Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila

BACKGROUND: The Ras-related GTPase, Rheb, regulates the growth of animal cells. Genetic and biochemical tests place Rheb upstream of the target of rapamycin (TOR) protein kinase, and downstream of the tuberous sclerosis complex (TSC1/TSC2) and the insulin-signaling pathway. TOR activity is regulated by nutritional cues, suggesting that Rheb might either control, or respond to, nutrient availability. RESULTS: We show that Rheb and TOR do not promote the import of glucose, bulk amino acids, or arginine in Drosophila S2 cells, but that both gene products are important regulators of ribosome biogenesis, protein synthesis, and cell size. S2 cell size, protein synthesis, and glucose import were largely insensitive to manipulations of insulin signaling components, suggesting that cellular energy levels and TOR activity can be maintained through insulin/PI3K-independent mechanisms in S2 cell culture. In vivo in Drosophila larvae, however, we found that insulin signaling can regulate protein synthesis, and thus may affect TOR activity. CONCLUSION: Rheb-TOR signaling controls S2 cell growth by promoting ribosome production and protein synthesis, but apparently not by direct effects on the import of amino acids or glucose. The effect of insulin signaling upon TOR activity varies according to cellular type and context

Intrinsic Negative Cell Cycle Regulation Provided by PIP Box- and Cul4Cdt2-Mediated Destruction of E2f1 during S Phase

E2F transcription factors are key regulators of cell proliferation that are inhibited by pRb family tumor suppressors. pRb-independent modes of E2F inhibition have also been described, but their contribution to animal development and tumor suppression is unclear. Here we show that S phase-specific destruction of Drosophila E2f1 provides a novel mechanism for cell cycle regulation. E2f1 destruction is mediated by a PCNA-interacting-protein (PIP) motif in E2f1 and the Cul4Cdt2 E3 ubiquitin ligase, and requires the Dp dimerization partner but not direct Cdk phosphorylation or Rbf1 binding. E2f1 lacking a functional PIP motif accumulates inappropriately during S phase and is more potent than wild type E2f1 at accelerating cell cycle progression and inducing apoptosis. Thus, S phase-coupled destruction is a key negative regulator of E2f1 activity. We propose that pRb-independent inhibition of E2F during S phase is an evolutionarily conserved feature of the metazoan cell cycle that is necessary for development

Meaning in life is associated with the psychopathology of eating disorders: differences depending on the diagnosis.

Previous studies indicated that meaning in life was inversely associated with eating behaviors and a negative attitude toward food, body satisfaction, and borderline symptoms. However, research on the association between meaning in life and eating disorder psychopathology is scarce, and there are no studies on the association between meaning in life and the eating disorder psychopathology depending on the diagnosis. The aim of the present study is to verify whether meaning in life is differentially associated with a broad range of psychopathology symptoms commonly observed in people with ED, depending on the diagnosis, in a sample of 240 ED patients. We found that meaning in life was negatively associated with eating behaviors and a negative attitude toward food, body satisfaction, borderline symptoms, and hopelessness in all types of eating disorders, regardless of the specific diagnosis. Moreover, the association with meaning in life was different depending on the type of eating disorders. Specifically in the participants with Anorexia Nervosa Restrictive, meaning in life had a higher percentage of explained variance in the eating disorders psychopathology (between 30%-65%). Therefore, these results seem to indicate that, although meaning in life is an important variable in all the eating disorders subtypes, it is especially relevant in participants with the Anorexia Nervosa Restrictive subtype

Exportación de conservas de pescado: revisión sistemática de la literatura científica (2001-2021)

