Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulating fragile X gene transcription in the brain and beyond

The past several years have seen remarkable growth in our understanding of the molecular processes underlying fragile X syndrome (FXS). Many studies have provided new insights into the regulation of Fmr1 gene expression and the potential function of its protein product. It is now known that the promoter elements modulating Fmr1 transcription involve a complex array of both cis and trans factors. Moreover, recent studies of epigenetic modification of chromatin have provided novel clues to unlocking the mysteries behind the regulation of Fmr1 expression. Here, we review the latest findings on the regulation of Fmr1 transcription. © 2005 Wiley‐Liss, Inc.
Effects of membrane molecular weight cutoff on performance of a novel bioartificial liver.

Immunoisolation using semipermeable membranes has been incorporated into bioartificial liver (BAL) devices to separate cellular components of the recipient's immune system from the cells within the BAL device. This study was designed to explore the influence of membrane molecular weight cutoff on performance of the multilayer radial-flow BAL using porcine hepatocytes cocultured with mesenchymal stem cells. In this study, healthy beagles underwent 6-h treatment with a BAL containing membrane with 200 kDa retention rating or 1200 kDa retention rating. Functional markers of BAL performance were monitored before and after treatment, as well as cytotoxic immune response to BAL therapy. The results showed that hepatocyte performance levels such as albumin secretion, urea synthesis, and viability were all significantly higher in 200 kDa retention rating group compared with the 1200 kDa retention rating group after treatment (P < 0.05). Significant levels of canine proteins were detected in BAL medium from the 1200 kDa retention rating group. Fluorescence microscopy further verified that heavy deposition of canine IgG, IgM, and complement (C3) on coculture cells was obtained after BAL treatment in the 1200 kDa retention rating group. However, only trace deposits of canine immunoproteins were observed on coculture cells obtained from BAL in the 200 kDa retention rating group. Small membrane molecular weight cutoff of the BAL could reduce the transfer of xenoreactive antibodies into the BAL medium and improve the performance of the BAL.
Effect of acute tryptophan depletion on mood and appetite in healthy female volunteers

Twelve healthy female subjects received the following three drinks in a double-blind, semi-balanced, cross over design: (a) 50 g of amino acids without L-tryptophan (LTP); (b) 50 g of amino acid with LTP (balanced); (c) plain water. Compared to both the balanced amino acid mixture and plain water, the LTP drink significantly lowered plasma total and free tryptophan at 4.5 h. However, compared to the two control conditions, there was no effect of the LTP drink on subjective ratings of mood or hunger. Similarly, the LTP drink did not alter significantly either total calorie intake or the macronutrient content of a test meal 5 h after drink ingestion.
Episode-specific drinking-to-cope motivation and next-day stress-reactivity

Background: Research consistently shows drinking-to-cope (DTC) motivation is uniquely associated with drinking-related problems. We furthered this line of research by examining whether DTC motivation is predictive of processes indicative of poor emotion regulation. Specifically, we tested whether nighttime levels of episode-specific DTC motivation, controlling for drinking level, were associated with intensified affective reactions to stress the following day (i.e. stress-reactivity). Design and Methods: We used a micro-longitudinal design to test this hypothesis in two college student samples from demographically distinct institutions: a large, rural state university (N = 1421; 54% female) and an urban historically Black college/university (N = 452; 59% female). Results: In both samples the within-person association between daily stress and negative affect on days following drinking episodes was stronger in the positive direction when previous night's drinking was characterized by relatively higher levels of DTC motivation. We also found evidence among students at the state university that average levels of DTC motivation moderated the daily stress-negative affect association. Conclusions: Findings are consistent with the notion that DTC motivation confers a unique vulnerability that affects processes associated with emotion regulation.
Analysis of the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer

Feline oral squamous cell carcinomas (FOSCC) are highly aggressive neoplasms with short survival times despite multimodal treatment. FOSCC are similar to squamous cell carcinomas of the head and neck (SCCHN) in humans, which also present therapeutic challenges. The current study was undertaken to identify novel chemotherapeutics using FOSCC cell lines. A high throughput drug screen using 1,952 drugs was performed to identify chemotherapeutics for further investigation. Two of the drugs identified in the drug screen, actinomycin D and methotrexate, and two drugs with similar molecular targets to drugs found to be efficacious in the screening, dinaciclib and flavopiridol, were selected for further investigation. Drug inhibition profiles were generated for each drug and cell line using an MTS assay. In addition, the effects of the drugs of interest on cell cycle progression were analyzed via a propidium iodide DNA labeling assay. Changes in caspase-3/7 activity after treatment with each drug were also determined. The findings demonstrated effectiveness of the drugs at nanomolar concentrations with sensitivity varying across cell lines. With all of the drugs except for actinomycin D, evidence for G1 arrest was found. Dinaciclib and flavopiridol were demonstrated to induce apoptosis. The results of the study suggest that the selected drugs are potential candidates for developing novel chemotherapeutic approaches to FOSCC. Through these studies, novel therapeutic strategies for the treatment of FOSCC can be developed to provide better care for affected cats which can also serve as proof of concept studies to inform translational studies in SCCHN in humans. www.oncotarget. com Oncotarget, 2018, Vol. 9, (No. 69), pp: 33098-33109
D ec 2 01 8 A pseudo-conformal structure in dense baryonic matter

We clarify and extend further the idea developed in [1, 2] that baryonic matter at high density has an emergent “pseudo-conformal symmetry. ” It is argued that as baryonic density exceeds n ≃ n1/2 ∼ 2n0, a topology change mimicking the baryon-quark continuity takes place at n1/2. In terms of skyrmions, this corresponds to the transition from skyrmions to half-skyrmions and impacts on the equation of state of dense baryonic matter. The emergence in medium at n1/2 of paritydoublet symmetry – which is invisible in QCD in matter-free vacuum – plays the crucial role. The consequence of the topology change is that massive compact stars carry the “pseudo-conformal sound velocity” v s/c 2 ≈ 1/3 at n ∼ > n1/2 signaling a precursor to precocious emergence of scale symmetry as well as a local symmetry hidden in QCD in the matter-free vacuum. A highly significant prediction of this work is that the topology change density from normal matter to half-skyrmion matter, upto-date inaccessible either by QCD proper or by terrestrial experiments, could possibly be pinned down within the range 2 < n1/2/n0 < 4, commensurate with the range expected for a continuous hadrons-to-quarks/gluons transition.
Renoprotective Effect of Grape Seed Extract against Oxidative Stress Induced by Gentamicin and Hypercholesterolemia in Rats

Abstract Rationale: Kidneys are dynamic organs and represent one of the major systems maintaining the body homeostasis; they are affected by many chemicals and drugs. Grape seed extract (GSE) has been targeted to prevent drug-induced renal toxicity. Objectives: This study investigates the possible renoprotective effect of GSE against oxidative stress, renal impairment, and hypercholesterolemia (HC) induced by gentamicin (GM) and cholesterol-enriched diet. Seventy adult male Wistar rats (160 ± 10 g) were divided into seven groups: (1) served as control, (2) GSE, (3) GM, (4) GSE + GM, (5) hypercholesterolemic (HC) group, (6) GM + HC group, and (7) GM + HC + GSE. Kidney functions, inflammatory mediators, cytokines, lipid profile, nitric oxide (NO), cyclic guanosine monophosphate (cGMP), and oxidative and antioxidative stress parameters were assessed in all groups. Main findings: GM induced renal dysfunction, which was exacerbated by the presence of HC as confirmed by laboratory determinations. Administration of GSE attenuated the renal toxicity evidenced in significant reduction in elevated kidney function, inflammatory cytokines as well as lipid profile, NO, cGMP, enzymatic, and nonenzymatic antioxidants. Conclusion: Administration of GSE simultaneously with GM attenuated oxidative stress, diminished renal toxicity, and improved lipid profile induced by GM and HC.
Kinetic Characterization of Alcohol Dehydrogenases and Matrix Metalloproteinases : A Reflection on Standardization of Assay Conditions

The present paper will focus on the characterization of enzymes from two different types of family, Short Chain Dehydrogenases/Reductases and Matrixins. The former family includes over 3000 enzymes, and I have worked mainly with different allelic variants of alcohol dehydrogenase (ADH) from the fruit fly Drosophila melanogaster and the ADH in Drosophila lebanonensis. To date, approximately 25 matrix metalloproteinases are known in humans. I will focus here on both similarities and differences in problems regarding the standardization of assay conditions and parameters that I have experienced during my work with these two different enzyme systems.
Calcium channel heterogeneity in canine left ventricular myocytes

