Ultrasensitivity in phosphorylation-dephosphorylation cycles with little substrate

Cellular decision-making is driven by dynamic behaviours, such as the preparations for sunrise enabled by circadian rhythms and the choice of cell fates enabled by positive feedback. Such behaviours are often built upon ultrasensitive responses where a linear change in input generates a sigmoidal change in output. Phosphorylation-dephosphorylation cycles are one means to generate ultrasensitivity. Using bioinformatics, we show that in vivo levels of kinases and phosphatases frequently exceed the levels of their corresponding substrates in budding yeast. This result is in contrast to the conditions often required by zero-order ultrasensitivity, perhaps the most well known means for how such cycles become ultrasensitive. We therefore introduce a mechanism to generate ultrasensitivity when numbers of enzymes are higher than numbers of substrates. Our model combines distributive and non-distributive actions of the enzymes with two-stage binding and concerted allosteric transitions of the substrate. We use analytical and numerical methods to calculate the Hill number of the response. For a substrate with [Formula: see text] phosphosites, we find an upper bound of the Hill number of [Formula: see text], and so even systems with a single phosphosite can be ultrasensitive. Two-stage binding, where an enzyme must first bind to a binding site on the substrate before it can access the substrate's phosphosites, allows the enzymes to sequester the substrate. Such sequestration combined with competition for each phosphosite provides an intuitive explanation for the sigmoidal shifts in levels of phosphorylated substrate. Additionally, we find cases for which the response is not monotonic, but shows instead a peak at intermediate levels of input. Given its generality, we expect the mechanism described by our model to often underlay decision-making circuits in eukaryotic cells

In-season internal and external training load quantification of an elite European soccer team

Elite soccer teams that participate in European competitions need to have players in the best physical and psychological status possible to play matches. As a consequence of congestive schedule, controlling the training load (TL) and thus the level of effort and fatigue of players to reach higher performances during the matches is therefore critical. Therefore, the aim of the current study was to provide the first report of seasonal internal and external training load that included Hooper Index (HI) scores in elite soccer players during an in-season period. Nineteen elite soccer players were sampled, using global position system to collect total distance, high-speed distance (HSD) and average speed (AvS). It was also collected session rating of perceived exertion (s-RPE) and HI scores during the daily training sessions throughout the 2015-2016 in-season period. Data were analysed across ten mesocycles (M: 1 to 10) and collected according to the number of days prior to a one-match week. Total daily distance covered was higher at the start (M1 and M3) compared to the final mesocycle (M10) of the season. M1 (5589m) reached a greater distance than M5 (4473m) (ES = 9.33 [12.70, 5.95]) and M10 (4545m) (ES = 9.84 [13.39, 6.29]). M3 (5691m) reached a greater distance than M5 (ES = 9.07 [12.36, 5.78]), M7 (ES = 6.13 [8.48, 3.79]) and M10 (ES = 9.37 [12.76, 5.98]). High-speed running distance was greater in M1 (227m), than M5 (92m) (ES = 27.95 [37.68, 18.22]) and M10 (138m) (ES = 8.46 [11.55, 5.37]). Interestingly, the s-RPE response was higher in M1 (331au) in comparison to the last mesocycle (M10, 239au). HI showed minor variations across mesocycles and in days prior to the match. Every day prior to a match, all internal and external TL variables expressed significant lower values to other days prior to a match (p<0.01). In general, there were no differences between player positions. Conclusions: Our results reveal that despite the existence of some significant differences between mesocycles, there were minor changes across the in-season period for the internal and external TL variables used. Furthermore, it was observed that MD-1 presented a reduction of external TL (regardless of mesocycle) while internal TL variables did not have the same record during in-season match-day-minus.: The authors state that there were no salaries’ fund from a tobacco company. Also, the authors are not aware of any competing interests. This project was supported by the National Funds through FCT—Portuguese Foundation for Science and Technology (UID/DTP/04045/2013)—and the European Fund for Regional Development (FEDER) allocated by European Union through the COMPETE 2020 Programme (POCI-01-0145- FEDER-006969)—competitiveness and internationalization (POCI). All funding received for this work from any of the following organizations: National Institutes of Health (NIH); Welcome Trust; Howard Hughes Medical Institute (HHMI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

In-season training load quantification of one-, two- and three-game week schedules in a top European professional soccer team

