O-MOORE-NICE!: new methodologies and algorithms for design and simulation of analog integrated circuits

No abstract

Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases

Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus (SIV) infection and may contribute to the development of cachexia. We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L -carnitine, i.e. an agent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice. In the mice, L -carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-treated group in the randomized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities. Further studies may be warranted to determine the effect of L -carnitine on the intramuscular GSH levels in cancer patients. © 2000 Cancer Research Campaig

Biodiversity promotes ecosystem functioning despite environmental change

Three decades of research have demonstrated that biodiversity can promote the functioning of ecosystems. Yet, it is unclear whether the positive effects of biodiversity on ecosystem functioning will persist under various types of global environmental change drivers. We conducted a meta-analysis of 46 factorial experiments manipulating both species richness and the environment to test how global change drivers (i.e. warming, drought, nutrient addition or CO2 enrichment) modulated the effect of biodiversity on multiple ecosystem functions across three taxonomic groups (microbes, phytoplankton and plants). We found that biodiversity increased ecosystem functioning in both ambient and manipulated environments, but often not to the same degree. In particular, biodiversity effects on ecosystem functioning were larger in stressful environments induced by global change drivers, indicating that high-diversity communities were more resistant to environmental change. Using a subset of studies, we also found that the positive effects of biodiversity were mainly driven by interspecific complementarity and that these effects increased over time in both ambient and manipulated environments. Our findings support biodiversity conservation as a key strategy for sustainable ecosystem management in the face of global environmental change

Environmental variability in aquatic ecosystems: avenues for future multifactorial experiments

The relevance of considering environmental variability for understanding and predicting biological responses to environmental changes has resulted in a recent surge in variability-focused ecological research. However, integration of findings that emerge across studies and identification of remaining knowledge gaps in aquatic ecosystems remain critical. Here, we address these aspects by: (1) summarizing relevant terms of variability research including the components (characteristics) of variability and key interactions when considering multiple environmental factors; (2) identifying conceptual frameworks for understanding the consequences of environmental variability in single and multi-factorial scenarios; (3) highlighting challenges for bridging theoretical and experimental studies involving transitioning from simple to more complex scenarios; (4) proposing improved approaches to overcome current mismatches between theoretical predictions and experimental observations; and (5) providing a guide for designing integrated experiments across multiple scales, degrees of control, and complexity in light of their specific strengths and limitations

Patient-directed self-management of pain (PaDSMaP) compared to treatment as usual following total knee replacement; a randomised controlled trial

Background Self-administration of medicines by patients whilst in hospital is being increasingly promoted despite little evidence to show the risks and benefits. Pain control after total knee replacement (TKR) is known to be poor. The aim of the study was to determine if patients operated on with a TKR who self-medicate their oral analgesics in the immediate post-operative period have better pain control than those who receive their pain control by nurse-led drug rounds (Treatment as Usual (TAU)). Methods A prospective, parallel design, open-label, randomised controlled trial comparing pain control in patient-directed self-management of pain (PaDSMaP) with nurse control of oral analgesia (TAU) after a TKR. Between July 2011 and March 2013, 144 self-medicating adults were recruited at a secondary care teaching hospital in the UK. TAU patients (n = 71) were given medications by a nurse after their TKR. PaDSMaP patients (n = 73) took oral medications for analgesia and co-morbidities after two 20 min training sessions reinforced with four booklets. Primary outcome was pain (100 mm visual analogue scale (VAS)) at 3 days following TKR surgery or at discharge (whichever came soonest). Seven patients did not undergo surgery for reasons unrelated to the study and were excluded from the intention-to-treat (ITT) analysis. Results ITT analysis did not detect any significant differences between the two groups’ pain scores. A per protocol (but underpowered) analysis of the 60% of patients able to self-medicate found reduced pain compared to the TAU group at day 3/discharge, (VAS -9.9 mm, 95% CI -18.7, − 1.1). One patient in the self-medicating group over-medicated but suffered no harm. Conclusion Self-medicating patients did not have better (lower) pain scores compared to the nurse-managed patients following TKR. This cohort of patients were elderly with multiple co-morbidities and may not be the ideal target group for self-medication

Functionally reversible impacts of disturbances on lake food webs linked to spatial and seasonal dependencies

Increasing human impact on the environment is causing drastic changes in disturbance regimes and how they prevail over time. Of increasing relevance is to further our understanding on biological responses to pulse disturbances (short duration) and how they interact with other ongoing press disturbances (constantly present). Because the temporal and spatial contexts of single experiments often limit our ability to generalize results across space and time, we conducted a modularized mesocosm experiment replicated in space (five lakes along a latitudinal gradient in Scandinavia) and time (two seasons, spring and summer) to generate general predictions on how the functioning and composition of multitrophic plankton communities (zoo-, phyto- and bacterioplankton) respond to pulse disturbances acting either in isolation or combined with press disturbances. As pulse disturbance, we used short-term changes in fish presence, and as press disturbance, we addressed the ongoing reduction in light availability caused by increased cloudiness and lake browning in many boreal and subarctic lakes. First, our results show that the top-down pulse disturbance had the strongest effects on both functioning and composition of the three trophic levels across sites and seasons, with signs for interactive impacts with the bottom-up press disturbance on phytoplankton communities. Second, community composition responses to disturbances were highly divergent between lakes and seasons: temporal accumulated community turnover of the same trophic level either increased (destabilization) or decreased (stabilization) in response to the disturbances compared to control conditions. Third, we found functional recovery from the pulse disturbances to be frequent at the end of most experiments. In a broader context, these results demonstrate that top-down, pulse disturbances, either alone or with additional constant stress upon primary producers caused by bottom-up disturbances, can induce profound but often functionally reversible changes across multiple trophic levels, which are strongly linked to spatial and temporal context dependencies. Furthermore, the identified dichotomy of disturbance effects on the turnover in community composition demonstrates the potential of disturbances to either stabilize or destabilize biodiversity patterns over time across a wide range of environmental conditions

Uncovering Ubiquitin and Ubiquitin-like Signaling Networks

Microscopic imaging and technolog

Prokayrotic Ubiquitin-Like Protein (Pup) Proteome of Mycobacterium tuberculosis

Prokaryotic ubiquitin-like protein (Pup) in Mycobacterium tuberculosis (Mtb) is the first known post-translational small protein modifier in prokaryotes, and targets several proteins for degradation by a bacterial proteasome in a manner akin to ubiquitin (Ub) mediated proteolysis in eukaryotes. To determine the extent of pupylation in Mtb, we used tandem affinity purification to identify its “pupylome”. Mass spectrometry identified 55 out of 604 purified proteins with confirmed pupylation sites. Forty-four proteins, including those with and without identified pupylation sites, were tested as substrates of proteolysis in Mtb. Under steady state conditions, the majority of the test proteins did not accumulate in degradation mutants, suggesting not all targets of pupylation are necessarily substrates of the proteasome under steady state conditions. Four proteins implicated in Mtb pathogenesis, Icl (isocitrate lyase), Ino1 (inositol-1-phosphate synthase), MtrA (Mtb response regulator A) and PhoP (phosphate response regulator P), showed altered levels in degradation defective Mtb. Icl, Ino1 and MtrA accumulated in Mtb degradation mutants, suggesting these proteins are targeted to the proteasome. Unexpectedly, PhoP was present in wild type Mtb but undetectable in the degradation mutants. Taken together, these data demonstrate that pupylation regulates numerous proteins in Mtb and may not always lead to degradation