bluuebunny/crossref_metadata_2025 huggingface dataset:
Microscopic image segmentation based on pixel classification and dimensionality reduction
Authors: Benazzouz Mourtada , Baghli Ismahan , Chikh Med Amine
Published: February 2013

Pathological image analysis plays a significant role in effective disease diagnostics. In this article, a tool for diagnosis assistance by automatic segmentation of bone marrow images is introduced. The aim of our segmentation is to demarcate cell's component: nucleus, cytoplasm, red cells, and background. Different color spaces were used to extract color's features to profit of their complementarity. We introduce several dimensionality reduction techniques. These techniques are exemplified on a support vector machine pixel‐based bone marrow image segmentation problem in which it is shown that it may give significant improvement in segmentation accuracy and time consuming. © 2013 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 23, 22–28, 2013
BMD changes and predictors of increased bone loss in postmenopausal women after a 5-year course of alendronate
Authors: McNabb Brian Louis , Vittinghoff Eric , Schwartz Ann V , Eastell Richard , Bauer Douglas C , Ensrud Kristine , Rosenberg Elizabeth , Santora Arthur , Barrett-Connor Elizabeth , Black Dennis M
Published: February 2013

Management of women discontinuing bisphosphonates after 3 to 5 years of treatment is controversial. Little is known about how much bone mineral density (BMD) is lost after discontinuation or whether there are risk factors for greater rates of bone loss post-discontinuation. We report patterns of change in BMD and prediction models for the changes in BMD in postmenopausal women during a 5-year treatment-free period after alendronate (ALN) therapy. We studied 406 women enrolled in the Fracture Intervention Trial (FIT) who had taken ALN for a mean of 5 years and were then enrolled in the placebo arm of the FIT Long-Term Extension (FLEX) trial for an additional 5 years, describing 5-year percent changes in total hip, femoral neck, and lumbar spine BMD over the treatment-free period. Prediction models of 5-year percent changes in BMD considered all linear combinations of candidate risk factors for bone loss such as BMD at the start of the treatment-free period, the change in BMD on ALN, age, and fracture history. Serum for three markers of bone turnover was available in 76 women, and these bone turnover markers were included as candidate predictors for these 76 women. Mean 5-year BMD changes were –3.6% at the total hip, –1.7% at the femoral neck, and 1.3% at the lumbar spine. Five-year BMD losses of >5% were experienced by 29% of subjects at the total hip, 11% of subjects at the femoral neck, and 1% of subjects at the lumbar spine. Several risk factors such as age and BMI were associated with greater bone loss, but no models based on these risk factors predicted bone loss rates. Although about one-third of women who discontinued ALN after 5 years experienced >5% bone loss at the total hip, predicting which women will lose at a higher rate was not possible.
Matrix Metalloproteinase–Driven Endochondral Fracture Union Proceeds Independently of Osteoclast Activity
Authors: McDonald Michelle M , Morse Alyson , Mikulec Kathy , Peacock Lauren , Baldock Paul A , Kostenuik Paul J , Little David G
Published: February 2013

As new insights into the complexities of endochondral fracture repair emerge, the temporal role of osteoclast activity remains ambiguous. With numerous antiresorptive agents available to treat bone disease, understanding their impact on bone repair is vital. Further, in light of recent work suggesting osteoclast activity may not be necessary during early endochondral fracture union, we hypothesize instead a pivotal role of matrix metalloproteinase (MMP) secreting cells in driving this process. Although the role of MMPs in fracture healing has been examined, no directly comparative experiments exist. We examined a number of antiresorptive treatments to either block osteoclast activity, including the potent bisphosphonates zoledronic acid (ZA) and clodronate (CLOD), which work via differing mechanisms, or antagonize osteoclastogenesis with recombinant OPG (HuOPG-Fc), comparing these directly to an inhibitor of MMP activity (MMI270). Endochondral ossification to union occurred normally in all antiresorptive groups. In contrast, MMP inhibition greatly impaired endochondral union, significantly delaying cartilage callus removal. MMP inhibition also produced smaller, denser hard calluses. Hard callus remodeling was, as expected, delayed with ZA, CLOD, and OPG treatment at 4 and 6 weeks, resulting in larger, more mineralized calluses at 6 weeks. As a result of reduced hard callus turnover, bone formation was reduced with antiresorptive agents at these time points. These results confirm that the achievement of endochondral fracture union occurs independently of osteoclast activity. Alternatively, MMP secretion by invading cells is obligatory to endochondral union. This study provides new insight into cellular contributions to bone repair and may abate concerns regarding antiresorptive therapies impeding initial fracture union.
Inhibition of Ca2+/Calmodulin–Dependent Protein Kinase Kinase 2 Stimulates Osteoblast Formation and Inhibits Osteoclast Differentiation
Authors: Cary Rachel L , Waddell Seid , Racioppi Luigi , Long Fanxin , Novack Deborah V , Voor Michael J , Sankar Uma
Published: February 2013

