bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring smooth muscle phenotype and function in a bioreactor model of abdominal aortic aneurysm
Authors: Riches Kirsten , Angelini Timothy G , Mudhar Gurprit S , Kaye Jean , Clark Emily , Bailey Marc A , Sohrabi Soroush , Korossis Sotirios , Walker Peter G , Scott D Julian A , Porter Karen E
Published: September 2013

Background

Vascular smooth muscle cells (SMC) are central to arterial structure and function yet their involvement in the progression of abdominal aortic aneurysm (AAA) disease is not well studied. The progressive and silent nature of AAA in man essentially restricts research to the use of “end-stage” tissue recovered during surgical repair. This study aimed to generate an ex vivo model of AAA using protease-treated porcine carotid arteries maintained in a novel bioreactor, and to compare the structural and functional changes in SMC cultured from the recovered vessels with those from human tissue acquired at elective surgical repair.

Methods

Freshly isolated porcine arteries were pretreated with collagenase and/or elastase before culturing under flow in a bioreactor for 12 days. Human end-stage aneurysmal tissue and saphenous veins from age-matched controls were collected from patients undergoing surgery. SMC were cultured and characterised (immunocytochemistry, measurement of spread cell area) and assessed functionally at the level of proliferation (cell-counting) and matrix-metalloproteinase (MMP) secretion (gelatin zymography). Cellular senescence was investigated using β-galactosidase staining and apoptosis was quantified using a fluorescence-based caspase 3 assay.

Results

Co-expression of alpha-smooth muscle actin and smooth muscle myosin heavy chain confirmed all cell populations as SMC. Porcine SMC harvested and cultivated after collagenase/elastase pretreatment displayed a prominent “rhomboid” morphology, increased spread area (32%, P < 0.01), impaired proliferation (47% reduction, P < 0.05), increased senescence (52%, P < 0.001), susceptibility to apoptosis and reduced MMP-2 secretion (60% decrease, P < 0.01) compared with SMC from vehicle, collagenase or elastase pre-treated vessels. Notably, these changes were comparable to those observed in human AAA SMC which were 2.4-fold larger than non-aneurysmal SMC (P < 0.001) and exhibited reduced proliferation (39% reduction, P < 0.001), greater apoptosis (4-fold increase, P < 0.001), and increased senescence (61%, P < 0.05).

Conclusions

Combined collagenase/elastase exposure of porcine artery maintained in a bioreactor under flow conditions induced a SMC phenotype characteristic of those cultured from end-stage AAA specimens. This model has potential and versatility to examine temporal changes in SMC biology and to identify the molecular mechanisms leading to early aberrancies in SMC function. In the longer term this may inform new targets to maintain aortic SMC content and drive cells to a “reparative” phenotype at early stages of the disease.
DSM-5: a collection of psychiatrist views on the changes, controversies, and future directions
Authors: Nemeroff Charles B , Weinberger Daniel , Rutter Michael , MacMillan Harriet L , Bryant Richard A , Wessely Simon , Stein Dan J , Pariante Carmine M , Seemüller Florian , Berk Michael , Malhi Gin S , Preisig Martin , Brüne Martin , Lysaker Paul
Published: September 2013

The recent release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the American Psychiatric Association has led to much debate. For this forum article, we asked BMC Medicine Editorial Board members who are experts in the field of psychiatry to discuss their personal views on how the changes in DSM-5 might affect clinical practice in their specific areas of psychiatric medicine. This article discusses the influence the DSM-5 may have on the diagnosis and treatment of autism, trauma-related and stressor-related disorders, obsessive-compulsive and related disorders, mood disorders (including major depression and bipolar disorders), and schizophrenia spectrum disorders.
Delayed seroconversion to STLV-1 infection is associated with mutations in the pol and rex genes
Authors: Dube Syamalima , Saksena Nitin , Spicer Timothy , Healey Jayne , Benz Patricia , Dube Dipak K , Poiesz Bernard J
Published: September 2013

Background

Simian T-cell lymphoma/leukemia virus-1 (STLV-1) infection of non-human primates can serve as a model for human T-cell lymphoma/leukemia virus infection.

Methods

Two tantalus and 2 patas monkeys were transfused with intraspecies whole blood infected with STLV-1. Infection was determined by ELISA, western blot and DNA PCR analyses. The entire genome of the STLV-1 Tan 90 strain and some of the STVL-1 Pat74 strain were amplified using over-lapping primer-pairs and subsequently sequenced.

Results

Followup studies conducted over 2 years indicated that all 4 monkeys remained healthy despite being infected with STLV-1, as determined by PCR, cloning and sequencing analyses. ELISA and Western blot analyses indicated that both patas monkeys seroconverted within 2 months of transfusion, while one tantalus monkey required one year to seroconvert and the other never fully seroconverted. The tantalus monkey which never fully seroconverted, failed to react to HTLV-1 p24 Gag antigen. Sequence analyses indicated that, while unique, the deduced p24 Gag amino acid sequence of the STLV-1 Tan 90 strain used for infection was still highly homologous to the HTLV-1 p24 Gag amino acids present in the ELISA and WB assays. However, a mutation in the pol sequence of STLV-1 Tan 90 encoded a putative stop codon, while a common deletion in the pol/rex regulatory gene causes significant changes in the Pol, and p27 Rex proteins. These same mutations were also observed in the viral DNA of both recipient infected tantalus monkeys and were not present in the STLV-1 Pat 74 strain.

