bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of leptin infusion during peak lactation on food intake, body composition, litter growth, and maternal neuroendocrine status in female Brandt's voles (Lasiopodomys brandtii)
Authors: Cui Jian-Guo , Tang Gang-Bin , Wang De-Hua , Speakman John R.
Published: December 2010

During lactation, female small mammals frequently reduce their fat reserves to very low levels. The function of this reduction is unclear, as calculations suggest that the contribution of the withdrawn energy from fat to the total energy balance of lactation is trivial. An alternative hypothesis is that reducing fat leads to a reduction in circulating adipokines, such as leptin, that play a role in stimulating the hyperphagia of lactation. We investigated the role of circulating leptin in lactation by repleting leptin levels using miniosmotic pumps during the last 7 days of lactation in Brandt's voles ( Lasiopodomys brandtii ), a model small wild mammal we have extensively studied in the context of lactation energy demands. Repletion of leptin resulted in a dose-dependent reduction of body mass and food intake in lactating voles. Comparisons to nonreproducing individuals suggests that the reduced leptin in lactation, due to reduced fat stores, may account for ∼16% of the lactational hyperphagia. Reduced leptin in lactation may, in part, cause lactational hyperphagia via stimulatory effects on hypothalamic orexigenic neuropeptides (neuropeptide Y and agouti-related peptide) and inhibition of the anorexigenic neuropeptide (proopiomelanocortin). These effects were reversed by the experimental repletion of leptin. There was no significant effect of leptin treatment on daily energy expenditure, milk production or pup growth, but leptin repletion did result in a reversal of the suppression of uncoupling protein-1 levels in brown adipose tissue, indicating an additional role for reducing body fat and leptin during peak lacation.
A high-protein neonatal formula induces a temporary reduction of adiposity and changes later adipocyte physiology
Authors: Sarr Ousseynou , Gondret Florence , Jamin Agnès , Le Huërou-Luron Isabelle , Louveau Isabelle
Published: December 2010

The high-protein content of formula offered to low-birth weight babies is suspected to increase the risk of obesity later in life. This study assesses the immediate and subsequent effects of a protein intake in excess during suckling on hormonal and metabolic status and adipose tissue features in a porcine model of intrauterine growth restriction. Piglets were fed milk replacers formulated to provide an adequate (AP) or a high (HP) protein supply from day 2 to day 28. A subset of piglets was killed at day 28. After weaning, the remaining piglets had free access to the same solid high-fat diet until day 160. From day 2 to day 28, HP piglets had a greater daily weight gain ( P < 0.05). Relative weight of perirenal adipose tissue (PAT), adipocyte mean diameters, activities of lipogenic enzymes in PAT and subcutaneous adipose tissue (SCAT), and leptinemia were lower ( P < 0.05) in HP piglets than in AP piglets. Genes related to glucose utilization and lipid anabolism in PAT and SCAT were ( P < 0.05) or tended ( P < 0.1) to be downregulated in HP piglets. At day 160, adipocytes were enlarged, whereas lipogenic rates in adipocytes were reduced ( P < 0.05) in SCAT of HP compared with AP pigs. Percent body fat, mRNA levels of genes controlling lipid metabolism, and plasma concentrations of hormones and metabolites were similar in HP and AP pigs. In conclusion, a HP neonatal formula induced a temporary reduction of adiposity and changed adipocyte physiology at peripubertal age.
AT1 receptors in the paraventricular nucleus mediate the hyperthermia-induced reflex reduction of renal blood flow in rats
Authors: Chen Feng , Liu Fang , Badoer Emilio
Published: December 2010

Increasing body core temperature reflexly decreases renal blood flow (RBF), and the hypothalamic paraventricular nucleus (PVN) plays an essential role in this response. ANG II in the brain is involved in the cardiovascular responses to hyperthermia, and ANG II receptors are highly concentrated in the PVN. The present study investigated whether ANG II in the PVN contributes to the cardiovascular responses elicited by hyperthermia. Rats anesthetized with urethane (1–1.4 g/kg iv) were microinjected bilaterally into the PVN (100 nl/side) with saline ( n = 5) or losartan (1 nmol/100 nl) ( n = 7), an AT1 receptor antagonist. Body core temperature was then elevated from 37°C to 41°C and blood pressure (BP), heart rate (HR), RBF, and renal vascular conductance (RVC) were monitored. In separate groups losartan ( n = 4) or saline ( n = 4) was microinjected into the PVN, but body core temperature was not elevated. Increasing body core temperature in control rats elicited significant decreases in RBF (−48 ± 5% from a resting level of 14.3 ± 1.4 ml/min) and MVC (−40 ± 4% from a resting level of 0.128 ± 0.013 ml/min·mmHg), and these effects were entirely prevented by pretreatment with losartan. In rats in which body core temperature was not altered, losartan microinjected into the PVN had no significant effects on these variables. The results suggest that endogenous ANG II acts on AT1 receptors in the PVN to mediate the reduction in RBF induced by hyperthermia.
The role of exercise intensity in the bone metabolic response to an acute bout of weight-bearing exercise
Authors: Scott Jonathan P. R. , Sale Craig , Greeves Julie P. , Casey Anna , Dutton John , Fraser William D.
Published: December 2010

