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A number of competing hypotheses, including hydroclimatic variations, environmental degradation and disturbance, and sociopolitical disintegration, have emerged to explain the dissolution of Cahokia, the largest prehistoric population center in the United States. Because it is likely that Cahokia's decline was precipitated by multiple factors, some environmental and some societal, a robust understanding of this phenomenon will require multiple lines of evidence along with a refined chronology. Here, we use fecal stanol data from Horseshoe Lake, Illinois, as a population proxy for Cahokia and the broader Horseshoe Lake watershed. We directly compare the fecal stanol data with oxygen stable-isotope and paleoenvironmental data from the same sediment cores to evaluate the role of flooding, drought, and environmental degradation in Cahokia's demographic decline and sociopolitical reorganization. We find that Mississippi River flooding and warm season droughts detrimental to agriculture occurred circa (ca.) 1150 CE and possibly generated significant stress for Cahokia's inhabitants. Our findings implicate climate change during the Medieval Climatic Anomaly to Little Ice Age transition as an important component of population and sociopolitical transformations at Cahokia, and demonstrate how climate transitions can simultaneously influence multiple environmental processes to produce significant challenges to society.
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Cambio Climático/historia , Heces/química , Inundaciones/historia , Dinámica Poblacional/historia , Sedimentos Geológicos/análisis , Historia Antigua , Humanos , Illinois , Lagos , Lluvia , Estaciones del AñoRESUMEN
BACKGROUND: Fundoscopy outside ophthalmology is in decline, and the technical demands of the traditional direct ophthalmoscope examination are likely contributing. Alternative fundoscopy technologies are increasingly available, yet valid comparisons between fundoscopy technologies are lacking. We aimed to assess medical students' perceptions of usefulness and ease of use of traditional and contemporary fundus-viewing technologies including smartphone fundoscopy. METHODS: One hundred forty-six second-year medical students participated in a cross-sectional, randomised, cross-over study of fundoscopy methods. Medical students completed small group training sessions using six current fundoscopy technologies including: a non-mydriatic fundus camera; two types of direct fundoscopy; and three types of smartphone fundoscopy. A novel survey of perceived usefulness and ease of use was then completed by students. RESULTS: Repeated-measures ANOVA found students rated both the perceived usefulness (p< 0.001) and ease of use (p< 0.001) of smartphone fundoscopy significantly higher than both the non-mydriatic camera and direct fundoscopy. CONCLUSIONS: Smartphone fundoscopy was found to be significantly more useful and easier to use than other modalities. Educators should optimise student access to novel fundoscopy technologies such as smartphone fundoscopy which may mitigate the technical challenges of fundoscopy and reinvigorate use of this valuable clinical examination.
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Estudiantes de Medicina , Estudios Cruzados , Estudios Transversales , Fondo de Ojo , Humanos , Oftalmoscopía , Teléfono InteligenteRESUMEN
Understanding many processes, e.g., fusion experiments, planetary interiors, and dwarf stars, depends strongly on microscopic physics modeling of warm dense matter and hot dense plasma. This complex state of matter consists of a transient mixture of degenerate and nearly free electrons, molecules, and ions. This regime challenges both experiment and analytical modeling, necessitating predictive ab initio atomistic computation, typically based on quantum mechanical Kohn-Sham density functional theory (KS-DFT). However, cubic computational scaling with temperature and system size prohibits the use of DFT through much of the warm dense matter regime. A recently developed stochastic approach to KS-DFT can be used at high temperatures, with the exact same accuracy as the deterministic approach, but the stochastic error can converge slowly and it remains expensive for intermediate temperatures (<50 eV). We have developed a universal mixed stochastic-deterministic algorithm for DFT at any temperature. This approach leverages the physics of KS-DFT to seamlessly integrate the best aspects of these different approaches. We demonstrate that this method significantly accelerated self-consistent field calculations for temperatures from 3 to 50 eV, while producing stable molecular dynamics and accurate diffusion coefficients.
