Different Psychophysiological Responses to a High-intensity Repetition Session Performed Alone or in a Group by Elite Middle-distance Runners

Internal training load refers to the degree of disturbance in psychophysiological homeostasis provoked by a training session and has been traditionally measured through session-RPE, which is the product of the session Rate of Perceived Exertion (RPE) and the duration. External training load refers to the actual physical work completed, and depends on session volume, intensity, frequency and density. Drafting, which is achieved by running closely behind another runner has been demonstrated to reduce the energy cost of running at a fixed speed and to improve performance. Therefore, it is hypothesized that psychophysiological responses might reflect different levels of internal load if training is performed individually or collectively. 16 elite middle-distance runners performed two high-intensity training sessions consisting of 4 repetitions of 500 m separated by 3 minutes of active recovery. Sessions were performed individually and collectively. Times for each repetition, RPE, core affect (valence and felt arousal) and blood lactate concentrations [BLa] were measured after each repetition. Main time effect was significant and increased across repetitions for [BLa] and RPE (p <0.001), and decreased for valence (p =0.001). Main group effect was significant and values were higher when training individually for [BLa] (p =0.003) and RPE (p =0.001), and lower for valence (p =0.001). No differential responses were found between conditions in terms of repeat time or felt arousal. Findings demonstrate that elite middle-distance athletes running collectively display lower levels of internal training load compared to running alone, despite external training load being similar

Widening the analysis of Energy Return on Investment (EROI) in agro-ecosystems: Socio-ecological transitions to industrialized farm systems (the Vallès County, Catalonia, c.1860 and 1999)

Energy balances of farm systems have overlooked the role of energy flows that remain within agro-ecosystems. Yet, such internal flows fulfil important socio-ecological functions, including maintenance of farmers themselves and agro-ecosystem structures. Farming can either give rise to complex landscapes that favour associated biodiversity, or the opposite. This variability can be understood by assessing several types of Energy Returns on Investment (EROI). Applying these measures to a farm system in Catalonia, Spain in 1860 and in 1999, reveals the expected decrease in the ratio of final energy output to total and external inputs. The transition from solar-based to a fossil fuel based agro-ecosystem was further accompanied by an increase in the ratio of final energy output to biomass reused, as well as an absolute increase of Unharvested Phytomass grown in derelict forestland. The study reveals an apparent link between reuse of biomass and the decrease of landscape heterogeneity along with its associated biodiversity

Opening the black box of energy throughputs in farm systems: A decomposition analysis between the energy returns to external inputs, internal biomass reuses and total inputs consumed (the Vallès County, Catalonia, c.1860 and 1999)

We present an energy analysis of past and present farm systems aimed to contribute to their sustainability assessment. Looking at agroecosystems as a set of energy loops between nature and society, and adopting a farm-operator standpoint at landscape level to set the system boundaries, enthalpy values of energy carriers are accounted for net Final Produce going outside as well as for Biomass Reused cycling inside, and External Inputs are accounted using embodied values. Human Labour is accounted for the fraction of the energy intake of labouring people devoted to perform farm work, considering the local or external origin of their food basket. In this approach the proportion of internal Biomass Reused becomes a hallmark of organic farm systems that tend to save External Inputs, whereas industrial farming and livestock breeding in feedlots tend to get rid of reuses replacing them with inputs coming from outside. Hence, decomposing the internal or external energy throughputs may bring to light their contrasting sociometabolic profiles. A Catalan case study in 1860 and 1990 is used as a test bench to show how revealing this decomposing analysis may be to plot the energy profiles of farm systems and their possible improvement pathways

PP2A is activated by cytochrome c upon formation of a diffuse encounter complex with SET/TAF-Iß

Intrinsic protein flexibility is of overwhelming relevance for intermolecular recognition and adaptability of highly dynamic ensemble of complexes, and the phenomenon is essential for the understanding of numerous biological processes. These conformational ensembles—encounter complexes—lack a unique organization, which prevents the determination of well-defined high resolution structures. This is the case for complexes involving the oncoprotein SET/template-activating factor-Iß (SET/TAF-Iß), a histone chaperone whose functions and interactions are significantly affected by its intrinsic structural plasticity. Besides its role in chromatin remodeling, SET/TAF-Iß is an inhibitor of protein phosphatase 2A (PP2A), which is a key phosphatase counteracting transcription and signaling events controlling the activity of DNA damage response (DDR) mediators. During DDR, SET/TAF-Iß is sequestered by cytochrome c (Cc) upon migration of the hemeprotein from mitochondria to the cell nucleus. Here, we report that the nuclear SET/TAF-Iß:Cc polyconformational ensemble is able to activate PP2A. In particular, the N-end folded, globular region of SET/TAF-Iß (a.k.a. SET/TAF-Iß ¿C)—which exhibits an unexpected, intrinsically highly dynamic behavior—is sufficient to be recognized by Cc in a diffuse encounter manner. Cc-mediated blocking of PP2A inhibition is deciphered using an integrated structural and computational approach, combining small-angle X-ray scattering, electron paramagnetic resonance, nuclear magnetic resonance, calorimetry and molecular dynamics simulations

Proteasome Dysfunction Associated to Oxidative Stress and Proteotoxicity in Adipocytes Compromises Insulin Sensitivity in Human Obesity

