bluuebunny/crossref_metadata_2025 huggingface dataset:
Native and recombinant Slc26a3 (downregulated in adenoma, Dra) do not exhibit properties of 2Cl−/1HCO3− exchange
Authors: Alper Seth L. , Stewart Andrew K. , Vandorpe David H. , Clark Jeffrey S. , Zachary Horack R. , Simpson Janet E. , Walker Nancy M. , Clarke Lane L.
Published: November 2010

The recent proposal that Dra/Slc26a3 mediates electrogenic 2Cl−/1HCO3− exchange suggests a required revision of classical concepts of electroneutral Cl− transport across epithelia such as the intestine. We investigated 1) the effect of endogenous Dra Cl−/HCO3− activity on apical membrane potential ( Va) of the cecal surface epithelium using wild-type (WT) and knockout (KO) mice; and 2) the electrical properties of Cl−/(OH−)HCO3− exchange by mouse and human orthologs of Dra expressed in Xenopus oocytes. Ex vivo 36Cl− fluxes and microfluorometry revealed that cecal Cl−/HCO3− exchange was abolished in the Dra KO without concordant changes in short-circuit current. In microelectrode studies, baseline Va of Dra KO surface epithelium was slightly hyperpolarized relative to WT but depolarized to the same extent as WT during luminal Cl− substitution. Subsequent studies indicated that Cl−-dependent Va depolarization requires the anion channel Cftr. Oocyte studies demonstrated that Dra-mediated exchange of intracellular Cl− for extracellular HCO3− is accompanied by slow hyperpolarization and a modest outward current, but that the steady-state current-voltage relationship is unaffected by Cl− removal or pharmacological blockade. Further, Dra-dependent 36Cl− efflux was voltage-insensitive in oocytes coexpressing the cation channels ENaC or ROMK. We conclude that 1) endogenous Dra and recombinant human/mouse Dra orthologs do not exhibit electrogenic 2Cl−/1HCO3− exchange; and 2) acute induction of Dra Cl−/HCO3− exchange is associated with secondary membrane potential changes representing homeostatic responses. Thus, participation of Dra in coupled NaCl absorption and in uncoupled HCO3− secretion remains compatible with electroneutrality of these processes, and with the utility of electroneutral transport models for predicting epithelial responses in health and disease.
UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression
Authors: Bromati Carla R. , Lellis-Santos Camilo , Yamanaka Tatiana S. , Nogueira Tatiane C. A. , Leonelli Mauro , Caperuto Luciana C. , Gorjão Renata , Leite Adriana R. , Anhê Gabriel F. , Bordin Silvana
Published: November 2010

Endocrine pancreas from pregnant rats undergoes several adaptations that comprise increase in β-cell number, mass and insulin secretion, and reduction of apoptosis. Lactogens are the main hormones that account for these changes. Maternal pancreas, however, returns to a nonpregnant state just after the delivery. The precise mechanism by which this reversal occurs is not settled but, in spite of high lactogen levels, a transient increase in apoptosis was already reported as early as the 3rd day of lactation (L3). Our results revealed that maternal islets displayed a transient increase in DNA fragmentation at L3, in parallel with decreased RAC-alpha serine/threonine-protein kinase (AKT) phosphorylation (pAKT), a known prosurvival kinase. Wortmannin completely abolished the prosurvival action of prolactin (PRL) in cultured islets. Decreased pAKT in L3-islets correlated with increased Tribble 3 (TRB3) expression, a pseudokinase inhibitor of AKT. PERK and eIF2α phosphorylation transiently increased in islets from rats at the first day after delivery, followed by an increase in immunoglobulin heavy chain-binding protein (BiP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in islets from L3 rats. Chromatin immunoprecipitation (ChIP) and Re-ChIP experiments further confirmed increased binding of the heterodimer ATF4/CHOP to the TRB3 promoter in L3 islets. Treatment with PBA, a chemical chaperone that inhibits UPR, restored pAKT levels and inhibited the increase in apoptosis found in L3. Moreover, PBA reduced CHOP and TRB3 levels in β-cell from L3 rats. Altogether, our study collects compelling evidence that UPR underlies the physiological and transient increase in β-cell apoptosis after delivery. The UPR is likely to counteract prosurvival actions of PRL by reducing pAKT through ATF4/CHOP-induced TRB3 expression.
Julius H. Comroe, Jr., Distinguished Lecture: Central chemoreception: then … and now
Authors: Nattie Eugene
Published: November 2010

The 2010 Julius H. Comroe, Jr., Lecture of the American Physiological Society focuses on evolving ideas in chemoreception for CO2/pH in terms of what is “sensed,” where it is sensed, and how the sensed information is used physiologically. Chemoreception is viewed as involving neurons (and glia) at many sites within the hindbrain, including, but not limited to, the retrotrapezoid nucleus, the medullary raphe, the locus ceruleus, the nucleus tractus solitarius, the lateral hypothalamus (orexin neurons), and the caudal ventrolateral medulla. Central chemoreception also has an important nonadditive interaction with afferent information arising at the carotid body. While ventilation has been viewed as the primary output variable, it appears that airway resistance, arousal, and blood pressure can also be significantly affected. Emphasis is placed on the importance of data derived from studies performed in the absence of anesthesia.
Double-stranded RNA-dependent protein kinase activation modulates endotoxin-induced diaphragm weakness
Authors: Supinski G. S. , Callahan L. A.
Published: November 2010

