Phase II trial of delta-tocotrienol in neoadjuvant breast cancer with evaluation of treatment response using ctDNA.

Neoadjuvant treatment of breast cancer is applied to an increasing extent, but treatment response varies and side effects pose a challenge. The vitamin E isoform delta-tocotrienol might enhance the efficacy of chemotherapy and reduce the risk of side effects. The aim of this study was to investigate the clinical effect of delta-tocotrienol combined with standard neoadjuvant treatment and the possible association between detectable circulating tumor DNA (ctDNA) during and after neoadjuvant treatment with pathological treatment response.

Quantifying SARS-CoV-2 nucleocapsid antigen in oropharyngeal swabs using single molecule array technology.

This study aimed to develop a highly sensitive SARS-CoV-2 nucleocapsid antigen assay using the single molecule array (Simoa) technology and compare it with real time RT-PCR as used in routine clinical practice with the ambition to achieve a comparative technical and clinical sensitivity. Samples were available from 148 SARS-CoV-2 real time RT-PCR positive and 73 SARS-CoV-2 real time RT-PCR negative oropharyngeal swabs. For determination of technical sensitivity SARS-CoV-2 virus culture material was used.

Daily monitoring of viral load measured as SARS-CoV-2 antigen and RNA in blood, IL-6, CRP and complement C3d predicts outcome in patients hospitalized with COVID-19.

Objectives: We hypothesized that the amount of antigen produced in the body during a COVID-19 infection might differ between patients, and that maximum concentrations would predict the degree of both inflammation and outcome for patients.

Methods: Eighty-four hospitalized and SARS-CoV-2 PCR swab-positive patients, were followed with blood sampling every day until discharge or death. A total of 444 serial EDTA plasma samples were analyzed for a range of biomarkers: SARS-CoV-2 nuclear antigen and RNA concentration, complement activation as well as several inflammatory markers, and KL-6 as a lung marker.

Detection of novel strains of cyprinid herpesvirus closely related to koi herpesvirus.

Cyprinid herpesvirus 3 (CyHV-3) or koi herpesvirus (KHV) is a devastating virus of carp. Using generic primers for the DNA polymerase and the major capsid protein genes of cyprinid herpesviruses, nucleotide sequences divergent from previously described CyHV-3 were obtained. At least 3 novel groups of putative CyHV-3-like viruses were identified, sharing 95 to 98% nucleotide identity with CyHV-3 strains.

Trade practices are main factors involved in the transmission of viral haemorrhagic septicaemia.

Viral haemorrhagic septicaemia (VHS), caused by the novirhabdovirus viral haemorrhagic septicaemia virus (VHSV), causes significant economic problems to European rainbow trout, Oncorhynchus mykiss (Walbaum), production. The virus isolates can be divided into four distinct genotypes with additional subgroups. The main source of outbreaks in European rainbow trout farming is sublineage Ia isolates.

Development and validation of a novel Taqman-based real-time RT-PCR assay suitable for demonstrating freedom from viral haemorrhagic septicaemia virus.

Viral haemorrhagic septicaemia (VHS) is a serious disease in several fish species. VHS is caused by the rhabdovirus viral haemorrhagic septicaemia virus (VHSV). To prevent spreading of the pathogen, it is important to use a fast, robust, sensitive and specific diagnostic tool to identify the infected fish.

European freshwater VHSV genotype Ia isolates divide into two distinct subpopulations.

Viral haemorrhagic septicaemia (VHS), caused by the novirhabdovirus VHSV, often leads to significant economic losses to European rainbow trout production. The virus isolates are divided into 4 distinct genotypes with additional subgroups including sublineage Ia, isolates of which are the main source of outbreaks in European rainbow trout farming. A significant portion of Danish rainbow trout farms have been considered endemically infected with VHSV since the first disease outbreak was observed in the 1950s.

The NSD3L histone methyltransferase regulates cell cycle and cell invasion in breast cancer cells.

NSD3/WHSC1L1 histone methyltransferase gene aberrations are observed in leukemia and in breast and lung carcinomas, suggesting that NSD3 is implicated in carcinogenesis. In this study we examined in human breast cancer cells the NSD3L isoform which contains the catalytic histone methyltransferase SET-domain. siRNA directed depletion of NSD3L followed by genome-wide microarray analysis identified NSD3L regulated genes which could be functionally linked to cellular signaling pathways such as cell growth, cell cycle, cell motility, transcription, and apoptosis.

Nizp1 zinc finger protein localization is determined by SCAN-domain inclusion regulated through alternative splicing.

The NSD1 histone methyl transferase is involved in childhood acute myeloid leukemia and the outgrowth disorders Sotos and Weaver syndromes. NSD1 is a transcriptional co-repressor for the zinc finger protein Nizp1 (also abbreviated Zfp496 and Zkscan17). Nizp1 includes a SCAN-domain, a KRAB-domain, four C2H2 Krüppel related zinc fingers, and a C2HR transcriptional repression and protein interaction domain required for NSD1 interaction.

Outbreak of viral haemorrhagic septicaemia (VHS) in seawater-farmed rainbow trout in Norway caused by VHS virus Genotype III.