AIMS: Obesity is characterized by a low-grade systemic inflammatory state and adipose tissue (AT) dysfunction, which predispose individuals to the development of insulin resistance (IR) and metabolic disease. However, a subset of obese individuals, referred to as metabolically healthy obese (MHO) individuals, are protected from obesity-associated metabolic abnormalities. Here, we aim at identifying molecular factors and pathways in adipocytes that are responsible for the progression from the insulin-sensitive to the insulin-resistant, metabolically unhealthy obese (MUHO) phenotype. RESULTS: Proteomic analysis of paired samples of adipocytes from subcutaneous (SC) and omental (OM) human AT revealed that both types of cells are altered in the MUHO state. Specifically, the glutathione redox cycle and other antioxidant defense systems as well as the protein-folding machinery were dysregulated and endoplasmic reticulum stress was increased in adipocytes from IR subjects. Moreover, proteasome activity was also compromised in adipocytes of MUHO individuals, which was associated with enhanced accumulation of oxidized and ubiquitinated proteins in these cells. Proteasome activity was also impaired in adipocytes of diet-induced obese mice and in 3T3-L1 adipocytes exposed to palmitate. In line with these data, proteasome inhibition significantly impaired insulin signaling in 3T3-L1 adipocytes. INNOVATION: This study provides the first evidence of the occurrence of protein homeostasis deregulation in adipocytes in human obesity, which, together with oxidative damage, interferes with insulin signaling in these cells. CONCLUSION: Our results suggest that proteasomal dysfunction and impaired proteostasis in adipocytes, resulting from protein oxidation and/or misfolding, constitute major pathogenic mechanisms in the development of IR in obesity.IMIBIC/Universidad de Córdoba-SCAI (ProteoRed, PRB2-ISCIII)MINECO/FEDERJunta de Andalucía/FEDERCIBERobn(Instituto de Salud Carlos III

Generating new fanca-deficient hnscc cell lines by genomic editing recapitulates the cellular phenotypes of fanconi anemia

Fanconi anemia (FA) patients have an exacerbated risk of head and neck squamous cell carcinoma (HNSCC). Treatment is challenging as FA patients display enhanced toxicity to standard treatments, including radio/chemotherapy. Therefore, better therapies as well as new disease models are urgently needed. We have used CRISPR/Cas9 editing tools in order to interrupt the human FANCA gene by the generation of insertions/deletions (indels) in exon 4 in two cancer cell lines from sporadic HNSCC having no mutation in FA-genes: CAL27 and CAL33 cells. Our approach allowed efficient editing, subsequent purification of single-cell clones, and Sanger sequencing validation at the edited locus. Clones having frameshift indels in homozygosis did not express FANCA protein and were selected for further analysis. When compared with parental CAL27 and CAL33, FANCA-mutant cell clones displayed a FA-phenotype as they (i) are highly sensitive to DNA interstrand crosslink (ICL) agents such as mitomycin C (MMC) or cisplatin(ii) do not monoubiquitinate FANCD2 upon MMC treatment and therefore (iii) do not form FANCD2 nuclear foci, and (iv) they display increased chromosome fragility and G2 arrest after diepoxybutane (DEB) treatment. These FANCA-mutant clones display similar growth rates as their parental cells. Interestingly, mutant cells acquire phenotypes associated with more aggressive disease, such as increased migration in wound healing assays. Therefore, CAL27 and CAL33 cells with FANCA mutations are phenocopies of FA-HNSCC cells

A multiple stakeholder multicriteria decision analysis in diabetic macular edema management: the MULTIDEX‑EMD study

Background The clinical and economic management of retinal diseases has become more complex following the introduction of new intravitreal treatments. Multicriteria decision analysis (MCDA) ofers the potential to overcome the challenges associated with traditional decision-making tools. Objectives A MCDA to determine the most relevant criteria to decision-making in the management of diabetic macular edema (DME) based on the perspectives of multiple stakeholders in Spain was developed. This MCDA was termed the MULTIDEX-EMD study. Methods Nineteen stakeholders (7 physicians, 4 pharmacists, 5 health authorities and health management experts, 1 psychologist, and 2 patient representatives) participated in this three-phase project. In phase A, an advisory board defned all of the criteria that could infuence DME treatment decision-making. These criteria were then screened using a discrete choice experiment (DCE) (phase B). Next, a multinomial logit model was ftted by applying the backward elimination algorithm (relevant criteria: p value<0.05). Finally, the results were discussed in a deliberative process (phase C). Results Thirty-one criteria were initially defned (phase A) and grouped into 5 categories: efcacy/efectiveness, safety, organizational and economic impact, patient-reported outcomes, and other therapeutic features. The DCE results (phase B) showed that 10 criteria were relevant to the decision-making process for a 50- to 65-year-old DME patient: mean change in best corrected visual acuity (p value<0.001), percentage of patients with an improvement of ≥15 letters (p value<0.001), efect duration per administration (p value=0.008), retinal detachment (p value<0.001), endophthalmitis (p value=0.012), myocardial infarction (p value<0.001), intravitreal hemorrhage (p value=0.021), annual treatment cost per patient (p value=0.001), health-related quality of life (HRQoL) (p value=0.004), and disability level (p value=0.021). Conclusions From a multi-stakeholder perspective, the selection of an appropriate treatment for DME patients should guarantee patient safety and maximize the visual acuity improvement and treatment efect duration. It should also contribute to system sustainability by being afordable, it should have a positive impact on HRQoL, and it should prevent disability

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN