Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunohistological and electrophysiological evidence that N‐acetylaspartylglutamate is a co‐transmitter at the vertebrate neuromuscular junction

Immunohistochemical studies previously revealed the presence of the peptide transmitter N‐acetylaspartylglutamate (NAAG) in spinal motor neurons, axons and presumptive neuromuscular junctions (NMJs). At synapses in the central nervous system, NAAG has been shown to activate the type 3 metabotropic glutamate receptor (mGluR3) and is inactivated by an extracellular peptidase, glutamate carboxypeptidase II. The present study tested the hypothesis that NAAG meets the criteria for classification as a co‐transmitter at the vertebrate NMJ. Confocal microscopy confirmed the presence of NAAG immunoreactivity and extended the resolution of the peptide's location in the lizard (Anolis carolinensis) NMJ. NAAG was localised to a presynaptic region immediately adjacent to postsynaptic acetylcholine receptors. NAAG was depleted by potassium‐induced depolarisation and by electrical stimulation of motor axons. The NAAG receptor, mGluR3, was localised to the presynaptic terminal consistent with NAAG's demonstrated role as a regulator of synaptic release at central synapses. In contrast, glutamate receptors, type 2 metabotropic glutamate receptor (mGluR2) and N‐methyl‐d‐aspartate, were closely associated with acetylcholine receptors in the postsynaptic membrane. Glutamate carboxypeptidase II, the NAAG‐inactivating enzyme, was identified exclusively in perisynaptic glial cells. This localisation was confirmed by the loss of immunoreactivity when these cells were selectively eliminated. Finally, electrophysiological studies showed that exogenous NAAG inhibited evoked neurotransmitter release by activating a group II metabotropic glutamate receptor (mGluR2 or mGluR3). Collectively, these data support the conclusion that NAAG is a co‐transmitter at the vertebrate NMJ.
Eating disorders and weight concern among lesbians.

OBJECTIVE This study estimated rates of bulimia nervosa and binge eating, and assessed risk factors among 203 lesbians. METHOD Participants completed questionnaires containing measures addressing lifestyle, self-esteem, body esteem, attitudes about attractiveness, and disordered eating. RESULTS The rate of bulimia nervosa among lesbians was similar to that of heterosexual women, but binge eating disorder was more frequent. Eating as negative affect regulation was a more significant predictor of binge eating than body dissatisfaction or dieting. Lesbians were not significantly different from heterosexual women in attitudes concerning weight and appearance, or dieting. Self-esteem was significantly related to body esteem, and actual-ideal weight discrepancy was associated with body dissatisfaction, suggesting that lesbians are not immune from the effects of not meeting societal ideals of thinness. Increased lesbian/gay involvement was associated with lower weight concern. DISCUSSION Implications for models of risk for eating disorders, and understanding the experience of lesbians, are discussed.
Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases.

OBJECTIVES To assess the proportion of RA patients who discontinued biologics in world registries and health care databases and to identify causes and predictors of discontinuation. METHODS Medline, Embase, Cochrane Library and Web of Science electronic databases and ACR and EULAR meeting abstracts were used. The selection of studies from world registries and health care databases including RA patients treated with biologics was independently performed. Data extracted from articles and abstracts were combined using a random effects model. Meta-analyses of percentages and hazard ratios were used to assess discontinuation. RESULTS Ninety-eight studies with >200 000 patients from 11 242 articles and 119 abstracts met the inclusion criteria. Overall discontinuation rates of TNF inhibitors at 0.5, 1, 2, 3 and 4 years were 21, 27, 37, 44 and 52%, respectively. Discontinuation of etanercept was significantly lower at 3 and 4 years (35% and 41%, respectively) than infliximab and adalimumab (46% and 52%, respectively). Predictors of time to discontinuation were etanercept [hazard ratios (HRs) 0.58 and 0.77 versus infliximab and adalimumab, respectively), concomitant use of DMARDs (HR 0.77), disease duration (HR 1.01) and female sex (HR 1.18). Studies from registries conducted after 2005 and from countries with lower biologics access showed higher percentages of discontinuation. Relevant data on abatacept and tocilizumab were missing. CONCLUSION In RA, treatment with etanercept has a lower percentage of discontinuation than infliximab and adalimumab. Concomitant use of DMARDs, disease duration before treatment with a biologic and female sex predict time to discontinuation.
Translocation of N-WASP by Nuclear Localization and Export Signals into the Nucleus Modulates Expression of HSP90*

