Immunogenic fusion proteins induce neutralizing SARS-CoV-2 antibodies in the serum and milk of sheep.

Antigen-specific polyclonal immunoglobulins derived from the serum, colostrum, or milk of immunized ruminant animals have potential as scalable therapeutics for the control of viral diseases including COVID-19. Here we show that the immunization of sheep with fusions of the SARS-CoV-2 receptor binding domain (RBD) to ovine IgG2a Fc domains promotes significantly higher levels of antigen-specific antibodies compared to native RBD or full-length spike antigens. This antibody population contained elevated levels of neutralizing antibodies that suppressed binding between the RBD and hACE2 receptors in vitro.

Low copper levels measured in the aortic wall of New Zealand patients with non-syndromic ascending thoracic aortic aneurysm.

Objectives: Studies in animals have shown causal relationships between copper (Cu) deficiency and the development of thoracic aortic aneurysms (TAAs) [1, 2]. Cu deficiency is widespread in New Zealand (NZ) soils; the high soil pH from the use of lime fertilizers reduces the bioavailability of Cu for grazing animals and growing plants; this, in turn, reduces Cu availability in the NZ human food chain. Our study is a pilot study to explore associations between Cu and TAA.

Comparison of three oral selenium compounds in cancer patients: Evaluation of differential pharmacodynamic effects in normal and malignant cells.

Background: Selenium (Se) compounds have demonstrated therapeutic synergism in combination with anticancer treatments whilst reducing normal tissue toxicities in a range of experimental models. While reduction in some toxicities of chemotherapy and radiation has been confirmed in randomised clinical trials, they have not been powered to evaluate improved anticancer efficacy. A lack of data on the clinical potencies of the main nutritionally-relevant forms of Se and the relationship between their pharmacokinetic (PK) profiles and pharmacodynamic (PD) effects in cancer patients has hampered progress to date.

Transcriptional changes in response to ketamine ester-analogs SN 35210 and SN 35563 in the rat brain.

Background: Ketamine ester analogs, SN 35210 and SN 35563, demonstrate different pharmacological profiles to ketamine in animal models. Both confer hypnosis with predictably rapid offset yet, paradoxically, SN35563 induces a prolonged anti-nociceptive state. To explore underlying mechanisms, broad transcriptome changes were measured and compared across four relevant target regions of the rat brain.

The Interaction of Selenium with Chemotherapy and Radiation on Normal and Malignant Human Mononuclear Blood Cells.

Selenium, a trace element with anticancer properties, can reduce harmful toxicities of chemotherapy and radiotherapy without compromising efficacy. However, the dose-response relationship in normal versus malignant human cells is unclear. We evaluated how methylseleninic acid (MSA) modulates the toxicity and efficacy of chemotherapy and radiation on malignant and non-malignant human mononuclear blood cells in vitro.

Comparative Safety and Pharmacokinetic Evaluation of Three Oral Selenium Compounds in Cancer Patients.

Selenium (Se) compounds have demonstrated anticancer properties in both preclinical and clinical studies, with particular promise in combination therapy where the optimal form and dose of selenium has yet to be established. In a phase I randomised double-blinded study, the safety, tolerability and pharmacokinetic (PK) profiles of sodium selenite (SS), Se-methylselenocysteine (MSC) and seleno-l-methionine (SLM) were compared in patients with chronic lymphocytic leukaemia and a cohort of patients with solid malignancies. Twenty-four patients received 400 μg of elemental Se as either SS, MSC or SLM for 8 weeks.

Development of a qPCR Method to Measure Mitochondrial and Genomic DNA Damage with Application to Chemotherapy-Induced DNA Damage and Cryopreserved Cells.

DNA damage quantitation assays such as the comet assay have focused on the measurement of total nuclear damage per cell. The adoption of PCR-based techniques to quantify DNA damage has enabled sequence- and organelle-specific assessment of DNA lesions. Here we report on an adaptation of a qPCR technique to assess DNA damage in nuclear and mitochondrial targets relative to control.

Association of innate immune single-nucleotide polymorphisms with the electroencephalogram during desflurane general anaesthesia.

The electroencephalogram (EEG) records the electrical activity of the brain and enables effects of anaesthetic drugs on brain functioning to be monitored. Identification of genes contributing to EEG variability during anaesthesia is important to the clinical application of anaesthesia monitoring and may provide an avenue to identify molecular mechanisms underlying the generation and regulation of brain oscillations. Central immune signalling can impact neuronal activity in the brain and accumulating evidence suggests an important role for cytokines as neuronal modulators.

Connexin36 knockout mice display increased sensitivity to pentylenetetrazol-induced seizure-like behaviors.

Objective: Large-scale synchronous firing of neurons during seizures is modulated by electrotonic coupling between neurons via gap junctions. To explore roles for connexin36 (Cx36) gap junctions in seizures, we examined the seizure threshold of connexin36 knockout (Cx36KO) mice using a pentylenetetrazol (PTZ) model.

Methods: Mice (2-3months old) with Cx36 wildtype (WT) or Cx36KO genotype were treated with vehicle or 10-40mg/kg of the convulsant PTZ by intraperitoneal injection.

Distinct gene expression profiles directed by the isoforms of the transcription factor neuron-restrictive silencer factor in human SK-N-AS neuroblastoma cells.

Neuron-restrictive silencer factor (NRSF) and its isoforms are differentially regulated in rodent models of self-sustaining status epilepticus (SSSE). NRSF isoforms regulate genes associated with SSSE, including the proconvulsant tachykinins, brain-derived neurotrophic factor and multiple ion channels. NRSF isoforms may direct distinct gene expression patterns during SSSE, and the ratio of each isoform may be a causative factor in traumatic damage to the central nervous system.

SCG3 transcript in peripheral blood is a prognostic biomarker for REST-deficient small cell lung cancer.

Purpose: Specific markers of circulating tumor cells may be informative in managing lung cancer. Because the RE-1 silencing transcription factor (REST/NRSF) is a transcriptional repressor that is inactivated in neuroendocrine lung cancer, we identified REST-regulated transcripts (CHGA, CHGB, SCG3, VGF, and PCSK1) for evaluation as biomarkers in peripheral blood.

Experimental Design: Transcripts were screened across lung cancer and normal cell lines.