Miracle-dz/UniFAR-FTUs huggingface dataset:
Opioid peptide receptor studies. 16. Chronic morphine alters G‐protein function in cells expressing the cloned mu opioid receptor

Chronic morphine treatment results in functional uncoupling of the mu opioid receptor and its G protein in both cell culture and animal models. In the present study, Chinese hamster ovary (CHO) cells stably expressing the cloned human mu opioid receptor (hMOR‐CHO cells) were incubated with 1 μM of morphine (or no drug) for 20 h. Subsequently, we assessed DAMGO‐ and morphine‐stimulated [35S]‐GTP‐γ‐S binding and agonist‐mediated inhibition of forskolin‐stimulated cAMP accumulation. Using a single concentration of [35S]‐GTP‐γ‐S (0.05 nM), chronic morphine treatment did not significantly change basal [35S]‐GTP‐γ‐S binding, shifted the morphine EC50 from 59 nM to 146 nM, and decreased the maximal stimulation (Emax) from 201% to 177%. Similar results were observed with DAMGO. Binding surface analysis resolved two [35S]‐GTP‐γ‐S binding sites (high‐affinity and low‐affinity sites). In control cells, morphine stimulated [35S]‐GTP‐γ‐S binding by increasing the Bmax of the high‐affinity site. In morphine‐treated cells, morphine stimulated [35S]‐GTP‐γ‐S binding by decreasing the high‐affinity Kd without changing the Bmax. Morphine treatment increased the EC50 (5–11‐fold) for agonist‐mediated inhibition of forskolin‐stimulated cAMP accumulation. These changes were not observed in cells expressing a mutant mu opioid receptor which does not develop morphine tolerance, suggesting that the changes in [35S]‐GTP‐γ‐S binding observed in hMOR‐CHO cells result from the development of morphine tolerance. Synapse 47:1–9, 2003. Published 2002 Wiley‐Liss, Inc.
Transfection of Syk protein tyrosine kinase reconstitutes high affinity IgE receptor-mediated degranulation in a Syk-negative variant of rat basophilic leukemia RBL-2H3 cells

Aggregation of the high affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells results in rapid tyrosine phosphorylation and activation of Syk, a cytoplasmic protein tyrosine kinase. To examine the role of Syk in the Fc epsilon RI signaling pathway, we identified a variant of RBL-2H3 cells that has no detectable Syk by immunoblotting and by in vitro kinase reactions. In these Syk-deficient TB1A2 cells, aggregation of Fc epsilon RI induced no histamine release and no detectable increase in total cellular protein tyrosine phosphorylation. However, stimulation of these cells with the calcium ionophore did induce degranulation. Fc epsilon RI aggregation induced tyrosine phosphorylation of the beta and gamma subunits of the receptor, but no increase in the tyrosine phosphorylation of phospholipase C-gamma 1 and phospholipase C-gamma 2 and no detectable increase in intracellular free Ca2+ concentration. By transfection, cloned lines were established with stable expression of Syk. In these reconstituted cells, Fc epsilon RI aggregation induced tyrosine phosphorylation of phospholipase C- gamma 1 and phospholipase C-gamma 2, an increase in intracellular free Ca2+ and histamine release. These results demonstrate that Syk plays a critical role in the early Fc epsilon RI-mediated signaling events. It further demonstrates that Syk activation occurs downstream of receptor phosphorylation, but upstream of most of the Fc epsilon RI-mediated protein tyrosine phosphorylations.
Association between Sleep Duration and Personality-Gene Variants: Sleep Duration is Longer in S/S Homozygotes of Serotonin Transporter than in L Allele Genotypes