We compared the effects of exercise intensity (EI) on bone metabolism during and for 4 days after acute, weight-bearing endurance exercise. Ten males [mean ± SD maximum oxygen uptake (V̇o2max): 56.2 ± 8.1 ml·min−1·kg−1] completed three counterbalanced 8-day trials. Following three control days, on day 4, subjects completed 60 min of running at 55%, 65%, and 75% V̇o2max. Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH2-terminal propeptides of procollagen type 1 (P1NP), osteocalcin (OC), bone-alkaline phosphatase (ALP)], osteoprotegerin (OPG), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate (PO4), and cortisol were measured during and for 3 h after exercise and on four follow-up days (FU1–FU4). At 75% V̇o2max, β-CTX was not significantly increased from baseline by exercise but was higher compared with 55% (17–19%, P < 0.01) and 65% (11–13%, P < 0.05) V̇o2maxin the first hour postexercise. Concentrations were decreased from baseline in all three groups by 39–42% ( P < 0.001) at 3 h postexercise but not thereafter. P1NP increased ( P < 0.001) during exercise only, while bone-ALP was increased ( P < 0.01) at FU3 and FU4, but neither were affected by EI. PTH and cortisol increased ( P < 0.001) with exercise at 75% V̇o2maxonly and were higher ( P < 0.05) than at 55% and 65% V̇o2maxduring and immediately after exercise. The increases ( P < 0.001) in OPG, ACa, and PO4with exercise were not affected by EI. Increasing EI from 55% to 75% V̇o2maxduring 60 min of running resulted in higher β-CTX concentrations in the first hour postexercise but had no effect on bone formation markers. Increased bone-ALP concentrations at 3 and 4 days postexercise suggest a beneficial effect of this type of exercise on bone mineralization. The increase in OPG was not influenced by exercise intensity, whereas PTH was increased at 75% V̇o2maxonly, which cannot be fully explained by changes in serum calcium or PO4concentrations.
Reactive oxygen species cause endothelial dysfunction in chronic flow overload
Authors: Lu X. , Guo X. , Wassall C. D. , Kemple M. D. , Unthank J. L. , Kassab G. S.
Published: December 2010

Although elevation of shear stress increases production of vascular reactive oxygen species (ROS), the role of ROS in chronic flow overload (CFO) has not been well investigated. We hypothesize that CFO increases ROS production mediated in part by NADPH oxidase, which leads to endothelial dysfunction. In six swine, CFO in carotid arteries was induced by contralateral ligation for 1 wk. In an additional group, six swine received apocynin (NADPH oxidase blocker and anti-oxidant) treatment in conjunction with CFO for 1 wk. The blood flow in carotid arteries increased from 189.2 ± 25.3 ml/min (control) to 369.6 ± 61.9 ml/min (CFO), and the arterial diameter increased by 8.6%. The expressions of endothelial nitric oxide synthase (eNOS), p22/p47phox, and NOX2/NOX4 were upregulated. ROS production increased threefold in response to CFO. The endothelium-dependent vasorelaxation was compromised in the CFO group. Treatment with apocynin significantly reduced ROS production in the vessel wall, preserved endothelial function, and inhibited expressions of p22/p47phox and NOX2/NOX4. Although the process of CFO remodeling to restore the wall shear stress has been thought of as a physiological response, the present data implicate NADPH oxidase-produced ROS and eNOS uncoupling in endothelial dysfunction at 1 wk of CFO.
Emergence of airway smooth muscle functions related to structural malleability
Authors: Seow Chun Y. , Fredberg Jeffrey J.
Published: December 2010

The function of a complex system such as a smooth muscle cell is the result of the active interaction among molecules and molecular aggregates. Emergent macroscopic manifestations of these molecular interactions, such as the length-force relationship and its associated length adaptation, are well documented, but the molecular constituents and organization that give rise to these emergent muscle behaviors remain largely unknown. In this minireview, we describe emergent properties of airway smooth muscle that seem to have originated from inherent fragility of the cellular structures, which has been increasingly recognized as a unique and important smooth muscle attribute. We also describe molecular interactions (based on direct and indirect evidence) that may confer malleability on fragile structural elements that in turn may allow the muscle to adapt to large and frequent changes in cell dimensions. Understanding how smooth muscle works may hinge on how well we can relate molecular events to its emergent macroscopic functions.
Membrane and synaptic properties of pyramidal neurons in the anterior olfactory nucleus
Authors: McGinley Matthew J. , Westbrook Gary L.
Published: December 2010

The anterior olfactory nucleus (AON) is positioned to coordinate activity between the piriform cortex and olfactory bulbs, yet the physiology of AON principal neurons has been little explored. Here, we examined the membrane properties and excitatory synapses of AON principal neurons in brain slices of PND22–28 mice and compared their properties to principal cells in other olfactory cortical areas. AON principal neurons had firing rates, spike rate adaptation, spike widths, and I-V relationships that were generally similar to pyramidal neurons in piriform cortex, and typical of cerebral cortex, consistent with a role for AON in cortical processing. Principal neurons in AON had more hyperpolarized action potential thresholds, smaller afterhyperpolarizations, and tended to fire doublets of action potentials on depolarization compared with ventral anterior piriform cortex and the adjacent epileptogenic region preendopiriform nucleus (pEN). Thus, AON pyramidal neurons have enhanced membrane excitability compared with surrounding subregions. Interestingly, principal neurons in pEN were the least excitable, as measured by a larger input conductance, lower firing rates, and more inward rectification. Afferent and recurrent excitatory synapses onto AON pyramidal neurons had small amplitudes, paired pulse facilitation at afferent synapses, and GABAB modulation at recurrent synapses, a pattern similar to piriform cortex. The enhanced membrane excitability and recurrent synaptic excitation within the AON, together with its widespread outputs, suggest that the AON can boost and distribute activity in feedforward and feedback circuits throughout the olfactory system.
CB1 modulation of temporally distinct synaptic facilitation among local circuit interneurons mediated by N-type calcium channels in CA1
Authors: Ali Afia B.
Published: December 2010

