bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct roles of GABAB1a‐ and GABAB1b‐containing GABAB receptors in spontaneous and evoked termination of persistent cortical activity
Authors: Craig Michael T. , Mayne Elizabeth W. , Bettler Bernhard , Paulsen Ole , McBain Chris J. 
Published: December 2012

Key points
GABAB receptors containing the GABAB1a subunit contribute to spontaneous termination of UP states.
GABAB receptors containing the GABAB1b subunit are essential for afferent‐evoked termination of UP states.
Abstract  During slow‐wave sleep, cortical neurons display synchronous fluctuations between periods of persistent activity (‘UP states’) and periods of relative quiescence (‘DOWN states’). Such UP and DOWN states are also seen in isolated cortical slices. Recently, we reported that both spontaneous and evoked termination of UP states in slices from the rat medial entorhinal cortex (mEC) involves GABAB receptors. Here, in order to dissociate the roles of GABAB1a‐ and GABAB1b‐containing receptors in terminating UP states, we used mEC slices from mice in which either the GABAB1a or the GABAB1b subunit had been genetically ablated. Pharmacological blockade of GABAB receptors using the antagonist CGP55845 prolonged the UP state duration in both wild‐type mice and those lacking the GABAB1b subunit, but not in those lacking the GABAB1a subunit. Conversely, electrical stimulation of layer 1 could terminate an ongoing UP state in both wild‐type mice and those lacking the GABAB1a subunit, but not in those lacking the GABAB1b subunit. Together with previous reports, indicating a preferential presynaptic location of GABAB1a‐ and postsynaptic location of GABAB1b‐containing receptors, these results suggest that presynaptic GABAB receptors contribute to spontaneous DOWN state transitions, whilst postsynaptic GABAB receptors are essential for the afferent termination of the UP state. Inputs to layer 1 from other brain regions could thus provide a powerful mechanism for synchronizing DOWN state transitions across cortical areas via activation of GABAergic interneurons targeting postsynaptic GABAB receptors.
α1A‐Adrenergic regulation of inhibition in the olfactory bulb
Authors: Zimnik Nathan C. , Treadway Tyler , Smith Richard S. , Araneda Ricardo C. 
Published: December 2012

Key points
Here, in mouse brain slices, we examined the cellular effects of noradrenaline to better understand its influence on olfactory bulb processing.
β‐ and α1‐adrenergic receptor activation increases GABA currents in mitral cells in an age‐dependent manner; the β‐adrenergic effect is prominent only during early postnatal weeks, while the α1 effect is present at all ages.
This study focused on the α1‐mediated increase in GABA inhibitory currents in mitral cells and found noradrenaline acts on the α1A‐adrenergic receptor subtype to produce long‐lasting excitation of granule cells.
The enhancement of inhibition by noradrenaline was consistent across a broad concentration range; at all concentrations, noradrenaline increased inhibitory currents in mitral cells.
Our studies highlight the important role of α1A‐adrenergic receptor subtypes in increasing inhibition at dendrodendritic synapses, suggesting a synaptic mechanism for noradrenergic modulation of olfactory driven behaviours.
Abstract  By regulating inhibition at dendrodendritic synapses between mitral and granule cells (GCs), noradrenergic neurons extending from the brainstem provide an input essential for odour processing in the olfactory bulb (OB). In the accessory OB (AOB), we have recently shown that noradrenaline (NA) increases GABA inhibitory input on to mitral cells (MCs) by exciting GCs. Here, we show that GCs in the main OB (MOB) exhibit a similar response to NA, indicating a common mechanism for noradrenergic regulation of GC→MC inhibition throughout the OB. In GCs of the MOB, NA (10 μm) produced a robust excitatory effect that included a slow afterdepolarization that followed a train of action potentials evoked by a current stimulus. The depolarization and slow afterdepolarization in GCs were blocked by the α1A‐adrenergic receptor (AR) selective antagonist WB 4101 (30 nm) and mimicked by the α1A‐AR selective agonist A 61603 (1 μm). In recordings from MCs, A 61603 (30 nm–1 μm) produced a sizeable increase in the frequency of spontaneous and miniature IPSCs, an effect completely abolished by the GABAA receptor antagonist gabazine (5 μm). Likewise, activation of β‐ARs increased the frequency of spontaneous IPSCs; however, this effect was smaller and confined to the first postnatal weeks. NA enhanced inhibition in MCs across a broad concentration range (0.1–30 μm) and its effects were completely abolished by a mixture of α1‐ and β‐AR antagonists (1 μm prazosin and 10 μm propranolol). Furthermore, the general α2‐AR agonist clonidine (10 μm) failed to affect sIPSC frequency. Thus, the NA‐mediated increase in GC→MC inhibition in the OB results mostly from activation of the α1A‐AR subtype.
Sparing of muscle mass and function by passive loading in an experimental intensive care unit model
Authors: Renaud Guillaume , Llano‐Diez Monica , Ravara Barbara , Gorza Luisa , Feng Han‐Zhong , Jin Jian‐Ping , Cacciani Nicola , Gustafson Ann‐Marie , Ochala Julien , Corpeno Rebeca , Li Meishan , Hedström Yvette , Ford G. Charles , Nair K. Sreekumaran , Larsson Lars 
Published: December 2012

