Miracle-dz/UniFAR-FTUs huggingface dataset:
kappa-opioid receptor agonists modulate excitatory transmission in substantia gelatinosa neurons of the rat spinal cord

This study examined the effects of selective activation of kappa 1- opioid receptors on excitatory transmission in substantia gelatinosa (SG) using intracellular recordings from SG neurons in transverse slices of the young rat lumbar spinal cord. Monosynaptic and polysynaptic excitatory postsynaptic potentials (EPSPs) were evoked by orthodromic electrical stimulation of A delta or C primary afferent fibers in the dorsal root after blocking inhibitory inputs with bicuculline and strychnine, NMDA receptors with D-2-amino-5- phosphonovaleric acid and mu- and delta-opioid receptors with CTAP and ICI 174,864, respectively. Bath application of dynorphin A1-17 or U-69, 593 caused dual modulation of the peak amplitude of presumed monosynaptic AMPA receptor-mediated EPSPs, decreasing synaptic potentials at nanomolar concentrations in a majority of SG cells examined (dynorphin, 63%; U-69,593, 91%), and increasing EPSPs at micromolar concentrations. Only the inhibitory action of dynorphin A1- 17 was consistently and completely blocked by norbinaltorphimine (nor- BNI). Since U-69,593 and nor-BNI are selective for the kappa 1-opioid receptors, the depression of EPSPs is likely to be mediated by the kappa1-opioid receptors. Under conditions of blockade of synaptic transmission with TTX and mu-and delta-opioid receptors, dynorphin A1- 17 and U-69,593 hyperpolarize most of SG neurons and decrease their membrane input resistance, the finding suggesting that direct interaction of kappa-agonists with a postsynaptic receptor is likely explanation for the inhibition of EPSPs. However, in some SG cells, the inhibition of EPSPs appears to be of presynaptic origin since dynorphin A1-17 and U-69,593 did depress the EPSPs in the absence of changes in passive membrane properties. Rp-cAMPS, a membrane permeant potent competitive inhibitor of cAMP-activated protein kinase, prevented the depressant effect of dynorphin A 1-17. This finding suggested a possibility that dynorphin A1-17, acting through a decrease in intracellular cyclic AMP levels, can reduce the synaptic responses of SG neurons. These results provide the first electrophysiological demonstration that the activation of kappa 1-opioid receptors inhibits AMPA receptor-mediated primary afferent neurotransmission in the substantia gelatinosa of the young rat spinal cord. This effect may mediate the ability of kappa-receptor agonists to produce antinociception.
Towards effective client-server based advent intrusion prevention system for WLAN

The implausible rise in the consumption of WLANs is practiced in most of the business and non-business, in the last few years, however motionless many vulnerabilities are found in present WLAN that anyone can take advantage of it. However rightful hosts that may be either intruders or RAP which are in attendance without knowledge or authorization. The adversaries take advantage of common vulnerabilities found in almost every network in order to make an intrusion attempt into the network. Entrancing into version all the offered network security standards, we put forward a hybrid IPS for WLAN main idea of our loom is to discriminate authorized and unauthorized users using passive IPS. We take into account various parameters like MAC address, IP, SSID along with session ids, while traditional uses MAC, IP address only.
Human Salivary Mucin MG1 Selectively Forms Heterotypic Complexes with Amylase, Proline-rich Proteins, Statherin, and Histatins

Heterotypic complexes between the high-molecular-weight mucin MG1 and other salivary proteins in human submandibular/sublingual secretion (HSMSL) could have a significant impact on the biological properties of these proteins in oral fluids in both health and disease. We describe a mild procedure for isolation and purification of native MG1 by gel filtration chromatography on Sepharose CL-2B which does not involve dialysis, lyophilization, use of denaturing agents, or covalent modification. Western blots of native MG1 probed with antibodies against 8 different salivary proteins showed that complexing occurs between MG1 and salivary amylase, proline-rich proteins (PRPs), statherins, and histatins but not MG1, slgA, secretory component, or cystatins. When native MG1 was placed in 4 M guanidine hydrochloride and chromatographed on Sepharose CL-4B, ELISA measurement of column fractions showed that amylase, PRPs, statherins, and histatins were released. Interestingly, gel filtration resolved the material which eluted into 4 or 5 distinct peaks, suggesting that the released entities were heterotypic complexes. From these studies, the occurrence of at least three different types of complexes between MG1 and other salivary proteins has been identified. Type I complexes are dissociated by SDS-PAGE and in 4 M guanidine hydrochloride. Type II complexes are not dissociated under these conditions. Type III complexes are dissociated during SDS-PAGE and by 4 M guanidine hydrochloride, but the released proteins appear to be complexes containing amylase, PRPs, statherins, and histatins. The possible functional role of heterotypic complexes between MG1 and other salivary proteins as a physiologic delivery system, a mechanism for protection against proteolysis, a repository for precursors of the acquired enamel pellicle, and a vehicle for modulation of the viscoelastic and rheological properties of saliva is discussed.
Associations of urinary, glomerular, and tubular markers with the development of diabetic kidney disease in type 2 diabetes patients