Diaphragm caspase-8 activation plays a key role in modulating sepsis-induced respiratory muscle dysfunction. It is also known that double-stranded RNA-dependent protein kinase (PKR) is a regulator of caspase-8 activation in neural tissue. We tested the hypothesis that the PKR pathway modulates sepsis-induced diaphragmatic caspase-8 activation. We first evaluated the time course of diaphragm PKR activation following endotoxin administration in mice. We then determined whether administration of a PKR inhibitor (2-aminopurine) prevents endotoxin-induced diaphragm caspase-8 activation and contractile dysfunction in mice. Finally, we investigated if inhibition of PKR (using either 2-aminopurine or transfection with dominant-negative PKR) blocks caspase-8 activation in cytokine treated C2C12 cells. Endotoxin markedly activated diaphragm PKR (with increases in both active phospho-PKR protein levels, P < 0.03, and directly measured PKR activity, P < 0.01) and increased active caspase-8 levels ( P < 0.01). Inhibition of PKR with 2-aminopurine prevented endotoxin-induced diaphragm caspase-8 activation ( P < 0.01) and diaphragm weakness ( P < 0.001). Inhibition of PKR with either 2-aminopurine or transfection with dominant-negative PKR blocked caspase-8 activation in isolated cytokine-treated C2C12 cells. These data implicate PKR activation as a major factor mediating cytokine-induced skeletal muscle caspase-8 activation and weakness.
Neural Correlates of Auditory Streaming of Harmonic Complex Sounds With Different Phase Relations in the Songbird Forebrain
Authors: Itatani Naoya , Klump Georg M.
Published: November 2010

It has been suggested that successively presented sounds that are perceived as separate auditory streams are represented by separate populations of neurons. Mostly, spectral separation in different peripheral filters has been identified as the cue for segregation. However, stream segregation based on temporal cues is also possible without spectral separation. Here we present sequences of ABA- triplet stimuli providing only temporal cues to neurons in the European starling auditory forebrain. A and B sounds (125 ms duration) were harmonic complexes (fundamentals 100, 200, or 400 Hz; center frequency and bandwidth chosen to fit the neurons' tuning characteristic) with identical amplitude spectra but different phase relations between components (cosine, alternating, or random phase) and presented at different rates. Differences in both rate responses and temporal response patterns of the neurons when stimulated with harmonic complexes with different phase relations provide first evidence for a mechanism allowing a separate neural representation of such stimuli. Recording sites responding >1 kHz showed enhanced rate and temporal differences compared with those responding at lower frequencies. These results demonstrate a neural correlate of streaming by temporal cues due to the variation of phase that shows striking parallels to observations in previous psychophysical studies.
Pneumatosis Coli Associated with Pseudomembranous Colitis in a Patient following Colonic Surgery
Authors: Bailey Jennifer , Shaffer Eldon A.
Published: November 2010

Pneumatosis intestinalis is a rare disorder characterized by gas-filled cysts within the subserosal and/or submucosal regions of the intestinal wall. The source of this gas and its translocation across the mucosa is incompletely understood. Most (85%) cases are associated with medical conditions, ranging from psychiatric through respiratory disorders to gastrointestinal-related diseases; the remaining 15% lack any recognizable cause or association. In this case report, pneumatosis coli (affecting the colon) occurred in a patient following abdominal surgery and was associated with pseudomembranous colitis, which wasClostridium difficiletoxin negative—presumably a false negative. Supportive care and appropriate antibacterial agents sufficed to alleviate symptoms and resolve the pneumatosis. Recognizing this uncommon but important association can avoid high financial and personal costs from unnecessary testing and invasive surgical explorations. Consideration should be given to pseudomembranous colitis as the basis for pneumatosis coli developing in patients who have received antibiotics, once gut ischemia has been ruled out.
Energy Saving Mechanisms for MAC Protocols in Wireless Sensor Networks
Authors: Al Ameen Moshaddique , Islam S. M. Riazul , Kwak Kyungsup
Published: November 2010

Energy efficiency is a primary requirement in a wireless sensor network (WSN). This is a major design parameter in medium access control (MAC) protocols for WSN due to limited resources in sensor nodes that include low battery power. Hence a proposed MAC protocol must be energy efficient by reducing the potential energy wastes. Developing such a MAC protocol has been a hot research area in WSN. To avoid wasting the limited energy, various energy saving mechanisms are proposed for MAC protocols. These mechanisms have a common design objective—to save energy to maximize the network lifetime. This paper presents a survey on various energy saving mechanisms that are proposed for MAC protocols in WSN. We present a detailed discussion of these mechanisms and discuss their strengths and weaknesses. We also discuss MAC protocols that use these energy saving mechanisms.
Wireless Healthcare Monitoring with RFID-Enhanced Video Sensor Networks
Authors: Alemdar Hande , Durmus Yunus , Ersoy Cem
Published: November 2010

