Dendritic cell modulation by 1α,25 dihydroxyvitamin D3 and its analogs: A vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo

Dendritic cells (DCs) play a central role in regulating immune activation and responses to self. DC maturation is central to the outcome of antigen presentation to T cells. Maturation of DCs is inhibited by physiological levels of 1α,25 dihydroxyvitamin D3 [1α,25(OH)2D3] and a related analog, 1α,25(OH)2-16-ene-23-yne-26,27-hexafluoro-19-nor-vitamin D3 (D3 analog). Conditioning of bone marrow cultures with 10−10 M D3 analog resulted in accumulation of immature DCs with reduced IL-12 secretion and without induction of transforming growth factor β1. These DCs retained an immature phenotype after withdrawal of D3 analog and exhibited blunted responses to maturing stimuli (CD40 ligation, macrophage products, or lipopolysaccharide). Resistance to maturation depended on the presence of the 1α,25(OH)2D3 receptor (VDR). In an in vivo model of DC-mediated antigen-specific sensitization, D3 analog-conditioned DCs failed to sensitize and, instead, promoted prolonged survival of subsequent skin grafts expressing the same antigen. To investigate the physiologic significance of 1α,25(OH)2D3/VDR-mediated modulation of DC maturity we analyzed DC populations from mice lacking VDR. Compared with wild-type animals, VDR-deficient mice had hypertrophy of subcutaneous lymph nodes and an increase in mature DCs in lymph nodes but not spleen. We conclude that 1α,25(OH)2D3/VDR mediates physiologically relevant inhibition of DC maturity that is resistant to maturational stimuli and modulates antigen-specific immune responses in vivo.

Tetraploid State Induces p53-dependent Arrest of Nontransformed Mammalian Cells in G1

A “spindle assembly” checkpoint has been described that arrests cells in G1 following inappropriate exit from mitosis in the presence of microtubule inhibitors. We have here addressed the question of whether the resulting tetraploid state itself, rather than failure of spindle function or induction of spindle damage, acts as a checkpoint to arrest cells in G1. Dihydrocytochalasin B induces cleavage failure in cells where spindle function and chromatid segregation are both normal. Notably, we show here that nontransformed REF-52 cells arrest indefinitely in tetraploid G1 following cleavage failure. The spindle assembly checkpoint and the tetraploidization checkpoint that we describe here are likely to be equivalent. Both involve arrest in G1 with inactive cdk2 kinase, hypophosphorylated retinoblastoma protein, and elevated levels of p21WAF1 and cyclin E. Furthermore, both require p53. We show that failure to arrest in G1 following tetraploidization rapidly results in aneuploidy. Similar tetraploid G1 arrest results have been obtained with mouse NIH3T3 and human IMR-90 cells. Thus, we propose that a general checkpoint control acts in G1 to recognize tetraploid cells and induce their arrest and thereby prevents the propagation of errors of late mitosis and the generation of aneuploidy. As such, the tetraploidy checkpoint may be a critical activity of p53 in its role of ensuring genomic integrity.

Luminosity dependent accretion state change in GRO J1008–57

In a former publication, we have analyzed the transient neutron star X-ray binary GRO J1008–57 using all available RXTE-, Swift-, and Suzaku-data. As we have found, the source’s spectral components, i.e., a power-law with high exponential cutoff and a black-body, are strongly correlated with the hard X-ray flux (15–50 keV). We update the analytical description of these dependence, including a change in the photon index behaviour from a flat to a logarithmic function. The flux, where the change occurs, is consistent with the onset of the black-body emission. Thus, a change of the accretion state always occurs in GRO J1008–57 at a particular flux level.

NAEP 1996 mathematics state report for Department of Defense domestic dependent elementary and secondary schools /

"NCES 97-974 DDESS"--P. [4] of cover.

Characteristics of state plans for aid to families with dependent children under the Social Security Act, Title IV-A, and for Guam, Puerto Rico, & Virgin Islands.