Objective. To show experiences and export plans of canned fish in South America presented in ScienceDirect, Redalyc, Scielo, Doaj, Econbiz, Sisbib, La Referencia and Fedesarrollo, between the years 2001 and 2021. In addition, the specific objectives were to identify the countries from which these experiences and export plans originate, to which countries they are oriented, their logistic methods, conclusions and recommendations. Method. A systematic review was conducted in which 1,069,944 records were identified, which, after application of exclusion and inclusion criteria, were reduced to 10 final records for analysis. Results. Data was extracted referring to the authors' names, the year of publication, the title of the record, the type of document (thesis, scientific article or technical report), the export product, exporting and importing country, logistic method and conclusions of the original authors. Conclusion. Of the selected records, most of the exports come from Ecuador (4 cases), the most used logistical method is maritime transport and their main destination is the U.S. market (5 cases), which concentrates the greatest demand for canned fish from the region, especially of Ecuadorian origin.Objetivo. Evidenciar experiencias y planes de exportación de conservas de pescado en Sudamérica presentadas en ScienceDirect, Redalyc, Scielo, Doaj, Econbiz, Sisbib, La Referencia y Fedesarrollo, entre los años 2001 y 2021. Además, se tuvo como objetivos específicos identificar de qué países provienen dichas experiencias y planes de exportación, a qué países se orientan, sus métodos logísticos, conclusiones y recomendaciones. Método. Se condujo una revisión sistemática en la que se identificaron 1 069 944 registros, los cuales, luego de la aplicación de criterios de exclusión e inclusión, se redujeron a 10 registros finales para el análisis. Resultados. Se extrajo data alusiva a los nombres de los autores, el año de publicación, el título del registro, el tipo de documento (tesis, artículo científico o informe técnico), el producto de exportación, país exportador e importador, método logístico y conclusiones de los autores originales. Conclusión. De los registros seleccionados, la mayoría de las exportaciones proviene de Ecuador (4 casos), el método logístico más utilizado es el transporte marítimo y tienen como destino principal el mercado estadounidense (5 casos) que concentra la mayor demanda por conservas de pescado de la región, especialmente de origen ecuatoriano

Characteristics and outcome of adult patients with acute promyelocytic leukemia and increased body mass index treated with the PETHEMA Protocols

Objective The obesity/overweight may have an influence on APL outcomes. Methods This is the biggest multicentre analysis on 1320 APL patients treated with AIDA-induction and risk-adapted consolidation between 1996 and 2012. Patients body mass index (BMI) was classified as underweight (= 30 kg/m(2)) according to the World Health Organization (WHO) criteria. Results and conclusions Relationship between male gender, older age, and other known laboratory abnormalities in overweight/obese patients was significant. The induction mortality rate was significantly higher in APL with BMI >= 25 vs BMI = 25 had a trend to lower OS (74% vs 80%; P = .06). However, in the multivariate analysis, BMI did not retain the independent predictive value (P = .46). There was no higher incidence of differentiation syndrome with BMI >= 25, but there was a trend in obese. There was no difference in relapse rate according to the BMI. In summary, overweight/obesity does not represent an independent risk factor for APL outcomes. The influence of obesity in APL patients treated with chemotherapy-free regimens remains to be established

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Building and surroundings: thermal coupling

Energy building performance can be different according to outdoor conditions or urban environment, at the same time that this last assess, buildings are also affected by the building envelope, as obvious consequence of the thermal and Aeraulic coupling existing between the indoor and outdoor conditions in buildings. Thus, in this coupling is fundamental to typify the transmission phenomenon through the building envelope. Doing this, it is possible to estimate transmission heating losses and gains and also the superficial temperatures of the envelope. In order to assess the transient behaviour of the building envelope it is necessary to develop a predictive model, precise enough, to be integrated in a simulating tool. Detailed and multidimensional models, based in numerical methods, like Finite Element Method (FEM), has a high precision, but its complexity imply resources consumption and computational time, too high to be integrated in these kind of tools. On the contrary, simplified methods are good enough because they are simple and fast, with an acceptable precision in almost all the situations. The present work is focused: (a) Firstly, to develop a simplified RC-network model. The aim of the model is to characterize and to implement with precision the behaviour of a wall in a simulating software tool based on urban environment, (b) secondly, to express in form of equivalences, the different indoor and outdoor excitations that can exist in the building envelope, and (c) finally, to calibrate the simplified model through its characteristic parameters. For a homogeneous wall and two types of excitations, it has been obtained the characteristic parameters of the model that represent the better adjustment to the real wall. In a first step, it has been obtained the results of the proposal model and a reference model based on FEM, in terms of wall external surface heat flow. Results of both models have been compared, and the resultant characteristic parameters of the model have been obtained through an optimisation method. Results for the wall and for the excitations under analysis show: (1) Characteristic longitude ec, or capacitive node position, it is determined according to a certain value of Fo equal to 2 for both excitations, this value remains constant in time, (2) useful wall thickness, on the contrary, vary as time function, according to a logarithmic law for both excitations, although this function is different depending on the considered excitation, (3) using a constant excitation, coefficients from the previous logarithmic function depends on the range of the excitation, while these are practically independent of the lineal excitation gradient