In pervasive healthcare systems, WSNs provide rich contextual information and alerting mechanisms against odd conditions with continuous monitoring. Furthermore, they minimize the need for caregivers and help the chronically ill and elderly to survive an independent life. In this paper, we propose an outdoor monitoring environment and evaluate the capabilities of video sensor networks for healthcare monitoring in an outdoor setting. The results exhibit that their capabilities are limited. For this reason, we proposed several enhancements for reducing the traffic load on the network for better performance. RFID is a very mature technology that has already been used in many areas. The RFID-enhanced video sensor networks reduce the network traffic load. Moreover, the proximity of the healthcare professionals who are also moving in the surveillance area is also used for better balancing the network load. Finally, for assuring the reporting of the emergency events with low latencies, we propose an emergency frame based queuing mechanism and evaluated its performance through simulations.
Two Major Archaeal Pseudomurein Endoisopeptidases: PeiW and PeiP
Authors: Visweswaran Ganesh Ram R. , Dijkstra Bauke W. , Kok Jan
Published: November 2010

PeiW (UniProtKB Q7LYX0) and PeiP (UniProtKB Q77WJ4) are the two major pseudomurein endoisopeptidases (Pei) that are known to cleave pseudomurein cell-wall sacculi of the members of the methanogenic ordersMethanobacterialesandMethanopyrales. Both enzymes, originating from prophages specific for some methanogenic archaeal species, hydrolyze the (Ala)-Lys bond of the peptide linker between adjacent pseudomurein layers. Because lysozyme is not able to cleave the pseudomurein cell wall, the enzymes are used in protoplast preparation and in DNA isolation from pseudomurein cell-wall-containing methanogens. Moreover, PeiW increases the probe permeability ratio and enables fluorescence in situ hybridization (FISH) and catalyzed reporter deposition (CARD-) FISH experiments to be performed on these methanogens.
Obstetrician-Gynecologists and Perinatal Infections: A Review of Studies of the Collaborative Ambulatory Research Network (2005–2009)
Authors: Leddy Meaghan A. , Gonik Bernard , Schulkin Jay
Published: November 2010

Background. Maternal infection is associated with adverse pregnancy outcomes, and ob-gyns are in a unique position to help prevent and treat infections.Methods. This paper summarizes studies completed by the Research Department of the American College of Obstetricians and Gynecologists regarding perinatal infections that were published between 2005 and 2009.Results. Obstetrician-gynecologists are routinely screening for hepatitis B and HIV, and many counsel prenatal patients regarding hepatitis B and toxoplasmosis. However, other infections are not regularly discussed, and many cited time constraints as a barrier to counseling. A majority discusses the transmission of giardiasis and toxoplasmosis, but few knew the source of cryptosporidiosis or cyclosporiasis.Conclusions. Many of the responding ob-gyns were unaware of or not adhering to infection management guidelines. Obstetrician-gynecologists are knowledgeable regarding perinatal infections; however, guidelines must be better disseminated perhaps via a single infection management summary. This paper identified knowledge gaps and areas in which practice can be improved and importantly highlights the need for a comprehensive set of management guidelines for a host of infections, so that physicians can have an easy resource when encountering perinatal infections.
Intravesical Dimethyl Sulfoxide Inhibits Acute and Chronic Bladder Inflammation in Transgenic Experimental Autoimmune Cystitis Models
Authors: Kim Ronald , Liu Wujiang , Chen Xiaohong , Kreder Karl J. , Luo Yi
Published: November 2010

New animal models are greatly needed in interstitial cystitis/painful bladder syndrome (IC/PBS) research. We recently developed a novel transgenic cystitis model (URO‐OVA mice) that mimics certain key aspects of IC/PBS pathophysiology. This paper aimed to determine whether URO‐OVA cystitis model was responsive to intravesical dimethyl sulfoxide (DMSO) and if so identify the mechanisms of DMSO action. URO‐OVA mice developed acute cystitis upon adoptive transfer of OVA‐specific OT‐I splenocytes. Compared to PBS‐treated bladders, the bladders treated with 50% DMSO exhibited markedly reduced bladder histopathology and expression of various inflammatory factor mRNAs. Intravesical DMSO treatment also effectively inhibited bladder inflammation in a spontaneous chronic cystitis model (URO‐OVA/OT‐I mice). Studies further revealed that DMSO could impair effector T cells in a dose‐dependent manner in vitro. Taken together, our results suggest that intravesical DMSO improves the bladder histopathology of IC/PBS patients because of its ability to interfere with multiple inflammatory and bladder cell types.
Dyspeptic Symptoms after Laparoscopic Large Hiatal Hernia Repair and Primary Antireflux Surgery for Gastroesophageal Reflux Disease: A Comparative Study
Authors: Furnée Edgar J.B. , Draaisma Werner A. , Hazebroek Eric J. , van Lelyveld Niels , Smout André J.P.M. , Broeders Ivo A.M.J.
Published: November 2010

