bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression profiles from discordant monozygotic twins suggest that molecular pathways are shared among multiple systemic autoimmune diseases
Authors: O'Hanlon Terrance P , Rider Lisa G , Gan Lu , Fannin Rick , Paules Richard S , Umbach David M , Weinberg Clarice R , Shah Ruchir R , Mav Deepak , Gourley Mark F , Miller Frederick W 
Published: April 2011

Abstract
Introduction
The objective of this study is to determine if multiple systemic autoimmune diseases (SAID) share gene expression pathways that could provide insights into pathogenic mechanisms common to these disorders.

Methods
RNA microarray analyses (Agilent Human 1A(V2) 20K oligo arrays) were used to quantify gene expression in peripheral blood cells from 20 monozygotic (MZ) twin pairs discordant for SAID. Six affected probands with systemic lupus erythematosus (SLE), six with rheumatoid arthritis (RA), eight with idiopathic inflammatory myopathies (IIM), and their same-gendered unaffected twins, were enrolled. Comparisons were made between discordant twin pairs and these were also each compared to 40 unrelated control subjects (matched 2:1 to each twin by age, gender and ethnicity) using statistical and molecular pathway analyses. Relative quantitative PCR was used to verify independently measures of differential gene expression assessed by microarray analysis.

Results
Probands and unrelated, matched controls differed significantly in gene expression for 104 probes corresponding to 92 identifiable genes (multiple-comparison adjusted P values < 0.1). Differentially expressed genes involved several overlapping pathways including immune responses (16%), signaling pathways (24%), transcription/translation regulators (26%), and metabolic functions (15%). Interferon (IFN)-response genes (IFI27, OASF, PLSCR1, EIF2AK2, TNFAIP6, and TNFSF10) were up-regulated in probands compared to unrelated controls. Many of the abnormally expressed genes played regulatory roles in multiple cellular pathways. We did not detect any probes expressed differentially in comparisons among the three SAID phenotypes. Similarly, we found no significant differences in gene expression when comparing probands to unaffected twins or unaffected twins to unrelated controls. Gene expression levels for unaffected twins appeared intermediate between that of probands and unrelated controls for 6535 probes (32% of the total probes) as would be expected by chance. By contrast, in unaffected twins intermediate ordering was observed for 84 of the 104 probes (81%) whose expression differed significantly between probands and unrelated controls.

Conclusions
Alterations in expression of a limited number of genes may influence the dysregulation of numerous, integrated immune response, cell signaling and regulatory pathways that are common to a number of SAID. Gene expression profiles in peripheral blood suggest that for genes in these critical pathways, unaffected twins may be in a transitional or intermediate state of immune dysregulation between twins with SAID and unrelated controls, perhaps predisposing them to the development of SAID given the necessary and sufficient environmental exposures.
Interleukin-17A differentially modulates BCG induction of cytokine production in human blood macrophages
Authors: Fang J W , Li James C B , Au K Y , Yim Howard C H , Lau Allan S Y 
Published: April 2011

ABSTRACTThe pathogenesis of Mtb depends in part on cytokine cross-regulation between macrophages and T cells in host immunity. Th17 cells produce IL-17A to induce granuloma formation and to restrict mycobacterial dissemination. IL-17A also mediates cytokine responses induced by proinflammatory cytokines such as TNF-α. Our previous results showed that BCG induces IL-6, IL-10, and TNF-α via activity of protein kinases, including dsRNA-activated serine/threonine protein kinase and glycogen synthase kinase-3 in primary human monocytes. Therefore, we investigated whether IL-17A, upon its induction by BCG, plays an additional role to aid the production of downstream proinflammatory cytokines in macrophages. Here, we showed that IL-17A enhanced IL-6 mRNA and protein levels inducible by BCG in a time- and dose-dependent manner, whereas it had no effect on IL-10 and TNF-α production. We also demonstrated that IL-17A activated the phosphorylation of ERK1/2 triggered by BCG. With the use of a specific chemical inhibitor of a MAPK/ERK-activating kinase (MEK1/2), we confirmed the correlation between the enhanced ERK1/2 activation and augmented IL-6 production. Additionally, we revealed that IL-17A acts in concert with BCG-induced TNF-α to enhance the level of IL-6 synthesis. Taken together, our results suggest a significant role of IL-17A to serve as a modulator of cytokine expression in innate immune response during mycobacterial infection.
Lithium in drinking water and suicide rates across the East of England
Authors: Kabacs Nikolett , Memon Anjum , Obinwa Thom , Stochl Jan , Perez Jesus 
Published: April 2011

