Reovirus genomic diversity confers plasticity for protease utility during adaptation to intracellular uncoating.

Reoviruses infect many mammals and are widely studied as a model system for enteric viruses. However, most of our reovirus knowledge comes from laboratory strains maintained on immortalized L929 cells. Herein, we asked whether naturally circulating reoviruses possess the same genetic and phenotypic characteristics as laboratory strains.

Mechanisms of trastuzumab induced cardiotoxicity - is exercise a potential treatment?

The use of the adjuvant therapeutic antibody trastuzumab in breast cancer is associated with a range of cardiotoxic side effects despite successfully reducing the severity of outcomes cancer patients,. The most common cardiac effect, a reduction in left ventricular ejection fraction (LVEF), is a known precursor to heart failure and often requires interruption of chemotherapy to avoid endangering patients further. An understanding of trastuzumab's cardiac-specific interactions is therefore critical in devising new methods to not only avoid permanent cardiac damage, but also prolong treatment time, and therefore effectiveness, for breast cancer patients.

p38 Mitogen-Activated Protein Kinase Signaling Enhances Reovirus Replication by Facilitating Efficient Virus Entry, Capsid Uncoating, and Postuncoating Steps.

Mammalian orthoreovirus serotype 3 Dearing is an oncolytic virus currently undergoing multiple clinical trials as a potential cancer therapy. Previous clinical trials have emphasized the importance of prescreening patients for prognostic markers to improve therapeutic success. However, only generic cancer markers such as epidermal growth factor receptor (EGFR), Hras, Kras, Nras, Braf, and p53 are currently utilized, with limited benefit in predicting therapeutic efficacy.

Reovirus uses temporospatial compartmentalization to orchestrate core versus outercapsid assembly.

Reoviridae virus family members, such as mammalian orthoreovirus (reovirus), encounter a unique challenge during replication. To hide the dsRNA from host recognition, the genome remains encapsidated in transcriptionally active proteinaceous core capsids that transcribe and release +RNA. De novo +RNAs and core proteins must repeatedly assemble into new progeny cores in order to logarithmically amplify replication.

Screening of potential novel candidate genes in schwannomatosis patients.

Schwannomatosis comprises a group of hereditary tumor predisposition syndromes characterized by, usually benign, multiple nerve sheath tumors, which frequently cause severe pain that does not typically respond to drug treatments. The most common schwannomatosis-associated gene is NF2, but SMARCB1 and LZTR1 are also associated. There are still many cases in which no pathogenic variants (PVs) have been identified, suggesting the existence of as yet unidentified genetic risk factors.

Increase in internetwork functional connectivity in the human brain with attention capture.

Attention is often extolled for its selective neural properties. Yet, when powerfully captured by a salient unexpected event, attention can give rise to a broad cascade of systemic effects for evaluating and adaptively responding to the event. Using graph theory analysis combined with fMRI, we show here that the extensive psychophysiological and cognitive changes associated with such attention capture are related to large-scale distributed changes in the brain's functional connectivity.

Generation of Recombinant Rotavirus Expressing NSP3-UnaG Fusion Protein by a Simplified Reverse Genetics System.

Rotavirus is a segmented double-stranded RNA (dsRNA) virus that causes severe gastroenteritis in young children. We have established an efficient simplified rotavirus reverse genetics (RG) system that uses 11 T7 plasmids, each expressing a unique simian SA11 (+)RNA, and a cytomegalovirus support plasmid for the African swine fever virus NP868R capping enzyme. With the NP868R-based system, we generated recombinant rotavirus (rSA11/NSP3-FL-UnaG) with a genetically modified 1.

Breast Tumor-Associated Metalloproteases Restrict Reovirus Oncolysis by Cleaving the σ1 Cell Attachment Protein and Can Be Overcome by Mutation of σ1.

Reovirus is undergoing clinical testing as an oncolytic therapy for breast cancer. Given that reovirus naturally evolved to thrive in enteric environments, we sought to better understand how breast tumor microenvironments impinge on reovirus infection. Reovirus was treated with extracellular extracts generated from polyomavirus middle T-antigen-derived mouse breast tumors.

Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study.

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated-gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review.

C3P3-G1: first generation of a eukaryotic artificial cytoplasmic expression system.

