Individual differences in subjective and objective alertness during sleep deprivation are stable and unrelated

This study examines the individual reproducibility of alterations of subjective, objective, and EEG measures of alertness during 27 h of continuous wakefulness and analyzes their interrelationships. Eight subjects were studied twice under similar constant-routine conditions. Scales and performance tasks were administered at hourly intervals to define temporal changes in subjective and objective alertness. The wake EEG was recorded every 2 h, 2 min with eyes open and 2 min with eyes closed. Plasma glucose and melatonin levels were measured to estimate brain glucose utilization and individual circadian phase, respectively. Decrements of subjective alertness and performance deficits were found to be highly reproducible for a given individual. Remarkably, there was no relationship between the impairments of subjective and objective alertness. With increased duration of wakefulness, EEG activity with eyes closed increased in the delta range and decreased in the alpha range, but the magnitudes of these changes were also unrelated. These findings indicate that sleep deprivation has highly reproducible, but independent, effects on brain mechanisms controlling subjective and objective alertness.     

Impact of fire and the recovery of molluscs in south‐east Australian salt marsh

Fire has long been recognised as a natural force in structuring Northern Hemisphere salt marshes, yet little is known about the impact of fire on molluscs and native vegetation dynamics of Southern Hemisphere coastal salt marshes. Following a fire at Ash Island, Hunter River New South Wales, Australia in the summer 2012, we assessed patterns of recovery through time of gastropod populations and resident salt marsh vegetation including biomass for three keystone native plant species, Native Rush (Juncus kraussii Hochst.), a chenopod (Sarcocornia quinqueflora Bunge ex Ungen‐Sternberg A.J. Scott), Salt Couch (Sporobolus virginicus, L. Kunth) and the invasive Spiny Rush (Juncus acutus). In temperate east‐coast Australian salt marshes, Spiny Rush is displacing native salt marsh vegetation. After twelve months, the biomass of Native Rush recovered to similar pre‐burn levels. While fire affected the abundance, richness and composition of the gastropod assemblage differences were also largely driven by spatial variability. Gastropod assemblages associated with two of the higher elevation native species (Native Rush and Salt Couch) were impacted the most by fire. Greater abundance (between 1 and 5 orders of magnitude difference in abundance) and richness of gastropods were found in unburnt compared with burnt Native Rush and Salt Couch vegetation, while more gastropods were found in Spiny Rush in one site. Species prevalent in burnt vegetation included larger species of gastropods Ophicardelus ornatus (Ferussac, 1821) and Phallomedusa solida (Martens, 1878) with an unexpected spike in number of the smaller gastropod Tatea huonensis (Tenison‐Woods, 1876) in the spiny rush at one site only. In salt marsh habitats, many gastropods have planktonic larval dispersal stages which are dependent on the tidal height for transport and the structural complexity provided by vegetation at settlement. Since fire appears to negatively affect salt marsh gastropod populations within structurally complex Native Rush and Salt Couch, due consideration of the importance of these refuges for gastropods is recommended when fire or other disturbances occur in ecologically endangered salt marsh in the Southern Hemisphere. Managers need to consider spatial heterogeneity of molluscs and their recovery in the event of fire in Southern Hemisphere salt marshes.     

Vitamin D Status in Rheumatoid Arthritis: Inflammation,Arterial Stiffness and Circulating Progenitor Cell Number

Background and Aims

Suboptimal vitamin D status was recently acknowledged as an independent predictor of cardiovascular diseases and all-cause mortality in several clinical settings, and its serum levels are commonly reduced in Rheumatoid Arthritis (RA). Patients affected by RA present accelerated atherosclerosis and increased cardiovascular morbidity and mortality with respect to the general population. In RA, it has been reported an impairment of the number and the activity of circulating proangiogenic haematopoietic cells (PHCs), including CD34+, that may play a role in endothelial homeostasis. The purpose of the study is to investigate the association between vitamin D levels and PHCs, inflammatory markers, and arterial stiffening in patients with RA.

Methods and Results

CD34+ cells were isolated from 27 RA patients and 41 controls. Vitamin D levels, C-reactive protein (CRP), fibrinogen, pulse wave velocity (PWV), and carotid intima-media thickness (cIMT) were also evaluated. CD34+ count and vitamin D levels were lower in RA patients as compared to controls, while fibrinogen, CRP, PWV and cIMT were higher in RA patients. CD34+ cell number appeared to be associated with vitamin D levels, and negatively correlated to fibrinogen and early atherosclerosis markers (PWV and cIMT); vitamin D levels appear also to be inversely associated to fibrinogen.

Conclusions

RA patients with moderate disease activity presented with low vitamin D levels, low CD34+ cell count, increased PWV and cIMT; we found that vitamin D deficiency is associated to CD34+ cell reduction in peripheral blood, and with fibrinogen levels. This suggests that vitamin D might contribute to endothelial homeostasis in patients with RA.     