Heavy Issue: Clarifying AHI Elevation after Contemporary Airway Surgery for OSA – The MACHO Graph Objective: Personality genes and lifestyle and depression scores of young women were analyzed to reevaluate conflicting findings regarding the relationship between worry and sleep schedule (sleep duration, bedtime etc.). Methods: Genes encoding serotonin transporter (5-HTT; S/S, S/L, L/L, and S/XL genotypes) and dopamine D4 receptor (DRD4; 2/4, 4/4, and other genotypes) and three clock genes were genotyped for 42 healthy female Japanese students (age range: 20-21). Their mood was assessed via the Center for Epidemiologic Studies Depression Scale (CES-D). Their personalities were assessed via the NEO Five-Factor Inventory (NEO-FFI). They maintained a diary and completed a questionnaire about sleep and dietary intake. Results: The variant frequencies for S/S homozygote of 5-HTT and 4/4 homozygote of DRD4 were higher among this group than among Caucasians. Sleep duration was 40.8 min longer (7.13 ± .94 hrs) in 5-HTT S/S homozygotes than in others (6.45 ± .69 hrs) (p=0.018), and the bedtime was earlier (0:16 ± 1:05 h:min) for 5-HTT S/S homozygotes than for L allele genotypes (1:14 ± 0:41 h:min) (p=0.005). A “delayed bedtime phenotype” was evident in 55% of S/S homozygotes and 100% of L allele-bearing individuals. Sleep duration was also 42.0 min longer in 4/4 homozygotes (7.09 ± 0.94 hrs) of DRD4 than that in 4/2 heterozygotes (6.39 ± .77 hrs) (p=0.042). An inverse correlation (r=-.316, p=.043) between ppppsleep duration and CES-D score was detected. When groups with high and low CES-D scores were compared, “Delayed bedtime phenotypes”, Neuroticism, and Conscientiousness of NEO-FFI were 100%:59.3%, 34.0:25.5, and 24.6:28.2, respectively. Conclusion: Both stress-susceptible genotypes, S/S homozygotes of 5-HTT and 4/4 homozygotes of DRD4, slept longer than genotypes with the L-allele of 5-HTT, and 4/2 heterozygotes of DRD4, respectively. The high CES-D group comprised short sleepers, irrespective of genotype.
Control and Regulation of Gene Expression

Isoenzymes of phosphoglycerate kinase in Trypanosoma brucei are differentially expressed in its two main life stages. This study addresses how the organism manages to make sufficient amounts of the isoenzyme with the correct localization, which processes (transcription, splicing, and RNA degradation) control the levels of mRNAs, and how the organism regulates the switch in isoform expression. For this, we combined new quantitative measurements of phosphoglycerate kinase mRNA abundance, RNA precursor stability, trans splicing, and ribosome loading with published data and made a kinetic computer model. For the analysis of regulation we extended regulation analysis. Although phosphoglycerate kinase mRNAs are present at surprisingly low concentrations (e.g. 12 molecules per cell), its protein is highly abundant. Substantial control of mRNA and protein levels was exerted by both mRNA synthesis and degradation, whereas splicing and precursor degradation had little control on mRNA and protein concentrations. Yet regulation of mRNA levels does not occur by transcription, but by adjusting mRNA degradation. The contribution of splicing to regulation is negligible, as for all cases where splicing is faster than RNA precursor degradation.
NOD2 Stimulation by Staphylococcus aureus-Derived Peptidoglycan Is Boosted by Toll-Like Receptor 2 Costimulation with Lipoproteins in Dendritic Cells

ABSTRACT Mutations in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) play an important role in the pathogenesis of Crohn's disease. NOD2 is an intracellular pattern recognition receptor (PRR) that senses bacterial peptidoglycan (PGN) structures, e.g., muramyl dipeptide (MDP). Here we focused on the effect of more-cross-linked, polymeric PGN fragments (PGNpol) in the activation of the innate immune system. In this study, the effect of combined NOD2 and Toll-like receptor 2 (TLR2) stimulation was examined compared to single stimulation of the NOD2 receptor alone. PGNpol species derived from a lipoprotein-containing Staphylococcus aureus strain (SA113) and a lipoprotein-deficient strain (SA113 Δlgt) were isolated. While PGNpol constitutes a combined NOD2 and TLR2 ligand, lipoprotein-deficient PGNpolΔlgt leads to activation of the immune system only via the NOD2 receptor. Murine bone marrow-derived dendritic cells (BMDCs), J774 cells, and Mono Mac 6 (MM6) cells were stimulated with these ligands. Cytokines (interleukin-6 [IL-6], IL-12p40, and tumor necrosis factor alpha [TNF-α]) as well as DC activation and maturation parameters were measured. Stimulation with PGNpolΔlgt did not lead to enhanced cytokine secretion or DC activation and maturation. However, stimulation with PGNpol led to strong cytokine secretion and subsequent DC maturation. These results were confirmed in MM6 and J774 cells. We showed that the NOD2-mediated activation of DCs with PGNpol was dependent on TLR2 costimulation. Therefore, signaling via both receptors leads to a more potent activation of the immune system than that with stimulation via each receptor alone.
Reliable Change Indexes for Memory Performance in Schizophrenia as a Means to Determine Drug-Induced Cognitive Decline