One of the critical factors in determining network behavior of neurons is the influence of local circuit connections among interneurons. The short-term synaptic plasticity and the subtype of presynaptic calcium channels used at local circuit connections of inhibitory interneurons in CA1 were investigated using dual whole-cell recordings combined with biocytin and double immunofluorescence labeling in acute slices of P18- to 21-day-old rat stratum radiatum (SR) and stratum lacunosum moleculare (SLM). Two forms of temporally distinct synaptic facilitation were observed among interneuron connections involving presynaptic cholecystokinin (CCK)-positive cells in SR, frequency-dependent facilitation, and a delayed onset of release (45–80 ms) with subsequent facilitation (DORF). Inhibition at both these synapses was under tonic cannabinoid-type 1 (CB1) receptor activity. DORF synapses did not display conventional release-dependent properties; however, blocking CB1 receptors with antagonist AM-251 (10 μM) altered the synaptic transmission to frequency-dependent depression with a fast onset of release (2–4 ms). Presynaptic CCK-negative interneurons in SLM elicited inhibitory postsynaptic potentials (IPSPs) insensitive to CB1 receptor pharmacology displayed frequency-dependent depression. Release of GABA at facilitating synapses was solely mediated via N-type presynaptic calcium channels, whereas depressing synapses utilized P/Q-type channels. These data reveal two distinct models of neurotransmitter release patterns among interneuron circuits that correlate with the subtype of presynaptic calcium channel. These data suggest that endocannabinoids act via CB1 receptors to selectively modulate N-type calcium channels to alter signal transmission.
B-Cell Pathology in Juvenile Idiopathic Arthritis
Authors: Wiegering V. , Girschick H. J. , Morbach H.
Published: December 2010

Juvenile Idiopathic Arthritis (JIA) is the most common cause of chronic arthritis in childhood and adolescents and encompasses a heterogeneous group of different diseases. Due to the promising results of B-cell depleting therapies in rheumatoid arthritis the role of B-cells in autoimmune diseases has to be discussed in a new context. Additionally, experiments in mouse models have shed new light on the antibody-independent role of B-cells in the development of autoimmune diseases. In this review we will discuss the importance of B-cells in the pathogenesis of JIA appraising the question for an immunological basis of B-cell targeted therapy in JIA.
BCR/ABL Stimulates WRN to Promote Survival and Genomic Instability
Authors: Slupianek Artur , Poplawski Tomasz , Jozwiakowski Stanislaw K. , Cramer Kimberly , Pytel Dariusz , Stoczynska Ewelina , Nowicki Michal O. , Blasiak Janusz , Skorski Tomasz
Published: December 2010

BCR/ABL-transformed chronic myeloid leukemia (CML) cells accumulate numerous DNA double-strand breaks (DSB) induced by reactive oxygen species (ROS) and genotoxic agents. To repair these lesions BCR/ABL stimulate unfaithful DSB repair pathways, homologous recombination repair (HRR), nonhomologous end-joining (NHEJ), and single-strand annealing (SSA). Here, we show that BCR/ABL enhances the expression and increase nuclear localization of WRN (mutated in Werner syndrome), which is required for processing DSB ends during the repair. Other fusion tyrosine kinases (FTK), such as TEL/ABL, TEL/JAK2, TEL/PDGFβR, and NPM/ALK also elevate WRN. BCR/ABL induces WRN mRNA and protein expression in part by c-MYC-mediated activation of transcription and Bcl-xL–dependent inhibition of caspase-dependent cleavage, respectively. WRN is in complex with BCR/ABL resulting in WRN tyrosine phosphorylation and stimulation of its helicase and exonuclease activities. Activated WRN protects BCR/ABL-positive cells from the lethal effect of oxidative and genotoxic stresses, which causes DSBs. In addition, WRN promotes unfaithful recombination-dependent repair mechanisms HRR and SSA, and enhances the loss of DNA bases during NHEJ in leukemia cells. In summary, we postulate that BCR/ABL-mediated stimulation of WRN modulates the efficiency and fidelity of major DSB repair mechanisms to protect leukemia cells from apoptosis and to facilitate genomic instability. Cancer Res; 71(3); 842–51. ©2010 AACR.
C Terminus of Clostridium perfringens Enterotoxin Downregulates CLDN4 and Sensitizes Ovarian Cancer Cells to Taxol and Carboplatin
Authors: Gao Zhijian , Xu Xiaoyin , McClane Bruce , Zeng Qing , Litkouhi Babak , Welch William R. , Berkowitz Ross S. , Mok Samuel C. , Garner Elizabeth I.O.
Published: December 2010

Purpose: We have previously shown that CLDN4 (encoding claudin-4), a cell tight junction (TJ) protein, is highly expressed in human epithelial ovarian carcinomas (EOC) but undetectable in normal ovaries. CLDN4 has been identified as a specific receptor for C terminus of Clostridium perfringens enterotoxin (C-CPE), a nontoxic molecule that may disrupt TJ barrier function and enhance cellular absorption. The purpose of this study was to determine the potential clinical applications of C-CPE and its effects on CLDN4 expression in EOC.

