer‐coated capillary. These results demonstrated that the QDED triblock copolymer coatings are suitable for analyzing biosamples.
Optimal design for detecting dependencies with an application in spatial ecology
Authors: Müller Werner G. , Rodríguez‐Díaz Juan M. , Rivas López María J.
Published: September 2011

The paper is concerned with further developing a spatial sampling method based upon optimal design concepts motivated by an application in the area of biodiversity monitoring. Statistical techniques for detecting spatial patterns in the distribution of species richness now have some long tradition in this field, specifically the use of correlograms. The issue of where (and when) to undertake observations has, but only rarely, been treated. In this paper, we aim to extend the existing literature with techniques of finding good designs to optimize the power of tests for spatial dependence. Special emphasis will be given to the difference in using the exact distribution of Moran'sand its normal approximation in this context. We uncover the remarkable effect that the use of optimal designs tends to improve the normal approximation. Two illustrative artificial examples will be followed by a real case analysis from the ecological literature. Copyright © 2011 John Wiley & Sons, Ltd.
State space approach to magnetohydrodynamic flow of perfectly conducting micropolar fluid with stretch
Authors: Ezzat Magdy A. , El‐Sapa Shreen
Published: September 2011

In this work we introduce a model of the boundary layer equations for a perfect conducting micropolar fluid with stretch, bounded by an infinite vertical flat plane surface of a constant temperature. This model is applied to study the effects of free convection currents on the flow of the fluid in the presence of a constant magnetic field. The state space technique is adopted for the solution of a one‐dimensional problem for any set of boundary conditions. The resulting formulation together with the Laplace transform techniques are applied to a thermal shock problem. The inversion of the Laplace transforms is carried out using a numerical approach. Numerical results are given and illustrated graphically for the problem. Copyright © 2011 John Wiley & Sons, Ltd.
Role of Stem Cell Factor and Granulocyte Colony–Stimulating Factor in Remodeling During Liver Regeneration
Authors: Meng Fanyin , Francis Heather , Glaser Shannon , Han Yuyan , DeMorrow Sharon , Stokes Allison , Staloch Dustin , Venter Julie , White Melanie , Ueno Yoshiyuki , Reid Lola M. , Alpini Gianfranco
Published: September 2011

Functional pluripotent characteristics have been observed in specific subpopulations of hepatic cells that express some of the known cholangiocyte markers. Although evidence indicates that specific cytokines, granulocyte macrophage colony–stimulating factors (GM–CSFs), and stem cell factors (SCFs) may be candidate treatments for liver injury, the role of these cytokines in intrahepatic biliary epithelium remodeling is unknown. Thus, our aim was to characterize the specific cytokines that regulate the remodeling potentials of cholangiocytes after 70% partial hepatectomy (PH). The expression of the cytokines and their downstream signaling molecules was studied in rats after 70% PH by immunoblotting and in small and large murine cholangiocyte cultures (SMCCs and LMCCs) by immunocytochemistry and real–time polymerase chain reaction (PCR). There was a significant, stable increase in SCF and GM–CSF levels until 7 days after PH. Real–time PCR analysis revealed significant increases of key remodeling molecules, such as S100 calcium–binding protein A4 (S100A4) and miR–181b, after SCF plus GM–CSF administration in SMCCs. SMCCs produced significant amounts of soluble and bound SCFs and GM–CSFs in response to transforming growth factor–beta (TGF–β). When SMCCs were incubated with TGF–β plus anti–SCF+GM–CSF antibodies, there was a significant decrease in S100A4 expression. Furthermore, treatment of SMCCs with SCF+GM–CSF significantly increased matrix metalloproteinases (MMP–2 and MMP–9) messenger RNA as well as miR–181b expression, along with a reduction of metalloproteinase inhibitor 3. Levels of MMP–2, MMP–9, and miR–181b were also up–regulated in rat liver and isolated cholangiocytes after PH.

Conclusion

: Our data suggest that altered expression of SCF+GM–CSF after PH can contribute to biliary remodeling (e.g., post–transplantation) by functional deregulation of the activity of key signaling intermediates involved in cell expansion and multipotent differentiation. (Hepatology 2012;;55:209–221)
Benefit of Initial Resection of Hepatocellular Carcinoma Followed by Transplantation in Case of Recurrence
Authors: Fuks David , Dokmak Safi , Paradis Valérie , Diouf Momar , Durand François , Belghiti Jacques
Published: September 2011