SummaryLithium can be found naturally in drinking water. In clinical practice, it is widely used in pharmacological doses for the treatment of bipolar disorder; and may also prevent suicidal behaviour in people with mood disorders. In two studies, lithium levels in tap water have been significantly and negatively correlated with suicide. We measured lithium levels in tap water in the 47 subdivisions of the East of England and correlated these with the respective suicide standardised mortality ratio in each subdivision. We found no association between lithium in drinking water and suicide rates across the East of England from 2006 to 2008.
Evaluation of secondary post-traumatic stress disorder symptoms in the spouses of chemical warfare victims 20 years after the Iran–Iraq war
Authors: Ahmadi Khodabakhsh , Reshadatjoo Mahmood , Karami GholamReza , Sepehrvand Nariman , Ahmadi Pegah , Bazargan-Hejazi Shahrzad 
Published: April 2011

Aims and methodPost-traumatic stress disorder (PTSD) has been reported in 90% of chemical warfare victims in previous studies. An individual's traumatic experience(s) may affect the lives of other family members as well. This cross-sectional case–control study compared the prevalence of PTSD symptoms in the husbands, the secondary PTSD symptoms in the wives and also aimed to identify if there was an association between the PTSD symptoms of the couples in the case group. Cases were 150 husband–wife couples where husbands were civilians exposed to chemical warfare; the controls were 156 husband–wife couples where there was no such exposure. Both cases and controls were recruited from Sardasht in Iran; this Kurdish city was attacked by four 250 kg sulphur mustard warheads in June 1987.ResultsAcross three sets of cut-off points for the Mississippi Scale for Combat-Related PTSD symptomotology (<120 and ⩾121; <106 and ⩾107; and <65, 65–130 and > 130) wives in the case group demonstrated higher rates of PTSD symptoms than did those in the control group; the difference was statistically significant. Furthermore, husbands in the case group had a significantly higher overall mean score (123.0 (s.d. = 17.2)) than the husbands in the control group (112.3 (s.d. = 21.7); P<0.001, t = 4.80). There was no statistically significant association between the overall PTSD score of the husbands in the case group with that of their wives (P = 0.274, correlation coefficient 0.092).Clinical implicationsHusbands who were exposed to the chemical agents reported higher PTSD symptoms and there were higher rates of PTSD symptoms among the wives of individuals who were exposed to chemical warfare. Study results suggest the need for coordinated treatments, policy efforts and interventions to improve the wellbeing of chemical warfare victims and their caregiver wives.
Still tilting at windmills
Authors: Shorter Edward 
Published: April 2011

SummaryThomas Szasz's essay misses several key points about the undoubted changes that psychiatry has undergone since he wrote his original screed against the discipline in 1961. Szasz fails to recognise that the discipline today acknowledges a neurological basis for much psychiatric illness. Thus, his fulminations against psychiatry for treating ‘mental illness' is off-base. Szasz's original diatribe was heavily against psychoanalysis. Yet today Freud's doctrines can scarcely be said to play even a marginal role in psychiatry, and it is absurd to keep levelling the same old charges of 50 years ago. One has the feeling of looking at one of the last veterans of the Esperanto movement in confronting Szasz: lunacy at the time, bizarrely outdated today.
Oxidative profile varies with personality in European greenfinches
Authors: Herborn Katherine A. , Coffey Jo , Larcombe Stephen D. , Alexander Lucille , Arnold Kathryn E. 
Published: April 2011