We describe the finding of a novel viral haemorrhagic septicaemia virus (VHSV) Genotype III strain that caused disease of both a neurological and septicaemic nature in seawater-farmed rainbow trout Oncorhynchus mykiss in Storfjorden, Norway. In November 2007, an outbreak of VHS associated with slightly elevated mortality was confirmed at a seawater site rearing rainbow trout (90 to 440 g). Within 3 to 4 mo, the disease was recognised in 3 neighbouring sea sites with ongrowing rainbow trout.

Identification of a novel vimentin promoter and mRNA isoform.

The intermediate filament protein vimentin is involved in a variety of cellular functions both during the normal developmental processes and in human malignancies. We here describe the identification of an alternative vimentin transcript initiating upstream for the canonical vimentin gene promoter and spliced using the vimentin promoter sequence as an intron. Expression analysis showed that the alternative vimentin promoter had the same expression profile as the canonical vimentin gene promoter.

FishPathogens.eu/vhsv: a user-friendly viral haemorrhagic septicaemia virus isolate and sequence database.

A database has been created, http://www.FishPathogens.eu, with the aim of providing a single repository for collating important information on significant pathogens of aquaculture, relevant to their control and management.

A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo.

Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or beta-globin mRNAs, harboring wild-type or various 5' splice site mutations, we demonstrate a strong positive correlation between splicing efficiency and transcription activity.

Cellular parkin mutants are soluble under non-stress conditions.

The parkin gene encodes an E3 ubiquitin ligase and loss of function mutations herein are the most frequent cause of early-onset Parkinson's disease. Reports have suggested that aggregation of mutant protein is the cause of the loss of function. We established stably transfected SH-SY5Y dopaminergic cell lines expressing wild-type and mutant parkin proteins.

Slowing down aging from within: mechanistic aspects of anti-aging hormetic effects of mild heat stress on human cells.

Since aging is primarily the result of a failure of maintenance and repair mechanisms, various approaches are being developed in order to stimulate these pathways and modulate the process of aging. One such approach, termed hormesis, involves challenging cells and organisms by mild stress that often results in anti-aging and life prolonging effects. In a series of experimental studies, we have reported that repeated mild heat stress (RMHS) has anti-aging hormetic effects on growth and various cellular and biochemical characteristics of human skin fibroblasts undergoing aging in vitro.

Parkin is recruited into aggresomes in a stress-specific manner: over-expression of parkin reduces aggresome formation but can be dissociated from parkin's effect on neuronal survival.

Parkinson's disease (PD) is characterized by loss of dopamine neurons in the substantia nigra and the presence of cytoplasmic inclusions known as Lewy bodies (LBs). Mutations in parkin cause autosomal recessive juvenile parkinsonism (AR-JP) that is distinct from sporadic PD by the general absence of LBs. Several studies have reported that parkin is present in LBs of sporadic PD but the role of parkin in LB formation is unclear.

Caspase-1 and caspase-8 cleave and inactivate cellular parkin.

Lesions in the parkin gene cause early onset Parkinson's disease by a loss of dopaminergic neurons, thus demonstrating a vital role for parkin in the survival of these neurons. Parkin is inactivated by caspase cleavage, and the major cleavage site is after Asp126. Caspases responsible for parkin cleavage were identified by several experimental paradigms.

Caspase-mediated parkin cleavage in apoptotic cell death.

The parkin protein is important for the survival of the neurons that degenerate in Parkinson's disease as demonstrated by disease-causing lesions in the parkin gene. The Chinese hamster ovary and the SH-SY5Y cell line stably expressing recombinant human parkin combined with epitope-specific parkin antibodies were used to investigate the proteolytic processing of human parkin during apoptosis by immunoblotting. Parkin is cleaved during apoptosis induced by okadaic acid, staurosporine, and camptothecin, thereby generating a 38-kDa C-terminal fragment and a 12-kDa N-terminal fragment.

The human elongation factor 1 A-2 gene (EEF1A2): complete sequence and characterization of gene structure and promoter activity.

The eukaryotic elongation factor 1 A (eEF1A, formerly EF1alpha) is a key factor in protein synthesis, where it promotes the transfer of aminoacylated tRNAs to the A site of the ribosome. Two differentially expressed isoforms of eEF1A, designated eEF1A-1 and eEF1A-2, are found in mammals. Here we report the isolation and sequencing of the gene (HGMW-approved symbol EEF1A2) coding for the human eEF1A-2 isoform.

The elongation factor 1 A-2 isoform from rabbit: cloning of the cDNA and characterization of the protein.

Eukaryotic elongation factor 1 A (eEF1A, formerly elongation factor-1 alpha) is an important component of the protein synthesis apparatus. Here we report the isolation and characterization of the cDNA sequence encoding rabbit eEF1A-2, an isoform of eEF1A, as well as a structural and functional comparison of the two rabbit isoforms. Northern analysis of the expression pattern of eEF1A-2 showed that this isoform is expressed in skeletal muscle, heart, brain and aorta, while transcripts are not detected in liver, kidney, spleen and lung.