bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomics by Mass Spectrometry: Approaches, Advances, and Applications
Authors: Yates John R. , Ruse Cristian I. , Nakorchevsky Aleksey
Published: July 2009

Mass spectrometry (MS) is the most comprehensive and versatile tool in large-scale proteomics. In this review, we dissect the overall framework of the MS experiment into its key components. We discuss the fundamentals of proteomic analyses as well as recent developments in the areas of separation methods, instrumentation, and overall experimental design. We highlight both the inherent strengths and limitations of protein MS and offer a rough guide for selecting an experimental design based on the goals of the analysis. We emphasize the versatility of the Orbitrap, a novel mass analyzer that features high resolution (up to 150,000), high mass accuracy (2–5 ppm), a mass-to-charge range of 6000, and a dynamic range greater than 103. High mass accuracy of the Orbitrap expands the arsenal of the data acquisition and analysis approaches compared with a low-resolution instrument. We discuss various chromatographic techniques, including multidimensional separation and ultra-performance liquid chromatography. Multidimensional protein identification technology (MudPIT) involves a continuum sample preparation, orthogonal separations, and MS and software solutions. We discuss several aspects of MudPIT applications to quantitative phosphoproteomics. MudPIT application to large-scale analysis of phosphoproteins includes (a) a fractionation procedure for motif-specific enrichment of phosphopeptides, (b) development of informatics tools for interrogation and validation of shotgun phosphopeptide data, and (c) in-depth data analysis for simultaneous determination of protein expression and phosphorylation levels, analog to western blot measurements. We illustrate MudPIT application to quantitative phosphoproteomics of the beta adrenergic pathway. We discuss several biological discoveries made via mass spectrometry pipelines with a focus on cell signaling proteomics.
Cell Mechanics: Dissecting the Physical Responses of Cells to Force
Authors: Hoffman Brenton D. , Crocker John C.
Published: July 2009

It is now widely appreciated that normal tissue morphology and function rely upon cells' ability to sense and generate forces appropriate to their correct tissue context. Although the effects of forces on cells have been studied for decades, our understanding of how those forces propagate through and act on different cell substructures remains at an early stage. The past decade has seen a resurgence of interest, with a variety of different micromechanical methods in current use that probe cells' dynamic deformation in response to a time-varying force. The ability of researchers to carefully measure the mechanical properties of cells subjected to a variety of pharmacological and genetic interventions, however, currently outstrips our ability to quantitatively interpret the data in many cases. Despite these challenges, the stage is now set for the development of detailed models for cell deformability, motility, and mechanosensing that are rooted at the molecular level.
Modulation of motor and sensory pathways of the peristaltic reflex by cannabinoids
Authors: Grider John R. , Mahavadi Sunila , Li Yan , Qiao Li-Ya , Kuemmerle John F. , Murthy Karnam S. , Martin Billy R.
Published: July 2009

Cannabinoids have long been known to be potent inhibitors of intestinal and colonic propulsion. This effect has generally been attributed to their ability to prejunctionally inhibit release of acetylcholine from excitatory motor neurons that mediate, in part, the ascending contraction phase of the peristaltic reflex. In the present study we examined the effect of cannabinoids on the other transmitters known to participate in the peristaltic reflex using a three-compartment preparation of rat colon that allows separation of ascending contraction, descending relaxation, and the sensory components of the reflex. On addition to the orad motor compartment, anandamide decreased and AM-251, a CB-1 antagonist, increased ascending contraction and the concomitant substance P (SP) release. Similarly, on addition to the caudad motor compartment, anandamide decreased and AM-251 increased descending relaxation and the concomitant vasoactive intestinal peptide (VIP) release. On addition to the central sensory compartment, anandamide decreased and AM-251 increased both ascending contraction and SP release orad, and descending relaxation and VIP release caudad. This suggested a role for CB-1 receptors in modulation of sensory transmission that was confirmed by the demonstration that central addition of anandamide decreased and AM-251 increased release of the sensory transmitter, calcitonin gene-related peptide (CGRP). We conclude that the potent antipropulsive effect of cannabinoids is the result of inhibition of both excitatory cholinergic/tachykininergic and inhibitory VIPergic motor neurons that mediate ascending contraction and descending relaxation, respectively, as well as inhibition of the intrinsic sensory CGRP-containing neurons that initiate the peristaltic reflex underlying propulsive motility.
Regeneration of intestinal stem/progenitor cells following doxorubicin treatment of mice
Authors: Dekaney Christopher M. , Gulati Ajay S. , Garrison Aaron P. , Helmrath Michael A. , Henning Susan J.
Published: July 2009

