High-affinity T cell receptor ImmTAC® bispecific efficiently redirects T cells to kill tumor cells expressing the cancer-testis antigen PRAME.

Background: PRAME (eferentially expressed ntigen in lanoma) is a cancer-testis antigen expressed in several tumor indications, representing an attractive anticancer target. However, its intracellular location limits targeting by traditional methods. PRAME peptides are presented on the surface of tumor cells by human leukocyte antigen (HLA) molecules, indicating that a T cell receptor (TCR)-based strategy that redirects T cells to kill PRAME tumors could be a novel immunotherapeutic option.

Improving value delivery in living donor kidney transplant through process improvement.

Introduction: Living donor kidney evaluation has substantial time variations with significant intercenter variation. One-day donor evaluation has shown to be clinically efficient and improve transplant rates. However, patients' perception of 1-day evaluation is unknown.

Biocoating-A Critical Step Governing the Oral Delivery of Polymeric Nanoparticles.

Decades of research into the topic of oral nanoparticle (NP) delivery has still not provided a clear consensus regarding which properties produce an effective oral drug delivery system. The surface properties-charge and bioadhesiveness-as well as in vitro and in vivo correlation seem to generate the greatest number of disagreements within the field. Herein, a mechanism underlying the in vivo behavior of NPs is proposed, which bridges the gaps between these disagreements.

Parent Teleconsultation to Increase Bites Consumed: A Demonstration Across Foods for a Child With ARFID and ASD.

Children with autism spectrum disorder (ASD) experience feeding dysfunction at a substantially higher proportion than their neurotypical peers. Feeding concerns can provide considerable challenges for parents, and as such, helping parents of children with ASD provide effective mealtime interventions for interfering behavior is critical, especially if parents have individual circumstances that affect their ability to effectively implement these feeding interventions. This study contributes to the parent-implemented feeding-intervention literature by demonstrating that a parent with ASD can implement a pediatric feeding intervention in the home with their child with ASD, despite contributing mental health factors.

Longitudinal variance of Donor-Derived Cell-Free DNA (dd-cfDNA) in Stable Kidney Transplant (KTx) patients are influenced by donor/recipient variables.

Background: The longitudinal time-course of dd-cfDNA after kidney transplant (KTx) is not well-described. The cut off values of dd-cfDNA in KTx derive from biopsy-coupled single measurements. Meaningful interpretation necessitates understanding of: (1) time variance of dd-cfDNA levels post-KTx, (2) factors determining biologic variability, and (3) relationship to donor and recipient characteristics.

Quantitative trait loci and transcriptome signatures associated with avian heritable resistance to Campylobacter.

Campylobacter is the leading cause of bacterial foodborne gastroenteritis worldwide. Handling or consumption of contaminated poultry meat is a key risk factor for human campylobacteriosis. One potential control strategy is to select poultry with increased resistance to Campylobacter.

Pellino-1 Regulates the Responses of the Airway to Viral Infection.

Exposure to respiratory pathogens is a leading cause of exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Pellino-1 is an E3 ubiquitin ligase known to regulate virally-induced inflammation. We wished to determine the role of Pellino-1 in the host response to respiratory viruses in health and disease.

Molecular cloning and characterisation of chicken IL-18 binding protein.

The human IL-1 receptor family is comprised of 11 membrane bound or soluble receptors and the IL-18 binding protein (IL-18BP). These receptors are dispersed across seven genomic loci, with the majority at a single locus. Direct orthologues were identified in the chicken at conserved genomic loci; however, the IL-18BP remained absent from the first four builds of the chicken genome sequence.

The Characterization of in Avian Coronavirus Infection In Vivo, Ex Vivo and In Vitro.

The coronaviruses are a large family of enveloped RNA viruses that commonly cause gastrointestinal or respiratory illnesses in the infected host. Avian coronavirus infectious bronchitis virus (IBV) is a highly contagious respiratory pathogen of chickens that can affect the kidneys and reproductive systems resulting in bird mortality and decreased reproductivity. The interferon-inducible transmembrane (IFITM) proteins are activated in response to viral infections and represent a class of cellular restriction factors that restrict the replication of many viral pathogens.

CD200R deletion promotes a neutrophil niche for Francisella tularensis and increases infectious burden and mortality.

Pulmonary immune control is crucial for protection against pathogens. Here we identify a pathway that promotes host responses during pulmonary bacterial infection; the expression of CD200 receptor (CD200R), which is known to dampen pulmonary immune responses, promotes effective clearance of the lethal intracellular bacterium Francisella tularensis. We show that depletion of CD200R in mice increases in vitro and in vivo infectious burden.

Comparative analysis of the chicken IFITM locus by targeted genome sequencing reveals evolution of the locus and positive selection in IFITM1 and IFITM3.

Background: The interferon-induced transmembrane (IFITM) protein family comprises a class of restriction factors widely characterised in humans for their potent antiviral activity. Their biological activity is well documented in several animal species, but their genetic variation and biological mechanism is less well understood, particularly in avian species.

Results: Here we report the complete sequence of the domestic chicken Gallus gallus IFITM locus from a wide variety of chicken breeds to examine the detailed pattern of genetic variation of the locus on chromosome 5, including the flanking genes ATHL1 and B4GALNT4.

Avian influenza viruses at the wild-domestic bird interface in Egypt.

Wild birds of the orders Anseriforme (mainly ducks, geese and swans) and Charadriiformes (mainly gulls, terns and waders) constitute the natural reservoir for low pathogenic avian influenza (LPAI) viruses. In Egypt, highly pathogenic avian influenza (HPAI) H5N1 and LPAI H9N2 viruses are endemic in domestic poultry, forming a threat to animal and human health and raising questions about the routes of introduction and mechanisms of persistence. Recently, HPAI H5N8 virus was also introduced into Egyptian domestic birds.