Top European soccer teams that play in UEFA competitions often participate in one, two- or three-games per week. Therefore, it is necessary to ensure optimal match-day performance and full recovery. The aim of this study was to quantify internal and external training load (TL) within five microcycles: M1 and M2 - one-game weeks; M3 and M4 - two-game weeks; M5 - three-game week). Thirteen elite soccer players participated in this study. A global positioning system (GPS) was used to measure the total distance covered and distances of different exercise training zones (1-5), the session ratings of perceived exertion (s-RPE) scores and the amount of creatine kinase (CK) created during daily training sessions for the 2015-2016 in-season period. The data were analysed with respect to the number of days prior to a given match. The main results indicate that there was a significant difference in training intensity for zone 1 between M2 and M4 (4010.2 ± 103.5 and 4507.6 ± 133.0 m, respectively); a significant difference in training intensity for zone 3 between M1 and M5 (686.1 ± 42.8 and 801.2 ± 61.2 m, respectively); a significant difference in the duration of the training sessions and matches between M2 and M5 (69.2 ± 2.1 and 79.6 ± 2.3) and M3 and M5 (69.7 ± 1.0 and 79.6 ± 2.3); and finally, there was a significant difference in CK between M3 and M2 (325.5 ± 155.0 and 194.4 ± 48.9). Moreover, there was a significant decrease in TL in the last day prior to a match, for all microcycles and all variables. There was no significant difference with respect to s-RPE. This study provides the first report of daily external and internal TLs and weekly accumulated load (training sessions and match demands) during one, two, and three-game week schedules in a group of elite soccer players. Expected significant differences are found in daily and accumulated loads for within- and between-game schedules. A similar pattern is exhibited for one- and two-game week microcycles regarding the day before the match, which exhibits a decrease in all variables. Despite the different number of games played per week, TL remain similar between microcycles for zone 2 and 5, plus s-RPE.This project was supported by the National Funds through FCT—Portuguese Foundation for Science and Technology (UID/DTP/04045/2013) and the European Fund for Regional Development (FEDER) allocated by European Union through the COMPETE 2020 Programme (POCI-01-0145-FEDER-006969)—competitiveness and internationalization (POCI). The authors disclose funding received for this work from any of the following organizations: National Institutes of Health (NIH); Welcome Trust; Howard Hughes Medical Institute (HHMI); and other(s).info:eu-repo/semantics/publishedVersio

Oscillatory instabilities during the electrocatalytic oxidation of methanol on platinum

It is described in this paper the experimental observation of oscillatory dynamics during the electrocatalytic oxidation of methanol on platinum. Besides the previously reported potential oscillations, current oscillations obtained under potentiostatic control are also presented. The existence region of current oscillations is mapped in an applied voltage x resistance bifurcation diagram. Conjointly with electrochemical investigations, in situ FTIR spectroscopy was also employed in the present studies. Although we were not able to follow eventual intermediate coverage changes during the oscillations, those experiments revealled that the mean coverage of adsorbed carbon monoxide remains appreciably high along the oscillations. Results are discussed and compared with the oscillations observed in the electrooxidation of formic acid, a system whose behavior is more understood and widely supported by in situ spectroscopic data.Descreve-se neste artigo a observação experimental de dinâmica oscilatória durante a oxidação eletrocatalítica de metanol sobre platina. Além das, previamente relatadas, oscilações de potencial, oscilações de corrente obtidas sob controle potenciostático também são apresentadas. A região de existência de oscilações de corrente é mapeada no plano de bifurcação voltagem aplicada x resistência. Conjuntamente com investigações eletroquímicas, espectroscopia FTIR in situ também foi aplicada nestes estudos. Apesar de não ter sido possível acompanhar eventuais variações de intermediários reacionais durante as oscilações, tais experimentos revelaram que a cobertura média de monóxido de carbono permanece consideravelmente alta durante as oscilações. Os resultados são discutidos e comparados com as oscilações observadas na eletrooxidação de ácido fórmico, um sistema cujo comportamento é mais entendido e amplamente fundamentado por dados espectroscópicos obtidos in situ.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CNP

The use of visible and near infrared reflectance spectroscopy to predict beef M. longissimus thoracis et lumborum quality attributes

Visible and near infrared reflectance spectroscopy was used to predict pH at 24 h (pH24) post-mortem, sarcomere length (SL), cooking loss (CL), Warner–Bratzler Shear Force (WBSF) and colour parameters (L*, a*, b*) in beef cattle samples. Samples from M. longissimus thoracis et lumborum from 30 bulls were aged at 4 C for 1, 3, 7 and 14 days and analysed for pH, SL, CL, WBSF and colour. NIRS calibrations for pH24, luminosity at 0 (L*t0) and 60 min (L*t60) showed good predictability (R2 = 0.97, 0.85 and 0.82; SECV = 0.10, 1.16, 1.36, respectively), whereas those related to the rest of the parameters were poore

Evaluation of chitosan-GP hydrogel biocompatibility in osteochondral defects: an experimental approach