Background: Several patients with gastroesophageal reflux disease suffer from functional dyspepsia. After laparoscopic Nissen fundoplication, these symptoms persist in a substantial number of patients. We hypothesized that, due to a higher chance of vagal nerve impairment during extensive hernia sac resection and esophageal mobilization, dyspeptic symptoms are more frequent after laparoscopic large hiatal hernia (types II–IV) repair than after primary antireflux surgery. Methods: From January 2003 to December 2007, 60 consecutive patients who primarily underwent an antireflux fundoplication for gastroesophageal reflux disease and 22 consecutive patients who had large hiatal hernia repair with fundoplication for concomitant gastroesophageal reflux disease were included. According to a system combining frequency and severity, patients scored 8 dyspeptic symptoms. Additionally, symptoms presenting preoperatively were scored according to the Visick grading system. Results: In 43 of the 49 available patients (87.8%) who primarily underwent antireflux surgery and in all 20 available patients who had hiatal hernia repair, preoperative symptoms resolved or improved. Mean symptom scores of all dyspeptic symptoms after surgery were comparable between both cohorts. General quality of life was equal in both cohorts. Conclusion: After laparoscopic large hiatal hernia repair, dyspeptic symptoms were present in similar frequencies as after primary antireflux surgery.
Prenatal Stress: Course and Interrelation of Emotional and Physiological Stress Measures
Authors: Rothenberger Steffi E. , Moehler Eva , Reck Corinna , Resch Franz
Published: November 2010

Background: Prenatal stress is known to be a potential risk factor for cognitive, behavioural and motor development that even last until adolescence. A consensus of how ‘prenatal stress’ can be measured, in which trimester of pregnancy women should be studied and whether subjective feelings of being stressed are associated with a hormonal response is still lacking. To close this gap, a prospective longitudinal study was conducted in pregnant women. Sampling and Methods: 108 subjects were asked to fill out questionnaires concerning pregnancy-related anxiety, perceived stress, marital satisfaction, critical life events and to collect salivary cortisol in each trimester of pregnancy. Results: Fear of giving birth increases until the end of pregnancy, and marital satisfaction is highest at the end of pregnancy. Perceived stress is related to a hormonal response in cortisol only in the first (r = 0.18, p < 0.10) and second (r = 0.18, p < 0.10) trimesters of pregnancy. Critical life events are linked to raised cortisol levels in early pregnancy only (r = 0.28, p < 0.01). Conclusion: Prenatal stress can be operationalized by using different subjective as well as physiological stress measures. Only in the first half of pregnancy self-report and physiological stress measures seem to be associated.
Selective Blockade of Oxytocin and Vasopressin V1a Receptors in Anaesthetised Rats: Evidence that Activation of Oxytocin Receptors rather than V1a Receptors Increases Sodium Excretion
Authors: Shirley D.G. , Walter M.F. , Keeler B.D. , Waters N.J. , Walter S.J.
Published: November 2010

Background: Although it is known that moderate-to-high doses of the neurohypophysial hormones oxytocin and vasopressin are natriuretic, doubts remain over the identity of the receptors responsible. To address this issue, we have used highly selective antagonists of oxytocin and vasopressin receptors in animals with elevated endogenous circulating levels of the 2 hormones. Methods: Rats were anaesthetised and prepared surgically for clearance studies, thereby raising plasma oxytocin and vasopressin concentrations. Sodium excretion, glomerular filtration rate and lithium clearance (an index of end-proximal fluid delivery) were measured: first during a control period, then after administration of the selective oxytocin receptor antagonist desGly-NH2,d(CH2)5[D-Trp2,Thr4,Dap5]OVT, the selective vasopressin V1a receptor antagonist d(CH2)5[Tyr(Me)2,Dab5]AVP, or vehicle alone. Results: Absolute and fractional sodium excretion fell in rats given the oxytocin antagonist (by 32 and 27%, respectively, compared with corresponding values in vehicle-infused rats), but not in those given the V1a antagonist or vehicle. Antinatriuresis was associated with a small reduction in the ratio of sodium clearance to lithium clearance (an index of the fraction of distally delivered sodium that escapes reabsorption in the distal nephron). Conclusions: These results corroborate previous studies showing that activation of oxytocin receptors increases sodium excretion and imply that the natriuretic effect of elevated plasma vasopressin concentrations results from stimulation of oxytocin receptors.
Genetic Disorders of Glomerular Basement Membranes
Authors: Kashtan Clifford E. , Segal Yoav
Published: November 2010

This review provides current information about glomerular disorders that arise directly from inherited abnormalities in extracellular matrix proteins intrinsic to the glomerular basement membrane (Alport syndrome, thin basement membrane nephropathy, HANAC syndrome and Pierson syndrome). The authors also discuss disorders involving genetic defects in cellular proteins that result in structural defects in glomerular basement membranes (MYH9-related disorders, nail-patella syndrome).
Disorders of the Renal Proximal Tubule
Authors: Bökenkamp Arend , Ludwig Michael
Published: November 2010

Following glomerular filtration, the bulk of solutes are reabsorbed in the proximal tubule to prevent excessive losses of vital metabolites. In this nephron segment, reabsorption is largely active via dedicated transporters. Hereditary defects in proximal tubular function are characterized by malabsorption affecting amino acids, glucose, potassium, phosphate, bicarbonate, low-molecular-weight proteins and other solutes handled by this nephron segment. Dysfunction may be isolated or generalized (Fanconi syndrome). Defects in specific transporters lead to increased urinary excretion of substrates, which are often diagnostic. In others, extrarenal gene expression causes a multisystem phenotype. In this review, we will give a short overview of the molecular genetics, clinical picture, pathophysiology and treatment of genetically defined proximal tubulopathies.
Genetic Disorders of NaCl Transport in the Distal Convoluted Tubule
Authors: Miller R. Tyler
Published: November 2010

