Structure and Activation Mechanism of the Drosophila Initiator Caspase Dronc

Activation of an initiator caspase is essential to the execution of apoptosis. The molecular mechanisms by which initiator caspases are activated remain poorly understood. Here we demonstrate that the autocatalytic cleavage of Dronc, an important initiator caspase in Drosophila, results in a drastic enhancement of its catalytic activity in vitro. The autocleaved Dronc forms a homodimer, whereas the uncleaved Dronc zymogen exists exclusively as a monomer. Thus the autocatalytic cleavage in Dronc induces its stable dimerization, which presumably allows the two adjacent monomers to mutually stabilize their active sites, leading to activation. Crystal structure of a prodomain-deleted Dronc zymogen, determined at 2.5 Å resolution, reveals an unproductive conformation at the active site, which is consistent with the observation that the zymogen remains catalytically inactive. This study revealed insights into mechanism of Dronc activation, and in conjunction with other observations, suggests diverse mechanisms for the activation of initiator caspases

Neural connectivity during reward expectation dissociates psychopathic criminals from non-criminal individuals with high impulsive/antisocial psychopathic traits

Criminal behaviour poses a big challenge for society. A thorough understanding of the neurobiological mechanisms underlying criminality could optimize its prevention and management. Specifically,elucidating the neural mechanisms underpinning reward expectation might be pivotal to understanding criminal behaviour. So far no study has assessed reward expectation and its mechanisms in a criminal sample. To fill this gap, we assessed reward expectation in incarcerated, psychopathic criminals. We compared this group to two groups of non-criminal individuals: one with high levels and another with low levels of impulsive/antisocial traits. Functional magnetic resonance imaging was used to quantify neural responses to reward expectancy. Psychophysiological interaction analyses were performed to examine differences in functional connectivity patterns of reward-related regions. The data suggest that overt criminality is characterized, not by abnormal reward expectation per se , but rather by enhanced communication between reward-related striatal regions and frontal brain regions. We establish that incarcerated psychopathic criminals can be dissociated from non-criminal individuals with comparable impulsive/antisocial personality tendencies based on the degree to which reward-related brain regions interact with brain regions that control behaviour. The present results help us understand why some people act according to their impulsive/antisocial personality while others are able to behave adaptively despite reward-related urges

Starch-Galactomannans Mixtures: Rheological and Viscosity Behavior in Aqueous Systems for Food Modeling

Starch properties during processing are major determinants of starch employment for food development. The gelatinization, pasting, and retrogradation of starch can be modified by the addition of galactomannans, which can improve rheological, textural, and nutritional properties. Rheology is an important key to obtain information about thermal transitions of starch and controlling characteristics required in food applications and to enhance understanding of the effect of starch-galactomannans systems and starch properties. This chapter provides information on starch transitions under heating and after cooling, including a definition of the process, molecular mechanisms, and rheological methods and its modification using starch-galactomannans mixtures and explains interactions throughout several investigations. The chapter also discusses how the rheological properties can affect the rate of the enzyme digestibility of starch on in vitro measurements and presents the starch-galactomannan systems as an alternative that can be used in structured foods as functional ingredients

Structural Characterization of the Extracellular Domain of CASPR2 and Insights into Its Association with the Novel Ligand Contactin1

Contactin-associated protein-like 2 (CNTNAP2) encodes for CASPR2, a multidomain single transmembrane protein belonging to the neurexin superfamily that has been implicated in a broad range of human phenotypes including autism and language impairment. Using a combination of biophysical techniques, including small angle x-ray scattering, single particle electron microscopy, analytical ultracentrifugation, and bio-layer interferometry, we present novel structural and functional data that relate the architecture of the extracellular domain of CASPR2 to a previously unknown ligand, Contactin1 (CNTN1). Structurally, CASPR2 is highly glycosylated and has an overall compact architecture. Functionally, we show that CASPR2 associates with micromolar affinity with CNTN1 but, under the same conditions, it does not interact with any of the other members of the contactin family. Moreover, by using dissociated hippocampal neurons we show that microbeads loaded with CASPR2, but not with a deletion mutant, co-localize with transfected CNTN1, suggesting that CNTN1 is an endogenous ligand for CASPR2. These data provide novel insights into the structure and function of CASPR2, suggesting a complex role of CASPR2 in the nervous system

Nanoscale structure determination of Murray Valley encephalitis and Powassan virus non-coding RNAs