Conclusion

Our data suggest that seroconversion to STLV-1 infection may be prolonged due to the above mutations, and that compensatory molecular events must have occurred to allow for virus transmission.
Prevalence of avian paramyxovirus type 1 in Mallards during autumn migration in the western Baltic Sea region
Authors: Tolf Conny , Wille Michelle , Haidar Ann-Katrin , Avril Alexis , Zohari Siamak , Waldenström Jonas
Published: September 2013

Background

Newcastle disease virus (NDV) is the causative agent of the Newcastle disease, a severe disease in birds associated with substantial economic losses to the poultry industry worldwide. Sweden is situated along the Western European waterfowl flyway and applies a non-vaccination policy combined with directives of immediate euthanisation of NDV infected flocks. During the last decades there have been several outbreaks with NDV in poultry in Sweden. However, less is known about the virus prevalence in the wild bird population including waterfowl, a well-established reservoir of avian paramyxovirus type 1 (APMV-1), the paramyxovirus serotype that include pathogenic NDV.

Methods

The survey constituted of 2332 samples from Mallards (Anas platyrhynchos), trapped in the southern part of Sweden during autumn migration in 2010. These samples were screened for APMV-1 by real-time reverse transcription PCR, and viral strains from positive samples were isolated and characterized by sequence analysis of the fusion gene and by phylogenetic analysis.

Conclusions

Twenty of these samples were positive for APMV-1, hence a virus prevalence of 0.9% (95% Confidence Interval [95% CI]=0.54%, 1.35%). The highest APMV-1 prevalence was detected in juvenile Mallards sampled in November (n=887, prevalence 1.24% ([95% CI])=0.67%, 2.24%). Sequence analysis and evaluation of phylogenetic relatedness indicated that isolated APMV-1 strains were lentogenic, and phylogenetically most closely related to genotype Ib strains within the clade of class II viruses. The sampling system employed enabled us to follow APMV-1 infections and the shedding of one particular viral strain in one individual bird over several days. Furthermore, combining previous screening results with the APMV-1 detections in this study showed that more than 50% of Mallards that tested positive for APMV-1 RNA were co-infected with influenza A virus.
Comparison of viremia of type II porcine reproductive and respiratory syndrome virus in naturally infected pigs by zip nucleic acid probe-based real-time PCR
Authors: Lin Chao-Nan , Lin Wei-Hao , Hung Li-Ning , Wang Sheng-Yuan , Chiou Ming-Tang
Published: September 2013

Background

Porcine reproductive and respiratory syndrome virus (PRRSV) is a RNA virus with high genetic variation. This virus causes significant economic losses in most pig-producing countries. The clinical presentation of PRRSV ranges from asymptomatic to devastating. In this study, we developed a sensitive and specific zip nucleic acid probe-based real-time PCR assay to evaluate the viremia of natural PRRSV-infected pigs in Taiwan. Serum samples were collected from 577 pigs aged 5–12 weeks. These include 444 clinically healthy pigs and 133 symptomatic pigs were confirmed to have porcine respiratory disease complex (PRDC).

Results

Viremia was quantified in 79 of the 444 (17.8%) clinically healthy pigs and in 112 of the 133 (84.2%) PRDC cases. Viremias were significantly more common in pigs with PRDC compared with the clinically healthy pigs (P <0.0001). These results suggest that a high viral load is a major feature of PRRSV-affected pigs.

Conclusions

ZNA probe-based real-time PCR can be a useful tool to diagnose symptomatic and asymptomatic PRRSV-infected pigs. The presence of this marker in a sample of animals with high PRRSV loads (>104.2 PRRSV genomes/μl of serum) seems to indicate that it correlates with the presence of PRDC in pigs.
Resolution of five-component mixture using mean centering ratio and inverse least squares chemometrics
Authors: Issa Mahmoud Mohamed , Nejem R’afat Mahmoud , Shanab Alaa Mohamed Abu , Shaat Nahed Talab
Published: September 2013

Background

A comparative study of the use of mean centering of ratio spectra and inverse least squares for the resolution of paracetamol, methylparaben, propylparaben, chlorpheniramine maleate and pseudoephedrine hydrochloride has been achieved showing that the two chemometric methods provide a good example of the high resolving power of these techniques. Method (I) is the mean centering of ratio spectra which depends on using the mean centered ratio spectra in four successive steps that eliminates the derivative steps and therefore the signal to noise ratio is improved. The absorption spectra of prepared solutions were measured in the range of 220–280 nm. Method (II) is based on the inverse least squares that depend on updating developed multivariate calibration model. The absorption spectra of the prepared mixtures in the range 230–270 nm were recorded.

Results

The linear concentration ranges were 0–25.6, 0–15.0, 0–15.0, 0–45.0 and 0–100.0 μg mL-1 for paracetamol, methylparaben, propylparaben, chlorpheniramine maleate and pseudoephedrine hydrochloride, respectively. The mean recoveries for simultaneous determination were between 99.9-101.3% for the two methods. The two developed methods have been successfully used for prediction of five-component mixture in Decamol Flu syrup with good selectivity, high sensitivity and extremely low detection limit.

Conclusion

No published method has been reported for simultaneous determination of the five components of this mixture so that the results of the mean centering of ratio spectra method were compared with those of the proposed inverse least squares method. Statistical comparison was performed using t-test and F-ratio at P = 0.05. There was no significant difference between the results.
Genotyping of human neutrophil antigens (HNA) from whole genome sequencing data
Authors: Chu Hsueh-Ting , Lin Han , Tsao Theresa Tsun-Hui , Chang Chun-Fan , Hsiao William WL , Yeh Tze-Jung , Chang Ching-Mao , Liu Yen-Wenn , Wang Tse-Yi , Yang Ko-Chun , Chen Tsung-Jui , Chen Jen-Chih , Chen Kuang-Chi , Kao Cheng-Yan
Published: September 2013

Background

Neutrophil antigens are involved in a variety of clinical conditions including transfusion-related acute lung injury (TRALI) and other transfusion-related diseases. Recently, there are five characterized groups of human neutrophil antigen (HNA) systems, the HNA1 to 5. Characterization of all neutrophil antigens from whole genome sequencing (WGS) data may be accomplished for revealing complete genotyping formats of neutrophil antigens collectively at genome level with molecular variations which may respectively be revealed with available genotyping techniques for neutrophil antigens conventionally.

