Problem Behaviours and Relinquishment: Challenges Faced by Clinical Animal Behaviourists When Assessing Fear and Frustration.

Fear and frustration are two emotions thought to frequently contribute to problem behaviour, often leading to relinquishment. Inferring these emotions is challenging as they may present with some similar general signs, but they potentially require different treatment approaches to efficiently address the behaviour of concern. Although behavioural assessment frameworks have been proposed, it is largely unknown how clinical animal behaviourists (CABs) assimilate information about the emotional state of an animal to inform their behavioural assessment.

Proximity labelling identifies pro-migratory endocytic recycling cargo and machinery of the Rab4 and Rab11 families.

Endocytic recycling controls the return of internalised cargoes to the plasma membrane to coordinate their positioning, availability and downstream signalling. The Rab4 and Rab11 small GTPase families regulate distinct recycling routes, broadly classified as fast recycling from early endosomes (Rab4) and slow recycling from perinuclear recycling endosomes (Rab11), and both routes handle a broad range of overlapping cargoes to regulate cell behaviour. We adopted a proximity labelling approach, BioID, to identify and compare the protein complexes recruited by Rab4a, Rab11a and Rab25 (a Rab11 family member implicated in cancer aggressiveness), revealing statistically robust protein-protein interaction networks of both new and well-characterised cargoes and trafficking machinery in migratory cancer cells.

Convergent somatic mutations in metabolism genes in chronic liver disease.

The progression of chronic liver disease to hepatocellular carcinoma is caused by the acquisition of somatic mutations that affect 20-30 cancer genes. Burdens of somatic mutations are higher and clonal expansions larger in chronic liver disease than in normal liver, which enables positive selection to shape the genomic landscape. Here we analysed somatic mutations from 1,590 genomes across 34 liver samples, including healthy controls, alcohol-related liver disease and non-alcoholic fatty liver disease.

Intracellular nanovesicles mediate α5β1 integrin trafficking during cell migration.

Membrane traffic is an important regulator of cell migration through the endocytosis and recycling of cell surface receptors such as integrin heterodimers. Intracellular nanovesicles (INVs) are transport vesicles that are involved in multiple membrane trafficking steps, including the recycling pathway. The only known marker for INVs is tumor protein D54 (TPD54/TPD52L2), a member of the TPD52-like protein family.

Translation factor mRNA granules direct protein synthetic capacity to regions of polarized growth.

mRNA localization serves key functions in localized protein production, making it critical that the translation machinery itself is present at these locations. Here we show that translation factor mRNAs are localized to distinct granules within yeast cells. In contrast to many messenger RNP granules, such as processing bodies and stress granules, which contain translationally repressed mRNAs, these granules harbor translated mRNAs under active growth conditions.

Control of adhesion and protrusion in cell migration by Rho GTPases.

Cell migration is a critical process that underpins a number of physiological and pathological contexts such as the correct functioning of the immune system and the spread of metastatic cancer cells. Central to this process are the Rho family of GTPases, which act as core regulators of cell migration. Rho GTPases are molecular switches that associate with lipid membranes and act to choreograph molecular events that underpin cell migration.

Vesicle trafficking pathways that direct cell migration in 3D matrices and in vivo.

Cell migration is a vital process in development and disease, and while the mechanisms that control motility are relatively well understood on two-dimensional surfaces, the control of cell migration in three dimensions (3D) and in vivo has only recently begun to be understood. Vesicle trafficking pathways have emerged as a key regulatory element in migration and invasion, with the endocytosis and recycling of cell surface cargos, including growth factor and chemokine receptors, adhesion receptors and membrane-associated proteases, being of major importance. We highlight recent advances in our understanding of how endocytic trafficking controls the availability and local activity of these cargoes to influence the movement of cells in 3D matrix and in developing organisms.

Phase II Weekly Vinblastine for Chemotherapy-Naïve Children With Progressive Low-Grade Glioma: A Canadian Pediatric Brain Tumor Consortium Study.

Purpose Vinblastine monotherapy has shown promising activity and a low-toxicity profile in patients with pediatric low-grade glioma (PLGG) who experienced treatment failure after initial treatment with chemotherapy and/or radiation. The aim of this study was to assess the activity of vinblastine in therapy-naïve children. Patients and Methods Patients < 18 years old with unresectable and/or progressive therapy-naïve PLGG were eligible.

The role of resection alone in select children with intracranial ependymoma: the Canadian Pediatric Brain Tumour Consortium experience.

Purpose: Gross total resection (GTR) of intracranial ependymoma is an accepted goal. More controversial is radiotherapy deferral. This study reports on children treated with gross total resection who did not receive upfront adjuvant radiotherapy.

Tissue fixation and the effect of molecular fixatives on downstream staining procedures.

It is impossible to underplay the importance of fixation in histopathology. Whether the scientist is interested in the extraction of information on lipids, proteins, RNA or DNA, fixation is critical to this extraction. This review aims to give a brief overview of the current "state of play" in fixation and focus on the effect fixation, and particularly the effect of the newer brand of "molecular fixatives" have on morphology, histochemistry, immunohistochemistry and RNA/DNA analysis.