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We develop a density matrix formalism to describe coupled electron-nuclear dynamics. To this end, we introduce an effective Hamiltonian formalism that describes electronic transitions and small (quantum) nuclear fluctuations along a classical trajectory of the nuclei. Using this Hamiltonian, we derive equations of motion for the electronic occupation numbers and for the nuclear coordinates and momenta. We show that, in the limit, when the number of nuclear degrees of freedom coupled to a given electronic transition is sufficiently high (i.e., the strong decoherence limit), the equations of motion for the electronic occupation numbers become Markovian. Furthermore, the transition rates in these (rate) equations are asymmetric with respect to the lower-to-higher energy transitions and vice versa. In thermal equilibrium, such asymmetry corresponds to the detailed balance condition. We also study the equations for the electronic occupations in the non-Markovian regime and develop a surface hopping algorithm based on our formalism. To treat the decoherence effects, we introduce additional "virtual" nuclear wave packets whose interference with the "real" (physical) wave packets leads to the reduction in coupling between the electronic states (i.e., decoherence) as well as to the phase shifts that improve the accuracy of the numerical approach. Remarkably, the same phase shifts lead to the detailed balance condition in the strong decoherence limit.
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In a consortium analysis of a large particle captured from the coma of comet 81P/Wild 2 by the Stardust spacecraft, we report the discovery of a field of fine-grained material (FGM) in contact with a large sulfide particle. The FGM was partially located in an embayment in the sulfide. As a consequence, some of the FGM appears to have been protected from damage during hypervelocity capture in aerogel. Some of the FGM particles are indistinguishable in their characteristics from common components of chondritic-porous interplanetary dust particles (CP-IDPs), including glass with embedded metals and sulfides (GEMS) and equilibrated aggregates (EAs). The sulfide exhibits surprising Ni-rich lamellae, which may indicate that this particle experienced a long-duration heating event after its formation but before incorporation into Wild 2.
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BACKGROUND/OBJECTIVE: Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring. SUBJECTS/METHODS: We conducted linear regressions to assess maternal plasma 25-hydroxyvitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10. RESULTS: Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l-m at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores (-0.43 units; CI: -0.79, -0.07; P=0.02 for Q1 and -0.56 units; CI: -0.89, -0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing. CONCLUSIONS: Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined.
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Peso al Nacer/fisiología , Metilación de ADN/genética , Impresión Genómica/genética , Vitamina D/sangre , Adulto , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Madres , Embarazo , Estudios Prospectivos , Factores Socioeconómicos , Adulto JovenRESUMEN
Electronic transport properties of warm dense matter, such as electrical or thermal conductivities and nonadiabatic stopping power, are of particular interest to geophysics, planetary science, astrophysics, and inertial confinement fusion (ICF). One example is the α-particle stopping power of dense deuterium-tritium (DT) plasmas, which must be precisely known for current small-margin ICF target designs to ignite. We have developed a time-dependent orbital-free density functional theory (TD-OF-DFT) method for ab initio investigations of the charged-particle stopping power of warm dense matter. Our current dependent TD-OF-DFT calculations have reproduced the recently well-characterized stopping power experiment in warm dense beryllium. For α-particle stopping in warm and solid-density DT plasmas, the ab initio TD-OF-DFT simulations show a lower stopping power up to â¼25% in comparison with three stopping-power models often used in the high-energy-density physics community.
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OBJECTIVE: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease typically associated with elevated serum immunoglobulin G (IgG). Hypogammaglobulinemia in SLE patients has been attributed to immunosuppressive treatment or a transient effect associated with nephrotic syndrome. We retrospectively reviewed pediatric SLE patients from a single institution to identify patients with hypogammaglobulinemia and risk factors for hypogammaglobulinemia. METHODS: A total of 116 pediatric SLE cases from 1997 to 2011 were reviewed and patients with hypogammaglobulinemia (IgG < 500 mg/dl) were identified. The two cohorts were evaluated for association with age, sex, presence of lupus nephritis at SLE diagnosis, disease activity at diagnosis, initial IgG level, and drug treatment. RESULTS: Eighty-six patients were included in our study, with a median age of 15 years and a median follow-up of 39.5 months. Seven percent (six of 86) of patients had hypogammaglobulinemia with a median onset of 27 months (0-72 months) after SLE diagnosis. Significant associations were noted for white race (p value 0.029), male sex (p value 0.009), and the presence of lupus nephritis at SLE diagnosis (p value 0.004). Use of immunosuppressive treatment did not show a statistical association with hypogammaglobulinemia, although two of the patients with hypogammaglobulinemia did receive rituximab. Most patients with hypogammaglobulinemia received intravenous immunoglobulin (IVIG) replacement therapy because of infections and/or concern for infection. CONCLUSION: Measurement of immunoglobulin levels during treatment in SLE could help identify patients with hypogammaglobulinemia who might require more aggressive follow-up to monitor for increased risk of infection and need for IVIG treatment. A prospective study is needed to validate associated risk factors identified in this study.
