Summary
Regulatory T cells (Tregs) constitute a fascinating subpopulation of CD4+ T cells due to their ability to limit the immune response against self and non‐self antigens. Murine models and ...antibodies directed against surface and intracellular molecules have allowed elucidation of the mechanisms that govern their development and function. However, these markers used to their classification lack of specificity, as they can be expressed by activated T cells. Similarly, there are slight differences between animal models, in steady state and pathological conditions, anatomical localization and strategy of analysis by flow cytometry. Here, we revised the most common markers utilized for Treg typification by flow cytometry such as CD25, forkhead box protein 3 (FoxP3) and CD127, along with our data obtained in different body compartments of humans, mice and rats. Furthermore, we revised and determined the expression of other molecules important for the phenotypical characterization of Treg cells. We draw attention to the drawbacks of those markers used in chronic states of inflammation. However, until a specific marker for the identification of Tregs is discovered, the best combination of markers will depend upon the tissue or the degree of inflammation from which Tregs derive.
Transition‐metal‐mediated cleavage of C−C single bonds can enable entirely new retrosynthetic disconnections in the total synthesis of natural products. Given that C−C bond cleavage inherently alters ...the carbon framework of a compound, and that, under transition‐metal catalysis, the generated organometallic or radical intermediate is primed for further complexity‐building reactivity, C−C bond‐cleavage events have the potential to drastically and rapidly remodel skeletal frameworks. The recent acceleration of the use of transition‐metal‐mediated cleavage of C−C single bonds in total synthesis can be ascribed to a communal recognition of this fact. In this Review, we highlight ten selected total syntheses from 2014 to 2019 that illustrate how transition‐metal‐mediated cleavage of C−C single bonds at either the core or the periphery of synthetic intermediates can streamline synthetic efforts.
Rapid remodeling of skeletal frameworks can be achieved by transition‐metal‐mediated cleavage of C−C single bonds and enable new retrosynthetic disconnections. In this Review, ten total syntheses from 2014–2019 are highlighted that illustrate how transition‐metal‐mediated cleavage of C−C single bonds can streamline synthetic efforts.
We develop in this paper a theoretical framework for the topological study of time series data. Broadly speaking, we describe geometrical and topological properties of sliding window embeddings, as ...seen through the lens of persistent homology. In particular, we show that maximum persistence at the point-cloud level can be used to quantify periodicity at the signal level, prove structural and convergence theorems for the resulting persistence diagrams, and derive estimates for their dependency on window size and embedding dimension. We apply this methodology to quantifying periodicity in synthetic data sets and compare the results with those obtained using state-of-the-art methods in gene expression analysis. We call this new method
SW1PerS
, which stands for Sliding Windows and 1-Dimensional Persistence Scoring.
Identifying periodically expressed genes across different processes (e.g. the cell and metabolic cycles, circadian rhythms, etc) is a central problem in computational biology. Biological time series ...may contain (multiple) unknown signal shapes of systemic relevance, imperfections like noise, damping, and trending, or limited sampling density. While there exist methods for detecting periodicity, their design biases (e.g. toward a specific signal shape) can limit their applicability in one or more of these situations.
We present in this paper a novel method, SW1PerS, for quantifying periodicity in time series in a shape-agnostic manner and with resistance to damping. The measurement is performed directly, without presupposing a particular pattern, by evaluating the circularity of a high-dimensional representation of the signal. SW1PerS is compared to other algorithms using synthetic data and performance is quantified under varying noise models, noise levels, sampling densities, and signal shapes. Results on biological data are also analyzed and compared.
On the task of periodic/not-periodic classification, using synthetic data, SW1PerS outperforms all other algorithms in the low-noise regime. SW1PerS is shown to be the most shape-agnostic of the evaluated methods, and the only one to consistently classify damped signals as highly periodic. On biological data, and for several experiments, the lists of top 10% genes ranked with SW1PerS recover up to 67% of those generated with other popular algorithms. Moreover, the list of genes from data on the Yeast metabolic cycle which are highly-ranked only by SW1PerS, contains evidently non-cosine patterns (e.g. ECM33, CDC9, SAM1,2 and MSH6) with highly periodic expression profiles. In data from the Yeast cell cycle SW1PerS identifies genes not preferred by other algorithms, hence not previously reported as periodic, but found in other experiments such as the universal growth rate response of Slavov. These genes are BOP3, CDC10, YIL108W, YER034W, MLP1, PAC2 and RTT101.
In biological systems with low noise, i.e. where periodic signals with interesting shapes are more likely to occur, SW1PerS can be used as a powerful tool in exploratory analyses. Indeed, by having an initial set of periodic genes with a rich variety of signal types, pattern/shape information can be included in the study of systems and the generation of hypotheses regarding the structure of gene regulatory networks.
