Biology subjects

Pereira, J. P.

Publications and source records attributed to Pereira, J. P..

3 recordsLinked to original sources

bioRxiv2023

Proteomic and Physiological Signatures of Altitude Adaptation in a Myrsine coriacea Population under Common Garden Conditions

Plants exhibit phenotypic plasticity in response to environmental variations, which can lead to stable genetic and physiological adaptations if exposure to specific conditions is prolonged. Myrsine coriacea demonstrates this through its ability to thrive in diverse environments. The objective of the article is to investigate the adaptive responses of M. coriacea by cultivating plants from seeds collected at four different altitudes in a common garden experiment. Through integrated physiological and proteomic analyses, we identified 170 differentially accumulated proteins and observed significant physiological differences among the populations. The high-altitude population (POP1) exhibited a unique proteomic profile with significant down-regulation of proteins involved in carbon fixation and energy metabolism, suggesting a potential reduction in photosynthetic efficiency. Physiological analyses showed lower leaf nitrogen content, net CO2 assimilation rate, specific leaf area, and relative growth rate in stem height for POP1, alongside higher leaf carbon isotopic composition ({delta}13C) and leaf carbon (C) content. These findings provide insight into the complex interplay between proteomic and physiological adaptations in M. coriacea and underscore the importance of local adaptations. This study enhances our understanding of how altitude-specific selection pressures can shape plant molecular biology and physiology, offering valuable perspectives for predicting plant responses to global environmental changes. HighlightThis study unveils proteomic and physiological adaptations in a high-altitude M. coriacea population with reduced carbon fixation and energy metabolism.

plant biology↗

bioRxiv2022

Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin-beta receptor signaling

Acute lymphoblastic and myeloblastic leukemias (ALL and AML) have been known to modify the bone marrow microenvironment and disrupt non-malignant hematopoiesis. However, the molecular mechanisms driving these alterations remain poorly defined. Here we show that leukemic cells turn-off lymphopoiesis and erythropoiesis shortly after colonizing the bone marrow. ALL and AML cells express lymphotoxin-1{beta}2 and activate LT{beta}R signaling in mesenchymal stem cells (MSCs), which turns off IL7 production and prevents non-malignant lymphopoiesis. We show that the DNA damage response pathway and CXCR4 signaling promote lymphotoxin-1{beta}2 expression in leukemic cells. Genetic or pharmacologic disruption of LT{beta}R signaling in MSCs restores lymphopoiesis but not erythropoiesis, reduces leukemic cell growth, and significantly extends the survival of transplant recipients. Similarly, CXCR4 blocking also prevents leukemia-induced IL7 downregulation, and inhibits leukemia growth. These studies demonstrate that acute leukemias exploit physiological mechanisms governing hematopoietic output as a strategy for gaining competitive advantage. One Sentence SummaryLeukemias colonize bone marrow niches and disrupt hematopoiesis. However, the cross-talk between leukemia and niche cells remains poorly understood. We show that leukemia activates LT{beta}R in mesenchymal stem cells which suppresses IL7 production and IL7-dependent lymphopoiesis and accelerates leukemia growth.

immunology↗

bioRxiv2020

Type I Interferon Limits Viral Dissemination-Driven Clinical Heterogeneity in a Native Murine Betacoronavirus Model of COVID-19

Emerging clinical data demonstrates that COVID-19, the disease caused by SARS-CoV2, is a syndrome that variably affects nearly every organ system. Indeed, the clinical heterogeneity of COVID-19 ranges from relatively asymptomatic to severe disease with death resultant from multiple constellations of organ failures. In addition to genetics and host characteristics, it is likely that viral dissemination is a key determinant of disease manifestation. Given the complexity of disease expression, one major limitation in current animal models is the ability to capture this clinical heterogeneity due to technical limitations related to murinizing SARS-CoV2 or humanizing mice to render susceptible to infection. Here we describe a murine model of COVID-19 using respiratory infection with the native mouse betacoronavirus MHV-A59. We find that whereas high viral inoculums uniformly led to hypoxemic respiratory failure and death, lethal dose 50% (LD50) inoculums led to a recapitulation of most hallmark clinical features of COVID-19, including lymphocytopenias, heart and liver damage, and autonomic dysfunction. We find that extrapulmonary manifestations are due to viral metastasis and identify a critical role for type-I but not type-III interferons in preventing systemic viral dissemination. Early, but not late treatment with intrapulmonary type-I interferon, as well as convalescent serum, provided significant protection from lethality by limiting viral dissemination. We thus establish a Biosafety Level II model that may be a useful addition to the current pre-clinical animal models of COVID-19 for understanding disease pathogenesis and facilitating therapeutic development for human translation.

immunology↗