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Agammaglobulinemia/inmunología , Inmunoglobulina G/sangre , Lupus Eritematoso Sistémico/inmunología , Adolescente , Agammaglobulinemia/sangre , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/tratamiento farmacológico , Agammaglobulinemia/etnología , Factores de Edad , Autoinmunidad , Biomarcadores/sangre , Niño , Progresión de la Enfermedad , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/etnología , Nefritis Lúpica/sangre , Nefritis Lúpica/inmunología , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Población BlancaRESUMEN
Nonlocal electron transport is important for understanding laser-target coupling for laser-direct-drive (LDD) inertial confinement fusion (ICF) simulations. Current models for the nonlocal electron mean free path in radiation-hydrodynamic codes are based on plasma-physics models developed decades ago; improvements are needed to accurately predict the electron conduction in LDD simulations of ICF target implosions. We utilized time-dependent density functional theory (TD-DFT) to calculate the electron stopping power (SP) in the so-called conduction-zone plasmas of polystyrene in a wide range of densities and temperatures relevant to LDD. Compared with the modified Lee-More model, the TD-DFT calculations indicated a lower SP and a higher stopping range for nonlocal electrons. We fit these electron SP calculations to obtain a global analytical model for the electron stopping range as a function of plasma conditions and the nonlocal electron kinetic energy. This model was implemented in the one-dimensional radiation-hydrodynamic code lilac to perform simulations of LDD ICF implosions, which are further compared with simulations by the standard modified Lee-More model. Results from these integrated simulations are discussed in terms of the implications of this TD-DFT-based mean-free-path model to ICF simulations.
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Catatonia is a rare manifestation in patients with systemic lupus erythematosus (SLE). As catatonia can be associated with both psychiatric and organic conditions, this could create a diagnostic dilemma once this occurs in SLE patients. The report describes a 15-year-old female with SLE who developed catatonia three days after the diagnosis of SLE was made. Her catatonia was refractory to the treatment with immunosuppressive therapy, which included pulse methylprednisolone, intravenous cyclophosphamide, rituximab, intravenous immunoglobulin (IVIG) and plasmapheresis. Given her persistent catatonia, electroconvulsive therapy (ECT) was initiated three months after the onset of her symptoms. After the third ECT treatment, her mental status dramatically improved and returned nearly to baseline while she was continued on the immunosuppression. This is the first report of a successful ECT therapy in catatonic lupus in children.
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Catatonia/terapia , Terapia Electroconvulsiva/métodos , Lupus Eritematoso Sistémico/complicaciones , Vasculitis por Lupus del Sistema Nervioso Central/terapia , Adolescente , Edad de Inicio , Catatonia/etiología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Resultado del TratamientoRESUMEN
Ion stopping in warm dense matter is a process of fundamental importance for the understanding of the properties of dense plasmas, the realization and the interpretation of experiments involving ion-beam-heated warm dense matter samples, and for inertial confinement fusion research. The theoretical description of the ion stopping power in warm dense matter is difficult notably due to electron coupling and degeneracy, and measurements are still largely missing. In particular, the low-velocity stopping range, that features the largest modelling uncertainties, remains virtually unexplored. Here, we report proton energy-loss measurements in warm dense plasma at unprecedented low projectile velocities. Our energy-loss data, combined with a precise target characterization based on plasma-emission measurements using two independent spectroscopy diagnostics, demonstrate a significant deviation of the stopping power from classical models in this regime. In particular, we show that our results are in closest agreement with recent first-principles simulations based on time-dependent density functional theory.