Bone remodeling, a physiological process characterized by bone formation by osteoblasts (OBs) and resorption of preexisting bone matrix by osteoclasts (OCs), is vital for the maintenance of healthy bone tissue in adult humans. Imbalances in this vital process result in pathological conditions including osteoporosis. Owing to its initial asymptomatic nature, osteoporosis is often detected only after the patient has sustained significant bone loss or a fracture. Hence, anabolic therapeutics that stimulate bone accrual is in high clinical demand. Here we identify Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) as a potential target for such therapeutics because its inhibition enhances OB differentiation and bone growth and suppresses OC differentiation. Mice null for CaMKK2 possess higher trabecular bone mass in their long bones, along with significantly more OBs and fewer multinuclear OCs. In vitro, although Camkk2−/− mesenchymal stem cells (MSCs) yield significantly higher numbers of OBs, bone marrow cells from Camkk2−/− mice produce fewer multinuclear OCs. Acute inhibition of CaMKK2 by its selective, cell-permeable pharmacological inhibitor STO-609 also results in increased OB and diminished OC formation. Further, we find phospho-protein kinase A (PKA) and Ser133 phosphorylated form of cyclic adenosine monophosphate (cAMP) response element binding protein (pCREB) to be markedly elevated in OB progenitors deficient in CaMKK2. On the other hand, genetic ablation of CaMKK2 or its pharmacological inhibition in OC progenitors results in reduced pCREB as well as significantly reduced levels of its transcriptional target, nuclear factor of activated T cells, cytoplasmic (NFATc1). Moreover, in vivo administration of STO-609 results in increased OBs and diminished OCs, conferring significant protection from ovariectomy (OVX)-induced osteoporosis in adult mice. Overall, our findings reveal a novel function for CaMKK2 in bone remodeling and highlight the potential for its therapeutic inhibition as a valuable bone anabolic strategy that also inhibits OC differentiation in the treatment of osteoporosis.
Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: A systematic review and meta-analysis
Authors: Gedmintas Lydia , Solomon Daniel H , Kim Seoyoung C
Published: February 2013

Although there is strong evidence that bisphosphonates prevent certain types of osteoporotic fractures, there are concerns that these medications may be associated with rare atypical femoral fractures (AFF). Recent published studies examining this potential association are conflicting regarding the existence and strength of this association. We conducted a systematic review and meta-analysis of published studies examining the association of bisphosphonates with subtrochanteric, femoral shaft, and AFF. The random-effects model was used to calculate the pooled estimates of adjusted risk ratios (RR). Subgroup analysis was performed by study design, for studies that used validated outcome definitions for AFF, and for studies reporting on duration of bisphosphonate use. Eleven studies were included in the meta-analysis: five case-control and six cohort studies. Bisphosphonate exposure was associated with an increased risk of subtrochanteric, femoral shaft, and AFF, with adjusted RR of 1.70 (95% confidence interval [CI], 1.22–2.37). Subgroup analysis of studies using the American Society for Bone and Mineral Research criteria to define AFF suggests a higher risk of AFF, with bisphosphonate use with RR of 11.78 (95% CI, 0.39–359.69) as compared to studies using mainly diagnosis codes (RR, 1.62; 95% CI, 1.18–2.22), although there is a wide confidence interval and severe heterogeneity (I2 = 96.15%) in this subgroup analysis. Subgroup analysis of studies examining at least 5 years of bisphosphonate use showed adjusted RR of 1.62 (95% CI, 1.29–2.04). This meta-analysis suggests there is an increased risk of subtrochanteric, femoral shaft, and AFF among bisphosphonate users. Further research examining the risk of AFF with long-term use of bisphosphonates is indicated as there was limited data in this subgroup. The public health implication of this observed increase in AFF risk is not clear.
A DERIVED TRANSFER OF ELICITING EMOTIONAL FUNCTIONS USING DIFFERENCES AMONG ELECTROENCEPHALOGRAMS AS A DEPENDENT MEASURE
Authors: Amd Micah , Barnes‐Holmes Dermot , Ivanoff Jason
Published: February 2013

Emotional responses have specific electroencephalographic (EEG) signatures that arise within a few hundred milliseconds post‐stimulus onset. In this experiment, EEG measures were employed to assess for transfer of emotional functions across three 3‐member equivalence classes in an extension of Dougher, Auguston, Markham, Greenway, & Wulfert's (1994) seminal work on the transfer of arousal functions. Specifically, 12 human participants were trained in the following match‐to‐sample performances A1 = B1, A2 = B2, A3 = B3 and B1 = C1, B2 = C2, B3 = C3. After successfully testing for the emergence of symmetry relations (B1 = A1, B2 = A2, B3 = A3 and C1 = B1, C2 = B2, C3 = B3), visual images depicting emotionally positive and emotionally negative content were presented with A1 and A3, respectively, using a mixed stimulus pairing–compounding procedure. A2 was paired with emotionally neutral images. Next, EEG data were recorded as participants were exposed to a forced‐choice recognition task with stimuli A1, B1, C1, A2, B2, C2, A3, B3, C3 and three novel stimuli A4, B4 and C4. Results yielded differential EEG effects for stimuli paired directly with emotional versus neutral images. Critically, differential EEG effects were also recorded across the C stimuli that were equivalently related to the A stimulus set. The EEG data coincide with previous reports of emotion‐specific EEG effects, indicating that the initial emotional impact of a stimulus may emerge based on direct stimulus pairing and derived stimulus relations.
Molecular Cloning, Tissue Distribution, and Ontogenetic Expression of Ghrelin and Regulation of Expression by Fasting and Refeeding in the Grass Carp (Ctenopharyngodon idellus)
Authors: FENG KE , ZHANG GUI‐RONG , WEI KAI‐JIAN , XIONG BANG‐XI
Published: February 2013