The intestinal epithelium is in a constant state of renewal. The rapid turnover of cells is fed by a hierarchy of transit amplifying and stem/progenitor cells destined to give rise to the four differentiated epithelial lineages of the small intestine. Doxorubicin (Dox) is a commonly used chemotherapeutic agent that preferentially induces apoptosis in the intestinal stem cell zone (SCZ). We hypothesized that Dox treatment would initially decrease “+4” intestinal stem cell numbers with a subsequent expansion during mucosal repair. Temporal assessment following Dox treatment demonstrated rapid induction of apoptosis in the SCZ leading to a decrease in the number of intestinal stem/progenitor cells as determined by flow cytometry for CD45(−) SP cells, and immunohistochemistry of cells positive for putative +4 stem cell markers β-catSer552 and DCAMKL1. Between 96 and 168 h postinjection, overall proliferation in the crypts increased concomitant with increases in both absolute and relative numbers of goblet, Paneth, and enteroendocrine cells. This regeneration phase was also associated with increases of CD45(−) SP cells, β-catSer552-positive cells, crypt fission, and crypt number. We used Lgr5-lacZ mice to assess behavior of Lgr5-positive stem cells following Dox and found no change in this cell population. Lgr5 mRNA level was also measured and showed no change immediately after Dox but decreased during the regeneration phase. Together these data suggest that, following Dox-induced injury, expansion of intestinal stem cells occurs during mucosal repair. On the basis of available markers this expansion appears to be predominantly the +4 stem cell population rather than those of the crypt base.
Responses of LDL and HDL particle size and distribution to omega-3 fatty acid supplementation and aerobic exercise
Authors: Wooten Joshua S. , Biggerstaff Kyle D. , Ben-Ezra Vic
Published: July 2009

The purpose of this investigation was to determine the independent and combined effects of aerobic exercise and omega-3 fatty acid (n-3fa) supplementation on lipid and lipoproteins. Sedentary, normoglycemic, nonsmoking men ( n = 11) were assigned to perform rest and exercise before and during n-3fa supplementation. Exercise consisted of 3 consecutive days of treadmill walking at 65% maximum O2consumption for 60 min. Supplementation consisted of 42 days of 4.55 g/day of n-3fa. A two-way factorial ANOVA with repeated measures revealed significant reductions in total cholesterol ( P = 0.001, −9.2%) and triglyceride ( P = 0.007, −32.4%) concentrations postexercise. In addition, exercise increased LDL peak particle size ( P = 0.001) from 26.2 to 26.4 nm, but not HDL size. The n-3fa supplementation resulted in a significant shift in the distribution of HDL-cholesterol (HDL-C) carried by HDL2b+2a( P = 0.001, 14.2%) and HDL3a+3b( P = 0.001, −22.8%), despite no significant changes in lipid and lipoprotein-cholesterol concentrations. The majority of the shift in HDL-C was noted in HDL2b( P = 0.001, 20.9%) and HDL3a( P < 0.001, −31.0%) particles. There were no combined effects of exercise and n-3fa supplementation on lipids and lipoproteins. Three consecutive days of aerobic exercise reduced triglyceride and total cholesterol concentrations with a concomitant increase in LDL peak particle size. In contrast, n-3fa supplementation shifted HDL-C from HDL3particles to HDL2particles, despite no significant changes in HDL2-C and HDL3-C concentrations. Exercise and n-3fa supplementation do not synergistically improve serum lipids and lipoproteins, but rather independently affect the metabolism of lipids and lipoproteins.
Genetic Aspects of the Obstructive Sleep Apnoea/Hypopnoea Syndrome – Is There a Common Link with Obesity?
Authors: Riha Renata L.
Published: July 2009

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is the third most common respiratory condition after asthma and chronic obstructive airway disease affecting approximately 2–4% of the middle-aged population. OSAHS has a hereditary component but owing to difficulties with phenotyping, its genetic basis has been difficult to elucidate. Despite this, limited progress has been made in considering the genetic basis of the ‘intermediate phenotypes’ of OSAHS such as craniofacial structure and upper airway control. Obesity is a risk factor for the development of OSAHS. The genetics of obesity are complex, but advances have been made recently using genome-wide association studies. Some authors postulate that OSAHS and common obesity share many pathophysiological pathways. However, the genes underpinning the development of sleep-disordered breathing and obesity are likely to be different, despite phenotypes that appear to overlap and influence each other’s expression. This paper focuses on human studies over-viewing the most recent work in the area and includes a brief discussion on methods of genetic studies.
The Use of Biofeedback in the Treatment of Chronic Dysphagia in Stroke Patients
Authors: Bogaardt H.C.A. , Grolman W. , Fokkens W.J.
Published: July 2009

Objective: To evaluate the efficacy of the use of surface electromyographic feedback in the treatment of stroke patients with chronic dysphagia. Patients and Methods: Data of 11 consecutive patients with chronic dysphagia after stroke were analyzed. Our patients were treated for dysphagia with surface electromyography as biofeedback as adjunct to normal exercises. All patients suffered from dysphagia after stroke. The average time after onset was 31.1 months. All patients had been previously treated by speech therapists without success. Functional swallowing was estimated using the Functional Oral Intake Scale (FOIS). At the start of the treatment 8 patients were tube dependent (FOIS ≤4). Three patients were on an oral diet, but with restrictions (FOIS ≥5). Results: The patients were treated on average seven 7 times. The time between the first and last treatment session was on average 76.1 days (SD ± 44.0; range = 29–168). Before treatment the average FOIS was 2.6 (SD ±2.3) and after treatment 5.6 (SD ±1.6). The median scores improved from 1 to 6, showing a significant and clinically relevant improvement (z = –2.820: p < 0.01) in swallowing function. In 6 of initially 8 patients with percutaneous enteral gastrostomy tubes, the feeding tube could be removed after treatment. Conclusion: Our data suggest that the use of surface electromyography as biofeedback in the treatment of chronic dysphagia after stroke could be an effective adjunct to standard therapy for swallowing disorders in 11 patients.
Risk Factors for Development of Microalbuminuria in Diabetic and Nondiabetic Normoalbuminuric Hypertensives with High or Very High Cardiovascular Risk – A Twelve-Month Follow-Up Study
Authors: Cotter Jorge , Oliveira Pedro , Cunha Pedro , Polónia Jorge
Published: July 2009