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The application of milk-derived proteins such as casein as anti-erosion agents in oral healthcare products is of current interest. The aim of this study was to investigate the potential of 3 commercially available, milk-derived proteins as agents to inhibit enamel erosion. Aqueous solutions of 0.5% w/v casein, casein phosphopeptide (CPP) or glycomacropeptide (GMP) with and without 300 ppm fluoride (F, as NaF) were investigated with regard to enamel softening and tissue loss, in comparison with a deionised water (DIW) negative control and 300 ppm F positive control. Casein and F reduced enamel surface softening compared to DIW, but CPP and GMP did not (DIW: 58.2% reduction in hardness; F: 13.3%; casein: 21.8%; CPP: 50.8%; GMP: 62.4%). Similar results were obtained with solutions containing protein and F, and the effects were statistically indistinguishable from protein alone (casein + F: 19.1%; CPP + F: 48.2%; GMP + F: 66.1%). By contrast, all protein solutions and F significantly reduced tissue loss (p < 0.050; DIW: 25.8 µm tissue loss; F: 21.6 µm; casein: 20.3 µm; CPP: 20.5 µm; GMP: 20.0 µm). Solutions containing protein and F reduced erosion more than protein alone, but this difference was only significant from protein alone for casein (casein + F: 12.2 µm; CPP + F: 17.3 µm; GMP + F: 18.2 µm). Casein and casein-derived proteins may therefore have the potential to act as agents to reduce or prevent enamel erosion. Furthermore, the erosion-reducing efficacy is not reduced by F, and is in some cases enhanced.
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Caseínas/uso terapéutico , Erosión de los Dientes/prevención & control , Animales , Bovinos , Esmalte Dental/química , Esmalte Dental/patología , Dureza , Fragmentos de Péptidos/uso terapéutico , Fosfopéptidos/uso terapéutico , Fluoruro de Sodio/química , Fluoruro de Sodio/uso terapéuticoRESUMEN
OBJECTIVE: We examined whether the prevalence of medical and behavioral conditions is higher in children of deployed veterans (DVs) versus non-deployed veterans (NDVs) after the 1991 Gulf War. METHODS: We examined 1387 children of 737 veterans. Children ages 2-18 had physical exams and parental reports of physical history and behavior. RESULTS: Physical health was analyzed using GEE models. Behavioral health [total, internalizing, and externalizing behavior problems (TBP, IBP, EBP)] was analyzed with mixed-effects regression models. Analyses were conducted by age group (2-3, 4-11, 12-18), and gender (ages 4-11, 12-18). Children of DVs ages 2-3 had significantly worse dentition (13.9% vs. 4.8%, P = 0.03) and more EBP {least square means (lsmeans) 54.31 vs. 47.59, P = 0.02}. Children of DVs ages 4-11 had significantly more obesity (18.8% vs. 12.7%, P = 0.02). Among children 4-11, male children of DVs had significantly more TBP (lsmeans 70.68 vs. 57.34, P = 0.003), IBP (lsmeans 63.59 vs. 56.16, P = 0.002) and EBP (lsmeans 61.60 vs. 52.93, P = 0.03), but female children did not. For children ages 12-18, male children of DVs had more EBP (lsmeans 63.73 vs. 43.51, P = 0.008), while female children of DVs had fewer EBP (lsmeans 45.50 vs. 50.48, P = 0.02). Veteran military characteristics and mental health, and children's social status and health, including obesity, predicted children's TBP for one or more age groups. CONCLUSIONS: Children of DVs experienced worse dentition, greater obesity, and more behavioral problems compared to NDV children, suggesting adverse health effects associated with parental deployment in need of further exploration.