SUMMARY
Where behavioural responses differ consistently between individuals, this is termed ‘personality’. There is the suggestion, but with little supporting data, that personality traits reflect underlying variation in physiology. Here, we tested whether greenfinches Carduelis chloris differing in personality traits differed in various plasma indices of oxidative profile: antioxidant capacity (OXY), pro-oxidant status (reactive oxygen metabolites, ROMs), oxidative stress (OS) and an end-product of oxidative damage: malondialdehyde (MDA). We measured two personality traits: neophobia (latency to approach food near novel objects) and object exploration (latency to approach novel objects). These traits were uncorrelated. ROMs, OXY, OS and MDA were also uncorrelated with each other. Highly neophobic birds had lower OXY, higher ROMs and higher OS than less neophobic birds. Fast exploring birds had higher OXY than slow explorers, but did not differ in ROMs or OS. Variation in MDA was described by a quadratic relationship with neophobia: birds with extremely high or low neophobia had lower MDA than birds with intermediate neophobia, despite highly neophobic birds exhibiting lower OS than intermediately neophobic birds. Additively in that model, fast explorers had lower MDA than slower explorers. To conclude: first, personality types can differ in oxidative profile. Second, although physiological differences (e.g. hormonal stress responsiveness) between personality types generally range along a linear continuum, physiological costs may not. Finally, relationships with oxidative profile differed between neophobia and object exploration. Understanding how oxidative profile and thus physiological costs vary within and between personality traits may explain how differences in personality traits can predict fitness.
Molecular physiology and functional morphology of SO42– excretion by the kidney of seawater-adapted eels
Authors: Watanabe Taro , Takei Yoshio 
Published: April 2011

SUMMARYMarine teleosts actively excrete SO42– and keep the plasma concentration of this ion much lower than that of environmental seawater (SW). We used the eel as a model to study the excretory mechanism of SO42– because this euryhaline species changes SO42– regulation drastically after transfer from freshwater (FW) to SW. Time-course studies showed that plasma SO42– concentration decreased 3 days after transfer of eels from FW to SW, while urine SO42– concentration increased on 1 day. Detailed analyses showed that urine SO42– concentration increased linearly from 6 h after SW transfer; however, this did not immediately translate to increased SO42– excretion because the volume of urine was decreased. We identified five SO42– transporters in the eel kidney. Three of these (Slc26a1, Slc26a6b and Slc26a6c) are expressed in both SW- and FW-acclimated eels while Slc26a6a and Slc13a1 are expressed in SW-acclimated eels and FW-acclimated eels, respectively. We showed that changes in Slc26a6a and Slc13a1 gene expression occurred 1–3 days after SW transfer. In SW eel kidneys, immunohistochemistry using specific antisera against each transporter protein showed that Slc26a6a and Slc26a6c are localized on the apical membrane of the P1 segment of the proximal tubule, while Slc26a6b is localized on the apical membrane and Slc26a1 on the basolateral membrane of the P2 segment. The current study revealed complex molecular mechanisms of SO42– excretion in the SW eel kidney that involve segment-specific localization of multiple Slc transporters in proximal tubules and modulation of their expression in different SO42– environments. This precise regulatory mechanism may endow the eel with euryhalinity.
Experimental evolution of sperm count in protandrous self-fertilizing hermaphrodites
Authors: Murray Rosalind L. , Cutter Asher D. 
Published: April 2011

SUMMARYSperm count evolution is driven by sexual selection, with an added role of selection on gamete resource allocation for hermaphrodite spermatogenesis. However, self-fertilization by hermaphrodites retards sexual selection and results in the evolution of reduced investment in sperm or pollen. In contrast to reproduction limited by female gametes (Bateman's Principle), self-fertilizing Caenorhabditis elegans hermaphrodites exhibit sperm-limited reproduction. Caenorhabditis elegans hermaphrodites are thought to experience a fitness trade-off between lifetime fecundity and generation time: longer sperm production decreases the risk of self-sperm depletion, but at the same time delays the onset of selfing and thus increases egg-to-egg generation time. Theory predicts that shorter larval development will favor lower sperm counts and longer development will favor more sperm. To investigate how developmental trajectories affect the evolution of sperm production, we performed experimental evolution by directly competing alleles controlling hermaphrodite sperm count, conducted under different environmental conditions that alter development time. Results are partially consistent with theory: rapid larval development generally favored alleles encoding production of few sperm. However, we identify some previously unrecognized simplifications of the theory and its application to our experimental system. In addition, we evaluated the generality of sperm limitation in C. elegans. Although optimal growth conditions yield sperm limitation, non-optimal conditions induce oocyte limitation, suggesting that this species might conform to Bateman's Principle under many natural settings. These findings demonstrate how developmental trajectories can shape the fitness landscape for the evolution of reproduction and sperm traits, even without sexual selection.
ATP distribution and localization of mitochondria in Suberites domuncula (Olivi 1792) tissue
Authors: Lukić-Bilela Lada , Perović-Ottstadt Sanja , Walenta Stefan , Natalio Filipe , Pleše Bruna , Link Thorben , Müller Werner E. G. 
Published: April 2011