Ghrelin is a recently discovered brain–gut peptide in fish and mammals. It has two main physiological functions—stimulating growth hormone secretion and regulating appetite. To investigate the biological function of ghrelin in appetite regulation in grass carp Ctenopharyngodon idellus, the full‐length cDNA sequence of the ghrelin gene was obtained by RT‐PCR and rapid amplification of cDNA ends methods. Homology analysis indicated that ghrelin cDNA sequence is conserved in teleosts. The grass carp ghrelin gene consists of four exons and three introns, which is similar to that of common carp, zebrafish and humans. Real‐time quantitative PCR was used to detect ghrelin mRNA expression in the study. In adult tissues, high levels of gene expression were found in the foregut; moderate levels in the muscle, liver, hypothalamus, white adipose tissue, midgut, heart, and pituitary; and lower levels in the three other examined tissues. During embryonic development, ghrelin mRNA expression could be detected as early as fertilized egg stage and displayed an increase in expression until heart appearance stage. After hatching, the level of ghrelin mRNA expression decreased sharply to the lowest level at 1 day post‐hatching (dph), then increased to a higher level at 7 dph and subsequently decreased to a relative stabilized level from 15 to 35 dph. The ghrelin mRNA expression was significantly upregulated in the brain and intestine during fasting and was downregulated after refeeding. The results suggest that ghrelin mRNA expression has obvious tissue specificity and may have a role in appetite regulation in grass carp. J. Exp. Zool. 319A:202–212, 2013. © 2013 Wiley Periodicals, Inc.
Mesoteloblast‐Like Mesodermal Stem Cells in the Polychaete Annelid Platynereis dumerilii (Nereididae)
Authors: Fischer Antje H.L. , Arendt Detlev
Published: February 2013

Spiral cleavage is observed in animals that belong to the lophotrochozoa, a large group of marine invertebrates. As characteristic for spiral cleavage, the bulk of mesoderm forms from one cell, the “4d blastomere.” This process has not yet been followed in cellular detail in annelids except in the leech, where “mesoteloblasts,” a pair of mesodermal stem cells, generate two bands of mesoderm precursor cells in an iterative fashion. It is so far unknown whether such stem cell‐like lineage is a general property of 4d‐derived mesoderm in spiralian larvae. To address this, we have analyzed the cell lineage of the 4d blastomere in the polychaete annelid Platynereis dumerilii, an emerging model for lophotrochozoan and spiralian embryology (Fischer et al., 2010), by 4D microscopy, a semi‐automated cell tracking technique based on differential interference contrast serial imaging (Schnabel et al. '97). Our data reveal that the two daughter cells of the 4d cell undergo seven consecutive rounds of unequal cell divisions. They bud off smaller cells in ventral‐vegetal orientation and thus show mesoteloblast‐ and stem cell‐like behavior. Based on these findings, we suggest that mesoteloblast‐like mesodermal stem cells that form continuous mesodermal bands are part of the Errantia + Sedentaria ground pattern. In the course of annelid evolution, the number consecutive divisions of these cells would have been low initially with <10 division cycles, giving rise to larval segments only, and then increased up to 35 as observed in clitellates. J. Exp. Zool. (Mol. Dev. Evol.) 320B:94–104, 2013. © 2013 Wiley Periodicals, Inc.
Nitrogen metabolism is related to improved water‐use efficiency of nodulated alfalfa grown with sewage sludge under drought
Authors: Laura Fiasconaro M. , Sánchez‐Díaz Manuel , Carmen Antolín M.
Published: February 2013

Leguminous plants grown in sewage sludge–amended soils can acquire nitrogen by assimilation of nitrate and ammonium from the soil solution or from atmospheric‐dinitrogen (N2) fixation through association with N2‐fixing bacteria. We proposed that operation of both metabolic processes could contribute to alleviate the impact of drought in sludge‐treated plants. A greenhouse experiment was conducted to evaluate the involvement of nodule metabolism in the use efficiency of water and N in sludge‐treated plants. Treatments comprised (1) plants inoculated with rhizobia and amended with sewage sludge; (2) plants inoculated with rhizobia without any amendment; and (3) noninoculated plants supplied with ammonium nitrate, each under well‐watered and drought conditions. Under drought, sludge‐treated plants had increased plant growth and higher photosynthetic and water‐use efficiencies than untreated plants. Drought stimulated nitrate reductase and GS/GOGAT activities but did not affect the activities of phosphoenolpyruvate carboxylase and malate dehydrogenase or the leghemoglobin concentration. The results suggest that under drought conditions, both N2 fixation and nitrate assimilation in nodules of sludge‐treated plants contributed to improve plant N supply and to increase the drought tolerance of alfalfa.
Acceptance Levels of Traditional and Nontraditional Superintendents by Experienced Educators
Authors: Thompson Elizabeth H. , Thompson Randall L. , Knight John Richard
Published: February 2013

This triangulated mixed methods study examines the differences in experienced educator acceptance of nontraditional and traditional superintendents in two southern California public high school districts. A researcher‐developed 5‐point Likert‐type survey instrument combined with open‐ended questions was used, which allowed simultaneous collection of both quantitative and qualitative data. Results indicate that participants did not trust, respect, support, or accept nontraditional superintendents in comparison to traditional superintendents. The major theme that emerged from the qualitative analysis was that nontraditional superintendents are not qualified to be superintendents because of a perceived lack of teaching or other educational experience. Traditional superintendents have educational experience that allows them to relate better to teachers and students as well as to deal with complex educational issues. Quantitative data were analyzed relative to the hypotheses that traditional superintendents are easier to (a) trust, (b) respect, (c) support, and (d) accept than are nontraditional superintendents. The results led to the acceptance of all four hypotheses. The major inference of the current study is that experienced educators may not accept the leadership of nontraditional superintendents, which may affect the ability of such superintendents to lead effectively. This result is especially relevant if a nontraditional superintendent has a mandate for change when hired.
Boundary Spanning Leadership: Six Practices for Solving Problems, Driving Innovations, and Transforming Organizations
Authors: Graham Paige
Published: February 2013