Experimental Design: Using a 3-dimensional culture model and monolayer culture of EOC cells, we examined the effects of C-CPE on CLDN4 expression by quantitative real-time PCR, immunofluorescence, and Western blot. The synergistic effect of C-CPE to clinically relevant chemotherapies (Taxol and Carboplatin) was observed in EOC culture and xenograft mice. Furthermore, we determined through oligonucleotide microarray analysis that the transcript profile alterations dysregulated as a consequence of C-CPE treatment.

Results: C-CPE treatment decreased protein expression and relocated CLDN4 from cell–cell contact regions to the cytoplasm. Particularly, C-CPE sensitized EOC cells to chemotherapeutic administration at low dosages and significantly inhibited tumor growth in a nontoxic manner. Furthermore, we provided genome-wide molecular evidence that C-CPE treatment is involved in the stimulation of the ubiquitin–proteasome pathway and the inhibition of cell metabolism in EOC cells.

Conclusions: The addition of C-CPE can enhance the effectiveness of Taxol or Carboplatin and significantly inhibited EOC cell growth in a CLDN4-dependent manner, suggesting that C-CPE may have promising therapeutic potential for EOC. Clin Cancer Res; 17(5); 1065–74. ©2010 AACR.
KNK437 Downregulates Heat Shock Protein 27 of Pancreatic Cancer Cells and Enhances the Cytotoxic Effect of Gemcitabine
Authors: Taba Kumiko , Kuramitsu Yasuhiro , Ryozawa Shomei , Yoshida Kanako , Tanaka Toshiyuki , Mori-Iwamoto Sayaka , Maehara Shin-ichiro , Maehara Yoshihiko , Sakaida Isao , Nakamura Kazuyuki
Published: December 2010

Background: Our previous proteomic study demonstrated that expression of heat shock protein 27 (HSP27) is upregulated in gemcitabine (GEM)-resistant pancreatic cancer cells and that it suppressed the cytotoxic effect of GEM on the cells. This report describes the benefits of a treatment strategy combining the HSP inhibitor KNK437 with GEM for GEM-resistant pancreatic cancer cells. Methods: We used 2 human pancreatic cancer cell lines, GEM-sensitive KLM1 and GEM-resistant KLM1-R. KLM1-R was treated with KNK437, and we examined the expression of HSP27 by Western blotting. The cytotoxicity of GEM and KNK437 for KLM1-R was investigated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Results: The expression of HSP27 in KLM1-R was dramatically reduced by KNK437. In addition, the in vitro antitumor cytotoxic effect of GEM on KLM1-R was enhanced by combination treatment with KNK437 compared to GEM alone. Conclusion: This study supports the potential therapeutic benefits of a treatment strategy combining KNK437 with GEM.
Short Report: Relationship between Quality Protein, Lean Mass and Bone Health
Authors: Loenneke Jeremy P. , Balapur Abhishek , Thrower Austin D. , Syler Georganne , Timlin Maureen , Pujol Thomas J.
Published: December 2010

Background: Quality protein intake, and distribution of that protein, could play an important role with lean mass (LM), bone mineral density (BMD) and bone mineral content (BMC). Research has demonstrated that muscle protein synthesis is maximally stimulated at approximately 10 g of essential amino acids (EAA)/meal. This study sought to determine the relationship between the amount of quality protein consumed and the amount of times the approximately 10 g EAA threshold was reached at a meal, with respect to LM, BMD and BMC. Methods: Twenty-seven subjects participated in this study. EAA intake was determined from a 3-day food record, and amino acid profiling was determined using a computer program (USDA Database, release 22). LM, BMD and BMC were measured using dual-energy X-ray absorptiometry. Quality protein was defined as the ratio of EAA to total dietary protein. Data were analyzed using Pearson partial coefficient correlations, controlling for body mass, with an α-level of 0.05. Results: Quality protein consumed in a 24-hour period and the amount of times reaching the EAA threshold per day was positively associated with LM, BMD and BMC, and had an inverse relationship with body fat percentage. Conclusion: Both quality protein intake and frequency are positively associated with favorable body composition and bone health.
Preliminary Assessment of Methods Used to Demonstrate Nut-Cracking Behavior to Five Captive Chimpanzees (Pan troglodytes)
Authors: Ross S.R. , Milstein M.S. , Calcutt S.E. , Lonsdorf E.V.
Published: December 2010

Chimpanzees acquire nut-cracking skills by observation and trial and error. Studies of captive chimpanzees have shown the effectiveness of a skilled demonstrator. We examined the effectiveness of 3 live demonstration forms from which subjects could learn nut-cracking skills: a video of proficient conspecifics, human demonstration and the presence of a skilled conspecific performing the task. A male subject did not learn to crack open nuts after viewing a video of proficient conspecifics but quickly learned the skill following a demonstration by a human facilitator. Subsequently, 4 female chimpanzees were given the opportunity to learn the skill from the now proficient male, as well as from a video and human demonstration, but failed to do so.
Early Transtympanic Steroid Injection in Patients with ‘Poor Prognosis’ Idiopathic Sensorineural Sudden Hearing Loss
Authors: Zhou Yide , Zheng Hongliang , Zhang Qing , Campione Peter A.
Published: December 2010