Aims: To investigate risk factors for progression to microalbuminuria in normoalbuminuric hypertensive patients. Methods: In a longitudinal study, 173 previously treated normoalbuminuric hypertensive patients with high cardiovascular risk (70% diabetics) were evaluated at study entry and after 12 months. Levels of urinary albumin excretion (UAE; study entry and end of study) were compared between patients remaining normoalbuminuric (RNA) and progressors to non-normoalbuminuric (NNA) levels. Results: Out of 173 patients (59 ± 13 years), 12% evolved to NNA levels. At baseline, NNA and RNA groups did not differ in age, sex, diabetes, lipids, blood pressure (BP), drug therapy, or glomerular filtration rate. In comparison with RNA patients, the NNA group showed higher hypertension duration, greater UAE and percentage of patients with UAE ≥10 mg/g creatinine (76.2 vs. 45.4%) at study entry and higher BP levels (158/92 ± 25/10 vs. 143/83 ± 20/12 mm Hg) at study end (all p < 0.05). Logistic regression analysis identified absolute UAE values at study entry and study end variation of BP and cholesterol as independent contributors to the increase in the log odds of developing microalbuminuria. Conclusions: Normoalbuminuric hypertensives with UAE within the upper two thirds of normal range are 3 times as likely to develop microalbuminuria after 1 year. A poor BP and lipid control are also associated with increased risk of microalbuminuria.
Adiponectin in Children on Peritoneal Dialysis: Relationship to Insulin Resistance and Nutritional Status
Authors: Kamariski Mariana , Biscardi Mónica , Cestino Laura , Miatello Roberto , Guntsche Enrique , Valles Patricia G.
Published: July 2009

Aim: To study whether adiponectin and resistin serum concentrations in children on peritoneal dialysis (PD) were related to insulin resistance (IR) and anthropometric parameters of nutritional status, 11 PD patients, 9 chronic kidney disease (CKD) patients and 10 healthy children were studied. Methods: Glucose and insulin were measured during the oral glucose tolerance test. Levels of adiponectin and resistin were evaluated by ELISA, insulin by RIA. Results: In CKD patients, higher homeostasis model assessment-insulin resistance (HOMA-IR), fasting and 2-hour serum insulin levels were shown compared to control and to PD patients. Body mass index (BMI) and body fat content were severely decreased while serum adiponectin levels were significantly higher in PD patients relative to controls. No differences among groups were shown in resistin levels. On regression modeling, inverse independent associations were observed between adiponectin with percentile BMI, weight and height z-score, and with body fat content. In contrast, no relationship was found between adiponectin and IR parameters. In multiple regression analysis, adiponectin was negatively correlated with BMI. A negative association of adiponectin and resistin with glomerular filtration rate was also shown. Conclusion: A role for adiponectin in terms of its association with clinical wasting parameters in PD pediatric patients might be suggested.
The Importance of Cellular VEGF Bioactivity in the Development of Glomerular Disease
Authors: Foster Rebecca R.
Published: July 2009

The bioactivity of glomerular VEGF (or activity of available VEGF) is critical to the physiological maintenance of the glomerular filtration barrier. Disturbances in glomerular VEGF expression have been linked to numerous glomerulopathies, highlighting its importance in disease progression within the kidney. However, the changes in expression are not consistent between conditions; enhanced expression sometimes appears to have a renoprotective effect, yet at other times it appears destructive. Also, the level of expression can change with the progression of disease. This review focuses on how other cellular factors, such as TGF-β and nitric oxide, work in concert to affect the bioactivity, which is not necessarily the same as the expression of VEGF, in different glomerulopathies and attempts to explain some of the paradoxes between glomerulopathies. In conclusion, the bioactivity of glomerular VEGF is regulated by many factors that are themselves moderated by changes in the local glomerular environment, such as mechanical strain and hyperglycaemia. Thus, to understand VEGF signalling in glomerular disease progression, we must examine it in the context of other appropriate cellular factors.
Heme Oxygenase-1 Inducer Hemin Attenuates the Progression of Remnant Kidney Model
Authors: Desbuards Nicolas , Hyvelin Jean-Marc , Machet Marie-Christine , Eder Véronique , Garrigue Marie-Ange , Halimi Jean-Michel , Antier Daniel
Published: July 2009

Backgrounds/Aims: Heme oxygenase-1 (HO-1) has been shown to protect against fibrotic proliferation and apoptosis in several models of renal damage. The purpose of this study was to evaluate the impact of a treatment with the HO-1 inducer hemin on the progression of chronic kidney disease in nephrectomized rats versus the AT1 receptor antagonist losartan. Methods: The rats underwent 5/6 renal ablation and after the procedure received either losartan (20 mg/kg/day; n = 9), hemin (50 mg/kg/twice a week; n = 8) or vehicle (n = 8) over a 12-week period. At week 12, blood pressure was measured, urine, blood and remnant kidney were collected for biochemical (proteinuria, urea, creatinine) and histopathological (degrees of glomerulosclerosis and tubular atrophy) analysis. The expressions of HO-1, bone morphogenic protein 7 (BMP-7) and TGF-β were assessed by immunochemistry, and the level of the apoptosis marker protein caspase-3 by Western blot, on the remnant kidney. Results: Hemin significantly reduced blood pressure, proteinuria, inhibited the expression of TGF-β and caspase-3 protein and increased BMP-7 expression protein. Hemin-treated rats had lower glomerulosclerosis and tubular atrophy indexes than controls. Conclusion: Hemin treatment attenuates the progression of chronic kidney disease and appears more efficient than losartan in our rat model hypothetically because of the impact of hemin on the renal expression of BMP-7.
An Inner Medullary Concentrating Process Actuated by Renal Pelvic/Calyceal Muscle Contractions: Assessment and Hypothesis
Authors: Pinter G.G. , Shohet J.L.
Published: July 2009

