bluuebunny/crossref_metadata_2025 huggingface dataset:
Participation in productive activities and depression among older Europeans: Survey of Health, Ageing and Retirement in Europe (SHARE)
Authors: Choi Kyeong‐Sook , Stewart Robert , Dewey Michael
Published: March 2013

Objective

Although engagement in productive activities is associated with favourable outcomes with respect to the health and well‐being of older individuals, the association between such activities and depression in older populations remains relatively unexplored. The purpose of this study was to evaluate the association among five productive activities (paid work, formal volunteering, caregiving, informal helping and caring for grandchildren) with depression in older adults in 14 European countries.

Methods

This cross‐sectional study used the first two waves of data collected by the Survey of Health, Ageing and Retirement in Europe and analysed a total sample of 7238 relatively healthy community residents aged 60 years and older from 14 European countries. The Survey of Health, Ageing and Retirement in Europe excluded potential participants with a past history of depression, cognitive impairment and physical limitations. Depression was categorised using the EURO‐D instrument, and associations with participating in productive activities were investigated.

Results

Depression was less prevalent among those individuals who were employed or self‐employed and those who participated in formal volunteering or informal helping, whereas caregiving was associated with a higher risk of depression. Caring for grandchildren was not associated positively or negatively with depression. Formal volunteering and caregiving remained associated with depression after adjustment for age, sex, marital status, education, economic status, country and presence of long‐term illness.

Conclusions

Availability of formal volunteering may be important in reducing depression risk, whereas caregiving is associated with a higher risk of depression in older European adults. Further research is required to clarify the direction of causation and evaluate interventions. Copyright © 2013 John Wiley & Sons, Ltd.
Satellite constraints of nitrogen oxide (NOx) emissions from India based on OMI observations and WRF‐Chem simulations
Authors: Ghude Sachin D. , Pfister Gabriele G. , Jena Chinmay , van der A R.J. , Emmons Louisa K. , Kumar Rajesh
Published: March 2013

In this work, we map and develop for the first time an independent satellite constrained NOx emission inventory for India for 2005 using an inverse technique and iterative procedure. We used OMI tropospheric NO2 column retrievals over the Indian region, with tropospheric NO2 columns simulated by the WRF‐Chem model using the INTEX‐B emission inventory. We determined the local relationship between modeled emissions and tropospheric columns and iteratively apply this relationship to OMI observations to derive an optimized NOx emission inventory on a 0.5° × 0.5° grid. The optimized total NOx emissions for India amount to 1.9 TgN/y and agree within 25% with EDGARv4.1 and the INTEX‐B estimate. Our top‐down inventory captures many of the missing hotspots in the original inventory and suggests that the INTEX‐B inventory overestimates emissions over the Western and Eastern Indo‐Gangetic region and underestimates point sources. We further evaluate the effect of the top‐down inventory on surface ozone, which clearly indicates significant changes in spatial distribution.
Extreme storms and changes in particulate and dissolved organic carbon in runoff: Entering uncharted waters?
Authors: Dhillon Gurbir Singh , Inamdar Shreeram
Published: March 2013

We determined the runoff exports of particulate (POC) and dissolved organic carbon (DOC) from a 12 ha forested catchment which received more than 14 storm events in a 16‐month period and three extreme events associated with hurricanes. While POC and DOC exports for the small events were comparable, POC exports for the hurricane‐associated events were six to eight times the DOC values. Hurricane Irene alone contributed to 56% (21.2 kg C ha–1) and 19% (3.3 kg C ha–1) of the 2011 exports of POC and DOC, respectively. A precipitation threshold beyond which POC fluxes rapidly outpaced the DOC values was also identified. Our study suggests that large, high‐intensity storm events that are predicted to increase under future climate‐change scenarios will dramatically alter the runoff C regime by enhancing the POC inputs to aquatic ecosystems. Such shift in C forms could have important consequences for aquatic biota, atmospheric C cycling, and ecosystem and human health.
A large‐scale flow vortex in the Venus plasma tail and its fluid dynamic interpretation
Authors: Lundin R. , Barabash S. , Futaana Y. , Holmström M. , Perez‐de‐Tejada H. , Sauvaud J.‐A.
Published: March 2013

We report on the existence of a large‐scale ion flow vortex, a curled tailward flow of solar wind H+ (SW H+), and ionospheric O+ in the Venus plasma tail. The vortex commences at dusk (−Y), driven by a transverse (to the solar wind) aberration flow component. Dusk magnetosheath and ionospheric ions move westward across the nightside into the dawn sector, from where the tailward and lateral flow merges into a tailward‐moving vortex. A fluid analysis of the SW H+ energy and momentum (E&M) transfer to O+ at the terminator, shows that E&M balance (efficiency ≈1) is achieved in the altitude range of 1200–600 km. Below 600 km a westward O+ flow, moving along the direction of the atmospheric superrotation, dominates. Conversely, SW H+ dominates the high‐altitude vortex. The Venus large‐scale tail vortex is hardly unique. Other gaseous celestial objects (comets) orbiting the Sun may develop similar tail vortices.
CHILD PROTECTION AND ADULT DEPRESSION: EVALUATING THE LONG‐TERM CONSEQUENCES OF EVACUATING CHILDREN TO FOSTER CARE DURING WORLD WAR II
Authors: Santavirta Nina , Santavirta Torsten
Published: March 2013

This paper combined data collected from war time government records with survey data including background characteristics, such as factors that affected eligibility, to examine the adult depression outcomes of individuals who were evacuated from Finland to temporary foster care in Sweden during World War II.