Results

We developed a computing method for the genotyping of human neutrophil antigens. Six samples from two families, available from the 1000 Genomes projects, were used for a HNA typing test. There are 500 ~ 3000 reads per sample filtered from the adopted human WGS datasets in order for identifying single nucleotide polymorphisms (SNPs) of neutrophil antigens. The visualization of read alignment shows that the yield reads from WGS dataset are enough to cover all of the SNP loci for the antigen system: HNA1, HNA3, HNA4 and HNA5. Consequently, our implemented Bioinformatics tool successfully revealed HNA types on all of the six samples including sequence-based typing (SBT) as well as PCR sequence-specific oligonucleotide probes (SSOP), PCR sequence-specific primers (SSP) and PCR restriction fragment length polymorphism (RFLP) along with parentage possibility.

Conclusions

The next-generation sequencing technology strives to deliver affordable and non-biased sequencing results, hence the complete genotyping formats of HNA may be reported collectively from mining the output data of WGS. The study shows the feasibility of HNA genotyping through new WGS technologies. Our proposed algorithmic methodology is implemented in a HNATyping software package with user’s guide available to the public at http://sourceforge.net/projects/hnatyping/.
Pronuclear morphology evaluation for fresh in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles: a systematic review
Authors: Nicoli Alessia , Palomba Stefano , Capodanno Francesco , Fini Maria , Falbo Angela , La Sala Giovanni Battista
Published: September 2013

The current systematic review was aimed to assess the effectiveness of the zygote morphology evaluation in fresh in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles. All available studies reporting on zygote morphology and clinical and/or biological outcomes were analyzed. Forty studies were included in the final analysis. Fourteen different zygote scoring systems were employed. Zygote morphology correlated significantly with embryo quality and cleavage, blastocyst stage, embryonic chromosome status, in a high proportion of the studies which assessed the specific outcome [15/25 (60%), 15/20 (75%), 7/8 (87.5%), 6/6 (100%), respectively]. On the other hand, only a reduced proportion of papers showed a statistically significant relationship between implantation, pregnancy and delivery/live-birth rates and zygote morphology score [12/23 (52.2%), 12/25 (48%), 1/4 (25%), respectively]. In conclusion, our findings demonstrate the lack of conclusive data on the clinical efficacy of the zygote morphology evaluation in fresh IVF/ICSI cycles, even if biological results showing a good relationship with embryo viability suggest a role in cycles in which the transfer/freezing is performed at day 1.
Renal replacement therapy with net fluid removal lowers intra-abdominal pressure and volumetric indices in critically ill patients
Authors: De laet Inneke , Deeren Dries , Schoonheydt Karen , Van Regenmortel Niels , Dits Hilde , Malbrain Manu LNG
Published: September 2013

Background

Little is known about the effects of renal replacement therapy (RRT) with fluid removal on intra-abdominal pressure (IAP). The global end-diastolic volume index (GEDVI) and extravascular lung water index (EVLWI) can easily be measured bedside by transpulmonary thermodilution (TPTD). The aim of this study is to evaluate the changes in IAP, GEDVI and EVLWI in critically ill patients receiving slow extended daily dialysis (SLEDD) or continuous venovenous haemofiltration (CVVH) with the intention of net fluid removal.

Methods

We performed a retrospective cohort study in ICU patients who were treated with SLEDD or CVVH and in whom IAP was also measured, and RRT sessions were excluded when the dose of vasoactive medication needed to be changed between the pre- and post-dialysis TPTD measurements and when net fluid loss did not exceed 500 ml. The TPTD measurements were performed within 2 h before and after SLEDD; in case of CVVH, before and after an interval of 12 h.

Results

We studied 25 consecutive dialysis sessions in nine patients with acute renal failure and cardiogenic or non-cardiogenic pulmonary oedema. The GEDVI and EVLWI values before dialysis were 877 ml/m² and 14 ml/kg, respectively. Average net ultrafiltration per session was 3.6 l, with a net fluid loss 1.9 l. The GEDVI decreased significantly during dialysis, but not more than 47.8 ml/m² (p = 0.008), as also did the EVLWI with 1 ml/kg (p = 0.03). The IAP decreased significantly from 12 to 10.5 mmHg (p < 0.0001).

Conclusions

Net fluid removal by SLEDD or CVVH in the range observed in this study decreased IAP, GEDVI and EVLWI in critically ill patients although EVLWI reduction was modest.
Cardioprotective effects of adenosine within the border and remote areas of myocardial infarction
Authors: Bousquenaud Mélanie , Maskali Fatiha , Poussier Sylvain , Zangrando Jennifer , Marie Pierre-Yves , Boutley Henri , Fay Renaud , Karcher Gilles , Wagner Daniel R , Devaux Yvan
Published: September 2013

Background

Adenosine may have beneficial effects on left ventricular function after myocardial infarction (MI), but the magnitude of this effect on remote and MI areas is controversial. We assessed the long-term effects of adenosine after MI using electrocardiogram-triggered 18 F-fluorodeoxyglucose positron emission tomography.

Methods

Wistar rats were subjected to coronary ligation and randomized into three groups treated daily for 2 months by NaCl (control; n = 7), 2-chloroadenosine (CADO; n = 8) or CADO with 8-sulfophenyltheophilline, an antagonist of adenosine receptors (8-SPT; n = 8).

