Miracle-dz/UniFAR-FTUs huggingface dataset:
Egress of Mature Murine Regulatory T Cells from the Thymus Requires RelA

The mechanism of egress of mature regulatory T cells (Tregs) from the thymus to the periphery remains enigmatic, as does the nature of those factors expressed in the thymic environment. In this study, we examined the fate of thymic Tregs in TNF-α/RelA double-knockout (TA-KO) mice, because TA-KO mice retain a Treg population in the thymus but have only a small Treg population at the periphery. Transplantation of whole TA-KO thymus to under the kidney capsule of Rag1-null mice failed to induce the production of donor-derived splenic Tregs expressing neuropilin-1, which is reported to be a marker of naturally occurring Tregs, indicating that TA-KO thymic Tregs either do not leave the thymus or are lost at the periphery. We next transplanted enriched TA-KO thymic Tregs to the peripheries of TA-KO mice and traced mouse survival. Transplantation of TA-KO thymic Tregs rescued the lethality in TA-KO mice, demonstrating that TA-KO thymic Tregs remained functional at the periphery. The TA-KO thymic Treg population had highly demethylated CpG motifs in the foxp3 locus, indicating that the cells were arrested at a late mature stage. Also, the population included a large subpopulation of Tregs expressing IL-7Rα, which is a possible marker of late-stage mature Tregs. Finally, TA-KO fetal liver chimeric mice developed a neuropilin-1+ splenic Treg population from TA-KO cells, suggesting that Treg arrest was caused by a lack of RelA in the thymic environment. Taken together, these results suggest that egress of mature Tregs from the thymus depends on RelA in the thymic environment.
Scorpion Potassium Channel-blocking Defensin Highlights a Functional Link with Neurotoxin*

The structural similarity between defensins and scorpion neurotoxins suggests that they might have evolved from a common ancestor. However, there is no direct experimental evidence demonstrating a functional link between scorpion neurotoxins and defensins. The scorpion defensin BmKDfsin4 from Mesobuthus martensii Karsch contains 37 amino acid residues and a conserved cystine-stabilized α/β structural fold. The recombinant BmKDfsin4, a classical defensin, has been found to have inhibitory activity against Gram-positive bacteria such as Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteus as well as methicillin-resistant Staphylococcus aureus. Interestingly, electrophysiological experiments showed that BmKDfsin4,like scorpion potassium channel neurotoxins, could effectively inhibit Kv1.1, Kv1.2, and Kv1.3 channel currents, and its IC50 value for the Kv1.3 channel was 510.2 nm. Similar to the structure-function relationships of classical scorpion potassium channel-blocking toxins, basic residues (Lys-13 and Arg-19) of BmKDfsin4 play critical roles in peptide-Kv1.3 channel interactions. Furthermore, mutagenesis and electrophysiological experiments demonstrated that the channel extracellular pore region is the binding site of BmKDfsin4, indicating that BmKDfsin4adopts the same mechanism for blocking potassium channel currents as classical scorpion toxins. Taken together, our work identifies scorpion BmKDfsin4 as the first invertebrate defensin to block potassium channels. These findings not only demonstrate that defensins from invertebrate animals are a novel type of potassium channel blockers but also provide evidence of a functional link between defensins and neurotoxins.
Specificity of Cognitive Deficits in Bipolar Disorder versus Schizophrenia

Background: More and more epidemiological, genetic and neuroimaging studies show similarities between bipolar disorder (BD) and schizophrenia (SZ). Cognitive functions are known to be highly impaired in SZ and are increasingly studied in BD. When both populations are compared, the conclusions appear to be contradictory. The purpose of this review is to help define the profile of cognitive deficits in BD and in SZ. Methods: A systematic review of the literature of neuropsychological studies comparing BD and SZ was made, beginning in January 1990 and ending in January 2005. Thirty-eight studies met the required quality criteria and were included in this review. Results: Bipolar patients exhibit extensive cognitive abnormalities with a pattern of deficits that is not unique to this disease. However, when compared to schizophrenic patients, bipolar patients demonstrate a lesser degree of deficits, particularly concerning premorbid and current intelligence quotient and perhaps attention, verbal memory and executive functions. When looking into effect sizes, there seem to be different profiles even in studies finding no significant differences. Conclusions: The neuropsychological differences reported between both groups could be due to the presence of psychotic features, to environmental factors (stressful events, duration of the disease and number of hospitalisations) and could also be related to differences during the neurodevelopmental phase. Further studies should confirm whether these results are truly related to different neurobiological backgrounds.
Coupling of an endogenous 5‐HT1B‐like receptor to increases in intracellular calcium through a pertussis toxin‐sensitive mechanism in CHO‐K1 cells