The distal convoluted tubule (DCT) reabsorbs 5–10% of filtered Na, and is an important site for regulation of Na balance. Additionally, the amount and composition of the tubular fluid that leaves the DCT affects H and K secretion in more distal nephrin segments. Mutations in five genes whose products are expressed in the DCT demonstrate these points and help to define the mechanisms by which the DCT contributes to control of electrolyte balance and volume. Loss of function mutations in the apical thiazide-sensitive NaCl cotransporter and the basolateral K channel Kir4.1, and activating mutations in the Ca-sensing receptor cause a phenotypically similar salt wasting syndrome. Mutation in two recently identified kinases, WNK1 and WNK4 cause a salt-retaining syndrome through increased apical expression of NaCl cotransporter. Recent studies indicate that these genes are important not only for understanding the physiology of the distal nephron, but that they and others may also contribute to blood pressure variation in the general population.
Practical Genetics for Autosomal Dominant Polycystic Kidney Disease
Authors: Pei York
Published: November 2010

Autosomal dominant polycystic kidney disease (ADPKD) is the most common mendelian disorder of the kidney and accounts for ∼5% of end-stage renal disease in North America. It is characterized by focal development of renal cysts which increase in number and size with age. Mutations of PKD1 and PKD2 account for most cases. Although the clinical manifestations of both gene types overlap completely, PKD1 is associated with more severe disease than PKD2, with larger kidneys and earlier onset of end-stage renal disease. Furthermore, marked within-family renal disease variability is well documented in ADPKD and suggests a strong modifier effect from as yet unknown genetic and environmental factors. In turn, the significant inter- and intra-familial renal disease variability poses a challenge for diagnosis and genetic counseling. In general, renal ultrasonography is commonly used for the diagnosis, and age-dependent criteria have been defined for subjects at risk of PKD1. However, the utility of the PKD1 ultrasound criteria in the clinical setting is unclear since their performance characteristics have not been defined for the milder PKD2 and the gene type for most test subjects is unknown. Recently, highly predictive ultrasound diagnostic criteria have been derived for at-risk subjects of unknown gene type. Additionally, both DNA linkage and gene-based direct sequencing are available for the diagnosis of ADPKD, especially in subjects with equivocal imaging results, a negative or indeterminate family history, or in younger at-risk individuals being evaluated as potential living related kidney donor. This review will highlight the utility and limitations of clinical predictors of gene types, imaging- and molecular-based diagnostic tests, and present an integrated approach for evaluating individuals suspected to have ADPKD.
Mechanisms of Nephronophthisis and Related Ciliopathies
Authors: Hurd Toby W. , Hildebrandt Friedhelm
Published: November 2010

An emerging group of human genetic diseases termed ‘ciliopathies’ are caused by dysfunction of two functionally and physically associated organelles, the centrosome and cilium. These organelles are central to perception of the physical environment through detection of a diverse variety of extracellular signals such as growth factors, chemicals, light and fluid flow. Many of the described ciliopathies display multi-organ involvement, with renal and retina being the most commonly affected. Nephronophthisis is a recessive disorder of the kidney that is the leading cause of end-stage renal failure in children. Through positional cloning, many of the causative mutations have been mapped to genes involved in centrosome and cilia function. In this review, we discuss the identified causative mutations that give rise to nephronophthisis and how these are related to the disease etiology in both the kidney and other organs.
Uromodulin-Associated Kidney Disease
Authors: Bleyer Anthony J. , Živná Martina , Kmoch Stanislav
Published: November 2010

Uromodulin (Tamm-Horsfall glycoprotein) is the most common protein excreted in the urine of healthy individuals, yet its function remains unclear. Mutations in the UMOD gene encoding uromodulin result in a marked decrease in the synthesis of uromodulin, as well as the accumulation of abnormal uromodulin in tubular cells, leading to tubular cell death. UMOD gene mutations are responsible for the autosomal dominant inheritance of chronic interstitial disease, leading to the need for renal replacement in the third through seventh decades of life. Individuals with UMOD mutations also suffer from hyperuricemia in childhood, and often suffer from gout in their teenage years. A similar clinical syndrome causing the autosomal dominant inheritance of chronic kidney disease, hyperuricemia, and anemia has recently been attributed to mutations in the REN gene encoding renin. Recently, polymorphisms in the UMOD gene have been found responsible for increased urinary uromodulin production and an increased risk of chronic kidney disease. This review summarizes information on uromodulin biology and clinical manifestations of mutations in the UMOD gene, as well as similar inherited interstitial diseases. It provides new information regarding UMOD gene polymorphisms and their association with chronic kidney disease.
Tuberous Sclerosis Complex Renal Disease
Authors: Dixon Bradley P. , Hulbert John C. , Bissler John J.
Published: November 2010

Although not as common as other genetic renal diseases such as autosomal dominant polycystic kidney disease, patients with tuberous sclerosis complex frequently have significant renal involvement. Recent revelations in the cell biology of these renal disease manifestations as well as effective therapies for tuberous sclerosis complex-related renal issues have heralded hope of improved renal survival and improved quality of life for the TSC patient. This review specifically addresses some of the major renal manifestations of this disease.
Renal Stone Disease
Authors: Sayer John A.
Published: November 2010