Key points
Early physical mobilization of mechanically ventilated intensive care unit (ICU) patients can reduce the length of stay in the ICU and hospital and improve muscle strength and functional outcomes.
A unique experimental rat ICU model has been used to study the effects and underlying mechanisms of unilateral passive mechanical loading on skeletal muscle size and function at durations varying between 6 h and 2 weeks.
Passive mechanical loading attenuated the loss of muscle mass and force‐generation capacity associated with the ICU intervention.
The maintained muscle mass and function by passive loading is probably due to lower oxidative stress and a reduced loss of the molecular motor protein myosin.
The beneficial effects of passive mechanical loading on muscle size and function strongly support the importance of early and intense physical therapy in immobilized ICU patients.
Abstract  The response to mechanical stimuli, i.e. tensegrity, plays an important role in regulating cell physiological and pathophysiological function, and the mechanical silencing observed in intensive care unit (ICU) patients leads to a severe and specific muscle wasting condition. This study aims to unravel the underlying mechanisms and the effects of passive mechanical loading on skeletal muscle mass and function at the gene, protein and cellular levels. A unique experimental rat ICU model has been used allowing long‐term (weeks) time‐resolved analyses of the effects of standardized unilateral passive mechanical loading on skeletal muscle size and function and underlying mechanisms. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force‐generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded versus the unloaded muscles after a 2‐week ICU intervention. We demonstrate that the improved maintenance of muscle mass and function is probably a consequence of a reduced oxidative stress revealed by lower levels of carbonylated proteins, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading‐induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, extracellular matrix/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle size and function associated with the mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients.
A method to vectorize the dose distribution, the dose volume histogram and create a dose vector histogram
Authors: Mayo Charles S. , Zankowski Corey , Herman Michael , Miller Robert , Olivier Kenneth , Vincent Abhilash , Suominen Jukka 
Published: December 2012

Purpose:This paper outlines and demonstrates a programmatic method to incorporate spatial information into a dose volume histogram (DVH) by adding vector data on the location of pixels in the dose array relative to structures in the plan to construct a vectorized dose distribution (VDD). With this data the DVH can be subgrouped according to a wide array of vector constraint sets, defining the spatial relationship of pixels to one or several structures to construct a vectorized DVH (VDVH) to reveal vector relationships of dose regions to structures.Methods:Mathematical models for construction of the VDD and VDVH are described and a dose‐vector‐histogram (DVctH) is introduced as a means of specifying the location of dose features such as “hot spots.” Practical detail on a programmatic approach to implement the methods is provided. A set of tests utilizing phantom and SBRT lung image sets were carried out to demonstrate ability of VDVH and DVctH to reveal clinically relevant spatial detail in dose distributions.Results:The VDVH and DVctH enabled decomposing DVH curves to reveal the relative location of pixels contributing to dose points on the curve. The metrics enabled specificity in defining the location and magnitude of dose features relevant to treatment plan evaluation. The VDD, VDVH, and DVctH differ from other methods described in the literature as a result of using vector based constraints for each pixel, rather than focusing only on distance by construction of a set of shells on around or within a structure and then subgrouping pixels in the overlap region.Conclusions:The method is an effective means to combine spatial information with DVH metrics and provides a practical means of specifying the location of dose features with respect other structures in the treatment plan.
Nerve growth factor receptor (NGFR): a potential marker for specific molecular subtypes of breast cancer
Authors: Tsang Julia Y S , Wong Ken H Y , Lai Michael W H , Lacambra Maribel D , Ko Chun-Wai , Chan Siu Ki , Lam Christopher C F , Yu Alex M C , Tan Puay-Hoon , Tse Gary M 
Published: December 2012