By Chris Ernst and Donna Chrobot‐Mason

Published in partnership—Center for Creative Leadership and New York: McGraw‐Hill. 2011. 302 pp. ISBN: 978‐0‐07‐163887‐6. $35.00 Hardcover

Reviewed by Paige Graham, PhD
Theory and application for the promotion of wheat production in China: past, present and future
Authors: Xu Zhenzhu , Yu Zhenwen , Zhao Junye
Published: February 2013

Food security is becoming a crucial concern worldwide. In this study, we focus on wheat – a staple crop in China – as a model to review its history, status quo and future scenarios, with regard to key production technologies and management practices for wheat production and associated food security issues since the new era in China: the post‐1949 era. First, the dominant technologies and management practices over the past 60 years are reviewed. Secondly, we outline several key innovative technologies and their theoretical bases over the last decade, including (i) prohibiting excessively early senescence at a later growth stage to maintain viable leaves with higher photosynthetic capacity, (ii) postponing top dressing nitrogen application to balance carbon and nitrogen nutrition, and (iii) achieving both high yield and better grain quality mainly by increasing soil productivity and balancing the ratio of nutrient elements. Finally, concerns such as water shortages and excessive application of chemical fertilizers are presented. Nevertheless, under high negative conditions, including global warming, rapid population growth, decreasing amounts of arable land, increasing competition with cash crops and severe environmental pollution, we conclude that domestic food production will be able to meet Chinese demand in the mid to long term, because increasingly innovative technologies and improved management practices have been and may continue to be applied appropriately. © 2013 Society of Chemical Industry
Hemodynamic response to propranolol in patients with recurrent hepatitis C virus–related cirrhosis after liver transplantation: A case-control study
Authors: Schepis Filippo , Vukotic Ranka , Berzigotti Annalisa , Carrión José A. , Forns Xavier , Abraldes Juan G. , García-Valdecasas Juan-Carlos , Navasa Miguel , García-Pagán Juan-Carlos , Bosch Jaime
Published: February 2013

Cirrhosis recurrence is frequent after orthotopic liver transplantation for hepatitis C virus (HCV). Because transplantation causes liver denervation, we hypothesized that the response to propranolol might differ in transplant patients versus nontransplant patients with cirrhosis and portal hypertension. Twenty-one patients with cirrhosis recurrence after orthotopic liver transplantation with portal hypertension were compared to 20 nontransplant patients with cirrhosis, HCV, and portal hypertension, and they were matched by sex, age, presence of varices, and Child-Pugh score. The patients underwent systemic and hepatic hemodynamic measurements at the baseline and 20 minutes after intravenous propranolol (0.15 mg/kg). At the baseline, the transplant patients with cirrhosis had a lower hepatic venous pressure gradient (HVPG) than the nontransplant patients with cirrhosis (14.8 ± 2.9 versus 17.3 ± 4.4 mm Hg, P = 0.03) but a higher mean arterial pressure (MAP; 100.3 ± 12.3 versus 91.8 ± 11.6 mm Hg, P = 0.04) and higher systemic vascular resistance (2253 ± 573 versus 1883 ± 525 dyn/second/cm−5, P = 0.03). There were no differences in the cardiac index (CI). Propranolol significantly decreased HVPG to similar extents in transplant patients and nontransplant patients with cirrhosis (−14.1% ± 8.0% versus −16.9% ± 9.5%, P > 0.99). MAP tended to increase in transplant patients with cirrhosis, whereas it slightly decreased in nontransplant patients (5.1% ± 14.2% versus −4.8% ± 6.4%, P = 0.007); however, the reduction in CI was less marked in transplant patients with cirrhosis (−18.6% ± 7.6% versus −26.9% ± 9.0%, P = 0.005). In conclusion, patients with HCV-related cirrhosis and portal hypertension after orthotopic liver transplantation have lower baseline HVPG values but similar HVPG responses to propranolol infusions in comparison with nontransplant patients with cirrhosis. In contrast to nontransplant patients, propranolol increases the systemic vascular resistance and arterial pressure in transplant patients with cirrhosis and attenuates the fall in CI. Liver Transpl 19:450–456, 2013. © 2013 AASLD.
How to identify tremor dominant and postural instability/gait difficulty groups with the movement disorder society unified Parkinson's disease rating scale: Comparison with the unified Parkinson's disease rating scale
Authors: Stebbins Glenn T. , Goetz Christopher G. , Burn David J. , Jankovic Joseph , Khoo Tien K. , Tilley Barbara C.
Published: February 2013

Background

Formulas were developed to define tremor dominant (TD) and postural instability/gait difficulty (PIGD) phenotypes of Parkinson's Disease (PD) using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS). TD and PIGD designations, based on the original Unified Parkinson's Disease Rating Scale (UPDRS), provided useful designations for classifying different phenotypes of PD. With the advent of the MDS‐UPDRS, a valid set of calculations for these phenotypes is needed.

