Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of G Protein-linked Guanine Nucleotide Exchange Factors for Rho, PDZ-RhoGEF, and LARG by Tyrosine Phosphorylation

A recently identified family of guanine nucleotide exchange factors for Rho that includes PDZ-RhoGEF, LARG, and p115RhoGEF exhibits a unique structural feature consisting in the presence of area of similarity to regulators of G protein signaling (RGS). This RGS-like (RGL) domain provides a structural motif by which heterotrimeric G protein α subunits of the Gα12family can bind and regulate the activity of RhoGEFs. Hence, these newly discovered RGL domain-containing RhoGEFs provide a direct link from Gα12 and Gα13 to Rho. Recently available data suggest, however, that tyrosine kinases can regulate the ability of G protein-coupled receptors (GPCRs) to stimulate Rho, although the underlying molecular mechanisms are still unknown. Here, we found that the activation of thrombin receptors endogenously expressed in HEK-293T cells leads to a remarkable increase in the levels of GTP-bound Rho within 1 min (11-fold) and a more limited but sustained activation (4-fold) thereafter, which lasts even for several hours. Interestingly, tyrosine kinase inhibitors did not affect the early phase of Rho activation, immediately after thrombin addition, but diminished the levels of GTP-bound Rho during the delayed phase. As thrombin receptors stimulate focal adhesion kinase (FAK) potently, we explored whether this non-receptor tyrosine kinase participates in the activation of Rho by GPCRs. We obtained evidence that FAK can be activated by thrombin, Gα12, Gα13, and Gαq through both Rho-dependent and Rho-independent mechanisms and that PDZ-RhoGEF and LARG can in turn be tyrosine-phosphorylated through FAK in response to thrombin, thereby enhancing the activation of Rho in vivo. These data indicate that FAK may act as a component of a positive feedback loop that results in the sustained activation of Rho by GPCRs, thus providing evidence of the existence of a novel biochemical route by which tyrosine kinases may regulate the activity of Rho through the tyrosine phosphorylation of RGL-containing RhoGEFs.
Molecular Cloning and Characterization of an Aquaporin cDNA from Salivary, Lacrimal, and Respiratory Tissues (*)

The Aquaporin family of water channels plays a fundamental role in transmembrane water movements in numerous plant and animal tissues. Since the molecular pathway by which water is secreted by salivary glands is unknown, a cDNA was isolated from rat submandibular gland by homology cloning. Similar to other Aquaporins, the salivary cDNA encodes a 265-residue polypeptide with six putative transmembrane domains separated by five connecting loops (A-E); the NH2- and COOH-terminal halves of the polypeptide are sequence-related, and each contains the motif Asn-Pro-Ala. A mercurial-inhibition site is present in extracellular loop E, and cytoplasmic loop D contains a cAMP-protein kinase phosphorylation consensus. In vitro translation yielded a 27-kDa polypeptide, and expression of the cRNA in Xenopus oocytes conferred a 20-fold increase in osmotic water permeability (P) which was reversibly inhibited by 1 mM HgCl2. Northern analysis demonstrated a 1.6-kilobase mRNA in submandibular, parotid, and sublingual salivary glands, lacrimal gland, eye, trachea, and lung. In situ hybridization revealed a strong hybridization over the corneal epithelium in eye and over the secretory lobules in salivary glands. These studies have identified a new mammalian member of the Aquaporin water channel family (gene symbol AQP5) which is implicated in the generation of saliva, tears, and pulmonary secretions.
Analysis of Notch1 Function by In Vitro T Cell Differentiation of Pax5 Mutant Lymphoid Progenitors1

