Baixa estatura nutricional e risco de obesidade futura: principais mecanismos fisiológicos

There is a fair amount of epidemiological evidence showing that nutritional stunting causes increased risks of obesity. Obesity is increasing dramatically not only in developed countries but also in developing countries, such as Brazil, especially among the poorer. The mere coexistence of undernutrition and obesity among poor people has a great impact, as the burden in the social, economic, and health care systems is remarkable. In addition, an increasing number of studies have shown that nutritional stunting causes a series of important long-lasting changes such as lower energy expenditure, higher susceptibility to the effects of high-fat diets, lower fat oxidation, and impaired regulation of food intake. These findings suggest that a broader and more detailed understanding of the long-lasting effects of early undernutrition, direct cause of nutritional stunting, is needed. Within this context, we present data of some physiological mechanisms that substantiate the association between previous undernutrition and future obesity.Existe uma quantidade significativa de evidências epidemiológicas mostrando que a baixa estatura nutricional aumenta o risco de obesidade futura. A obesidade vem aumentando dramaticamente, não apenas nos países desenvolvidos, mas também nos países em desenvolvimento, como o Brasil, especialmente entre indivíduos mais pobres. A mera coexistência de desnutrição e obesidade na população pobre tem um grande impacto, gerando enorme sobrecarga para o sistema de saúde e a estrutura sócio-econômica. Além disso, um número cada vez maior de estudos tem mostrado que a baixa estatura nutricional causa uma série de mudanças a longo prazo, como menor gasto energético, maior susceptibilidade aos efeitos de dietas com alto teor de gorduras, menor oxidação de gorduras e prejuízo na regulação da ingestão alimentar. Esses achados sugerem a necessidade de um entendimento mais amplo e detalhado dos efeitos tardios da desnutrição no início da vida, causa direta da baixa estatura para a idade. Dentro desse contexto, apresentamos alguns dados relacionados aos mecanismos fisiológicos subjacentes à associação entre desnutrição e obesidade futura.Universidade Federal de São Paulo (UNIFESP) Departamento de FisiologiaAging at Tufts University Human Nutrition Research CenterUNIFESP, Depto. de FisiologiaSciEL

Electrochemical recovery of ruthenium via carbon black nano-impacts

The recovery of ruthenium from low-concentration solutions poses a significant challenge due to its scarcity and rising economic value, and nano-impact electrochemistry has emerged as a promising method for efficient recovery of critical metals from solution through deposition during impacts of non-metallic nanoparticles. In this study, we investigate the redox chemistry of ruthenium on carbon black via the impact technique and demonstrate the ability to recover ruthenium from solution. The reduction (electrodeposition) and oxidation of Ru3+ ions in solution onto carbon black nanoparticles can be observed during nano-impacts with the respective onset potentials of these redox processes agreeing with those obtained from solution voltammetry. Upscaled experiments focusing on the electroreduction process, led to the formation of RuOx deposits, confirmed through scanning electron microscopy/energy-dispersive X-ray (SEM/EDX) analysis, X-ray photoelectron spectroscopy (XPS) analysis, and thermogravimetric analysis (TGA). Under partially-optimised conditions, >90 % recovery of Ru(III) from a 1 mM solution was achieved in ca. 8

A new family of phosphoinositide phosphatases in microorganisms: identification and biochemical analysis

<p>Abstract</p> <p>Background</p> <p>Phosphoinositide metabolism is essential to membrane dynamics and impinges on many cellular processes, including phagocytosis. Modulation of phosphoinositide metabolism is important for pathogenicity and virulence of many human pathogens, allowing them to survive and replicate in the host cells. Phosphoinositide phosphatases from bacterial pathogens are therefore key players in this modulation and constitute attractive targets for chemotherapy. MptpB, a virulence factor from <it>Mycobacterium tuberculosis</it>, has phosphoinositide phosphatase activity and a distinct active site P-loop signature HCXXGKDR that shares characteristics with eukaryotic lipid phosphatases and protein tyrosine phosphatases. We used this P-loop signature as a "diagnostic motif" to identify related putative phosphatases with phosphoinositide activity in other organisms.</p> <p>Results</p> <p>We found more than 200 uncharacterised putative phosphatase sequences with the conserved signature in bacteria, with some related examples in fungi and protozoa. Many of the sequences identified belong to recognised human pathogens. Interestingly, no homologues were found in any other organisms including Archaea, plants, or animals. Phylogenetic analysis revealed that these proteins are unrelated to classic eukaryotic lipid phosphatases. However, biochemical characterisation of those from <it>Listeria monocytogenes </it>and <it>Leishmania major</it>, demonstrated that, like MptpB, they have phosphatase activity towards phosphoinositides. Mutagenesis studies established that the conserved Asp and Lys in the P-loop signature (HCXXG<b>KD</b>R) are important in catalysis and substrate binding respectively. Furthermore, we provide experimental evidence that the number of basic residues in the P-loop is critical in determining activity towards poly-phosphoinositides.</p> <p>Conclusion</p> <p>This new family of enzymes in microorganisms shows distinct sequence and biochemical characteristics to classic eukaryotic lipid phosphatases and they have no homologues in humans. This study provides a foundation for examining the biological role of this new family of phosphatases and their potential as pharmaceutical targets against infectious diseases.</p

Students\u27 Perceptions of STEM Learning After Participating in a Summer Informal Learning Experience

Background: Informal learning environments increase students’ interest in STEM (e.g., Mohr‐Schroeder et al. School Sci Math 114: 291–301, 2014) and increase the chances a student will pursue a STEM career (Kitchen et al. Sci Educ 102: 529–547, 2018). The purpose of this study was to examine the impact of an informal STEM summer learning experience on student participants, to gain in-depth perspectives about how they felt this experience prepared them for their in-school mathematics and science classes as well as how it influenced their perception of STEM learning. Students’ attitudes and perceptions toward STEM are affected by their motivation, experience, and self-efficacy (Brown et al. J STEM Educ Innov Res 17: 27, 2016). The academic and social experiences students’ have are also important. Traditionally, formal learning is taught in a solitary form (Martin Science Education 88: S71–S82, 2004), while, informal learning is brimming with chances to connect and intermingle with peers (Denson et al. J STEM Educ: Innovations and Research 16: 11, 2015). Results: Informal learning environments increase students’ interest in STEM (e.g., Mohr‐Schroeder et al. School Sci Math 114: 291–301, 2014) and increase the chances a student will pursue a STEM career (Kitchen et al. Sci Educ 102: 529–547, 2018). The purpose of this study was to examine the impact of an informal STEM summer learning experience on student participants, to gain in-depth perspectives about how they felt this experience prepared them for their in-school mathematics and science classes as well as how it influenced their perception of STEM learning. Students’ attitudes and perceptions toward STEM are affected by their motivation, experience, and self-efficacy (Brown et al. J STEM Educ Innov Res 17: 27, 2016). The academic and social experiences students’ have are also important. Traditionally, formal learning is taught in a solitary form (Martin Science Education 88: S71–S82, 2004), while, informal learning is brimming with chances to connect and intermingle with peers (Denson et al. J STEM Educ: Innovations and Research 16: 11, 2015). Conclusions: By using authentic STEM workplaces, the STEM summer learning experience fostered a learning environment that extended and deepened STEM content learning while providing opportunity and access to content, settings, and materials that most middle level students otherwise would not have access to. Students also acknowledged the access they received to hands-on activities in authentic STEM settings and the opportunities they received to interact with STEM professionals were important components of the summer informal learning experience

Structure and tethering mechanism of dynein-2 intermediate chains in intraflagellar transport

Dynein-2 is a large multiprotein complex that powers retrograde intraflagellar transport (IFT) of cargoes within cilia/flagella, but the molecular mechanism underlying this function is still emerging. Distinctively, dynein-2 contains two identical force-generating heavy chains that interact with two different intermediate chains (WDR34 and WDR60). Here, we dissect regulation of dynein-2 function by WDR34 and WDR60 using an integrative approach including cryo-electron microscopy and CRISPR/Cas9-enabled cell biology. A 3.9 Å resolution structure shows how WDR34 and WDR60 use surprisingly different interactions to engage equivalent sites of the two heavy chains. We show that cilia can assemble in the absence of either WDR34 or WDR60 individually, but not both subunits. Dynein-2-dependent distribution of cargoes depends more strongly on WDR60, because the unique N-terminal extension of WDR60 facilitates dynein-2 targeting to cilia. Strikingly, this N-terminal extension can be transplanted onto WDR34 and retain function, suggesting it acts as a flexible tether to the IFT "trains" that assemble at the ciliary base. We discuss how use of unstructured tethers represents an emerging theme in IFT train interactions

CK2 phosphorylation of CMTR1 promotes RNA cap formation and influenza virus infection

Funding: This work was supported by Cancer Research UK core grant number A17196/A31287 to the CRUK Scotland Institute and CTRQQR-2021\100006 to the CRUK Scotland Centre. Research was funded by European Research Council Award 769080 TCAPS, Medical Research Council Senior Fellowship MR/K024213/1, a Lister Research Prize Fellowship, a Wellcome Trust PhD studentship 097462/Z/11/Z, Royal Society Wolfson Research Merit Award WRM\R1\180008, Wellcome Trust Investigator Award 219416/A/19/Z, and Wellcome Trust GRE Centre Award 097945/Z/11/Z.The RNA cap methyltransferase CMTR1 methylates the first transcribed nucleotide of RNA polymerase II transcripts, impacting gene expression mechanisms, including during innate immune responses. Using mass spectrometry, we identify a multiply phosphorylated region of CMTR1 (phospho-patch [P-Patch]), which is a substrate for the kinase CK2 (casein kinase II). CMTR1 phosphorylation alters intramolecular interactions, increases recruitment to RNA polymerase II, and promotes RNA cap methylation. P-Patch phosphorylation occurs during the G1 phase of the cell cycle, recruiting CMTR1 to RNA polymerase II during a period of rapid transcription and RNA cap formation. CMTR1 phosphorylation is required for the expression of specific RNAs, including ribosomal protein gene transcripts, and promotes cell proliferation. CMTR1 phosphorylation is also required for interferon-stimulated gene expression. The cap-snatching virus, influenza A, utilizes host CMTR1 phosphorylation to produce the caps required for virus production and infection. We present an RNA cap methylation control mechanism whereby CK2 controls CMTR1, enhancing co-transcriptional capping.Peer reviewe