Non-neuronal brain biology and its relevance to animal welfare.

Non-neuronal cells constitute a significant portion of brain tissue and are seen as having key roles in brain homeostasis and responses to challenges. This review illustrates how non-neuronal biology can bring new perspectives to animal welfare through understanding mechanisms that determine welfare outcomes and highlighting interventions to improve welfare. Most obvious in this respect is the largely unrecognised relevance of neuroinflammation to animal welfare which is increasingly found to have roles in determining how animals respond to challenges.

Improving the study of brain-behavior relationships by revisiting basic assumptions.

Neuroimaging research has been at the forefront of concerns regarding the failure of experimental findings to replicate. In the study of brain-behavior relationships, past failures to find replicable and robust effects have been attributed to methodological shortcomings. Methodological rigor is important, but there are other overlooked possibilities: most published studies share three foundational assumptions, often implicitly, that may be faulty.

Stage 1 Registered Report: Refinement of tickling protocols to improve positive animal welfare in laboratory rats.

Rat tickling is a heterospecific interaction for experimenters to mimic the interactions of rat play, where they produce 50 kHz ultrasonic vocalisations (USV), symptoms of positive affect; tickling can improve laboratory rat welfare. The standard rat tickling protocol involves gently pinning the rat in a supine position. However, individual response to this protocol varies.

Defining the pig microglial transcriptome reveals its core signature, regional heterogeneity, and similarity with human and rodent microglia.

Microglia play key roles in brain homeostasis as well as responses to neurodegeneration and neuroinflammatory processes caused by physical disease and psychosocial stress. The pig is a physiologically relevant model species for studying human neurological disorders, many of which are associated with microglial dysfunction. Furthermore, pigs are an important agricultural species, and there is a need to understand how microglial function affects their welfare.

Sex differences in 50 kHz call subtypes emitted during tickling-induced playful behaviour in rats.

'Tickling' induces positive affective states in laboratory rats as evidenced by the production of 50-kHz ultrasonic vocalisations (USVs), although this has mostly been investigated in males. Juvenile rats emit distinctive 50-kHz USV subtypes. Frequency-modulated (FM) 50-kHz USVs are thought to be associated with positive affect and flat 50-kHz USVs with social communication.

p53-Bad: A Novel Tumor Suppressor/Proapoptotic Factor Hybrid Directed to the Mitochondria for Ovarian Cancer Gene Therapy.

Clinical trials involving p53 gene therapy for ovarian cancer failed due to the dominant negative inhibition of wild-type p53 and multiple genetic aberrations in ovarian cancer. To overcome this problem, we have designed a more potent chimeric gene fusion, called p53-Bad, that combines p53 with the mitochondrial pro-apoptotic factor Bad. Unlike wild-type p53, which acts as a nuclear transcription factor, this novel p53-Bad construct has multiple unique mechanisms of action including a direct and rapid apoptotic effect at the mitochondria.

Mitochondrially targeted p53 or DBD subdomain is superior to wild type p53 in ovarian cancer cells even with strong dominant negative mutant p53.

Background: While tumor suppressor p53 functions primarily as a transcription factor in the nucleus, cellular stress can cause p53 to translocate to the mitochondria and directly trigger a rapid apoptotic response. We have previously shown that fusing p53 (or its DNA binding domain, DBD, alone) to the mitochondrial targeting signal (MTS) from Bak or Bax can target p53 to the mitochondria and induce apoptosis in gynecological cancer cell lines including cervical cancer cells (HeLa; wt p53), ovarian cancer cells (SKOV-3; p53 267del non-expressing), and breast cancer cells (T47D; L194F p53 mutation). However, p53 with Bak or Bax MTSs have not been previously tested in cancers with strong dominant negative (DN) mutant p53 which are capable of inactivating wt p53 by homo-oligomerization.

Associations between Oxytocin Receptor Gene Polymorphisms, Empathy towards Animals and Implicit Associations towards Animals.

Oxytocin has been well researched in association with psychological variables and is widely accepted as a key modulator of human social behaviour. Previous work indicates involvement of oxytocin receptor gene () single nucleotide polymorphisms (SNPs) in human-human empathy, however little is known about associations of SNPs with empathy and affective reactions of humans towards animals. Five SNPs previously found to associate with human social behaviour were genotyped in 161 students.

A descriptive model for a multidisciplinary unit for colorectal and pelvic malformations.

Introduction: Patients with anorectal malformations (ARM), Hirschsprung disease (HD), and colonic motility disorders often require care from specialists across a variety of fields, including colorectal surgery, urology, gynecology, and GI motility. We sought to describe the process of creating a collaborative process for the care of these complex patients.

Methods: We developed a model of a devoted center for these conditions that includes physicians, psychologists, social workers, nurses, and advanced practice nurses.

Controlling Phlebotomy Volume Diminishes PICU Transfusion: Implementation Processes and Impact.

Background And Objectives: Phlebotomy excess contributes to anemia in PICU patients and increases the likelihood of red blood cell transfusion, which is associated with risk of adverse outcomes. Excessive phlebotomy reduction (EPR) strategies may reduce the need for transfusion, but have not been evaluated in a PICU population. We hypothesized that EPR strategies, facilitated by implementation science methods, would decrease excess blood drawn and reduce transfusion frequency.

Up-regulation of IGF-1 in the frontal cortex of piglets exposed to an environmentally enriched arena.