1 Chinese hamster ovary cells (CHO‐K1) express an endogenous 5‐hydroxytryptamine (5‐HT)1B‐like receptor that is negatively coupled to adenylyl cyclase through a pertussis toxin (PTX)‐sensitive mechanism. Furthermore, the human adenosine A1 receptor when expressed in CHO‐K1 cells (CHO‐A1) has been shown to mobilize intracellular Ca2+ through a PTX‐sensitive mechanism. Therefore the aim of this investigation was to determine whether the endogenous 5‐HT1B‐like receptor was able to stimulate increases in intracellular free [Ca2+] ([Ca2+]i) in CHO‐A1 cells. 2 In agreement with previous studies using CHO cells, 5‐hydroxytryptamine (5‐HT) elicited a concentration‐dependent inhibition of forskolin‐stimulated [3H]‐cyclic AMP production in CHO‐A1 cells (p[EC50] = 7.73±0.13). 5‐HT (1 μm) inhibited 47±5% of the [3H]‐cyclic AMP accumulation induced by 3 μm forskolin. Forskolin stimulated [3H]‐cyclic AMP accumulation was also inhibited by the 5‐HT1 receptor agonists (p[EC50] values) 5‐carboxyamidotryptamine (5‐CT; 8.07±0.08), RU 24969 (8.12 ±0.33) and sumatriptan (5.80 ±0.31). 3 5‐HT elicited a concentration‐dependent increase in [Ca2+]i in CHO‐A1 cells (p[EC50] = 8.07 ±0.05). In the presence of 2mM extracellular Ca2+, 5‐HT (1 μm) increased [Ca2+]i from 174±17nM to 376 ±22 nM. The 5‐HT1 receptor agonists (p[EC50] values), 5‐carboxyamidotryptamine (5‐CT; 7.9 ±0.02), RU 24969 (8.1 ±0.07) and sumatriptan (5.9 ±0.11) all elicited concentration‐dependent increases in [Ca2+]i. Similar maximal increases in [Ca2+]i were obtained with each agonist. The selective 5‐HT1A receptor agonist, 8‐OH‐DPAT (10 μm) did not stimulate increases in [Ca2+]i. 5‐HT (100 μm) and 5‐CT (10 μm) did not stimulate a measurable increase in [3H]‐inositol phosphate accumulation in CHO‐A1 cells. 4 5‐HT (1 μm)‐mediated increases in [Ca2+]i were insensitive to the 5‐HT receptor antagonist, ritanserin (5‐HT2; 100 nM), ketanserin (5‐HT2; 100 nM), LY‐278,584 (5‐HT3; 1 μm) and WAY 100635 (5‐HT1A; 1 μm). The response to 5‐HT (100 nM) was antagonized by the non‐selective 5‐HT1 antagonist, methiothepin (pKb = 8.90±0.09) and the 5‐HT1D antagonist GR 127935 (pKb= 10.44±0.06). 5 Pretreatment with PTX (200 ng ml−1 for 4 h) completely attenuated the Ca2+ response to 100 μm 5‐HT. 6 In untransfected CHO‐K1 cells, 5‐HT (1 μm), RU 24969 (1 μm), and 5‐CT (1 μm) elicited increases in [Ca2+]i similar to those observed in CHO‐A1 cells. 7 These data demonstrate that in CHO‐K1 cells the endogenously expressed 5‐HT1B‐like receptor couples to the phospholipase C/Ca2+ signalling pathway through a PTX‐sensitive pathway, suggesting the involvement of Gi/Go protein(s).
Tryptophan to competing amino acids ratio in depressive disorder: relation to efficacy of antidepressive treatments

