The operationalization of fatigue in frailty scales : a systematic review

Purpose: To identify the different fatigue items in existing frailty scales. Methods: PubMed, Web of Knowledge and PsycINFO were systematically screened for frailty scales. 133 articles were included, describing 158 frailty scales. Fatigue items were extracted and categorized in 4 fatigue constructs: “mood state related tiredness”, “general feeling of tiredness”, “activity based feeling of tiredness” and “resistance to physical tiredness”. Results: 120 fatigue items were identified, of which 100 belonged to the construct “general feeling of tiredness” and only 9 to the construct “resistance to physical tiredness”. 49,4% of the frailty scales included at least 1 fatigue item, representing 15±9,3% of all items in these scales. Fatigue items have a significantly higher weight in single domain (dominantly physical frailty scales) versus multi domain frailty scales (21±3.2 versus 10.6±9.8%, p=<0,05 ). Conclusion: Fatigue is prominently represented in frailty scales, covering a great diversity in fatigue constructs and underlying pathophysiological mechanisms by which fatigue relates to frailty. Although fatigue items were more prevalent and had a higher weight in physical frailty scales, the operationalization of fatigue leaned more towards psychological constructs. This review can be used as a reference for choosing a suitable frailty scale depending on the type of fatigue of interest

Correlation of gene expression and protein production rate - a system wide study

<p>Abstract</p> <p>Background</p> <p>Growth rate is a major determinant of intracellular function. However its effects can only be properly dissected with technically demanding chemostat cultivations in which it can be controlled. Recent work on <it>Saccharomyces cerevisiae </it>chemostat cultivations provided the first analysis on genome wide effects of growth rate. In this work we study the filamentous fungus <it>Trichoderma reesei </it>(<it>Hypocrea jecorina</it>) that is an industrial protein production host known for its exceptional protein secretion capability. Interestingly, it exhibits a low growth rate protein production phenotype.</p> <p>Results</p> <p>We have used transcriptomics and proteomics to study the effect of growth rate and cell density on protein production in chemostat cultivations of <it>T. reesei</it>. Use of chemostat allowed control of growth rate and exact estimation of the extracellular specific protein production rate (SPPR). We find that major biosynthetic activities are all negatively correlated with SPPR. We also find that expression of many genes of secreted proteins and secondary metabolism, as well as various lineage specific, mostly unknown genes are positively correlated with SPPR. Finally, we enumerate possible regulators and regulatory mechanisms, arising from the data, for this response.</p> <p>Conclusions</p> <p>Based on these results it appears that in low growth rate protein production energy is very efficiently used primarly for protein production. Also, we propose that flux through early glycolysis or the TCA cycle is a more fundamental determining factor than growth rate for low growth rate protein production and we propose a novel eukaryotic response to this i.e. the lineage specific response (LSR).</p

Oxygen dependence of metabolic fluxes and energy generation of Saccharomyces cerevisiae CEN.PK113-1A

<p>Abstract</p> <p>Background</p> <p>The yeast <it>Saccharomyces cerevisiae </it>is able to adjust to external oxygen availability by utilizing both respirative and fermentative metabolic modes. Adjusting the metabolic mode involves alteration of the intracellular metabolic fluxes that are determined by the cell's multilevel regulatory network. Oxygen is a major determinant of the physiology of <it>S. cerevisiae </it>but understanding of the oxygen dependence of intracellular flux distributions is still scarce.</p> <p>Results</p> <p>Metabolic flux distributions of <it>S. cerevisiae </it>CEN.PK113-1A growing in glucose-limited chemostat cultures at a dilution rate of 0.1 h^-1with 20.9%, 2.8%, 1.0%, 0.5% or 0.0% O₂in the inlet gas were quantified by ¹³C-MFA. Metabolic flux ratios from fractional [U-¹³C]glucose labelling experiments were used to solve the underdetermined MFA system of central carbon metabolism of <it>S. cerevisiae</it>.</p> <p>While ethanol production was observed already in 2.8% oxygen, only minor differences in the flux distribution were observed, compared to fully aerobic conditions. However, in 1.0% and 0.5% oxygen the respiratory rate was severely restricted, resulting in progressively reduced fluxes through the TCA cycle and the direction of major fluxes to the fermentative pathway. A redistribution of fluxes was observed in all branching points of central carbon metabolism. Yet only when oxygen provision was reduced to 0.5%, was the biomass yield exceeded by the yields of ethanol and CO₂. Respirative ATP generation provided 59% of the ATP demand in fully aerobic conditions and still a substantial 25% in 0.5% oxygenation. An extensive redistribution of fluxes was observed in anaerobic conditions compared to all the aerobic conditions. Positive correlation between the transcriptional levels of metabolic enzymes and the corresponding fluxes in the different oxygenation conditions was found only in the respirative pathway.</p> <p>Conclusion</p> <p>¹³C-constrained MFA enabled quantitative determination of intracellular fluxes in conditions of different redox challenges without including redox cofactors in metabolite mass balances. A redistribution of fluxes was observed not only for respirative, respiro-fermentative and fermentative metabolisms, but also for cells grown with 2.8%, 1.0% and 0.5% oxygen. Although the cellular metabolism was respiro-fermentative in each of these low oxygen conditions, the actual amount of oxygen available resulted in different contributions through respirative and fermentative pathways.</p