Background/Aims: Renal stone disease may be seen as a clinical symptom of an underlying pathological process predisposing to crystallization within the renal tract. Renal stones may be comprised of calcium salts, uric acid, cystine and various other insoluble complexes. Nephrolithiasis may be the manifestation of rare single gene disorders or part of more common idiopathic renal stone-forming diseases. Methods and Results: Molecular genetics has allowed significant progress to be made in our understanding of certain stone-forming conditions. The molecular defect underlying single gene disorders often contributes to a significant metabolic risk factor for stone formation. In contrast, idiopathic renal stone formation relates to the interplay of environmental, dietary and genetic factors, with hypercalciuria being the most commonly found metabolic risk factor. Candidate genes for idiopathic stone formers have been identified using numerous approaches, some of which are outlined here. Despite this, the genetic basis underlying familial hypercalciuria and calcium stone formation remains elusive. The molecular basis of other metabolic risk factors such as hyperuricosuria, hyperoxaluria and hypocitraturia is being unraveled and is allowing new insights into renal stone pathogenesis. Conclusion: The discovery of both rare and common molecular defects leading to renal stones will hopefully increase our understanding of the disease pathogenesis. Such knowledge will allow screening for genetic defects and the use of specific drug therapies in order to prevent renal stone formation.
Genetic Variations and Transplant Outcomes
Authors: Krüger Bernd , Schröppel Bernd
Published: November 2010

Extensive genetic variation has been described in molecules regulating innate and adaptive immunity, pharmacokinetics, coagulation, and fibrosis. However, large prospective studies need to be performed to define the clinical consequences of such variation and the potential benefits of genotyping these markers for patients. The purpose of this review is to summarize recent data describing associations of polymorphisms in both immunological and non-immunological molecules with transplant outcomes, and discuss their clinical implications and limitations.
Genetics of Chronic Kidney Disease
Authors: O’Seaghdha Conall M. , Fox Caroline S.
Published: November 2010

The current review collates what is already known of the genetics of chronic kidney disease (CKD), and focuses on new trends in genome-wide assessment of the inherited component of susceptibility to this condition. Early efforts to identify kidney disease susceptibility genetic loci using linkage and candidate gene strategies proved disappointing. More recently, genome-wide association studies have yielded highly promising results suggesting a number of potential candidate genes and genomic regions that may contribute to the pathogenesis of CKD. Renal failure susceptibility genes identified by these methods, such as MYH9, have yielded novel insights into the pathogenesis of CKD. Genome-wide association studies of CKD are beginning to define the genomic architecture of kidney disease and will impact our understanding of how genetic variation influences susceptibility to this condition.
Regulation of NADPH Oxidase Activity Is Associated with miRNA-25-Mediated NOX4 Expression in Experimental Diabetic Nephropathy
Authors: Fu Yibing , Zhang Yan , Wang Ziying , Wang Linlin , Wei Xinbing , Zhang Bin , Wen Zeqing , Fang Hao , Pang Qi , Yi Fan
Published: November 2010

Background/Aims: Although numerous studies have explored the mechanisms regulating the enzyme activity of NADPH oxidase in diabetic nephropathy (DN), little information is available for the contribution of microRNAs (miRNAs) to the regulation of NADPH oxidase expression. Therefore, the present study was to test whether miRNAs importantly contribute to the regulation of NOX4 expression, a major catalytic subunit of NADPH oxidase under hyperglycemia. Methods: Diabetic rats were induced by streptozotocin. miRNA microarray, Western blot, real-time RT-PCR and luciferase reporter assays were employed in this study. Results: Among 5 miRNAs, which are predicted to have a binding capacity to rat NOX4, the miRNA-25 level was significantly reduced both in the kidney from diabetic rats and in high glucose-treated mesangial cells, accompanied by the increases in NOX4 expression levels. In an in vitrostudy, we found that NADPH activity was increased by 226.2% in miRNA-25 inhibitor transfected cells and decreased by 51.0% in miRNA-25 precursor transfected cells. miR-25 inhibitor dramatically increased both NOX4 mRNA and protein levels. We then showed that miR-25 negatively regulated NOX4 expression by directly targeting the 3′-UTR by luciferase reporter assays. It was found that transfection of miR-25 precursor significantly decreased the luciferase activity of NOX4 3′-UTR by 39.5%, whereas the mutant sequence restored levels to 79.4%. Finally, our results indicated that the miR-25-mediated NOX4 mRNA level may result from the regulation of mRNA stability. Conclusions: These findings for the first time indicate that miRNA-25 may serve as an endogenous gene silencing factor and contributes to the regulation of NOX4 expression and function in DN.
Factors Associated With Outcome in Heart Failure With Preserved Ejection Fraction
Authors: Komajda Michel , Carson Peter E. , Hetzel Scott , McKelvie Robert , McMurray John , Ptaszynska Agata , Zile Michael R. , DeMets David , Massie Barry M.
Published: November 2010

Background—

The determinants of prognosis in patients with heart failure and preserved ejection fraction (HF-PEF) are poorly documented.