Determination of the absolute configurations of flexible molecules: synthesis and theoretical simulation of electronic circular dichroism/optical rotation of some pyrrolo[2,3-b]indoline alkaloids--a case study

The paper describes the synthesis and chiroptical properties of (-)-1,2,3,3a,8,8a,-hexahydro-1,3a-dimethyl-pyrrolo[2,3-b]indole, (-)-1, one of the monomeric units of many flexible polypyrroloindoline alkaloids and (-)-chimonanthine, (-)-2. The aim of this investigation is to show that, under certain circumstances, namely, with molecules for which the sign and order of magnitude of [alpha](D) are determined by the lowest-energy valence-shell transitions (referred to as class (a) molecules), a small basis set calculation of chiroptical properties provides reliable results, and that such a treatment can be employed for absolute configurational assignment of larger oligomers, for which the increased flexibility renders the analysis as formidable task. Actually, as the aforementioned two molecules belong to class (a) systems, a TDDFT/B3LYP/6-31G* calculation of the ECD and ORD spectra gives rise to a more than satisfactory simulation of these data, assuming the reported absolute configurations. In other words, the use of the TDDFT/B3LYP method with the small 6-31G* basis set enables one to treat large and flexible molecules such as (-)-2 (52 atoms and 6 conformers) by usage of a simple PC in about 2 weeks. This protocol demonstrates that an ab initio prediction of ECD/ORD spectra results in reliable assignments of absolute configuration of even relatively large natural products, thus economizing computation time.     

Association between cytosolic low molecular weight phosphotyrosine-phosphatase and malaria—a possible mechanism

Cytosolic low molecular weight phosphotyrosine-phosphatase shows dephosphorylating activity of the band 3 protein. Increased phosphorylation of this protein increases membrane rigidity and resistance to invasion of red blood cells by malarial parasites. This observation may explain the negative association previously reported by our group between the high activity ^*C allele of cytosolic low molecular weight phosphotyrosine-phosphatase and past malarial morbidity. Am J Phys Anthropol 108:241–244, 1999. © 1998 Wiley-Liss, Inc.     

Down-regulation of ABCB1 transporter by atorvastatin in a human hepatoma cell line and in human peripheral blood mononuclear cells

PURPOSE: The effect of atorvastatin, an HMG-CoA reductase inhibitor, on expression and activity of the drug transporter ABCB1 in HepG2 cells and peripheral blood mononuclear cells (PBMCs) was examined. METHODS: Localization and expression of ABCB1 in hepatocytes was examined by indirect immunofluorescence. Expression of ABCB1 mRNA and ABCB1 activity were examined in atorvastatin-treated and control cells and PBMCs using real-time PCR and Rhodamine 123 efflux assay. RESULTS: Immunohistochemical analysis revealed that ABCB1 is located at the apical membrane of the bile canaliculi. Atorvastatin at 10 and 20 microM up-regulated ABCB1 expression resulting in a significant 1.4-fold increase of the protein levels. Treatment of HepG2 cells with 20 microM atorvastatin caused a 60% reduction on mRNA expression (p<0.05) and a 41% decrease in ABCB1-mediated efflux of Rhodamine123 (p<0.01) by flow cytometry. Correlation was found between ABCB1 mRNA levels and creatine kinase (r=0.30; p=0.014) and total cholesterol (r=-0.31; p=0.010). CONCLUSIONS. Atorvastatin leads to decreased ABCB1 function and modulates ABCB1 synthesis in HepG2 cells and in PBMCs. ABCB1 plays a role in cellular protection as well as in secretion and/or disposition, therefore, inhibition of ABCB1 synthesis may increase the atorvastatin efficacy, leading to a more pronounced reduction of plasma cholesterol.     

Cutting edge: IFN-gamma regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection

T cell responses are important to the control of infection but are deleterious if not regulated. IFN-gamma-deficient mice infected with mycobacteria exhibit enhanced accumulation of activated effector T cells and neutrophils within granulomatous lesions. These cells do not control bacterial growth and compromise the integrity of the infected tissue. We show that IFN-gamma-deficient mice have increased numbers of IL-17-producing T cells following infection with Mycobacterium bovis bacille Calmette Guérin. Furthermore, exogenous IFN-gamma increases IL-12 and decreases IL-23 production by bacille Calmette Guérin-infected bone marrow-derived dendritic cells and reduces the frequency of IL-17-producing T cells induced by these bone marrow-derived dendritic cells. These data support the hypothesis that, during mycobacterial infection, both IFN-gamma- and IL-17-producing T cells are induced, but that IFN-gamma serves to limit the IL-17-producing T cell population. This counterregulation pathway may be an important factor in limiting mycobacterially associated immune-mediated pathology.