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Salud Infantil , Familia Militar , Calidad de Vida , Adolescente , Niño , Preescolar , Emociones , Femenino , Guerra del Golfo , Humanos , Masculino , Trastornos Mentales/epidemiología , VeteranosRESUMEN
The aim of this study was to investigate the effects of two common food proteins on human enamel erosion in vitro. Erosion was measured by non-contact profilometry in citric, malic and lactic acids at pH 2.8, 3.2 and 3.8 and five commercially available soft drinks, in the presence of a salivary pellicle. Whole milk casein or hen egg ovalbumin was added to the acid solutions and drinks at 0.2% w/v, and the effect on erosion was determined by comparison with the corresponding solution without protein. Casein significantly reduced erosion in all but two solutions. The effects of the individual subfractions of casein in citric acid at pH 3.2 were similar to that of whole casein. Ovalbumin reduced erosion in some solutions, but the magnitude of the reduction was less than that with casein. A greater proportional reduction in erosion was seen in citric acid than in malic or lactic acids. We postulate that the mechanism involves adsorption of proteins to the pellicle or the enamel surface, forming a protein film with enhanced erosion-inhibiting properties. The citrate ion may play an active stabilising role, since erosion reduction was less in the other acids. In conclusion, casein and, to a lesser extent, ovalbumin show promise as potential anti-erosive additives to drinks.
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Ácidos/efectos adversos , Caseínas/administración & dosificación , Esmalte Dental/efectos de los fármacos , Ovalbúmina/administración & dosificación , Polímeros/administración & dosificación , Erosión de los Dientes/prevención & control , Administración Tópica , Animales , Bebidas/efectos adversos , Solubilidad del Esmalte Dental , Película Dental , Suplementos Dietéticos , Humanos , Concentración de Iones de Hidrógeno , Erosión de los Dientes/inducido químicamenteRESUMEN
We present the formulation, simulations, and results for multicomponent mutual diffusion coefficients in the warm, dense matter regime. While binary mixtures have received considerable attention for mass transport, far fewer studies have addressed ternary and more complex systems. We therefore explicitly examine ternary systems utilizing the Maxwell-Stefan formulation that relates diffusion to gradients in the chemical potential. Onsager coefficients then connect the macroscopic diffusion to microscopic particle motions, evinced in trajectories characterized by positions and velocities, through various autocorrelation functions (ACFs). These trajectories are generated by molecular dynamics (MD) simulations either through the Born-Oppenheimer approximation, which treats the ions classically and the electrons quantum-mechanically by an orbital-free density-functional theory, or through a classical MD approach with Yukawa pair-potentials, whose effective ionizations and electron screening length derive from quantal considerations. We employ the reference-mean form of the ACFs and determine the center-of-mass coefficients through a simple reference-frame-dependent similarity transformation. The Onsager terms in turn determine the mutual diffusion coefficients. We examine a representative sample of ternary mixtures as a function of density and temperature from those with only light elements (D-Li-C, D-Li-Al) to those with highly asymmetric mass components (D-Li-Cu, D-Li-Ag, H-C-Ag). We also follow trends in the diffusion as a function of number concentration and evaluated the efficacy of various approximations such as the Darken approximation.
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Decreased zinc ion availability in ageing is associated with altered immune response. One of the main regulators of zinc availability is metallothionein. Metallothionein induction is under the control of interleukin-6, a pro-inflammatory cytokine whose production is associated with poor ageing. The production of interleukin-6 is controlled, in part, by variability in the -174 nucleotide position. Under conditions of chronic inflammation, such as in ageing, zinc release by metallothionein is limited and may reduce zinc availability. Understanding the precise nature of the interactions between interleukin-6 and metallothioneins will aid in identifying individuals who are at risk of zinc deficiency. In the current study, we used gene arrays to investigate the effects of in vitro zinc supplementation on gene expression in elderly donors with described interleukin-6 and metallothionein 1a polymorphisms. Ingenuity Pathway Analysis identified several zinc-responsive genetic networks uniquely regulated only in elderly individuals with the pro-inflammatory interleukin-6 polymorphism. These include zinc-dependent decreased transcription of pro-inflammatory cytokines and alterations in metabolic regulatory pathways. The genomic effects of zinc increased in significance in the presence of the metallothionein 1a +647 C/A transition, suggesting that the interleukin-6 and metallothionein 1a genes act in a concerted manner to control zinc-regulated gene expression.