To evaluate the associations of urinary markers (eg albumin), glomerular (eg transferrin [TRF], immunoglobulin G [IgG]), and tubular (eg α1‐microglobulin [α1‐MG], β2‐microglobulin [β2‐MG]) markers with the development of diabetic kidney disease (DKD) in type 2 diabetes patients, as assessed by estimated glomerular filtration rate (eGFR) and albuminuria.
Stretch activation, unloaded shortening velocity, and myosin heavy chain isoforms of rat skeletal muscle fibres.

1. Contractile properties were investigated on single skinned‐fibre preparations from rat leg muscles. Following the mechanical measurements, the myosin heavy chain (HC) composition of the same fibre was analysed by gradient gel electrophoresis. 2. Fibres were typed according to their myosin HC isoform composition (HCI, type I; HCIIA, type IIA; HCIID, type IID; HCIIB, type IIB). Many fibres showed the co‐existence of two myosin HC isoforms (hybrid fibres). 3. A strong correlation was found between fibre type and time characteristics of stretch‐induced delayed force increase (stretch activation) of fully Ca(2+)‐activated fibres. 4. The maximal unloaded shortening velocity (Vmax), as measured with the slack test, was lowest in type I fibres. Within the type II group, a continuum of Vmax values was found, with large overlaps of the different fibre types. 5. The results suggest that the kinetics of stretch activation is determined by the myosin HCs whereas unloaded fibre shortening seems to be determined by other myofibrillar proteins in addition to the myosin HCs. Assuming that stretch activation represents certain steps of the cross‐bridge turnover under isometric conditions and Vmax reflects cross‐bridge detachment under unloaded conditions it can be deduced that different myofibrillar proteins are responsible for different steps within the cross‐bridge turnover.
Gene fusions and RNA trans-splicing in normal and neoplastic human cells

Chimeric gene products, most often resulting from chromosome translocations, have been considered unique features of cancer, or at least of cells at high risk for becoming cancerous. Chimeric JAZF1-JJAZ1 mRNA transcribed from DNA spanning the site of recombination in the (7;17)(p15;q21) chromosomal translocation found in half of endometrial stromal sarcomas and most cases of benign stromal nodules is one such example. The recent finding that chimeric JAZF1-JJAZ1 mRNA can also be detected in normal endometrial stromal cells suggests that chimeric gene products are not limited to cancer or pre-cancerous cells. The JAZF1-JJAZ1 mRNA and the protein encoded by it appear to be identical to that synthesized from the gene fusion in neoplastic cells. In cultured cells, the chimeric protein has anti-apoptotic properties and is pro-proliferative when unrearranged JJAZ1 alleles are silenced, as they are in endometrial stromal sarcomas but not in the stromal nodules. These observations are consistent with the conclusion that chromosomal rearrangements and gene fusions in neoplastic cells may represent mechanisms for the deregulated expression of chimeric gene products that are generated at specific stages in cell development and have physiologic functions in normal cells. Furthermore, it may be possible that other means for abnormal production of chimeric gene products, such as hyperactive trans-splicing of RNA, may be another mechanism underlying the neoplastic properties of tumor cells.
Androgen-insensitivity syndrome as a possible coactivator disease.

Androgen-insensitivity syndromes in 46,XY fetuses result in various degrees of impairment in genital virilization.1 These syndromes are caused by mutations in the androgen receptor gene that result in decreased binding of androgen to the receptor.2–9 As a consequence, the transcriptional activity of the androgen–androgen-receptor complex is reduced, and therefore, genital virilization is reduced. The androgen receptor, like other steroid hormone receptors, has two major transactivation domains10 — activation function 1 (AF-1) in the N-terminal region11–13 and activation function 2 (AF-2) in the C-terminal ligand-binding domain14 — that interact with the target genes directly as well as indirectly by .
Prevalence of Cardiovascular Risk Factors in Schoolchildren in a Rural Georgia Community

Background:In the context of a national childhood obesity epidemic, this study sought to document the cardiovascular risk status of children in a rural Georgia community. Methods:Anthropometrics and blood pressure were measured in 211 children, and fasting glucose and lipid profile in 160, recruited from schools in 2002 (grades 2 to 11, ages 7 to 18 years). Results:Nearly half the schoolchildren (48%) were overweight or at risk of overweight; 15% had metabolic syndrome. Overweight children were at higher risk for metabolic syndrome and had more risk factors. Blood pressure: 19% had elevated systolic blood pressure; 4% had elevated diastolic blood pressure. Glycemia: 14% had impaired fasting glucose levels; no diabetes cases were detected. Lipid profile: 26% had high total cholesterol (>170 mg/dL), 20% had high low-density lipoprotein (>110 mg/dL), 13% had high triglycerides (>150 mg/dL), 43% had low high-density lipoprotein (females, <50 mg/dL; males, <40 mg/dL). Ethnicity, gender, and grade level were not predictive of risk except that fewer black children had low high-density lipoprotein, and blood pressure and body mass index increased with grade, as expected. Conclusions:Results from this study indicate a significant problem with overweight and cardiovascular risk in rural schoolchildren. Notably, younger children were just as likely to have risk factors as adolescents, suggesting that screening and intervention ought to begin by school age. Ethnic and gender differences in prevalence were not found, suggesting that contextual factors in a rural setting may outweigh demographic influences on risk.
Improving Transplant Patient Safety Through Pharmacist Discharge Medication Reconciliation

Greater than 50% of medication errors are estimated to occur during transitions of care, and solid‐organ transplant recipients are at an increased risk for errors due to significant changes in their medication regimen following transplantation. This prospective, observational study with a historical control group was conducted to evaluate the discharge process for transplant recipients and determine if transplant pharmacist involvement would improve safety. During the prospective period, a total of 191 errors were made on discharge medication reconciliations (n = 64, mean rate 3.0 per patient); however, pharmacists prevented 119 of these errors (1.9 errors per patient). In the retrospective period, none of the 430 errors identified were prevented at the time of discharge (n = 128, p < 0.0001). The 72 errors not prevented at the time of discharge in the prospective cohort were identified by the pharmacist at the patient's first clinic visit (1.1 errors per patient). In the historical cohort, all 430 errors made at discharge persisted until at least the time of the first clinic visit (3.4 errors per patient, p < 0.0001). This study demonstrates that transplant recipients are at a high risk for medication errors and that transplant pharmacist involvement leads to improved safety through the significant reduction of medication errors.
Bisphenol‐A Affects Spermatogenesis in the Adult Rat Even at a Low Dose

Bisphenol‐A Affects Spermatogenesis in the Adult Rat Even at a Low Dose: Motoharu Sakaue,et al. Environmental Health Sciences Division, National Institute for Environmental Studies—Bisphenol‐A (BPA), a xenobiotic estrogenic compound widely used as a plastics monomer, has been suspected to have a so‐called low dose effect on the reproductive system when administered transplacentally. In the present study, we investigated possible low‐dose effects of BPA on spermatogenesis in adult rats. Male rats (13 weeks old; W13) were administrated a daily oral dose of BPA, ranging from 2 ng to 200 mg/kg, for 6 days and examined for testicular weight (TW) and daily sperm production (DSP) at W14 and W18. A BPA dose as low as 20 jug/kg tended to decrease TW and significantly reduced both DSP and the efficiency of spermatogenesis (DSP per gram testis) at W18, showing that BPA suppressed a normal increase in DSP and TW from W13 to W18. A single administration of 20 fig BPA/kg to W13 rats affected the intensity or mobility of several protein spots in the testicular cytosol fraction as shown by two‐dimensional gel electrophoresis analysis. The present study showed that BPA at a low dose affects spermatogenesis in the adult rat.
A Cross-Entropy based subcarrier, bit, and power allocation algorithm for multiuser OFDMA

