The Early Postnatal Life: A Dynamic Period in Thymic Epithelial Cell Differentiation

The microenvironments formed by cortical (c) and medullary (m) thymic epithelial cells (TECs) play a non-redundant role in the generation of functionally diverse and self-tolerant T cells. The role of TECs during the first weeks of the murine postnatal life is particularly challenging due to the significant augment in T cell production. Here, we critically review recent studies centered on the timely coordination between the expansion and maturation of TECs during this period and their specialized role in T cell development and selection. We further discuss how aging impacts on the pool of TEC progenitors and maintenance of functionally thymic epithelial microenvironments, and the implications of these chances in the capacity of the thymus to sustain regular thymopoiesis throughout life.This work was supported by a starting grant from the European Research Council (ERC) under the project 637843 and by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-029129 (PTDC/MED-IMU/29129/2017) and PTDC/ MED-IMU/1416/2020. NA is supported by the FCT program “Scientific Employment Stimulus” and RP by a FCT PhD fellowship

Editorial: Thymic Epithelial Cells: New Insights Into the Essential Driving Force of T-Cell Differentiation

M.B. is supported by the Intramural Research Program of the NIH. I.O. is supported by grant from the MEXT-JSPS 17K08884 and Takeda Science Foundation. The laboratory of N.L.A. is supported by a starting grant from the European Research Council (ERC) under the project 637843 and by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-029129 (PTDC/MED-IMU/29129/2017) and PTDC/ MED-IMU/1416/2020

Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus.

Cortical and medullary thymic epithelial cells (cTECs and mTECs, respectively) provide inductive microenvironments for T-cell development and selection. The differentiation pathway of cTEC/mTEC lineages downstream of common bipotent progenitors at discrete stages of development remains unresolved. Using IL-7/CCRL1 dual reporter mice that identify specialized TEC subsets, we show that the stepwise acquisition of chemokine (C-C motif) receptor-like 1 (CCRL1) is a late determinant of cTEC differentiation. Although cTECs expressing high CCRL1 levels (CCRL1(hi) ) develop normally in immunocompetent and Rag2(-/-) thymi, their differentiation is partially blocked in Rag2(-/-) Il2rg(-/-) counterparts. These results unravel a novel checkpoint in cTEC maturation that is regulated by the cross-talk between TECs and immature thymocytes. Additionally, we identify new Ulex europaeus agglutinin 1 (UEA)(+) mTEC subtypes expressing intermediate CCRL1 levels (CCRL1(int) ) that conspicuously emerge in the postnatal thymus and differentially express Tnfrsf11a, Ccl21, and Aire. While rare in fetal and in Rag2(-/-) thymi, CCRL1(int) mTECs are restored in Rag2(-/-) Marilyn TCR-Tg mice, indicating that the appearance of postnatal-restricted mTECs is closely linked with T-cell selection. Our findings suggest that alternative temporally restricted routes of new mTEC differentiation contribute to the establishment of the medullary niche in the postnatal thymus.We thank James Di Santo, Jocelyne Demengeot, and Thomas Boehm for Rag2−/−Il2rg−/−, CCRL1-reporter, and Marilyn-Rag2−/− mice, respectively. We thank Dr. Catarina Leit˜ao for critical reading of the manuscript and technical assistance. We thank FEDER funds through the Operational Competitiveness Programme – COMPETE and by National Funds through Fundaçao para a Ciência e a Tecnologia (FCT) under the project PTDC/SAU-IMU/117057/2010 funded this work. N.L.A., A.R.R.,C.M., and P.M.R. are supported by FCT Investigator program and PhD fellowships

Serious Games Application for Memory Training Using Egocentric Images

Mild cognitive impairment is the early stage of several neurodegenerative diseases, such as Alzheimer's. In this work, we address the use of lifelogging as a tool to obtain pictures from a patient's daily life from an egocentric point of view. We propose to use them in combination with serious games as a way to provide a non-pharmacological treatment to improve their quality of life. To do so, we introduce a novel computer vision technique that classifies rich and non rich egocentric images and uses them in serious games. We present results over a dataset composed by 10,997 images, recorded by 7 different users, achieving 79% of F1-score. Our model presents the first method used for automatic egocentric images selection applicable to serious games.Comment: 11 page