We propose a mechanism of an inner medullary concentrating process in which water extraction is accomplished by a colloid osmotic mechanism and hydrostatic pressure. There are 3 essential features of the proposal: 1. the fluid compartmental structure of the inner medullary interstitium: owing to molecular exclusion, negatively charged macromolecules, i.e. hyaluronan and extravasated plasma albumin form separate compartments (the HA and the EPA compartments); the resulting Gibbs-Donnan effect governs the movements of both ions and water. 2. NaCl, in high concentration in the inner medulla conditioned by the outer medullary countercurrent processes, significantly reduces the equilibrium colloid osmotic pressure between these compartments. 3. Urea, also accumulated here by special transport mechanisms, increases the mobility of water molecules and the flexibility of the HA fibrils by loosening hydrogen bonds. These features suggest that rhythmic, small pressure increases of the pelvic/calyceal muscles squeeze dilute fluid out of the HA compartment and, at the same time, accelerate the outflow of fluid and albumin into the ascending vasa recta from the EPA compartment. Further, they suggest a mechanism for the phenomenon that living organisms utilize hydrostatic pressure generated by muscle contractions in water economy namely, concentrating and diluting body fluids.
Functioning and Disability in Bipolar Disorder: An Extensive Review
Authors: Sanchez-Moreno J. , Martinez-Aran A. , Tabarés-Seisdedos R. , Torrent C. , Vieta E. , Ayuso-Mateos J.L.
Published: July 2009

Background: Bipolar disorder has generally been regarded as having a better functional outcome than schizophrenia. However, studies have suggested low functioning in bipolar patients even when they are in clinical remission. Our aim was to determine the degree of functioning and disability in bipolar patients. Secondly, we reviewed factors potentially associated with the low functioning of bipolar patients. Method: The authors conducted an extensive Medline and Pubmed search of the published literature from 1980 up to December 2007, using a variety of search terms to find relevant articles. Bibliographies of retrieved papers were further analysed for publications of interest. Articles that reported clinically significant findings on functioning and disability, and research reports were reviewed in detail. Results: From these articles, we determined that bipolar disorder is associated with significant impairment in work, family and social life, beyond the acute phases of the illness. The aspects that appear to increase the risk of low functioning and disability in bipolar patients are mainly subsyndromal symptoms and neurocognitive impairment, among others. Conclusions: Suitable pharmacological and psychological interventions may improve the level of functioning and reduce the disability in bipolar patients. Potential targets to be considered for intervention should be residual symptoms, comorbid conditions and neurocognitive deficits. Further research is required to better identify the factors that best predict functioning in bipolar patients.
Cognitive and Noncognitive Neurological Features of Young-Onset Dementia
Authors: Kelley Brendan J. , Boeve Bradley F. , Josephs Keith A.
Published: July 2009

Background: The rarity of young-onset dementia (YOD), the broad differential diagnosis and unusual clinical presentations present unique challenges to correctly recognize the condition and establish an accurate diagnosis. Limited data exist regarding clinical features associated with dementia prior to the age of 45. Methods: We retrospectively assessed cognitive and noncognitive neurological characteristics of 235 patients who presented for evaluation of YOD to investigate the clinical characteristics of YOD compared to later-onset dementias and to identify clinical features associated with specific etiologies that may aid in the evaluation of YOD. Results: Multiple cognitive domains were affected in most patients, and no significant differences in affected domains existed between groups. Early psychiatric and behavioral features occurred at very high frequencies. Nearly 80% of this YOD cohort had additional noncognitive symptoms or signs as a feature of their disease. Chorea was strongly associated with Huntington disease. Parkinsonism was not seen in patients having an autoimmune/inflammatory etiology. Conclusions: The rarity of YOD and the high frequency of early psychiatric features led to frequent misdiagnosis early in the clinical course. The high frequency of noncognitive symptoms and signs may aid clinicians in distinguishing patients requiring a more extensive evaluation for YOD.
Spanish Version of the Bayer Activities of Daily Living Scale in Mild Cognitive Impairment and Mild Alzheimer Disease: Discriminant and Concurrent Validity
Authors: Sánchez-Benavides G. , Manero R.M. , Quiñones-Úbeda S. , de Sola S. , Quintana M. , Peña-Casanova J.
Published: July 2009