Description based on: 1981 ed.

Research tables based on Characteristics of state plans for aid to families with dependent children : need, eligibility, administration in effect...

Description based on: 1980 ed.; title from cover.

For employees of State Public School for Dependent and Neglected Children.

Cover title.

Summary of state laws relating to the dependent classes, 1913.

Mode of access: Internet.

Profile of state performance in the Aid to Families with Dependent Children Program, 1979-1980.

"October 1982"--P. [4] of cover.

Market reform and state paternalism in Hungary: a path-dependent approach

Hungary is one of the worst-hit countries of the current financial crisis in Central and Eastern Europe. The deteriorating economic performance of the country is, however, not a recent phenomenon. A relatively high ratio of redistribution, a high and persistent public deficit and accelerated indebtedness characterised the country not just in the last couple of years but also well before the transformation, which also continued in the postsocialist years. The gradualist success of the country – which dates back to at least 1968 – in the field of liberalisation, marketisation and privatisation was accompanied by a constant overspending in the general government. The paper attempts to explore the reasons behind policymakers’ impotence to reform public finances. By providing a path-dependent explanation, it argues that both communist and postcommunist governments used the general budget as a buffer to compensate losers of economic reforms, especially microeconomic restructuring. The ever-widening circle of net benefiters of welfare provisions paid from the general budget, however, has made it simply unrealistic to implement sizeable fiscal adjustment, putting the country onto a deteriorating path of economic development.

Burnout Syndrome In Nursing Assistants Of A Public Hospital In The State Of São Paulo.

The burnout syndrome is a psychosocial phenomenon that arises as a response to chronic interpersonal stressors present at work. There are many aspects that make nursing assistants vulnerable to chronic stress situations that may lead to burnout, highlighting the low degree of autonomy in the healthcare staff and spending more in direct contact with patients. To assess the prevalence of the burnout syndrome in nursing assistants in a public hospital, as well as its association with socio-demographic and professional variables. A socio-demographic and professional questionnaire and the Maslach Burnout Inventory (MBI-SS) were applied to 534 nursing assistants. The prevalence of burnout syndrome among nursing assistants was 5.9%. High emotional exhaustion was observed in 23.6%, 21.9% showed high depersonalization, and 29.9% low professional achievement. It was found statistically significant associations between emotional exhaustion, job sector and marital status; depersonalization, having children and health problems; low professional achievement and job sector and number of jobs. There was association between job satisfaction and the three dimensions. Professionals working in the health area must pay intense and extended attention to people who are dependent upon others. The intimate contact of the nursing assistants with hard-to-handle patients, as well as being afraid to make mistakes in healthcare are additional chronic stress factors and burnout syndrome cases related in this study.

Equation of state for the magnetic-color-flavor-locked phase and its implications for compact star models

Using the solutions of the gap equations of the magnetic-color-flavor-locked (MCFL) phase of paired quark matter in a magnetic field, and taking into consideration the separation between the longitudinal and transverse pressures due to the field-induced breaking of the spatial rotational symmetry, the equation of state of the MCFL phase is self-consistently determined. This result is then used to investigate the possibility of absolute stability, which turns out to require a field-dependent ""bag constant"" to hold. That is, only if the bag constant varies with the magnetic field, there exists a window in the magnetic field vs bag constant plane for absolute stability of strange matter. Implications for stellar models of magnetized (self-bound) strange stars and hybrid (MCFL core) stars are calculated and discussed.