Methods

UPDRS and MDS‐UPDRS scores were collected on 877 PD patients. TD/PIGD scores were calculated using the UPDRS formula for all patients. Comparable TD and PIGD items from the MDS‐UPDRS were used to calculate new ratios. Data were analyzed using receiver operating characteristic models.

Results

The new MDS‐UPDRS TD/PIGD ratios accounted for a significant area under the curve compared with the UPDRS classification. Optimal sensitivity and specificity were obtained with MDS‐UPDRS cutoff scores of ≥1.15 for TD classification and ≤0.90 for PIGD.

Conclusions

The development of comparable and valid PIGD and TD scores from the MDS‐UPDRS provides a clear method for clinicians and researchers to transition from the original UPDRS to the new MDS‐UPDRS in categorizing patients with different clinical phenotypes. © 2013 Movement Disorder Society
Individual, family, social, and cultural predictors of depressed mood in former soviet immigrant couples
Authors: Miller Arlene M. , Sorokin Olga , Fogg Louis
Published: February 2013

Gender differences in predictors of depression for married couples from the former Soviet Union were examined in a cross‐sectional, descriptive analysis. Data were collected during a longitudinal study of post‐migration health and adaptation. The sample included 308 men and women (154 couples), ages 40–79, who had lived in the US for an average of 6 years. Generativity, marital satisfaction and communication, social support, immigration challenges, and alienation were independent predictors of depressed mood. A gender interaction was found for generativity, indicating that diminished opportunities to guide the next generation and be productive members of society may have been more depressing for women. Interventions should attend to gender differences in developmental needs, reduce immigration‐related challenges, and strengthen family and social support. Res Nurs Health 36:271–283, 2013
Technologies and challenges in large‐scale phosphoproteomics
Authors: Engholm‐Keller Kasper , Larsen Martin R.
Published: February 2013

Phosphorylation, the reversible addition of a phosphate group to amino acid side chains of proteins, is a fundamental regulator of protein activity, stability, and molecular interactions. Most cellular processes, such as inter‐ and intracellular signaling, protein synthesis, degradation, and apoptosis, rely on phosphorylation. This PTM is thus involved in many diseases, rendering localization and assessment of extent of phosphorylation of major scientific interest. MS‐based phosphoproteomics, which aims at describing all phosphorylation sites in a specific type of cell, tissue, or organism, has become the main technique for discovery and characterization of phosphoproteins in a nonhypothesis driven fashion. In this review, we describe methods for state‐of‐the‐art MS‐based analysis of protein phosphorylation as well as the strategies employed in large‐scale phosphoproteomic experiments with focus on the various challenges and limitations this field currently faces.
Efficient synthesis of monodisperse, highly crosslinked, and “living” functional polymer microspheres by the ambient temperature iniferter‐induced “living” radical precipitation polymerization
Authors: Zhao Man , Zhang Hongtao , Ma Fengning , Zhang Ying , Guo Xianzhi , Zhang Huiqi
Published: February 2013

The facile and efficient one‐pot synthesis of monodisperse, highly crosslinked, and “living” functional copolymer microspheres by the ambient temperature iniferter‐induced “living” radical precipitation polymerization (ILRPP) is described for the first time. The simple introduction of iniferter‐induced “living” radical polymerization (ILRP) mechanism into precipitation polymerization system, together with the use of ethanol solvent, allows the direct generation of such uniform functional copolymer microspheres. The polymerization parameters (including monomer loading, iniferter concentration, molar ratio of crosslinker to monovinyl comonomer, and polymerization time and scale) showed much influence on the morphologies of the resulting copolymer microspheres, thus permitting the convenient tailoring of the particle sizes by easily tuning the reaction conditions. In particular, monodisperse poly(4‐vinylpyridine‐co‐ethylene glycol dimethacrylate) microspheres were prepared by the ambient temperature ILRPP even at a high monomer loading of 18 vol %. The general applicability of the ambient temperature ILRPP was confirmed by the preparation of uniform copolymer microspheres with incorporated glycidyl methacrylate. Moreover, the “livingness” of the resulting polymer microspheres was verified by their direct grafting of hydrophilic polymer brushes via surface‐initiated ILRP. Furthermore, a “grafting from” particle growth mechanism was proposed for ILRPP, which is considerably different from the “grafting to” particle growth mechanism in the traditional precipitation polymerization. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
Stimuli‐responsive polypeptide materials prepared by ring‐opening polymerization of α‐amino acid N‐carboxyanhydrides
Authors: Zhang Shusheng , Li Zhibo
Published: February 2013

Design and synthesis of biodegradable stimuli‐responsive polypeptides are important areas considering their promising applications in biomedical fields. This article summarizes the most recent progresses in the development of stimuli‐responsive polypeptide materials prepared via ring‐opening polymerization of α‐amino acid N‐carboxyanhydrides. We discuss the design, synthesis and structure‐property correlation of emerging materials including thermo‐responsive, redox‐responsive, photo‐responsive and biomolecule responsive polypeptides. Considering the unique structural features of amino acids, we try to emphasize that the thermo‐responsive properties not only depend on the amino acid structure but also rely on the secondary structures of polypeptides. © 2013 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013
Rainbow hamilton cycles in random graphs
Authors: Frieze Alan , Loh Po‐Shen
Published: February 2013

One of the most famous results in the theory of random graphs establishes that the threshold for Hamiltonicity in the Erdős‐Rényi random graph Gn,p is around . Much research has been done to extend this to increasingly challenging random structures. In particular, a recent result by Frieze determined the asymptotic threshold for a loose Hamilton cycle in the random 3‐uniform hypergraph by connecting 3‐uniform hypergraphs to edge‐colored graphs.