Results

After 2 months, control rats exhibited left ventricular remodelling, with increased end-diastolic volume and decreased ejection fraction. Left ventricular remodelling was not significantly inhibited by CADO. Segmental contractility, as assessed by the change in myocardial thickening after 2 months, was improved in CADO rats compared to control rats (+1.6% ± 0.8% vs. −2.3% ± 0.8%, p < 0.001). This improvement was significant in border (+5.6% ± 0.8% vs. +1.5% ± 0.8%, p < 0.001) and remote (−4.0% ± 1.0% vs. −10.4% ± 1.3%, p < 0.001) segments, but absent in MI segments. Histological analyses revealed that CADO reduced fibrosis, cardiomyocyte hypertrophy and apoptosis. Protective effects of CADO were blunted by 8-SPT.

Conclusion

Long-term administration of adenosine protects the left ventricle from contractile dysfunction following MI.
Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation
Authors: Alves Ana Carolina Araruna , Vieira Rodolfo de Paula , Leal-Junior Ernesto Cesar Pinto , dos Santos Solange Almeida , Ligeiro Ana Paula , Albertini Regiane , Junior Jose Antonio Silva , de Carvalho Paulo de Tarso Camillo
Published: September 2013

Introduction

Inflammation of the synovial membrane plays an important role in the pathophysiology of osteoarthritis (OA). The synovial tissue of patients with initial OA is characterized by infiltration of mononuclear cells and production of proinflammatory cytokines and other mediators of joint injury. The objective was to evaluate the effect of low-level laser therapy (LLLT) operating at 50 mW and 100 mW on joint inflammation in rats induced by papain, through histopathological analysis, differential counts of inflammatory cells (macrophages and neutrophils), as well as gene expression of interleukin 1-beta and 6 (IL-1β and IL-6), and protein expression of tumor necrosis factor alpha (TNFα).

Methods

Male Wistar rats (n = 60) were randomly divided into four groups of 15 animals, namely: a negative control group; an inflammation injury positive control group; a 50 mW LLLT group, subjected to injury and treated with 50 mW LLLT; and a 100 mW LLLT group, subjected to injury and treated with 100 mW LLLT. The animals were subject to joint inflammation (papain solution, 4%) and then treated with LLLT (808 nm, 4 J, 142.4 J/cm2, spot size 0.028 for both groups). On the day of euthanasia, articular lavage was collected and immediately centrifuged; the supernatant was saved for analysis of expression of TNFα protein by enzyme-linked immunosorbent assay and expression of IL-1β and IL-6 mRNA by real-time polymerase chain reaction. A histologic examination of joint tissue was also performed. For the statistical analysis, analysis of variance with Tukey's post-hoc test was used for comparisons between each group. All data are expressed as mean values and standard deviation, with P < 0.05.

Results

Laser treatment with 50 mW was more efficient than 100 mW in reducing cellular inflammation, and decreased the expression of IL-1β and IL-6. However, the 100 mW treatment led to a higher reduction of TNFα compared with the 50 mW treatment.

Conclusions

LLLT with 50 mW was more efficient in modulating inflammatory mediators (IL-1β, IL-6) and inflammatory cells (macrophages and neutrophils), which correlated with the histology that showed a reduction in the inflammatory process.
Predicting persistent inflammatory arthritis amongst early arthritis clinic patients in the UK: is musculoskeletal ultrasound required?
Authors: Pratt Arthur G , Lorenzi Alice R , Wilson Gill , Platt Philip N , Isaacs John D
Published: September 2013

Introduction

Analyses of large clinical datasets from early arthritis cohorts permit the development of algorithms that may be used for outcome prediction in individual patients. The value added by routine use of musculoskeletal ultrasound (MSUS) in an early arthritis setting, as a component of such predictive algorithms, remains to be determined.

Methods

The authors undertook a retrospective analysis of a large, true-to-life, observational inception cohort of early arthritis patients in Newcastle upon Tyne, UK, which included patients with inflammatory arthralgia but no clinically swollen joints. A pragmatic, 10-minute MSUS assessment protocol was developed, and applied to each of these patients at baseline. Logistic regression was used to develop two "risk metrics" that predicted the development of a persistent inflammatory arthritis (PIA), with or without the inclusion of MSUS parameters.

Results

A total of 379 enrolled patients were assigned definitive diagnoses after ≥12 months follow-up (median 28 months), of whom 162 (42%) developed a persistent inflammatory arthritis. A risk metric derived from 12 baseline clinical and serological parameters alone had an excellent discriminatory utility with respect to an outcome of PIA (area under receiver operator characteristic (ROC) curve 0.91; 95% CI 0.88 to 0.94). The discriminatory utility of a similar metric, which incorporated MSUS parameters, was not significantly superior (area under ROC curve 0.91; 95% CI 0.89 to 0.94). Neither did this approach identify an added value of MSUS over the use of routine clinical parameters in an algorithm for discriminating PIA patients whose outcome diagnosis was rheumatoid arthritis (RA).

Conclusions

MSUS use as a routine component of assessment in an early arthritis clinic did not add substantial discriminatory value to a risk metric for predicting PIA.
Induced expression and functional effects of aquaporin-1 in human leukocytes in sepsis
Authors: Vassiliou Alice G , Maniatis Nikolaos A , Orfanos Stylianos E , Mastora Zafeiria , Jahaj Edison , Paparountas Triantafillos , Armaganidis Apostolos , Roussos Charis , Aidinis Vassilis , Kotanidou Anastasia
Published: September 2013

Introduction

Gene expression profiling was performed via DNA microarrays in leukocytes from critically ill trauma patients nonseptic upon admission to the ICU, who subsequently developed either sepsis (n = 2) or severe sepsis and acute respiratory distress syndrome (n = 3). By comparing our results with published expression profiling studies in animal models of sepsis and lung injury, we found aquaporin-1 to be differentially expressed across all studies. Our aim was to determine how the water channel aquaporin-1 is involved in regulating the immune response in critically ill patients during infection acquired in the ICU.