AimsNerve growth factor receptor (NGFR) is a transmembrane receptor for the neurotrophin family. It acts either as tumour suppressor or oncogene depending on cellular context. Its role in breast cancers remained conflicting, possibly due to the heterogeneity of breast cancer subtypes.MethodsIn this study, we have analysed NGFR expression in 602 cases of breast cancers by immunohistochemistry. Its expression was correlated with biomarker expression and different breast cancer subtypes.ResultsNGFR expression was found to be positively correlated with basal markers, including Ki67, Cytokeratin (CK5/6), CK14, p63, c-kit and Epidermal growth factor receptor (EGFR) , but negatively with hormonal receptors. Among different molecular subtypes, it was negatively associated with luminal A, but positively with luminal B, and basal-like breast cancer BLBC subtypes. When comparing NGFR with other basal markers in BLBC, though less sensitive, its specificity was comparable to or better than other basal markers. For luminal B cancers, NGFR showed a high specificity which was also comparable to or better than the defining markers (estrogen receptor (ER), progesterone receptor (PR), Human epidermal growth receptor 2 (HER2) and Ki-67) for the subtype.ConclusionsOverall, these findings suggested that NGFR expression could be indicative for the BLBCs or luminal B subtypes. It may represent a potential adjunct marker for these two subtypes.
Gonadal malignancy in 13 consecutive collected patients with disorders of sex development (DSD) from Semarang (Indonesia)
Authors: Juniarto Achmad Zulfa , Setyawati Bestari A , Miranti Ika P , Santosa Ardy , Hersmus Remko , Stoop Hans , Cools Martine , Oosterhuis J Wolter , Drop Stenvert L S , Faradz Sultana M H , Looijenga Leendert H J 
Published: December 2012

AimsCaucasian patients with disorders of sex development (DSD) are at a high risk of developing germ cell cancer (GCC). GCC is prominent in young adults in Western countries, while the incidence is significantly lower in Asia. So far, the risk of GCC in Asian DSD patients is unknown.Methods and resultsA detailed study of gonad histology , morphology and immunohistochemistry (OCT3/4, testis-specific protein Y-encoded, VASA, SCF/KITLG, SOX9, FOXL2) of 16 Indonesian DSD patients was undertaken. 13 cases could be analysed, including ovarian tissue (n=3), streak gonad (n=1), undifferentiated gonad (n=1) and testicular tissue (n=8), diagnosed as 46, XX (n=1), 46, XY (n=7) and sex chromosome DSD (n=5). The precursor lesion gonadoblastoma or carcinoma in situ,or GCC was diagnosed in four cases (30.8%; three 46, XY and one sex chromosome DSD ). A hormone producing ovarian Leydig cell tumour was identified in a 46, XX patient, supposed to be a late onset congenital adrenal hyperplasia.ConclusionsIn spite of the significantly lower risk of GCC in the general Asian population, DSD is a dominant risk factor. The study demonstrates the power of immunohistochemical markers for (early) diagnosis. This knowledge will deepen understanding of the pathobiology of GCC and clinical handling of patients with DSD, globally.
Comparison of two antimicrobial regimens on the prevalence of incisional infections after colic surgery
Authors: Durward‐Akhurst S. A. , Mair T. S. , Boston R. , Dunkel B. 
Published: December 2012

Appropriate durations of perioperative antimicrobial therapy following exploratory coeliotomy in horses are controversial, and with the rising prevalence of multiresistant bacteria there is a strong incentive to use antimicrobials for the shortest time possible. Following exploratory coeliotomies, incisional infections are an important cause of morbidity in horses and could be influenced by the duration of systemic antimicrobial therapy. The aim of this study was to investigate whether 72 hours of perioperative antimicrobial therapy is as effective as 120 hours at preventing the development of postoperative incisional infections. Horses undergoing exploratory coeliotomy at two referral hospitals were assigned randomly into Group 1 (receiving 72 hours of perioperative antimicrobial therapy) and Group 2 (receiving 120 hours of perioperative antimicrobial therapy). Only horses recovering from surgery and surviving for >120 hours were included in the study. Ninety‐two horses met the criteria for inclusion in the study, 42 in Group 1 and 50 in Group 2. The overall incisional complication rate was 42.2 per cent, and no significant difference in the number of incisional complications in the two groups was identified. Results of the study suggest that there is no benefit in using 120 hours over 72 hours of perioperative antimicrobial therapy to prevent incisional infections.
LAMB WAVES IN A POROELASTIC PLATE
Authors: GILBERT ROBERT P. , LEE DOO-SUNG , OU M. YVONNE 
Published: December 2012