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Envejecimiento/genética , Interleucina-6/genética , Metalotioneína/genética , Polimorfismo de Nucleótido Simple/genética , Zinc/fisiología , Anciano , Femenino , Expresión Génica , Homeostasis , Humanos , Masculino , Metalotioneína/metabolismo , Análisis por Matrices de Proteínas , ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
A series of silicon-centered connecting units, Me(n)Si(p-C6H4CO2H)(4-n) (n = 0, 1, 2), have been prepared and their coordination polymers with Zn(II) metal atoms studied. The tetra-acid L1 (n = 0) acts as a tetrahedral node and reacts with Zn(II) centers to give 1, a novel interpenetrating 3D network containing distorted tetrahedral bimetallic secondary building units (SBUs). The triacid L2 (n = 1) acts as a trigonal pyramidal node and forms an intercalated 2D layered network, 2, with Zn(II) ions, containing distorted octahedral tetranuclear SBUs. Last, the bent diacid L3 (n = 2) reacts with Zn(II) centers to give 3, a corrugated 2D layered structure containing 1D zinc hydroxo chains. Together these three new coordination polymers demonstrate the potential versatility of tetravalent silicon containing connecting ligands for metal-organic framework construction.
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A new series of aluminium complexes bearing 'catam' ligands has been synthesised and fully characterised. They were found to exhibit high activity at room temperature for rac-lactide ring-opening polymerisation, a rather rare feature for aluminium-based catalysts.
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The migration of vascular smooth muscle cells (VSMCs) is thought to play a key role in the pathogenesis of many vascular diseases and is regulated by soluble growth factors/ chemoattractants as well as interactions with the extracellular matrix. We have studied the effects of antibodies to rat beta3 and human alphavbeta3 integrins on the migration of VSMCs. Both integrin antibodies as well as cyclic RGD peptides that bind to the vitronectin receptors alphavbeta3 and alphavbeta5 significantly inhibited PDGF-directed migration. This resulted in a reduction in the accumulation of inositol (1,4,5) trisphosphate and the activation of calcium/calmodulin-dependent protein kinase II (CamKII), an important regulatory event in VSMC migration identified previously. PDGF-directed VSMC migration in the presence of the anti-integrin antibodies and cyclic RGD peptides was restored when intracellular CamKII activity was elevated by either raising intracellular calcium levels with the ionophore, ionomycin, or infecting with a replication-defective recombinant adenovirus expressing a constitutively activated CamKII cDNA (AdCMV.CKIID3). Rescue of rat VSMCs was also observed in stably transfected cell lines expressing constitutively activated but not wild-type CamKII. These observations identify a key intermediate in the regulation of VSMC migration by outside-in signaling from the integrin alphavbeta3.
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Anticuerpos/farmacología , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Movimiento Celular , Músculo Liso Vascular/citología , Oligopéptidos/farmacología , Receptores de Vitronectina/antagonistas & inhibidores , Transducción de Señal , Animales , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Humanos , Músculo Liso Vascular/metabolismo , Ratas , Ratas Wistar , Receptores de Vitronectina/inmunologíaRESUMEN
Mild zinc deficiency, which is prevalent in vegetarians, diseased individuals, and the general aging population, depresses immunity and increases risk of disease in later life. However, human zinc intervention trials have produced conflicting results, perhaps because many of these trials included young or zinc-sufficient subjects. Since heterogeneity of the adult population may impact on response to dietary zinc, nutrigenomic approaches aimed at understanding the impact of zinc on modulation of gene and protein activities may aid in identifying subsets of the population-in particular the aging population-with increased risk of zinc deficiency who might receive benefit from a dietary zinc intervention and in this way may influence the success of the intervention. In the current study we used nutrigenomic approaches to investigate the impact of age on zinc-regulated gene expression in peripheral blood mononuclear cells. Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, CA) identified several genetic networks and functional canonical pathways which appeared responsive to zinc that were differentially regulated in young and elderly individuals. These include tryptophan metabolism, eicosanoid signaling, p38 mitogen-activated protein kinase (MAPK) signaling, integrin signaling, purine metabolism, G-protein-coupled receptor signaling, and most significantly, peroxisome proliferator-activated receptor (PPAR) signaling. These data suggest that age impacts strongly on the transcriptional effects of zinc and provides evidence to support the hypothesis that young and elderly individuals may respond differentially to zinc intervention.