The Emergence and Early Evolution of Biological Carbon-Fixation

The fixation of into living matter sustains all life on Earth, and embeds the biosphere within geochemistry. The six known chemical pathways used by extant organisms for this function are recognized to have overlaps, but their evolution is incompletely understood. Here we reconstruct the complete early evolutionary history of biological carbon-fixation, relating all modern pathways to a single ancestral form. We find that innovations in carbon-fixation were the foundation for most major early divergences in the tree of life. These findings are based on a novel method that fully integrates metabolic and phylogenetic constraints. Comparing gene-profiles across the metabolic cores of deep-branching organisms and requiring that they are capable of synthesizing all their biomass components leads to the surprising conclusion that the most common form for deep-branching autotrophic carbon-fixation combines two disconnected sub-networks, each supplying carbon to distinct biomass components. One of these is a linear folate-based pathway of reduction previously only recognized as a fixation route in the complete Wood-Ljungdahl pathway, but which more generally may exclude the final step of synthesizing acetyl-CoA. Using metabolic constraints we then reconstruct a “phylometabolic” tree with a high degree of parsimony that traces the evolution of complete carbon-fixation pathways, and has a clear structure down to the root. This tree requires few instances of lateral gene transfer or convergence, and instead suggests a simple evolutionary dynamic in which all divergences have primary environmental causes. Energy optimization and oxygen toxicity are the two strongest forces of selection. The root of this tree combines the reductive citric acid cycle and the Wood-Ljungdahl pathway into a single connected network. This linked network lacks the selective optimization of modern fixation pathways but its redundancy leads to a more robust topology, making it more plausible than any modern pathway as a primitive universal ancestral form

Tpc1 is an important Zn(II)(2)Cys(6) transcriptional regulator required for polarized growth and virulence in the rice blast fungus

The establishment of polarity is a critical process in pathogenic fungi, mediating infection-related morphogenesis and host tissue invasion. Here, we report the identification of TPC1 (Transcription factor for Polarity Control 1), which regulates invasive polarized growth in the rice blast fungus Magnaporthe oryzae. TPC1 encodes a putative transcription factor of the fungal Zn(II)(2)Cys(6) family, exclusive to filamentous fungi. Tpc1-deficient mutants show severe defects in conidiogenesis, infection-associated autophagy, glycogen and lipid metabolism, and plant tissue colonisation. By tracking actin-binding proteins, septin-5 and autophagosome components, we show that Tpc1 regulates cytoskeletal dynamics and infection-associated autophagy during appressorium-mediated plant penetration. We found that Tpc1 interacts with Mst12 and modulates its DNA-binding activity, while Tpc1 nuclear localisation also depends on the MAP kinase Pmk1, consistent with the involvement of Tpc1 in this signalling pathway, which is critical for appressorium development. Importantly, Tpc1 directly regulates NOXD expression, the p22(phox) subunit of the fungal NADPH oxidase complex via an interaction with Mst12. Tpc1 therefore controls spatial and temporal regulation of cortical F-actin through regulation of the NADPH oxidase complex during appressorium re-polarisation. Consequently, Tpc1 is a core developmental regulator in filamentous fungi, linking the regulated synthesis of reactive oxygen species and the Pmk1 pathway, with polarity control during host invasion

Contribution to the knowledge of the dissolution mechanism of stainless steel in nitric acid highlight Cr(VI) in the oxide layer