Liver resection (LR) for hepatocellular carcinoma (HCC) as the first–line treatment in transplantable patients followed by “salvage transplantation” (ST) in case of recurrence is an attractive concept. The aim was to identify patients who gain benefit from this approach in an intention–to–treat study. From 1998 to 2008, among 329 potential candidates for liver transplantation (LT) with HCC within the Milan criteria (MC), 138 with good liver function were resected (LR group) from a perspective of ST in case of recurrence, and 191 were listed for LT first (LT group). The two groups were compared on an intention–to–treat basis with special reference to management of recurrences and transplantability after LR. Univariate and multivariate analyses were performed to identify resected patients who developed recurrence beyond MC. Five–year overall and disease–free survival was similar in both groups: LT versus LR group, 60% versus 77% and 56% versus 40%, respectively. Among the 138 patients in the LR group, 20 underwent LT before recurrence, 39 (28%) had ST, and 51 (37%) with recurrence were not transplanted including 21 within MC who were excluded for advanced age, acquired comorbidities, or refusal and 30 (22%) with recurrence beyond MC. Predictive factors for nontransplantability due to recurrence beyond MC included microscopic vascular invasion (hazard ratio [HR] 2.38 [range, 1.10–7.29]), satellite nodules (HR 2.46 [range, 1.01–6.68]), tumor size > 3 cm (HR 1.34 [range, 1.03–3.12]), poorly differentiated tumor (HR 3.18 [range, 1.31–7.70]), and liver cirrhosis (HR 1.90 [range, 1.04–3.12]).

Conclusion

: The high risk of failure of ST after initial LR for HCC within MC suggests the use of tissue analysis as a selection criterion. The salvage LT strategy should be restricted to patients with favorable oncological factors. (Hepatology 2012;;55:132–140)
Activation of Autophagy Protects Against Acetaminophen–Induced Hepatotoxicity
Authors: Ni Hong–Min , Bockus Abigail , Boggess Nikki , Jaeschke Hartmut , Ding Wen–Xing
Published: September 2011

Autophagy can selectively remove damaged organelles, including mitochondria, and, in turn, protect against mitochondria–damage–induced cell death. Acetaminophen (APAP) overdose can cause liver injury in animals and humans by inducing mitochondria damage and subsequent necrosis in hepatocytes. Although many detrimental mechanisms have been reported to be responsible for APAP–induced hepatotoxicity, it is not known whether APAP can modulate autophagy to regulate hepatotoxicity in hepatocytes. To test the hypothesis that autophagy may play a critical protective role against APAP–induced hepatotoxicity, primary cultured mouse hepatocytes and green fluorescent protein/light chain 3 transgenic mice were treated with APAP. By using a series of morphological and biochemical autophagic flux assays, we found that APAP induced autophagy both in the

in vivo

mouse liver and in primary cultured hepatocytes. We also found that APAP treatment might suppress mammalian target of rapamycin in hepatocytes and that APAP–induced autophagy was suppressed by

N

–acetylcysteine, suggesting APAP mitochondrial protein binding and the subsequent production of reactive oxygen species may play an important role in APAP–induced autophagy. Pharmacological inhibition of autophagy by 3–methyladenine or chloroquine further exacerbated APAP–induced hepatotoxicity. In contrast, induction of autophagy by rapamycin inhibited APAP–induced hepatotoxicity.

Conclusion

: APAP overdose induces autophagy, which attenuates APAP–induced liver cell death by removing damaged mitochondria. (Hepatology 2012)
A multilevel examination of the influence of trainee‐trainer gender dissimilarity and trainee‐classroom gender composition dissimilarity on trainee knowledge acquisition
Authors: Bell Suzanne T. , Towler Annette J. , Fisher David M.
Published: September 2011

We examined the extent to which a trainee's gender interacts with the gender of the trainer, as well as the gender composition of the classroom, to influence the trainee's knowledge acquisition. Hypotheses based on asymmetrical relational demography arguments were tested with a multilevel model on data collected from 1,515 predominantly Hispanic adult trainees in 115 classrooms taught by a total of 22 different trainers. Results supported an asymmetrical relational demography effect for the relationship between trainee‐trainer gender dissimilarity and knowledge acquisition, such that trainer‐trainee dissimilarity was related to knowledge acquisition for female trainees, but not for male trainees. No effects on trainee knowledge acquisition were observed for the trainee gender and classroom gender composition interaction. Exploratory analyses suggested that the racial diversity of the classroom was related to the knowledge acquisition of female trainees, but not male trainees.
Married Thai working mothers: Coping with initial part‐time doctoral study
Authors: Thinnam Thanit
Published: September 2011

Advanced educational attainment can “grow” a career. But acquiring a doctoral qualification adds study to existing work and family responsibilities, especially for women. This phenomenological research explores the experiences of eight Thai working mothers enrolled in the initial stage of part‐time doctoral programs in Thailand. A majority enrolled for work‐related reasons: some believe that the qualification would support their careers, others that it would help them escape their present work situation. Work can be an ally and/or an enemy of study, or there may be no relation. Workplace support is an important factor. Findings elucidate subjects' difficulties and indicate differential levels of adaptive capacity. Copers had the ability to integrate all three demands. Doctoral study impacts on work‐life balance raise unexplored issues for HRD managers.
AUTOMATIC IN SITU DETERMINATION OF FIELD CAPACITY USING SOIL MOISTURE SENSORS
Authors: Fazackerley Scott , Lawrence Ramon
Published: September 2011