A Cross-Entropy (CE) based subcarrier, bit, and power allocation algorithm is studied in this paper for orthogonal frequency division multiple access systems, where the total transmit power is minimized under the given quality of service requirements such as data rate and bit error rate. Although those power allocation problems can be translated into a non-deterministic polynomial time hard combinatorial optimization problem via coding the assignment information into a binary sequence, the globe optimal solution cannot be found in polynomial time. To address this problem, cross-entropy method is adopted to search a sub-optimum solution of the allocation type. The simulation results show that our proposed CE method can find a lower overall transmit power than genetic algorithm.
Novel glucocorticoid receptor agonists in the treatment of asthma

Introduction: Inhaled corticosteroids are the only drugs that effectively suppress the airway inflammation, but they can induce considerable systemic and adverse effects when they are administered chronically at high doses. Consequently, the pharmaceutical industry is still searching for newer entities with an improved therapeutic index. Areas covered: Herein, the authors review the research in the glucocorticoid field to identify ligands of the glucocorticoid receptor (GR). These ligands preferentially induce transrepression with little or no transactivating activity, in order to have a potent anti-inflammatory action and a low side-effects profile. Expert opinion: Several agents have been synthesized, but few have been tested in experimental models of asthma. Furthermore, only three (BI-54903, GW870086X and AZD5423) have entered clinical development, although the development of at least one of them (BI-54903) was discontinued. The reason for the limited success so far obtained is that the model of transactivation versus transrepression is a too simplistic representation of GR activity. It is difficult to uncouple the therapeutic and harmful effects mediated by GR, but some useful information that might change the current perspective is appearing in the literature. The generation of gene expression ‘fingerprints’ produced by different GR agonists in target and off-target human tissues could be useful in identifying drug candidates with an improved therapeutic ratio.
VP22‐mediated intercellular transport correlates with enhanced biological activity of MybEngrailed but not (HSV‐I) thymidine kinase fusion proteins in primary vascular cells following non‐viral transfection

The intercellular transport properties of the herpes simplex virus (HSV) protein VP22 have been harnessed to enhance the effectiveness of viral gene transfer. We investigated the intercellular transport and biological effects of VP22 fused with the dominant negative c‐Myb chimera, MybEngrailed (MybEn) and HSV‐I thymidine kinase (TK), in primary vascular smooth muscle cells (VSMC) following non‐viral transfection.
ADAMTSL3/punctin‐2, a gene frequently mutated in colorectal tumors, is widely expressed in normal and malignant epithelial cells, vascular endothelial cells and other cell types, and its mRNA is reduced in colon cancer

ADAMTSL3/punctin‐2 is a secreted glycoprotein that resembles the ADAMTS proteases. Recently, identification of frequent ADAMTSL3 mutations in colorectal cancer suggested it might have a regulatory role in cellular homeostasis in colorectal epithelium or in pathways to colorectal malignancy. Here, we used in situ hybridization to validate ADAMTSL3 antibodies for IHC of a variety of normal and malignant tissues, including colon cancer. Quantitative real‐time PCR (RTQ‐PCR) was used to compare mRNA expression levels in colon carcinoma (n = 10) and adjacent normal colon. ADAMTSL3 is expressed in epithelial cells of the colon, fallopian tube, skin, breast, prostate, epididymis, liver, pancreatic islets and bile ducts, as well as by vascular endothelial cells, smooth muscle cells, fibroblasts, cortical and ganglionic neurons and cardiac myocytes. Malignant epithelial cells in colon cancer, as well as breast, prostate, renal and skin tumors expressed ADAMTSL3. Normal colon showed stronger immunostaining of surface than basal crypt epithelium and staining of a variety of cells within the lamina propria and submucosa. Colon carcinomas demonstrated weaker staining in tumor cells than normal colon epithelium and weak stromal staining. RTQ‐PCR comparison of ADAMTSL3 mRNA in colon carcinoma and adjacent normal colon demonstrated a statistically significant reduction in the tumors, possibly reflecting their decreased stromal content and lack of complete differentiation of tumor samples. The major findings of these studies are that ADAMTSL3 is expressed in numerous tissues, suggesting a broader regulatory role than in colorectal epithelium alone, and that colorectal cancer has both structural mutations as well as decreased expression of ADAMTSL3. © 2007 Wiley‐Liss, Inc.
Antibody to platelet/endothelial cell adhesion molecule-1 reduces myocardial infarct size in a rat model of ischemia-reperfusion injury.

