116 research outputs found
The Parasitoid, Verticia fasciventris Causes Morphological and Behavioral Changes in Infected Soldiers of the Fungus-Growing Termite, Macrotermes carbonarius
The larval parasitoid Verticia fasciventris Malloch (Diptera: Calliphoridae) develops in the head of soldiers of the fungus-growing termite Macrotermes carbonarius (Hagen) (Isoptera: Termitidae). Morphological and behavioral changes in the host were evaluated and the termite castes and stages that were parasitized were identified. The larval emergence process is also described and possible mechanisms for the parasitoid fly's entry into the host body are discussed based on qualitative observations. Only a single larva per host was found. The mature larva pupated outside the host's body by exiting between the abdominal cerci. Parasitized soldiers possess a short and square-shaped head capsule, a pair of notably short mandibles, and a pair of 18-segmented antennae. Although parasitized soldiers were statistically less aggressive than healthy soldiers (P < 0.05), they expressed varying levels of aggression. Both minor and major soldiers can be parasitized and based on evidence from presoldiers, parasitization may begin during the precursor stages of soldiers. However, the stage at which parasitism first occurs has not been determined
CONFIRM: a double-blind, placebo controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial
Background: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure
to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched,
with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted
treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need
to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.
Methods: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in
the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336
patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be
recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to
epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min
intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab
increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free
survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed
according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and
for other time-to-event endpoints).
Discussion: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab
in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely
to become the new standard of care in the UK
Human U87 Astrocytoma Cell Invasion Induced by Interaction of ÎČig-h3 with Integrin α5ÎČ1 Involves Calpain-2
It is known that ÎČig-h3 is involved in the invasive process of many types of tumors, but its mechanism in glioma cells has not been fully clarified. Using immunofluorescent double-staining and confocal imaging analysis, and co-immunoprecipitation assays, we found that ÎČig-h3 co-localized with integrin α5ÎČ1 in U87 cells. We sought to elucidate the function of this interaction by performing cell invasion assays and gelatin zymography experiments. We found that siRNA knockdowns of ÎČig-h3 and calpain-2 impaired cell invasion and MMP secretion. Moreover, ÎČig-h3, integrins and calpain-2 are known to be regulated by Ca2+, and they are also involved in tumor cell invasion. Therefore, we further investigated if calpain-2 was relevant to ÎČig-h3-integrin α5ÎČ1 interaction to affect U87 cell invasion. Our data showed that ÎČig-h3 co-localized with integrin α5ÎČ1 to enhance the invasion of U87 cells, and that calpain-2, is involved in this process, acting as a downstream molecule
Interferon-Îł Activates Nuclear Factor-Îș B in Oligodendrocytes through a Process Mediated by the Unfolded Protein Response
Our previous studies have demonstrated that the effects of the immune cytokine interferon-Îł (IFN-Îł) in immune-mediated demyelinating diseases are mediated, at least in part, by the unfolded protein response (UPR) in oligodendrocytes. Data indicate that some biological effects of IFN-Îł are elicited through activation of the transcription factor nuclear factor-ÎșB (NF-ÎșB). Interestingly, it has been shown that activation of the pancreatic endoplasmic reticulum kinase (PERK) branch of the UPR triggers NF-ÎșB activation. In this study, we showed that IFN-Îł-induced NF-ÎșB activation was associated with activation of PERK signaling in the oligodendroglial cell line Oli-neu. We further demonstrated that blockage of PERK signaling diminished IFN-Îł-induced NF-ÎșB activation in Oli-neu cells. Importantly, we showed that NF-ÎșB activation in oligodendrocytes correlated with activation of PERK signaling in transgenic mice that ectopically express IFN-Îł in the central nervous system (CNS), and that enhancing IFN-Îł-induced activation of PERK signaling further increased NF-ÎșB activation in oligodendrocytes. Additionally, we showed that suppression of the NF-ÎșB pathway rendered Oli-neu cells susceptible to the cytotoxicity of IFN-Îł, reactive oxygen species, and reactive nitrogen species. Our results indicate that the UPR is involved in IFN-Îł-induced NF-ÎșB activation in oligodendrocytes and suggest that NF-ÎșB activation by IFN-Îł represents one mechanism by which IFN-Îł exerts its effects on oligodendrocytes in immune-mediated demyelinating diseases
Differential Gene Expression Patterns of EBV Infected EBNA-3A Positive and Negative Human B Lymphocytes
The genome of Epstein-Barr virus (EBV) encodes 86 proteins, but only a limited set is expressed in EBVâgrowth transformed B cells, termed lymphoblastoid cell lines (LCLs). These cells proliferate via the concerted action of EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), some of which are rate limiting to establish a stable homeostasis of growth promoting and anti-apoptotic activities. We show here that EBV mutants, which lack the EBNA-3A gene, are impaired but can still initiate cell cycle entry and proliferation of primary human B cells in contrast to an EBNA-2 deficient mutant virus. Surprisingly, and in contrast to previous reports, these viral mutants are attenuated in growth transformation assays but give rise to permanently growing EBNA-3A negative B cell lines which exhibit reduced proliferation rates and elevated levels of apoptosis. Expression profiles of EBNA-3A deficient LCLs are characterized by 129 down-regulated and 167 up-regulated genes, which are significantly enriched for genes involved in apoptotic processes or cell cycle progression like the tumor suppressor gene p16/INK4A, or might contribute to essential steps of the viral life cycle in the infected host. In addition, EBNA-3A cellular target genes remarkably overlap with previously identified targets of EBNA-2. This study comprises the first genome wide expression profiles of EBNA-3A target genes generated within the complex network of viral proteins of the growth transformed B cell and permits a more detailed understanding of EBNA-3A's function and contribution to viral pathogenesis
White-gutted soldiers: simplification of the digestive tube for a non-particulate diet in higher Old World termites (Isoptera: Termitidae)
Previous observations have noted that in some species of higher termites the soldier caste lacks pigmented particles in its gut and, instead, is fed worker saliva that imparts a whitish coloration to the abdomen. In order to investigate the occurrence of this trait more thoroughly, we surveyed a broad diversity of termite specimens and taxonomic descriptions from the Old World subfamilies Apicotermitinae, Cubitermitinae, Foraminitermitinae, Macrotermitinae, and Termitinae. We identified 38 genera that have this âwhite-guttedâ soldier (WGS) trait. No termite soldiers from the New World were found to possess a WGS caste. Externally, the WGS is characterized by a uniformly pale abdomen, hyaline gut, and proportionally smaller body-to-head volume ratio compared with their âdark-guttedâ soldier (DGS) counterparts found in most termitid genera. The WGS is a fully formed soldier that, unlike soldiers in other higher termite taxa, has a small, narrow, and decompartmentalized digestive tube that lacks particulate food contents. The presumed saliva-nourished WGS have various forms of simplified gut morphologies that have evolved at least six times within the higher termites
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field
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