Methods

Following the results of the initial genetic screening study, we prospectively followed aquaporin-1 leukocyte expression patterns in patients with ICU-acquired sepsis who subsequently developed septic shock (n = 16) versus critically ill patients who were discharged without developing sepsis (n = 13). We additionally determined aquaporin-1 expression upon lipopolysaccharide (LPS) exposure and explored functional effects of aquaporin-1 induction in polymorphonuclear granulocytes (PMNs).

Results

Leukocyte aquaporin-1 expression was induced at the onset of sepsis (median 1.71-fold increase; interquartile range: 0.99 to 2.42, P = 0.012 from baseline) and was further increased upon septic shock (median 3.00-fold increase; interquartile range: 1.20 to 5.40, P = 0.023 from sepsis, Wilcoxon signed-rank test); no difference was observed between baseline and discharge in patients who did not develop sepsis. Stimulation of PMNs by LPS led to increased expression of aquaporin-1 in vitro, which could be abrogated by the NF-κB inhibitor EF-24. PMN hypotonic challenge resulted in a transient increase of the relative cell volume, which returned to baseline after 600 seconds, while incubation in the presence of LPS resulted in persistently increased cell volume. The latter could be abolished by blocking aquaporin-1 with mercury and restored by incubation in β-mercaptoethanol, which abrogated the action of mercury inhibition.

Conclusions

Aquaporin-1 is induced in leukocytes of patients with ICU-acquired sepsis and exhibits higher expression in septic shock. This phenomenon may be due to LPS-triggered NF-κB activation that can also lead to alterations in plasma membrane permeability.
Differential Control of Sex Differences in Estrogen Receptor α in the Bed Nucleus of the Stria Terminalis and Anteroventral Periventricular Nucleus
Authors: Kelly D. A. , Varnum M. M. , Krentzel A. A. , Krug S. , Forger N. G.
Published: September 2013

The principal nucleus of the bed nucleus of the stria terminalis (BNSTp) and anteroventral periventricular nucleus of the hypothalamus (AVPV) are sexually dimorphic, hormone-sensitive forebrain regions. Here we report a profound sex difference in estrogen receptor-α (ERα) immunoreactivity (IR) in the BNSTp, with robust ERα IR in females and the near absence of labeling in males. This sex difference is due to the suppression of ERα IR by testicular hormones in adulthood: it was not present at birth and was not altered by neonatal treatment of females with estradiol; gonadectomy of adult males increased ERα IR to that of females, whereas gonadectomy of adult females had no effect. Treating gonadally intact males with an aromatase inhibitor partially feminized ERα IR in the BNSTp, suggesting that testicular suppression required aromatization. By contrast, in AVPV we found a modest sex difference in ERα IR that was relatively insensitive to steroid manipulations in adulthood. ERα IR in AVPV was, however, masculinized in females treated with estradiol at birth, suggesting that the sex difference is due to organizational effects of estrogens. The difference in ERα IR in the BNSTp of males and females appears to be at least in part due to greater expression of mRNA of the ERα gene (Esr1) in females. The sex difference in message is smaller than the difference in immunoreactivity, however, suggesting that posttranscriptional mechanisms also contribute to the pronounced suppression of ERα IR and presumably to functions mediated by ERα in the male BNSTp.
Bradykinin B2 Receptor in the Adrenal Medulla of Male Rats and Mice: Glucocorticoid-Dependent Increase With Immobilization Stress
Authors: Nostramo Regina , Tillinger Andrej , Serova Lidia , Kvetnansky Richard , Sabban Esther L.
Published: September 2013

Bradykinin, acting via the bradykinin B2 receptor (B2R), is a potent stimulator of adrenomedullary catecholamine biosynthesis and release and likely plays an important role in the adrenomedullary stress response. However, the effects of stress on the expression of this receptor in the adrenal medulla are currently unclear. Here, we examined the changes in adrenomedullary B2R gene expression in male rats in response to single (1 time) and repeated (6 times) exposure to 2 hours immobilization stress (IMO). Immediately after 1 or 6 times IMO, B2R mRNA levels were increased by 9-fold and 7-fold, respectively, and returned to unstressed control levels 3 hours later. This large, but transient, increase in mRNA elicited a doubling of protein levels 3 hours after the stress exposure. Next, the role of the hypothalamic-pituitary-adrenocortical axis in the stress-induced upregulation of B2R gene expression was examined. Treatment with endogenous (corticosterone) and synthetic (dexamethasone) glucocorticoids dose-dependently increased B2R mRNA levels in adrenomedullary-derived PC12 cells. Furthermore, cortisol supplementation at levels mimicking stress exposure elevated B2R mRNA levels in the adrenal medulla of hypophysectomized rats. In response to 1 exposure to IMO, the stress-triggered rise in plasma corticosterone and adrenomedullary B2R mRNA levels was attenuated in CRH-knockout mice and absent in pharmacologically adrenalectomized rats, indicating a requirement for glucocorticoids in the upregulation of B2R gene expression with stress. Overall, the increase in B2R gene expression in response to the stress-triggered rise in glucocorticoids likely enhances catecholamine biosynthesis and release and may serve as an adaptive response of the adrenomedullary catecholaminergic system to stress.
Stranger Artisans and the London Sanctuary of St. Martin le Grand in the Reign of Henry VIII
Authors: McSheffrey Shannon
Published: September 2013