Field capacity is a frequently used concept in irrigation systems and agriculture. Although there is some debate on how field capacity is defined, it is generally accepted as being the upper limit on the available water that is stored in a soil profile that can be held against the pull of gravity. Standard methods for determining field capacity require waiting two days before measuring volumetric water content after raising the water content above field capacity. This is time‐consuming and subject to natural water inputs during the monitoring period. The contribution of this work is a method for rapidly estimating field capacity in situ using volumetric water sensors, a specific irrigation schedule, and a nonlinear curve fitting model that predicts field capacity using a drainage model. The result allows for determining field capacity rapidly with very good accuracy and can be used with automatic irrigation systems in landscaping and agriculture. Copyright © 2011 John Wiley & Sons, Ltd.
Proteoglycan 4: A dynamic regulator of skeletogenesis and parathyroid hormone skeletal anabolism
Authors: Novince Chad M , Michalski Megan N , Koh Amy J , Sinder Benjamin P , Entezami Payam , Eber Matthew R , Pettway Glenda J , Rosol Thomas J , Wronski Thomas J , Kozloff Ken M , McCauley Laurie K
Published: September 2011

Proteoglycan 4 (Prg4), known for its lubricating and protective actions in joints, is a strong candidate regulator of skeletal homeostasis and parathyroid hormone (PTH) anabolism. Prg4 is a PTH-responsive gene in bone and liver. Prg4 null mutant mice were used to investigate the impact of proteoglycan 4 on skeletal development, remodeling, and PTH anabolic actions. Young Prg4 mutant and wild-type mice were administered intermittent PTH(1–34) or vehicle daily from 4 to 21 days. Young Prg4 mutant mice had decreased growth plate hypertrophic zones, trabecular bone, and serum bone formation markers versus wild-type mice, but responded with a similar anabolic response to PTH. Adult Prg4 mutant and wild-type mice were administered intermittent PTH(1–34) or vehicle daily from 16 to 22 weeks. Adult Prg4 mutant mice had decreased trabecular and cortical bone, and blunted PTH-mediated increases in bone mass. Joint range of motion and animal mobility were lower in adult Prg4 mutant versus wild-type mice. Adult Prg4 mutant mice had decreased marrow and liver fibroblast growth factor 2 (FGF-2) mRNA and reduced serum FGF-2, which were normalized by PTH. A single dose of PTH decreased the PTH/PTHrP receptor (PPR), and increased Prg4 and FGF-2 to a similar extent in liver and bone. Proteoglycan 4 supports endochondral bone formation and the attainment of peak trabecular bone mass, and appears to support skeletal homeostasis indirectly by protecting joint function. Bone- and liver-derived FGF-2 likely regulate proteoglycan 4 actions supporting trabeculae formation. Blunted PTH anabolic responses in adult Prg4 mutant mice are associated with altered biomechanical impact secondary to joint failure. © 2012 American Society for Bone and Mineral Research
Mindfulness and modification therapy for behavioral dysregulation: results from a pilot study targeting alcohol use and aggression in women
Authors: Wupperman Peggilee , Marlatt G. Alan , Cunningham Amy , Bowen Sarah , Berking Matthias , Mulvihill‐Rivera Nicole , Easton Caroline
Published: September 2011

Objectives: Increasing evidence suggests that deficits in mindfulness (awareness, attentiveness, and acceptance of the present moment) play a role in a range of disorders involving behavioral dysregulation. This paper adds to that literature by describing a transdiagnostic psychotherapy (Mindfulness & Modification Therapy; MMT) developed to target behavioral dysregulation. Design: An open‐treatment pilot‐trial investigated the feasibility, acceptability, and pre‐post effects of MMT targeting women (N = 14) court‐referred for alcohol abuse/dependence and aggression. Results: Pre‐post comparisons revealed significant decreases in alcohol use, drug use, and aggression. In addition, the retention rate was 93%. Conclusion: Preliminary evidence suggests that MMT is a feasible and acceptable treatment that decreases dysregulated behaviors such as substance use and aggression, while also potentially increasing retention. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–17, 2011.
Arachidonic acid metabolism via cytosolic phospholipase A2α induces cytotoxicity in niemann–pick disease type C cells
Authors: Nakamura Hiroyuki , Yasufuku Kana , Makiyama Tomohiko , Matsumoto Ikiru , Fujino Hiromichi , Murayama Toshihiko
Published: September 2011

