The histone-like nucleoid structuring (H-NS) protein is a DNA binding factor, found in gammaproteobacteria, with functional equivalents in diverse microbes. Universally, such proteins are understood to silence transcription of horizontally acquired genes. Here, we identify transposon capture as a major overlooked function of H-NS.
View Article and Find Full Text PDFBackground: Pathological complete response (pathCR) in rectal cancer is beneficial, as up to 75% of patients do not experience regrowth of the primary tumour, but it is poorly understood. We hypothesised that the changes seen in the pre-treatment biopsies of pathCR but not seen in residual tumour after chemoradiotherapy were the determinants of responsiveness.
Methods: Two groups of patients with either complete response (pathCR group, N = 24) or no response (poor response group, N = 24) were retrieved.
Purpose: Salvage options for patients who relapse after allogeneic stem-cell transplantation (allo-SCT) for acute myeloid leukemia (AML) and myelodysplasia (MDS) remain limited, and novel treatment strategies are required. Both lenalidomide (LEN) and azacitidine (AZA) possess significant antitumor activity effect in AML. Administration of LEN post-transplantation is associated with excessive rates of graft-versus-host disease (GVHD), but AZA has been shown to ameliorate GVHD in murine transplantation models.
View Article and Find Full Text PDFTherapeutic approaches which aim to target Acute Myeloid Leukaemia through enhancement of patients' immune responses have demonstrated limited efficacy to date, despite encouraging preclinical data. Examination of AML patients treated with azacitidine (AZA) and vorinostat (VOR) in a Phase II trial, demonstrated an increase in the expression of Cancer-Testis Antigens (MAGE, RAGE, LAGE, SSX2 and TRAG3) on blasts and that these can be recognised by circulating antigen-specific T cells. Although the T cells have the potential to be activated by these unmasked antigens, the low arginine microenvironment created by AML blast Arginase II activity acts a metabolic brake leading to T cell exhaustion.
View Article and Find Full Text PDFBackground: Quantifying individual variability in movement behavior is critical to understanding population-level patterns in animals. Here, we explore intraspecific variation in movement strategies of bald eagles () in the north Pacific, where there is high spatiotemporal resource variability. We tracked 28 bald eagles (five immature, 23 adult) using GPS transmitters between May 2010 and January 2016.
View Article and Find Full Text PDFNoninvasive genetic sampling is an important tool in wildlife ecology and management, typically relying on hair snaring or scat sampling techniques, but hair snaring is labor and cost intensive, and scats yield relatively low quality DNA. New approaches utilizing environmental DNA (eDNA) may provide supplementary, cost-effective tools for noninvasive genetic sampling. We tested whether eDNA from residual saliva on partially-consumed Pacific salmon (Oncorhynchus spp.
View Article and Find Full Text PDFTumor development driven by inflammation is now an established phenomenon, but the role that complement plays remains uncertain. Recent evidence has suggested that various components of the complement (C) cascade may influence tumor development in disparate ways; however, little attention has been paid to that of the membrane attack complex (MAC). This is despite abundant evidence documenting the effects of this complex on cell behavior, including cell activation, protection from/induction of apoptosis, release of inflammatory cytokines, growth factors, and ECM components and regulators, and the triggering of the NLRP3 inflammasome.
View Article and Find Full Text PDFGreat leaps forward in scientific understanding are often spurred by innovations in technology. The explosion of miniature sensors that are driving the boom in consumer electronics, such as smart phones, gaming platforms, and wearable fitness devices, are now becoming available to ecologists for remotely monitoring the activities of wild animals. While half a century ago researchers were attaching balloons to the backs of seals to measure their movement, today ecologists have access to an arsenal of sensors that can continuously measure most aspects of an animal's state (e.
View Article and Find Full Text PDFSalmon and other anadromous fish are consumed by vertebrates with distinct life history strategies to capitalize on this ephemeral pulse of resource availability. Depending on the timing of salmon arrival, this resource may be in surplus to the needs of vertebrate consumers if, for instance, their populations are limited by food availability during other times of year. However, the life history of some consumers enables more efficient exploitation of these ephemeral resources.
View Article and Find Full Text PDFNeuroblastoma is the most common extracranial solid tumor of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response.
View Article and Find Full Text PDFDinotefuran (DNT), imidacloprid (IMD), and thiamethoxam (THM) are commonly used neonicotinoid insecticides in a variety of agriculture operations. Although these insecticides help growers control pest infestation, the residual environmental occurrence of insecticides may cause unintended adverse ecological consequences to non-target species. In this study, the leaching behavior of DNT, IMD, and THM was investigated in soils collected from an active AgriLife Research Extension Center (AREC) vineyard.
View Article and Find Full Text PDFUnlabelled: Merkel cell carcinoma (MCC) is an aggressive skin cancer of neuroendocrine origin with a high propensity for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) causes the majority of MCC cases due to the expression of the MCPyV small and large tumor antigens (ST and LT, respectively). Although a number of molecular mechanisms have been attributed to MCPyV tumor antigen-mediated cellular transformation or replication, to date, no studies have investigated any potential link between MCPyV T antigen expression and the highly metastatic nature of MCC.