N-WASP regulates the actin cytoskeleton through activation of the Arp2/3 complex. N-WASP localizes at the cell periphery, where it controls actin polymerization downstream of signal molecules such as adapter proteins, Cdc42, Src family kinases, and phosphoinositides. N-WASP also localizes in the nucleus; however, the role of N-WASP in the nucleus is unclear. Here, we show that localization of N-WASP is controlled through phosphorylation by Src family kinases in which phosphorylated N-WASP is exported from the nucleus in a nuclear export signal (NES) and leptomycin B-dependent manner. N-WASP had nuclear localization signal (NLS) at its basic region and NES close to the phosphorylation site by Src family kinases, indicating that phosphorylation controls the accessibility to the NES through conformational changes. Increased levels of unphosphorylated N-WASP in the nucleus suppressed expression of HSP90 and transcription from a heat shock element (HSE). N-WASP bound heat shock transcription factor (HSTF) and enhanced the HSTF association with HSE. In addition, nuclear N-WASP was present in the protein complex that associates with HSE, suggesting that N-WASP participates in suppression of HSP90 transcription. Increased levels of unphosphorylated N-WASP also decreased the activities of Src family kinases in cells but not in experiments in vitro with pure N-WASP and Fyn. Because HSP90 is essential for the activities of Src family kinases, these results suggest that localization of N-WASP modulates Src kinase activity by regulating HSP90 expression.
Related eIF3 subunits TIF32 and HCR1 interact with an RNA recognition motif in PRT1 required for eIF3 integrity and ribosome binding

eIF3 binds to 40S ribosomal subunits and stimulates recruitment of Met‐tRNAiMet and mRNA to the pre‐initiation complex. Saccharomyces cerevisiae contains an ortholog of human eIF3 subunit p35, HCR1, whose interactions with yeast eIF3 are not well defined. We found that HCR1 has a dual function in translation initiation: it binds to, and stabilizes, the eIF3–eIF5– eIF1–eIF2 multifactor complex and is required for the normal level of 40S ribosomes. The RNA recognition motif (RRM) of eIF3 subunit PRT1 interacted simultaneously with HCR1 and with an internal domain of eIF3 subunit TIF32 that has sequence and functional similarity to HCR1. PRT1, HCR1 and TIF32 were also functionally linked by genetic suppressor analysis. We propose that HCR1 stabilizes or modulates interaction between TIF32 and the PRT1 RRM. Removal of the PRT1 RRM resulted in dissociation of TIF32, NIP1, HCR1 and eIF5 from eIF3 in vivo, and destroyed 40S ribosome binding by the residual PRT1–TIF34–TIF35 subcomplex. Hence, the PRT1 RRM is crucial for the integrity and ribosome‐binding activity of eIF3.
Displaced Diffusion Option Pricing with Two Risky Assets

Firms usually hold several assets and liabilities that are not tradable separately, but tradable in aggregation as the firm’s equity, as first modeled by Rubinstein (1983) in his well-known displaced diffusion option pricing model with one risky and one riskless asset. When the Rubinstein model is extended to a firm with two risky assets, the standard riskless hedge argument cannot justify that the options on the firm’s equity can be priced by the risk-neutral valuation, because the two assets are not separately tradable. However, this paper shows that the aggregate tradability is likely to be sufficient for supporting the risk neutral option valuation.
Effects of vanadate on MgATP stimulation of Na-Ca exchange support kinase-phosphatase modulation in squid axons.

