Type VII protein secretion systems play an important role in the survival and virulence of pathogens and in the competition among some microbes. Potential polymorphic toxin substrates of the type VII secretion system (T7SS) in are important for competition in the context of biofilm communities. Within a biofilm, there is significant physiological heterogeneity as cells within the population take on differential cell fates.
View Article and Find Full Text PDFImmune checkpoint inhibitors that overcome T cell suppressive mechanisms in tumors have revolutionized the treatment of cancer but are only efficacious in a small subset of patients. Targeting suppressive mechanisms acting on innate immune cells could significantly improve the incidence of clinical response by facilitating a multi-lineage response against the tumor involving both adaptive and innate immune systems. Here, we show that intra-tumoral interleukin (IL)-38 expression is a feature of a large frequency of head and neck, lung and cervical squamous cancers and correlates with reduced immune cell numbers.
View Article and Find Full Text PDFMonoclonal antibodies are an efficacious therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, rapid viral mutagenesis led to escape from most of these therapies, outlining the need for an antibody cocktail with a broad neutralizing potency. Using an unbiased interrogation of the memory B cell repertoire of patients with convalescent COVID-19, we identified human antibodies with broad antiviral activity in vitro and efficacy in vivo against all tested SARS-CoV-2 variants of concern, including Delta and Omicron BA.
View Article and Find Full Text PDFXenobiotics may activate the estrogen receptor, resulting in alteration of normal endocrine functions in animals and humans. Consequently, this necessitates development of assay end points capable of identifying estrogenic xenobiotics. In the present study, we screened the potential estrogenicity of chemicals via their ability to induce vitellogenin (VTG) expression in cultured primary hepatocytes from male trout.
View Article and Find Full Text PDFThe elaboration of a novel scaffold for the inhibition of JAK2 and FAK kinases was targeted in order to provide a dual inhibitor that could target divergent pathways for tumor cell progression.
View Article and Find Full Text PDFJ Neurosci Methods
December 2009
Histamine H(3) receptor antagonists have been proposed as a novel approach to the treatment of cognitive, attentional, and sleep disorders. It is apparent that H(3) receptor antagonists produce in vivo effects in preclinical animal models of central diseases across a wide dose range. In order to characterize the relationship between efficacy in the preclinical models and H(3) receptor occupancy, a brain slice receptor autoradiography method was used.
View Article and Find Full Text PDFInt J Sports Physiol Perform
June 2007
Background: Despite the thermal challenge of demanding workloads performed in high cabin temperatures while wearing heavy heat-retardant clothing, information on physiological responses to racing V8 Supercars in hot conditions is not readily available.
Purpose: To describe the thermal, cardiovascular, and perceptual strain on V8 Supercar drivers competing in hot conditions.
Methods: Thermal strain was indicated by body-core temperature using an ingested thermosensitive pill.
J Sports Sci Med
December 2003
The main finding of this study was that for heat acclimatised athletes, there was no significant difference (p=0.58) in anaerobic capacity for temperate (21.8 ± 0.
View Article and Find Full Text PDFOverexpression of gp120, the major coat protein of the HIV-1 virus, in central glial cells, or treatment of neurons with gp120 in culture, produces apoptotic neuronal death. Here we demonstrate that CEP-1347 (KT7515), an inhibitor of mixed lineage kinase 3 (MLK3), an upstream activator of JNK, inhibits gp120IIIB-induced apoptosis of hippocampal neurons. Furthermore, expression of wild type MLK3 in hippocampal pyramidal neurons enhanced gp120IIIB-induced neurotoxicity, whereas expression of a dominant negative MLK3 protected neurons from the toxic effects of the glycoprotein.
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