The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation

The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity

Satisfação materna com o cuidado da enfermeira materno-infantil em Campeche, México

OBJECTIVE: Evaluate and compare maternal-satisfaction (global and areas) with maternal-child nursing care (MSMINC) and to explore the relationship of MSMINC with wait time, length of visit, and maternal age and education. METHODS: Cross-sectional descriptive study comprising 213 mothers. Group 1 (n = 84), mothers of children agedEl objetivo de este estudio fue evaluar y comparar la satisfacción materna (global/áreas) con el cuidado de la enfermera materno infantil (MSMINC) y explorar la relación de MSMINC con el tiempo de espera, duración de la visita, edad y educación materna. Se trata de un estudio descriptivo transversal. Participaron 213 madres. Grupo 1, n = 84 madres de niñosOBJETIVO: Avaliar e comparar a satisfação materna (global e áreas) com o cuidado da enfermeira materno-infantil (SMAEMI) e explorar a relação da SMAEMI com o tempo de espera e duração da visita, idade e educação da mãe. MÉTODOS: ESTUdo descritivo-transversal com a participação de 213 mães. Grupo 1, n = 84 mães de criança

Lymphotoxin-β receptor in microenvironmental cells promotes the development of T-cell acute lymphoblastic leukaemia with cortical/mature immunophenotype.

Lymphotoxin-mediated activation of the lymphotoxin-β receptor (LTβR; LTBR) has been implicated in cancer, but its role in T-cell acute lymphoblastic leukaemia (T-ALL) has remained elusive. Here we show that the genes encoding lymphotoxin (LT)-α and LTβ (LTA, LTB) are expressed in T-ALL patient samples, mostly of the TAL/LMO molecular subtype, and in the TEL-JAK2 transgenic mouse model of cortical/mature T-ALL (Lta, Ltb). In these mice, expression of Lta and Ltb is elevated in early stage T-ALL. Surface LTα1 β2 protein is expressed in primary mouse T-ALL cells, but only in the absence of microenvironmental LTβR interaction. Indeed, surface LT expression is suppressed in leukaemic cells contacting Ltbr-expressing but not Ltbr-deficient stromal cells, both in vitro and in vivo, thus indicating that dynamic surface LT expression in leukaemic cells depends on interaction with its receptor. Supporting the notion that LT signalling plays a role in T-ALL, inactivation of Ltbr results in a significant delay in TEL-JAK2-induced leukaemia onset. Moreover, young asymptomatic TEL-JAK2;Ltbr(-/-) mice present markedly less leukaemic thymocytes than age-matched TEL-JAK2;Ltbr(+/+) mice and interference with LTβR function at this early stage delayed T-ALL development. We conclude that LT expression by T-ALL cells activates LTβR signalling in thymic stromal cells, thus promoting leukaemogenesis.Grants from Fundação para a Ciencia e a Tecnologia (PTDC/SAU-OBD/103336/2008 and PEst-OE/EQB/LA0023/2013), Nucleo Regional Sul da Liga Portuguesa Contra o Cancro (NRS/LPCC-Terry Fox) and Fundacao MSD to NRdS; grants from the Sao Paulo Research Foundation (FAPESP 08/10034-1 and 12/12802-1) to JAY; and Plan Cancer Action 29 to ED. MTF (SFRH/BD/75137/2010) MNG (SFRH/BD/80503/2011), and RKK (SFRH/BPD/70718/2010) were recipients of FCT PhD or postdoctoral fellowships. ABS and JAY are supported by PhD and Productivity Fellowships, respectively, from the Brazilian National Council for Scientific and Technological Development (CNPq). NRdS has been supported by FCT Ciencia 2007 and FCT Investigator contracts (IF/00056/2012)

An investigation of the predictability of the Brazilian three-modal hand-based behavioural biometric: a feature selection and feature-fusion approach