Using war time government records and survey data for a random sample of 723 exposed individuals and 1321 matched unexposed individuals, the authors conducted least squares adjusted means comparison to examine the association between evacuation and adult depression (Beck Depression Inventory). The random sample was representative for the whole population of evacuees who returned to their biological families after World War II. The authors found no statistically significant difference in depressive symptoms during late adulthood between the two groups; for example, the exposed group had a 0.41 percentage points lower average Beck Depression Inventory score than the unexposed group (p = 0.907). This study provides no support for family disruption during early childhood because of the onset of sudden shocks elevating depressive symptoms during late adulthood. Copyright © 2013 John Wiley & Sons, Ltd.
Overexpressed-eIF3I interacted and activated oncogenic Akt1 is a theranostic target in human hepatocellular carcinoma
Authors: Wang Yi-Wei , Lin Kuen-Tyng , Chen Shu-Chuan , Gu De-Leung , Chen Chian-Feng , Tu Pang-Hsien , Jou Yuh-Shan
Published: March 2013

Eukaryotic translation initiation factor 3 subunit I (eIF3I) with transforming capability is often overexpressed in human hepatocellular carcinoma (HCC) but its oncogenic mechanisms remain unknown. We demonstrate that eIF3I is overexpressed in various cancers along with activated Akt1 phosphorylation and kinase activity in an eIF3I dose-dependent manner. A novel eIF3I and Akt1 protein interaction was identified in HCC cell lines and tissues and was required for eIF3I-mediated activation of Akt1 signaling. Expression of either antisense eIF3I or dominant negative Akt1 mutant suppressed eIF3I-mediated Akt1 oncogenic signaling and various other tumorigenic effects. Oncogenic domain mapping of the eIF3I and Akt1 interaction suggested that the C-terminal eIF3I interacted with the Akt1 kinase domain and conferred the majority of oncogenic functions. In addition, eIF3I interaction with Akt1 prevented PP2A dephosphorylation of Akt1 and resulted in constitutively active Akt1 oncogenic signaling. Importantly, concordant expression of endogenous eIF3I and phospho-Akt1 was detected in HCC cell lines and tissues. Treatment of eIF3I overexpressing HCC cells with the Akt1 specific inhibitor API-2 suppressed eIF3I-mediated tumorigenesis in vitro and in vivo. Conclusion: We describe a constitutive Akt1 oncogenic mechanism resulting from interaction of overexpressed eIF3I with Akt1 that prevents PP2A-mediated dephosphorylation. Overexpression of eIF3I in HCC is oncogenic and is a surrogate marker and therapeutic target for treatment with Akt1 inhibitors. (HEPATOLOGY 2013;)
Pre‐ and post‐impoundment nitrogen in the lower Missouri River
Authors: Blevins Dale W. , Wilkison Donald H. , Niesen Shelley L.
Published: March 2013

Large water‐sample sets collected from 1899 through 1902, 1907, and in the early 1950s allow comparisons of pre‐impoundment and post‐impoundment (1969 through 2008) nitrogen concentrations in the lower Missouri River. Although urban wastes were not large enough to detectably increase annual loads of total nitrogen at the beginning of the 20th century, carcass waste, stock‐yard manure, and untreated human wastes measurably increased ammonia and organic‐nitrogen concentrations during low flows. Average total‐nitrogen concentrations in both periods were about 2.5 mg/l, but much of the particulate‐organic nitrogen, which was the dominant form of nitrogen around 1900, has been replaced by nitrate. This change in speciation was caused by the nearly 80% decrease in suspended‐sediment concentrations that occurred after impoundment, modern agriculture, drainage of riparian wetlands, and sewage treatment. Nevertheless, bioavailable nitrogen has not been low enough to limit primary production in the Missouri River since the beginning of the 20th century. Nitrate concentrations have increased more rapidly from 2000 through 2008 (5 to 12% per year), thus increasing bioavailable nitrogen delivered to the Mississippi River and affecting Gulf Coast hypoxia. The increase in nitrate concentrations with distance downstream is much greater during the post‐impoundment period. If strategies to decrease total‐nitrogen loads focus on particulate N, substantial decreases will be difficult because particulate nitrogen is now only 23% of total nitrogen in the Missouri River. A strategy aimed at decreasing particulates also could further exacerbate land loss along the Gulf of Mexico, which has been sediment starved since Missouri River impoundment. In contrast, strategies or benchmarks aimed at decreasing nitrate loads could substantially decrease nitrogen loadings because nitrates now constitute over half of the Missouri's nitrogen input to the Mississippi. Ongoing restoration and creation of wetlands along the Missouri River could be part of such a nitrate‐reduction strategy. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
Estimating precipitation phase using a psychrometric energy balance method
Authors: Harder Phillip , Pomeroy John
Published: March 2013