We have proposed that in squid axons MgATP stimulation of Na-Ca exchange involves a phosphorylation-dephosphorylation process catalyzed by a kinase-phosphatase system. In the present work, we used vanadate as a tool to gather further evidence about the mechanism of metabolic control of the Na-Ca exchanger in internally dialyzed and voltage-clamped squid axons. Vanadate, at concentrations up to 100 microM, stimulated extracellular Na (Nao)-dependent Ca efflux only in the presence of MgATP but failed to do so when the axons were dialyzed with the nonhydrolyzable ATP analogue beta, gamma-methyleneadenosine 5'-triphosphate or with CrATP, a MgATP analogue that completely abolishes MgATP stimulation of the Na-Ca exchange. In axons fully activated by Mg-adenosine 5'-O-(3-thiotriphosphate), vanadate had no effect on Na-Ca exchange. The dose-response curve for vanadate stimulation followed Michaelian kinetics with a Km of 5.6 +/- 0.4 microM and a maximum velocity of 216 +/- 10 fmol.cm-2.s-1 (intracellular Ca concentration = 0.8 microM). This coincides with the high affinity of vanadate in inhibiting the in vitro phosphatase activity of an alkaline phosphatase extracted from rat liver. In addition, vanadate increased fivefold the apparent affinity for MgATP (Km from 220 +/- 14 to 40 +/- 4 microM). Concentrations of vanadate in the millimolar range inhibited the MgATP-stimulated Na-Ca exchange (apparent Ki of 5.7 +/- 0.3 mM) and the in vitro phosphorylation by the catalytic subunit of a adenosine 3',5'-cyclic monophosphate protein kinase (apparent Ki 2.64 +/- 0.04 mM). We conclude that MgATP stimulation of Na-Ca exchange is proportional to the levels of phosphorylation that result from the balance of the activity of a kinase and a phosphatase activity.
Prolactin Stimulation of Ornithine Decarboxylase Activity in the Mammary Gland May Involve an Activation of Protein Kinase C 1

Abstract Phorbol myristate acetate (TPA), a protein kinase C activator, stimulates ornithine decarboxylase (ODC) activity in mammary gland explants derived from 12-14 day pregnant mice. The calcium ionophore A23187 similarly stimulates ODC activity. Maximally stimulatory concentrations of TPA and A-23187 produce additive responses. The prolactin (PRL) stimulation of ODC activity is nonadditive to that caused by TPA, A23187 or TPA plus A23187. These observations are compatible with the thesis that the stimulation of ODC activity by PRL may occur via an activation of protein kinase C.
Osteogenic differentiation of MC3T3-E1 cells on different titanium surfaces

mRNA expressions related to osteogenic differentiation of MC3T3-E1 cells on electro-polished smooth (S), sandblasted small-grit (SSG) and sandblasted large-grit (SLG) surfaces of titanium alloys were investigated in vitro. Gene expression profiles of cells were evaluated using the RT2 Profiler PCR microarray on day 7. Mineralizing tissue-associated proteins, differentiation factors and extracellular matrix enzymes mRNA expressions were measured using Q-PCR. SLG surface upregulated 23 genes over twofolds and downregulated 3 genes when compared to the S surface. In comparison to the SSG surface, at least a twofold increase in 25 genes was observed in the SLG surface. BSP, OCN, OPN, COL I and ALP mRNA expressions increased in the SLG group when compared to the S and the SSG groups. BMP-2, BMP-6 and TGF-β mRNA expressions increased in both the SSG and the SLG surfaces. MMP-2 and MMP-9 mRNA expressions increased as the surface roughness increased. This study demonstrated that surface roughness of titanium implants has a significant effect on cellular behavior and SLG surface apparently increased gene expressions related to osteogenesis when compared to the S and the SSG surfaces.
Isoprenoids and protein prenylation: implications in the pathogenesis and therapeutic intervention of Alzheimer’s disease

Abstract The mevalonate–isoprenoid–cholesterol biosynthesis pathway plays a key role in human health and disease. The importance of this pathway is underscored by the discovery that two major isoprenoids, farnesyl and geranylgeranyl pyrophosphate, are required to modify an array of proteins through a process known as protein prenylation, catalyzed by prenyltransferases. The lipophilic prenyl group facilitates the anchoring of proteins in cell membranes, mediating protein–protein interactions and signal transduction. Numerous essential intracellular proteins undergo prenylation, including most members of the small GTPase superfamily as well as heterotrimeric G proteins and nuclear lamins, and are involved in regulating a plethora of cellular processes and functions. Dysregulation of isoprenoids and protein prenylation is implicated in various disorders, including cardiovascular and cerebrovascular diseases, cancers, bone diseases, infectious diseases, progeria, and neurodegenerative diseases including Alzheimer’s disease (AD). Therefore, isoprenoids and/or prenyltransferases have emerged as attractive targets for developing therapeutic agents. Here, we provide a general overview of isoprenoid synthesis, the process of protein prenylation and the complexity of prenylated proteins, and pharmacological agents that regulate isoprenoids and protein prenylation. Recent findings that connect isoprenoids/protein prenylation with AD are summarized and potential applications of new prenylomic technologies for uncovering the role of prenylated proteins in the pathogenesis of AD are discussed. Graphical Abstract
Effects of antiretroviral therapy and opportunistic illness primary chemoprophylaxis on survival after AIDS diagnosis. Adult/Adolescent Spectrum of Disease Group.