Objective: The present trial is aimed to evaluate the effectiveness of early transtympanic steroid injection in patients with ‘poor prognosis’ idiopathic sensorineural sudden hearing loss (ISSHL). Methods: Seventy-six patients, diagnosed as having ISSHL with ‘poor prognosis’, were randomized into a transtympanic group and a control group. Thirty-nine patients received conventional steroid treatment and 37 patients received 4 courses of additional transtympanic injections of methylprednisolone 7 days after conventional steroid treatment. Results: In the transtympanic group 45.9% of the patients had at least 15 dB improvement in pure tone average compared with 20.5% of the patients in the control group at the 8-week follow-up audiogram. In the transtympanic group 43.2% of the patients had an improvement of ≧15% in speech discrimination, compared with 17.9% of the patients in the control group 8 weeks after the treatment. The differences between the 2 groups were statistically significantly. Conclusion: The outcome was better for the patients with ‘poor prognosis’ ISSHL if the transtympanic steroid therapy could be applied early.
Gene Coexpression Network Topology of Cardiac Development, Hypertrophy, and Failure
Authors: Dewey Frederick E. , Perez Marco V. , Wheeler Matthew T. , Watt Clifton , Spin Joshua , Langfelder Peter , Horvath Steve , Hannenhalli Sridhar , Cappola Thomas P. , Ashley Euan A.
Published: December 2010

Background—

Network analysis techniques allow a more accurate reflection of underlying systems biology to be realized than traditional unidimensional molecular biology approaches. Using gene coexpression network analysis, we define the gene expression network topology of cardiac hypertrophy and failure and the extent of recapitulation of fetal gene expression programs in failing and hypertrophied adult myocardium.

Methods and Results—

We assembled all myocardial transcript data in the Gene Expression Omnibus (n=1617). Because hierarchical analysis revealed species had primacy over disease clustering, we focused this analysis on the most complete (murine) dataset (n=478). Using gene coexpression network analysis, we derived functional modules, regulatory mediators, and higher-order topological relationships between genes and identified 50 gene coexpression modules in developing myocardium that were not present in normal adult tissue. We found that known gene expression markers of myocardial adaptation were members of upregulated modules but not hub genes. We identified ZIC2 as a novel transcription factor associated with coexpression modules common to developing and failing myocardium. Of 50 fetal gene coexpression modules, 3 (6%) were reproduced in hypertrophied myocardium and 7 (14%) were reproduced in failing myocardium. One fetal module was common to both failing and hypertrophied myocardium.

Conclusions—

Network modeling allows systems analysis of cardiovascular development and disease. Although we did not find evidence for a global coordinated program of fetal gene expression in adult myocardial adaptation, our analysis revealed specific gene expression modules active during both development and disease and specific candidates for their regulation.
Atrial Fibrillation Induces Myocardial Fibrosis Through Angiotensin II Type 1 Receptor–Specific Arkadia-Mediated Downregulation of Smad7
Authors: He Xuyu , Gao Xiuren , Peng Longyun , Wang Shenming , Zhu Yingying , Ma Hong , Lin Jun , Duan Dayue Darrel
Published: December 2010

Rationale:

Tachycardia-induced atrial fibrosis is a hallmark of structural remodeling of atrial fibrillation (AF). The molecular mechanisms underlying the AF-induced atrial fibrosis remain unclear.

Objective:

To determine the role of angiotensin II (Ang II)/Ang II type 1 (AT
1
) receptor–coupled transforming growth factor (TGF)-β
1
/Smad signaling pathway in the AF-induced atrial fibrosis.

Methods and Results:

Rapid atrial pacing (1000 ppm) was applied to the left atrium of rabbit heart to induce atrial fibrillation and fibrosis. Quantitative PCR and Western blot analysis revealed that rapid atrial pacing caused a marked increase in the expression of Ang II, TGF-β
1
, phosphorylated Smad2/3 (P-Smad2/3), Arkadia, and hydroxyproline synthesis. However, the expression of Smad7, a key endogenous antagonist of the TGF-β
1
/Smad-mediated fibrosis, was significantly decreased. These changes were dose-dependently reversed by AT
1
receptor antagonist losartan, implicating the involvement of AF-induced release of Ang II and activation of AT
1
receptor–specific pathway. In the adult rabbit cardiac fibroblasts, Ang II increased the expression of TGF-β
1
, P-Smad2/3, Smad4, Arkadia, and collagen I synthesis and significantly reduced Smad7 expression. These effects of Ang II were reversed by losartan but not by the AT
2
antagonist (PD123319). In addition, extracellular signal-regulated kinase inhibitor and anti–TGF-β
1
antibody also blocked the Ang II–induced downregulation of Smad7. Silencing of Smad7 gene by small interfering RNA abolished the antagonism of losartan on the fibrogenic effects of Ang II on cardiac fibroblasts, whereas overexpression of Smad7 blocked Ang II–induced increase in collagen I synthesis.