In this work, we consider that setting of edge‐colored graphs, and prove a result which achieves the best possible first order constant. Specifically, when the edges of Gn,p are randomly colored from a set of (1 + o(1))n colors, with , we show that one can almost always find a Hamilton cycle which has the additional property that all edges are distinctly colored (rainbow).Copyright © 2013 Wiley Periodicals, Inc. Random Struct. Alg., 44, 328‐354, 2014
MELK-Dependent FOXM1 Phosphorylation is Essential for Proliferation of Glioma Stem Cells
Authors: Joshi Kaushal , Banasavadi-Siddegowda Yeshavanth , Mo Xiaokui , Kim Sung-Hak , Mao Ping , Kig Cenk , Nardini Diana , Sobol Robert W. , Chow Lionel M.L. , Kornblum Harley I. , Waclaw Ronald , Beullens Monique , Nakano Ichiro
Published: February 2013

Glioblastoma multiforme (GBM) is a life-threatening brain tumor. Accumulating evidence suggests that eradication of glioma stem-like cells (GSCs) in GBM is essential to achieve cure. The transcription factor FOXM1 has recently gained attention as a master regulator of mitotic progression of cancer cells in various organs. Here, we demonstrate that FOXM1 forms a protein complex with the mitotic kinase MELK in GSCs, leading to phosphorylation and activation of FOXM1 in a MELK kinase-dependent manner. This MELK-dependent activation of FOXM1 results in a subsequent increase in mitotic regulatory genes in GSCs. MELK-driven FOXM1 activation is regulated by the binding and subsequent trans-phosphorylation of FOXM1 by another kinase PLK1. Using mouse neural progenitor cells (NPCs), we found that transgenic expression of FOXM1 enhances, while siRNA-mediated gene silencing diminishes neurosphere formation, suggesting that FOXM1 is required for NPC growth. During tumorigenesis, FOXM1 expression sequentially increases as cells progress from NPCs, to pretumorigenic progenitors and GSCs. The antibiotic Siomycin A disrupts MELK-mediated FOXM1 signaling with a greater sensitivity in GSC compared to neural stem cell. Treatment with the first-line chemotherapy agent for GBM, Temozolomide, paradoxically enriches for both FOXM1 (+) and MELK (+) cells in GBM cells, and addition of Siomycin A to Temozolomide treatment in mice harboring GSC-derived intracranial tumors enhances the effects of the latter. Collectively, our data indicate that FOXM1 signaling through its direct interaction with MELK regulates key mitotic genes in GSCs in a PLK1-dependent manner and thus, this protein complex is a potential therapeutic target for GBM.
Human Fetal Hepatic Progenitor Cells Are Distinct from, but Closely Related to, Hematopoietic Stem/Progenitor Cells
Authors: Chen Qingfeng , Khoury Maroun , Limmon Gino , Choolani Mahesh , Chan Jerry K.Y. , Chen Jianzhu
Published: February 2013

Much controversy surrounds the identity and origin of human hepatic stem and progenitor cells in part because of a lack of small animal models in which the developmental potential of isolated candidate cell populations can be functionally evaluated. We show here that adoptive transfer of CD34+ cells from human fetal liver into sublethally irradiated NOD-SCID Il2rg−/− (NSG) mice leads to an efficient development of not only human hematopoietic cells but also human hepatocyte-like cells in the liver of the recipient mice. Using this simple in vivo assay in combination with cell fractionation, we show that CD34+ fetal liver cells can be separated into three distinct subpopulations: CD34hiCD133hi, CD34loCD133lo, and CD34hiCD133neg. The CD34hiCD133hi population contains hematopoietic stem/progenitor cells (HSPCs) as they give rise to T cells, B cells, NK cells, dendritic cells, and monocytes/macrophages in NSG mice and colony-forming unit (CFU)-GEMM cells in vitro. The CD34loCD133lo population does not give rise to hematopoietic cells, but reproducibly generates hepatocyte-like cells in NSG mice and in vitro. The CD34hiCD133neg population only gives rise to CFU-GM and burst-forming unit-erythroid in vitro. Furthermore, we show that the CD34loCD133lo cells express hematopoietic, hepatic, and mesenchymal markers, including CD34, CD133, CD117, epithelial cell adhesion molecule, CD73, albumin, α-fetal protein, and vimentin and transcriptionally are more closely related to HSPCs than to mature hepatocytes. These results show that CD34loCD133lo fetal liver cells possess the hepatic progenitor cell properties and that human hepatic and hematopoietic progenitor cells are distinct, although they may originate from the same precursors in the fetal liver.
Brief Report: Mesenchymal Stromal Cell Atrophy in Coculture Increases Aggressiveness of Transformed Cells
Authors: Castellone Maria D. , Laatikainen Lilja E. , Laurila Juha P. , Langella Angela , Hematti Peiman , Soricelli Andrea , Salvatore Marco , Laukkanen Mikko O.
Published: February 2013