Some psychotropic medications frequently prescribed in schizophrenia, especially agents that contain anticholinergic properties, have adverse effects on learning and memory. Given the impact of memory on both functional and symptomatic outcome in schizophrenia, it is important to determine if patients suffer from medication-related memory impairment. This study provides a statistical methodology for identifying medication-related changes in memory functioning. Reliable change estimates were determined for Rey Auditory Verbal Learning Test performance in 38 inpatients with schizophrenia. When an 80% confidence criterion was applied, improvement or decline of 12 words in the total score (sum score: Trials 1-5) cannot be attributed to measurement error. These findings should help clinicians better understand cognitive side effects and facilitate decision making regarding changes to individual patient's psychopharmacotherapy.
Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer

In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models. We identified abnormal expression of the TRKA protein in tumor and liver metastases of a CRC patient refractory to standard therapy. Molecular characterization unveiled a novel LMNA-NTRK1 rearrangement within chromosome 1 with oncogenic potential, and the patient was treated with the pan-TRK inhibitor entrectinib, achieving partial response with decrease in hepatic target lesions from 6.8 and 8.2cm in longest diameter to 4.7 and 4.3cm, respectively. To our knowledge, this is the first clinical evidence of efficacy for therapeutic inhibition of TRKA in a solid tumor, illuminating a genomic-driven strategy to identify CRCs reliant on this oncogene to be clinically targeted with entrectinib.
Impact of Early Synchronous Lip and Palatal Repair on Speech

Aims: The purpose of this study was to describe articulation and resonance characteristics of Ugandan English-speaking children with cleft lip and palate (CLP) after synchronous lip and palatal closure (Sommerlad technique) prior to the age of 6 months in comparison with an age- and gender-matched control group. Methods: Eleven Ugandan patients with CLP (mean age 4;9 years), repaired during a synchronous lip and (soft and hard) palatal closure at a mean age of 3.4 months, were included as well as a control group (n = 22) consisting of 2 Ugandan age- and gender-matched noncleft children for each patient (mean age 4;10 years). Objective and perceptual speech assessment techniques were applied. Results: Consonant inventories were significantly smaller in the CLP group. Moreover, phonetic disorders and phonological processes occurred in 91 and 100% of the CLP group, respectively. Perceptual consensus evaluation revealed absence of hyponasality and cul-de-sac resonance in all patients. Hypernasality and nasal emission/turbulence occurred in 18 and 27% of the patients, respectively. No significant group differences were observed regarding the mean nasalance values of oral speech samples. Conclusion: Various deviations from normal speech development seem to occur in patients with CLP following synchronous lip and palatal closure before 6 months of age.
Corneal first surface wavefront aberrations before and after pterygium surgery.

PURPOSE To determine the higher order aberrations at the corneal first surface before and after surgery for pterygium. METHODS Data were drawn from a longitudinal study of patients undergoing pterygium excision at Royal Victoria Infirmary, Newcastle upon Tyne, England between September 1998 and May 2004. Corneal topography was taken with the TMS-2 Topographic Modeling System (Computed Anatomy Corp) prior to and 6 months after surgery, exported to VOLPro software v7.08 (Sarver & Associates), and wavefront aberrations were derived for a 5.0-mm pupil using a 10th order Zernike polynomial expansion. Pre- to postoperative changes were assessed for significance using analyses of variance, and the relative risk of significant postoperative aberrations by pterygium size was determined. RESULTS Satisfactory corneal topography was available on 67 eyes (mean age 53.8 +/- 16.7 years [range: 25-86 years]). The root-mean-square (RMS) fit error in preoperative eyes was 0.15 +/- 0.10 microm. Preoperatively, the total higher order RMS wavefront aberration was 0.94 +/- 0.83 microm. All Zernike modes were elevated, with trefoil being the major contributor 0.52 +/- 0.50 microm. Pterygium excision significantly reduced wavefront aberrations across all modes and orders (F(1, 129) = 6.7 to 22.6, P < . 01): total higher order RMSpostop 0.45 +/- 0.35 microm. Cases with visually significant postoperative aberrations occurred and were more likely with larger pterygia: relative risk compared to pterygia 1.0 to 1.9 mm was 1.3 for 2.0 to 2.9 mm, 8.5 for 3.0 to 3.9 mm, 13.3 for 4.0 to 4.9 mm, and 10.2 for 5.0 to 5.9 mm. CONCLUSIONS Zernike polynomial fitting well describes wavefront aberrations in eyes with pterygia. Pterygia are associated with wavefront aberrations, especially trefoil, but these were largely eliminated by surgery. Earlier excision of pterygia reduces the likelihood of significant residual aberrations.
AQM with Dual Virtual PI Queues for TCP Uplink/Downlink Fairness in Infrastructure WLANs

