Molecular crowding defines a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology

Aerobic glycolysis is a seemingly wasteful mode of ATP production that is seen both in rapidly proliferating mammalian cells and highly active contracting muscles, but whether there is a common origin for its presence in these widely different systems is unknown. To study this issue, here we develop a model of human central metabolism that incorporates a solvent capacity constraint of metabolic enzymes and mitochondria, accounting for their occupied volume densities, while assuming glucose and/or fatty acid utilization. The model demonstrates that activation of aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles, because it provides higher ATP yield per volume density than mitochondrial oxidative phosphorylation. In the case of muscle physiology, the model also predicts that before the lactate switch, fatty acid oxidation increases, reaches a maximum, and then decreases to zero with concomitant increase in glucose utilization, in agreement with the empirical evidence. These results are further corroborated by a larger scale model, including biosynthesis of major cell biomass components. The larger scale model also predicts that in proliferating cells the lactate switch is accompanied by activation of glutaminolysis, another distinctive feature of the Warburg effect. In conclusion, intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating- and non-proliferating cells with high metabolic demand. Addition of this constraint to metabolic flux balance models can explain several observations of mammalian cell metabolism under steady state conditions

An on-board data management solution

A Marine Data Management System (MDM-400) has been installed on the Instituto Español de Oceanografía (IEO) research vessel B/O Cornide de Saavedra. It is an experience of how a commercial solution has been developed and fully adapted to the ship characteristics, including an external communication by Universal Mobile Telecommunications System (UMTS) connection that facilitates the maintenance works. The system runs on 4 windows based computers interconnected by a LAN (Local Area Network). The current work mainly focuses on discussing the technical solutions that have been taken, real-time integration, data storage and transmission, and external communications.Peer Reviewe

An evaluation of enteral nutrition practices and nutritional provision in children during the entire length of stay in critical care

<b>Background</b> Provision of optimal nutrition in children in critical care is often challenging. This study evaluated exclusive enteral nutrition (EN) provision practices and explored predictors of energy intake and delay of EN advancement in critically ill children.<p></p> <b>Methods</b> Data on intake and EN practices were collected on a daily basis and compared against predefined targets and dietary reference values in a paediatric intensive care unit. Factors associated with intake and advancement of EN were explored.<p></p> <b>Results</b> Data were collected from 130 patients and 887 nutritional support days (NSDs). Delay to initiate EN was longer in patients from both the General Surgical and congenital heart defect (CHD) Surgical groups [Median (IQR); CHD Surgical group: 20.3 (16.4) vs General Surgical group: 11.4 (53.5) vs Medical group: 6.5 (10.9) hours; p <= 0.001]. Daily fasting time per patient was significantly longer in patients from the General Surgical and CHD Surgical groups than those from the Medical group [% of 24 h, Median (IQR); CHD Surgical group: 24.0 (29.2) vs General Surgical group: 41.7 (66.7) vs Medical group: 9.4 (21.9); p <= 0.001]. A lower proportion of fluids was delivered as EN per patient (45% vs 73%) or per NSD (56% vs 73%) in those from the CHD Surgical group compared with those with medical conditions. Protein and energy requirements were achieved in 38% and 33% of the NSDs. In a substantial proportion of NSDs, minimum micronutrient recommendations were not met particularly in those patients from the CHD Surgical group. A higher delivery of fluid requirements (p < 0.05) and a greater proportion of these delivered as EN (p < 0.001) were associated with median energy intake during stay and delay of EN advancement. Fasting (31%), fluid restriction (39%) for clinical reasons, procedures requiring feed cessation and establishing EN (22%) were the most common reasons why target energy requirements were not met.<p></p> <b>Conclusions</b> Provision of optimal EN support remains challenging and varies during hospitalisation and among patients. Delivery of EN should be prioritized over other "non-nutritional" fluids whenever this is possible.<p></p&gt

Relative Stability of Core Groups in Pollination Networks in a Biodiversity Hotspot over Four Years

Plants and their pollinators form pollination networks integral to the evolution and persistence of species in communities. Previous studies suggest that pollination network structure remains nested while network composition is highly dynamic. However, little is known about temporal variation in the structure and function of plant-pollinator networks, especially in species-rich communities where the strength of pollinator competition is predicted to be high. Here we quantify temporal variation of pollination networks over four consecutive years in an alpine meadow in the Hengduan Mountains biodiversity hotspot in China. We found that ranked positions and idiosyncratic temperatures of both plants and pollinators were more conservative between consecutive years than in non-consecutive years. Although network compositions exhibited high turnover, generalized core groups – decomposed by a k-core algorithm – were much more stable than peripheral groups. Given the high rate of turnover observed, we suggest that identical plants and pollinators that persist for at least two successive years sustain pollination services at the community level. Our data do not support theoretical predictions of a high proportion of specialized links within species-rich communities. Plants were relatively specialized, exhibiting less variability in pollinator composition at pollinator functional group level than at the species level. Both specialized and generalized plants experienced narrow variation in functional pollinator groups. The dynamic nature of pollination networks in the alpine meadow demonstrates the potential for networks to mitigate the effects of fluctuations in species composition in a high biodiversity area