Signaling through the Notch1 receptor is essential for T cell development in the thymus. Stromal OP9 cells ectopically expressing the Notch ligand Delta-like1 mimic the thymic environment by inducing hemopoietic stem cells to undergo in vitro T cell development. Notch1 is also expressed on Pax5−/− pro-B cells, which are clonable lymphoid progenitors with a latent myeloid potential. In this study, we demonstrate that Pax5−/− progenitors efficiently differentiate in vitro into CD4+CD8+ αβ and γδ T cells upon coculture with OP9-Delta-like1 cells. In vitro T cell development of Pax5−/− progenitors strictly depends on Notch1 function and progresses through normal developmental stages by expressing T cell markers and rearranging TCRβ, γ, and δ loci in the correct temporal sequence. Notch-stimulated Pax5−/− progenitors efficiently down-regulate the expression of B cell-specific genes, consistent with a role of Notch1 in preventing B lymphopoiesis in the thymus. At the same time, Notch signaling rapidly induces cell surface expression of the c-Kit receptor and transcription of the target genes Deltex1 and pre-Tα concomitant with the activation of TCR Vβ germline transcription and the regulatory genes GATA3 and Tcf1. These data suggest that Notch1 acts upstream of GATA3 and Tcf1 in early T cell development and regulates Vβ-DJβ rearrangements by controlling the chromatin accessibility of Vβ genes at the TCRβ locus.
Simultaneous Measurement of Microscopic Image and Discharge Pulses at the Moment of Electrical Tree Initiation

This paper reports some experimental results concerning the tree initiation from a semiconductive needle electrode in polyethylene under a 50 Hz AC voltage. With a newly developed measuring system, the correspondence between partial discharge pulses and tree initiation and growth up to 10-20 µm in length was clarified for the first time. Tree observation and pulse measurement were made simultaneously. At the moment of tree initiation, positive pulses (current from the needle towards the grounding electrode) of 0.05-0.1 pC were first observed. A very small shade of the initial tree was observed when continuous positive pulses appeared; it grew rapidly to about 10 µm in length, along with the positive and negative pulses. After the tree branched, the growth rate dropped for a while. In many cases, the negative pulses disappeared during this stage.
Validation of the DINAMAP ProCare blood pressure device according to the international protocol in an adult population

ObjectiveInaccurate blood pressure measurement has serious implications for both the patient and the health service. It results in inappropriate treatment and underestimation of clinical risk. Few automated devices have been shown to be accurate when compared with mercury sphygmomanometery. The DINAMAP ProCare has been developed to be accurate compared with an auscultatory standard. We used the International Protocol of the European Society of Hypertension to assess the accuracy of this device in an adult population. MethodsThirty-eight participants were recruited from outpatient clinics and staff at Groote Schuur Hospital, Cape Town, RSA. Of these, 33 participants who fulfilled the requirements of the International Protocol were selected for final analysis. Demographic data were obtained from each participant, followed by nine sequential same-arm measurements, alternating between two trained observers and the device. The last seven readings were analysed according to the guidelines of the International Protocol. ResultsThe ProCare Monitor achieved all the required criteria of the International Protocol by successfully passing phase 1, phase 2.1 and phase 2.2 of the study protocol. The mean difference (standard deviation) for systolic and diastolic pressures, respectively, were –2.5 (5.4) and 0.5 (4.5) mmHg, which also falls within the passing criteria for the Association for the Advancement of Medical Instrumentation Standard (ANSI/AAMI SP-10). ConclusionThe DINAMAP ProCare Monitor can be recommended for clinical use in an adult population.
Amyloid-β Oligomers Induce Differential Gene Expression in Adult Human Brain Slices*