In this paper we consider the propagation of Lamb waves in a poroelastic plate containing a linear crack, the special case where the surface of the plate is unloaded, by employing the Wiener-Hopf technique. The problem we solve here is a mathematically interesting toy problem. Physically speaking the more reasonable problem would be to consider there to be fluid pressure on both sides of the plate. This problem can be solved using the solution we derive here and will be presented in a subsequent work. Also dealt in this paper are the characteristic equations for a viscous fluid Biot systems and the orthogonality relations for a free boundary poroelastic slab.
MnSOD Promotes Tumor Invasion via Upregulation of FoxM1–MMP2 Axis and Related with Poor Survival and Relapse in Lung Adenocarcinomas
Authors: Chen Po-Ming , Wu Tzu-Chin , Shieh Shwn-Huey , Wu Yi-Hui , Li Min-Chin , Sheu Gwo-Tarng , Cheng Ya-Wen , Chen Chih-Yi , Lee Huei 
Published: December 2012

Abstract
Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme responsible for the elimination of superoxide radical. The role of MnSOD in tumor progression in different human cancers is still controversial. In the present study, MnSOD expression in lung cancer cells was explored by knockdown or overexpression using transfection of a short hairpin RNA (shRNA) or an expression vector, respectively, to determine whether MnSOD expression mediates lung cancer cell migration, invasion, and oncogenic potential by increasing FoxM1 and MMP2 expression. Western blotting showed that FoxM1 and MMP2 expression was dependent on MnSOD expression, suggesting that FoxM1 could be upregulated by MnSOD. Three FoxM1 promoters were constructed to verify this activation of FoxM1 by MnSOD and to determine the transcription factors responsible. Luciferase reporter and chromatin immunoprecipitation assays indicated that MnSOD overexpression in lung cancer cells promoted binding of E2F1 and Sp1 to their putative FoxM1 promoter-binding sites and activated FoxM1 reporter activity. MnSOD also enhanced the potential for cell migration, invasion, and anchorage-independent colony growth on soft-agar plates, again via upregulation of FoxM1 and MMP2 expression. In patients with lung cancer, evaluation of MnSOD expression in lung tumors by immunohistochemistry indicated a positive correlation between FoxM1 and MMP2 mRNA expressions. Kaplan–Meier and Cox regression analysis revealed a poorer overall survival (OS) and relapse-free survival (RFS) in patients with MnSOD-positive tumors than with MnSOD-negative tumors. We conclude that MnSOD may promote tumor aggressiveness via upregulation of the FoxM1–MMP2 axis, and that MnSOD expression can independently predict survival and relapse in patients with resected lung adenocarcinoma. Mol Cancer Res; 11(3); 261–71. ©2012 AACR.
Quantitative Analysis of Mitral Valve Morphology in Mitral Valve Prolapse With Real-Time 3-Dimensional Echocardiography
Authors: Lee Alex Pui-Wai , Hsiung Ming C. , Salgo Ivan S. , Fang Fang , Xie Jun-Min , Zhang Yan-Chao , Lin Qing-Shan , Looi Jen-Li , Wan Song , Wong Randolph H.L. , Underwood Malcolm J. , Sun Jing-Ping , Yin Wei-Hsian , Wei Jeng , Tsai Shen-Kou , Yu Cheuk-Man 
Published: December 2012

Background—
Few data exist on the relation of the 3-dimensional morphology of mitral valve and degree of mitral regurgitation (MR) in mitral valve prolapse.

Methods and Results—

Real-time 3-dimensional transesophageal echocardiography of the mitral valve was acquired in 112 subjects, including 36 patients with mitral valve prolapse and significant MR (≥3+; MR+ group), 32 patients with mitral valve prolapse but no or mild MR (≤2+; MR− group), 12 patients with significant MR resulting from nonprolapse pathologies (nonprolapse group), and 32 control subjects. The 3-dimensional geometry of mitral valve apparatus was measured with dedicated quantification software. Compared with the normal and MR− groups, the MR+ group had more dilated mitral annulus (
P
<0.0001), a reduced annular height to commissural width ratio (AHCWR) (
P
<0.0001) indicating flattening of annular saddle shape, redundant leaflet surfaces (
P
<0.0001), greater leaflet billow volume (
P
<0.0001) and billow height (
P
<0.0001), longer lengths from papillary muscles to coaptation (
P
<0.0001), and more frequent chordal rupture (
P
<0.0001). Prevalence of chordal rupture increased progressively with annulus flattening (7% versus 24% versus 42% for AHCWR >20%, 15%–20%, and <15%, respectively;
P
=0.004). Leaflet billow volume increased exponentially with decreasing AHCWR in patients without chordal rupture (
r
2
=0.66,
P
<0.0001). MR severity correlated strongly with leaflet billow volume (
r
2
=0.74,
P
<0.0001) and inversely with AHCWR (
r
2
=0.44,
P
<0.0001). In contrast, annulus dilatation but not flattening occurred in nonprolapse MR patients. An AHCWR <15% (odds ratio=7.1;
P
=0.0004) was strongly associated with significant MR in mitral valve prolapse.

