bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic development of the first synapse impinging on adult-born neurons in the olfactory bulb circuit
Authors: Katagiri Hiroyuki , Pallotto Marta , Nissant Antoine , Murray Kerren , Sassoè-Pognetto Marco , Lledo Pierre-Marie 
Published: February 2011

Abstract
The olfactory bulb (OB) receives and integrates newborn interneurons throughout life. This process is important for the proper functioning of the OB circuit and consequently, for the sense of smell. Although we know how these new interneurons are produced, the way in which they integrate into the pre-existing ongoing circuits remains poorly documented. Bearing in mind that glutamatergic inputs onto local OB interneurons are crucial for adjusting the level of bulbar inhibition, it is important to characterize when and how these inputs from excitatory synapses develop on newborn OB interneurons. We studied early synaptic events that lead to the formation and maturation of the first glutamatergic synapses on adult-born granule cells (GCs), the most abundant subtype of OB interneuron. Patch-clamp recordings and electron microscopy (EM) analysis were performed on adult-born interneurons shortly after their arrival in the adult OB circuits. We found that both the ratio of N-methyl-D-aspartate receptor (NMDAR) to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and the number of functional release sites at proximal inputs reached a maximum during the critical period for the sensory-dependent survival of newborn cells, well before the completion of dendritic arborization. EM analysis showed an accompanying change in postsynaptic density shape during the same period of time. Interestingly, the latter morphological changes disappeared in more mature newly-formed neurons, when the NMDAR to AMPAR ratio had decreased and functional presynaptic terminals expressed only single release sites. Together, these findings show that the first glutamatergic inputs to adult-generated OB interneurons undergo a unique sequence of maturation stages.
IIb or not IIb? Regulation of myosin heavy chain gene expression in mice and men
Authors: Harrison Brooke C , Allen David L , Leinwand Leslie A 
Published: February 2011

Abstract

Background
While the myosin heavy chain IIb isoform (MyHC-IIb) is the predominant motor protein in most skeletal muscles of rats and mice, the messenger RNA (mRNA) for this isoform is only expressed in a very small subset of specialized muscles in adult large mammals, including humans.

Results
We identify the DNA sequences limiting MyHC-IIb expression in humans and explore the activation of this gene in human skeletal muscle. We demonstrate that the transcriptional activity of ~1.0 kb of the human MyHC-IIb promoter is greatly reduced compared to that of the corresponding mouse sequence in both mouse and human myotubes in vitro and show that nucleotide differences that eliminate binding sites for myocyte enhancer factor 2 (MEF2) and serum response factor (SRF) account for this difference. Despite these differences, we show that MyHC-IIb mRNA is expressed in fetal human muscle cells and that MyHC-IIb mRNA is significantly up-regulated in the skeletal muscle of Duchene muscular dystrophy patients.

Conclusions
These data identify the genetic basis for a key phenotypic difference between the muscles of large and small mammals, and demonstrate that mRNA expression of the MyHC-IIb gene can be re-activated in human limb muscle undergoing profound degeneration/regeneration.
Mannose-binding lectin does not explain the course and outcome of pregnancy in rheumatoid arthritis
Authors: van de Geijn Fleur E , de Man Yaël A , Wuhrer Manfred , Willemsen Sten P , Deelder André M , Hazes Johanna MW , Dolhain Radboud JEM 
Published: February 2011

Abstract
Introduction
Rheumatoid arthritis (RA) improves during pregnancy and flares after delivery. It has been hypothesized that high levels of the complement factor mannose-binding lectin (MBL) are associated with a favourable disease course of RA by facilitating the clearance of pathogenic immunoglobulin G (IgG) lacking galactose sugar moieties. During pregnancy, increased galactosylation of IgG and simultaneously increased MBL levels can be observed, with the latter being strictly related to maternal MBL genotypes. Therefore, increased MBL levels in concert with increased IgG galactosylation may be associated with pregnancy-induced improvement of RA. The objective of this study was to investigate whether MBL genotypes are associated with changes in RA disease activity and with changes in IgG galactosylation during pregnancy and in the postpartum period. We also studied the association between MBL genotypes and pregnancy outcomes in RA.