Regional variations in the electrophysiological properties of myocytes across the left ventricular wall play an important role in both the normal physiology of the heart and the genesis of arrhythmias. To investigate the possible contributions of calcium channels to transmural electrical heterogeneity, whole‐cell patch‐clamp recordings were made from isolated canine epicardial and endocardial left ventricular myocytes. Two major differences in Ca2+ channel properties were found between epi‐ and endocardial cells. First, the L‐type Ca2+ current was larger in endocardial than in epicardial myocytes. The average peak current density at +10 mV in endocardial myocytes was 3.4 ± 0.2 pA pF−1, and was 45 % higher than that in epicardium (2.3 ± 0.1 pA pF−1). The kinetic properties of the L‐type current in epi‐ and endocardial cells were not significantly different. Second, a low‐threshold, rapidly activating and inactivating Ca2+ current that resembled the T‐type current was present in all endocardial myocytes but was small or absent in epicardial myocytes. This T‐like current had an average peak density of 0.5 pA pF−1 at −40 mV in endocardial cells. In most endocardial cells the T‐like Ca2+ current comprised two components: a Ni2+‐sensitive T‐type current and a tetrodotoxin‐sensitive Ca2+ current. We conclude that there are considerable regional variations in the density and properties of Ca2+ channels across the canine left ventricular wall. These variations may contribute to the overall transmural electrical heterogeneity.
The TRPV1 channel in rodents is a major target for antinociceptive effect of the probiotic Lactobacillus reuteri DSM 17938

Certain probiotic bacteria have been shown to reduce distension‐dependent gut pain, but the mechanisms involved remain obscure. Live luminal Lactobacillus reuteri (DSM 17938) and its conditioned medium dose dependently reduced jejunal spinal nerve firing evoked by distension or capsaicin, and 80% of this response was blocked by a specific TRPV1 channel antagonist or in TRPV1 knockout mice. The specificity of DSM action on TRPV1 was further confirmed by its inhibition of capsaicin‐induced intracellular calcium increases in dorsal root ganglion neurons. Another lactobacillus with ability to reduce gut pain did not modify this response. Prior feeding of rats with DSM inhibited the bradycardia induced by painful gastric distension. These results offer a system for the screening of new and improved candidate bacteria that may be useful as novel therapeutic adjuncts in gut pain.
Mean value results and $\Omega$-results for the hyperbolic lattice point problem in conjugacy classes

For $\Gamma$ a Fuchsian group of finite covolume, we study the lattice point problem in conjugacy classes on the Riemann surface $\Gamma \backslash \mathbb{H}$. Let $\mathcal{H}$ be a hyperbolic conjugacy class in $\Gamma$ and $\ell$ the $\mathcal{H}$-invariant closed geodesic on the surface. The main asymptotic for the counting function of the orbit $\mathcal{H} \cdot z$ inside a circle of radius $t$ centered at $z$ grows like $c_{\mathcal{H}} \cdot e^{t/2}$. This problem is also related with counting distances of the orbit of $z$ from the geodesic $\ell$. For $X \sim e^{t/2}$ we study mean value and $\Omega$-results for the error term $e(\mathcal{H}, X ;z)$ of the counting function. We prove that a normalized version of the error $e(\mathcal{H}, X ;z)$ has finite mean value in the parameter $t$. Further, we prove that if $\Gamma$ is cocompact then \begin{eqnarray*} \int_{\ell} e(\mathcal{H}, X;z) d s(z) = \Omega \left( X^{1/2} \log \log \log X \right). \end{eqnarray*} We prove that the same $\Omega$-result holds for $\Gamma = {\hbox{PSL}_2( {\mathbb Z})}$ if we assume a subconvexity bound for the Epstein zeta function associated to an indefinite quadratic form in four variables. We also study pointwise $\Omega_{\pm}$-results for the error term. Our results extend the work of Phillips and Rudnick for the classical lattice problem to the conjugacy class problem.
Isolation , screening and optimization of L-asparaginase producing bacterial strains inhabiting agricultural soils