Background: Soluble Aβ oligomers (AβOs) have been increasingly proposed as the cause of synapse failure and cognitive dysfunction in Alzheimer disease. Results: Sublethal AβO concentrations induce changes in gene expression in adult human brain slices. Conclusion: AβOs impact transcription in important neuronal pathways preceding neurodegeneration. Significance: Results establish early mechanisms involved in AβO-triggered neuronal dysfunction in a novel human-derived experimental model. Cognitive decline in Alzheimer disease (AD) is increasingly attributed to the neuronal impact of soluble oligomers of the amyloid-β peptide (AβOs). Current knowledge on the molecular and cellular mechanisms underlying the toxicity of AβOs stems largely from rodent-derived cell/tissue culture experiments or from transgenic models of AD, which do not necessarily recapitulate the complexity of the human disease. Here, we used DNA microarray and RT-PCR to investigate changes in transcription in adult human cortical slices exposed to sublethal doses of AβOs. The results revealed a set of 27 genes that showed consistent differential expression upon exposure of slices from three different donors to AβOs. Functional classification of differentially expressed genes revealed that AβOs impact pathways important for neuronal physiology and known to be dysregulated in AD, including vesicle trafficking, cell adhesion, actin cytoskeleton dynamics, and insulin signaling. Most genes (70%) were down-regulated by AβO treatment, suggesting a predominantly inhibitory effect on the corresponding pathways. Significantly, AβOs induced down-regulation of synaptophysin, a presynaptic vesicle membrane protein, suggesting a mechanism by which oligomers cause synapse failure. The results provide insight into early mechanisms of pathogenesis of AD and suggest that the neuronal pathways affected by AβOs may be targets for the development of novel diagnostic or therapeutic approaches.
The Mental Health Impact of Volunteering in a Disaster Setting: A Review

This article reviews the literature on mental health of volunteers after working in disasters. When mobilized they often are a community's major source for rescue and recovery. PsychINFO, PubMED, and Web of Science were searched for relevant articles published until October 2009. Of 448 articles screened, only 9 articles fulfilled our inclusion criteria. They examined the aftermath of earthquakes (4 articles), terrorist bombings (1), explosions (1), aviation disasters (1), tsunami (1), and a bus accident (1). Findings showed that, compared with professional workers, volunteers tend to have higher complaint levels. The following factors were found to contribute to mental health complaints of volunteers: Identification with victims as a friend, severity of exposure to gruesome events during disaster work, anxiety sensitivity, and lack of postdisaster social support. The review reveals the need for more research regarding predictors of stress in volunteers.
A General Scheme Implicit Force Control for a Flexible-Link Manipulator

In this paper we propose an implicit force control scheme for a one-link flexible manipulator that interact with a compliant environment. The controller was based in the mathematical model of the manipulator, considering the dynamics of the beam flexible and the gravitational force. With this method, the controller parameters are obtained from the structural parameters of the beam (link) of the manipulator. This controller ensure the stability based in the Lyapunov Theory. The controller proposed has two closed loops: the inner loop is a tracking control with gravitational force and vibration frequencies compensation and the outer loop is a implicit force control. To evaluate the performance of the controller, we have considered to three different manipulators (the length, the diameter were modified) and three environments with compliance modified. The results obtained from simulations verify the asymptotic tracking and regulated in position and force respectively and the vibrations suppression of the beam in a finite time.
Prevalence of Anaplasma phagocytophilum in North Carolina Eastern Black Bears (Ursus americanus)

Abstract We detected Anaplasma phagocytophilum by DNA amplification in whole blood from free-ranging, hunter-killed American black bears (Ursus americanus) from the east coast of North Carolina, US. Molecular prevalence for Anaplasma phagocytophilum was 3% from 68 black bears. No DNA of other Anaplasma or Ehrlichia spp. was identified.
A smoker with cyanosis and hypotension

Involvement of the pericardium and pericardial effusion at postmortem is common in advanced malignant disease. However, cardiac tamponade presenting as the first manifestation of malignancy is uncommon. We present the case of a patient who presented with malignant pericardial effusion who had advanced lung cancer with metastasis and paraneoplastic features
Methicillin-resistant Staphylococcus aureus disease in three communities.