Methods and Results—

We evaluated data from 4128 patients in the I-PRESERVE trial (Irbesartan in Heart Failure with Preserved Ejection Fraction Study). Multivariable Cox regression models were developed using 58 baseline demographic, clinical, and biological variables to model the primary outcome of all-cause mortality or cardiovascular hospitalization (1505 events), all-cause mortality (881 events), and HF death or hospitalization (716 events). Log N-terminal pro–B-type natriuretic peptide, age, diabetes mellitus, and previous hospitalization for HF were the most powerful factors associated with the primary outcome and with the HF composite. For all-cause mortality, log N-terminal pro–B-type natriuretic peptide, age, diabetes mellitus, and left ventricular EF were the strongest independent factors. Other independent factors associated with poor outcome included quality of life, a history of chronic obstructive lung disease, log neutrophil count, heart rate, and estimated glomerular filtration rate. The models accurately stratified the actual 3-year rate of outcomes from 8.1% to 59.9% (primary outcome) 2.7% to 36.5% (all-cause mortality), and 2.1% to 38.9% (HF composite) for the lowest to highest septiles of predicted risks.

Conclusions—

In a large sample of elderly patients with HF and preserved EF enrolled in I-Preserve, simple clinical, demographic, and biological variables were associated with outcome and identified subgroups at very high and very low risk of events.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00095238.
Novel Lipid Mediators Promote Resolution of Acute Inflammation
Authors: Spite Matthew , Serhan Charles N.
Published: November 2010

The resolution of acute inflammation is a process that allows for inflamed tissues to return to homeostasis. Resolution was held to be a passive process, a concept now overturned with new evidence demonstrating that resolution is actively orchestrated by distinct cellular events and endogenous chemical mediators. Among these, lipid mediators, such as the lipoxins, resolvins, protectins, and newly identified maresins, have emerged as a novel genus of potent and stereoselective players that counter-regulate excessive acute inflammation and stimulate molecular and cellular events that define resolution. Given that uncontrolled, chronic inflammation is associated with many cardiovascular pathologies, an appreciation of the endogenous pathways and mediators that control timely resolution can open new terrain for therapeutic approaches targeted at stimulating resolution of local inflammation, as well as correcting the impact of chronic inflammation in cardiovascular disorders. Here, we overview and update the biosynthesis and actions of proresolving lipid mediators, highlighting their diverse protective roles relevant to vascular systems and their relation to aspirin and statin therapies.
Another Citation of Philo in Clement of Alexandria’s Protrepticus (10,93,1-2)
Authors: Dinan Andrew
Published: November 2010

Prot. 10,93,1-2 should be added to the long list of passages in which Clement has made use of the writings of Philo. Clement is attracted by, and in large measure appropriates, Philo’s description of repentance in Virt. 181, yet he alters the Philonic text in several ways, notably by making explicit a citation that also appears partially in Plato, Phd 114D and more fully in Horace, C. 3,25.
The Active Nature of the Soul in Sense Perception: Robert Kilwardby and Peter Olivi
Authors: Silva José Filipe , Toivanen Juhana
Published: November 2010

This article discusses the theories of perception of Robert Kilwardby and Peter of John Olivi. Our aim is to show how in challenging certain assumptions of medieval Aristotelian theories of perception they drew on Augustine and argued for the active nature of the soul in sense perception. For both Kilwardby and Olivi, the soul is not passive with respect to perceived objects; rather, it causes its own cognitive acts with respect to external objects and thus allows the subject to perceive them. We also show that Kilwardby and Olivi differ substantially regarding where the activity of the soul is directed to and the role of the sensible species in the process, and we demonstrate that there are similarities between their ideas of intentionality and the attention of the soul towards the corporeal world.
Ontological Insecurity: A Guiding Framework for Borderline Personality Disorder
Authors: Wilson John , McDonald Matthew , Pietsch Tina
Published: November 2010

The purpose of this inquiry is to explore the experience of Borderline Personality Disorder with the aim of developing a more liberating approach to its diagnosis and treatment. Eight participants (seven females and one male) diagnosed with Borderline Personality Disorder were recruited from a psychiatric hospital operated by the Surrey and Borders NHS Trust and an outpatient daycentre based in London, United Kingdom. A narrative approach to methodology was employed to collect and analyse the participants’ life-stories. Themes to emerge from the participant’s narratives were found to coincide with R.D. Laing’s concept of ontological insecurity. Ontological insecurity describes a number of aspects of the participant’s distress. To conclude, some general implications of this research for psychotherapy are briefly explored.
Forms of Hate Speech and the Convention on the Elimination of all Forms of Racial Discrimination (ICERD)
Authors: Thornberry Patrick
Published: November 2010

In this article, issues are raised concerning freedom of expression and forms of hate speech including advocacy of religious hatred in light of proposals to combat defamation of religions. In particular, it is asked whether parallels can be drawn between freedom of expression and protection from forms of hate speech in the area of race and ethnicity, and expression and protection in the field of religion. The present article offers a brief summary of relevant ICERD (‘the Convention’)2 principles and practice. The sketch of principles revolves around key areas of the Convention: the concept of discrimination including the ‘grounds’ of prohibited discrimination and how they relate to religious groups; the Convention’s stance on hate speech and rights to freedom of thought, conscience and religion3 and freedom of opinion and expression.4 The concluding section reflects on the concept of defamation of religions, the boundaries of ICERD in its current interpretation, and the idea of ICERD as a model for wider exercises in standard setting. The Committee on the Elimination of Discrimination (CERD) has the longest practice of any treaty body in the fields within its mandate and has developed a distinctive discourse in key areas. ‘Hate speech’ in the present article is used as shorthand for a range of international provisions protecting individuals and groups from discrimination and other assaults on their dignity and does not imply a special definition beyond the examples cited.
Responsible careers: Systemic reflexivity in shifting landscapes
Authors: Tams Svenja , Marshall Judi
Published: November 2010