Conclusions:

Ang II/AT
1
receptor–specific activation of Arkadia-mediated poly-ubiquitination and degradation of Smad7 may decrease the inhibitory feedback regulation of TGF-β
1
/Smad signaling and serves as a key mechanism for AF-induced atrial fibrosis.
At the Edge of Semantic Space: The Breakdown of Coherent Concepts in Semantic Dementia Is Constrained by Typicality and Severity but Not Modality
Authors: Mayberry Emily J. , Sage Karen , Lambon Ralph Matthew A.
Published: December 2010

Hub-and-spoke models of semantic representation suggest that coherent concepts are formed from the integration of multiple, modality-specific information sources with additional modality-invariant representations—most likely stored in the ventrolateral anterior temporal lobe (vATL). As well as providing the necessary computational mechanisms for the complexities of feature integration, these modality-invariant representations also license a key aspect of semantic memory—semantic-based generalization. Semantic dementia allows us to investigate this aspect of conceptual knowledge because (a) the patients have a selective and progressive semantic degradation and (b) this is associated with profound ventrolateral ATL atrophy. Specifically, the boundaries between concepts become degraded in semantic dementia and, when tested using the appropriate materials, the patients make simultaneous under- and overgeneralization errors. We found that the rate of these errors were a function of typicality and psuedotypicality of the items as well as the severity of the patients' semantic impairment. Following the modality-invariant nature of the vATL hub representation, we also confirmed that the patients were impaired on both verbal- and picture-based versions of the same task.
MODIS Reflectance and Active Fire Data for Burn Mapping in Colombia
Authors: Merino-de-Miguel Silvia , González-Alonso Federico , Huesca Margarita , Armenteras Dolors , Franco Carol
Published: December 2010

Satellite-based strategies for burned area mapping may rely on two types of remotely sensed data: postfire reflectance images and active fire detection. This study uses both methods in a synergistic way. In particular, burned area mapping is carried out using MCD43B4 [Moderate Resolution Imaging Spectrometer (MODIS); Terra + Aqua nadir bidirectional reflectance distribution function (BRDF); adjusted reflectance 16-day L3 global 1-km sinusoidal grid V005 (SIN)] postfire datasets and MODIS active fire products. The developed methodology was tested in Colombia, an area not covered by any known MODIS ground antenna, using data from 2004. The resulting burned area map was validated using a high-spatial-resolution Landsat-7 Enhanced Thematic Mapper Plus (ETM+) image and compared to two global burned area products: L3JRC (terrestrial ecosystem monitoring global burnt area product) and MCD45A1 (MODIS Terra + Aqua burned area monthly global 500-m SIN grid V005). The results showed that this method would be of great interest at regional to national scales because it proved to be quick, accurate, and cost effective.
Quality Control and Tilt Correction Effects on the Turbulent Fluxes Observed at an Ocean Platform
Authors: Oh Hyun-Mi , Kim Kyung-Eak , Ha Kyung-Ja , Mahrt Larry , Shim Jae-Seol
Published: December 2010

This study investigates atmospheric factors influencing the quality and the postprocessing (e.g., tilt correction) of fast-response measurements of turbulent fluxes for difficult open-sea measurements over an offshore platform. The data were collected at the Ieodo Ocean Research Station over the Yellow Sea during the period from 5 November 2007 to 19 February 2008. The quality control removal of the data generally depends on wind speed, relative humidity, significant wave height, visibility, and stability. The removal of substantial water vapor data with weak-wind stable conditions is investigated. Three different tilt correction algorithms (double rotation, triple rotation, and planar fit) are applied to correct the data because of inadvertent tilt of sonic anemometers. The choice of tilt correction method significantly influences the angle between the wind and stress direction.
A Climatology of Rossby Wave Breaking on the Southern Hemisphere Tropopause
Authors: Ndarana Thando , Waugh Darryn W.
Published: December 2010

A 30-yr climatology of Rossby wave breaking (RWB) on the Southern Hemisphere (SH) tropopause is formed using 30 yr of reanalyses. Composite analysis of potential vorticity and meridional fluxes of wave activity show that RWB in the SH can be divided into two broad categories: anticyclonic and cyclonic events. While there is only weak asymmetry in the meridional direction and most events cannot be classified as equatorward or poleward in terms of the potential vorticity structure, the position and structure of the fluxes associated with equatorward breaking differs from those of poleward breaking. Anticyclonic breaking is more common than cyclonic breaking, except on the lower isentrope examined (320 K). There are marked differences in the seasonal variations of RWB on the two surfaces, with a winter minimum for RWB around 350 K but a summer minimum for RWB around 330 K. These seasonal variations are due to changes in the location of the tropospheric jets and dynamical tropopause. During winter the subtropical jet and tropopause at 350 K are collocated in the Australian–South Pacific Ocean region, resulting in a seasonal minimum in the 350-K RWB. During summer the polar front jet and 330-K tropopause are collocated over the Southern Atlantic and Indian Oceans, inhibiting RWB in this region.
Experimental Quantification of the Sampling Uncertainty Associated with Measurements from PARSIVEL Disdrometers
Authors: Jaffrain Joël , Berne Alexis
Published: December 2010