Niemann–Pick disease type C (NPC) is a neurodegenerative lipid storage disorder caused by mutations in NPC1 or NPC2 genes. Loss of function of either protein results in the endosomal accumulation of cholesterol and other lipids. Here, we report that NPC1‐deficient Chinese hamster ovary cells exhibit increased release of arachidonic acid (AA) and synthesis of prostaglandin E2 compared with wild‐type cells. The enhanced release of AA was inhibited by both treatment with the selective inhibitor of cytosolic phospholipase A2α (cPLA2α) and cultivation in lipoprotein‐deficient medium. There was no difference in the expression of both cyclooxygenase‐1 and ‐2 between NPC cells and wild‐type cells. U18666A, a cholesterol transport‐inhibiting agent commonly used to mimic NPC, also increased the release of AA in L929 mouse fibrosarcoma cells. Furthermore, U18666A‐induced formation of reactive oxygen species (ROS) resulted in the induction of cell death and cell cycle delay/arrest in L929 cells. Interestingly, these responses induced by U18666A were much weaker in cPLA2α knockdown L929 cells. These results suggest that cPLA2α‐AA pathway plays important roles in the cytotoxicity and the ROS formation in NPC cells. J. Cell. Physiol. 227: 2847–2855, 2012. © 2011 Wiley Periodicals, Inc.
Perfusion fraction of diffusion‐weighted MRI for predicting the presence of blood supply in ovarian masses
Authors: Morita Satoru , Kojima Shinya , Hirata Masami , Suzuki Kazufumi , Ueno Eiko
Published: September 2011

Purpose:

To evaluate whether perfusion fraction (PF) calculated with diffusion‐weighted magnetic resonance imaging (MRI) predicts the presence of blood supply in ovarian masses.

Materials and Methods:

PFs of 92 ovarian lesions in 53 patients administered gadolinium were retrospectively calculated with diffusion‐weighted images at b‐values of 0, 500, and 1000 sec/mm2. PFs were compared between ovarian lesions, except for fat, with (n = 21) or without contrast enhancement (n = 57), using Student's t‐test and receiver operating characteristics (ROC) curve analysis. Lesion enhancement rates of contrast‐enhanced images at 30 and 180 seconds after gadolinium injection (ER30sec and ER180sec) and PFs were compared using Pearson's correlation coefficient.

Results:

PFs of the lesions with contrast enhancement were significantly higher than those without contrast enhancement (0.22 ± 0.09 and 0.02 ± 0.08, respectively, P < 0.0001). The ROC curve identified the best cutoff point for PF at 0.135 (95.2% sensitivity and 94.7% specificity) as a predictor of the contrast enhancement effect. The area under the ROC curve was 0.984. PF correlated moderately with ER30sec (0.62, y = 0.13x + 0.04, P < 0.0001) and ER180sec (0.74, y = 0.13x + 0.03, P < 0.0001).

Conclusion:

PF calculated with diffusion‐weighted images can potentially predict blood supply in ovarian masses. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc.
High‐resolution MRI of excised human prostate specimens acquired with 9.4T in detection and identification of cancers: Validation of a technique
Authors: Fan Xiaobing , Haney Chad R. , Agrawal Garima , Pelizzari Charles A. , Antic Tatjana , Eggener Scott E. , Sethi Ila , River Jonathan N. , Zamora Marta , Karczmar Gregory S. , Oto Aytekin
Published: September 2011

Purpose:

To evaluate feasibility of high‐resolution, high‐field ex vivo prostate magnetic resonance imaging (MRI) as an aid to guide pathologists' examination and develop in vivo MRI methods.

Materials and Methods:

Unfixed excised prostatectomy specimens (n = 9) were obtained and imaged immediately after radical prostatectomy under an Institutional Review Board‐approved protocol. High‐resolution T2‐weighted (T2W) MRI of specimens were acquired with a Bruker 9.4 T scanner to correlate with whole‐mount histology. Additionally, T2 and apparent diffusion coefficient (ADC) maps were generated.

Results:

By visual inspection of the nine prostate specimens imaged, high‐resolution T2W MRI showed improved anatomical detail compared to published low‐resolution images acquired at 4 T as published by other investigators. Benign prostatic hyperplasia, adenocarcinomas, curvilinear duct architecture distortion due to adenocarcinomas, and normal radial duct distribution were readily identified. T2 was ≈10 msec longer (P < 0.03) and the ADC was ≈1.4 times larger (P < 0.002) in the normal peripheral zone compared to the peripheral zone with prostate cancer.