Methods
Serum from 216 patients with RA and 31 healthy controls participating in the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) Study was collected before, during and after pregnancy. IgG galactosylation was determined by performing matrix-assisted laser desorption/ionization time of flight mass spectrometry. Disease activity was determined using the internationally recognized Disease Activity Score 28 (DAS28). MBL genotypes were determined. The pregnancy outcome measures studied were gestational age, birth weight, miscarriage and hypertensive disorders.

Results
No association was found between the MBL genotype groups and changes in RA disease activity (P = 0.89) or changes in IgG galactosylation (patients, P = 0.75, and controls, P = 0.54) during pregnancy and in the postpartum period. Furthermore, MBL genotype groups were not related to the studied pregnancy outcome measures.

Conclusions
This study does not provide evidence for a role for MBL in the improvement of RA during pregnancy or for a role for MBL in pregnancy outcome.
A polymorphism in the interleukin-4 receptor affects the ability of interleukin-4 to regulate Th17 cells: a possible immunoregulatory mechanism for genetic control of the severity of rheumatoid arthritis
Authors: Wallis Susan K , Cooney Laura A , Endres Judith L , Lee Min Jie , Ryu Jennifer , Somers Emily C , Fox David A 
Published: February 2011

Abstract
Introduction
Rheumatoid arthritis (RA) is now suspected to be driven by pathogenic Th17 cells that secrete interleukin (IL)-17 and can be regulated by IL-4. A single-nucleotide polymorphism (SNP), I50V, in the coding region of the human IL-4 receptor (IL-4R) is associated with rapid development of erosive disease in RA. The present study was undertaken to determine whether this SNP renders the IL-4R less able to transduce signals that regulate IL-17 production.

Methods
Peripheral blood mononuclear cells were activated under Th17-stimulating conditions in the presence or absence of IL-4, and IL-17 production was measured by both enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Serum IL-17 was also measured by ELISA. Paired comparisons were performed using the two-tailed t-test. IL-4 receptor gene alleles were determined by polymerase chain reaction.

Results
In healthy individuals, IL-4 significantly inhibited IL-17 production by cells from subjects with the I/I genotype (P = 0.0079) and the I/V genotype (P = 0.013), but not the V/V genotype (P > 0.05). In a cross-sectional sample of patients with established RA, the magnitude of the in vitro effect of IL-4 was lower and was not associated with a specific IL-4R allele. Serum IL-17 levels were higher in RA patients than in healthy individuals, as was the percentage of CD4+ cells that produced IL-17.

Conclusions
These results indicate that an inherited polymorphism of the IL-4R controls the ability of the human immune system to regulate the magnitude of IL-17 production. However, in established RA, this pattern may be altered, possibly due to secondary effects of both RA itself as well as immunomodulatory medications. Ineffective control of Th17 immune responses is a potential mechanism to explain why IL-4R is an important severity gene in RA, but this issue will require careful study of a cohort of new-onset RA patients.
Knockdown of miR-21 in human breast cancer cell lines inhibits proliferation, in vitro migration and in vivotumor growth
Authors: Yan Li Xu , Wu Qi Nian , Zhang Yan , Li Yang Yang , Liao Ding Zhun , Hou Jing Hui , Fu Jia , Zeng Mu Sheng , Yun Jing Ping , Wu Qiu Liang , Zeng Yi Xin , Shao Jian Yong 
Published: February 2011

Abstract
Introduction
MicroRNAs (miRNAs) are a class of small non-coding RNAs (20 to 24 nucleotides) that post-transcriptionally modulate gene expression. A key oncomir in carcinogenesis is miR-21, which is consistently up-regulated in a wide range of cancers. However, few functional studies are available for miR-21, and few targets have been identified. In this study, we explored the role of miR-21 in human breast cancer cells and tissues, and searched for miR-21 targets.

Methods
We used in vitro and in vivo assays to explore the role of miR-21 in the malignant progression of human breast cancer, using miR-21 knockdown. Using LNA silencing combined to microarray technology and target prediction, we screened for potential targets of miR-21 and validated direct targets by using luciferase reporter assay and Western blot. Two candidate target genes (EIF4A2 and ANKRD46) were selected for analysis of correlation with clinicopathological characteristics and prognosis using immunohistochemistry on cancer tissue microrrays.

