Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals.

The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-free (GF) mice display altered daily oscillation of clock gene expression with a concomitant change in the expression of clock output regulators. Mice exposed to microbes typically exhibit characterized activities of nuclear receptors, some of which (PPARα, LXRβ) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiome-sensitive gene expression patterns are associated with daily alterations in lipid, glucose, and xenobiotic metabolism, protein turnover, and redox balance, as revealed by hepatic metabolome analyses. Moreover, at the systemic level, daily changes in the abundance of biomarkers such as HDL cholesterol, free fatty acids, FGF21, bilirubin, and lactate depend on the microbiome. Altogether, our results indicate that the microbiome is required for integration of liver clock oscillations that tune output activators and their effectors, thereby regulating metabolic gene expression for optimal liver function.

Sacral fusion as an aid in age estimation

The degree of fusion at the anterior aspect of the sacral vertebrae has been scored in 242 male and female skeletons from the Lisbon documented collection, ranging in age from 16 to 59 years old. Statistical tests indicate a sex difference towards earlier fusion in young females compared with young males, as well as a clear association between degree of fusion and age. Similar results have been found in documented skeletal samples from Coimbra and Sassari, and the recommendations stated by these authors regarding age estimation have been positively tested in the Lisbon collection. Although more research from geographically diverse samples is required, a general picture of the pattern of sacral fusion and its associations with age and sex is emerging. We also provide a practical example of the usefulness of the sacrum in age estimation in a forensic setting, a mass grave from the Spanish Civil War. It is concluded that the scoring of the degree of fusion of the sacral vertebrae, specially of S1-2, can be a simple tool for assigning skeletons to broad age groups, and it should be implemented as another resource for age estimation in the study of human skeletal remains.

The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma.

Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not β-catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking β-catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation.

O SUS na medicina nuclear do Brasil: avaliação e comparação dos dados fornecidos pelo Datasus e CNEN

Objetivo: Investigar o acesso a procedimentos ambulatoriais de medicina nuclear por intermédio do Sistema Único de Saúde (SUS) do Brasil e analisar a correspondência dos dados fornecidos por este sistema com os da Comissão Nacional de Energia Nuclear (CNEN). Materiais e Métodos: Foram obtidos e avaliados os dados disponíveis no Datasus quanto a quantidade de câmaras de cintilação, procedimentos ambulatoriais de 2008 a 2012, esfera administrativa responsável por estes procedimentos, tipo de prestador de serviços e terceirização de serviços. Também foi feita comparação com os dados de estabelecimentos autorizados pela CNEN. Resultados: O estudo mostrou que ainda falta amadurecimento do sistema quanto à sua completa alimentação, especialmente no campo de equipamentos disponíveis. Foi possível elencar os procedimentos mais realizados e verificar o crescimento da especialidade no período estudado. Estabelecimentos privados são responsáveis pela maior parte dos procedimentos cobertos pelo SUS. Entretanto, muitos estabelecimentos de saúde não são autorizados pela CNEN. Conclusão: O Datasus oferece dados importantes para uma análise como a feita neste estudo, embora alguns pontos ainda demandem atenção. O trabalho mostrou, quantitativamente, a realidade brasileira quanto ao acesso a procedimentos de medicina nuclear oferecidos pelo/para o SUS.

Aplicativo para dosimetria interna usando a distribuição biocinética de fótons baseada em imagens de medicina nuclear

Objetivo: Este artigo apresenta uma forma de se obterem estimativas de dose em pacientes submetidos a tratamentos radioterápicos a partir da análise das regiões de interesse em imagens de medicina nuclear. Materiais e Métodos: Foi desenvolvido o software denominado DoRadIo (Dosimetria das Radiações Ionizantes), que recebe as informações sobre os órgãos fontes e o órgão alvo e retorna resultados gráficos e numéricos. As imagens de medicina nuclear utilizadas foram obtidas de catálogos disponibilizados por físicos médicos. Nas simulações utilizaram-se modelos computacionais de exposição constituídos por fantomas de voxels acoplados ao código Monte Carlo EGSnrc. O software foi desenvolvido no Microsoft Visual Studio 2010 com o modelo de projeto Windows Presentation Foundation e a linguagem de programação C#. Resultados: Da aplicação das ferramentas foram obtidos: o arquivo para otimização das simulações Monte Carlo utilizando o EGSnrc, a organização e compactação dos resultados dosimétricos com todas as fontes, a seleção das regiões de interesse, a contagem da intensidade dos tons de cinza nas regiões de interesse, o arquivo das fontes ponderadas e, finalmente, todos os resultados gráficos e numéricos. Conclusão: A interface de usuários pode ser adaptada para uso em clínicas de medicina nuclear como ferramenta computacional auxiliar na estimativa da atividade administrada.

Ressonância magnética nuclear de platina-195 em compostos organometálicos

A brief review of 195Pt NMR is presented, focusing organometallic compounds. This article gives initially basic information of NMR processes involving 195Pt nucleus. It is followed by a discussion of the factors which affect the chemical shifts and coupling constants. Finally, some aspects of 195Pt NMR of solids are commented.

Nuclear magnetic resonance investigation of structure and dynamics of some electrolyte solutions

Electrolyte solutions are of importance in a wide range of scientific contexts and as such have attracted considerable theoretical and experimental effort over many years. Nuclear Magnetic resonance provides a precise and versatile tool for investigation of electrolyte solutions, both in water and in organic solvents. Many structural and dynamic properties can be obtained through NMR experiments. The solution of aluminum chloride in water was studied. Different concentrations were taken for investigation. Independence of maximum line shift from concentration and acidity was shown. Six-coordinated structure of solvation shell was confirmed by experiments on 'H and 27A1 nuclei. Diffusion coefficients were studied. The solution of nickel chloride in methanol was studied. Lines, corresponding to coordinated and bulk methanol were found. Four-, five- and six-coordinated structures were found in different temperatures. The line for coordinated -OD group of deuterated methanol was observed on 2H spectrum for the first time. Partial deuteration of CH3 group was detected. Inability to observe coordinated -OH group was explained.

Lamellarin D bioconjugates II: synthesis and cellular internalization of dendrimer and nuclear location signal derivatives

The design and synthesis of Lamellarin D conjugates with a nuclear localization signal peptide and a poly(ethylene glycol)-based dendrimer are described. Conjugates 1-4 were obtained in 8-84% overall yields from the corresponding protected Lamellarin D. Conjugates 1 and 4 are 1.4 to 3.3-fold more cytotoxic than the parent compound against three human tumor cell lines(MDA-MB-231 breast, A-549 lung, and HT-29 colon). Besides, conjugates 3, 4 showed a decrease in activity potency in BJ skin fibroblasts, a normal cell culture. Cellular internalization was analyzed and nuclear distribution pattern was observed for 4, which contains a nuclear localization signalling sequence.

Caracterização de polimorfismo em fármacos por ressonância magnética nuclear no estado sólido

This review aims to present some features about solid state NMR and its application in the field of pharmaceutical chemistry, for the characterization of polymorphism of pharmaceutical molecules.

Parâmetros e símbolos a serem utilizados em Ressonância Magnética Nuclear

NMR is now frequently the technique of choice for determination of chemical structure in solution. Its uses also span structure in solids and mobility at the molecular level in all phases. The research literature in the subject is vast and ever-increasing. Unfortunately, many articles do not contain sufficient information for experiments to be repeated elsewhere, and there are many variations in the usage of symbols for the same physical quantity. It is the aim of the present recommendations to provide simple check-lists that will enable such problems to be minimised in a way that is consistent with general IUPAC formulation. The area of medical NMR and imaging is not specifically addressed in these recommendations, which are principally aimed at mainstream use of NMR by chemists (of all sub-disciplines) and by many physicists, biologists, material scientists and geologists etc. working with NMR.

Interação tensoativo/hidrótropo em sistemas aquosos, utilizando ressonância magnética nuclear de ¹H e 13C

In this work, it was studied the behavior of the nonionic surfactant aqueous solutions, containing or not a hydrotropic agent, by resonance magnetic nuclear (NMR). We have studied monofunctional diblock copolymers of poly(propylene oxide-ethylene oxide) (R-PPO-PEO-OH, where R length is linear C4) as nonionic surfactant and sodium p-toluenesulfonate (NaPTS) as hydrotropic agent. The critical micelle concentration (CMC) of the aqueous copolymer solution was obtained from ¹H-NMR. The preliminary study of the interaction between the copolymer, under the unimer and micelle forms, and the hydrotrope, in aqueous solutions, was evaluated by ¹H-NMR and 13C-NMR.