Environmental enrichment (EE) is widely used in the life sciences to study effects of environment on the brain. In pigs, despite lack of EE being a key welfare issue there is little understanding of brain effects of EE in pigs. This project aimed to study the effects of exposure to an EE arena on piglet behaviours and on brain gene expression levels with a focus on IGF-1 and related genes.

Systemic medications used in treatment of common dermatological conditions: safety profile with respect to pregnancy, breast feeding and content in seminal fluid.

Prescribing for pregnant or lactating patients and male patients wishing to father children can be a difficult area for dermatologists. There is a lack of review articles of commonly used systemic medications in dermatology with respect to their effects on developing embryogenesis and their potential transfer across the placenta, in breast milk and in seminal fluid. This paper aims to provide an up to date summary of evidence to better equip dermatologists to inform patients about the effects of systemic medications commonly used in dermatology to treat conditions such as atopic dermatitis, psoriasis and acne, on current and future embryogenesis and fertility.

Evidence for litter differences in play behaviour in pre-weaned pigs.

The aim of this study was to analyse spontaneous play behaviour in litters of domestic pigs () for sources of variation at individual and litter levels and to relate variation in play to measures of pre and postnatal development. Seven litters of commercially bred piglets ( = 70) were born (farrowed) within a penning system (PigSAFE) that provided opportunities for the performance of spontaneous play behaviours. Individual behaviour was scored based on an established play ethogram for 2 days per week over the 3 week study period.

Transient receptor potential A1 activation prolongs isoflurane induction latency and impairs respiratory function in mice.

Background: Isoflurane is a potent volatile anesthetic; however, it evokes airway irritation and neurogenic constriction through transient receptor potential (TRP) A1 channels and sensitizes TRPV1 channels, which colocalizes with TRPA1 in most of the vagal C-fibers innervating the airway. However, little is known about the precise effects of these two channels on the respiratory function during isoflurane anesthesia.

Methods: By using a rodent behavioral model and whole-body plethysmograph, the authors examined the response of Trpa1 and Trpv1 mice to isoflurane anesthesia and monitored their respiratory functions during anesthesia.

Sweating the small stuff: adequacy and accuracy in sweat chloride determination.

Objectives: Sweat chloride testing is the gold standard for diagnosis of cystic fibrosis (CF). Our objectives were to: 1) describe variables that determine sweat rate; 2) determine the analytic and diagnostic capacity of sweat chloride analysis across the range of observed sweat rates; and 3) determine the biologic variability of sweat chloride concentration.

Methods: A retrospective analysis was performed using data from all sweat chloride tests performed at St.

Functional analysis of the putative integrin recognition motif on adeno-associated virus 9.

Adeno-associated viruses (AAVs) display a highly conserved NGR motif on the capsid surface. Earlier studies have established this tripeptide motif as being essential for integrin-mediated uptake of recombinant AAV serotype 2 (AAV2) in cultured cells. However, functional attributes of this putative integrin recognition motif in other recombinant AAV serotypes displaying systemic transduction in vivo remain unknown.

Experience-Dependent, Layer-Specific Development of Divergent Thalamocortical Connectivity.

The main input to primary sensory cortex is via thalamocortical (TC) axons that form the greatest number of synapses in layer 4, but also synapse onto neurons in layer 6. The development of the TC input to layer 4 has been widely studied, but less is known about the development of the layer 6 input. Here, we show that, in neonates, the input to layer 6 is as strong as that to layer 4.

Engraftment of a galactose receptor footprint onto adeno-associated viral capsids improves transduction efficiency.

New viral strains can be evolved to recognize different host glycans through mutagenesis and experimental adaptation. However, such mutants generally harbor amino acid changes that affect viral binding to a single class of carbohydrate receptors. We describe the rational design and synthesis of novel, chimeric adeno-associated virus (AAV) strains that exploit an orthogonal glycan receptor for transduction.

Limited population structure, genetic drift and bottlenecks characterise an endangered bird species in a dynamic, fire-prone ecosystem.

Fire is a major disturbance process in many ecosystems world-wide, resulting in spatially and temporally dynamic landscapes. For populations occupying such environments, fire-induced landscape change is likely to influence population processes, and genetic patterns and structure among populations. The Mallee Emu-wren Stipiturus mallee is an endangered passerine whose global distribution is confined to fire-prone, semi-arid mallee shrublands in south-eastern Australia.

Effects on carbon and nitrogen emissions due to swine manure removal for biofuel production.

Methane (CH) and ammonia (NH) are emitted from swine-manure processing lagoons, contributing to global climate change and reducing air quality. Manure diverted to biofuel production is proposed as a means to reduce CH emissions. At a swine confined animal feeding operation in the U.

Glycan binding avidity determines the systemic fate of adeno-associated virus type 9.

Glycans are key determinants of host range and transmissibility in several pathogens. In the case of adeno-associated viruses (AAV), different carbohydrates serve as cellular receptors in vitro; however, their contributions in vivo are less clear. A particularly interesting example is adeno-associated virus serotype 9 (AAV9), which displays systemic tropism in mice despite low endogenous levels of its primary receptor (galactose) in murine tissues.

P-glycoprotein is a major determinant of norbuprenorphine brain exposure and antinociception.

Norbuprenorphine is a major metabolite of buprenorphine and potent agonist of μ, δ, and κ opioid receptors. Compared with buprenorphine, norbuprenorphine causes minimal antinociception but greater respiratory depression. It is unknown whether the limited antinociception is caused by low efficacy or limited brain exposure.