Precipitation phase is fundamental to a catchment's hydrological response to precipitation events. Phase is particularly variable over time and space in the Canadian Rockies where snowfall or rainfall can occur any month of the year. Phase is controlled by the microphysics of the falling hydrometeor, but microphysical calculations require detailed atmospheric information that is often lacking for hydrological analyses. In hydrology, there have been many methods developed to estimate phase, but most are regionally calibrated, and many depend on air temperature (Ta) and use daily time steps. Phase is not only related to Ta, but to other meteorological variables, and precipitation events are temporally dynamic, adding uncertainty to the use of daily indices to estimate phase. To better predict precipitation phase, the psychrometric energy balance of a falling hydrometeor was calculated and used to develop a method to estimate precipitation phase. High quality precipitation phase and meteorological data were observed at multiple elevations in a small Canadian Rockies catchment, Marmot Creek Research Basin, at 15‐min intervals over several years to develop and test the method. The results of the psychrometric energy balance method were compared to phase observations, to other methods over varying time scales and seasons and at varying elevations and topographic exposures. The results indicate that the psychrometric energy balance method performs much better than Ta index methods and that this improvement, and the accuracy of the psychrometric energy balance method, increases as the time step of calculation decreases. Copyright © 2013 John Wiley & Sons, Ltd.
Using hydrogeochemical signatures of stream water to assess pathways for rainfall events: towards a predictive model
Authors: Figueiredo J. A. , Menor E. A. , Taboada‐Castro M. T. , Taboada‐Castro M. M. , Rodríguez‐Blanco M. L. , Braga E. S.
Published: March 2013

Thanks to its simple division into agricultural and forestry land use, the Corbeira catchment (Galicia, Spain) is used as a case study to build a predictive model using hydrogeochemical signatures. Stream data acquired under recessional flow conditions over a one year period were obtained from a sampling station near the downstream end of the catchment, and using principal component analysis, it is shown that some of the analytical parameters are covariant, and some are negatively correlated. These findings support inferences about the pathways of rainfall in the catchment. Specific signatures may be associated with the dominant hydrological source, either surface runoff or subsurface waters: additionally, the dominant land use in that part of the catchment, where the flow originated, can also be predicted. The dominant runoff shows a strong covariance between suspended solids (SS) and particulate phosphorus (PP), with a clear negative correlation with pH. Dissolved organic carbon (DOC) data are associated with this covariant set when these compounds are available in the soils in question. Dissolved phosphorus, total organic nitrogen and dissolved nitrates are also associated with the same covariant set when the runoff flows through areas of extensive agricultural use. The SS − PP covariance is less significant at lower flows. Typical base flow regimes show a significant covariance between salinity and pH, with a marked negative correlation with SS − PP set, confirming the dominance of subsurface waters in the baseflow, as expected. Seasonally divergent DOC − SS behaviour proves to be a useful tracer for rainfall regimes. The DOC trend shows a sinusoidal annual variation in amplitude, determined by the rainfall regime. As a result, flow from the catchment is dominated by surface water whenever there is synchronicity between the peaks of DOC and SS. Copyright © 2013 John Wiley & Sons, Ltd.
Physical exercise, body mass index and risk of chronic arm pain: Longitudinal data on an adult population in Norway
Authors: Mork P.J. , Holtermann A. , Nilsen T.I.L.
Published: March 2013

Aim

The aim of this study was to prospectively investigate the association between leisure time physical exercise, body mass index (BMI) and risk of chronic arm pain.

Methods

The study population comprises 14,041 women and 13,674 men in the Norwegian HUNT Study without musculoskeletal pain or physical impairment at baseline in 1984–86. Chronic arm pain was assessed at follow‐up in 1995–97. A generalized linear model was used to calculate adjusted relative risks (RRs).

Results

At follow‐up, 2205 women and 1458 men reported chronic arm pain. Level of physical exercise was inversely associated with risk of chronic arm pain (P‐trend, ≤0.03 for both sexes). Compared with inactive persons, women and men who exercised ≥ 2 h/week had adjusted RRs of 0.84 [95% confidence interval (CI), 0.73–0.96] and 0.74 (95% CI, 0.63–0.87), respectively. BMI was positively associated with risk of chronic arm pain (P‐trend, ≤0.002 for both sexes). Compared with normal‐weight persons, women and men classified as obese (BMI ≥ 30 kg/m2) had adjusted RRs of 1.26 (95% CI, 1.11–1.44) and 1.29 (95% CI, 1.07–1.57), respectively. Combined analysis showed that obese women and men who exercised ≥ 1 h/week had a RR of 1.20 (95% CI 0.97–1.48) compared with normal‐weight women and men with a similar activity level, whereas the RR was 1.41 (95% CI 1.21–1.65) for obese women and men who were physically inactive.

Conclusion

Regular physical exercise reduces risk of chronic arm pain while high BMI increases the risk. Exercise can to some extent compensate for the adverse effect of obesity on risk of chronic arm pain.
The Effect of Rosiglitazone on Bone Mass and Fragility Is Reversible and Can Be Attenuated With Alendronate
Authors: Kumar Sanjay , Hoffman Sandra J , Samadfam Rana , Mansell Peter , Jolette Jacquelin , Smith Susan Y , Guldberg Robert E , Fitzpatrick Lorraine A
Published: March 2013