The variability of the (rain)drop size distribution (DSD) in time and space is an intrinsic property of rainfall, which is of primary importance for various environmental fields such as remote sensing of precipitation, for example. DSD observations are usually collected using disdrometers deployed at the ground level. Like any other measurement of a physical process, disdrometer measurements are affected by noise and sampling effects. This uncertainty must be quantified and taken into account in further analyses. This paper addresses this issue for the Particle Size Velocity (PARSIVEL) optical disdrometer by using a large dataset corresponding to light and moderate rainfall and collected from two collocated PARSIVELs deployed during 15 months in Lausanne, Switzerland. The relative sampling uncertainty associated with quantities characterizing the DSD—namely the total concentration of drops Nt and the median-volume diameter D0—is quantified for different temporal resolutions. Similarly, the relative sampling uncertainty associated with the estimates of the most commonly used weighted moments of the DSD (i.e., the rain-rate R, the radar reflectivity at horizontal polarization Zh, and the differential reflectivity Zdr) is quantified as well for different weather radar frequencies. The relative sampling uncertainty associated with estimates of Nt is below 13% for time steps longer than 60 s. For D0, it is below 8% for D0 values smaller than 1 mm. The associated sampling uncertainty for estimates of R is on the order of 15% at a temporal resolution of 60 s. For Zh, the sampling uncertainty is below 9% for Zh values below 35 dBZ at a temporal resolution of 60 s. For Zdr values below 0.75 dB, the sampling uncertainty is below 36% for all temporal resolutions. These analyses provide relevant information for the accurate quantification of the variability of the DSD from disdrometer measurements.
Master andMunshī
Authors: Kinra Rajeev
Published: December 2010

This article aims to contribute to a growing body of scholarship on the cultural world of the early modern Indo-Persian state secretary, or munshī. Our guide will be the celebrated Mughal munshī, Chandar Bhān Brahman (d. 1662-63), whose life and career shed considerable light on the ideals of administrative conduct that informed political and intellectual culture during the reigns of the emperors Jahāngīr and Shāh Jahān. After examining Chandar Bhān's background and socio-intellectual milieu, we will focus in particular on a section of his prose magnum opus, Chahār Chaman (_The Four Gardens’), which served as both a memoir of his career in Mughal service and a didactic guide for exemplary ministerial theory and practice, or wizārat. Chandar Bhān's ideal wazīr, embodied by ministers like Afzal Khān Shirazi (d. 1639), Sa’d Allāh Khān (d. 1656), and Raghūnāth Rāy-i Rāyān (d. 1664), was not only tolerant and humane in the exercise of power, but also an expert in the secretarial arts in his own right, and a model of civility (akhlāq) and mystical awareness (ma’rifat) for others. In modern historiography such virtues tend to be primarily associated with Akbar's court, but at least in Chandar Bhān's eyes, they continued to have lasting relevance throughout the Mughal seventeenth century.
Corporate social responsibility and corporate financial performance: Evidence from Korea
Authors: Choi Jong-Seo , Kwak Young-Min , Choe Chongwoo
Published: December 2010

This paper studies the empirical relation between corporate social responsibility (CSR) and corporate financial performance in Korea using a sample of 1222 firm-years during 2002—2008. We measure corporate social responsibility by both an equal-weighted CSR index and a stakeholder-weighted CSR index suggested by Akpinar et al. (2008). Corporate financial performance is measured by return on equity, return on assets, and Tobin’s Q. We find a positive and significant relationship between corporate financial performance and the stakeholder-weighted CSR index, but not the equal-weighted CSR index. This finding is robust to alternative model specifications and several additional tests, providing evidence in support of instrumental stakeholder theory.
Transaction costs and institutional trading in small-cap equity funds
Authors: Comerton-Forde Carole , Gallagher David R. , Nahhas Jumana , Walter Terry S.
Published: December 2010

This paper examines the magnitude and determinants of trading costs for small-cap funds in Australia. The total price impact for these funds is 0.99% (—0.34%) for purchases (sales). This is considerably larger than costs reported in prior literature. Both purchases and sales exhibit price continuations after the trade package, consistent with an information effect. Although we do not observe the directional asymmetry typically shown in the literature, the magnitude of the total and permanent effects for purchases is larger than for sales. We also show that price impact is related to fund inflows and outflows.
A generalized single-input mixed eigenvalue assignment problem
Authors: Ramadan Mohamed A , El-Sayed Ehab A
Published: December 2010

In this paper we propose a simple recursive algorithm to assign eigenvalues real or mixed (real and complex) in a Hessenberg matrix. This problem of assigning eigenvalues in a Hessenberg matrix is considered by many authors. Among these methods is the conceptually easy and simple algorithm introduced by Datta for real eigenvalue assignment case. Recently, the problem was reconsidered by Ramadan and El-Shazly where mixed eigenvalues are assigned by modifying the Datta algorithm. In the presented paper, we consider the general case: that is the controllable pair (H, e1) where e1 is the first column of the n x n identity matrix I considered in both Datta and El-Shazly is in the more general form: (H, b) where b is an arbitrary vector. This will be carried out by modifying both algorithms. Numerical examples are given to demonstrate the performance and accuracy of the proposed algorithm.
Procedural and party effects in European Parliament roll-call votes
Authors: Høyland Bjørn
Published: December 2010

I extend the standard spatial model of legislative voting to account for vote-specific party inducements and procedural differences. Focusing on voting in the 1999—2004 European Parliament, I find evidence of vote-specific party inducements in a large share of the roll call votes. Furthermore, MEPs position themselves differently across procedures. As most roll call votes are taken on non-legislative votes, these estimates may overemphasize voting pattern on these votes and downplay voting pattern on legislative votes. As such, these estimates may be a poorly suited for studying within party heterogeneity on legislative votes.
Who to lobby and when: Institutional determinants of interest group strategies in European Parliament committees
Authors: Marshall David
Published: December 2010

