Glycans as regulatory elements of the insulin/IGF system: Impact in cancer progression

The insulin/insulin-like growth factor (IGF) system in mammals comprises a dynamic network of proteins that modulate several biological processes such as development, cell growth, metabolism, and aging. Dysregulation of the insulin/IGF system has major implications for several pathological conditions such as diabetes and cancer. Metabolic changes also culminate in aberrant glycosylation, which has been highlighted as a hallmark of cancer. Changes in glycosylation regulate every pathophysiological step of cancer progression including tumour cell-cell dissociation, cell migration, cell signaling and metastasis. This review discusses how the insulin/IGF system integrates with glycosylation alterations and impacts on cell behaviour, metabolism and drug resistance in cancer.Financial support from Portugal: Institute of Molecular Pathology and Immunology of University of Porto (IPATIMUP) integrates the i3S research unit, which is partially supported by the Portuguese Foundation for Science and Technology (FCT). This article is a result of the project NORTE-01-0145-FEDER-000029, supported by the Norte Portugal Regional Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF). This work was also funded by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Inovação in the framework of the project (POCI-01/0145-FEDER-016601). Financial support from Brazil: Ministério da Saúde and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), under the project 336/13

Chitosan/virgin-coconut-oil-based system enriched with cubosomes: a 3D drug-delivery approach

Emulsion-based systems that combine natural polymers with vegetable oils have been identified as a promising research avenue for developing structures with potential for biomedical applications. Herein, chitosan (CHT), a natural polymer, and virgin coconut oil (VCO), a resource obtained from coconut kernels, were combined to create an emulsion system. Phytantriol-based cubosomes encapsulating sodium diclofenac, an anti-inflammatory drug, were further dispersed into CHT/VCO- based emulsion. Then, the emulsions were frozen and freeze-dried to produce scaffolds. The scaffolds had a porous structure ranging from 20.4 to 73.4 µm, a high swelling ability (up to 900%) in PBS, and adequate stiffness, notably in the presence of cubosomes. Moreover, a well-sustained release of the entrapped diclofenac in the cubosomes into the CHT/VCO-based system, with an accumulated release of 45 ± 2%, was confirmed in PBS, compared to free diclofenac dispersed (80 ± 4%) into CHT/VCO-based structures. Overall, the present approach opens up new avenues for designing porous biomaterials for drug delivery through a sustainable pathway.The authors especially acknowledge the financial support from the Portuguese FCT (grants CEECIND/01306/2018, SFRH/BPD/93697/2013, and SFRH/BPD/85790/2012). This work was also financially supported by the FCT R&D&I project, with reference PTDC/BII-BIO/31570/2017, and the R&D&I Structured Projects, with reference NORTE-01-0145-FDER-000021. We also acknowledge the financial support from São Paulo Research Foundation (FAPESP) in Brasil through projects 2015/25406-5 and 2021/12071-6, and for the postdoctoral grant to D.G.V., 2019/12665-3. The project 2018/08045-7 is part of a bilateral agreement between FAPESP and the FCT (Portugal), involving the project Nature4Health

Childcare in infancy and later obesity: A narrative review of longitudinal studies

Purpose of Review The purpose of this review was to summarize the current literature on the longitudinal relationship between non-parental childcare during infancy and later obesity. Recent Findings Eleven studies met the inclusion criteria, comprising 74 associations relevant to the review. Studies were highly heterogeneous in terms of defining childcare, categorizing different types of childcare, assessing obesity, and age at measurement of outcome and exposure. Most of the associations were either non-significant (42 associations, 57%) or showed a significant association between increased exposure to childcare and greater obesity (30 associations, 41%). There were very few examples of associations indicating that childcare was associated with lower obesity. Summary There is limited research on the longitudinal relationship between childcare in infancy and later obesity. Existing studies showed mixed results, similar to recent reviews reporting on cross-sectional studies and older ages. The different definitions of childcare and wide variety of measures of exposure make comparisons between studies challenging.Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged

Stand dynamics modulate water cycling and mortality risk in droughted tropical forest

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Transpiration from the Amazon rainforest generates an essential water source at a global and local scale. However, changes in rainforest function with climate change can disrupt this process, causing significant reductions in precipitation across Amazonia, and potentially at a global scale. We report the only study of forest transpiration following a long-term (>10 year) experimental drought treatment in Amazonian forest. After 15 years of receiving half the normal rainfall, drought-related tree mortality caused total forest transpiration to decrease by 30%. However, the surviving droughted trees maintained or increased transpiration because of reduced competition for water and increased light availability, which is consistent with increased growth rates. Consequently, the amount of water supplied as rainfall reaching the soil and directly recycled as transpiration increased to 100%. This value was 25% greater than for adjacent nondroughted forest. If these drought conditions were accompanied by a modest increase in temperature (e.g., 1.5°C), water demand would exceed supply, making the forest more prone to increased tree mortality.This work is a product of UK NERC grant NE/J011002/1 to PM and MM, CNPQ grant 457914/2013-0/MCTI/CNPq/FNDCT/LBA/ESECAFLOR to ACLD, an ARC grant FT110100457 to PM and a UK NERC independent fellowship grant NE/N014022/1 to LR. It was previously supported by NERC NER/A/S/2002/00487, NERC GR3/11706, EU FP5-Carbonsink and EU FP7-Amazalert to PM. RP acknowledges support of MINECO (Spain), grant CGL2014-5583-JIN