St. Martin le Grand, a precinct within the walls of London, was both a sanctuary and a liberty: it offered asylum to accused felons, and it allowed immigrant craftsmen to work and sell within its bounds despite London’s strict restrictions on alien labor. St. Martin’s privileges had long rankled civic governors and guilds, sparking a series of legal and political skirmishes between the City and St. Martin’s in the 1520s and 1530s. This article examines St. Martin’s community of Dutch and French immigrants, who constituted the densest concentration of aliens in the metropolitan area. Living cheek by jowl with felonious sanctuary seekers, the strangers came to share both a conceptual and a physical space with the felons who sought St. Martin’s sanctuary privilege. In the reign of Henry VIII, the control of labor and retailing came to be tightly imbricated with the larger issues surrounding crime, mercy, and punishment that sanctuary inspired.
The parietal cell gastric H, K-ATPase also functions as the Na, K-ATPase and Ca-ATPase in altered states
Authors: Ray Tushar
Published: September 2013

This article offers an explanation for the apparent lack of Na, K-ATPase activity in parietal cells although ouabain has been known to inhibit gastric acid secretion since 1962. The gastric H, K-ATPase (proton-pump) seems to be acting in altered states, thus behaving like a Na, K-ATPase (Na-pump) and/or Ca-ATPase (Ca-pump) depending on cellular needs.  This conclusion is based on the following findings. First, parietal cell fractions do not exhibit Na, K-ATPase activity at pH 7.0 but do at pH 8.5. Second, the apical plasma membrane (APM) fraction exhibits a (Ca or Mg)-ATPase activity with negligible H, K-ATPase activity. However, when assayed with Mg alone in presence of the 80 k Da cytosolic proton-pump activator (HAF), the APM fraction reveals remarkably high H, K-ATPase activity, suggesting the observed low affinity of Ca (or Mg)-ATPase is an altered state of the latter. Third, calcium (between 1 and 4 µM) shows both stimulation and inhibition of the HAF-stimulated H, K-ATPase depending on its concentration, revealing a close interaction between the  proton-pump activator and local Ca concentration in gastric H, K-ATPase function. Such interactions suggest that Ca is acting as a terminal member of the intracellular signaling system for the HAF-regulated proton-pump. It appears that during resting state, the HAF-associated H, K-ATPase remains inhibited by Ca (>1 µM) and, prior to resumption of acid secretion the gastric H, K-ATPase acts temporarily as a Ca-pump for removing excess Ca from its immediate environment. This conclusion is consistent with the recent reports of immunochemical co-localization of the gastric H, K-ATPase and Ca-ATPase by superimposition in parietal cells, and a transitory efflux of Ca immediately preceding the onset of acid secretion. These new perspectives on proton-pump function would open new avenues for a fuller understanding of the intracellular regulation of the ubiquitous Na-pump.
Multivariate spectral multipliers for the Dunkl transform and the Dunkl harmonic oscillator
Authors: Wróbel Błażej
Published: September 2013

In the case

G
=

ℤ
2
d

$G=\mathbb {Z}_2^d$

, we prove a multivariate Marcinkiewicz-type multiplier theorem for the Dunkl transform and a multivariate Marcinkiewicz-type multiplier theorem for the system of Dunkl harmonic oscillators.
Subgroups which admit extensions of homomorphisms
Authors: Breaz Simion , Călugăreanu Grigore , Schultz Phill
Published: September 2013

We classify by numerical invariants the finite subgroups H of a
primary abelian group G for which every homomorphism or
monomorphism of H into G, or every endomorphism of H,
extends to an endomorphism of G. We apply these results to show
that for finitely generated subgroups of general abelian groups,
the extendibility of monomorphisms implies the extendibility of
all homomorphisms.
Analyse der Regelungsstrategien eines Osteotomie-Instruments auf Basis multimodaler Informationen / Analysis of the Control Strategies of an Instrument for Osteotomy on the Basis of Multimodal Information
Authors: Korff Alexander , Müller Meiko , Follmann Axel , Kaphengst Felix , Habor Daniel , Kellermann Christoph , Radermacher Klaus
Published: September 2013

Um den Chirurgen bei der Eröffnung des Schädels in der Neurochirurgie oder des Brustbeins in der Herz- und Thoraxchirurgie zu unterstützen, wurde ein semiautomatisches, handgeführtes Sägeinstrument entwickelt. Die Schnitttiefe wird auf Basis von drei unterschiedlichen Messverfahren (Computertomographie, Ultraschall, Licht) automatisch geregelt. Nach erfolgreichen Machbarkeitsstudien zu den einzelnen Ansätzen wird in diesem Beitrag darauf aufbauend ein detaillierter Vergleich der Verfahren mit einer Untersuchung der strukturellen Vor- und Nachteile sowie Optimierungspotentiale durchgeführt.
Seriell-Elastische Aktoren als Antrieb für aktive Orthesen / Serial-Elastic Actuators for Active Orthoses
Authors: Pott Peter P. , Müller Roman , Grün Markus , Konigorski Ulrich , Schlaak Helmut F.
Published: September 2013