Results
Anti-miR-21 inhibited growth and migration of MCF-7 and MDA-MB-231 cells in vitro, and tumor growth in nude mice. Knockdown of miR-21 significantly increased the expression of ANKRD46 at both mRNA and protein levels. Luciferase assays using a reporter carrying a putative target site in the 3' untranslated region of ANKRD46 revealed that miR-21 directly targeted ANKRD46. miR-21 and EIF4A2 protein were inversely expressed in breast cancers (rs = -0.283, P = 0.005, Spearman's correlation analysis).

Conclusions
Knockdown of miR-21 in MCF-7 and MDA-MB-231 cells inhibits in vitro and in vivo growth as well as in vitro migration. ANKRD46 is newly identified as a direct target of miR-21 in BC. These results suggest that inhibitory strategies against miR-21 using peptide nucleic acids (PNAs)-antimiR-21 may provide potential therapeutic applications in breast cancer treatment.
Tumor-specific HMG-CoA reductase expression in primary premenopausal breast cancer predicts response to tamoxifen
Authors: Brennan Donal J , Laursen Henriette , O'Connor Darran P , Borgquist Signe , Uhlen Mathias , Gallagher William M , Pontén Fredrik , Millikan Robert C , Rydén Lisa , Jirström Karin 
Published: February 2011

Abstract
Introduction
We previously reported an association between tumor-specific 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) expression and a good prognosis in breast cancer. Here, the predictive value of HMG-CoAR expression in relation to tamoxifen response was examined.

Methods
HMG-CoAR protein and RNA expression was analyzed in a cell line model of tamoxifen resistance using western blotting and PCR. HMG-CoAR mRNA expression was examined in 155 tamoxifen-treated breast tumors obtained from a previously published gene expression study (Cohort I). HMG-CoAR protein expression was examined in 422 stage II premenopausal breast cancer patients, who had previously participated in a randomized control trial comparing 2 years of tamoxifen with no systemic adjuvant treatment (Cohort II). Kaplan-Meier analysis and Cox proportional hazards modeling were used to estimate the risk of recurrence-free survival (RFS) and the effect of HMG-CoAR expression on tamoxifen response.

Results
HMG-CoAR protein and RNA expression were decreased in tamoxifen-resistant MCF7-LCC9 cells compared with their tamoxifen-sensitive parental cell line. HMG-CoAR mRNA expression was decreased in tumors that recurred following tamoxifen treatment (P < 0.001) and was an independent predictor of RFS in Cohort I (hazard ratio = 0.63, P = 0.009). In Cohort II, adjuvant tamoxifen increased RFS in HMG-CoAR-positive tumors (P = 0.008). Multivariate Cox regression analysis demonstrated that HMG-CoAR was an independent predictor of improved RFS in Cohort II (hazard ratio = 0.67, P = 0.010), and subset analysis revealed that this was maintained in estrogen receptor (ER)-positive patients (hazard ratio = 0.65, P = 0.029). Multivariate interaction analysis demonstrated a difference in tamoxifen efficacy relative to HMG-CoAR expression (P = 0.05). Analysis of tamoxifen response revealed that patients with ER-positive/HMG-CoAR tumors had a significant response to tamoxifen (P = 0.010) as well as patients with ER-positive or HMG-CoAR-positive tumors (P = 0.035). Stratification according to ER and HMG-CoAR status demonstrated that ER-positive/HMG-CoAR-positive tumors had an improved RFS compared with ER-positive/HMG-CoAR-negative tumors in the treatment arm (P = 0.033); this effect was lost in the control arm (P = 0.138), however, suggesting that HMG-CoAR predicts tamoxifen response.

Conclusions
HMG-CoAR expression is a predictor of response to tamoxifen in both ER-positive and ER-negative disease. Premenopausal patients with tumors that express ER or HMG-CoAR respond to adjuvant tamoxifen.
Pathophysiological aspects of hyperglycemia in children with meningococcal sepsis and septic shock: a prospective, observational cohort study
Authors: Verhoeven Jennifer J , den Brinker Marieke , Hokken-Koelega Anita CS , Hazelzet Jan A , Joosten Koen FM 
Published: February 2011

Abstract
Introduction
The objective of this study was to investigate the occurrence of hyperglycemia and insulin response in critically ill children with meningococcal disease in the intensive care unit of an academic children's hospital.

Methods
Seventy-eight children with meningococcal disease were included. The group was classified into shock non-survivors, shock survivors and sepsis survivors. There were no sepsis-only non-survivors. The course of laboratory parameters during 48 hours was assessed. Insulin sensitivity and β-cell function on admission were investigated by relating blood glucose level to insulin level and C-peptide level and by homeostasis model assessment (HOMA) [β-cell function (HOMA-%B) and insulin sensitivity (HOMA-%S)].