Aims: To test the discriminant and concurrent validity of the Spanish version of the Bayer Activities of Daily Living scale (B-ADL) in mild cognitive impairment (MCI) and mild Alzheimer disease (AD). Methods: The B-ADL scale, the Blessed Dementia Rating Scale (BDRS), and the Interview for Deterioration in Daily Living in Dementia (IDDD) were administered to 277 elderly Spanish patients (78 MCI and 199 AD). Correlations between scales were performed, and ROC curves were plotted. Results: In MCI and mild AD discrimination, an area under the ROC curve of 0.84 was found; a cut-off point of 3.3 was proposed with values of 0.81 for sensitivity and 0.72 for specificity. The B-ADL correlated positively to both the BDRS (r = 0.7) and the IDDD (r = 0.8). Conclusion: The B-ADL is a valid and sensitive scale that can be used to discriminate mild AD from MCI.
Excessive Daytime Sleepiness in Idiopathic Restless Legs Syndrome: Characteristics and Evolution under Dopaminergic Treatment
Authors: Kallweit Ulf , Siccoli Massimiliano M. , Poryazova Rositsa , Werth Esther , Bassetti Claudio L.
Published: July 2009

Background/Aims: Whereas insomnia is frequent in restless legs syndrome (RLS), little is known about daytime sleepiness. We studied a series of 27 consecutive patients with idiopathic RLS in order to identify the characteristics and evolution of excessive daytime sleepiness (EDS) under dopaminergic treatment. Methods: Patients were assessed by clinical examination, questionnaires and video-polysomnography (PSG). Sleepy patients, as defined by Epworth Sleepiness Scale (ESS) >10, were also assessed by the multiple sleep latency test (MSLT). We excluded RLS patients with other sleep-wake disorders, in particular chronic sleep deprivation. Results: Mean age was 56 years, the mean International RLS Study Group Rating Scale score was 24 at baseline. Ten (37%) of the 27 patients reported EDS. RLS patients with sleepiness had a higher amount of total sleep time (p = 0.029) on PSG and a mean sleep latency of 6.4 min on MSLT. No other differences regarding clinical or polysomnographic parameters were found. RLS severity improved in all patients under dopaminergic treatment (p = 0.001); this was also the case for the ESS score in sleepy patients (p = 0.007). Conclusion: In our series of RLS patients, EDS was common, characterized by longer sleep (PSG) and reduced sleep latencies on MSLT. Under dopaminergic treatment, both RLS severity and ESS improved.
Yawning in Diseases
Authors: Walusinski Olivier
Published: July 2009

Yawning is a physiological behavior, an emotional stereotypy that indicates the homeostatic process of the mechanisms regulating rhythms, such as sleeping/waking, hunger/satiety or mating/relaxation, generated by the diencephalon. As with all physiological behaviors, its deregulation reveals disorders. In daily practice, yawning as a symptom is generally neglected. That is why we propose a wide overview of yawning in diseases, its consequences and significance.
Prolactin Released in vitro from the Pituitary of Lactating, Pregnant, and Steroid-Treated Female or Male Rats Stimulates Prolactin Secretion from Pituitary Lactotropes of Male Rats
Authors: Mena Flavio , Navarro Nilda , Castilla Alejandra , Morales Teresa , Fiordelisio Tatiana , Cárabez Alfonso , Aguilar Manuel B. , Huerta-Ocampo Icnelia
Published: July 2009

We have previously shown that soluble factor(s) in conditioned media (CM) from the central and peripheral regions of the anterior pituitary (AP) gland of lactating rats promoted the in vitro dose-related release of prolactin (PRL) from pituitary glands of male rats. In the present experiments we sought to determine whether CM from rats in different physiological states provoked similar effects (like those of lactating rats), and the nature of the factors, whether 23K PRL or other variants of the hormone, were responsible for these effects. Stimulatory effects were induced by CM from pregnant females and steroid-treated castrated males or females, but not from untreated castrated rats, intact males, or by a PRL standard. More potent effects occurred with CM from APs of early- than from mid- or late-lactating rats, and from rats unsuckled for 8 or 16 h than from those unsuckled for 32 h. With respect to the nature of factor(s) responsible for these effects, immunoprecipitation of PRL from the CM of lactating females and of steroid-treated, castrated males eliminated, whereas dephosphorylation or deglycosylation of CM of lactating rats greatly increased its effects upon PRL release. Also, electrophoretic analysis and Western blotting of the CM proteins under native and denaturing conditions revealed a variety of PRL variants, ranging from 14 to <90 kDa, in CM from lactating rats, and the main effects on PRL release were provoked by the 23- to 46-kDa PRL variants. These results indicate that specific effects upon male rat lactotropes may be exerted by PRL variants released from APs of lactating and non-lactating rats.
Angiomotin-Like Protein 1 Controls Endothelial Polarity and Junction Stability During Sprouting Angiogenesis
Authors: Zheng Yujuan , Vertuani Simona , Nyström Staffan , Audebert Stéphane , Meijer Inèz , Tegnebratt Tetyana , Borg Jean-Paul , Uhlén Per , Majumdar Arindam , Holmgren Lars
Published: July 2009

Rationale:

We have previously shown that angiomotin (Amot) is essential for endothelial cell migration during mouse embryogenesis. However, ≈5% of Amot knockout mice survived without any detectable vascular defects. Angiomotin-like protein 1 (AmotL1) potentially compensates for the absence of Amot as it is 62% homologous to Amot and exhibits similar expression pattern in endothelial cells.

Objective:

Here, we report the identification of a novel isoform of AmotL1 that controls endothelial cell polarization and directional migration.