This study aimed at isolation, screening and characterization of indigenous L-asparaginase producing bacteria from Egyptian agricultural soils. Several soil bacterial isolates were screened, and plate assayed for their abilities to produce, biotechnological and environmental important enzyme, Lasparaginase. Nine isolates belong to seven genera were proven to produce L-asparaginase i.e. Escherichia (FS-2), Pectobacterium (FS-4), Pseudomonas (FS-6 and GS-2), Bacillus (FS-7 and GS-4), Aeromonas (GS-3), Proteus (GS-5) and Serratia (GS-7). The most potent L-asparaginase producing isolates, Pectobacterium (FS-4) and Serratia (GS-7), were identified as P. carotovorum and S. marcescens following biochemical (BIOLOG) and molecular based methods with GeneBank accession numbers of MG808385 and MG808384, respectively. The optimization of enzyme productivity results under submerged fermentation conditions indicated that, lactose and ammonium nitrate as C and N sources, pH 7 and incubating temperature at 35 oC were the optimum for P. carotovorum. Furthermore, S. marcescens was optimized utilizing sucrose and asparagine as C and N sources, respectively, pH 7.5 and 30 oC for incubation. Optimized growth parameters improved L–asparaginase activities by 7.51% and 23.19% for P. carotovorum and S. marcescens, respectively. Partially purified L–asparaginase produced from P. carotovorum and S. marcescens at optimized conditions displayed molecular weights of approximately 34 and 40 kDa, respectively. Many environmental, medical and industrial bioprocesses could benefits from the isolated L–asparaginase producing bacteria as well as the purified enzyme.
Real-Life Cause-Effect Relations Between Urinary IL-6 Levels and Specific and Nonspecific Symptoms in a Patient With Mild SLE Disease Activity

Background Little is known about the real-time cause-effect relations between IL-6 concentrations and SLE symptoms. Methods A 52-year-old woman with mild SLE activity collected her entire urine for the determination of IL-6/creatinine and protein/creatinine levels (ELISA, HPLC) for a period of 56 days in 12 h intervals (total: 112 measurements). Additionally, she answered questionnaires (VAS) on oral ulceration, facial rash, joint pain, fatigue and tiredness and measured her temperature orally twice a day. Time-series analyses consisted of ARIMA modeling and cross-correlational analyses (one lag = 12 h, significance level = p < 0.05). Results Statistical analyses showed that increased urinary IL-6 concentrations preceded increased urinary protein levels by 36–48 h (lag3: r=+.225; p=.017) and that, in the opposite direction of effect, increased urinary protein preceded urinary IL-6 decreases by 12–24 h (lag1: r=–.322; p<.001). Moreover, urinary IL-6 increases co-occurred with increased oral ulceration (lag0: r=+.186; p=.049); after 48–60 h, however, IL-6 increases showed a strong tendency to precede oral ulceration decreases (lag4: r=–.170; p=.072). Increases in facial rash preceded decreases in urinary IL-6 after 84–96 h (lag7: r=–.215; p=.023). As to fatigue, increases in urinary IL-6 co-occurred with decreased fatigue (lag0: r=–.193; p=.042); after 84–96 h, however, IL-6 increases preceded fatigue increases (+lag7: r=+.189; p=.046). Finally, joint pain, tiredness and body temperature did not significantly correlate with urinary IL-6 concentrations in either direction of effect. Conclusions The results of this evaluation point to real-life feedback mechanisms between immune activity and SLE symptoms. Comparison with a previous evaluation of this patient suggests a counterregulatory mechanism between Th1 activity and IL-6. These findings are preliminary and require replication to draw firm conclusions about the real-time relation between IL-6 and SLE disease activity.
Sliding mode control of a nonholonomic wheeled mobile robot for trajectory tracking

We propose a tracking control of a nonholonomic wheeled mobile robot using variable structure systems. The posture of the mobile robot is represented by polar coordinates and a sliding mode control algorithm is presented for asymptotically stabilizing the mobile robot to a desired trajectory. It is shown that the proposed scheme is robust to system perturbations and measurement errors. Simulation and experimental results confirm the validity of accurate tracking capability and the robust performance of the proposed scheme.
Joint Effects of XRCC 1 Polymorphisms and Polycyclic Aromatic Hydrocarbons Exposure on Sperm DNA Damage and Male Infertility

X-ray repair cross-complementing group 1 (XRCC1) plays a role in repairing polycyclic aromatic hydrocarbons (PAHs)induced DNA damage. We examined the effects of exposure to PAHs and XRCC1 polymorphism, alone or combined, on sperm DNA integrity and male fertility. A total of 620 idiopathic infertile subjects and 273 fertile controls were recruited in this study. PAHs exposure was indicated by urinary 1-hydroxypyrene level. Genotypes were determined by PCR-RFLP, and sperm DNA damage was detected by Tdt-mediated dUTP nick end labelling assay using flow cytometry. A positive correlation was found between PAHs exposure and sperm DNA damage (beta coefficients 5 0.183, p < 0.001), whereas there was no significant association between the XRCC1 polymorphisms and sperm DNA damage. However, when the patients were dichotomized for PAHs exposure, higher sperm DNA damage was found among 399Gln allele carriers compared with the wild-type homozygotes (p 5 0.033). Further analysis based on a case-control study revealed the joint effect of XRCC1-399 polymorphism and PAHs exposure on the risk of male infertility (p interaction 5 0.041). These findings provided the first evidence about potential joint effects of PAHs exposure and DNA repair gene polymorphisms on male reproductive system and may be helpful in improving our understanding of the etiology of male infertility.
Positive and Negative Regulation of Phosphoinositide 3-Kinase-Dependent Signaling Pathways by Three Different Gene Products of the p85α Regulatory Subunit