Results
On admission, hyperglycemia (glucose >8.3 mmol/l) was present in 33% of the children. Shock and sepsis survivors had higher blood glucose levels compared with shock non-survivors. Blood glucose level on admission correlated positively with plasma insulin, C-peptide, cortisol, age and glucose intake. Multiple regression analysis revealed that both age and plasma insulin on admission were significantly related to blood glucose. On admission, 62% of the hyperglycemic children had overt insulin resistance (glucose >8.3 mmol/l and HOMA-%S <50%); 17% had β-cell dysfunction (glucose >8.3 mmol/l and HOMA-%B <50%) and 21% had both insulin resistance and β-cell dysfunction. Hyperglycemia was present in 11% and 8% of the children at 24 and 48 hours after admission, respectively.

Conclusions
Children with meningococcal disease often show hyperglycemia on admission. Both insulin resistance and β-cell dysfunction play a role in the occurrence of hyperglycemia. Normalization of blood glucose levels occurs within 48 hours, typically with normal glucose intake and without insulin treatment.
Administration of hydrogen sulfide via extracorporeal membrane lung ventilation in sheep with partial cardiopulmonary bypass perfusion: a proof of concept study on metabolic and vasomotor effects
Authors: Derwall Matthias , Francis Roland CE , Kida Kotaro , Bougaki Masahiko , Crimi Ettore , Adrie Christophe , Zapol Warren M , Ichinose Fumito 
Published: February 2011

Abstract
Introduction
Although inhalation of 80 parts per million (ppm) of hydrogen sulfide (H2S) reduces metabolism in mice, doses higher than 200 ppm of H2S were required to depress metabolism in rats. We therefore hypothesized that higher concentrations of H2S are required to reduce metabolism in larger mammals and humans. To avoid the potential pulmonary toxicity of H2S inhalation at high concentrations, we investigated whether administering H2S via ventilation of an extracorporeal membrane lung (ECML) would provide means to manipulate the metabolic rate in sheep.

Methods
A partial venoarterial cardiopulmonary bypass was established in anesthetized, ventilated (fraction of inspired oxygen = 0.5) sheep. The ECML was alternately ventilated with air or air containing 100, 200, or 300 ppm H2S for intervals of 1 hour. Metabolic rate was estimated on the basis of total CO2 production (

V
˙

CO

2

) and O2 consumption (

V
˙

O

2

). Continuous hemodynamic monitoring was performed via indwelling femoral and pulmonary artery catheters.

Results

V
˙

CO

2

,

V
˙

O

2

, and cardiac output ranged within normal physiological limits when the ECML was ventilated with air and did not change after administration of up to 300 ppm H2S. Administration of 100, 200 and 300 ppm H2S increased pulmonary vascular resistance by 46, 52 and 141 dyn·s/cm5, respectively (all P ≤ 0.05 for air vs. 100, 200 and 300 ppm H2S, respectively), and mean pulmonary artery pressure by 4 mmHg (P ≤ 0.05), 3 mmHg (n.s.) and 11 mmHg (P ≤ 0.05), respectively, without changing pulmonary capillary wedge pressure or cardiac output. Exposure to 300 ppm H2S decreased systemic vascular resistance from 1,561 ± 553 to 870 ± 138 dyn·s/cm5 (P ≤ 0.05) and mean arterial pressure from 121 ± 15 mmHg to 66 ± 11 mmHg (P ≤ 0.05). In addition, exposure to 300 ppm H2S impaired arterial oxygenation (PaO2 114 ± 36 mmHg with air vs. 83 ± 23 mmHg with H2S; P ≤ 0.05).

Conclusions
Administration of up to 300 ppm H2S via ventilation of an extracorporeal membrane lung does not reduce

V
˙

CO

2

and

V
˙

O

2

, but causes dose-dependent pulmonary vasoconstriction and systemic vasodilation. These results suggest that administration of high concentrations of H2S in venoarterial cardiopulmonary bypass circulation does not reduce metabolism in anesthetized sheep but confers systemic and pulmonary vasomotor effects.
Transthoracic echocardiography for the diagnosis of left ventricular thrombosis in the postoperative care unit
Authors: Saranteas Theodosios , Alevizou Anastasia , Tzoufi Maria , Panou Fotios , Kostopanagiotou Georgia 
Published: February 2011

Abstract
Introduction
Transthoracic echocardiography (TTE) is a reliable, noninvasive imaging method that is useful in the evaluation of cardiovascular thrombosis. We conducted a retrospective study of all the echocardiograms from patients in the postoperative care unit to assess the role of TTE in thrombus identification in the left ventricle.

