Assessment of the impact of increased solar ultraviolet radiation upon marine ecosystems

Specifically, the study has addressed the following: (1) potential for irreversible damage to the productivity, structure and/or functioning of a model estuarine ecosystem by increased UV-B radiation or ecosystems highly stable or amenable to adaptive change, and (2) the sensitivity of key community components (the primary producers, consumers, and decomposers) to increased UV-B radiation. Three areas of study were examined during the past year: (1) a continuation of the study utilizing the two seminatural ecosystem chambers, (2) a pilot study utilizing three flow-through ecosystem tanks enclosed in a small, outdoor greenhouse, and (3) sensitivity studies of representative primary producers and consumers

Assessment of the impact of increased solar ultraviolet radiation upon marine ecosystems

Data was provided to assess the potential impact upon marine ecosystems if space shuttle operations contribute to a reduction of the stratospheric ozone layer. The potential for irreversible damage to the productivity, structure and/or functioning of a model estuarine ecosystem by increased UV-B radiation was established. The sensitivity of key community components (the primary producers) to increased UV-B radiation was delineated

The tyrosine kinase inhibitor dasatinib (SPRYCEL) inhibits chondrocyte activity and proliferation

Letter to the EditorK Vandyke, S Fitter and ACW Zannettin

Investigating an API for resilient exascale computing.

Increased HPC capability comes with increased complexity, part counts, and fault occurrences. In- creasing the resilience of systems and applications to faults is a critical requirement facing the viability of exascale systems, as the overhead of traditional checkpoint/restart is projected to outweigh its bene ts due to fault rates outpacing I/O bandwidths. As faults occur and propagate throughout hardware and software layers, pervasive noti cation and handling mechanisms are necessary. This report describes an initial investigation of fault types and programming interfaces to mitigate them. Proof-of-concept APIs are presented for the frequent and important cases of memory errors and node failures, and a strategy proposed for lesystem failures. These involve changes to the operating system, runtime, I/O library, and application layers. While a single API for fault handling among hardware and OS and application system-wide remains elusive, the e ort increased our understanding of both the mountainous challenges and the promising trailheads.

Modelling a Historic Oil-Tank Fire Allows an Estimation of the Sensitivity of the Infrared Receptors in Pyrophilous Melanophila Beetles

Pyrophilous jewel beetles of the genus Melanophila approach forest fires and there is considerable evidence that these beetles can detect fires from great distances of more than 60 km. Because Melanophila beetles are equipped with infrared receptors and are also attracted by hot surfaces it can be concluded that these infrared receptors are used for fire detection

Dasatinib as a Bone-Modifying Agent: Anabolic and Anti-Resorptive Effects

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Bone loss, in malignant or non-malignant diseases, is caused by increased osteoclast resorption and/or reduced osteoblast bone formation, and is commonly associated with skeletal complications. Thus, there is a need to identify new agents capable of influencing bone remodeling. We aimed to further pre-clinically evaluate the effects of dasatinib (BMS-354825), a multitargeted tyrosine kinase inhibitor, on osteoblast and osteoclast differentiation and function. [Methods]: For studies on osteoblasts, primary human bone marrow mensenchymal stem cells (hMSCs) together with the hMSC-TERT and the MG-63 cell lines were employed. Osteoclasts were generated from peripheral blood mononuclear cells (PBMC) of healthy volunteers. Skeletally-immature CD1 mice were used in the in vivo model. [Results]: Dasatinib inhibited the platelet derived growth factor receptor-β (PDGFR-β), c-Src and c-Kit phosphorylation in hMSC-TERT and MG-63 cell lines, which was associated with decreased cell proliferation and activation of canonical Wnt signaling. Treatment of MSCs from healthy donors, but also from multiple myeloma patients with low doses of dasatinib (2-5 nM), promoted its osteogenic differentiation and matrix mineralization. The bone anabolic effect of dasatinib was also observed in vivo by targeting endogenous osteoprogenitors, as assessed by elevated serum levels of bone formation markers, and increased trabecular microarchitecture and number of osteoblast-like cells. By in vitro exposure of hemopoietic progenitors to a similar range of dasatinib concentrations (1-2 nM), novel biological sequelae relative to inhibition of osteoclast formation and resorptive function were identified, including F-actin ring disruption, reduced levels of c-Fos and of nuclear factor of activated T cells 1 (NFATc1) in the nucleus, together with lowered cathepsin K, αVβ3 integrin and CCR1 expression. [Conclusions]: Low dasatinib concentrations show convergent bone anabolic and reduced bone resorption effects, which suggests its potential use for the treatment of bone diseases such as osteoporosis, osteolytic bone metastasis and myeloma bone disease. © 2012 Garcia-Gomez et al.This work was supported by grants from the Spanish Ministry of Science and Innovation – ISCIII (PI081825); Mutua Madrileña Medical Research Foundation (AP27262008); Centro en Red of Regenerative Medicine and Cellular Therapy from Castilla y León, Consejería de Sanidad JCyL – ISCIII; the Cooperative Research Thematic Network in Cancer (RTICC; RD06/0020/0006 and RD03/0020/0041); and Spanish FIS (PS09/01897). AG-G and CS are supported by the Centro en Red of Regenerative Medicine and Cellular Therapy from Castilla y León Project.Peer Reviewe