Methods and Results:

Small interfering RNA–mediated silencing of AmotL1 in mouse aortic endothelial cells caused a significant reduction in migration. In confluent mouse pancreatic islet endothelial cells (MS-1), AmotL1 colocalized with Amot to tight junctions. Small interfering RNA knockdown of both Amot and AmotL1 in MS-1 cells exhibited an additive effect on increasing paracellular permeability compared to that of knocking down either Amot or AmotL1, indicating both proteins were required for proper tight junction activity. Moreover, as visualized using high-resolution 2-photon microscopy, the morpholino-mediated knockdown of
amotl1
during zebrafish embryogenesis resulted in vascular migratory defect of intersegmental vessels with strikingly decreased junction stability between the stalk cells and the aorta. However, the phenotype was quite distinct from that of
amot
knockdown which affected polarization of the tip cells of intersegmental vessels. Double knockdown resulted in an additive phenotype of depolarized tip cells with no or decreased connection of the stalk cells to the dorsal aorta.

Conclusions:

These results cumulatively validate that Amot and AmotL1 have similar effects on endothelial migration and tight junction formation in vitro. However, in vivo Amot appears to control the polarity of vascular tip cells whereas AmotL1 mainly affects the stability of cell–cell junctions of the stalk cells.
ASIC2a and ASIC3 Heteromultimerize to Form pH-Sensitive Channels in Mouse Cardiac Dorsal Root Ganglia Neurons
Authors: Hattori Tomonori , Chen Jie , Harding Anne Marie S. , Price Margaret P. , Lu Yongjun , Abboud Francois M. , Benson Christopher J.
Published: July 2009

Rationale:

Acid-sensing ion channels (ASICs) are Na
+
channels that are activated by acidic pH. Their expression in cardiac afferents and remarkable sensitivity to small pH changes has made them leading candidates to sense cardiac ischemia.

Objective:

Four genes encode six different ASIC subunits, however it is not yet clear which of the ASIC subunits contribute to the composition of ASICs in cardiac afferents.

Methods and Results:

Here, we labeled cardiac afferents using a retrograde tracer dye in mice, which allowed for patch-clamp studies of murine cardiac afferents. We found that a higher percentage of cardiac sensory neurons from the dorsal root ganglia respond to acidic pH and generated larger currents compared to those from the nodose ganglia. The ASIC-like current properties of the cardiac dorsal root ganglia neurons from wild-type mice most closely matched the properties of ASIC2a/3 heteromeric channels. This was supported by studies in ASIC-null mice: acid-evoked currents from ASIC3
−/−
cardiac afferents matched the properties of ASIC2a channels, and currents from ASIC2
−/−
cardiac afferents matched the properties of ASIC3 channels.

Conclusions:

We conclude that ASIC2a and -3 are the major ASIC subunits in cardiac dorsal root ganglia neurons and provide potential molecular targets to attenuate chest pain and deleterious reflexes associated with cardiac disease.
Collateral Vessels on CT Angiography Predict Outcome in Acute Ischemic Stroke
Authors: Maas Matthew B. , Lev Michael H. , Ay Hakan , Singhal Aneesh B. , Greer David M. , Smith Wade S. , Harris Gordon J. , Halpern Elkan , Kemmling André , Koroshetz Walter J. , Furie Karen L.
Published: July 2009

Background and Purpose—

Despite the abundance of emerging multimodal imaging techniques in the field of stroke, there is a paucity of data demonstrating a strong correlation between imaging findings and clinical outcome. This study explored how proximal arterial occlusions alter flow in collateral vessels and whether occlusion or extent of collaterals correlates with prehospital symptoms of fluctuation and worsening since onset or predict in-hospital worsening.

Methods—

Among 741 patients enrolled in a prospective cohort study involving CT angiographic imaging in acute stroke, 134 cases with proximal middle cerebral artery occlusion and 235 control subjects with no occlusions were identified. CT angiography was used to identify occlusions and grade the extent of collateral vessels in the sylvian fissure and leptomeningeal convexity. History of symptom fluctuation or progressive worsening was obtained on admission.

Results—

Prehospital symptoms were unrelated to occlusion or collateral status. In cases, 37.5% imaged within 1 hour were found to have diminished collaterals versus 12.1% imaged at 12 to 24 hours (
P
=0.047). No difference in worsening was seen between cases and control subjects with adequate collaterals, but cases with diminished sylvian and leptomeningeal collaterals experienced greater risk of worsening compared with control subjects measured either by admission to discharge National Institutes of Health Stroke Scale increase ≥1 (55.6% versus 16.6%,
P
=0.001) or ≥4 (44.4% versus 6.4%,
P
<0.001).

Conclusion—

Most patients with proximal middle cerebral artery occlusion rapidly recruit sufficient collaterals and follow a clinical course similar to patients with no occlusions, but a subset with diminished collaterals is at high risk for worsening.
P-Selectin 1087G/A Polymorphism Is Associated With Neuropsychological Test Performance in Older Adults With Cardiovascular Disease
Authors: Gunstad John , Benitez Andreana , Hoth Karin F. , Spitznagel Mary Beth , McCaffery Jeanne , McGeary John , Kakos Lynn S. , Poppas Athena , Paul Robert H. , Jefferson Angela L. , Sweet Lawrence H. , Cohen Ronald A.
Published: July 2009

Background and Purpose—

There is growing evidence that the cell adhesion molecule P-selectin (SELP) contributes to the adverse vascular processes that promote cognitive impairment in individuals with cardiovascular disease. Previous research has shown that SELP genotypes moderate circulating levels of P-selectin and that patients undergoing coronary artery bypass graft with the SELP 1087A allele were less likely to show postoperative cognitive decline and more likely to exhibit lower levels of C-reactive protein than noncarriers. Thus, we expected that carriers of the 1087A allele (n=43) would exhibit better cognitive functioning than persons with 2 1087G alleles (n=77) and that C-reactive protein levels would be important for this relationship.