Aktive Kniegelenkorthesen können eingesetzt werden, um älteren Menschen im Alltag ein selbstbestimmtes Leben im vertrauten Umfeld zu ermöglichen. Als Antrieb für solche Geräte erweisen sich seriell-elastische Antriebe (SEA) als vorteilhaft, da sie im engen Kontakt zum Menschen besser regelbar sind als direkt gekoppelte getriebeunterstützte DC-Motoren. Sie weisen darüber hinaus in vielen Fällen ein besseres Systemleistungsgewicht als fluidische Antriebe oder elektrodynamische Direktantriebe auf. Im Folgenden werden die Auswahl und Auslegung eines SEA für eine aktive Kniegelenkorthese, seine Regelung mit einem Zustandsregler sowie erste experimentelle Ergebnisse präsentiert und diese in den Stand der Technik eingeordnet.
Iterativ Lernende Regelung mit variabler Zykluslänge für FES-basierte Kompensation einer Fußheberschwäche / Iterative Learning Control with Variable Pass Length applied to FES-based Drop Foot Treatment
Authors: Seel Thomas , Schauer Thomas , Raisch Jörg
Published: September 2013

Mit funktioneller Elektrostimulation kann die Dorsalflexion des Fußes in der Schwungphase des Ganges unterstützt und dadurch eine Fußheberschwäche kompensiert werden. Um eine möglichst natürliche Fußwinkeltrajektorie zu generieren, wird eine iterativ lernende Regelung eingesetzt. Dieser Artikel betrachtet die Abhängigkeit eines verfrühten Aufsetzens des Fußes vom Stimulationsprofil des jeweiligen Schrittes und untersucht die sich daraus ergebende verkoppelte Lern- und Zykluslängendynamik. Dazu werden zunächst geeignete theoretische Konzepte diskutiert, anhand derer dann der Reglerentwurf erfolgt. Abschließend wird experimentell das erreichte Konvergenzverhalten untersucht.
Fast Food and Fun.
Authors: Zirfas Jörg
Published: September 2013

The text contrasts two eating situations and the sentimental values associated with each: the paper proposes that we can relate eating fast food primarily with present happiness, namely fun, while the traditional family meal is associated with satisfaction and a sense of well-being. Well-being has a stronger emphasis on the emotional dimension of the experience of more or less extensive states and developments of happiness; the concept of satisfaction targets more the cognitive factor of happiness, and fun is defined as an emotion which expresses individual self-determination and self-compliance. The fun in fast food involves the public, the individual experience and the character of the event; the well-being at the dining table involves privacy, duration and the social experience. A modern imperative is expressed in fast-food eating: Live your life now as a happy one: Eat it, be happy and show it!
Rite of Redemption.
Authors: Omori Hisako
Published: September 2013

Across Canada, people commemorate the lives of fallen soldiers by wearing red poppy flower pins for Remembrance Day on November 11. In recent years, Canadians have increasingly taken pride in the symbols used in Remembrance Day, such as poppy flowers and a poem called In Flanders Fields. The day celebrates the notions of sacrifice, belonging, and the nation state of Canada. Japanese Canadians also celebrate this holiday by wearing poppies and remembering the war dead. World War II, however, marked a turning point for the lives of second generation Japanese Canadians. The majority of them were interned in the “relocation camps” during the war years as “enemy aliens” irrespective of their Canadian citizenship status. This paper will describe a present-day Remembrance Day service held in a Japanese Canadian Christian congregation in Ontario, in which its veterans are remembered. The article argues that this ritual of remembrance reverses the historical and social location of Japanese Canadians from those who were the victims of the war to those who were contributors to it, enabling Japanese Canadians to assert their rightful position in Canadian society. This paper also includes a discussion of the author’s personal transformation of historical consciousness about World War II and being Japanese in Canada during this research.
Statistisch abgesicherte Interpretation von SPR-Biochipsignalen via SPRING / Statistically Verified SPR Data Analysis via SPRING
Authors: Krügener Sven , Hettwer Karina , Simon Kirsten , Uhlig Steffen
Published: September 2013

Für das Datenmanagement bei Messungen der Oberflächenplasmonresonanz (SPR) wurden neue mathematische Verfahren entwickelt und in die eigens entwickelte Software SPRING integriert. Die Software ermöglicht eine Auswertung von SPR-Messdaten und liefert statistisch abgesicherte Aussagen zur Charakterisierung molekularer Interaktionen. Versuchsparameter, Sensorgramme und die statistische Bewertung werden in einem umfangreichen Report zur Verfügung gestellt.
Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind study
Authors: Norenstedt Sophie , Pernow Ylva , Brismar Kerstin , Sääf Maria , Ekip Ayla , Granath Fredrik , Zedenius Jan , Nilsson Inga-Lena
Published: September 2013

Background

Vitamin D insufficiency may increase the risk for cardio metabolic disturbances in patients with primary hyperparathyroidism (PHPT).

Objective

To analyze the vitamin D status and indices of the metabolic syndrome in PHPT patients and the effect of vitamin D supplementation after parathyroid adenomectomy (PTX).

Design and methods

Double-blinded, randomized clinical trial (ClinicalTrials.gov Identifier: NCT00982722) performed at Karolinska University Hospital, Sweden, April 2008 to November 2011. One hundred and fifty consecutive patients with PHPT (119 women) were randomized after PTX, 75 to oral treatment with calcium carbonate 1000 mg daily and 75 to calcium carbonate 1000 mg and cholecalciferol 1600 IU daily over 12 months. Changes in metabolic profile and ambulatory blood pressure (BP) were analyzed. Main outcome measures were changes in metabolic factors, BP, and body composition.

Results

The 25-hydroxyvitamin D (25-OH-D)-level was <50 nmol/l in 76% of the patients before PTX. After PTX, glucose, insulin, and IGF1 decreased, while the 25-OH-D and the IGF-binding protein 1 increased and remained unchanged at follow-up after study medication. One year of vitamin D supplementation resulted in lower parathyroid hormone (PTH) (40 (34–52) vs 49 (38–66) ng/l) and higher 25-OH-D (76 (65–93) vs 49 (40–62) nmol/l;P<0.05). Other laboratory parameters were stable compared with after PTX. Systolic BP decreased and total bone mineral content increased in both groups.