Genome-wide effect of pulmonary airway epithelial cell-specific deletion.

Pulmonary airway epithelial cells (AECs) form a critical interface between host and environment. We investigated the role of the circadian clock using mice bearing targeted deletion of the circadian gene brain and muscle ARNT-like 1 () in AECs. Pulmonary neutrophil infiltration, biomechanical function, and responses to influenza infection were all disrupted.

The Genomic Architecture of Fowl Typhoid Resistance in Commercial Layers.

serovar Gallinarum causes devastating outbreaks of fowl typhoid across the globe, especially in developing countries. With the use of antimicrobial agents being reduced due to legislation and the absence of licensed vaccines in some parts of the world, an attractive complementary control strategy is to breed chickens for increased resistance to . The potential for genetic control of salmonellosis has been demonstrated by experimental challenge of inbred populations.

The genome of the biting midge Culicoides sonorensis and gene expression analyses of vector competence for bluetongue virus.

Background: The new genomic technologies have provided novel insights into the genetics of interactions between vectors, viruses and hosts, which are leading to advances in the control of arboviruses of medical importance. However, the development of tools and resources available for vectors of non-zoonotic arboviruses remains neglected. Biting midges of the genus Culicoides transmit some of the most important arboviruses of wildlife and livestock worldwide, with a global impact on economic productivity, health and welfare.

Axl and MerTK receptor tyrosine kinases maintain human macrophage efferocytic capacity in the presence of viral triggers.

The requirement to remove apoptotic cells is equally important in homeostasis and inflammatory disease. In particular, during viral infections large quantities of infected cells undergo apoptosis and need to be efficiently cleared by phagocytes to prevent secondary necrosis. Although specific roles of several apoptotic cell sensors, such as the TAM (Tyro3, Axl, MerTK) receptor family, have been characterized in mouse models, little is known about their regulation and involvement in apoptotic cell uptake (efferocytosis) by human macrophages under inflammatory conditions.

Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes.

Background: Interferon inducible transmembrane (IFITM) proteins are effectors of the immune system widely characterized for their role in restricting infection by diverse enveloped and non-enveloped viruses. The chicken IFITM (chIFITM) genes are clustered on chromosome 5 and to date four genes have been annotated, namely chIFITM1, chIFITM3, chIFITM5 and chIFITM10. However, due to poor assembly of this locus in the Gallus Gallus v4 genome, accurate characterization has so far proven problematic.

On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier.

Immuno-surveillance networks operating at barrier sites are tuned by local tissue cues to ensure effective immunity. Site-specific commensal bacteria provide key signals ensuring host defense in the skin and gut. However, how the oral microbiome and tissue-specific signals balance immunity and regulation at the gingiva, a key oral barrier, remains minimally explored.

Reversal of TREM-1 ectodomain shedding and improved bacterial clearance by intranasal metalloproteinase inhibitors.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is expressed on neutrophils and monocyte/macrophages and amplifies Toll-like receptor-mediated inflammation during infection. TREM-1 also exists in an antagonistic soluble form (sTREM-1) that has been used as a peripheral biomarker in sepsis, though the mechanisms of its release are not entirely clear. The requirement of TREM-1 in single microbial infections is controversial, with some studies showing a protective role and others a contribution to immunopathology.

Selection of reference genes for gene expression analysis by real-time qPCR in avian cells infected with infectious bronchitis virus.

Infectious bronchitis virus (IBV) causes infectious bronchitis in poultry, a respiratory disease that is a source of major economic loss to the poultry industry. Detection and the study of the molecular pathogenesis of the virus often involve the use of real-time quantitative PCR assays (qPCR). To account for error within the experiments, the levels of target gene transcription are normalized to that of suitable reference genes.

A Versatile Panel of Reference Gene Assays for the Measurement of Chicken mRNA by Quantitative PCR.

Quantitative real-time PCR assays are widely used for the quantification of mRNA within avian experimental samples. Multiple stably-expressed reference genes, selected for the lowest variation in representative samples, can be used to control random technical variation. Reference gene assays must be reliable, have high amplification specificity and efficiency, and not produce signals from contaminating DNA.

The genomic architecture of resistance to Campylobacter jejuni intestinal colonisation in chickens.

Background: Campylobacter is the leading cause of foodborne diarrhoeal illness in humans and is mostly acquired from consumption or handling of contaminated poultry meat. In the absence of effective licensed vaccines and inhibitors, selection for chickens with increased resistance to Campylobacter could potentially reduce its subsequent entry into the food chain. Campylobacter intestinal colonisation levels are influenced by the host genetics of the chicken.

The chicken IL-1 family: evolution in the context of the studied vertebrate lineage.

The interleukin-1 gene family encodes a group of related proteins that exhibit a remarkable pleiotropy in the context of health and disease. The set of indispensable functions they control suggests that these genes should be found in all eukaryotic species. The ligands and receptors of this family have been primarily characterised in man and mouse.

Glutamate alterations associated with transcranial magnetic stimulation in youth depression: a case series.

Objective: We hypothesized an increase in dorsolateral prefrontal cortex (DLPFC) glutamate levels would occur after 3 weeks of repetitive transcranial magnetic stimulation (rTMS) treatment and a decrease in major depressive disorder (MDD) symptoms.

Methods: We report 6 patients (4 females) 15 to 21 years of age with treatment-resistant MDD. Participants had a mean (SD) age of 18.