Glutaredoxin GRXS17 associates with the cytosolic iron-sulfur cluster assembly pathway

Cytosolic monothiol glutaredoxins (GRXs) are required in iron-sulfur (Fe-S) cluster delivery and iron sensing in yeast and mammals. In plants, it is unclear whether they have similar functions. Arabidopsis (Arabidopsis thaliana) has a sole class II cytosolic monothiol GRX encoded by GRXS17. Here, we used tandem affinity purification to establish that Arabidopsis GRXS17 associates with most known cytosolic Fe-S assembly (CIA) components. Similar to mutant plants with defective CIA components, grxs17 loss-of-function mutants showed some degree of hypersensitivity to DNA damage and elevated expression of DNA damage marker genes. We also found that several putative Fe-S client proteins directly bind to GRXS17, such as XANTHINE DEHYDROGENASE1 (XDH1), involved in the purine salvage pathway, and CYTOSOLIC THIOURIDYLASE SUBUNIT1 and CYTOSOLIC THIOURIDYLASE SUBUNIT2, both essential for the 2-thiolation step of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) modification of tRNAs. Correspondingly, profiling of the grxs17-1 mutant pointed to a perturbed flux through the purine degradation pathway and revealed that it phenocopied mutants in the elongator subunit ELO3, essential for the mcm5 tRNA modification step, although we did not find XDH1 activity or tRNA thiolation to be markedly reduced in the grxs17-1 mutant. Taken together, our data suggest that plant cytosolic monothiol GRXs associate with the CIA complex, as in other eukaryotes, and contribute to, but are not essential for, the correct functioning of client Fe-S proteins in unchallenged conditions

Review on solving the forward problem in EEG source analysis

Background. The aim of electroencephalogram (EEG) source localization is to find the brain areas responsible for EEG waves of interest. It consists of solving forward and inverse problems. The forward problem is solved by starting from a given electrical source and calculating the potentials at the electrodes. These evaluations are necessary to solve the inverse problem which is defined as finding brain sources which are responsible for the measured potentials at the EEG electrodes. Methods. While other reviews give an extensive summary of the both forward and inverse problem, this review article focuses on different aspects of solving the forward problem and it is intended for newcomers in this research field. Results. It starts with focusing on the generators of the EEG: the post-synaptic potentials in the apical dendrites of pyramidal neurons. These cells generate an extracellular current which can be modeled by Poisson's differential equation, and Neumann and Dirichlet boundary conditions. The compartments in which these currents flow can be anisotropic (e.g. skull and white matter). In a three-shell spherical head model an analytical expression exists to solve the forward problem. During the last two decades researchers have tried to solve Poisson's equation in a realistically shaped head model obtained from 3D medical images, which requires numerical methods. The following methods are compared with each other: the boundary element method (BEM), the finite element method (FEM) and the finite difference method (FDM). In the last two methods anisotropic conducting compartments can conveniently be introduced. Then the focus will be set on the use of reciprocity in EEG source localization. It is introduced to speed up the forward calculations which are here performed for each electrode position rather than for each dipole position. Solving Poisson's equation utilizing FEM and FDM corresponds to solving a large sparse linear system. Iterative methods are required to solve these sparse linear systems. The following iterative methods are discussed: successive over-relaxation, conjugate gradients method and algebraic multigrid method. Conclusion. Solving the forward problem has been well documented in the past decades. In the past simplified spherical head models are used, whereas nowadays a combination of imaging modalities are used to accurately describe the geometry of the head model. Efforts have been done on realistically describing the shape of the head model, as well as the heterogenity of the tissue types and realistically determining the conductivity. However, the determination and validation of the in vivo conductivity values is still an important topic in this field. In addition, more studies have to be done on the influence of all the parameters of the head model and of the numerical techniques on the solution of the forward problem.peer-reviewe

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Crystallization and polymorphic behavior of enzymatically produced sunflower oil based cocoa butter equivalents