Conclusion:

Differences in T2 and ADC between benign and malignant tissue are consistent with in vivo data. High‐resolution, high‐field MRI has the potential to improve the detection and identification of prostate structures. The protocols and techniques developed in this study could augment routine pathological analysis of surgical specimens and guide treatment of prostate cancer patients. J. Magn. Reson. Imaging 2011. © 2011 Wiley‐Liss, Inc.
Quantitative assessment of liver fat with magnetic resonance imaging and spectroscopy
Authors: Reeder Scott B. , Cruite Irene , Hamilton Gavin , Sirlin Claude B.
Published: September 2011

Hepatic steatosis is characterized by abnormal and excessive accumulation of lipids within hepatocytes. It is an important feature of diffuse liver disease, and the histological hallmark of nonalcoholic fatty liver disease (NAFLD). Other conditions associated with steatosis include alcoholic liver disease, viral hepatitis, human immunodeficiency virus (HIV) and genetic lipodystrophies, cystic fibrosis liver disease, and hepatotoxicity from various therapeutic agents. Liver biopsy, the current clinical gold standard for assessment of liver fat, is invasive and has sampling errors, and is not optimal for screening, monitoring, clinical decision‐making, or well suited for many types of research studies. Noninvasive methods that accurately and objectively quantify liver fat are needed. Ultrasound (US) and computed tomography (CT) can be used to assess liver fat but have limited accuracy as well as other limitations. Magnetic resonance (MR) techniques can decompose the liver signal into its fat and water signal components and therefore assess liver fat more directly than CT or US. Most MR techniques measure the signal fat‐fraction (the fraction of the liver MR signal attributable to liver fat), which may be confounded by numerous technical and biological factors and may not reliably reflect fat content. By addressing the factors that confound the signal fat‐fraction, advanced MR techniques measure the proton density fat‐fraction (the fraction of the liver proton density attributable to liver fat), which is a fundamental tissue property and a direct measure of liver fat content. These advanced techniques show promise for accurate fat quantification and are likely to be commercially available soon. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
A new monoclonal antibody, 4F2, specific for the oligodendroglial cell lineage, recognizes ATP‐dependent RNA helicase Ddx54: Possible association with myelin basic protein
Authors: Ueki Toshiyuki , Tsuruo Yoshihiro , Yamamoto Yuta , Yoshimura Kazunori , Takanaga Hiromi , Seiwa Chika , Motojima Kiyoto , Asou Hiroaki , Yamamoto Masahiro
Published: September 2011

Recent research in neural development has highlighted the importance of markers to discriminate phenotypic alterations of neural cells at various developmental stages. We isolated a new monoclonal antibody, 4F2, which was shown to be specific for an oligodendrocyte lineage. In primary cultures of oligodendroglial and mixed neural cells, the 4F2 antibody labeled a large proportion of Sox2+, Sox10+, A2B5+, NG2+, Olig2+, O4+, and myelin basic protein (MBP)+ cells but did not label any GFAP+ or NeuN+ cells. In immunohistochemisty of rat embryos, the 4F2 antibody labeled a portion of neuroepithelial cells of the neural tube at embryonic day 9. The 4F2‐positive cells were located initially in the ventricular zone as Musashi1+ Tuj1− populations and distributed throughout the striatum; thereafter, they populated the whole brain and spinal cord. These cells showed ramified processes during embryonal development. The 4F2 antigen was associated with all four isoforms of MBP in coimmunoprecipitation experiments using brain homogenates or cell lysates of cultured oligodendrocytes. Immunoscreening of a brain cDNA library identified the antigen as DEAD (Asp‐Glu‐Ala‐Asp) box polypeptide 54 (Ddx54), a member of the DEAD box family of RNA helicases involved in RNA metabolism, transcription, and translation. Cotransfection of the Ddx54 gene with MBP isoform genes increased the nuclear localization of the 21.5‐kDa MBP isoform, which has been reported to function as a nuclear signal transduction molecule. These data indicate that Ddx54 might be not only a useful marker for investigating the ontogeny of oligodendrocytes but also an important factor in oligodendrocyte differentiation and myelination. Journal of Neuroscience Research (2011) © 2011 Wiley Periodicals, Inc.
Dynamic loss of surface‐expressed AMPA receptors in mouse cortical and striatal neurons during anesthesia
Authors: Carino Charlene , Fibuch Eugene E. , Mao Li‐Min , Wang John Q.
Published: September 2011

Ionotropic glutamate receptors, especially the α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptor subtype, undergo dynamic trafficking between the surface membrane and intracellular organelles. This trafficking activity determines the efficacy and strength of excitatory synapses and is subject to modulation by changing synaptic inputs. Given the possibility that glutamate receptors in the central nervous system might be a sensitive target of anesthetic agents, this study investigated the possible impact of anesthesia on trafficking and subcellular expression of AMPA receptors in adult mouse brain neurons in vivo. We found that anesthesia induced by a systemic injection of pentobarbital did not alter total protein levels of three AMPA receptor subunits (GluR1–3) in cortical neurons. However, an anesthetic dose of pentobarbital reduced GluR1 and GluR3 proteins in the surface pool and elevated these proteins in the intracellular pool of cortical neurons. The similar redistribution of GluR1/3 was observed in mouse striatal neurons. Pentobarbital did not significantly alter GluR2 expression in the two pools. Chloral hydrate at an anesthetic dose also reduced surface GluR1/3 expression and increased intracellular levels of these proteins. The effect of pentobarbital on subcellular distribution of AMPA receptors was reversible. Altered subcellular distribution of GluR1/3 returned to normal levels after the anesthesia subsided. These data indicate that anesthesia induced by pentobarbital and chloral hydrate can alter AMPA receptor trafficking in both cortical and striatal neurons. This alteration is characterized by the concurrent loss and addition of GluR1/3 subunits in the respective surface and intracellular pools. Journal of Neuroscience Research (2011) © 2011 Wiley Periodicals, Inc.
Measuring system optimizes the running training
Authors: Hinz Oliver , Wenzlau Carsten
Published: September 2011