Most eukaryotic expression systems make use of host-cell nuclear transcriptional and post-transcriptional machineries. Here, we present the first generation of the chimeric cytoplasmic capping-prone phage polymerase (C3P3-G1) expression system developed by biological engineering, which generates capped and polyadenylated transcripts in host-cell cytoplasm by means of two components. First, an artificial single-unit chimeric enzyme made by fusing an mRNA capping enzyme and a DNA-dependent RNA polymerase.

The effectiveness of integrative healthcare for chronic disease: A systematic review.

Background: The past few decades have witnessed a surge in consumer, clinician and academic interest in the field of integrative healthcare (IHC). Yet, there is still uncertainty regarding the effectiveness of IHC for complex, long-term health conditions.

Objective: To assess the effectiveness of IHC for the management of any chronic health condition.

Enablers of psychological well-being for refugees and asylum seekers living in transitional countries: A systematic review.

The purpose of this systematic review was to locate and synthesise existing peer-reviewed quantitative and qualitative evidence regarding enablers of psychological well-being among refugees and asylum seekers living in transitional countries and for whom migration status is not final. Systematic searches were conducted in nine databases: Academic Search Premier, CINAHL, Embase, Emcare, Medline, Psychology and Behavioral Science, PsycINFO, Scopus, and Web of Science. Search terms were related to refugees and asylum seekers, enablers, and psychological well-being.

Functional Fractionation of the Cingulo-opercular Network: Alerting Insula and Updating Cingulate.

The anterior insula (AI) and dorsal anterior cingulate cortex (dACC) are engaged in various cognitive and affective processes. An influential account posits that the AI and dACC's ubiquitous engagements reflect their role in the transient capture of attention by salient stimuli. Using fMRI here we tested this claim and functionally dissociated these regions.

African Swine Fever Virus NP868R Capping Enzyme Promotes Reovirus Rescue during Reverse Genetics by Promoting Reovirus Protein Expression, Virion Assembly, and RNA Incorporation into Infectious Virions.

Reoviruses, like many eukaryotic viruses, contain an inverted 7-methylguanosine (m7G) cap linked to the 5' nucleotide of mRNA. The traditional functions of capping are to promote mRNA stability, protein translation, and concealment from cellular proteins that recognize foreign RNA. To address the role of mRNA capping during reovirus replication, we assessed the benefits of adding the African swine fever virus NP868R capping enzyme during reovirus rescue.

Vaccinia virus Western Reserve induces rapid surface expression of a host molecule detected by the antibody 4C7 that is distinct from CLEC2D.

In this study, the effect of active infection with vaccinia virus Western Reserve (VACV WR) on expression of C-type lectin domain family 2 (CLEC2D), a ligand of the human NK cell inhibitory receptor NKR-P1, was examined. As predicted, VACV infection led to a loss of CLEC2D mRNA in 221 cells, a B cell lymphoma line. Surprisingly, VACV infection of 221 cells caused a dramatic increase in cell surface staining for one CLEC2D-specific antibody, 4C7.

Learned Value Shapes Responses to Objects in Frontal and Ventral Stream Networks in Macaque Monkeys.

We have an incomplete picture of how the brain links object representations to reward value, and how this information is stored and later retrieved. The orbitofrontal cortex (OFC), medial frontal cortex (MFC), and ventrolateral prefrontal cortex (VLPFC), together with the amygdala, are thought to play key roles in these processes. There is an apparent discrepancy, however, regarding frontal areas thought to encode value in macaque monkeys versus humans.

The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice.

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe).

Laboratory evaluation of bioaugmentation for aerobic treatment of RDX in groundwater.

The potential for bioaugmentation with aerobic explosive degrading bacteria to remediate hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) contaminated aquifers was demonstrated. Repacked aquifer sediment columns were used to examine the transport and RDX degradation capacity of the known RDX degrading bacterial strains Gordonia sp. KTR9 (modified with a kanamycin resistance gene) Pseudomonas fluorescens I-C, and a kanamycin resistant transconjugate Rhodococcus jostii RHA1 pGKT2:Km+.

SMARCB1 mutations in schwannomatosis and genotype correlations with rhabdoid tumors.

Mutations in the SMARCB1 gene are involved in several human tumor-predisposing syndromes. They were established as an underlying cause of the tumor suppressor syndrome schwannomatosis in 2008. There is a much higher rate of mutation detection in familial disease than in sporadic disease.