This article examines responsible careers, in which people seek to have an impact on societal challenges such as environmental sustainability and social justice. We propose a dynamic model of responsible careers based on studying 32 individuals in the emerging organizational fields of corporate responsibility, social entrepreneurship, sustainability, and social investing. We describe six career practices — expressing self, connecting to others, constructing contribution, institutionalizing, field shaping, and engaging systemically. Observations suggest that development of these practices is influenced by four learning dynamics: people’s perceptions of ‘shifting landscapes’ in which they seek to orient themselves, exploration and both biographical and systemic reflexivity. Our interdisciplinary and empirically grounded approach, integrating psychological intentions and institutional context, strengthens theorizing about responsible careers. The proposed model depicts responsible careers as continually evolving, sometimes precarious, and as dynamically enacted in relation to pluralist, shifting landscapes.
Into the Woods
Authors: Evans Karen G.
Published: November 2010

In 2010, the state is not merely hollow but increasingly empty, and those of us in government have to find their energy and purpose in the process of rebuilding it. Our happy endings—the specific outcomes we claim to want—somehow come along with unexpected twists and losses. We’ve discovered that life and governance aren’t linear and predictable. In the 20th century, public administration (PA) ignored pragmatism, in large part, because it did not provide blueprints or formulas or promise specific outcomes. When PA asked, “How will this inclusive process of inquiry produce efficient results?” Pragmatism answered, “Efficiency? Does our Constitution call for efficiency? No, it’s the process that matters. Trust the process, involve as many citizens in the process as possible, invest in the development of citizens’ capacity to join and contribute to the process. If the process is right, our path through the woods will go in the right direction, and ‘right’ (if not predictable) outcomes will follow. The process is continuous, and as circumstances change, the process adapts.” In the past we rejected Pragmatism. Today, perhaps, we need to reflect on our understanding of what governance is, and possibly to reexamine those strange ideas Pragmatism offered once upon a time.
Sex, Feminism, and Advertising: The Politics of Advertising Feminism in a Competitive Marketplace
Authors: D'Enbeau Suzy
Published: November 2010

Feminist media organizations must balance ideology with financial viability via advertising revenue. Yet advertising rests on the assumption that sex sells. Research considering sex appeals in women’s magazines has shown that women are often portrayed in a demeaning manner. However, research has not considered that alternative media, such as Bust magazine, may construct sex appeals differently. This textual analysis applies third wave and feminist political economy theories to analyze how sex appeals are constructed in the discourse and images of advertisements in Bust. This analysis offers three strategies that indicate how sex functions in Bust advertising: (a) sex appeals that equate sexual commodities with a tenet of feminism; (b) sex appeals that foster feminist political protest; and (c) sex appeals that promote a feminist commitment to alternative identities. Findings suggest that sex appeals not only provide opportunities for revenue streams but also opportunities to reinforce feminist ideology.
Gender Differences in Physical Disability Among Older Adults in Underprivileged Communities in Lebanon
Authors: Zeki Al Hazzouri Adina , Mehio Sibai Abla , Chaaya Monique , Mahfoud Ziyad , Yount Kathryn M.
Published: November 2010

Objective: To examine the role of health conditions, socioeconomic, and socioenvironmental factors in explaining gender differences in physical disability among older adults. Method: We compared 412 women and 328 men residing in underprivileged communities in Lebanon on their activities of daily living (ADL), instrumental activities of daily living (IADL), and physical tasks (PT). Binary logistic regression analyses adjusting for possible explanatory covariates were conducted sequentially. Results: Women showed higher prevalence rates of ADL, IADL, and PT compared to men. Gender disparities in ADL disability were explained by chronic-disease risk factors and health conditions (OR = 1.46; 95% CI = 0.94-2.25). The odds of disability in IADL and PT remained significantly higher for women compared to men after accounting for all available covariates. Discussion: These results suggest underlying differences in functional status between women and men, yet, may have been influenced by the sensitivity of the measures to the social context and gendered environment surrounding daily activities.
Object-Based Warping
Authors: Vickery Timothy J. , Chun Marvin M.
Published: November 2010

Visual objects are high-level primitives that are fundamental to numerous perceptual functions, such as guidance of attention. We report that objects warp visual perception of space in such a way that spatial distances within objects appear to be larger than spatial distances in ground regions. When two dots were placed inside a rectangular object, they appeared farther apart from one another than two dots with identical spacing outside of the object. To investigate whether this effect was object based, we measured the distortion while manipulating the structure surrounding the dots. Object displays were constructed with a single object, multiple objects, a partially occluded object, and an illusory object. Nonobject displays were constructed to be comparable to object displays in low-level visual attributes. In all cases, the object displays resulted in a more powerful distortion of spatial perception than comparable non-object-based displays. These results suggest that perception of space within objects is warped.