A multi-methodological approach was used to study the isothermal crystallization of cocoa butter (CB) in the presence of sunflower oil based cocoa butter equivalents (CBEs). pNMR, DSC, oscillatory rheology, XRD, and PLM were used for this purpose. All the techniques confirmed that at 20°C isothermal crystallization of all the blends is a two-step process with formation of α crystals in the first step and formation of β’ crystals in the second step. The blends with high amount of CBEs contained more high-melting triacylglycerols (TAGs) and diacylglycerol (DAG) in compare with CB acting as seed crystals enhancing the formation of a- crystals in the first crystallization step. Therefore, the induction time of the first crystallization step was inversely related to the amount of CBE. In contrast, the subsequent polymorphic transition was delayed by the presence of the CBE due to their low-melting TAGs. However, adding up to 5% CBE did not change the Foubert’s parameters for isothermal crystallization significantly. All the blends (except 5% HOSO CBE), had a mediated β’ crystallization. Picturing of the microstructure showed that for the CB and the blends up to 50% large microstructures, indicative of the bV polymorph developed during storage. At 100%, a dense network of spherulites was formed at the beginning of the crystallization period, but upon further storage, no large morphological changes were observed. Practical applications: In recent years, the production of CB has been delayed owing to its cultivation difficulty and low yield due to pest attack, while the world cocoa prices have increased with rising demand and higher chocolate consumption. Therefore, there is a need to develop low-priced and appropriate alternatives to CB. Accordingly, in this study two sunflower oil based CBEs were produced with fatty acid mixtures in the presence of immobilized 1,3-regiospecific lipase. The results from this study could help the fats and oils industries to extend their knowledge on the crystallization and polymorphic behavior of two enzymatically produced sunflower oil based CBEs

Analysis of a discrete-time queue with time-limited overtake priority

In this paper, we investigate a single-server discrete-time queueing system subject to two independent batch Bernoulli arrival processes, each supplying the queue with different customer classes. The two classes of customers have different priority levels in the queue, and different service-time distributions. The studied priority mechanism is time-limited, i.e., customers of the high-priority class cannot overtake customers of lower priority if the latter arrived at least N slots earlier than the former. The parameter N makes the mechanism versatile, spanning a bridge between absolute (fixed) priority and slot-bound priority (see De Clercq et al. in Math Probl Eng. doi: 10.1155/2012/425630, 2012). The time-limited overtake priority mechanism maintains levels of fairness that are unattainable by a pure absolute priority mechanism, and offers more service differentiation than the slot-bound priority alternative studied earlier. By using a censoring argument, we obtain expressions for the steady-state probability generating functions of the delays of both customer classes, as well as the steady-state joint probability generating function of the system content, by using a censoring argument

Fine-Scale Mapping of the Contact Risk Between Cattle and African Buffaloes near the Kruger National Park

info:eu-repo/semantics/nonPublishe

Personality Symptoms and Self-Esteem as Correlates of Psychopathology in Child Psychiatric Patients: Evaluating Multiple Informant Data

Research on adulthood posits personality and self-esteem as important predictors of psychopathology. In childhood, however, the study of these relationships is complicated by the lack of consensus on how to combine data from multiple informants of child behavior. This study evaluates the relationships among personality symptoms, self-esteem and psychopathology in 60 child psychiatric patients (M (age) = 10.6) using principal component analysis (PCA) to aggregate data from multiple informants and compares this strategy with a single informant approach. When predictor and criterion measures were rated by a single informant, strong and differential relationships between personality symptoms, self-esteem and psychopathology are found. When multiple informant data were combined into composite scores by PCA, correlations decreased but remained significant. Hierarchical regression analyses affirm the robustness of the following pattern: Emotional Instability, Introversion and Global Self-Esteem are associated with internalizing whereas Disagreeableness and Behavioral Conduct primarily relate to externalizing problems