BACKGROUND Antibodies to selected neutrophil or endothelial cell adhesion molecules decrease myocardial infarct size in vivo. Platelet/endothelial cell adhesion molecule-1 (PECAM-1) is an immunoglobulin gene superfamily member expressed constitutively on neutrophils and endothelium. F(ab')2 fragments of antibody against PECAM-1 inhibit transendothelial migration of neutrophils in several in vivo models of acute inflammation. Therefore, we examined the effect of F(ab')2 fragments of anti-PECAM-1 antibody in a rat model of myocardial infarction. METHODS AND RESULTS F(ab')2 fragments of the anti-PECAM-1 antibody SEW16 and control normal rabbit IgG (NRIgG) were administered at 5 mg/kg to male Wistar rats, and the rats were subjected to a 30-minute coronary artery occlusion followed by 2 hours of reperfusion. At the completion of each experiment, the area at risk, infarct size (IS), and myeloperoxidase (MPO) activity were determined. Compared with untreated (n = 8; IS, 57 +/- 5%) or NRIgG-treated (n = 10; IS, 62 +/- 3%) control rats, SEW16-treated rats (n = 15; IS, 28.5 +/- 4%) displayed a 54% decrease in myocardial infarct size (P < .001). Hemodynamic parameters, leukocyte counts, total left ventricular weight, and area-at-risk weights did not differ significantly between the treatment groups. However, measurement of MPO activity revealed that neutrophil accumulation was reduced 83% (NRIgG, 975 +/- 55 mU/g; SEW16, 167 +/- 62 mU/g). CONCLUSIONS These results demonstrate that blocking PECAM-1 exerts a significant protective effect in a rat model of myocardial ischemia-reperfusion injury via blockade of neutrophil accumulation in the myocardium.
Caveolin-3 Knock-out Mice Develop a Progressive Cardiomyopathy and Show Hyperactivation of the p42/44 MAPK Cascade*

A growing body of evidence suggests that muscle cell caveolae may function as specialized membrane micro-domains in which the dystrophin-glycoprotein complex and cellular signaling molecules reside. Caveolin-3 (Cav-3) is the only caveolin family member expressed in striated muscle cell types (cardiac and skeletal). Interestingly, skeletal muscle fibers from Cav-3 (−/−) knock-out mice show a number of myopathic changes, consistent with a mild-to-moderate muscular dystrophy phenotype. However, it remains unknown whether a loss of Cav-3 affects the phenotypic behavior cardiac myocytes in vivo. Here, we present a detailed characterization of the hearts of Cav-3 knock-out mice. We show that these mice develop a progressive cardiomyopathic phenotype. At four months of age, Cav-3 knock-out hearts display significant hypertrophy, dilation, and reduced fractional shortening, as revealed by gated cardiac MRI and transthoracic echocardiography. Histological analysis reveals marked cardiac myocyte hypertrophy, with accompanying cellular infiltrates and progressive interstitial/peri-vascular fibrosis. Interestingly, loss of Cav-3 expression in the heart does not change the expression or the membrane association of the dystrophin-glycoprotein (DG) complex. However, a marker of the DG complex, α-sarcoglycan, was specifically excluded from lipid raft domains in the absence of Cav-3. Because activation of the Ras-p42/44 MAPK pathway in cardiac myocytes can drive cardiac hypertrophy, we next assessed the activation state of this pathway using a phospho-specific antibody probe. We show that p42/44 MAPK (ERK1/2) is hyperactivated in hearts derived from Cav-3 knock-out mice. These results are consistent with previous in vitro data demonstrating that caveolins may function as negative regulators of the p42/44 MAPK cascade. Taken together, our data argue that loss of Cav-3 expression is sufficient to induce a molecular program leading to cardiac myocyte hypertrophy and cardiomyopathy.
The Influence of On-Line Brand Community Characteristics on Community Commitment and Brand Loyalty

The relationship between on-line communities and on-line brands is investigated by examining how on-line brand community's characteristics affect community commitment and brand loyalty-in particular, how the hosting type of an on-line brand community affects the relationships between characteristics and community commitment. A survey of 250 respondents revealed that their community commitment was significantly influenced by their community interaction and the rewards for their activities, but not by information quality and system quality. The analysis shows that the hosting type of a community has a significant moderating effect and that community commitment increases brand loyalty. Interpretations and implications of the findings, as well as future research directions, are discussed.