Publications by authors named "Barata J"

Article Synopsis
  • Some babies with a specific mutation in the IL7R gene have a serious immune problem called SCID, where they lack a certain type of immune cells called T cells, but still have normal B and NK cells.
  • In a study of 6 adults who have a similar genetic issue, they showed low levels of T cells but had relatively normal levels of other immune cells, indicating a more specific problem in T cell development.
  • Even though their T cells didn’t grow well in the lab, the study hints that there might be another way T cells can develop that doesn’t depend solely on the IL-7 cytokine.
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Article Synopsis
  • Combining ATR inhibition with radiotherapy enhances the activation of specific T cells in head and neck squamous cell carcinoma (HNSCC) animal models.
  • The addition of NKG2A and PD-L1 blockade to this combination leads to a stronger antitumor response by increasing the presence of activated cytotoxic T cells in tumors.
  • The effectiveness of this treatment relies on specific immune signaling and the diversity of T cell receptors, suggesting promising new strategies for HNSCC therapy.
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  • γδ T cells play a crucial role in immune responses by quickly producing interferon-γ (IFN-γ), especially during the perinatal period when there's an increase in these cells that express CD8αβ heterodimers.
  • Their development relies on low T cell receptor signaling, supported by interleukin (IL)-4 and IL-7, which helps regulate their growth.
  • Aberrations in IL-7R-STAT5B signaling can lead to an excessive number of these cells in certain diseases, and they are also linked to pediatric cases of acute lymphoblastic leukemia.
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The globalization of food markets has led companies to buy products not only locally, but also from other corners of the world. This has introduced complexity into supply chains, as products have to move longer distances and pass through more companies before reaching the end consumer. The meat industry has been no different.

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CASZ1 is a conserved transcription factor involved in neural development, blood vessel assembly and heart morphogenesis. CASZ1 has been implicated in cancer, either suppressing or promoting tumor development depending on the tissue. However, the impact of CASZ1 on hematological tumors remains unknown.

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Triple-negative breast cancer (TNBC) is a devastating BC subtype. Its aggressiveness, allied to the lack of well-defined molecular targets, usually culminates in the appearance of metastases that account for poor prognosis, particularly when they develop in the brain. Nevertheless, TNBC has been associated with epidermal growth factor receptor (EGFR) overexpression, leading to downstream phosphoinositide 3-kinase (PI3K) signaling activation.

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Background: Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies.

Methods: Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of , a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins.

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The downstream signaling of the interleukin-7 (IL-7) receptor (IL-7R) plays important physiological and pathological roles, including the differentiation of lymphoid cells and proliferation of acute lymphoblastic leukemia cells. Gain-of-function mutations in the IL-7Rα chain, the specific component of the receptor for IL-7, result in constitutive, IL-7-independent signaling and trigger acute lymphoblastic leukemia. Here, we show that the loss of the phosphoinositide 5-phosphatase INPP5K is associated with increased levels of the INPP5K substrate phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P2) and causes an altered dynamic structure of the IL-7 receptor.

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The role of IL-7 and IL-7R for normal lymphoid development and an adequately functioning immune system has been recognized for long, with severe immune deficiency and lymphoid leukemia as extreme examples of the consequences of deregulation of the IL-7-IL-7R axis. In this review, we provide an update (focusing on the past couple of years) on IL-7 and IL-7R in health and disease. We highlight the findings on IL-7/IL-7R signaling mechanisms and the, sometimes controversial, impact of IL-7 and its receptor on leukocyte biology, COVID-19, acute lymphoblastic leukemia, and different solid tumors, as well as their relevance as therapeutic tools or targets.

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Details on the unexpected formation of two new (dimethylamino)methyl corrole isomers from the reaction of 5,10,15-tris(pentafluorophenyl)corrolatogallium(III) with sarcosine and paraformaldehyde are presented. Semi-empirical calculations on possible mechanism pathways seem to indicate that the new compounds are probably formed through a Mannich-type reaction. The extension of the protocol to the free-base 5,10,15-tris(pentafluorophenyl)corrole afforded an unexpected new seven-membered ring corrole derivative, confirming the peculiar behavior of corroles towards known reactions when compared to the well-behaved porphyrin counterparts.