Are Nested Networks More Robust to Disturbance? A Test Using Epiphyte-Tree, Comensalistic Networks

Recent research on ecological networks suggests that mutualistic networks are more nested than antagonistic ones and, as a result, they are more robust against chains of extinctions caused by disturbances. We evaluate whether mutualistic networks are more nested than comensalistic and antagonistic networks, and whether highly nested, host-epiphyte comensalistic networks fit the prediction of high robustness against disturbance. A review of 59 networks including mutualistic, antagonistic and comensalistic relationships showed that comensalistic networks are significantly more nested than antagonistic and mutualistic networks, which did not differ between themselves. Epiphyte-host networks from old-growth forests differed from those from disturbed forest in several topological parameters based on both qualitative and quantitative matrices. Network robustness increased with network size, but the slope of this relationship varied with nestedness and connectance. Our results indicate that interaction networks show complex responses to disturbances, which influence their topology and indirectly affect their robustness against species extinctions

Activation of Serine One-Carbon Metabolism by Calcineurin A beta 1 Reduces Myocardial Hypertrophy and Improves Ventricular Function

Background In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria. Objectives The authors aimed to determine the role of the calcineurin splicing variant CnAβ1 in the context of cardiac hypertrophy and its mechanism of action. Methods Transgenic mice overexpressing CnAβ1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnAβ1 (CnAβ1Δi12 mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured by echocardiography. Mice were characterized using various molecular analyses. Results In contrast to other calcineurin isoforms, the authors show here that cardiac-specific overexpression of CnAβ1 in transgenic mice reduces cardiac hypertrophy and improves cardiac function. This effect is mediated by activation of serine and one-carbon metabolism, and the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production. The induction of enzymes involved in this metabolic pathway by CnAβ1 is dependent on mTOR activity. Inhibition of serine and one-carbon metabolism blocks the beneficial effects of CnAβ1. CnAβ1Δi12 mice show increased cardiac hypertrophy and declined contractility. Conclusions The metabolic reprogramming induced by CnAβ1 redefines the role of calcineurin in the heart and shows for the first time that activation of the serine and one-carbon pathway has beneficial effects on cardiac hypertrophy and function, paving the way for new therapeutic approaches

The abundant marine bacterium Pelagibacter simultaneously catabolizes dimethylsulfoniopropionate to the gases dimethyl sulfide and methanethiol

Marine phytoplankton produce ~109 tons of dimethylsulfoniopropionate (DMSP) per year1,2, an estimated 10% of which is catabolized by bacteria through the DMSP cleavage pathway to the climatically active gas dimethyl sulfide (DMS)3,4. SAR11 Alphaproteobacteria (order Pelagibacterales), the most abundant chemoorganotrophic bacteria in the oceans, have been shown to assimilate DMSP into biomass, thereby supplying this cell’s unusual requirement for reduced sulfur5,6. Here we report that Pelagibacter HTCC1062 produces the gas methanethiol (MeSH) and that simultaneously a second DMSP catabolic pathway, mediated by a cupin-like DMSP lyase, DddK, shunts as much as 59% of DMSP uptake to DMS production. We propose a model in which the allocation of DMSP between these pathways is kinetically controlled to release increasing amounts of DMS as the supply of DMSP exceeds cellular sulfur demands for biosynthesis

Turbulence and galactic structure

Interstellar turbulence is driven over a wide range of scales by processes including spiral arm instabilities and supernovae, and it affects the rate and morphology of star formation, energy dissipation, and angular momentum transfer in galaxy disks. Star formation is initiated on large scales by gravitational instabilities which control the overall rate through the long dynamical time corresponding to the average ISM density. Stars form at much higher densities than average, however, and at much faster rates locally, so the slow average rate arises because the fraction of the gas mass that forms stars at any one time is low, ~10^{-4}. This low fraction is determined by turbulence compression, and is apparently independent of specific cloud formation processes which all operate at lower densities. Turbulence compression also accounts for the formation of most stars in clusters, along with the cluster mass spectrum, and it gives a hierarchical distribution to the positions of these clusters and to star-forming regions in general. Turbulent motions appear to be very fast in irregular galaxies at high redshift, possibly having speeds equal to several tenths of the rotation speed in view of the morphology of chain galaxies and their face-on counterparts. The origin of this turbulence is not evident, but some of it could come from accretion onto the disk. Such high turbulence could help drive an early epoch of gas inflow through viscous torques in galaxies where spiral arms and bars are weak. Such evolution may lead to bulge or bar formation, or to bar re-formation if a previous bar dissolved. We show evidence that the bar fraction is about constant with redshift out to z~1, and model the formation and destruction rates of bars required to achieve this constancy.Comment: in: Penetrating Bars through Masks of Cosmic Dust: The Hubble Tuning Fork strikes a New Note, Eds., K. Freeman, D. Block, I. Puerari, R. Groess, Dordrecht: Kluwer, in press (presented at a conference in South Africa, June 7-12, 2004). 19 pgs, 5 figure