Selection and T-cell antigenicity of synthetic long peptides derived from SARS-CoV-2.

The pandemic caused by SARS-CoV-2 has led to the successful development of effective vaccines however the prospect of variants of SARS-CoV-2 and future coronavirus outbreaks necessitates the investigation of other vaccine strategies capable of broadening vaccine mediated T-cell responses and potentially providing cross-immunity. In this study the SARS-CoV-2 proteome was assessed for clusters of immunogenic epitopes restricted to diverse human leucocyte antigen. These regions were then assessed for their conservation amongst other coronaviruses representative of different alpha and beta coronavirus genera.

Directing T-Cell Immune Responses for Cancer Vaccination and Immunotherapy.

Cancer vaccination and immunotherapy revolutionised the treatment of cancer, a result of decades of research into the immune system in health and disease. However, despite recent breakthroughs in treating otherwise terminal cancer, only a minority of patients respond to cancer immunotherapy and some cancers are largely refractive to immunotherapy treatment. This is due to numerous issues intrinsic to the tumour, its microenvironment, or the immune system.

Correlation of Antibody Responses to a Peptide Antigen gp120-C5/gp41 with HIV Disease Progression.

Antibodies to the carboxy-terminal constant (C5) region 5 of the HIV-1 envelope glycoprotein gp120 have previously been associated with slow disease progression. This is one of the regions on gp120 that interact with the transmembrane glycoprotein, gp41, anchoring it to the viral and infected cell membrane. This study analyzed humoral responses to a novel heterodimeric peptide construct comprising the C5 region and a compatible region on gp41.

Temporal Characterization of Microglia/Macrophage Phenotypes in a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury.

Immune cells display a high degree of phenotypic plasticity, which may facilitate their participation in both the progression and resolution of injury-induced inflammation. The purpose of this study was to investigate the temporal expression of genes associated with classical and alternative polarization phenotypes described for macrophages and to identify related cell populations in the brain following neonatal hypoxia-ischemia (HI). HI was induced in 9-day old mice and brain tissue was collected up to 7 days post-insult to investigate expression of genes associated with macrophage activation.

Effect of the Modification of p24 Peptide Antigen on Dendritic Cell Uptake and T Cell Activation.

Background: Vacc-4x is a candidate therapeutic vaccine consisting of 4 modified peptides based on conserved regions of HIV-1 p24Gag. Vacc4x has been shown to induce long term cellular immunity in immunized infected individuals resulting a reduction in viral load on treatment interruption.

Objective: Vacc-4x peptides are modified.

Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS).

Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood.

TLR2-mediated leukocyte trafficking to the developing brain.

Inflammation is a significant risk factor for brain injury in the perinatal period. In this study, we tested the hypothesis that activation of peripheral TLR induces inflammation in the brain, including leukocyte trafficking. Postnatal day 8 mice were injected intraperitoneally with a TLR1/2 (Pam3CSK4, P3C), TLR2/6 (FSL-1) or TLR4 (LPS) agonist, and the peripheral and central cytokine and chemokine response was determined.

Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia.

Insults to the developing brain often result in irreparable damage resulting in long-term deficits in motor and cognitive functions. The only treatment today for hypoxic-ischemic encephalopathy (HIE) in newborns is hypothermia, which has limited clinical benefit. We have studied changes to the blood-brain barriers (BBB) as well as regional cerebral blood flow (rCBF) in a neonatal model of HIE to further understand the underlying pathologic mechanisms.

A bio-artificial renal epithelial cell system conveys survival advantage in a porcine model of septic shock.

Renal cell therapy using the hollow fiber based renal assist device (RAD) improved survival time in an animal model of septic shock (SS) through the amelioration of cardiac and vascular dysfunction. Safety and ability of the RAD to improve clinical outcomes was demonstrated in a Phase II clinical trial, in which patients had high prevalence of sepsis. Even with these promising results, clinical delivery of cell therapy is hampered by manufacturing hurdles, including cell sourcing, large-scale device manufacture, storage and delivery.

Developments in HIV-1 immunotherapy and therapeutic vaccination.

Since the human immunodeficiency virus (HIV-1) pandemic began, few prophylactic vaccines have reached phase III trials. Only one has shown partial efficacy in preventing HIV-1 infection. The introduction of antiretroviral therapy (ART) has had considerable success in controlling infection and reducing transmission but in so doing has changed the nature of HIV-1 infection for those with access to ART.

Neonatal peripheral immune challenge activates microglia and inhibits neurogenesis in the developing murine hippocampus.

The early postnatal period represents an important window in rodent hippocampal development with peak hilar neurogenesis and widespread microgliogenesis occurring in the first week of life. Inflammation occurring during this period may negatively influence development, potentially facilitating or increasing susceptibility to later-life pathology. We administered the Gram-negative bacterial coat protein lipopolysaccharide (LPS) systemically at postnatal day 5 (1 mg/kg i.

Cell-based approaches for the treatment of systemic inflammation.

Acute and chronic solid organ failures are costly disease processes with high mortality rates. Inflammation plays a central role in both acute and chronic organ failure, including heart, lung and kidney. In this regard, new therapies for these disorders have focused on inhibiting the mediators of inflammation, including cytokines and free radicals, with little or no success in clinical studies.

Selective cytopheretic inhibitory device with regional citrate anticoagulation and portable sorbent dialysis.

Selective cytopheretic inhibitory device (SCD) therapy is an immunomodulatory treatment provided by a synthetic biomimetic membrane in an extracorporeal circuit, which has shown promise in preclinical large animal models of severe sepsis as well as in clinical trials treating patients with acute kidney injury and multiple organ failure. During SCD therapy, citrate is administered to lower ionized calcium levels in blood for anticoagulation and inhibition of leukocyte activation. Historically, citrate has been known to interfere with sorbent dialysis, therefore, posing a potential issue for the use of SCD therapy with a portable dialysis system.