Methods
This retrospective database evaluation included all echocardiograms during a 14-month period. The echocardiographic examination protocol included the subcostal four-chamber view, the apical four-chamber view, the apical two-chamber view and the parasternal view, along the long and short axes in both spontaneously and mechanically ventilated patients. All echocardiograms were obtained within the 48 hours immediately following surgery.

Results
In total, 160 postoperative echocardiograms were obtained from 160 patients and resulted in the detection of five cases of left ventricular thrombosis. Subgroup analysis showed that 21 and 35 of the 160 patients examined had either dilated or ischemic cardiomyopathy, respectively. In these patients, preoperative echocardiograms had been obtained recently prior to surgery and were negative for left ventricular thrombus. In three of 35 patients with ischemic cardiomyopathy and two of 21 patients with dilated cardiomyopathy, thrombus was identified in the left ventricle. The thrombi were mobile, uncalcified and pedunculated and were located in the apex of the left ventricle. In addition, no clinical consequences of the left ventricular thrombi were recorded.

Conclusions
Low-flow conditions in heart chambers due to ischemic or dilated cardiomyopathy in conjunction with the hypercoagulability caused by perioperative prothrombotic factors may lead to thrombotic events in the left ventricle.
Availability of critical care resources to treat patients with severe sepsis or septic shock in Africa: a self-reported, continent-wide survey of anaesthesia providers
Authors: Baelani Inipavudu , Jochberger Stefan , Laimer Thomas , Otieno Dave , Kabutu Jane , Wilson Iain , Baker Tim , Dünser Martin W 
Published: February 2011

Abstract
Introduction
It is unknown whether resources necessary to implement the Surviving Sepsis Campaign guidelines and sepsis bundles are available in Africa. This self-reported, continent-wide survey compared the availability of these resources between African and high-income countries, and between two African regions (Sub-Sahara Africa vs. South Africa, Mauritius and the Northern African countries).

Methods
The study was conducted as an anonymous questionnaire-based, cross-sectional survey among anaesthesia providers attending a transcontinental congress. Based on the respondents' country of practice, returned questionnaires were grouped into African and high-income countries. The questionnaire contained 74 items and evaluated all material resources required to implement the most recent Surviving Sepsis Campaign guidelines. Group comparisons were performed with the Chi2, Fisher's Exact or Mann Whitney U test, as appropriate.

Results
The overall response rate was 74.3% (318/428). Three-hundred-seven questionnaires were analysed (African countries, n = 263; high-income countries, n = 44). Respondents from African hospitals were less likely to have an emergency room (85.5 vs. 97.7%, P = 0.03) or intensive care unit (73.8 vs. 100%, P < 0.001) than respondents from high-income countries. Drugs, equipment, and disposable materials required to implement the Surviving Sepsis Campaign guidelines or sepsis bundles were less frequently available in African than high-income countries. Of all African and Sub-Saharan African countries, 1.5% (4/263) and 1.2% (3/248) of respondents had the resources available to implement the Surviving Sepsis Campaign guidelines in entirety. The percentage of implementable recommendations was lower in African than in high-income countries (72.6 (57.7 to 87.7)% vs. 100 (100 to 100)%, P < 0.001) and lower in Sub-Saharan African countries than South Africa, Mauritius, and the Northern African countries (72.6 (56.2 to 86.3)% vs. 90.4 (71.2 to 94.5)%, P = 0.02).

Conclusions
The results of this self-reported survey strongly suggest that the most recent Surviving Sepsis guidelines cannot be implemented in Africa, particularly not in Sub-Saharan Africa, due to a shortage of required hospital facilities, equipment, drugs and disposable materials. However, availability of resources to implement the majority of strong Surviving Sepsis Campaign recommendations and the sepsis bundles may allow modification of current sepsis guidelines based on available resources and implementation of a substantial number of life-saving interventions into sepsis care in Africa.