SUMMARY
The metabolic energy state of sponge tissue in vivo is largely unknown. Quantitative bioluminescence-based imaging was used to analyze the ATP distribution of Suberites domuncula (Olivi 1792) tissue, in relation to differences between the cortex and the medulla. This method provides a quantitative picture of the ATP distribution closely reflecting the in vivo situation. The obtained data suggest that the highest ATP content occurs around channels in the sponge medulla. HPLC reverse-phase C-18, used for measurement of ATP content, established a value of 1.62 μmol ATP g–1 dry mass in sponge medulla, as opposed to 0.04 μmol ATP g–1 dry mass in the cortex, thus indicating a specific and defined energy distribution. These results correlate with the mitochondria localization, determined using primary antibodies against cytochrome oxidase c subunit 1 (COX1) (immunostaining), as well as with the distribution of arginine kinase (AK), essential for cellular energy metabolism (in situ hybridization with AK from S. domuncula; SDAK), in sponge sections. The highest energy consumption seemed to occur in choanocytes, the cells that drive the water through the channel system of the sponge body. Taken together, these results showed that the majority of energetic metabolism in S. domuncula occurs in the medulla, in the proximity of aqueous channels.
Histaminergic signaling in the central nervous system of Daphnia and a role for it in the control of phototactic behavior
Authors: McCoole Matthew D. , Baer Kevin N. , Christie Andrew E. 
Published: April 2011

SUMMARY
Daphnia magna and Daphnia pulex are well-established model organisms in the fields of ecotoxicology and toxicogenomics. Among the many assays used for determining the effects of environmental and anthropogenic stressors on these animals is monitoring for changes in their phototactic behavior. In most arthropods, histamine has been shown to play a key role in the visual system. Currently, nothing is known about histaminergic signaling in either D. magna or D. pulex. Here, a combination of immunohistochemistry and genome mining was used to identify and characterize the histaminergic systems in these daphnids. In addition, a behavioral assay was used to assess the role of histamine in their phototactic response to ultraviolet (UV) light exposure. An extensive network of histaminergic somata, axons and neuropil was identified via immunohistochemistry within the central nervous system of both daphnids, including labeling of putative photoreceptors in the compound eye and projections from these cells to the brain. Mining of the D. pulex genome using known Drosophila melanogaster proteins identified a putative ortholog of histidine decarboxylase (the rate-limiting biosynthetic enzyme for histamine), as well as two putative histamine-gated chloride channels (hclA and hclB orthologs). Exposure of D. magna to cimetidine, an H2 receptor antagonist known to block both hclA and hclB in D. melanogaster, inhibited their negative phototactic response to UV exposure in a reversible, time-dependent manner. Taken collectively, our results show that an extensive histaminergic system is present in Daphnia species, including the visual system, and that this amine is involved in the control of phototaxis in these animals.
Vitamin D Status and Response to Daily 400 IU Vitamin D3 and Weekly Alendronate 70 mg in Men and Women with Osteoporosis
Authors: Karaplis Andrew C , Chouha Fridon , Djandji Michel , Sampalis John S , Hanley David A 
Published: April 2011