The relationship between the ratio in plasma of tryptophan to competing amino acids, which indicates brain serotonin synthesis, and the clinical response in depressed patients to treatments that act by enhancing brain serotoninergic function has been studied. There was a significantly positive correlation between the pretreatment plasma tryptophan ratio and the final depression score in patients treated with L-tryptophan or amitriptyline, and a trend towards a positive correlation in patients treated with lithium plus L-tryptophan or clomipramine. Patients with a low plasma tryptophan ratio generally showed greater clinical improvement than patients with a high ratio. When the plasma tryptophan ratio and the ratio in plasma of tyrosine to competing amino acids were considered together there was also a significant relationship between clinical and biochemical findings in patients treated with imipramine. These studies strongly indicate that brain serotoninergic function can be disturbed in depressed patients and, thus, lend support to the serotonin deficiency hypothesis in depression. Evidence has furthermore been presented which suggests that, rather than a low brain serotonin level per se, the hypofunction may be associated with disturbances in adaptive and regulatory mechanisms, e.g. postsynaptic serotonin receptors.
The products of the SUP45 (eRF1) and SUP35 genes interact to mediate translation termination in Saccharomyces cerevisiae.

The product of the yeast SUP45 gene (Sup45p) is highly homologous to the Xenopus eukaryote release factor 1 (eRF1), which has release factor activity in vitro. We show, using the two‐hybrid system, that in Saccharomyces cerevisiae Sup45p and the product of the SUP35 gene (Sup35p) interact in vivo. The ability of Sup45p C‐terminally tagged with (His)6 to specifically precipitate Sup35p from a cell lysate was used to confirm this interaction in vitro. Although overexpression of either the SUP45 or SUP35 genes alone did not reduce the efficiency of codon‐specific tRNA nonsense suppression, the simultaneous overexpression of both the SUP35 and SUP45 genes in nonsense suppressor tRNA‐containing strains produced an antisuppressor phenotype. These data are consistent with Sup35p and Sup45p forming a complex with release factor properties. Furthermore, overexpression of either Xenopus or human eRF1 (SUP45) genes also resulted in anti‐suppression only if that strain was also overexpressing the yeast SUP35 gene. Antisuppression is a characteristic phenotype associated with overexpression of both prokaryote and mitochondrial release factors. We propose that Sup45p and Sup35p interact to form a release factor complex in yeast and that Sup35p, which has GTP binding sequence motifs in its C‐terminal domain, provides the GTP hydrolytic activity which is a demonstrated requirement of the eukaryote translation termination reaction.
Bilateral Symptomatic Synovial Cysts of the Lumbar Spine Caused by Calcium Pyrophosphate Deposition Disease: A Case Report

Study Design. A case of bilateral symptomatic facet joint synovial cysts arising in association with calcium pyrophosphate deposition disease is reported. Objective. To present a previously unreported cause for symptomatic synovial cysts of the lumbar spine. Summary of Background Data. Synovial cysts of the facet joints occur most commonly in association with degenerative disease of the spine in older individuals. The association of these cysts with trauma, rheumatoid arthritis, spondylolysis, and kissing spinous processes also has been reported. These cysts can cause symptoms and signs from direct compression of the dura. Chondrocalcinosis has not been previously reported to cause symptomatic synovial cysts. Methods. A 67-year-old woman presented with right lower limb sciatica caused by a right L4–L5 facet joint cyst, which resolved after surgical decompression. A year later, she presented with left lower limb sciatica caused by development of a new L4–L5 facet joint cyst, which also resolved after surgical decompression. Results. Histopathologic examination of each cyst showed a cyst wall of fibrous tissue with synovial lining, inflammation, and granulation tissue. Examination of the tissue under polarized light showed positively birefringent, short blunt crystals of calcium pyrophosphate dihydrate. Conclusions. In patients with a history of gout or pseudogout, a rare possibility of a synovial cyst should be considered in the differential diagnosis during investigation for the cause of neural compression resulting in sciatic syndrome.
Compact Low-Profile Circularly Polarized Fabry–Perot Resonator Antenna Fed by Linearly Polarized Microstrip Patch

A novel compact low-profile circularly polarized Fabry-Perot resonator (CP-FPR) antenna fed by a linearly polarized microstrip patch tilting by 45° with respect to the axes is presented. The FP cavity consists of a partially reflective surface formed by cross-slot frequency selective surface (FSS) and a nonstandard artificial magnetic conductor (AMC) acting as reflective ground plane. Its profile is reduced to a quarter of a wavelength. For verification, a prototype antenna is designed and simulated by HFSS. Reasonable agreement between the simulated and measured results is observed. The prototype has a common frequency bandwidth of 6.4% for S11 ≤ - 10 dB, gain-drop ≤ 3 dB, and axial ratio ≤ 3 dB.
Stochastic dynamics for reinfection by transmitted diseases