Rosiglitazone (RSG) is an antidiabetic drug that has been associated with increased peripheral fractures, primarily in postmenopausal women. In this report, we investigated the underlying mechanisms of RSG-associated bone loss in ovariectomized (OVX) rats and determined whether changes in bone parameters associated with RSG administration are reversible on treatment cessation or preventable by coadministration with an antiresorptive agent. Nine-month-old Sprague-Dawley rats underwent OVX or sham operation. Sham-operated rats received oral vehicle only; OVX animals were randomized to receive vehicle, RSG, alendronate (ALN), or RSG plus ALN for 12 weeks. All treatment started the day after ovariectomy. After the 12-week treatment period, the OVX and RSG groups also underwent an 8-week treatment-free recovery period. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Microcomputed tomography was also used to investigate changes in microarchitecture. RSG significantly increased deoxypyridinoline levels compared with OVX. Significant exacerbation of OVX-induced loss of bone mass, strength, and microarchitectural deterioration was observed in RSG-treated OVX animals compared with OVX controls. These effects were observed predominantly at sites rich in trabecular bone, with less pronounced effects in cortical bone. Coadministration of RSG and ALN prevented the bone loss associated with RSG treatment. Following cessation of RSG treatment, effects on bone mass and strength showed evidence of reversal. Thus, treatment of OVX rats with RSG results in loss of bone mass and strength, primarily at sites rich in trabecular bone, mainly due to increased bone resorption. These effects can be prevented by concomitant treatment with ALN and may be reversed following discontinuation of RSG.
Fast Trabecular Bone Strength Predictions of HR-pQCT and Individual Trabeculae Segmentation–Based Plate and Rod Finite Element Model Discriminate Postmenopausal Vertebral Fractures
Authors: Liu X Sherry , Wang Ji , Zhou Bin , Stein Emily , Shi Xiutao , Adams Mark , Shane Elizabeth , Guo X Edward
Published: March 2013

Although high-resolution peripheral quantitative computed tomography (HR-pQCT) has advanced clinical assessment of trabecular bone microstructure, nonlinear microstructural finite element (µFE) prediction of yield strength using a HR-pQCT voxel model is impractical for clinical use due to its prohibitively high computational costs. The goal of this study was to develop an efficient HR-pQCT-based plate and rod (PR) modeling technique to fill the unmet clinical need for fast bone strength estimation. By using an individual trabecula segmentation (ITS) technique to segment the trabecular structure into individual plates and rods, a patient-specific PR model was implemented by modeling each trabecular plate with multiple shell elements and each rod with a beam element. To validate this modeling technique, predictions by HR-pQCT PR model were compared with those of the registered high-resolution micro–computed tomography (HR-µCT) voxel model of 19 trabecular subvolumes from human cadaveric tibia samples. Both the Young's modulus and yield strength of HR-pQCT PR models strongly correlated with those of µCT voxel models (r2 = 0.91 and 0.86). Notably, the HR-pQCT PR models achieved major reductions in element number (>40-fold) and computer central processing unit (CPU) time (>1200-fold). Then, we applied PR model µFE analysis to HR-pQCT images of 60 postmenopausal women with (n = 30) and without (n = 30) a history of vertebral fracture. HR-pQCT PR model revealed significantly lower Young's modulus and yield strength at the radius and tibia in fracture subjects compared to controls. Moreover, these mechanical measurements remained significantly lower in fracture subjects at both sites after adjustment for areal bone mineral density (aBMD) T-score at the ultradistal radius or total hip. In conclusion, we validated a novel HR-pQCT PR model of human trabecular bone against µCT voxel models and demonstrated its ability to discriminate vertebral fracture status in postmenopausal women. This accurate nonlinear µFE prediction of the HR-pQCT PR model, which requires only seconds of desktop computer time, has tremendous promise for clinical assessment of bone strength.
Plasminogen Plays a Crucial Role in Bone Repair
Authors: Kawao Naoyuki , Tamura Yukinori , Okumoto Katsumi , Yano Masato , Okada Kiyotaka , Matsuo Osamu , Kaji Hiroshi
Published: March 2013

The further development in research of bone regeneration is necessary to meet the clinical demand for bone reconstruction. Plasminogen is a critical factor of the tissue fibrinolytic system, which mediates tissue repair in the skin and liver. However, the role of the fibrinolytic system in bone regeneration remains unknown. Herein, we investigated bone repair and ectopic bone formation using plasminogen-deficient (Plg–/–) mice. Bone repair of the femur is delayed in Plg–/– mice, unlike that in the wild-type (Plg+/+) mice. The deposition of cartilage matrix and osteoblast formation were both decreased in Plg–/– mice. Vessel formation, macrophage accumulation, and the levels of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) were decreased at the site of bone damage in Plg–/– mice. Conversely, heterotopic ossification was not significantly different between Plg+/+ and Plg–/– mice. Moreover, angiogenesis, macrophage accumulation, and the levels of VEGF and TGF-β were comparable between Plg+/+ and Plg–/– mice in heterotopic ossification. Our data provide novel evidence that plasminogen is essential for bone repair. The present study indicates that plasminogen contributes to angiogenesis related to macrophage accumulation, TGF-β, and VEGF, thereby leading to the enhancement of bone repair.
Noninvasive Diagnosis of Liver Fibrosis and Cirrhosis in Chronic Hepatitis C Patients
Authors: Attallah Abdelfattah M. , El‐Far Mohamed , Omran Mohamed M. , Farid Khaled , Albannan Mohamed S. , El‐Dosoky Ibrahim
Published: March 2013

Background

We aimed to derive a simple noninvasive test for liver‐fibrosis staging and then estimate its performance against four simple noninvasive tests in chronic hepatitis C (CHC) patients.

Methods

CHC patients were divided into two cohorts: an estimation set (n = 324) and a validation set (n = 524). Liver fibrosis was staged according to the METAVIR scoring system. Statistical analysis was done using stepwise linear discriminant analysis and area under receiver‐operating characteristic curves (AUCs).