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) infection has emerged in patients who do not have the established risk factors. The national burden and clinical effect of this novel presentation of MRSA disease are unclear. METHODS We evaluated MRSA infections in patients identified from population-based surveillance in Baltimore and Atlanta and from hospital-laboratory-based sentinel surveillance of 12 hospitals in Minnesota. Information was obtained by interviewing patients and by reviewing their medical records. Infections were classified as community-associated [correction] MRSA disease if no established risk factors were identified. RESULTS From 2001 through 2002, 1647 cases of community-associated [correction] MRSA infection were reported, representing between 8 and 20 percent of all MRSA isolates. The annual disease incidence varied according to site (25.7 cases per 100,000 population in Atlanta vs. 18.0 per 100,000 in Baltimore) and was significantly higher among persons less than two years old than among those who were two years of age or older (relative risk, 1.51; 95 percent confidence interval, 1.19 to 1.92) and among blacks than among whites in Atlanta (age-adjusted relative risk, 2.74; 95 percent confidence interval, 2.44 to 3.07). Six percent of cases were invasive, and 77 percent involved skin and soft tissue. The infecting strain of MRSA was often (73 percent) resistant to prescribed antimicrobial agents. Among patients with skin or soft-tissue infections, therapy to which the infecting strain was resistant did not appear to be associated with adverse patient-reported outcomes. Overall, 23 percent of patients were hospitalized for the MRSA infection. CONCLUSIONS Community-associated MRSA infections are now a common and serious problem. These infections usually involve the skin, especially among children, and hospitalization is common.
Convergence in car prices among European countries

This article contributes to the literature on price convergence in Europe by investigating the existence of stochastic and deterministic convergence of car prices in the EU15 countries. We apply recently developed econometric techniques that allow for multiple structural breaks to an up-to-date dataset. We find considerable evidence of both types of convergence in our sample of countries and car models, therefore suggesting a tendency for relative prices to equalize over time. In addition, we find evidence regarding the importance in this convergence process of both legislative changes taking place in the years 1996 and 2002, and the implementation of Economic and Monetary Union (EMU).
Vitamin E suppression of microglial activation is neuroprotective

Neurotoxic microglial–neuronal interactions have been implicated in the pathogenesis of various neurodegenerative diseases such as Alzheimer's disease, and vitamin E has been shown to have direct neuroprotective effects. To determine whether vitamin E also has indirect neuroprotective effects through suppression of microglial activation, we used a microglial–neuronal coculture. Lipopolysaccharide (LPS) treatment of a microglial cell line (N9) induced a time‐dependent activation of both p38 mitogen‐activated protein kinase (p38 MAPK) and nuclear factor‐κB (NFκB), with consequent increases in interleukin‐1α (IL‐1α), tumor necrosis factor‐α (TNF‐α), and nitric oxide (NO) production. Differentiated neuronal cells (PC12 cells treated with nerve growth factor) exhibited marked loss of processes and decreased survival when cocultured with LPS‐activated microglia. Preincubation of microglia with vitamin E diminished this neurotoxic effect, independently of direct effects of the antioxidant on the neuronal cells. Microglial NO production and the induction of IL‐1α and TNFα expression also were attenuated by vitamin E. Such antiinflammatory effects of vitamin E were correlated with suppression of p38 MAPK and NFκB activation and were mimicked by an inhibition of either p38 MAPK (by SB203580) or NFκB (by decoy oligonucleotides). These results suggest that, in addition to the beneficial effects of providing direct antioxidant protection to neurons reported by others, vitamin E may provide neuroprotection in vivo through suppression of signaling events necessary for microglial activation. J. Neurosci. Res. 66:163–170, 2001. Published 2001 Wiley‐Liss, Inc.
Hypervitaminosis a in early human pregnancy and malformations of the central nervous system

Abstract. A case of malformations of the fetal central nervous system following hypervitaminosis A in early pregnancy is reported. The mother was treated with 150000 IU vitamin A daily during gestation days 19 to 40. Determination of urinary oestriol carried out in the 42nd week of pregnancy revealed a very low excretion (4.2‐6.6 μmol/24 h). Induced delivery resulted in a microcephalic child who died after 18 min. The child had multiple malformations of the central nervous system and very small adrenal glands (1.5 g; normal 11±4g). The very low urinary oestriol excretion is well explained by the hypoplastic adrenals, which in turn can be related to insufficient ACTH stimulation, a condition similar to anencephaly. The malformations shown in the present case are considered to be related to the high doses of vitamin A given to the mother, and the authors wish to warn against uncritical use of high doses of vitamin A in women of childbearing age.
Local chicken production: strategy of household poultry development in coastal regions of Niger Delta, Nigeria