Background: Articular cartilage, because of its avascular nature, has little capacity for spontaneous healing, and tissue engineering approaches, employing different biomaterials and cells, are under development. Among the investigated biomaterials are the chitosan-based hydrogels. Although thoroughly studied in other mammalian species, studies are scarce in equines. So, the aim of the present study was to investigate the biocompatibility of chitosan-GP in horse joints submitted to high mechanical loads.Results: An osteochondral defect was created by arthroscopy in the medial surface of lateral trochlea of talus of left or right leg, randomly selected, from six healthy geldings. the defect was filled up with chitosan-GP. the contralateral joint received an identical defect with no implant. the chondral fragment removed to produce the defect was collected, processed and used as the Initial sample (normal cartilage) for histology, immunohistochemistry, and metabolic labelling of PGs. After 180 days, the repair tissues were collected, and also analyzed. At the end of the experiment (180 days after lesion), the total number of cells per field in repair tissues was equal to control, and macrophages and polymorphonuclear cells were not detected, suggesting that no significant inflammation was present. These cells were able to synthesize type II collagen and proteoglycans (PGs). Nevertheless, the cell population in these tissues, both in presence of chitosan-GP and in untreated controls, were heterogeneous, with a lower proportion of type II collagen-positives cells and some with a fibroblastic aspect. Moreover, the PGs synthesized in repair tissues formed in presence or absence of chitosan-GP were similar to those of normal cartilage. However, the chitosan-GP treated tissue had an disorganized appearance, and blood vessels were present.Conclusions: Implanted chitosan-GP did not evoke an important inflammatory reaction, and permitted cell growth. These cells were able to synthesize type II collagen and PGs similar to those synthesized in normal cartilage and in healing tissue without implant, indicating its chondrocyte nature.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Fac Med Vet & Zootecnia, Dept Cirurgia, BR-09500900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Bioquim, BR-04044020 São Paulo, BrazilUniv São Paulo, Fac Med Vet & Zootecnia, Dept Clin Med, BR-09500900 São Paulo, BrazilUniv São Paulo, Fac Med Vet & Zootecnia, Dept Patol, BR-09500900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Bioquim, BR-04044020 São Paulo, BrazilWeb of Scienc

Improving processes in a postgraduate office of a university through lean office tools

This paper reports the administrative processes improvement based on Lean Office tools in an office environment of a University department. Lean tools such as electronic standardization were applied on the six educational projects of the department. Also, some were used to organize the computer desktop and network drives to improve the supporting educational projects information. Additionally, due to the absence of Key Performance Indicators (KPI), some here defined and implemented on the department. The main results were the electronic standardization successful implementation, reorganization of the drives and the desktop. The impacts were a reduction of 84% on the files search time, improvements on the development of forms for student I registration and projects managing, a 69% reduction of time searching for student information or data, a reduction of the input times and information handling in an estimated total of 12 hours/year, identification of KPI and development of a dashboard for visual analysis and monitoring of these.The authors want to acknowledge the LeanOffice@DPS team to support this work and the Department of Production and System-University of Minho where it was developed. The authors also would like to express their acknowledgments to national funds by COMPETE: POCI-01-0145-FEDER-007043 and FCT - Fundação para a Ciencia e Tecnologia within the Project Scope: UID/CEC/00319/2013

O risco de ravinamento: o exemplo das ravinas de Seirós (norte de Portugal)

Neste trabalho, é apresentado o exemplo de um conjunto de ravinas formadas numa área agrícola, sobre um coluvião, em Seirós, próximo de Ribeira de Pena, no Norte de Portugal. As ravinas formaram-se durante um episódio de chuva intensa e concentrada, em dezembro de 2015. A existência de um canal retangular de 49 metros de comprimento, 0,70 metros de largura e 0,75 metros de altura, construído pelo proprietário do terreno, como forma de proteção da escorrência a montante do terreno de cultivo, contribuiu para uma concentração excecional da escorrência que, sendo insuficiente para a conter, permitiu o transbordo e a consequente formação de 8 ravinas. A presença dessas ravinas impossibilitou a prática agrícola durante cerca de um ano, após o qual o proprietário, com recurso a maquinaria, não só neutralizou as ravinas, mas também procedeu à reconstrução do canal de proteção, parcialmente destruído durante o episódio chuvoso, tendo voltado a funcionar novamente como único meio de controlo de erosão. O estudo apresentado tem como objetivo a caracterização das ravinas, bem como, analisar os fatores determinantes na sua formação. Além disso, pretende-se ainda discutir a adequação da estratégia existente como forma de prevenção e mitigação do risco de ravinamentoinfo:eu-repo/semantics/publishedVersio