Results

Biotechnology Research Center (BRC) score was constructed combining several blood markers that proved useful to stage liver fibrosis. Aspartate aminotransferase /alanine aminotransferase ratio (AAR), aspartate to platelet ratio index (APRI), Fibro‐α, King, and BRC scores correlated with the histological fibrosis stages with correlation coefficient 0.26, 0.36, 0.58, 0.45, and 0.73, respectively. BRC score produced AUCs 0.87, 0.83, and 0.89 for significant (F2–F4), advanced fibrosis (F3–F4), and cirrhosis (F4), respectively. These results were reproduced in the validation study with no significant difference yielding AUCs 0.85 for F2–F4, 0.82 for F3–F4, and 0.88 for F4.

Conclusion

BRC score, a novel noninvasive test, is a useful and easy tool to evaluate liver fibrosis in CHC patients and seems more efficient than AAR, APRI, Fibro‐α score, and King's score in this group of Egyptian patients. J. Clin. Lab. Anal. 27:121–129, 2013. © 2013 Wiley Periodicals, Inc.
Linking membrane dynamics and trafficking to autophagy and the unfolded protein response
Authors: Chua Christelle En Lin , Tang Bor Luen
Published: March 2013

Cellular stressors typically induce two protective counter‐responses—autophagy and the unfolded protein response (UPR). It is conceivable that these two endoplasmic reticulum (ER) membrane‐based processes would intersect/interact somehow with the constitutive housekeeping process of exocytic membrane traffic from the ER. How exactly might this occur? Recent evidence indicates that a conserved Rab protein, Rab1/Ypt1p, has functional roles in UPR and autophagy. This molecular switch and its associated effectors may therefore serve to link up a network of cellular responses to stress through changes in membrane dynamics and protein turnover. The notion provides further explanations as to why elevation of Rab1/Ypt1p levels could counter the cytotoxicity of α‐synuclein, and a similar mode of protection may well be at work against other stresses. J. Cell. Physiol. 228: 1638–1640, 2013. © 2013 Wiley Periodicals, Inc.
MicroRNA transport: A new way in cell communication
Authors: Xu Ling , Yang Bao‐feng , Ai Jing
Published: March 2013

MicroRNAs (miRNAs) can efficiently regulate gene expression by targeting mRNA to cause mRNA cleavage or translational repression. Growing evidence indicates that miRNAs exist not only in cells but also in a variety of body fluids, which stimulates substantial interest in the transport mechanism and regulating process of extracellular miRNAs. This article reviews the basic biogenesis of miRNAs in detail to explore the origin of extracellular miRNAs. Different miRNA transporters have been summarized (e.g., exosomes, microvesicles, apoptosis bodies, and RNA‐binding proteins). In addition, we discuss the regulators affecting miRNA transport (e.g., ATP and ceramide) and the selection mechanism for different miRNA transporters. Studies about miRNA transporters and the transport mechanism are new and developing. With the progress of the research, new functions of extracellular miRNAs may be uncovered in the future. J. Cell. Physiol. 228: 1713–1719, 2013. © 2013 Wiley Periodicals, Inc.
Cardiac resident nestin+ cells participate in reparative vascularisation
Authors: El‐Helou Vivianne , Chabot Andréanne , Gosselin Hugues , Villeneuve Louis , Clavet‐Lanthier Marie‐Elaine , Tanguay Jean‐Francois , Enikolopov Grigori , Fernandes Karl J.L. , Jasmin Jean‐Francois , Calderone Angelino
Published: March 2013

The rodent heart contains a population of nestin(+) cells derived from the embryonic neural crest and migrate to the scar after myocardial infarction (MI). The present study tested the hypothesis that intron 2 of the nestin gene drives expression and a subpopulation of nestin(+) cells participate in reparative vascularisation. The directed expression of the green fluorescent protein (GFP) by the second intron of the nestin gene identified GFP/nestin(+) cells intercalated among ventricular myocytes in the heart of normal transgenic mice. Ischemic injury led to the migration of GFP(+) cells to the scar and a subpopulation was detected in CD31/nestin(+) endothelial cells of newly formed blood vessels. The direct contribution to reparative vascularisation provided the impetus to test the hypothesis that increasing the population of nestin(+) cells in the infarcted heart will improve scar healing. Skin‐derived cells isolated from E18 Sprague–Dawley rats grew as spheres, expressed nestin, sox2, neural crest‐related transcriptional genes and a panel of peptide growth factors. Skin‐derived cells transplanted in the non‐infarcted left ventricle of 3‐day post‐MI rats migrated to the peri‐infarct/infarct region and remained engrafted for 21 days. A significantly smaller infarct, increased number of small calibre blood vessels and improved ventricular function were observed in engrafted infarcted rat hearts. Thus, the second intron of the nestin gene drives expression in the mouse heart and a subpopulation of GFP/nestin(+) cells directly participate in reparative vascularisation. Increasing the population of nestin(+) cells via the transplantation of skin‐derived cells represents a potential approach to limit ischemic damage to the heart. J. Cell. Physiol. 228: 1844–1853, 2013. © 2013 Wiley Periodicals, Inc.
Carcinoma‐associated fibroblasts: Non‐neoplastic tumour‐promoting mesenchymal cells
Authors: Polanska Urszula M. , Orimo Akira
Published: March 2013