Background Suboptimal vitamin D status is common in elderly individuals. However, the extent of vitamin D inadequacy in men and women being treated for osteoporosis in a family practice setting has not been well characterized. Objective: To describe the distribution of serum 25-hydroxyvitamin D (25-[OH] D) in Canadian men and postmenopausal women with osteoporosis taking 400 IU or less of vitamin D daily and to evaluate the safety, tolerability, and impact of vitamin D3 supplementation 400 IU daily taken concurrently with alendronate sodium 70 mg weekly. Methods: This was a prospective, single-cohort, open-label, multicenter study. Community-dwelling men and postmenopausal women with osteoporosis were recruited at 197 sites across Canada. Patients received vitamin D3 400 IU/day supplementation coadministered with alendronate 70 mg/wk for 16 weeks. The primary outcome was the distribution of serum 25-(OH) D at baseline. Secondary outcome measures included changes from baseline in serum 25-(OH) D levels, adherence to study treatments, and incidence of treatment-related adverse events (AEs). Results: Of the 681 patients included in the analysis, 485 (71.2%) completed the study. Patients were predominantly female (83.1%) with a mean (SD) age of 67.6 (10.7) years. At baseline, mean (SD) serum 25-(OH) D concentration was 25.4 (9.9) ng/mL and 68.0% of the patients had inadequate (less than 30 ng/mL) vitamin D status. At week 16, concentrations increased by 35.1% to 31.2 (9.2) ng/mL (p < 0.001) and the proportion of patients with inadequate 25-(OH) D levels was reduced to 47.0%. Adherence to the treatment regimen was high (greater than 95%). Gastrointestinal disorders were the most frequently reported (6.9%) treatment-related AEs. Conclusions: About two thirds of patients previously diagnosed with osteoporosis have inadequate vitamin D status. A treatment regimen consisting of alendronate 70 mg/wk administered with daily vitamin D3 400 IU supplementation significantly increased patients' serum 25-(OH) D levels, but 47% did not achieve optimal levels. These results support both the National Osteoporosis Foundation and Osteoporosis Canada recommendations for higher vitamin D supplement doses (at least 800 IU daily) in osteoporotic patients receiving pharmacologic therapy for osteoporosis and for monitoring their serum 25-(OH) D response.
Symptom Reporting Compared with Audiometry for the Detection of Cochleotoxicity in Patients on Long-Term Aminoglycoside Therapy
Authors: Palmay Lesley , Walker Sandra AN , Walker Scott E , Simor Andrew E 
Published: April 2011

Background Aminoglycoside-associated auditory toxicity (cochleotoxicity) is a major concern in patients receiving prolonged aminoglycoside therapy. There are no published data comparing symptom monitoring to audiometry testing for the detection of aminoglycoside-induced cochleotoxicity; thus, agreement regarding the optimal monitoring of these patients for early detection of this effect is lacking. Objective: To compare the sensitivity of symptom monitoring to that of audiometry in identifying cochleotoxicity in patients on prolonged aminoglycoside therapy. Methods: A retrospective chart review of adult inpatients at Sunnybrook Health Sciences Centre prescribed prolonged aminoglycoside therapy (≥21 days) who completed at least 1 audiometry test between January 1, 1999, and December 31, 2009, was conducted. Data pertaining to results of audiometry testing and development of symptoms of auditory toxicity were collected. Symptom monitoring was compared with audiology testing for the detection of cochleotoxicity. Results: Forty eligible patients were included for analysis. Audiometry was significantly better than symptom monitoring to identify early cochleotoxicity (absolute risk reduction = 17.5% and number needed to treat = 6; p = 0.023). Compared to audiometry, symptom monitoring has a sensitivity, negative predictive value, and accuracy for the detection of early cochleotoxicity of 61%, 75%, and 82%, respectively. Conclusions: Audiometry testing is significantly better than monitoring symptoms to identify early aminoglycoside-induced auditory toxicity in patients prescribed prolonged aminoglycoside therapy (≥21 days). Subclinical cochleotoxicity identified with audiometry may allow early termination of aminoglycoside therapy to prevent progression of cochlear damage to the audible frequency range.
Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R-/- mice
Authors: Rafferty Eamon P. , Wylie Alastair R. , Hand Katharine H. , Elliott Chris E. , Grieve David J. , Green Brian D. 
Published: April 2011

AbstractPhysiological secretion of bile acids has previously been linked to the regulation of blood glucose. GLP-1 is an intestinal peptide hormone with important glucose-lowering actions, such as stimulation of insulin secretion and inhibition of glucagon secretion. In this investigation, we assessed the ability of several bile acid compounds to secrete GLP-1in vitroin STC-1 cells. Bile acids stimulated GLP-1 secretion from 3.3- to 6.2-fold but some were associated with cytolytic effects. Glycocholic and taurocholic acids were selected forin vivostudies in normal and GLP-1R-/-mice. Oral glucose tolerance tests revealed that glycocholic acid did not affect glucose excursions. However, taurocholic acid reduced glucose excursions by 40% in normal mice and by 27% in GLP-1R-/-mice, and plasma GLP-1 concentrations were significantly elevated 30 min post-gavage. Additional studies used incretin receptor antagonists to probe involvement of GLP-1 and GIP in taurocholic acid-induced glucose lowering. The findings suggest that bile acids partially aid glucose regulation by physiologically enhancing nutrient-induced GLP-1 secretion. However, GLP-1 secretion appears to be only part of the glucose-lowering mechanism and our studies indicate that the other major incretin GIP is not involved.