Summary
Regulatory T cells (Tregs) modulate the magnitude of immune responses and possess therapeutic potential in an array of immune diseases. Statins reduce the activation and proliferation of ...conventional T cells (Tcons), and they seem to up‐regulate the frequency and function of Tregs. However, there is a lack of simultaneous evaluation of the in‐vitro effect of statins on the functional profile of Tregs versus Tcons. Herein, magnetically purified Tcons and Tregs were stimulated with CD3/CD28/interleukin (IL)‐2 in the presence of atorvastatin (ATV) at 1 or 10 µM. The suppressive function of Tregs, the expression of markers associated with Treg function, activation levels, cytokine production and calcium flux in both subpopulations were assessed by flow cytometry. ATV had no cytotoxic effect on T cells at the concentrations used. Interestingly, 10 µM ATV hampered the suppressive capacity of Tregs. Moreover, this higher concentration reduced the expression of forkhead box protein 3 (FoxP3), cytotoxic T lymphocyte antigen (CTLA‐4) and programmed death 1 (PD‐1). In Tcons, ATV at 10 µM decreased PD‐1 and CD45RO expression. The expression of CD25, CD69, CD95, CD38, CD62L, CCR7 and perforin was not affected in both subpopulations or at any ATV concentrations. Remarkably, 10 µM ATV increased the percentage of tumour necrosis factor (TNF)‐α‐producing Tregs. Although there was a reduction of calcium flux in Tcons and Tregs, it was only significant in 10 µM ATV‐treated Tcons. These results suggested that 10 µM ATV affects the cellular functions of both populations; however, this concentration particularly affected several aspects of Treg biology: its suppressive function, cytokine production and expression of Treg‐specific markers.
High atorvastatin concentrations (10 µM) affect the suppressive capacity of Tregs in vitro, as well as cytokine production and expression of Treg specific markers.
The synthesis of diverse
N
-fused heterocycles, including the pyrido1,2-
a
indole scaffold, using an efficient pyrone remodeling strategy is described. The pyrido1,2-
a
indole core was demonstrated ...to be a versatile scaffold that can be site-selectively functionalized. The utility of this novel annulation strategy was showcased in a concise formal synthesis of three fascaplysin congeners.
The synthesis of diverse
N
-fused heterocycles, including the pyrido1,2-
a
indole scaffold, using an efficient pyrone remodeling strategy is described.
Food protein‐induced enterocolitis syndrome (FPIES) is a non‐IgE‐mediated gastrointestinal food hypersensitivity usually due to cow′s milk or soy. Recent researches show that fish is 1 of the most ...important triggers of FPIES in the Mediterranean countries. Due to the risk of multiple‐food FPIES, avoiding foods in the same category or that often occur together may be reasonable. The aim of this study was to evaluate the evolution and follow‐up of FPIES related to fish over a period of 20 years. We describe the clinical features of our population, discuss different approaches to oral food challenges, and analyze the possibility of introducing the culprit fish or other nonrelated fish to avoid unnecessary restricted diets.
Methods to functionalize arenes and heteroarenes in a site-selective manner are highly sought after for rapidly constructing value-added molecules of medicinal, agrochemical, and materials interest. ...One effective approach is the site-selective cross-coupling of polyhalogenated arenes bearing multiple, but identical, halogen groups. Such cross-coupling reactions have proven to be incredibly effective for site-selective functionalization. However, they also present formidable challenges due to the inherent similarities in the reactivities of the halogen substituents. In this Review, we discuss strategies for site-selective cross-couplings of polyhalogenated arenes and heteroarenes bearing identical halogens, beginning first with an overview of the reaction types that are more traditional in nature, such as electronically, sterically, and directing-group-controlled processes. Following these examples is a description of emerging strategies, which includes ligand- and additive/solvent-controlled reactions as well as photochemically initiated processes.
This longitudinal study describes and analyses the shifts in students’ perceptions on the usefulness of language learning strategies (LLS) when learning Spanish as a foreign language, and explains ...the roles that these learning strategies play at various moments in time during students’ language learning journey at the undergraduate level. The richness of this investigation lies in the examination of the changing roles and the perceived usefulness of these strategies over a period of 3 years by using a mixed-method approach. Its main contribution is twofold. On the one hand, it offers practical insights within the linguistic field of language acquisition that can be applied to the learning of foreign languages by students with no previous knowledge of them. On the other hand, its longitudinal design not only goes beyond the traditional quantitative approach that offers a limited snapshot view, but also captures changes in strategy use over time while providing details on why strategies were or were not used in the new language at different proficiency levels. The study found some strategies that were initially perceived as useful and helpful at the beginning of the journey were later perceived as neutral, useless or obstructive by the same group of students who had become more proficient in the foreign language. And, conversely, other strategies that were initially perceived as neutral, unhelpful or frustrating, were later perceived as necessary to improve language proficiency, useful and stimulating by the same cohort of students. In this respect, it was found that the perceived role played by these strategies alternated between essential roles to catalytic roles, imperceptible roles, retarding roles and preventing roles, and vice versa.Contribution The main contribution of this study is that it shows that students’ perceptions on the usefulness of certain LLS over time are influenced by their level of proficiency. This in turn influences, and is influenced by, language attitudes and language learning policy, which fall under the scope of this journal.
Many and varied methods currently exist for featurization, which is the process of mapping persistence diagrams to Euclidean space, with the goal of maximally preserving structure. However, and to ...our knowledge, there are presently no methodical comparisons of existing approaches, nor a standardized collection of test data sets. This paper provides a comparative study of several such methods. In particular, we review, evaluate, and compare the stable multi-scale kernel, persistence landscapes, persistence images, the ring of algebraic functions, template functions, and adaptive template systems. Using these approaches for feature extraction, we apply and compare popular machine learning methods on five data sets: MNIST, Shape retrieval of non-rigid 3D Human Models (SHREC14), extracts from the Protein Classification Benchmark Collection (Protein), MPEG7 shape matching, and HAM10000 skin lesion data set. These data sets are commonly used in the above methods for featurization, and we use them to evaluate predictive utility in real-world applications.
PDF