Biochemical evidence for an alternate pathway in N-linked glycoprotein biosynthesis

Asparagine-linked glycosylation is a complex protein modification conserved among all three domains of life. Herein we report the in vitro analysis of N-linked glycosylation from the methanogenic archaeon Methanococcus voltae. Using a suite of synthetic and semisynthetic substrates, we show that AglK initiates N-linked glycosylation in M. voltae through the formation of α-linked dolichyl monophosphate N-acetylglucosamine, which contrasts with the polyprenyl diphosphate intermediates that feature in both eukaryotes and bacteria. Notably, AglK has high sequence homology to dolichyl phosphate β-glucosyltransferases, including Alg5 in eukaryotes, suggesting a common evolutionary origin. The combined action of the first two enzymes, AglK and AglC, afforded an α-linked dolichyl monophosphate glycan that serves as a competent substrate for the archaeal oligosaccharyl transferase AglB. These studies provide what is to our knowledge the first biochemical evidence revealing that, despite the apparent similarity of the overall pathways, there are actually two general strategies to achieve N-linked glycoproteins across the domains of life.National Institutes of Health (U.S.) (Grant GM039334

Effects of N-Glycosylation Site Removal in Archaellins on the Assembly and Function of Archaella in Methanococcus maripaludis

In Methanococcus maripaludis S2, the swimming organelle, the archaellum, is composed of three archaellins, FlaB1S2, FlaB2S2 and FlaB3S2. All three are modified with an N-linked tetrasaccharide at multiple sites. Disruption of the N-linked glycosylation pathway is known to cause defects in archaella assembly or function. Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). Of the 6 double-site mutation complementations all were archaellated except D1,3. Of the 4 triple-site mutation complements, only D2,3,4 was archaellated. Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. All complementations that led to a return of archaella also resulted in motile cells with the exception of the D4 version. In addition, a series of FlaB2S2 scanning deletions each missing 10 amino acids was also generated and tested for their ability to complement the ΔflaB2S2 strain. While most variants were expressed, none of them restored archaellation, although FlaB2S2 harbouring a smaller 3-amino acid deletion was able to partially restore archaellation

An alternative perspective on biofeedback efficacy studies: A reply to Steiner and Dince

Clinical applications of biofeedback have proliferated and considerable lore surrounding the application of these techniques has evolved. Many assertions about the effectiveness of biofeedback training are based on findings of the least well-controlled studies, while many of the better controlled studies have failed to show that biofeedback directly mediates target symptoms or is superior to other treatments. Steiner and Dince (1981) suggest that the failure of these controlled studies is primarily attributable to methodological deficiencies. We believe that the question of whether or not there is a specific effect of biofeedback training is still frequently confused with the question of whether or not the treatment package as a whole has therapeutic value. Biofeedback is often therapeutic; however, evidence is often lacking that its effectiveness is due to biofeedback-trained changes in a target physiological process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44088/1/10484_2005_Article_BF00998755.pd

Depression and anxiety in patients with rheumatoid arthritis: prevalence rates based on a comparison of the Depression, Anxiety and Stress Scale (DASS) and the hospital, Anxiety and Depression Scale (HADS)

<p>Abstract</p> <p>Background</p> <p>While it is recognised that depression is prevalent in Rheumatoid Arthritis (RA), recent studies have also highlighted significant levels of anxiety in RA patients. This study compared two commonly used scales, the Depression Anxiety and Stress Scale (DASS) and the Hospital Anxiety and Depression Scale (HADS), in relation to their measurement range and cut points to consider the relative prevalence of both constructs, and if prevalence rates may be due to scale-specific case definition.</p> <p>Methods</p> <p>Patients meeting the criteria for RA were recruited in Leeds, UK and Sydney, Australia and asked to complete a survey that included both scales. The data was analysed using the Rasch measurement model.</p> <p>Results</p> <p>A total of 169 RA patients were assessed, with a repeat subsample, resulting in 323 cases for analysis. Both scales met Rasch model expectations. Using the 'possible+probable' cut point from the HADS, 58.3% had neither anxiety nor depression; 13.5% had anxiety only; 6.4% depression only and 21.8% had both 'possible+probable' anxiety and depression. Cut points for depression were comparable across the two scales while a lower cut point for anxiety in the DASS was required to equate prevalence.</p> <p>Conclusions</p> <p>This study provides further support for high prevalence of depression and anxiety in RA. It also shows that while these two scales provide a good indication of possible depression and anxiety, the estimates of prevalence so derived could vary, particularly for anxiety. These findings are discussed in terms of comparisons across studies and selection of scales for clinical use.</p