Open access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) appliesViral infections are responsible for numerous deaths worldwide. Flaviviruses, which contain RNA as their genetic material, are one of the most pathogenic families of viruses. There is an increasing amount of evidence suggesting that their 5’ and 3’ non-coding terminal regions are critical for their survival. Information on their structural features is essential to gain detailed insights into their functions and interactions with host proteins. In this study, the 5’ and 3’ terminal regions of Murray Valley encephalitis virus and Powassan virus were examined using biophysical and computational modeling methods. First, we used size exclusion chromatography and analytical ultracentrifuge methods to investigate the purity of in-vitro transcribed RNAs. Next, we employed small-angle X-ray scattering techniques to study solution conformation and low-resolution structures of these RNAs,which suggest that the 3’ terminal regions are highly extended as compared to the 5’ terminal regions for both viruses. Using computational modeling tools, we reconstructed 3-dimensional structures of each RNA fragment and compared them with derived small-angle X-ray scattering low-resolution structures. This approach allowed us to reinforce that the 5’ terminal regions adopt more dynamic structures compared to the mainly double-stranded structures of the 3’ terminal regions.Ye

Modelos estatísticos para avaliação da qualidade culinária de arroz: textura e propriedades viscoamilográficas.

Buscou-se verificar a relação existente entre medidas de textura sensorial e instrumental; minimizar a quantidade de medidas de perfil viscoamilográfico (gelatinização, viscosidade e tendência à retrogradação do amido) necessária para explicar as medidas de textura sensorial; comparar e identificar modelos estatísticos que melhor representem a relação entre medidas de textura sensorial e viscoamilográficas, a fim de propor alternativas para a classificação de textura do arroz cozido na seleção de linhagens promissoras em programas de melhoramento genético

Investigation of Ionospheric Effects in the Planning of the AlfaCrux UHF Satellite Communication System

Recent technological advances and new launch opportunities have allowed the development and spread of small satellite missions for commercial and educational purposes and different applications. Among this category of small satellites, CubeSats have attracted lots of attention given their low design-and-deployment costs. Such satellites usually operate in the narrow ranges of the UHF frequency band to perform the communication activities. Although it provides lower data rate, the use of narrowband can be advantageous when compared to broadband, due to its better penetration and lower attenuation in the troposphere. However, the signals in this frequency band can be significantly affected by the ionosphere. This work investigates the ionospheric effects, namely the Faraday rotation and scintillation, on the UHF satellite communication systems, taking as a case study the AlfaCrux CubeSat mission, which is an 1U CubeSat mission planned for conducting research activities in the field of satellite-mediated communication. In particular, we investigate the variability of Faraday rotation and amplitude scintillation with the daytime, season, and geographic position for periods of low and high solar activity. In addition, this work presents a methodology of risk estimation for communication outage over the Brazilian sector. Aiming to address the most realistic communication scenario, we include in this analysis the effects due to scintillation, free-space propagation, tropospheric attenuation, and polarization losses. By doing so, the regions with the high risk of communication outage may be estimated in advance and used for optimal mission planning

Aplicação de modelo de regressão logística para predição da qualidade culinária de arroz.

Buscou-se verificar a relação existente entre medidas de textura sensorial e instrumental; minimizar a quantidade de medidas de perfil viscoamilográfico (gelatinização, viscosidade e tendência à retrogradação do amido) necessária para explicar as medidas de textura sensorial; comparar e identificar modelos estatísticos que melhor representem a relação entre medidas de textura sensorial e viscoamilográficas, a fim de propor alternativas para a classificação de textura do arroz cozido na seleção de linhagens promissoras em programas de melhoramento genético

Kindlin-3 maintains marginal zone B cells but confines follicular B cell activation and differentiation

Integrin-mediated interactions between hematopoietic cells and their microenvironment are important for the development and function of immune cells. Here, the role of the integrin adaptor Kindlin-3 in B cell homeostasis is studied. Comparing the individual steps of B cell development in B cell-specific Kindlin-3 or alpha4 integrin knockout mice, we found in both conditions a phenotype of reduced late immature, mature, and recirculating B cells in the bone marrow. In the spleen, constitutive B cell-specific Kindlin-3 knockout caused a loss of marginal zone B cells and an unexpected expansion of follicular B cells. Alpha4 integrin deficiency did not induce this phenotype. In Kindlin-3 knockout B cells VLA-4 as well as LFA-1-mediated adhesion was abrogated, and short-term homing of these cells in vivo was redirected to the spleen. Upon inducible Kindlin-3 knockout, marginal zone B cells were lost due to defective retention within 2 weeks, while follicular B cell numbers were unaltered. Kindlin-3 deficient follicular B cells displayed higher IgD, CD40, CD44, CXCR5, and EBI2 levels, and elevated PI3K signaling upon CXCR5 stimulation. They also showed transcriptional signatures of spontaneous follicular B cell activation. This activation manifested in scattered germinal centers in situ, early plasmablasts differentiation, and signs of IgG class switch

Ajuste de escalas de classificação de arroz cozido para avaliação de pegajosidade e dureza.

O objetivo deste trabalho foi ajustar e redefinir as notas e padrões da escala sensorial de classificação da textura do arroz cozido, a fim de facilitar a compreensão dos painelistas e aproximar os resultados laboratoriais da análise feita pelas indústria