Methods—

One hundred twenty older adults with diagnosed cardiovascular disease were recruited from outpatient cardiology clinics. Each participant underwent a comprehensive neuropsychological test battery and a blood draw.

Results—

Participants with the SELP 1087A allele performed more poorly on tests of attention (Trail Making Test A: t[116]=3.20,
P
=0.002), executive function (Trail Making Test B: t[116]=2.89,
P
=0.005), psychomotor speed (Digit–Symbol Coding: t[117]=2.54,
P
=0.012), and memory (California Verbal Learning Test Discrimination: t[116]=2.05,
P
=0.04). There were no significant differences between the SELP genotype groups on demographic/medical variables or C-reactive protein levels.

Conclusions—

Contrary to expectations, the present analyses showed that older patients with cardiovascular disease with the SELP 1087A allele performed more poorly on neuropsychological testing. Findings from the present study were counter to previous research with coronary artery bypass graft candidates. Further work using neuroimaging and alternative measures of cardiovascular function is needed to clarify the mechanisms of this association.
Algonquian Languages Have A-Movement and A-Agreement
Authors: Bruening Benjamin
Published: July 2009

Ritter and Rosen (2005) claim that Algonquian languages lack A-movement and A-binding, and they theorize that all agreement in Algonquian is agreement with Ā-positions. I show that this proposal cannot be maintained, given facts of quantifier scope in Passamaquoddy. These facts require recognizing a step of A-movement to a derived A-position, comparable to Spec, TP in languages like English. I further contrast this movement with the movement involved in crossclausal agreement (Branigan and MacKenzie 2002) and show that the two differ in exactly the ways that A-movement and Ā-movement differ. Algonquian languages clearly have A-movement as distinct from Ā-movement.
Equal Treatment for All Antecedents: How Children Succeed with Principle B
Authors: Conroy Anastasia , Takahashi Eri , Lidz Jeffrey , Phillips Colin
Published: July 2009

Children have repeatedly been found to exhibit Principle B violations, with some reports that these violations occur only with nonquantified antecedents. This quantificational asymmetry (QA) in the delay of Principle B effect (DPBE) has been taken as support for a theory that restricts the scope of binding theory to bound variable anaphora (Reinhart 1983). However, the QA has been challenged, on the basis of discrepant findings and methodological concerns (Elbourne 2005). Here, we resolve the status of the QA with 3 studies and a review of over 30 previous studies. Using improved experimental materials, we show that children disallow local pronoun binding with both referential and quantificational antecedents when Principle B is at issue (Experiment 1), but not when Principle B is neutralized (Experiment 2). When methodological flaws are reintroduced, we replicate the QA (Experiment 3). Drawing on evidence from adult language processing, we suggest that the role of Principle B as a filter on representations during sentence understanding, in concert with pragmatic infelicities in the tasks used, accounts for the wide variability in the DPBE in the literature.
Bilateral Investment Treaties and the European Union. Recent Developments in Arbitration and Before the ECJ
Authors: Potestà Michele
Published: July 2009

The issue of the relationship between Bilateral Investment Treaties (BITs) and the EU legal order has recently attracted attention amongst scholars and practitioners in the field of international investment arbitration. Under a first perspective of the problem, the Arbitral Tribunal in Eastern Sugar B.V. v. The Czech Republic was confronted with the question of whether there was any room left for BITs between EU Member States. The Tribunal discussed the legal arguments advanced for and against the applicability of such "intra-EU BITs" between Member States. The issue, which is particularly relevant considering that there are currently more than 190 BITs concluded between EU Member States, will be analysed in the first part of this article. Under a second point of view of the problem, the European Court of Justice (ECJ) handed down two judgments on 3 March 2009 addressing incompatibilities with EC Law resulting from certain BITs entered into by Sweden and Austria with third countries. The second part of this article will deal with the consequences arising out of the Court's rulings with regard to existing and future BITs entered into by Member States with third countries.
Silicone-based Composite for Relining of Removable Dental Prosthesis
Authors: Cazacu Maria , Racles Carmen , Vlad Angelica , Antohe Magda , Forna Norina
Published: July 2009

A high molecular weight dimethylmethylvinylsiloxane copolymer (Mv = 450, 000) has been synthesized, analyzed, and used as matrix to prepare a composite by mixing with a proper amount of silica. A mixture of Fe2O 3/TiO2 was added to obtain a color close to the natural. 2,4-Dichlorobenzoyl peroxide was also incorporated as a crosslinking catalyst. This heat curable silicone-based formulation was used for relining removable dental prosthesis. The optimum conditions to appliance and hardening of the silicone composite on the prosthesis were established. The main surface (morphology, water contact angle, and water vapor sorption capacity) and mechanical characteristics were evaluated for the crosslinked silicone processed as thick film. The prosthesis relined with silicone was tested on a machine simulating mandible biomechanics both from kinematics and dynamic points of view. The results revealed a good behavior of our composite that remained unmodified after 700,000 mastication cycles.
Balance Across Contexts: Importance of Balanced Need Satisfaction Across Various Life Domains
Authors: Milyavskaya Marina , Gingras Isabelle , Mageau Geneviève A. , Koestner Richard , Gagnon Hugo , Jianqun Fang  , Boiché Julie
Published: July 2009