Cancerous stroma coevolves alongside tumour progression, thereby promoting the malignant conversion of epithelial carcinoma cells. To date, an abundance of data have supported crucial roles of the tumour microenvironment (TME) in providing cancer cells with proliferative, migratory, survival and invasive propensities favouring the processes of tumourigenesis. The cancerous reactive stroma is frequently populated by a large number of myofibroblasts (MFs), which are activated, non‐transformed fibroblasts expressing α‐smooth muscle actin (α‐SMA). MFs together with non‐MF cells present in the tumour‐associated stroma are collectively referred to as carcinoma‐associated fibroblasts (CAFs), one of the major stromal cell types recognised in various human carcinomas. Recruitment of fibroblasts and/or their progenitors to a tumour mass and their subsequent transdifferentiation into MFs, as well as ongoing maintenance of their activated state, are believed to be essential processes facilitating tumour progression. However, the complex networks of signalling pathways mediating the phenotypic conversion into CAFs, as well as those underlying their tumour‐promoting interactions with other tumour‐constituting cells, have yet to be fully explored. Histopathological confirmation of the presence of large numbers of CAF MFs within TME and their altered gene expression profiles are known to be associated with disease progression and to serve as independent negative prognostic factors for a wide range of tumour types. In this review, we examine the current evidence shedding light on the emerging roles of tumour‐promoting CAFs, cells that are pivotal for epithelial cancer development and progression, and discuss the therapeutic potential of targeting these cells. J. Cell. Physiol. 228: 1651–1657, 2013. © 2013 Wiley Periodicals, Inc.
Adenosine, Adenosine Receptors and Their Role in Glucose Homeostasis and Lipid Metabolism
Authors: Koupenova Milka , Ravid Katya
Published: March 2013

Adenosine is an endogenous metabolite that is released from all tissues and cells including liver, pancreas, muscle, and fat, particularly under stress, intense exercise, or during cell damage. The role of adenosine in glucose homeostasis has been attributed to its ability to regulate, through its membrane receptors, processes such as insulin secretion, glucose release and clearance, glycogenolysis, and glycogenesis. Additionally, adenosine and its multiple receptors have been connected to lipid metabolism by augmenting insulin‐mediated inhibition of lipolysis, and the subsequent increase in free fatty acids and glycerol levels. Furthermore, adenosine was reported to control liver cholesterol synthesis, consequently affecting plasma levels of cholesterol and triglycerides, and the amount of adipose tissue. Alterations in the balance of glucose and lipid homeostasis have implications in both cardiovascular disease and diabetes. The ability of different adenosine receptors to activate and inhibit the same signaling cascades has made it challenging to study the influence of adenosine, adenosine analogs and their receptors on health and disease. This review focuses on the role and significance of different adenosine receptors in mediating the effect of adenosine on glucose and lipid homeostasis. J. Cell. Physiol. 228: 1703–1712, 2013. © 2013 Wiley Periodicals, Inc.
Inactivation of p27kip1 promotes chemical hepatocarcinogenesis through enhancing inflammatory cytokine secretion and STAT3 signaling activation
Authors: Guo Jian , Ma Qingyong , Zhou Xiaojie , Fan Ping , Shan Tao , Miao Dengshun
Published: March 2013

Although the expression of p27 has been regarded as a prognostic parameter in human liver cancer since the implication of decreased p27 expression levels in the genesis and progression of hepatocellular carcinoma (HCC), the molecular mechanism linking p27 deficiency and HCC development is still unclear. Here, we report an increase in tumorigenesis and progression as well as an enhanced inflammatory response in p27 deficient mice (p27−/−) and hypothesize the possible mechanism. We show that p27−/− mice display increased proliferation and decreased apoptosis of tumor cells, accompanied by an increase in the serum inflammatory cytokines IL‐6 and TNF‐α. Furthermore, our data indicated that the increased number and signal transducers and activator of transcription 3 (STAT3) phosphorylation status of infiltrated inflammatory cells was accompanied by increased IL‐6 and TNF‐α mRNA levels in tumor and normal liver tissue in the p27−/− mice. Moreover, using tumor cell and splenocytes co‐culture and tumor homologous transplantation, we validated our hypothesis in vitro and in vivo. Collectively, these data demonstrate that the loss of p27 promotes carcinogens‐induced HCC genesis and progression via the elevation of inflammatory cytokines and the augmented activation of STAT3 signaling in tumor cells and infiltrated inflammatory cells. Altogether, the loss of the cyclin kinase inhibitor p27, traditionally regarded as a consequence of DNA damage, can in turn promote HCC progression through enhancing the inflammatory response, potentially representing a promising therapeutic target in the prevention of HCC genesis and progression. J. Cell. Physiol. 228: 1967–1976, 2013. © 2013 Wiley Periodicals, Inc.
Transcriptional profiling of endometriosis tissues identifies genes related to organogenesis defects
Authors: Crispi Stefania , Piccolo Maria Teresa , D'avino Alfredo , Donizetti Aldo , Viceconte Rosa , Spyrou Maria , Calogero Raffaele A. , Baldi Alfonso , Signorile Pietro G.
Published: March 2013

Endometriosis is a common benign pathology, characterised by the presence of endometrial tissue outside the endometrial cavity with a prevalence of 10–15% in reproductive‐aged women. The pathogenesis is not completely understood, and several theories have been proposed to explain the aetiology. Our group has recently described the presence of ectopic endometrium in a consistent number of human female foetuses analysed by autopsy, reinforcing the hypothesis that endometriosis may be generated by defects during the organogenesis of the female reproductive trait. Herein, in order to identify, at molecular level, changes involved in the disease, we compared the transcriptional profiling of ectopic endometrium with the corresponding eutopic one. Statistical analyses lead us to identify some genes specifically deregulated in the ectopic endometrium, that are involved in gonad developmental process or in wound healing process. Among them, we identified BMP4 and GREM1. BMP4 was never associated before to endometriosis and is involved in the mesoderm‐Müllerian duct differentiation. GREM1 is needed for the initial step of the ureter growth and perhaps could possibly be involved in Müller ducts differentiation. These molecules might be related to the endometriosis aetiology since we showed that their expression is not related to the menstrual cycle phase both at RNA and at protein levels. These data support the theory that embryological defects could be responsible of the endometriosis generation. J. Cell. Physiol. 228: 1927–1934, 2013. © 2013 Wiley Periodicals, Inc.
CONDITIONED REINFORCEMENT IN CHAIN SCHEDULES WHEN TIME TO REINFORCEMENT IS HELD CONSTANT
Authors: Bell Matthew C. , Williams Ben A.
Published: March 2013