The use of stochastic models to study the dynamics of infectious diseases is an important tool to understand the epidemiological process. For several directly transmitted diseases, reinfection is a relevant process, which can be expressed by endogenous reactivation of the pathogen or by exogenous reinfection due to direct contact with an infected individual (with smaller reinfection rate σβ than infection rate β). In this paper, we examine the stochastic susceptible, infected, recovered, infected (SIRI) model simulating the endogenous reactivation by a spontaneous reaction, while exogenous reinfection by a catalytic reaction. Analyzing the mean-field approximations of a site and pairs of sites, and Monte Carlo (MC) simulations for the particular case of exogenous reinfection, we obtained continuous phase transitions involving endemic, epidemic, and no transmission phases for the simple approach; the approach of pairs is better to describe the phase transition from endemic phase (susceptible, infected, susceptible (SIS)-like model) to epidemic phase (susceptible, infected, and removed or recovered (SIR)-like model) considering the comparison with MC results; the reinfection increases the peaks of outbreaks until the system reaches endemic phase. For the particular case of endogenous reactivation, the approach of pairs leads to a continuous phase transition from endemic phase (SIS-like model) to no transmission phase. Finally, there is no phase transition when both effects are taken into account. We hope the results of this study can be generalized for the susceptible, exposed, infected, and removed or recovered (SEIRIE) model, for which the state exposed (infected but not infectious), describing more realistically transmitted diseases such as tuberculosis. In future work, we also intend to investigate the effect of network topology on phase transitions when the SIRI model describes both transmitted diseases (σ<1) and social contagions (σ>1).
The basic subdomain of the c-Jun oncoprotein. A joint CD, Fourier-transform infrared and NMR study.

The structural properties of the basic subdomain of the basic zipper (bZIP) protein c-Jun were examined by joint means of 1H-NMR, CD and Fourier-transform infrared (FTIR) spectroscopies. The basic subdomain (residues 252-281 in c-Jun) is responsible for sequence-specific recognition of DNA. A modified basic subdomain bSD (residues 1-35) and its N-terminal part and C-terminal part fragments (NP, residues 1-19; and, CP, residues 16-35) were prepared by solid-phase synthesis and purified by HPLC. In aqueous solution, in the absence of DNA, bSD behaved mostly as an unstructured peptide characterized by only 5% alpha helix. However, upon mixing bSD and a specific DNA fragment, i.e. a CRE(cAMP-responsive element)-containing hexadecanucleotide, the alpha helix was stabilized to an extent of 20% at 20 degrees C or 35% at 2 degrees C. At the same time, no significant change could be detected in the DNA spectra. Addition of trifluoroethanol to an aqueous bSD sample resulted in an increase of the alpha-helix content so that about 60% of alpha helix was found at a ratio of 75% trifluoroethanol (20 degrees C). These effects were reflected in both CD and FTIR measurements. Changes shown by the CD spectra during the process suggested a mechanism dominated by a two-state helix/unordered transition. NMR data, namely alpha H chemical shifts, NOE cross-peaks and NH temperature coefficients provided indications for extended or nascent helix structures within four short stretches dispersed along the sequence for c-Jun bSD, contrasting with the unique and continuous stretch reported for Gcn4 (yeast general control protein 4) bSD in aqueous solution. Trifluoroethanol stabilized the alpha-helix structure mainly at these four sites. The malleability of the basic subdomain of c-Jun was emphasized in relation to its ability to fit the DNA helix in adopting an alpha-helix structure. The complex formation apparently requires substantial conformational change from the peptide and only little from the oligonucleotide.
Quantitative correlation of the effect of process conditions on the capping tendencies of tablet formulations.