Ordinary Percolation with Discontinuous Transitions

Percolation on a one-dimensional lattice and fractals such as the Sierpinski gasket is typically considered to be trivial because they percolate only at full bond density. By dressing up such lattices with small-world bonds, a novel percolation transition with explosive cluster growth can emerge at a nontrivial critical point. There, the usual order parameter, describing the probability of any node to be part of the largest cluster, jumps instantly to a finite value. Here, we provide a simple example of this transition in form of a small-world network consisting of a one-dimensional lattice combined with a hierarchy of long-range bonds that reveals many features of the transition in a mathematically rigorous manner.Comment: RevTex, 5 pages, 4 eps-figs, and Mathematica Notebook as Supplement included. Final version, with several corrections and improvements. For related work, see http://www.physics.emory.edu/faculty/boettcher

Validação conceitual das características definidoras de diagnósticos de enfermagem respiratórios em neonatos

OBJECTIVE:To develop and validate conceptual and operational definitions for the defining characteristics of the respiratory nursing diagnoses, ineffective breathing pattern, impaired gas exchange and impaired spontaneous ventilation, in newborns.METHODS:This was a methodological study of conceptual validation of the defining characteristics of three respiratory nursing diagnoses, by consensus analysis of a committee of five specialist nurses, and then a group of five non-nursing professionals, using the Delphi technique.RESULTS:After two rounds of evaluation, consensus was obtained that was equal to or greater than 80% on all of the definitions, which were then considered validated.CONCLUSION:The definitions developed for the defining characteristics of three nursing diagnoses were validated with a high level of consensus.OBJETIVO:Elaborar e validar definições conceituais e operacionais para as características definidoras dos diagnósticos de enfermagem respiratórios, Padrão Respiratório Ineficaz, Troca de Gases Prejudicada e Ventilação Espontânea Prejudicada em recém-nascidos.MÉTODOS:Estudo metodológico, de validação conceitual das características definidoras dos três diagnósticos de enfermagem respiratórios por meio da análise de consenso de um comitê de cinco enfermeiras especialistas e de cinco profissionais não enfermeiros, utilizando a técnica Delphi.RESULTADOS:Após duas rodadas de avaliação, obteve-se consenso igual ou superior a 80% na totalidade das definições, sendo consideradas validadas.CONCLUSÃO:As definições elaboradas para as características definidoras dos três diagnósticos de enfermagem foram validadas com elevado grau de consenso.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de EnfermagemUNIFESP, EPESciEL

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions. Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal

Gravitational collapse and thermalization in the hard wall model

We study a simple example of holographic thermalization in a confining field theory: the homogeneous injection of energy in the hard wall model. Working in an amplitude expansion, we find black brane formation for sufficiently fast energy injection and a scattering wave solution for sufficiently slow injection. We comment on our expectations for more sophisticated holographic QCD models.Comment: 33 pages, 5 figure

Amazonian trees have limited capacity to acclimate plant hydraulic properties in response to long‐term drought

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordThe fate of tropical forests under future climate change is dependent on the capacity of their trees to adjust to drier conditions. The capacity of trees to withstand drought is likely to be determined by traits associated with their hydraulic systems. However, data on whether tropical trees can adjust hydraulic traits when experiencing drought remain rare. We measured plant hydraulic traits (e.g. hydraulic conductivity and embolism resistance) and plant hydraulic system status (e.g. leaf water potential, native embolism and safety margin) on >150 trees from 12 genera (36 species) and spanning a stem size range from 14 to 68 cm diameter at breast height (DBH) at the world's only long‐running tropical forest drought experiment. Hydraulic traits showed no adjustment following 15 years of experimentally imposed moisture deficit. This failure to adjust resulted in these drought‐stressed trees experiencing significantly lower leaf water potentials, and higher, but variable, levels of native embolism in the branches. This result suggests that hydraulic damage caused by elevated levels of embolism is likely to be one of the key drivers of drought‐induced mortality following long‐term soil moisture deficit. We demonstrate that some hydraulic traits changed with tree size, however, the direction and magnitude of the change was controlled by taxonomic identity. Our results suggest that Amazonian trees, both small and large, have limited capacity to acclimate their hydraulic systems to future droughts, potentially making them more at risk of drought‐induced mortality.Natural Environment Research Council (NERC)Brazilian Higher Education Coordination Agency (CAPES)Royal SocietyEuropean Union FP7ARCFAPESP/Microsof