This paper explains how institutional conditions in the European Parliament’s committees shape lobbyists’ strategic behaviour. Committees’ informal organization and formal procedures structure both the distribution of legislative influence and the opportunity to obtain advocacy. It is demonstrated how influence and, by implication, lobbying activity are skewed in favour of a committee elite. Here new evidence is provided to highlight the significant impact that open amendments play in a committee’s final report. The theory also emphasizes the role that message quality plays in the decision about who to lobby, and defines the limits to lobbyists’ preference to obtain advocacy from friendly legislators. Analysis is carried out on data obtained from 94 structured interviews combined with a unique data set of committee-stage voting outcomes.
Out in the cold? Flexible integration and the political status of Euro opt-outs
Authors: Naurin Daniel , Lindahl Rutger
Published: December 2010

A common argument against flexible integration as a solution to increased preference heterogeneity is that a likely consequence for those member states opting out of the enhanced cooperation is a loss of status and influence generally in the European Union (EU). It has been argued, for example, that the decisions by Denmark, Sweden and the UK not to join the Euro is considered to be free-riding, which leads to a bad reputation and exclusion from informal networks. We test this proposed free-rider effect by comparing the network capital of Euro-outsiders with insiders in the Council of the EU, using survey data of more than 600 member state representatives. The findings speak strongly against the free-rider hypothesis, as the Euro-outsiders are highly ranked in terms of network capital.
Effects of Interviewer Experience on Components of Nonresponse in the European Social Survey
Authors: Lipps Oliver , Pollien Alexandre
Published: December 2010

The authors analyze interviewer-related nonresponse differences in face-to-face surveys, distinguishing three types of interviewers: those who have previous experience with the same high standard cross-sectional survey (‘‘experienced’’), those who were chosen by the survey agency to complete refusal conversions (‘‘seniors’’), and usual interviewers. The nonresponse components are obtaining household contact, target person contact, and target person cooperation. In addition, the authors consider whether interviewer homogeneity with respect to these components is different across the three interviewer groups. Data come from the European Social Survey (ESS) contact forms from four countries that participated in the rounds of 2002, 2004, and 2006 and used the same survey agency that, in turn, used the same interviewers to some extent. To analyze interviewer effects, the authors use discrete two-level models. The authors find some evidence of better performance by both senior and experienced interviewers and indications of greater homogeneity for nonresponse components, especially for those with room for improvement. Surprisingly, the senior interviewers do not outperform the experienced ones. The authors conclude that survey agencies should make more efforts to decrease the comparatively high interviewer turnover.
2012 Olympics: A catalyst for behaviour change?
Authors: Prest Sarah , Partridge Rachel
Published: December 2010

Aiming to make the most of the Olympic legacy, Sarah Prest and Rachel Partridge, from NHS Dorset, explain how one county is encouraging lifestyle change
Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL
Authors: Slager Susan L. , Rabe Kari G. , Achenbach Sara J. , Vachon Celine M. , Goldin Lynn R. , Strom Sara S. , Lanasa Mark C. , Spector Logan G. , Rassenti Laura Z. , Leis Jose F. , Camp Nicola J. , Glenn Martha , Kay Neil E. , Cunningham Julie M. , Hanson Curtis A. , Marti Gerald E. , Weinberg J. Brice , Morrison Vicki A. , Link Brian K. , Call Timothy G. , Caporaso Neil E. , Cerhan James R.
Published: December 2010

Prior genome-wide association (GWA) studies have identified 10 susceptibility loci for risk of chronic lymphocytic leukemia (CLL). To identify additional loci, we performed a GWA study in 407 CLL cases (of which 102 had a family history of CLL) and 296 controls. Moreover, given the strong familial risk of CLL, we further subset our GWA analysis to the CLL cases with a family history of CLL to identify loci specific to these familial CLL cases. Our top hits from these analyses were evaluated in an additional sample of 252 familial CLL cases and 965 controls. Using all available data, we identified and confirmed an independent association of 4 single-nucleotide polymorphisms (SNPs) that met genome-wide statistical significance within the IRF8 (interferon regulatory factor 8) gene (combined P values ≤ 3.37 × 10−8), located in the previously identified 16q24.1 locus. Subsetting to familial CLL cases, we identified and confirmed a new locus on chromosome 6p21.3 (combined P value = 6.92 × 10−9). This novel region harbors the HLA-DQA1 and HLA-DRB5 genes. Finally, we evaluated the 10 previously reported SNPs in the overall sample and replicated 8 of them. Our findings support the hypothesis that familial CLL cases have additional genetic variants not seen in sporadic CLL. Additional loci among familial CLL cases may be identified through larger studies.
Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis
Authors: Abdeldaim Guma MK , Strålin Kristoffer , Korsgaard Jens , Blomberg Jonas , Welinder-Olsson Christina , Herrmann Björn
Published: December 2010

Background

Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR) for detection of S. pneumoniae (9802 gene fragment), H. influenzae (omp P6 gene) and N. meningitidis (ctrA gene). The method was evaluated on bronchoalveolar lavage (BAL) samples from 156 adults with lower respiratory tract infection (LRTI) and 31 controls, and on 87 cerebrospinal fluid (CSF) samples from meningitis patients.

Results

The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis) in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 105 genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively.

In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both bacteria.

Conclusions

The PCR provides increased sensitivity and the multiplex format facilitates diagnosis of S. pneumoniae, H. influenzae and N. meningitidis and the assay enable detection after antibiotic treatment has been installed. Quantification increases the specificity of the etiology for pneumonia.