The egg and meat production of local chicken (Gallus domesticus) is an indispensable component of household poultry development. The rapid production of local chicken has become a commercial trend in coastal regions of Niger Delta. Consumers prefer local chicken equally to that of cockerel and they consider it tastier than the broiler meat. Local chicken production management is easier than the broiler production particularly in the coastal regions where modern facilities including electric supply are not available. In this region, the household poultry keeper derived an economic importance of lower chicken price, lower mortality and morbidity, lower management cost, lower initial investment, better market demand, low abdominal fact, less disease susceptibility, more organoleptic preference. Household labour utilization and easy management are the strategic advantages of local chicken rearing at household poultry farming. The government should adopt a system of approach to local chicken development which will encourage adaptive and basic research in genetics and breeding, health care packages, feeds, feeding and nutrition, general management, economic and social aspects of raising the profitability and usability of local chicken for high productivity.
Re-Evaluation of Amino Acid Sequence and Structural Consensus Rules for Cysteine-Nitric Oxide Reactivity

Abstract Nitric oxide (NO), produced in different cell types through the conversion of Larginine into Lcitrulline by the enzyme NO synthase, has been proposed to exert its action in several physiological and pathological events. The great propensity for nitrosothiol formation and breakdown represents a mechanism which modulates the action of macromolecules containing NOreactive Cys residues at their active centre and/or allosteric sites. Based on the human haemoglobin (Hb) structure and accounting for the known acidbase catalysed Cys? 93-nitrosylation and Cys? 93NOdenitrosylation processes, the putative amino acid sequence (Lys/Arg/His/Asp/Glu)Cys(Asp/Glu) (sites 1, 0, and + 1, respectively) has been proposed as the minimum consensus motif for CysNO reactivity. Although not found in human Hb, the presence of a polar amino acid residue (Gly/Ser/Thr/Cys/Tyr/Asn/Gln) at the 2 position has been observed in some NOreactive protein sequences (e.g., NMDA receptors). However, the most important component of the tri or tetrapeptide consensus motif has been recognised as the Cys(Asp/Glu) pair [Stamler et al., Neuron (1997) 18, 691 696]. Here, we analyse the threedimensional structure of several proteins containing NOreactive Cys residues, and show that their nitrosylation and denitrosylation processes may depend on the CysS? atomic structural microenvironment rather than on the tri or tetrapeptide sequence consensus motif.
Protein Binding and the Metabolism of Thiamylal Enantiomers In Vitro

Thiamylal, a chiral thiobarbiturate, is marketed as a racemic product. We studied the serum protein binding and microsomal metabolism of thiamylal enantiomers in vitro. The unbound fraction of R(+)-thiamylal was greater than that of S(−)-thiamylal. The analysis of binding data revealed that both enantiomers bound to human serum albumin through only one site. In displacement studies with site-specific probes, dansylsarcosine, but not warfarin, significantly decreased the binding of both enantiomers. The bindings of enantiomers were also decreased by octanoate and a large concentration of oleate. These findings suggest that both enantiomers bind to Site II of albumin with higher affinity for S(−)-enantiomer. R(+)-thiamylal was metabolized more rapidly than S(−)-enantiomer by human liver microsomes. An experiment with isoform-selective inhibitors and cytochrome P-450 (CYP) isoforms showed that CYP2C9 had the highest activity for the metabolism of both enantiomers, the activity being 7 to 10 times that of CYP2E1 and CYP3A4. CYP2C9 showed a significantly rapid metabolism of R(+)-enantiomer, suggesting that CYP2C9 is mainly involved in the enantioselective metabolism of thiamylal. Implications Because clinically marketed thiamylal is a racemic compound, a pharmacokinetic study of each enantiomer may be beneficial. We found that the enantioselectivity of thiamylal existed in protein binding and metabolism. This may be caused by the differences in the affinities of enantiomers for albumin and cytochrome P-450 isoform.