In this paper the authors address the unfairness problem between uplink and downlink TCP flows in the IEEE 802.11 infrastructure WLANs. It has been shown that TCP flows exhibit resource allocation (e.g., bandwidth) inequalities mainly due to two reasons: TCP's asymmetric reactions towards data and ACK losses when the downlink buffer overflows at the AP; and the AP's inability to distinguish itself from other contending stations when accessing the medium with the 802.11 DCF MAC. To overcome this problem, we propose an AQM (active queue management) approach (V2PI AQM) to be implemented at the AP, which utilizes two virtual queues, namely the data queue and the ACK queue, with their lengths controlled by the PI controllers. As a result, data losses can be reduced since the AP's downlink buffer is no longer overwhelmed by the ACK packets destined to the uplink stations. In addition, when a discrepancy is observed by the AP monitoring the traffic intensity on the wireless link and the lengths of both queues, it uses an AIMD (additive increase multiplicative decrease) approach to adjust its contention window size, which compensates for the unfairness induced by the DCF MAC. We demonstrate using ns-2 simulations that fair bandwidth sharing between uplink and downlink TCP flows can be achieved by the AP's buffer management in conjunction with contention window adaptation.
An Internet-based program for depressive symptoms using human and automated support: a randomized controlled trial

Purpose The purpose of this study was to analyze the efficacy of an Internet-based program for depressive symptoms using automated support by information and communication technologies (ICTs) and human support. Patients and methods An Internet-based program was used to teach adaptive ways to cope with depressive symptoms and daily problems. A total of 124 participants who were experiencing at least one stressful event that caused interference in their lives, many of whom had clinically significant depressive symptoms, were randomly assigned into either an intervention group with ICT support (automated mobile phone messages, automated emails, and continued feedback through the program); an intervention group with ICT support plus human support (brief weekly support phone call without clinical content); or a waiting-list control. At pre-, post-, and 12-month follow-up, they completed depression, anxiety, positive and negative effect, and perceived stress measures. Results were analyzed using both intention-to-treat and completers data. The majority were women (67.7%), with a mean age of 35.6 years (standard deviation =9.7). Results The analysis showed that the two intervention groups improved significantly pre- to posttreatment, compared with the control group. Furthermore, improvements were maintained at the 12-month follow-up. Adherence and satisfaction with the program was high in both conditions. Conclusion The Internet-based program was effective and well accepted, with and without human support, showing that ICT-based automated support may be useful. It is essential to continue to study other ICT strategies for providing support.
Sequelae in the Abdominal Wall After Pedicled or Free TRAM Flap Surgery

Twenty-seven free transverse rectus abdominis musculocutaneous (TRAM) and 16 pedicled TRAM flap breast reconstruction patients were studied for 7 to 41 months (mean, 23 months) postoperatively to compare abdominal sequelae after these two operations. The patient groups were demographically similar; mean age was 47 years in both groups. Subjective grading of the results was similar in both groups. The incidence of minor lower abdominal bulges was higher (44%, 7/16) in the pedicled group than in the free TRAM flap group (4%, 1/27). No hernias were found. Delayed healing of the abdominal scar occurred in 3 free TRAM flap and 1 pedicled TRAM flap patients. Two free TRAM flap (8%) and 7 pedicled TRAM (44%) flap patients had minor edge necrosis of the breast. Trunk strength was tested using an isokinetic device (Lido Multi Joint II), and peak torque for flexion (mean, 111 Nm ± 25 Nm in the free TRAM flap group and 123 Nm ± 28 Nm in the pedicled TRAM flap group) and extension (mean, 144 Nm ± 38 Nm and 167 Nm ± 45 Nm) were measured. No statistical differences occurred between these groups. Sit-up performance was tested and graded from 1 to 6. Both groups performed equally (4.8 and 4.8) and within normal values for this age group. Ultrasonography of the rectus muscles revealed that in the free TRAM flap group, the rectus muscle of the operated side was significantly thinner (cranial segment 6.8 mm vs. 7.8 mm, p < 0.05), thus the harvesting of a segment of muscle below the umbilicus seems to disturb the quality of the entire muscle. The mean size of the muscular defect in the free TRAM flap group was 4.3 x 6.1 cm. In this study no differences in patient satisfaction or trunk strength could be found between free and pedicled TRAM flap patients.
Multiple R, the “Parametric Strategy,” and Measurement Imprecision