Tests ràpids d'infeccions respiratòries pediàtriques

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Tests ràpids; Pacient pediàtricCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Tests rápidos; Paciente pediátricoCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Quick tests; Pediatric patientL’atenció als infants suposa al voltant de 7,5 milions de visites anuals a l’atenció primària. D’aquestes, al voltant d’1,6 milions estan relacionades amb les infeccions respiratòries. La majoria de les infeccions són víriques i les més freqüents estan originades per rinovirus, adenovirus, parainfluença, influença i virus respiratori sincític. El diagnòstic diferencial entre les infeccions respiratòries pediàtriques és difícil en infants, una dificultat que està en relació inversa amb l’edat. La pandèmia obliga a descartar la infecció per COVID-19 en els infants que es presenten amb símptomes d’infecció respiratòria. La incertesa del diagnòstic, donada la clínica i la sensibilitat dels tests disponibles, i el diferent tractament que s’ha de fer en el cas d’una infecció per SARS-CoV-2, fa necessari posar a disposició dels professionals d’atenció primària totes les eines disponibles per poder millorar el diagnòstic diferencial de les infeccions respiratòries. Per aquesta raó, s’ha considerat necessari dotar les consultes de pediatria d’atenció primària de tests ràpids d’infeccions respiratòries (VRS, influença A i B i adenovirus). El protocol que es presenta ha estat elaborat per un conjunt de pediatres que representen la Societat Catalana de Pediatria, les entitats proveïdores agrupades en les patronals (UCH i CSC) i l’Institut Català de la Salut. És un protocol clínic però que té en consideració la situació epidemiològica actual de pandèmia per COVID-19. Com qualsevol protocol d’aquest període 2020-21, haurà d’anar canviant conforme es disposi de més coneixement sobre la COVID-19. Els resultats dels tests ràpids han de ser interpretats sempre en el context de la clínica que presenta el pacient

Protein–protein interactions as a proxy to monitor conformational changes and activation states of the tomato resistance protein I-2

Plant resistance proteins (R) are involved in pathogen recognition and subsequent initiation of defence responses. Their activity is regulated by inter- and intramolecular interactions. In a yeast two-hybrid screen two clones (I2I-1 and I2I-2) specifically interacting with I-2, a Fusarium oxysporum f. sp. lycopersici resistance protein of the CC-NB-LRR family, were identified. Sequence analysis revealed that I2I-1 belongs to the Formin gene family (SlFormin) whereas I2I-2 has homology to translin-associated protein X (SlTrax). SlFormin required only the N-terminal CC I-2 domain for binding, whereas SlTrax required both I-2 CC and part of the NB-ARC domain. Tomato plants stably silenced for these interactors were not compromised in I-2-mediated disease resistance. When extended or mutated forms of I-2 were used as baits, distinct and often opposite, interaction patterns with the two interactors were observed. These interaction patterns correlated with the proposed activation state of I-2 implying that active and inactive R proteins adopt distinct conformations. It is concluded that the yeast two hybrid system can be used as a proxy to monitor these different conformational states

Modifiable risk factors associated with prediabetes in men and women: A cross-sectional analysis of the cohort study in primary health care on the evolution of patients with prediabetes

Background: Prediabetes is a high-risk state for diabetes development, but little is known about the factors associated with this state. The aim of the study was to identify modifiable risk factors associated with the presence of prediabetes in men and women. Methods: Cohort Study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS-Study) is a prospective study on a cohort of 1184 subjects with prediabetes and another cohort of 838 subjects without glucose metabolism disorders. It is being conducted by 125 general practitioners in Spain. Data for this analysis were collected during the baseline stage in 2012. The modifiable risk factors included were: smoking habit, alcohol consumption, low physical activity, inadequate diet, hypertension, dyslipidemia, and obesity. To assess independent association between each factor and prediabetes, odds ratios (ORs) were estimated using logistic regression models. Results: Abdominal obesity, low plasma levels of high-density lipoprotein cholesterol (HDL-cholesterol), and hypertension were independently associated with the presence of prediabetes in both men and women. After adjusting for all factors, the respective ORs (95% Confidence Intervals) were 1.98 (1.41-2.79), 1.88 (1.23-2.88) and 1.86 (1.39-2.51) for men, and 1.89 (1.36-2.62), 1.58 (1.12-2.23) and 1.44 (1.07-1.92) for women. Also, general obesity was a risk factor in both sexes but did not reach statistical significance among men, after adjusting for all factors. Risky alcohol consumption was a risk factor for prediabetes in men, OR 1.49 (1.00-2.24). Conclusions: Obesity, low HDL-cholesterol levels, and hypertension were modifiable risk factors independently related to the presence of prediabetes in both sexes. The magnitudes of the associations were stronger for men than women. Abdominal obesity in both men and women displayed the strongest association with prediabetes. The findings suggest that there are some differences between men and women, which should be taken into account when implementing specific recommendations to prevent or delay the onset of diabetes in adult population