Two alternative approaches describe determinants of responding to a stimulus temporally distant from primary reinforcement. One emphasizes the temporal relation of each stimulus to the primary reinforcer, with relative proximity of the stimulus determining response rate. A contrasting view emphasizes immediate consequences of responding to the stimulus, the key factor being the conditioned reinforcement value of those immediate consequences. To contrast these approaches, 4 pigeons were exposed to a two‐component multiple schedule with three‐link chain schedules in each component. Only middle‐link stimuli differed between chains. Baseline reinforcement probabilities were 0.50 for both chains; during discrimination phases it was 1.0 for one chain and 0.0 for the other. During discrimination phases pigeons responded more to the reinforcement‐correlated middle link than to the extinction‐correlated middle link, demonstrating that responding was affected by the probability change. Terminal link responding was also higher in the reinforced chain, even though the terminal link stimulus was identical in both chains. Of greatest interest is initial link responding, which was temporally most distant from reinforcement. Initial link responding, necessarily equal in the two chains, was significantly higher during the 1.0/0.0 discrimination phases, even though overall reinforcement probability remained constant. For 3 of 4 birds, in fact, initial‐link response rates were higher than terminal‐link response rates, an outcome that can be ascribed only to the potent conditioned reinforcement properties of the middle‐link stimulus during the discrimination phases. Results are incompatible with any account of chain behavior based solely on relative time to reinforcement.
PIGEONS' CHOICES WITH TOKEN STIMULI IN CONCURRENT VARIABLE‐INTERVAL SCHEDULES
Authors: Mazur James E. , Biondi Dawn R.
Published: March 2013

Twelve pigeons responded on concurrent variable‐interval schedules that delivered token stimuli (stimulus lights for some pigeons, and white circles on the response keys for others). During exchange periods, each token could be exchanged for food on a fixed‐ratio 1 schedule. Across conditions, the exchange requirements (number of tokens that had to be earned before they could be exchanged for food) varied between one and four for the two response keys. The main findings were that the pigeons' response percentages varied as a function of the number of tokens earned at any given moment, and they were determined by both the delays to food and by the number of food deliveries in the exchange periods. In some conditions, tokens had to be earned but were not visible during the variable‐interval schedules for one or both keys. When one key had visible tokens and the other did not, the pigeons showed a preference for the key without visible tokens. A model based on the matching law and a hyperbolic delay‐discounting equation could account for the main patterns of choice responding, and for how response percentages changed as successive tokens were earned. The results are consistent with the view that the token stimuli served as discriminative stimuli that signaled the current delays to food.
RESPONSE ACQUISITION WITH INTERMITTENT IMMEDIATE AND DELAYED CONDITIONED REINFORCEMENT
Authors: Bermúdez Karina , Bruner Carlos A. , Lattal Kennon A.
Published: March 2013

The acquisition of lever pressing by rats was studied under intermittent immediate and delayed conditioned reinforcement. Rats were exposed to two schedules operating concomitantly. One was a random‐time schedule that delivered reinforcers on average of once per min. Each such reinforcer was paired with a 1‐s illumination of a cue light located above the lever. The other was a tandem random‐interval (RI) t1‐ s fixed‐time (FT) t2‐ s schedule that controlled the rate and the delay of the illumination of the cue‐light after a given lever press. For the RI, t1 was 7.5, 15 or 30 s. For the FT, t2 was 0, 1, 2, 4, 8, 16 or 32 s. Three rats each were exposed to each combination of RI and FT values for 40 sessions. Response rates decreased with longer response‐conditioned reinforcer (Sr) delays under the three different overall rates of Sr. At most response‐Sr delays, absolute response rates were higher with RI 15 s than with RI 30 s but both were similar to those obtained with RI 7.5 s. The results were similar to those from previous research on response acquisition with delayed primary reinforcement. These findings suggest that a previously neutral stimulus that has been correlated with primary reinforcement can reinforce new responses even when the conditioned reinforcer is intermittent and delayed from the responses that produce it.
Effects of Anatomy and Diet on Gastrointestinal pH in Rodents
Authors: Kohl Kevin D. , Stengel Ashley , Samuni‐Blank Michal , Dearing M. Denise
Published: March 2013