This analysis examines the efficacy of using “the parametric strategy” when doing multiple regression analyses using multiple R and related statistics. The parametric strategy involves transforming ordinal scale data into interval scale measures by assigning rank ordered equal interval scale values to ordinal categories. Studies that have examined the adequacy of the parametric strategy in regression analyses have (1) examined only bivariate, and not multivariate, relations, (2) usually not adequately examined measurement imprecision effects due to ordered polytomies in the data and (3) used simulation data, not real data from substantive sociological contexts. In this study an experiment using real data is undertaken to assess measurement imprecision effects in multiple regressions; observed values of multivariate regression statistics are found to diverge substantially from true values where the parametric strategy is applied to data involving ordered polytomies. The implications of these findings are discussed.
MR Imaging Findings of Medulla Oblongata Involvement in Posterior Reversible Encephalopathy Syndrome Secondary to Hypertension

SUMMARY: Although the combination of MR imaging findings and clinical evidence of hypertension may suggest the diagnosis of posterior reversible encephalopathy syndrome (PRES), MR imaging findings with only involvement of the medulla oblongata pose a diagnostic dilemma. In the cases presented here, we demonstrated MR imaging findings of a presumed brain stem (medulla oblongata) variant of PRES and emphasized the diagnostic value of diffusion-weighted imaging (DWI).
Immune Response to Neutralizing Epitope on Human Cytomegalovirus Glycoprotein B in Japanese: Correlation of Serologic Response with HLA‐Type

Antigenic domain 1 (AD‐1), located between amino acids 608 and 625 of human cytomegalovirus (CMV) gB protein, is the major domain recognized by neutralizing antibodies. Amino acids 552 to 630 are essential for the binding of neutralizing antibodies. We developed an enzyme‐linked immunosorbent assay (ELISA) to detect antibodies against a fusion protein containing amino acid residues 549 to 644 of the gB polypeptide and maltose binding protein (MBP). Of 180 seropositive samples, 106 (58.9%) showed positive immuno‐reactivity against the fusion protein. None of the seronegative samples reacted with the fusion protein. Among 57 seropositive individuals typed for HLA, subjects with HLA‐DR9 had a higher positive rate against the fusion protein (13/14=92.9%) than those without HLA‐DR9 (25/43=58.1%). In addition, subjects with HLA‐DR15 had a lower positive rate against the fusion protein (7/16=43.3%) than those without HLA‐DR15 (31/41 = 75.6%). Mean OD values of HLA‐DR15‐positive individuals were significantly lower than those of HLA‐DR15‐negative individuals. Thus, among CMV‐infected individuals, HLA‐DR9 may be associated with responders for neutralizing antibodies and HLA‐DR15 may be associated with non/low‐responders.
A new coordination complex based on a polynitrile ligand: bis(4-amino-3,5-di-2-pyridyl-4H-1,2,4-triazole)diaquairon(II) bis(1,1,3,3-tetracyano-2-methylsulfanylpropenide).

The new high-spin iron(II) complex, [Fe(C(12)H(10)N(6))(2)(H(2)O)(2)](C(8)H(3)N(4)S)(2) or [Fe(abpt)(2)(H(2)O)(2)](tcnsme)(2) [where abpt is 4-amino-3,5-di-2-pyridyl-4H-1,2,4-triazole and tcnsme is the 1,1,3,3-tetracyano-2-methylthiopropenide anion], consists of discrete [Fe(abpt)(2)(H(2)O)(2)](2+) dications, where the Fe(II) ion is coordinated by two N,N'-bidentate chelating abpt ligands in the equatorial plane and two water molecules in trans positions, generating a distorted octahedral [FeN(4)O(2)] environment. The cationic unit is neutralized by two polynitrile tcnsme anions, in which the C-N, C-C and C-S bond lengths indicate extensive electronic delocalization. In the crystal structure, the dications and anions are linked through O-H.N and N-H.N hydrogen bonds involving the water H atoms and those of the NH(2) groups and the N atoms of the CN groups, leading to the formation of a three-dimensional network.