Abstract: New security systems, methods or techniques need to have their performance evaluated in conditions that closely resemble a real-life situation. The effectiveness with which individual identity can be predicted in different scenarios can benefit from seeking a broad base of identity evidence. Many approaches to the implementation of biometric-based identification systems are possible, and different configurations are likely to generate significantly different operational characteristics. The choice of implementational structure is, therefore, very dependent on the performance criteria, which is most important in any particular task scenario. The issue of improving performance can be addressed in many ways, but system configurations based on integrating different information sources are widely adopted in order to achieve this. Thus, understanding how each data information can influence performance is very important. The use of similar modalities may imply that we can use the same features. However, there is no indication that very similar (such as keyboard and touch keystroke dynamics, for example) basic biometrics will perform well using the same set of features. In this paper, we will evaluate the merits of using a three-modal hand-based biometric database for user prediction focusing on feature selection as the main investigation point. To the best of our knowledge, this is the first thought-out analysis of a database with three modalities that were collected from the same users, containing keyboard keystroke, touch keystroke and handwritten signature. First, we will investigate how the keystroke modalities perform, and then, we will add the signature in order to understand if there is any improvement in the results. We have used a wide range of techniques for feature selection that includes filters and wrappers (genetic algorithms), and we have validated our findings using a clustering technique

Risks to Birds Traded for African Traditional Medicine: A Quantitative Assessment

Few regional or continent-wide assessments of bird use for traditional medicine have been attempted anywhere in the world. Africa has the highest known diversity of bird species used for this purpose. This study assesses the vulnerability of 354 bird species used for traditional medicine in 25 African countries, from 205 genera, 70 families, and 25 orders. The orders most represented were Passeriformes (107 species), Falconiformes (45 species), and Coraciiformes (24 species), and the families Accipitridae (37 species), Ardeidae (15 species), and Bucerotidae (12 species). The Barn owl (Tyto alba) was the most widely sold species (seven countries). The similarity of avifaunal orders traded is high (analogous to ‘‘morphospecies’’, and using Sørensen’s index), which suggests opportunities for a common understanding of cultural factors driving demand. The highest similarity was between bird orders sold in markets of Benin vs. Burkina Faso (90%), but even bird orders sold in two geographically separated countries (Benin vs. South Africa and Nigeria vs. South Africa) were 87% and 81% similar, respectively. Rabinowitz’s ‘‘7 forms of rarity’’ model, used to group species according to commonness or rarity, indicated that 24% of traded bird species are very common, locally abundant in several habitats, and occur over a large geographical area, but 10% are rare, occur in low numbers in specific habitats, and over a small geographical area. The order with the highest proportion of rare species was the Musophagiformes. An analysis of species mass (as a proxy for size) indicated that large and/or conspicuous species tend to be targeted by harvesters for the traditional medicine trade. Furthermore, based on cluster analyses for species groups of similar risk, vultures, hornbills, and other large avifauna, such as bustards, are most threatened by selective harvesting and should be prioritised for conservation action.University of the Witwatersrand SPARC Prestigious and URC Postdoctoral Fellowships; National Research Foundatio

Kinin-B2 Receptor Mediated Neuroprotection after NMDA Excitotoxicity Is Reversed in the Presence of Kinin-B1 Receptor Agonists

Background: Kinins, with bradykinin and des-Arg 9-bradykinin being the most important ones, are pro-inflammatory peptides released after tissue injury including stroke. Although the actions of bradykinin are in general well characterized; it remains controversial whether the effects of bradykinin are beneficial or not. Kinin-B2 receptor activation participates in various physiological processes including hypotension, neurotransmission and neuronal differentiation. The bradykinin metabolite des-Arg 9-bradykinin as well as Lys-des-Arg 9-bradykinin activates the kinin-B1 receptor known to be expressed under inflammatory conditions. We have investigated the effects of kinin-B1 and B2 receptor activation on N-methyl-Daspartate (NMDA)-induced excitotoxicity measured as decreased capacity to produce synaptically evoked population spikes in the CA1 area of rat hippocampal slices. Principal Findings: Bradykinin at 10 nM and 1 mM concentrations triggered a neuroprotective cascade via kinin-B2 receptor activation which conferred protection against NMDA-induced excitotoxicity. Recovery of population spikes induced by 10 nM bradykinin was completely abolished when the peptide was co-applied with the selective kinin-B2 receptor antagonist HOE-140. Kinin-B2 receptor activation promoted survival of hippocampal neurons via phosphatidylinositol 3-kinase, while MEK/MAPK signaling was not involved in protection against NMDA-evoked excitotoxic effects. However, 100 nM Lys-des-Arg 9-bradykinin, a potent kinin-B1 receptor agonist, reversed bradykinin-induced population spik