The pH of the gastrointestinal tract can have profound influences on digestive processes. Rodents exhibit wide variation in both stomach morphology and dietary strategies, both of which may influence gut pH. Various rodent species have evolved bilocular (or semi‐segmented) stomachs that may allow for more microbial growth compared to unilocular (single‐chambered) stomachs. Additionally, herbivory has evolved multiple times in rodents. The high dietary fiber typical of an herbivorous diet is known to induce secretion of bicarbonate in the gut. We predicted that stomach segmentation might facilitate the separation of contents in the proximal chamber from that of the gastric stomach, facilitating a chemical environment suitable to microbial growth. To investigate the effect of stomach anatomy and diet on gut pH, several species of rodent with varying stomach morphology were fed either a high or low‐fiber diet for 7 days, and pH of the proximal stomach, gastric stomach, small intestine, and cecum were measured. We discovered that rodents with bilocular stomach anatomy maintained a larger pH gradient between the proximal and gastric stomach compartments, and were able to achieve a lower absolute gastric pH compared to those with unilocular stomachs. Dietary fiber increased the pH of the small intestine, but not in any other gut regions. The stomach pH data supports the century old hypothesis that bilocular stomach anatomy creates an environment in the proximal stomach that is suitable for microbial growth. Additionally, the alkaline small intestinal pH on a high fiber diet may enhance digestion. J. Exp. Zool. 319A:225–229, 2013. © 2013 Wiley Periodicals, Inc.
Chiral discrimination and interaction mechanism between enantiomers and serum albumins
Authors: Fang ZhiLi , Su WenCui , Zhang WeiGuang , Xu Yan , Xiong YaJin , Luo MiaoLi , Fan Jun , Yin Xia
Published: March 2013

The chiral discrimination studies of biological system are theoretically and practically significant for the development of chiral drugs and life science. Our work has embarked upon the interaction between serum albumin (SA) (including human SA and bovine SA), R,S‐1‐(4‐methoxyphenyl)ethylamine, and R,S‐1‐(3‐methoxyphenyl)ethylamine. The formation of intermediate transition state, binding sites, and chiral discrimination ability can be investigated by ultraviolet‐visible spectra and fluorescence spectra. Moreover, both the changes of hydrophobic microenvironment and energy transfer can be detected by synchronous fluorescence spectra and fluorescence lifetime. Copyright © 2013 John Wiley & Sons, Ltd.
Opening dynamics of 8‐oxoguanine in DNA
Authors: Every Alicia E. , Russu Irina M.
Published: March 2013

8‐oxoguanine is a major lesion of genomic DNA that results from oxidation of guanine by reactive oxygen species. The repair of this lesion is initiated by 8‐oxoguanine glycosylases, which excise the damaged base by “flipping” it outside the DNA double helix. The molecular mechanisms involved in the specific recognition of the damaged base by the enzyme are not yet fully understood. Several models have proposed that, in DNA, the base pair between 8‐oxoguanine and cytosine may possess altered dynamic properties that could help the enzyme locate the lesion and could favor the selective extra‐helical flipping of the damaged base. To test this proposal, we have characterized the spontaneous opening of the base pair between 8‐oxoguanine and cytosine in a DNA double helix using NMR spectroscopy and proton exchange. The results show that the rate of spontaneous opening of 8‐oxoguanine and the lifetime of the base in the extra‐helical state are the same as those of a canonical guanine‐cytosine base pair, in the same base sequence context. This finding suggests that the opening dynamics of 8‐oxoguanine, when paired with cytosine in DNA, does not play a significant role in the recognition of the lesion by glycosylases. Copyright © 2013 John Wiley & Sons, Ltd.
The promiscuous protein binding ability of erythrosine B studied by metachromasy (metachromasia)
Authors: Ganesan Lakshmi , Buchwald Peter
Published: March 2013

The present study aims to elucidate aspects of the protein binding ability of erythrosine B (ErB), a poly‐iodinated xanthene dye and an FDA‐approved food colorant (FD&C Red No. 3), which we have identified recently as a promiscuous inhibitor of protein–protein interactions (PPIs) with a remarkably consistent median inhibitory concentration (IC50) in the 5‐ to 30‐μM range. Because ErB exhibits metachromasy, that is, color change upon binding to several proteins, we exploited this property to quantify its binding to proteins such as bovine serum albumin (BSA) and CD40L (CD154) and to determine the corresponding binding constants (Kd) and stoichiometry (nb) using spectrophotometric methods. Binding was reversible, and the estimated affinities for both protein targets obtained here (Kd values of 14 and 20 μM for BSA and CD40L, respectively) were in good agreement with that expected from the PPI inhibitory activity of ErB. A stoichiometry greater than one was observed both for CD40L and BSA binding (nb of 5–6 and 8–9 for BSA and CD40L, respectively), indicating the possibility of nonspecific binding of the flat and rigid ErB molecule at multiple sites, which could explain the promiscuous PPI inhibitory activity if some of these overlap with the binding site of the protein partner and interfere with the binding. Copyright © 2013 John Wiley & Sons, Ltd.
Analysis of internal winding short circuit faults in power transformers using transient finite element method coupling with external circuit equations
Authors: Behjat Vahid , Vahedi Abolfazl
Published: March 2013

Interturn short circuit faults are the leading cause of power transformer failures. If not quickly detected, these faults usually develop into more serious faults, which would result in irreversible damage to the transformer, unexpected outages, and consequential costs. The aim of this research is to obtain a better understanding of the physical behavior of the power transformers in the presence of interturn faults as well as to discover the best indicators for detection of interturn short circuit faults. To this end, a time stepping finite element model of power transformer has been developed to analyze the transient behavior of a real power transformer when the transformer is working under winding short circuit fault conditions. The transient model, coupled with external circuit equations, allows us to simulate the dynamic behavior of the transformer with the real power supply and external loads connections. The FEM computations show the ability of the electromagnetic flux inside the transformer, transformer terminal currents, and circulating current in the shorted turns as useful monitoring parameters for transformer fault detection. Copyright © 2013 John Wiley & Sons, Ltd.