The most popular types of sport all over the world are walking and running. Many sportsmen have ambitions to reach a higher level. Others have even made their passion into their occupation. In all cases it needs a lot of training to reach the ambitious targets. A laser welded step sensor is able to support the running persons – indoor and outdoor.
Gases – the invisible secret of laser material processing
Authors: Hildebrandt Bernd , Wolters Michael
Published: September 2011

Gases used in laser material processing are classified as auxiliary materials and are required in a variety of different process steps depending on the process and the laser source used. In spite of their invisibility, the choice of gases is one of the crucial factors for the optimum success of laser technology.
Efficacy and Safety of Sorafenib in Combination With Mammalian Target of Rapamycin Inhibitors for Recurrent Hepatocellular Carcinoma After Liver Transplantation
Authors: Gomez-Martin Carlos , Bustamante Javier , Castroagudin Javier F. , Salcedo Magdalena , Garralda Elena , Testillano Milagros , Herrero Ignacio , Matilla Ana , Sangro Bruno
Published: September 2011

There is currently no consensus on the most suitable treatment for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation. This open, multicenter, retrospective, uncontrolled cohort study was designed to evaluate the safety and preliminary efficacy of the combined use of a mammalian target of rapamycin (mTOR) inhibitor and sorafenib in this setting. In 31 patients who suffered from HCC recurrence after liver transplantation, the immunosuppressive therapy was changed to mTOR inhibitors, and systemic treatment with sorafenib was initiated. This combination was maintained until symptomatic tumor progression, death, hepatic decompensation, or unacceptable toxicity occurred. Primary treatment efficacy was determined by overall survival and progression-free survival, and secondary efficacy was determined by the overall response rate. Toxicity parameters associated with the use of sorafenib and mTOR inhibitors were also analyzed. The overall response rate according to the Response Evaluation Criteria in Solid Tumors was 3.8% (1/26), and there was sustained stabilization of the disease in 13 additional cases (50.0%). The median overall survival was 19.3 months [95% confidence interval (CI) = 13.4–25.1 months], and the median time to progression was 6.77 months (95% CI = 2.3–11.1 months). Only 2 grade 3/4 cases of hyperglycemia and 1 case of grade 3/4 mucositis were reported, and they were possibly related to mTOR inhibitors. The most common severe adverse event probably related to sorafenib was diarrhea (12.9%). In conclusion, the coadministration of sorafenib and an mTOR inhibitor could be effective despite notable toxicity in patients with post–liver transplant HCC recurrence not suitable for radical therapy. The toxicity and efficacy need to be further evaluated in randomized controlled studies for this combination to be considered a valid option.
Synthesis, Assembled Structures, and Optoelectronic Properties of Amphiphilic Block Copolymers Containing Anthracene Units in the Main Chain
Authors: Mori Hideharu , Tanaka Hiromi
Published: September 2011

Novel amphiphilic block copolymers containing the anthracene unit in the main chain are synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization of a cyclic monomer, 10‐methylene‐9,10‐dihydroanthryl‐9‐spirophenylcyclopropane (MDS). A hydrophilic macro‐chain transfer agent is prepared by RAFT polymerization of 2‐hydroxyethyl acrylate (HEA). The polymerizations of MDS using the poly(HEA) afford amphiphilic block copolymers, in which the hydrophobic poly(MDS) segment has a perfectly alternating structure composed of an anthracene unit and a styrene unit, owing to the ring‐opening polymerization system. Characteristic assembled structures and optoelectronic properties of the amphiphilic block copolymers are investigated in various selective solvents.
Proteomic analysis of placentas from cloned cat embryos identifies a set of differentially expressed proteins related to oxidative damage, senescence and apoptosis
Authors: Bang Jae‐Il , Bae Dong‐Won , Lee Hyo‐Sang , Deb Gautam K. , Kim Myeong‐Ok , Sohn Sea‐Hwan , Han Chang‐Hee , Kong Il‐Keun
Published: September 2011

