939 research outputs found
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
No full textThe majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire
A Potentially New Oxidation State in the Binuclear Manganese Active Site of T. Thermophilus Manganese Catalase
No full textEstuarine habitat ecology of adult weakfish (Cynoscion regalis): a multi-scale approach
No full textThe habitat ecology of adult weakfish (Cynoscion regalis) remains poorly understood, although they comprise an important ecological and economic portion of estuarine environments. Weakfish are particularly susceptible to confusion over how to best delineate important habitat resources, such as those used for reproduction, because they may change over multiple spatial (coastal and estuary) and temporal (seasonal and diel) scales. In this study, weakfish habitat dynamics were evaluated at multiple scales using acoustic telemetry within the Mullica River-Great Bay estuary in southern New Jersey. At the broader estuary scale, residency, habitat use, and movements were quantified across the reproductive/post-reproductive season. Tagged adult weakfish were resident in bay, lower river, and subtidal creek habitats during reproduction (May through July) and following the reproductive season (August through November) but showed limited use of inlet and upriver habitats in both seasons. Movement rates increased at the end of the post-reproductive season and weakfish apparently moved into fringing, unmonitored habitats within the study area following the reproductive period. Estuarine egress occurred throughout the study period but was lowest during July and highest during the final month of emigration in November. At smaller spatial scales, weakfish displayed patterns of site fidelity both seasonally and daily. At the seasonal scale, a majority of weakfish tagged in 2008 maintained fidelity to their original tagging location or established new “core areas” in other parts of the estuary. In both cases, fish were detected at these areas for the duration of their residency or made short- or long-term excursions before returning to their original core area. At the diel scale, weakfish displayed movements of varying distances from their original tagging location beginning around sundown and returning around the sunrise period, which also corresponds to the timing of nightly weakfish reproduction. These findings represent new evidence of the role that estuary habitats may play in adult weakfish life history and, because weakfish habitat dynamics may be influenced by reproduction, it will be important to incorporate these changes into future management of the fishery.M.S.Includes bibliographical referencesby Jason T. Turnur
T Cell responses to whole SARS Coronavirus in humans
No full textEffective vaccines should confer long-term protection against future outbreaks of severe acute respiratory syndrome (SARS) caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. We conducted a cohort study examining multiple parameters of immune responses to SARS-CoV infection, aiming to identify the immune correlates of protection. We used a matrix of overlapping peptides spanning whole SARS-CoV proteome to determine T cell responses from 128 SARS convalescent samples by ex vivo IFN-γ ELISPOT assays. Approximately 50% of convalescent SARS patients were positive for T cell responses, and 90% possessed strongly neutralizing Abs. Fifty-five novel T cell epitopes were identified, with spike protein dominating total T cell responses. CD8+ T cell responses were more frequent and of a greater magnitude than CD4+ T cell responses (p < 0.001).
Polychromatic cytometry analysis indicated that the virus-specific T cells from the severe group tended to be a central memory phenotype (CD27+/CD45RO+) with a significantly higher frequency of polyfunctional CD4+ T cells producing IFN-γ, TNF-α, and IL-2, and CD8+ T cells producing IFN-γ, TNF-α, and CD107a (degranulation), as compared with the mild-moderate group. Strong T cell responses correlated significantly (p < 0.05) with higher neutralizing Ab. The serum cytokine profile during acute infection indicated a significant elevation of innate immune responses. Increased Th2 cytokines were observed in patients with fatal infection. Our study provides a roadmap for the immunogenicity of SARS-CoV and types of immune responses that may be responsible for the virus clearance, and should serve as a benchmark for SARS-CoV vaccine design and evaluation
Zarathustra / Zoroaster
No full textThe name Zarathustra refers to a prophet or religious reformer of ancient Iran. He is believed to be the
author of the Gathas, the linguistically oldest part of the Avestan corpus. Information relating to
his life is extremely scarce: mentions in the sources are contradictory and there is no agreement among
the scholars on the time in which he lived or the place where he was active. Some scholars believe that
he was amythical figure and never really existed. Even his name is problematic froma linguistic point of
view and there is still no generally accepted etymology. He is a figure who had a deep impact both on the
Classical world (particularly ancient Greece) and in the Middle Ages and in modern and contemporary
Europe
Correction: Saadah et al. Developing Robust Safety Protocols for Radiosurgery within Patient Positioning System Framework. Machines 2024, 12, 106
No full textAfter the publication of the paper, Endre Takacs from Clemson University contacted the corresponding author Alaa Saadah to ask for multiple individuals (Laszlo Fadgyas, Jason Henderson, Tibor Koroknai, Máté Koroknai, David Takacs, Peter Panko, and Endre Takacs) to be added as additional co-authors of the original publication [...
Novel insights into the epigenetics of diffuse glioma
No full textLoss-of-function mutations of the chromatin regulator ATRX (α-thalassemia mental retardation X-linked) occur frequently in diffuse gliomas, but the molecular mechanisms by which ATRX inactivation promotes oncogenesis remain unclear. We recently reported that Atrx deficiency drives glioma-relevant phenotypes, such as increased motility and astrocytic differentiation profiles, by directly modulating epigenomic lanscapes in glioma cells of origin. Our work has significant implications on the role of epigenetic regulator dysfunction in the oncogenic process
Neurotransmitter Power Plays: The Synaptic Communication Nexus Shaping Brain Cancer
No full textGliomas and brain metastases are notorious for their dismal prognosis and low survival rates, a challenge exacerbated by our incomplete grasp of the complex dynamics that govern brain cancers. Recently, a groundbreaking paradigm shift has emerged, highlighting the crucial role of synaptic communication between neurons and brain tumor cells in reshaping neuronal signaling to favor tumor growth. This review delves into the pivotal interplay of synaptic mechanisms, focusing on excitatory glutamatergic and inhibitory GABAergic pathways. Glutamatergic synapses utilize glutamate to propagate excitatory signals, while GABAergic synapses employ gamma-aminobutyric acid (GABA) to inhibit neuronal firing. Glutamatergic signaling can be broadly classified into ionotropic (NMDAR, AMPAR and kainite receptors) and metabotropic subtypes. The harmonious orchestration of these synaptic types is essential for normal brain function, and their dysregulation is implicated in neurodegenerative disorders such as Alzheimer\u27s disease and epilepsy. Emerging evidence reveals that glioma and brain metastatic cells exploit these synaptic pathways and neurotransmitters to enhance their proliferation and survival. In this review, we will first explore the intricate mechanisms underlying glutamatergic and GABAergic signaling. Next, we will summarize recent advancements in understanding how brain cancer cells hijack these pathways to their advantage. Finally, we will propose novel therapeutic strategies aimed at disrupting the aberrant neuron-tumor synaptic communication, offering potential treatment strategies for combating these otherwise incurable brain cancers
Tropical cyclone precipitation climatology: A study on the proportionality of rainfall along the Gulf Coast during peak tropical storm season
No full textThe goal of the study is to perform a quantitative, trend analysis on precipitation source proportionality in the month of September for the Gulf Coast region. The initial study area includes portions of Escambia County, Florida and Baldwin County. Alabama. As these areas are processed, grid zones along the coast through Mississippi, Louisiana, and Texas may be included. The study will be performed on a temporal scale of every September between 1948 and 2018. Future work may seek to include multiple TCP datasets
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