Mesenchymal stromal cells (MSCs) are able to influence the growth abilities of transformed cells. Here, we show that papillary thyroid cancer TPC1 and HEK 293T cells interact physically with human primary bone marrow-derived MSCs followed by evanescence of MSC cytoplasm. Interestingly, transformed cells were able to connect only to apoptotic MSCs that had lost their migration ability, whereas naïve MSCs avoided the direct contact. The interaction stimulated the proliferation of the cocultured transformed cells, activated mitogen and stress signaling, and increased resistance to cytotoxins. Consistent with in vitro data, the MSC interaction stimulated transformed cells had enhanced ability to grow and metastasize in vivo. The parental control cells showed mild tumorigenicity as compared to MSC interaction stimulated cells yielding measurable tumors in 31 days and 7 days, respectively. Our coculture model system describes how adjacent transformed cells absorb stromal cells thereby leading to the stroma-driven evolution of moderately carcinogenic cells to highly aggressive metastatic cells.
Context change and associative learning
Authors: Rosas Juan M. , Todd Travis P. , Bouton Mark E.
Published: February 2013

This article reviews the effects of changing the background context on performance in associative learning tasks in humans and animals. The findings are complementary and consistent over animal conditioning (Pavlovian and instrumental learning) and human predictive learning and memory paradigms. In many cases, a context change after learning can have surprisingly little disruptive influence on performance. Extinction, or retroactive interference treatments more generally, is more context‐specific than the initial learning. Contexts become important if the participant is exposed to any of several treatments that involve prediction error, which may serve to increase attention to the context. Contexts also become important if they are given predictive or informational value. Studies of instrumental (operant) learning are further consistent with the idea that the context might also influence affordances that support voluntary actions. Context switch effects are not universal, but mainly occur when certain attention and perception processes can come into play. WIREs Cogn Sci 2013, 4:237–244. doi: 10.1002/wcs.1225

This article is categorized under:

Psychology > Learning
Solute transport in fractured rocks with stagnant water zone and rock matrix composed of different geological layers—Model development and simulations
Authors: Mahmoudzadeh Batoul , Liu Longcheng , Moreno Luis , Neretnieks Ivars
Published: February 2013

Key Points

A model is developed to describe solute transport in channels in fractures

The analytical solution to the Laplace‐transformed concentration is derived

Simulations show that diffusion into stagnant water is important
Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation
Authors: Manteiga Sara , Choi Kyungoh , Jayaraman Arul , Lee Kyongbum
Published: February 2013

Adipose tissue (AT) depots actively regulate whole body energy homeostasis by orchestrating complex communications with other physiological systems as well as within the tissue. Adipocytes readily respond to hormonal and nutritional inputs to store excess nutrients as intracellular lipids or mobilize the stored fat for utilization. Co‐ordinated regulation of metabolic pathways balancing uptake, esterification, and hydrolysis of lipids is accomplished through positive and negative feedback interactions of regulatory hubs comprising several pleiotropic protein kinases and nuclear receptors. Metabolic regulation in adipocytes encompasses biogenesis and remodeling of uniquely large lipid droplets (LDs). The regulatory hubs also function as energy and nutrient sensors, and integrate metabolic regulation with intercellular signaling. Over‐nutrition causes hypertrophic expansion of adipocytes, which, through incompletely understood mechanisms, initiates a cascade of metabolic and signaling events leading to tissue remodeling and immune cell recruitment. Macrophage activation and polarization toward a pro‐inflammatory phenotype drives a self‐reinforcing cycle of pro‐inflammatory signals in the AT, establishing an inflammatory state. Sustained inflammation accelerates lipolysis and elevates free fatty acids in circulation, which robustly correlates with development of obesity‐related diseases. The adipose regulatory network coupling metabolism, growth, and signaling of multiple cell types is exceedingly complex. While components of the regulatory network have been individually studied in exquisite detail, systems approaches have rarely been utilized to comprehensively assess the relative engagements of the components. Thus, need and opportunity exist to develop quantitative models of metabolic and signaling networks to achieve a more complete understanding of AT biology in both health and disease. WIREs Syst Biol Med 2013, 5:425–447. doi: 10.1002/wsbm.1213

This article is categorized under:

Biological Mechanisms > Metabolism

Physiology > Mammalian Physiology in Health and Disease

Biological Mechanisms > Regulatory Biology
The Effect of Synthetic C-Reactive Protein on the In Vitro Immune Response of Human PBMCs Stimulated with Bacterial Reagents
Authors: Sato Atsushi , Nakashima Hiroyuki , Kinoshita Manabu , Nakashima Masahiro , Ogawa Yoshiko , Shono Satoshi , Ikarashi Masami , Seki Shuhji
Published: February 2013

Synthetic C-reactive protein (CRP) rescues mice from lethal endotoxin shock orbacterialinfection by suppressing tumor necrosis factor (TNF-α), but in turn, enhances Kupffer cell phagocytic activity. We herein assessed the influence of CRP in human peripheral blood mononuclear cells (PBMCs). When human PBMCs were stimulatedin vitrowith penicillin-treatedStreptococcus pyogenes, bacterial DNA motifs and lipopolysaccharide with or without synthetic CRP, CRP suppressed the production of TNF-α and IL-12, but not that of IFN-γ. This was also the case for thein vitroShwartzman reaction induced in PBMCs. CRP also decreased high-mobility group box 1 production from macrophages, which is crucial in the later phase of endotoxin/septic shock. However, CRP upregulated the perforin expression by CD56+NK cells and increased their antitumor cytotoxicity. CRP may thus be a potent immunomodulatory factor in the human immune system, suggesting its therapeutic potential for use against human septic shock.
Interpersonal relationships and emotional distress in adolescence
Authors: Kenny Rachel , Dooley Barbara , Fitzgerald Amanda
Published: February 2013