Self-determination theory posits that satisfaction of three basic psychological needs—autonomy, competence, and relatedness—are required for psychological well-being, and a recent study showed that the balance in the satisfaction of these three needs independently affects well-being. The present investigation builds on these findings by examining the balance of adolescents' need satisfaction across distinct life contexts. The results of three studies show that adolescents who experience a balance of need satisfaction across important life contexts, including at school, at home, with friends, and in part-time jobs, reported higher well-being and better school adjustment. This finding emerged consistently across four countries and across multiple measures of school adjustment, including teacher reports. Together, these results support previous research that highlights the importance of consistency for psychological functioning.
Personalization and de-schooling: Uncommon trajectories in contemporary education policy
Authors: Pykett Jessica
Published: July 2009

`Personalized learning' has become a popular term within education policy and practice in England, and is part of wider moves towards the `personalization' of public services and the promotion of personal responsibility within social policy discourse — including education, welfare, health and adult social care. In analysing personalization in education policy as a discursive formation, this paper visits some of the tensions, ambiguities and apparently `uncommon' trajectories in contemporary education policy, including its association with the `de-schooling' movement. It is argued that personalization cannot be understood simply as the most recent incarnation of the neoliberalization of education policy, nor as a politically neutral set of learning practices. In conclusion, unpacking personalization as a generative discourse enables us to understand the continuities and contradictions in New Labour social policy without relying on the sometimes heroic, revelatory and emancipatory intentions of critical analysis.
Privatizing employment services in Britain
Authors: Grover Chris
Published: July 2009

This paper focuses upon the privatization of Britain's employment services. It explores the extent to which the private sector is involved in the delivery of state-funded employment services, and the reasons why its involvement is to be extended in the future. The paper examines the catalyst — the Freud review of work-related social security policies — for extending private sector involvement in employment services before going on to critically engage with the privatization of such services. Here, the focus is upon ways in which such developments commodify non-employed people by creating an economic value for them, and the amount and nature of paid work that will be available through such services. The paper argues that the privatization of employment services will be more advantageous to the private sector than it will be to non-employed people because it is essentially a conservative policy that will not address the barriers that people face in securing paid employment.
Still on the Long Road to Theory
Authors: Little Richard
Published: July 2009

This review endeavours to identify the essential features of Lebow's attempt in A Cultural Theory of International Relations to provide a new grand theory of international relations. Lebow's starting point is that all existing grand theories in the field are fundamentally flawed because they operate on the basis of one-dimensional and oversimplified views of human motivation. He is particularly critical of interest-based theories of international relations, and his aim is to establish a conception of the human psyche that will allow him to introduce a cultural or social dimension to human motivation, and it is on this basis that he then endeavours to generate a cultural theory of international relations.
Radiation Therapy for HIV-Associated Diffuse Large Cell Non-Hodgkin Lymphoma
Authors: Rothschild Sacha , Dolder Mathias , Seifert Burkhardt , Lütolf Urs M. , Ciernik I. Frank
Published: July 2009

Purpose. To report the clinical experience with external beam radiotherapy (RT) for AIDS-related lymphoma (ARL) with or without the involvement of the central nervous system (CNS) in HIV-infected patients. Patients and Methods. Clinical outcome of 24 HIV-seropositive patients with ARL treated with RT from 1995 to 2004 was reviewed, testing factors associated with outcome. Results. After 1 and 5 years, the overall survival was 65% and 35%, respectively. The mean RT dose was 31 Gy after normalization to fractions of daily 2 Gy (range, 7.8-47.2 Gy). Radiotherapy dose was associated with survival in univariate (P = .04) and multivariate analysis (P = .01). Other factors in univariate analysis associated with outcome were viral load (VL), highly active antiretroviral therapy (HAART), ARL stage, and CNS involvement. Patients with CNS involvement achieved complete response in 46% and improved clinical performance was seen in 73%. Conclusions. After chemotherapy, RT in combination with HAART is highly active, and RT should be encouraged especially after suboptimal responses to induction treatment.
The Importance of Sonography in the Evaluation of Neonatal Adrenal Hemorrhage
Authors: Valdespino Rini-Sultana
Published: July 2009

Neonatal adrenal hemorrhage is a relatively common condition of the newborn. Etiologies of neonatal adrenal hemorrhage include maternal/ fetal stress, birth trauma, congenital syphilis, dehydration, anoxia, or other systemic disorders. Clinical presentation ranges from asymptomatic to anemia, hypotension, vomiting, jaundice/hyperbilirubinemia, scrotal discoloration, hyponatremia, and palpable abdominal mass. Adrenal hemorrhage sonographically appears as an abdominal mass with displacement of the kidney inferiorly, known as mass effect. Differentiation of adrenal hemorrhage from more serious pathologies such as adrenal carcinoma, neuroblastoma, or pheochromocytoma is critical. Bluish discoloration of the scrotum may also occur due to extravasation of blood from the hemorrhage, leading to an incorrect diagnosis of testicular torsion or acute scrotum. Proper sonographic evaluation conservatively avoids unnecessary surgical exploration. Power Doppler imaging, color Doppler imaging, and serial gray-scale sonography can document the characteristics and progression of the condition for accurate diagnosis. Sonography is a preferred noninvasive screening modality for evaluating abdominal masses within the pediatric population because of its sensitivity, avoidance of radiation and sedation, and potential value for avoiding exploratory surgery.