Production of cloned mammals by somatic cell nuclear transfer is associated with functional and structural abnormalities of placentation and with abnormal fetal development. A proteomic analysis was performed in domestic cats (Felis catus) to compare cloned term placentas (CTP) obtained from cesarean section (CS) to control placentas obtained from CS or vaginal delivery. The expression of 20 proteins was altered in CTP (p<0.05) compared to control placentas. The two control groups showed that the method of delivery, vaginal delivery or CS, did not affect protein expression (p>0.05). A total of 13 proteins were up‐regulated in CTP, including apoptosis‐related cathepsin D (CD), annexin A1 and heat shock protein 27 (HSP 27), and seven proteins were down‐regulated in CTP, including prohibitin (PHB). The expression of PHB and CD was confirmed by Western blotting and immunofluorescence staining. The abnormal expression of PHB and CD correlated with the generation of reactive oxygen species, leading to decreased mitochondrial membrane potential and telomeric DNA, which are associated with cellular senescence and apoptosis. In summary, a specific pattern of abnormal protein expression is associated with the impaired development and functions of cloned placentas and hence with decreased fetal viability. Strategies aimed at restoring normal placental protein expression may increase the efficiency of somatic cell nuclear transfer and transgenic cat production and help restore endangered species.
IMAC/TiO2 enrich for peptide modifications other than phosphorylation: Implications for chromatographic choice and database searching in phosphoproteomics
Authors: Worthington Jenny , Cutillas Pedro R. , Timms John F.
Published: September 2011

Protein regulation by reversible phosphorylation is fundamental in nature, and large‐scale phosphoproteomic analyses are becoming routine in proteomics laboratories. These analyses utilise phosphopeptide separation and enrichment techniques linked to LC‐MS/MS. Herein, we report that IMAC and TiO2 also enrich for non‐phosphorylated modified peptides such as acetylated, deamidated and carbamylated peptides. Urea and digestion conditions commonly used in phosphoproteomic workflows are the likely sources of the induced modifications (deamidation and carbamylation) and can easily modify phosphopeptides. Including these variable modifications in database searches increased the total number of identified phosphopeptides by 15%. We also show that strong cation exchange fractionation provides poor resolution of phosphopeptides and actually enriches these alternatively modified peptides. By switching to reverse‐phase chromatography, we show a significant improvement in the number of identified phosphopeptides. We recommend that the users of phosphopeptide enrichment strategies avoid using urea as a denaturant and that careful consideration is given to chromatographic conditions and the types of variable modifications used in database searches. Thus, the capacity of IMAC and TiO2 to enrich phosphopeptides bearing modifications other than phosphorylation is a previously unappreciated property of these chromatographies with practical implications for the field of phosphoproteomics.
The selective inhibitory effect of a synthetic tanshinone derivative on prostate cancer cells
Authors: Xu Defeng , Lin Tzu‐Hua , Zhang Caixia , Tsai Yu‐Chieh , Li Shaoshun , Zhang Jing , Yin Min , Yeh Shuyuan , Chang Chawnshang
Published: September 2011

BACKGROUND

Androgen receptor (AR) is the main therapeutic target for the treatment of prostate cancer (PCa). Anti‐androgens to reduce or prevent androgens binding to AR are widely used to suppress AR‐mediated PCa growth; however, the androgen depletion therapy (ADT) is only effective for a short period of time. Here we tested PTS33, a new sodium derivative of cryptotanshinone, which can effectively inhibit the DHT‐induced AR transactivation and PCa cell growth, and then explored the effects of PTS33 on inhibiting the expressions of AR target genes and proteins.

METHODS

PCa cells, LNCaP, CWR22Rv1, C4‐2, PC‐3, and DU145, were treated with PTS33 and luciferase assay was used to evaluate the ability of each to regulate AR transactivation. RT‐PCR was used to evaluate the mRNA levels of AR target genes such as PSA, TMPRSS2, and TMEPA1. Western blot was used to determine AR, PSA, estrogen receptor alpha (ERα), glucocorticoid receptor (GR), and progesterone receptor (PR) protein expression. Cell growth and IC50 were determined by MTT assay after 48 hr treatment.

RESULTS

Our data showed that PTS33 selectively inhibits AR activities, but PTS33 does not repress the activities of other nuclear receptors, including ERα, GR, and PR. At a low concentration, 2 µM of PTS33 effectively suppresses the growth of AR‐positive PCa cells, and has little effect on AR‐negative PCa cells. Furthermore, our data indicated that PTS33 could modulate AR transactivation and suppress the AR target genes (PSA, TMPRSS2, and TMEPA1) expression in both androgen responsive PCa LNCaP cells and castration‐resistant C4‐2 cells. In addition, PTS33 can also inhibit estrogen/Δ5‐androstenediol induced AR activities. The mechanistic studies indicate that PTS33 can inhibit AR function by suppression of AR protein expression, the AR N–C interaction, and AR–coregulator interaction.