The aim of this study was to examine positive and negative qualities in adolescents' interpersonal relationships and their relative importance in predicting emotional distress. Participants were 260 students from three schools in the Dublin area (119 girls; 141 boys), aged 12–18 years (M = 15.32, SD = 1.91). Students completed questionnaires assessing qualities in important interpersonal relationships in their lives and emotional distress. Girls reported more positive qualities in their relationships with mothers and best friends than boys. Younger students reported more positive qualities in their relationships with parents than older students. Stepwise multiple regression analysis revealed high levels of satisfaction in interpersonal relationships were predictive of low levels of emotional distress whereas high levels of criticism and exclusion were predictive of high levels of distress. High levels of support and disclosure were also linked to emotional distress. These findings and their implications are discussed in detail.
Dysmetabolic features of the overweight patients receiving antipsychotic drugs: A comparison with normal weight and obese subjects
Authors: Manu P. , Correll C.-U. , Wampers M. , van Winkel R. , Yu W. , Shiffeldrim D. , De Hert M.
Published: February 2013

Background:

Extensive research indicates that obesity, defined by a body mass index (BMI) greater or equal to 30, is common in patients treated with antipsychotic drugs and is frequently associated with carbohydrate and lipid abnormalities leading to metabolic syndrome and diabetes. In contrast, the metabolic health of overweight patients (BMI = 25–29.9) without metabolic syndrome or diabetes has not been thoroughly investigated.

Objective:

To assess the metabolic health of overweight patients receiving antipsychotic drugs.

Methods:

We compared standard metabolic parameters (BMI; waist circumference; hemoglobin A1c; fasting lipids; and fasting and post-challenge glucose and insulin) of normal weight, overweight and obese individuals from a consecutive cohort of antipsychotic-treated patients without metabolic syndrome and/or diabetes.

Results:

Compared with the normal weight subjects (n = 286), overweight patients (n = 212) had higher fasting insulin resistance as assessed with the homeostatic model (P = 0.023), insulin secretion during the oral glucose tolerance test (P = 0.0037), triglycerides (P = 0.0004) and low-density lipoprotein cholesterol (P = 0.0089), and lower levels of high-density lipoprotein cholesterol (P = 0.0014). The obese (n = 50) were different from the overweight subjects only with respect to higher post-challenge insulin levels (P = 0.0002). The average fasting glucose, post-challenge glucose, and hemoglobin A1c, severity of psychiatric disorders and antipsychotics used were similar in the three groups.

Conclusions:

Overweight (BMI = 25–29.9) patients receiving antipsychotics are metabolically closer to the obese than to normal weight counterparts. The findings suggest that interventions promoting weight loss and metabolic health are required for overweight patients even in the absence of metabolic syndrome or diabetes.
A contested landscape: Monuments, public memory, and post-Soviet identity in Stavropol’, Russia
Authors: Foxall Andrew
Published: February 2013

Much recent literature in cultural, political and social geography has considered the relationship between identity, memory, and the urban landscape. This paper interrogates such literature through exploring the complex materialisation of memorialisation in post-Soviet Russia. Using the example of the statue of General Alexei Ermolov in Stavropol’, an analysis of the cityscape reveals interethnic tensions over differing interpretations of the life and history of the person upon whom the statue is based. The existence of a rich literature on Ermolov and the Russian colonial experience in the North Caucasus helps to explain this. The symbolic cityscape of Stavropol’ plays an important role in interethnic relations in the multi-ethnic city; it is both an arena through which Russian identity is communicated with people and produced and reproduced, and an arena through which Russian citizens compete with each other for authority on historical narratives that operate at and between a number of scales. People’s readings of the cityscape can reveal much about power and space in contemporary Russia.
Long-Term Adaptation of Cerebral Hemodynamic Response to Somatosensory Stimulation during Chronic Hypoxia in Awake Mice
Authors: Takuwa Hiroyuki , Masamoto Kazuto , Yamazaki Kyoko , Kawaguchi Hiroshi , Ikoma Yoko , Tajima Yousuke , Obata Takayuki , Tomita Yutaka , Suzuki Norihiro , Kanno Iwao , Ito Hiroshi
Published: February 2013

Effects of chronic hypoxia on hemodynamic response to sensory stimulation were investigated. Using laser-Doppler flowmetry, change in cerebral blood flow ( CBF) was measured in awake mice, which were housed in a hypoxic chamber (8% O2) for 1 month. The degree of increase in CBF evoked by sensory stimulation was gradually decreased over 1 month of chronic hypoxia. No significant reduction of increase in CBF induced by hypercapnia was observed during 1 month. Voltage-sensitive dye (VSD) imaging of the somatosensory cortex showed no significant decrease in neural activation over 1 month, indicating that the reduction of increase in CBF to sensory stimulation was not caused by cerebrovascular or neural dysfunction. The simulation study showed that, when effective diffusivity for oxygen in the capillary bed ( D) value increases by chronic hypoxia due to an increase in capillary blood volume, an increase in the cerebral metabolic rate of oxygen utilization during neural activation can occur without any increase in CBF. Although previous study showed no direct effects of acute hypoxia on CBF response, our finding showed that hemodynamic response to neural activation could be modified in response to a change in their balance to energy demand using chronic hypoxia experiments.