View Article and Find Full Text PDFMerkel cell carcinoma (MCC) is an aggressive poorly differentiated neuroendocrine cutaneous carcinoma associated with older age, immunodeficiency and Merkel cell polyomavirus (MCPyV) integrated within malignant cells. The presence of intra-tumoural CD8+ lymphocytes reportedly predicts better MCC-specific survival. In this study, the distribution of inflammatory cells and properties of CD8+ T lymphocytes within 20 primary MCC specimens were characterised using immunohistochemistry and multicolour immunofluorescent staining coupled to confocal microscopy.
View Article and Find Full Text PDFKaposi's sarcoma-associated herpesvirus (KSHV) is the aetiologic agent of Kaposi's sarcoma (KS), a tumour of endothelial cell origin. The study of KS development was aided by the generation of a recombinant GFP (latent)/RFP (lytic)-expressing KSHV (rKSHV.219) by Vieira and O'Hearn (2004).
View Article and Find Full Text PDFThe mechanisms by which CC chemokine receptor (CCR)7 ligands are selectively presented on lymphatic endothelium in the presence of inflammatory chemokines are poorly understood. The chemokine-scavenging receptor D6 is expressed on lymphatic endothelial cells (LEC) and contributes to selective presentation of CCR7 ligands by suppressing inflammatory chemokine binding to LEC surfaces. As well as preventing inappropriate inflammatory cell attachment to LECs, D6 is specifically involved in regulating the ability of LEC to discriminate between mature and immature dendritic cells (DCs).
View Article and Find Full Text PDFDinetofuran (DNT), imidacloprid (IMD) and thiamethoxam (THM) are among the neonicotinoid insecticides widely used for managing insect pests of agricultural and veterinary importance. Environmental occurrence of neonicotinoid in post-application scenario poses unknown issues to human health and ecology. A sorption kinetic study provides much needed information on physico-chemical interaction of neonicotinoid with soil material.
View Article and Find Full Text PDFIn this article we discuss the utility of crowdfunding from the perspective of individual scientists or laboratory groups looking to fund research. We address some of the main factors determining the success of crowdfunding campaigns, and compare this approach with the use of traditional funding sources.
View Article and Find Full Text PDFEndothelial cells (EC) can present antigen to either CD8(+) T lymphocytes through constitutively expressed major histocompatibility complex class I (MHC-I) or CD4(+) T lymphocytes through gamma interferon (IFN-γ)-induced MHC-II. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), an EC neoplasm characterized by dysregulated angiogenesis and a substantial inflammatory infiltrate. KSHV is understood to have evolved strategies to inhibit MHC-I expression on EC and MHC-II expression on primary effusion lymphoma cells, but its effects on EC MHC-II expression are unknown.
View Article and Find Full Text PDFThe hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway.
View Article and Find Full Text PDFKaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), an endothelial cell (EC) neoplasm characterized by dysregulated angiogenesis and inflammation. KSHV infection of EC causes production of proinflammatory mediators, regarded as possible initiators of the substantial mononuclear leukocyte recruitment seen in KS. Conversely, KSHV immune evasion strategies exist, such as degradation of EC leukocyte adhesion receptors by viral proteins.
View Article and Find Full Text PDFJ Virol Methods
September 2003
Acute virus replication in murine (M) CMV infected C57BL/6 (Cmv1(r)) mice is severely limited by Ly49H+ NK cells, but not in MCMV infected BALB/c or BXD8 (Cmv1(s)) mice that lack Ly49H+ NK cells. Interestingly, other NK cell receptors may also play a role in MCMV immunity, as CMV encoded gp40 protein can diminish expression of protein ligands recognized by the NK cell receptor NKG2D. To determine whether other additional gene products might influence MCMV immunity, we designed an efficient, sensitive and reliable method for screening resistance or susceptibility phenotypes in mice.
View Article and Find Full Text PDFThe NK gene complex (NKC) controls murine cytomegalovirus (MCMV) immunity through Cmv1-dependent natural killer (NK) cell responses. Ly49H expression correlates with Cmv1 phenotypes in different inbred strains, is required for MCMV resistance in C57BL/6 (B6) mice, and its interaction with the MCMV encoded m157 protein leads to NK cell-mediated destruction of virus-infected cells. However, genetic mapping studies have previously indicated that Cmv1 should reside in the D6Wum9-16 NKC interval, distal to Ly49h.
View Article and Find Full Text PDFPurpose: To evaluate the efficacy and safety of two dose levels of an orally administered ferric ammonium citrate-based contrast agent for bowel enhancement on T1-weighted spin-echo magnetic resonance (MR) images in 222 patients with known or suspected abnormality of the upper abdomen.
Materials And Methods: Adverse reactions were graded for intensity, frequency, duration, and relationship to the contrast agent. Twelve unblinded readers compared enhanced with unenhanced images; all MR images were evaluated by two independent offsite radiologists in a blinded review.
A total of 231 isolates of Candida species including 163 of Candida albicans (132 of serotype A and 31 of serotype B), 42 of Candida tropicalis, 17 of Candida glabrata, 7 of Candida parapsilosis and 2 of Candida krusei were collected from clinical specimens in two medical centers, one in Japan and the other in the United States. The in vitro antifungal activities of amphotericin B, 5-fluorocytosine, miconazole and fluconazole were evaluated for the above isolates by means of a photo-read broth microdilution method for determination of the 30% inhibitory concentration (IC30). The results showed that IC30 values of fluconazole were generally great compared with those of the other drugs, regardless of Candida species.
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