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Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant brain tumor in infants that is characterized by loss of nuclear expression of SMARCB1 or SMARCA4 proteins. Recent studies show that AT/RTs comprise three molecular subgroups, namely AT/RT-TYR, AT/RT-MYC and AT/RT-SHH. The subgroups show distinct expression patterns of genes involved in ciliogenesis, however, little is known about the functional roles of primary cilia in the biology of AT/RT.

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Corroles possess key photophysical and photochemical properties to be exploited as therapeutic agents in antimicrobial photodynamic therapy (aPDT). Herein, we present for the first time the antimicrobial efficiency of three corrole dimers and of the corresponding precursor against the Gram(+) bacterium Staphylococcus aureus. Additionally, to explore future clinical applications, the cytotoxicity of the most promising derivatives towards Vero cells was evaluated.

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A 30-year-old man presents with dry cough and dyspnea on exertion (modified Medical Research Council dyspnea scale of 3), with progressive worsening over several months. He denies other respiratory or cardiac symptoms such as wheezing, hemoptysis, thoracalgia, palpitations, or leg swelling. He also denies constitutional symptoms, namely fever, sweating, anorexia, or weight loss.

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Dissemination of cancer cells from primary tumors to the brain occurs in many cancer patients, increasing morbidity and death. There is an unmet medical need to develop translational platforms to evaluate therapeutic responses. Toward this goal, we established a library of 23 patient-derived xenografts (PDXs) of brain metastases (BMs) from eight distinct primary tumors.

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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric cancer. Amongst the wide array of driver mutations, 10% of T-ALL patients display gain-of-function mutations in the IL-7 receptor α chain (IL-7Rα, encoded by IL7R), which occur in different molecular subtypes of this disease. However, it is still unclear whether IL-7R mutational activation is sufficient to transform T-cell precursors.

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Background: Intratumoral heterogeneity is crucially involved in metastasis, resistance to therapy, and cancer relapse. Amplifications of the proto-oncogene MYC display notable heterogeneity at the single-cell level and are associated with a particularly dismal prognosis in high-risk medulloblastomas (MBs). The aim of this study was to establish the relevance of interclonal cross-talk between MYC-driven and non-MYC-driven MB cells.

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Commitment to the CD4+ or CD8+ T cell lineages is linked to the acquisition of a functional program broadly defined by helper and cytotoxic properties, respectively. The mechanisms underlying these processes in the human thymus remain largely unclear. Moreover, recent thymic emigrants are thought to have some degree of plasticity, which may be important for the shaping of the immune system and adjustment to specific peripheral needs.

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Kinase signaling fuels growth of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Yet its role in leukemia initiation is unclear and has not been shown in primary human hematopoietic cells. We previously described activating mutations in interleukin-7 receptor alpha (IL7RA) in poor-prognosis "ph-like" BCP-ALL.

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Mobile health (mHealth) technologies, such as symptom tracking apps, are crucial for coping with the global pandemic crisis by providing near real-time, in situ information for the medical and governmental response. However, in such a dynamic and diverse environment, methods are still needed to support public health decision-making. This paper uses the lens of strong structuration theory to investigate networks of COVID-19 symptoms in the Belfast metropolitan area.

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Interleukin-7 receptor α (encoded by IL7R) is essential for lymphoid development. Whether acute lymphoblastic leukemia (ALL)-related IL7R gain-of-function mutations can trigger leukemogenesis remains unclear. Here, we demonstrate that lymphoid-restricted mutant IL7R, expressed at physiological levels in conditional knock-in mice, establishes a pre-leukemic stage in which B-cell precursors display self-renewal ability, initiating leukemia resembling PAX5 P80R or Ph-like human B-ALL.

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Community pharmacies have made significant advances in digital technology; however, mobile systems are only emerging in this sector and mostly focusing patient-centric connections. This study reveals a case of digital transformation in a mobile connected pharmacy, balancing efficient pharmaceutical services and digital innovation. A mobile connected pharmacy solution (mPharmaCare) is developed for a community of near 100.

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