Capping is a mechanical defect in tablet formulation and manufacture. Understanding what influences tablet capping in terms of process variables and formulation properties and developing specialized techniques to correlate these variables with mechanical failures are practical interests of the pharmaceutical industry. Tablet compression emulator was used to rank order capping tendencies of a diverse sample set. The compression forces of 5-25 kN were used to compress round, beveled edge, and oval shape tablets. Compression speeds of 25, 40, and 80 rpm were chosen as representative ranges for bench-to-manufacturing-scale processing. Tablets were tested by in-house developed nondestructive ultrasonic method. The measurements revealed that elastic modulus vary with different testing orientations that indicated elastic modulus anisotropy in tablets. It was shown that altering process conditions such as tooling, compression force, and compression speed significantly impact the capping tendencies of formulations. A systematic approach has been applied to develop a predictive tool to assess capping tendencies of formulations. The developed tool is fast, material sparing, and has potential to flag the risk of manufacturability issues and provide insight into the performance of formulations during early development.
In vitro reconstitution of anticodon nuclease from components encoded by phage T4 and Escherichia coli CTr5X.

During phage T4 infection of Escherichia coli strains containing the prr locus the host tRNALys undergoes cleavage‐ligation in reactions catalyzed by anticodon nuclease, polynucleotide kinase and RNA ligase. Known genetic determinants of anticodon nuclease are prr, which restricts T4 mutants lacking polynucleotide kinase or RNA ligase, and stp, the T4 suppressor of prr encoded restriction. The present communication describes an in vitro anticodon nuclease assay in which the specific cleavage of tRNALys is driven by an extract from E. coli prrr (restrictive) cells infected by phage T4. The in vitro anticodon nuclease reaction requires factor(s) encoded by prr, is stimulated by a synthetic Stp polypeptide and appears to require additional T4 induced factor(s) distinct from Stp.
Evaluation of North Carolina child care safety regulations

Introduction: The goal of this study was to track any changes in injuries and injury hazards during the first 3.5 years of implementation of the North Carolina Child Care Commission’s 1996 playground safety regulations. Methods: All reports (n=5402) of medically attended injuries in regulated child care settings in North Carolina during the period 1 January 1997 through 30 June 2000 were reviewed and analyzed. A total of 294 playground safety inspections were conducted in November and December 1998 in randomly selected North Carolina child care centers, and the playground safety inspections were repeated in 76 child care centers in August 2000. Finally, in 1999 a 1992 child care center director self assessment of safety features in classrooms was sent to the directors of 291 of the 294 centers. Results: The annual rate of reported, medically attended injuries occurring in regulated child care facilities in North Carolina declined by 22% from 1997 to 1999. The playground safety inspections in the year 2000 revealed that, for nine of 10 playground concerns and 12 of 18 playground safety hazards, average ratings were equal to or better than those of 1998. Finally, the director surveys revealed no dramatic changes in classroom safety hazards since 1992. Discussion: This study represents the first time that the authors are aware of that a significant decline in state-wide child care injury rates has been associated with improved regulation of playground safety in the US.
Rsp5 WW Domains Interact Directly with the Carboxyl-terminal Domain of RNA Polymerase II*

RSP5 is an essential gene inSaccharomyces cerevisiae and was recently shown to form a physical and functional complex with RNA polymerase II (RNA pol II). The amino-terminal half of Rsp5 consists of four domains: a C2 domain, which binds membrane phospholipids; and three WW domains, which are protein interaction modules that bind proline-rich ligands. The carboxyl-terminal half of Rsp5 contains a HECT (homologous to E6-AP carboxyl terminus) domain that catalytically ligates ubiquitin to proteins and functionally classifies Rsp5 as an E3 ubiquitin-protein ligase. The C2 and WW domains are presumed to act as membrane localization and substrate recognition modules, respectively. We report that the second (and possibly third) Rsp5 WW domain mediates binding to the carboxyl-terminal domain (CTD) of the RNA pol II large subunit. The CTD comprises a heptamer (YSPTSPS) repeated 26 times and a PXY core that is critical for interaction with a specific group of WW domains. An analysis of synthetic peptides revealed a minimal CTD sequence that is sufficient to bind to the second Rsp5 WW domain (Rsp5 WW2) in vitro and in yeast two-hybrid assays. Furthermore, we found that specific “imperfect” CTD repeats can form a complex with Rsp5 WW2. In addition, we have shown that phosphorylation of this minimal CTD sequence on serine, threonine and tyrosine residues acts as a negative regulator of the Rsp5 WW2-CTD interaction. In view of the recent data pertaining to phosphorylation-driven interactions between the RNA pol II CTD and the WW domain of Ess1/Pin1, we suggest that CTD dephosphorylation may be a prerequisite for targeted RNA pol II degradation.