OBJECTIVE To examine the effects of antiretroviral therapy (ART) and opportunistic illness chemoprophylaxis on the survival of persons with AIDS and survival time based on year of AIDS diagnosis. DESIGN Longitudinal medical record review. SETTING Ninety-three hospitals and clinics in nine cities in the USA. PATIENTS We observed 19,565 persons with AIDS from 1990 through January 1998. INTERVENTIONS Prescribed use of antiretroviral monotherapy, dual- and triple-combination therapies, primary prophylaxis against Pneumocystis carinii pneumonia and Mycobacterium avium complex, and pneumococcal vaccine. MAIN OUTCOME MEASURES Time from AIDS diagnosis to death in the presence and absence of ART. Survival curves were compared of AIDS cases diagnosed during 1990-1992 and 1993-1995. RESULTS Triple ART had the greatest effect on the risk of death [relative risk (RR), 0.15; 95% confidence limit (CL), 0.12, 0.17], followed by dual ART (RR, 0.24; 95% CL, 0.22, 0.26), and monotherapy (RR, 0.38; 95% CL, 0.36, 0.40). Risk of death was decreased among persons receiving Pneumocystis carinii pneumonia prophylaxis (RR, 0.79; 95% CL, 0.70, 0.89) and Mycobacterium avium complex prophylaxis (RR, 0.76; 95% CL, 0.68, 0.86). Median survival increased from 31 months [95% confidence interval (CI), 30-32 months] for AIDS cases diagnosed during 1990-1992 to 35 months (95% CI, 35-38 months) for cases diagnosed during 1993-1995. CONCLUSIONS The risk of death was decreased for persons receiving triple ART compared with persons receiving dual therapy and persons receiving monotherapy. Increased use of ART and improved ART regimens probably contributed to prolonged survival of persons whose diagnosis was made during 1993-1995 compared with persons whose diagnosis was made during 1990-1992.
Protesting Police Violence: "Blacklivesmatter" And Visual and Performance Art in the Era of Extrajudicial Police Killings

This visual essay is an exploration of the art, performance, and visual iconography associated with the BlackLivesMatter social movement organization. [1]Here I examine art that is used to protest and draw awareness to extrajudicial violence and the “increasingly militarized systems of killer cops.in the United States of America. ”[2]In this review, secondary themes of racism, dehumanization, racial profiling and political and economic injustice will also be highlighted.
Effects of New Calcium Channel Blocker, Azelnidipine, and Amlodipine on Baroreflex Sensitivity and Ambulatory Blood Pressure

The effect of dihydropyridine calcium channel blocker (CCB) on baroreflex sensitivity (BRS) is not well described. We studied the effect of a new CCB, azelnidipine, compared with amlodipine, on BRS and ambulatory blood pressure (BP) in newly diagnosed untreated hypertension. This study was a prospective, randomized, and open-label study. We randomized patients to either azelnidipine or amlodipine treatment. Azelnidipine 8 to 16 mg (average 14.5 mg) and amlodipine 2.5 to 7.5 mg (average 4.9 mg) were used to lower the clinical BP <140/90 mm Hg. BRS, evaluated by the spontaneous and the Valsalva methods, and clinical and ambulatory BP were evaluated at baseline and after 13 weeks of each treatment. A total of 47 patients (age 53.1 ± 10.8 years, 51% male), 26 in the azelnidipine group and 21 in the amlodipine group, completed the study. For baseline and after therapy respectively, both Valsalva-BRS (4.8 ± 1.7 vs. 8.4 ± 3.1 msec/mm Hg, P = 0.001) and spontaneous-BRS (5.5 ± 2.5 vs. 8.2 ± 5.6 msec/mm Hg, P = 0.019) were increased by azelnidipine, but amlodipine did not change them. Clinical and awake BPs were similarly reduced by each drug therapy. In conclusion, BRS was increased by azelnidipine therapy, but not by amlodipine therapy. This differential effect may be important in cardiovascular risk reduction.
Intractable Epilepsy as the Presentation of Vitamin B12 Deficiency in the Absence of Macrocytic Anemia