Control of the Intracellular Redox State by Glucose Participates in the Insulin Secretion Mechanism

Background: Production of reactive oxygen species (ROS) due to chronic exposure to glucose has been associated with impaired beta cell function and diabetes. However, physiologically, beta cells are well equipped to deal with episodic glucose loads, to which they respond with a fine tuned glucose-stimulated insulin secretion (GSIS). In the present study, a systematic investigation in rat pancreatic islets about the changes in the redox environment induced by acute exposure to glucose was carried out. Methodology/Principal Findings: Short term incubations were performed in isolated rat pancreatic islets. Glucose dose- and time-dependently reduced the intracellular ROS content in pancreatic islets as assayed by fluorescence in a confocal microscope. This decrease was due to activation of pentose-phosphate pathway (PPP). Inhibition of PPP blunted the redox control as well as GSIS in a dose-dependent manner. The addition of low doses of ROS scavengers at high glucose concentration acutely improved beta cell function. The ROS scavenger N-acetyl-L-cysteine increased the intracellular calcium response to glucose that was associated with a small decrease in ROS content. Additionally, the presence of the hydrogen peroxide-specific scavenger catalase, in its membrane-permeable form, nearly doubled glucose metabolism. Interestingly, though an increase in GSIS was also observed, this did not match the effect on glucose metabolism. Conclusions: The control of ROS content via PPP activation by glucose importantly contributes to the mechanisms that couple the glucose stimulus to insulin secretion. Moreover, we identified intracellular hydrogen peroxide as an inhibitor of glucose metabolism intrinsic to rat pancreatic islets. These findings suggest that the intracellular adjustment of the redox environment by glucose plays an important role in the mechanism of GSIS.

Low-Level Laser Irradiation (InGaAlP-660 nm) Increases Fibroblast Cell Proliferation and Reduces Cell Death in a Dose-Dependent Manner

Background and Objective: Impaired cell metabolism and increased cell death in fibroblast cells are physiological features of chronic tendinopathy. Although several studies have shown that low-level laser therapy (LLLT) at certain parameters has a biostimulatory effect on fibroblast cells, it remains uncertain if LLLT effects depend on the physiological state. Study Design/Material and Methods: High-metabolic immortal cell culture and primary human keloid fibroblast cell culture were used in this study. Trypan blue exclusion and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test were used to determine cell viability and proliferation. Propidium iodide stain was used for cell-cycle analysis by flow cytometry. Laser irradiation was performed daily on three consecutive days with a GaAlAs 660-nm laser (mean output: 50 mW, spot size 2 mm(2), power density = 2.5 W/cm(2)) and a typical LLLT dose and a high LLLT dose (irradiation times: 60 or 420 s; fluences: 150 or 1050 J/cm(2); energy delivered: 3 or 21 J). Results: Primary fibroblast cell culture from human keloids irradiated with 3 J showed significant proliferation by the trypan blue exclusion test (p < 0.05), whereas the 3T3 cell culture showed no difference using this method. Propidium iodide staining flow cytometry data showed a significant decrease in the percentage of cells being in proliferative phases of the cell cycle (S/g(2)/M) when irradiated with 21 J in both cell types (hypodiploid cells increased). Conclusions: Our data support the hypothesis that the physiological state of the cells affects the LLLT results, and that high-metabolic rate and short-cell-cycle 3T3 cells are not responsive to LLLT. In conclusion, LLLT with a dose of 3 J reduced cell death significantly, but did not stimulate cell cycle. A LLLT dose of 21 J had negative effects on the cells, as it increased cell death and inhibited cell proliferation.

Gradient-dependent density functionals of the Perdew-Burke-Ernzerhof type for atoms, molecules, and solids

One of the standard generalized-gradient approximations (GGAs) in use in modern electronic-structure theory [Perdew-Burke-Ernzerhof (PBE) GGA] and a recently proposed modification designed specifically for solids (PBEsol) are identified as particular members of a family of functionals taking their parameters from different properties of homogeneous or inhomogeneous electron liquids. Three further members of this family are constructed and tested, together with the original PBE and PBEsol, for atoms, molecules, and solids. We find that PBE, in spite of its popularity in solid-state physics and quantum chemistry, is not always the best performing member of the family and that PBEsol, in spite of having been constructed specifically for solids, is not the best for solids. The performance of GGAs for finite systems is found to sensitively depend on the choice of constraints stemming from infinite systems. Guidelines both for users and for developers of density functionals emerge from this work.