Conclusion

Except for the lowering of the PTH level, no additive effect of vitamin D supplementation was seen. However, PTX proved effective in reducing insulin resistance.
The thyroid cancer PAX8–PPARG fusion protein activates Wnt/TCF-responsive cells that have a transformed phenotype
Authors: Vu-Phan Dang , Grachtchouk Vladimir , Yu Jingcheng , Colby Lesley A , Wicha Max S , Koenig Ronald J
Published: September 2013

A chromosomal translocation results in the production of a paired box 8–peroxisome proliferator-activated receptor gamma (PAX8–PPARG) fusion protein (PPFP) in ∼35% of follicular thyroid carcinomas. To examine the role of PPFP in thyroid oncogenesis, the fusion protein was stably expressed in the non-transformed rat thyroid cell line PCCL3. PPFP conferred on PCCL3 cells the ability to invade through Matrigel and to form colonies in anchorage-independent conditions. PPFP also increased the fraction of cells with Wnt/TCF-responsive green fluorescent protein reporter gene expression. This Wnt/TCF-activated population was enriched for colony-forming and invading cells. These actions of PPFP required a functional PPARG DNA binding domain (DBD) within PPFP and were further stimulated by PPARG agonists. These data indicate that PPFP, through its PPARG DBD, induces Wnt/TCF pathway activation in a subpopulation of cells, and these cells have properties of cellular transformation including increased invasiveness and anchorage-independent growth.
Analysis of Allele-Specific Expression in Mouse Liver by RNA-Seq: A Comparison With Cis-eQTL Identified Using Genetic Linkage
Authors: Lagarrigue Sandrine , Martin Lisa , Hormozdiari Farhad , Roux Pierre-François , Pan Calvin , van Nas Atila , Demeure Olivier , Cantor Rita , Ghazalpour Anatole , Eskin Eleazar , Lusis Aldons J
Published: September 2013

We report an analysis of allele-specific expression (ASE) and parent-of-origin expression in adult mouse liver using next generation sequencing (RNA-Seq) of reciprocal crosses of heterozygous F1 mice from the parental strains C57BL/6J and DBA/2J. We found a 60% overlap between genes exhibiting ASE and putative cis-acting expression quantitative trait loci (cis-eQTL) identified in an intercross between the same strains. We discuss the various biological and technical factors that contribute to the differences. We also identify genes exhibiting parental imprinting and complex expression patterns. Our study demonstrates the importance of biological replicates to limit the number of false positives with RNA-Seq data.
Phylogenies of Central Element Proteins Reveal the Dynamic Evolutionary History of the Mammalian Synaptonemal Complex: Ancient and Recent Components
Authors: Fraune Johanna , Brochier-Armanet Céline , Alsheimer Manfred , Benavente Ricardo
Published: September 2013

During meiosis, the stable pairing of the homologous chromosomes is mediated by the assembly of the synaptonemal complex (SC). Its tripartite structure is well conserved in Metazoa and consists of two lateral elements (LEs) and a central region (CR) that in turn is formed by several transverse filaments (TFs) and a central element (CE). In a previous article, we have shown that not only the structure, but also the major structural proteins SYCP1 (TFs) and SYCP3 (LEs) of the mammalian SC are conserved in metazoan evolution. In continuation of this work, we now investigated the evolution of the mammalian CE-specific proteins using phylogenetic and biochemical/cytological approaches. In analogy to the observations made for SYCP1 and SYCP3, we did not detect homologs of the mammalian CE proteins in insects or nematodes, but in several other metazoan clades. We were able to identify homologs of three mammalian CE proteins in several vertebrate and invertebrate species, for two of these proteins down to the basal-branching phylum of Cnidaria. Our approaches indicate that the SC arose only once, but evolved dynamically during diversification of Metazoa. Certain proteins appear to be ancient in animals, but successive addition of further components as well as protein loss and/or replacements have also taken place in some lineages.
Simojovelhyus is a peccary, not a helohyid (Mammalia, Artiodactyla)
Authors: Prothero Donald R. , Beatty Brian L. , Stucky Richard M.
Published: September 2013

Simojovelhyus pocitosense is based on a lower jaw fragment with three molars from the late Oligocene amber mine deposits near the village of Simojovel, Chiapas Province, Mexico. It is the oldest fossil mammal known from Central America. It was described by Ferrusquia-Villafranca in 2006 as a helohyid, a group of primitive artiodactyls known from the Bridgerian and Uintan (older than 49–42 Ma), yet it comes from early Arikareean deposits about 25–27 Ma, suggesting that it was a very late helohyid living more than 10 m.y. after their apparent Uintan extinction. We re-examined the specimen, and compared it to the large collection of recently described peccaries from the Chadronian (Perchoerus minor) and Orellan (Perchoerus nanus) and Bridgerian helohyids (Helohyus sp.). Once the range of variation of characters in helohyids and peccaries is accounted for, Simojovelhyus shows derived similarities to early peccaries, especially in the bunodont molars with inflated cusps and the configuration of cristids and accessory cuspulids, and none of the incipient lophodonty and primitive morphology seen in helohyids. In fact, the only real similarity other than symplesiomorphies between Simojovelhyus and helohyids is its small size, but it is close to the size range of the tiny Chadronian peccary P. minor. Thus, based on both derived tooth characters and its age, it is much more parsimonious to regard Simojovelhyus as a tiny Mexican peccary from the Arikareean, not a very late helohyid. This removes the anomalously late occurrence of helohyids from the mammalian fossil record, and forces a re-examination of our view of mammalian evolution in Central America.