International audienceThe materials aging (mainly stainless steels) of the spent nuclear fuel reprocessing plant is the focus of an important RetD activity at CEA. The control of this aging will be achieved by a better understanding of stainless steels corrosion mechanisms in the dissolution medium. This medium is mainly hot concentrated nitric acid and sometimes in the presence of oxidizing ions. Thus it's really important to describe precisely the mechanism of corrosion during the dissolution and find an indicator of the transition between passive field and transpassive field where the intergranular corrosion lead to an important increase of corrosion rate. First, a literature highlight by electrochemistry experiment (potential imposition) the presence of Cr(VI) in the oxide layer of stainless steel 304L in nitric acid [1]. Secondly a study of chemical corrosion was undertaken through immersion tests on stainless steel 304L in boiling nitric acid and which contain sometimes oxidizing species (Ce(IV), V(V)) [2]. By using several analytical techniques (X-ray photoelectron spectroscopy, Scanning Electron Microscopy, Ultravioletvisible spectroscopy ), those experiments have improved the knowledge of the dissolution mechanism including highlighting the presence of an extreme surface layer of Cr(VI) that could be related to a grain marking and a preliminary step of intergranular corrosion

Modelisation du comportement electrochimique du plutonium en milieu acide nitrique

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Etude du comportement electrochimique des ions oxydants Np et Pu en milieu acide nitrique en fonction de la temperature

National audienceLe combustible nucleaire use presente a l'issue de son sejour en reacteur, un panel de radionucleides aux proprietes tres diverses provenant des reactions de capture et de fission nucleaires. Parmi ces radionucleides, le plutonium et le neptunium sont presents a differents degres d'oxydation dans les differentes etapes de traitement-recyclage du combustible. En milieu acide nitrique, les ions Np(VI) et Pu(VI) ont un fort pouvoir oxydant (dans 1 mol/L d'acide nitrique a 25 DC, E0 (Np(VI)/Np(V) = 1,105 V/ESH [1] et E0 Pu(VI)/Pu(V) = 0,909 V/ESH [2]) et sont donc susceptibles d'augmenter la vitesse de corrosion des aciers inoxydables austenitiques presents dans les installations de traitement du combustible use [3]. La comprehension de leur comportement redox et des differents mecanismes reactionnels en milieu acide nitrique sur electrode inerte est une etape importante prealable avant d'etudier leur effet sur des aciers de structure.Ce travail presente le comportement electrochimique des ions oxydants du neptunium (Np) et du plutonium (Pu) en milieu acide nitrique sur electrode inerte, a differentes temperatures. Cette etude permet de comparer la stabilite chimique et le comportement redox de ces deux actinides en milieu acide nitrique. Des parametres cinetiques et thermodynamiques ont ete determines a differentes temperatures et permettront d'extrapoler leurs comportements a des temperatures plus elevees rencontrees lors des etapes de traitement du combustible

Influence of the occurrence and duration of partial remission on short-term metabolic control in type 1 diabetes: the DIABHONEY pediatric study

Objective: To evaluate the residual effect of partial remission (PR) on immediate post-PR glycemic control according to its occurrence and duration in a cohort of children with type 1 diabetes mellitus (T1DM). Patients and Methods: Values of glycemic control parameters [i.e. HbA 1C , insulin dose–adjusted hemoglobin A 1C (IDAA 1C ), glycemic target–adjusted HbA 1C (GTAA 1C )] and data from glucose monitoring devices from 189 pediatric patients with new-onset type 1 diabetes were collected retrospectively from 24 months. Patients were characterized according to their remission status (PR + and PR − ). PR + patients were subdivided into three subgroups regarding PR duration [i.e. short (⩾3–⩽6 months), intermediate (>6–⩽12 months), and long PR (>12–⩽14 months)]. We compared glycemic control data from each PR + subgroup at +6 and +12 months post-PR with PR − patients at the same postdiagnosis time. Second, PR + subgroups were compared with each other. Results: PR + patients showed improved glycemic control (i.e. HbA 1C , IDAA 1C , and GTAA 1C ) at + 6 months post-PR when compared with nonremitters (PR − ), independently of the PR duration subgroups (p < 0.05). Interestingly, patients in long PR + subgroup exhibited higher positive residual effect than short PR + subgroup with lower GTAA 1C scores (p = 0.02), better time in range (TIR) (p = 0.003), less time in hypoglycemia (10.45 versus 16.13%, p = 0.03) and less glycemic variability (83.1 mg/dl versus 98.84 mg/dl, p = 0.03). No significant differences were found for glucose control between PR + and PR − patients at +12 months post-PR. Conclusion: This study supports the positive impact of PR occurrence and duration on short-term metabolic control (better HbA 1C levels, IDAA 1C and GTAA 1C scores, TIR, and less glycemic variability) with the residual effect increasing according to PR duration