ABSTRACT Phosphoinositide (PI) 3-kinase is a key mediator of insulin-dependent metabolic actions, including stimulation of glucose transport and glycogen synthesis. The gene for the p85α regulatory subunit yields three splicing variants, p85α, AS53/p55α, and p50α. All three have (i) a C-terminal structure consisting of two Src homology 2 domains flanking the p110 catalytic subunit-binding domain and (ii) a unique N-terminal region of 304, 34, and 6 amino acids, respectively. To determine if these regulatory subunits differ in their effects on enzyme activity and signal transduction from insulin receptor substrate (IRS) proteins under physiological conditions, we expressed each regulatory subunit in fully differentiated L6 myotubes using adenovirus-mediated gene transfer with or without coexpression of the p110α catalytic subunit. PI 3-kinase activity associated with p50α was greater than that associated with p85α or AS53. Increasing the level of p85α or AS53, but not p50α, inhibited both phosphotyrosine-associated and p110-associated PI 3-kinase activities. Expression of a p85α mutant lacking the p110-binding site (Δp85) also inhibited phosphotyrosine-associated PI 3-kinase activity but not p110-associated activity. Insulin stimulation of two kinases downstream from PI-3 kinase, Akt and p70 S6 kinase (p70S6K), was decreased in cells expressing p85α or AS53 but not in cells expressing p50α. Similar inhibition of PI 3-kinase, Akt, and p70S6K was observed, even when p110α was coexpressed with p85α or AS53. Expression of p110α alone dramatically increased glucose transport but decreased glycogen synthase activity. This effect was reduced when p110α was coexpressed with any of the three regulatory subunits. Thus, the three different isoforms of regulatory subunit can relay the signal from IRS proteins to the p110 catalytic subunit with different efficiencies. They also negatively modulate the PI 3-kinase catalytic activity but to different extents, dependent on the unique N-terminal structure of each isoform. These data also suggest the existence of a mechanism by which regulatory subunits modulate the PI 3-kinase-mediated signals, independent of the kinase activity, possibly through subcellular localization of the catalytic subunit or interaction with additional signaling molecules.
Complement activation in infective endocarditis: correlation with extracardiac manifestations and prognosis

In an infectious process complement activation is necessary for a proper immune and inflammatory response, but when exacerbated may cause tissue injuries. In infective endocarditis (IE) patients tend to develop high titres of circulating immune complexes (CIC) that activate complement. The aim of this study was to evaluate for the first time complement activation in IE for possible correlation with extracardiac manifestations and clinical prognosis. Twenty patients with IE, 14 healthy controls and 15 patients presenting mitral and aortic valve lesions (with no signs of either infection or other associated diseases), were studied. Plasma levels of C3adesArg, SC5b‐9, C1rs‐C1Inh and C3b(Bb)P were determined by ELISA and C3d by double decker immunoelectrophoresis. C3 and C4 levels were assayed by turbidimetry and CIC by ELISA. Elevation of plasma levels of all complement activation products, with the exception of C3b(Bb)P, indicated a significant classical pathway activation in IE patients when compared to controls (C3d: P < 0·00004; C3adesArg: P < 0·03, SC5b‐9: P < 0·01, C1rs‐C1Inh: P < 0·00007). CIC levels were significantly increased (P < 0·005) and C3 reduced in IE patients (P < 0·05). Elevated C3d (P < 0·02) and C3adesArg (P < 0·03) levels were associated with pulmonary manifestations. In addition, C3d was significantly elevated in the patients who died when compared to those who had a good recovery (P < 0·02). Our data demonstrate the activation of the complement classical pathway, most probably mediated by CIC, in IE and suggests C3d and C3adesArg as possible markers for extracardiac lesion and severity of the disease.