Astrocytes negatively regulate neurogenesis through the Jagged1-mediated Notch pathway.

Adult neurogenesis is regulated by a number of cellular players within the neurogenic niche. Astrocytes participate actively in brain development, regulation of the mature central nervous system (CNS), and brain plasticity. They are important regulators of the local environment in adult neurogenic niches through the secretion of diffusible morphogenic factors, such as Wnts.

Emissions of PCDD/Fs, PCBs, and PAHs from legacy on-road heavy-duty diesel engines.

Exhaust emissions of seventeen 2,3,7,8-substituted polychlorinated dibenzo-p-dioxin/furan (PCDD/F) congeners, tetra-octa PCDD/F homologues, 12 WHO 2005 polychlorinated biphenyl (PCB) congeners, mono-nona chlorinated biphenyl homologues, and 19 polycyclic aromatic hydrocarbons (PAHs) from three legacy diesel engines were investigated. The three engines tested were a 1985 model year GM 6.2J-series engine, a 1987 model year Detroit Diesel Corporation 6V92 engine, and a 1993 model year Cummins L10 engine.

Regulation of toll-like receptor 1 and -2 in neonatal mice brains after hypoxia-ischemia.

Background: Hypoxic-ischemic (HI) brain injury remains a major problem in newborns, resulting in increased risk of neurological disorders. Neonatal HI triggers a broad inflammatory reaction in the brain, including activation of the innate immune system. Toll-like receptors (TLRs), which are key components of the innate immune system, are believed to play a role in adult cerebral ischemic injury.

A biomimetic membrane device that modulates the excessive inflammatory response to sepsis.

Objective: Septic shock has a clinical mortality rate approaching fifty percent. The major clinical manifestations of sepsis are due to the dysregulation of the host's response to infection rather than the direct consequences of the invading pathogen. Central to this initial immunologic response is the activation of leukocytes and microvascular endothelium resulting in cardiovascular instability, lung injury and renal dysfunction.

Oscillator strengths and line widths of dipole-allowed transitions in (14)N2 between 86.0 and 89.7 nm.

Oscillator strengths of 23 electric-dipole-allowed bands of (14)N(2) in the 86.0-89.7 nm (111,480-116,280 cm(-1)) region are reported from synchrotron-based photoabsorption measurements at an instrumental resolution of 6.

Increased neurogenesis and astrogenesis from neural progenitor cells grafted in the hippocampus of GFAP-/- Vim-/- mice.

After neurotrauma, ischemia, or neurodegenerative disease, astrocytes upregulate their expression of the intermediate filament proteins glial fibrillary acidic protein (GFAP), vimentin (Vim), and nestin. This response, reactive gliosis, is attenuated in GFAP(-/-)Vim(-/-) mice, resulting in the promotion of synaptic regeneration after neurotrauma and improved integration of retinal grafts. Here we assessed whether GFAP(-/-)Vim(-/-) astrocytes affect the differentiation of neural progenitor cells.

Signaling through C5aR is not involved in basal neurogenesis.

The complement system, an important part of the innate immune system, provides protection against invading pathogens, in part through its proinflammatory activities. Although most complement proteins are synthesized locally in the brain and the relevant complement receptors are expressed on resident brain cells, little is known about brain-specific role(s) of the complement system. C3a and C5a, complement-derived peptides with anaphylatoxic properties, have been implicated in noninflammatory functions, such as tissue regeneration and neuroprotection.

Kidney epithelial cells.

Kidney tubules are an essential component of an organism's blood clearance mechanism, recovering essential metabolites from glomerular filtration by active transport. Tubules are subject to injury, usually as the result of ischemia-reperfusion events that damage the polarized tubular cell layer that coats the tubule basement membrane, causing dysfunction and necrosis that is often associated with acute renal failure. However, tubules are capable of self-repair, forming new proximal tubular cells to replace failing or necrotic cells.

Oscillator strength and linewidth measurements of dipole-allowed transitions in 14N2 between 93.5 and 99.5 nm.

Line oscillator strengths in 16 electric dipole-allowed bands of 14N2 in the 93.5-99.5 nm (106,950-100,500 cm(-1)) region have been measured at an instrumental resolution of 6.

Type I interferons and the innate immune response--more than just antiviral cytokines.

The role of type I interferon (referred to as IFN in this review) in early antiviral immunity is well known. More recently IFN has been shown to be a potent regulator of adaptive immunity. It is now becoming clear that a broad range of viruses, bacteria and even parasites express ligands capable of stimulating a growing number of signalling pathways that results in, often subtype specific, induction of IFN.

Doubly ionized carbon observed in the plasma tail of comet Kudo-Fujikawa.

Comet C/2002 X5 (Kudo-Fujikawa) was observed near its perihelion of 0.19 astronomical unit by the Ultraviolet Coronagraph Spectrometer aboard the Solar and Heliospheric Observatory spacecraft. Images of the comet reconstructed from high-resolution spectra reveal a quasi-spherical cloud of neutral hydrogen and a variable tail of C+ and C2+ that disconnects from the comet and subsequently regenerates.

Castleman's disease associated with myasthenia gravis.

Castleman's disease presents as a peculiar type of lymph node hyperplasia. Traditionally, the disease has been classified on clinical grounds (solitary or multicentric) and by histologic appearance (hyaline vascular pattern, plasma cell predominance, or mixed lesions). It is now increasingly clear that there are different etiologies for each of these different subtypes.