CONCLUSIONS

PTS33 has shown a good efficacy to inhibit AR transactivation, block AR regulated gene expression, and reduce cell growth in AR positive PCa cells. The structure of PTS33 could be used as a base for development of novel AR signaling inhibitors to treat PCa. Prostate 72:803–816, 2012. © 2011 Wiley Periodicals, Inc.
Radioresistance of prostate cancer cells with low proteasome activity
Authors: Della Donna Lorenza , Lagadec Chann , Pajonk Frank
Published: September 2011

BACKGROUND

Prostate cancer is frequently treated with radiotherapy. While treatment results are in general excellent, some patients relapse and current systemic therapies are not curative, thus, underlining the need for novel targeted therapies. Proteasome inhibitors have been suggested as promising new agents against solid tumors including prostate cancer but initial results from clinical trials are disappointing.

METHODS

In this study we tested if prostate cancer cells are heterogeneous with regard to their intrinsic 26S proteasome activity, which could explain the lack of clinical responses to bortezomib. PC‐3 and DU145 prostate cancer cells and an imaging system for proteasome activity were used to identify individual cells with low proteasome activity. Clonogenic survival assays, a sphere‐forming assay and an in vivo limiting dilution assay were used to characterize radiation sensitivity, self‐renewal capacity, and tumorigenicity of the different subsets of cells.

RESULTS

We identified a small population of cells with intrinsically low 26S proteasome activity. Fractionated radiation enriched for these cells and clonogenic survival assays and sphere‐forming assays revealed a radioresistant phenotype and increased self‐renewal capacity.

CONCLUSIONS

We conclude that low 26S proteasome activity identifies a radioresistant prostate cancer cell population. This population of cells could be responsible for the clinical resistance of advanced prostate cancer to proteasome inhibitors and radiation. Prostate 72:868–874, 2012. © 2011 Wiley Periodicals, Inc.
XMRV accelerates cellular proliferation, transformational activity, and invasiveness of prostate cancer cells by downregulating p27Kip1
Authors: Pandhare‐Dash Jui , Mantri Chinmay K. , Gong Yuanying , Chen Zhenbang , Dash Chandravanu
Published: September 2011

BACKGROUND

Xenotropic murine leukemia virus‐related retrovirus (XMRV) is a recently discovered gammaretrovirus that was originally detected in prostate tumors. However, a causal relationship between XMRV and prostate cancer remains controversial due to conflicting reports on its etiologic occurrence. Even though gammaretroviruses are known to induce cancer in animals, a mechanism for XMRV‐induced carcinogenesis remains unknown. Several mechanisms including insertional mutagenesis, proinflammatory effects, oncogenic viral proteins, immune suppression, and altered epithelial/stromal interactions have been proposed for a role of XMRV in prostate cancer. However, biochemical data supporting any of these mechanisms are lacking. Therefore, our aim was to evaluate a potential role of XMRV in prostate carcinogenesis.

METHODS

Growth kinetics of prostate cancer cells are conducted by MTT assay. In vitro transformation and invasion was carried out by soft agar colony formation, and Matrigel cell invasion assay, respectively. p27Kip1 expression was determined by Western blot and MMP activation was evaluated by gelatin‐zymography. Up‐regulation of miR221 and miR222 expression was examined by real‐time PCR.

RESULTS

We demonstrate that XMRV infection can accelerate cellular proliferation, enhance transformation, and increase invasiveness of slow growing prostate cancer cells. The molecular basis of these viral induced activities is mediated by the downregulation of cyclin/cyclin dependent kinase inhibitor p27Kip1. Downstream analyses illustrated that XMRV infection upregulates miR221 and miR222 expression that target p27Kip1 mRNA.

CONCLUSIONS

We propose that downregulation of p27Kip1 by XMRV infection facilitates transition of G1 to S, thereby accelerates growth of prostate cancer cells. Our findings implicate that if XMRV is present in humans, then under appropriate cellular microenvironment it may serve as a cofactor to promote cancer progression in the prostate. Prostate 72:886–897, 2012. © 2011 Wiley Periodicals, Inc.
On the molecular structure of human neuroserpin polymers
Authors: Santangelo Maria Grazia , Noto Rosina , Levantino Matteo , Cupane Antonio , Ricagno Stefano , Pezzullo Margherita , Bolognesi Martino , Mangione Maria Rosalia , Martorana Vincenzo , Manno Mauro
Published: September 2011

The polymerization of serpins is at the root of a large class of diseases; the molecular structure of serpin polymers has been recently debated. In this work, we study the polymerization kinetics of human neuroserpin by Fourier Transform Infra Red spectroscopy and by time‐lapse Size Exclusion Chromatography. First, we show that two distinct neuroserpin polymers, formed at 45 and 85°C, display the same isosbestic points in the Amide I′ band, and therefore share common secondary structure features. We also find a concentration independent polymerization rate at 45°C suggesting that the polymerization rate‐limiting step is the formation of an activated monomeric species. The polymer structures are consistent with a model that predicts the bare insertion of portions of the reactive center loop into the A β‐sheet of neighboring serpin molecule, although with different extents at 45 and 85°C. Proteins 2012; © 2011 Wiley Periodicals, Inc.