Conclusion—
Flattening of the annular saddle shape is associated with progressive leaflet billowing and increased frequencies of chordal rupture and may be important in the pathogenesis of MR in mitral valve prolapse.
Signal Transducer and Activator of Transcription 3 (STAT3) Regulates Collagen-Induced Platelet Aggregation Independently of Its Transcription Factor Activity
Authors: Zhou Zhou , Gushiken Francisca C. , Bolgiano Doug , Salsbery Breia J. , Aghakasiri Niloufar , Jing Naijie , Wu Xiaoping , Vijayan K. Vinod , Rumbaut Rolando E. , Adachi Roberto , Lopez Jose A. , Dong Jing-fei 
Published: December 2012

Background—
Platelet hyperactivity induced by inflammation is a known risk factor for atherosclerosis and thrombosis, but its underlying mechanisms remain poorly understood.

Methods and Results—
The signal transducer and activator of transcription 3 (STAT3) was activated in collagen-stimulated platelets. Activated STAT3 served as a protein scaffold to facilitate the catalytic interaction between the kinase Syk (spleen tyrosine kinase) and the substrate PLCγ2 to enhance collagen-induced calcium mobilization and platelet activation. The same interaction of STAT3 with Syk and PLCγ2 was detected in HEK293 cells transfected with cDNAs for Syk and PLCγ2 and stimulated with interleukin-6. Pharmacological inhibition of STAT3 blocked ≈50% of collagen- and a collagen-related peptide–induced but not thrombin receptor–activating peptide– or ADP-induced aggregation and ≈80% of thrombus formation of human platelets on a collagen matrix. This in vitro phenotype was reproduced in mice infused with STAT3 inhibitors and mice with platelet-specific STAT3 deficiency. By forming a complex with its soluble receptor, the proinflammatory cytokine interleukin-6 enhanced the collagen-induced STAT3 activation in human platelets.

Conclusions—
These data demonstrate a nontranscriptional activity of STAT3 that facilitates a crosstalk between proinflammatory cytokine and hemostasis/thrombosis signals in platelets. This crosstalk may be responsible for the platelet hyperactivity found in conditions of inflammation.
Cognitive Impairment Evaluated With Vascular Cognitive Impairment Harmonization Standards in a Multicenter Prospective Stroke Cohort in Korea
Authors: Yu Kyung-Ho , Cho Soo-Jin , Oh Mi Sun , Jung San , Lee Ju-Hun , Shin Joon-Hyun , Koh Im-Suck , Cha Jae-Kwan , Park Jong-Moo , Bae Hee-Joon , Kang Yeonwook , Lee Byung-Chul 
Published: December 2012

Background and Purpose—
Since the Vascular Cognitive Impairment Harmonization Standards (VCIHS) neuropsychological test protocol was proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network, no studies have applied this neuropsychological protocol to poststroke survivors in a large-scale, multicenter stroke cohort. We determined the frequency of vascular cognitive impairment (VCI) and investigated the feasibility of using the Korean version of the VCIHS neuropsychological protocol in a multicenter, hospital-based stroke cohort in Korea.

Methods—
We prospectively enrolled 620 subjects with ischemic stroke within 7 days of symptom onset among 899 patients who were consecutively admitted to 12 university hospitals in Korea. Neuropsychological assessments using the 60-minute Korean VCIHS neuropsychological protocol were administered at 3 months after stroke.

Results—

Of the 620 patients, 506 were followed up at 3 months after stroke. Of these, 353 (69.8%) were evaluated for cognitive function using the 60-minute Korean VCIHS neuropsychological protocol. The frequency of VCI at 3 months was 62.6%: VCI with no dementia in 49.9% and vascular dementia in 12.7%. Old age (
P
=0.014), poor functional outcomes at 3 months (
P
=0.029), and stroke subtypes other than small vessel disease (
P
=0.004) were independent risk factors of VCI.

Conclusions—
VCI, evaluated using the Korean VCIHS neuropsychological protocol, is substantial at 3 months after ischemic stroke in Korea. The use of the 60-minute Korean VCIHS neuropsychological protocol was feasible in large-scale multicenter studies.