A 76-year-old man began to experience frequent gen-eralized tonic–clonic seizures 3 years before visiting ourhospital. The frequency was ∼3–5 times monthly. Theinitial investigations in a local hospital were normal ex-cept for mild normocytic anemia. He was diagnosedwith epilepsy of an unknown etiology, and phenytoin(PHT), 300 mg once daily, was given to prevent seizurerecurrence. In spite of a plasma drug concentration of15.4
Intrauterine Growth Restriction Impairs Small Intestinal Mucosal Immunity in Neonatal Piglets

Intrauterine growth restriction (IUGR) is a very common problem in both piglet and human neonate populations. We hypothesized that IUGR neonates have impaired intestinal mucosal immunity from birth. Using neonatal piglets as IUGR models, immune organ weights, the weight and length of the small intestine (SI), intestinal morphology, intraepithelial immune cell numbers, levels of cytokines and immunoglobulins, and the relative gene expression of cytokines in the SI were investigated. IUGR neonatal piglets were observed to have lower absolute immune organ weight and SI length, decreased relative weights of the thymus, spleen, mesenteric lymph node, and thinner but longer SIs. Damaged and jagged villi, shorter microvilli, presence of autophagosomes, swelled mitochondria, and decreased villus surface areas were also found in the SIs of IUGR neonatal piglets. We also found a smaller number of epithelial goblet cells and lymphocytes in the SIs of IUGR neonates. In addition, we detected reduced levels of the cytokines TNF-α and IFN-γ and decreased gene expression of cytokines in IUGR neonates. In conclusion, IUGR was shown to impair the mucosal immunity of the SI in neonatal piglets, and the ileum was the major site of impairment.
Soil Type-Dependent Responses to Phenanthrene as Revealed by Determining the Diversity and Abundance of Polycyclic Aromatic Hydrocarbon Ring-Hydroxylating Dioxygenase Genes by Using a Novel PCR Detection System

ABSTRACT A novel PCR primer system that targets a wide range of polycyclic aromatic hydrocarbon ring-hydroxylating dioxygenase (PAH-RHDα) genes of both Gram-positive and Gram-negative bacteria was developed and used to study their abundance and diversity in two different soils in response to phenanthrene spiking. The specificities and target ranges of the primers predicted in silico were confirmed experimentally by cloning and sequencing of PAH-RHDα gene amplicons from soil DNA. Cloning and sequencing showed the dominance of phnAc genes in the contaminated Luvisol. In contrast, high diversity of PAH-RHDα genes of Gram-positive and Gram-negative bacteria was observed in the phenanthrene-spiked Cambisol. Quantitative real-time PCR based on the same primers revealed that 63 days after phenanthrene spiking, PAH-RHDα genes were 1 order of magnitude more abundant in the Luvisol than in the Cambisol, while they were not detected in both control soils. In conclusion, sequence analysis of the amplicons obtained confirmed the specificity of the novel primer system and revealed a soil type-dependent response of PAH-RHDα gene-carrying soil bacteria to phenanthrene spiking.
Motion perception model with interaction between spatial frequency channels

Numerous studies have recently been made on the mechanism of human motion perception, especially on the model for the local motion detection using the spatio-temporal filter. The feature of such a model is that it is not required to solve the matching problem which is inherent to the feature matching problem. Another point is that the model can account for several properties of human motion perception. However, earlier models are limited in their performance since the motion is detected using only a single spatial frequency channel. The usual scene contains a large number of spatial frequency components. To detect the motion with a high accuracy, it is desirable to integrate the information obtained from a number of channels. It is suggested by several psychological experiments that an interaction occurs between channels of the human visual system. From such a viewpoint, this paper proposes a model for local motion detection based on the model by Watson et al., integrating the information from a number of spatial frequency channels. The model determines the motion velocity from the intersection of straight lines on the velocity plane, where the straight line is calculated from the spatio-temporal filter output, to represent the candidate for the velocity. The interaction between channels is represented by drawing the straight lines obtained from various channels on the same velocity plane. The effectiveness of the proposed method is shown by a simulation using a random dot pattern.