IL-27 maintains cytotoxic Ly6C γδ T cells that arise from immature precursors.

In mice, γδ-T lymphocytes that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage during thymic development. In the periphery, these cells play a critical role in host defense and anti-tumor immunity. Unlike αβ-T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted γδ-T cells undergo further functional maturation after exiting the thymus.

Beta-blockers or Placebo for Primary Prophylaxis (BOPPP) of oesophageal varices: study protocol for a randomised controlled trial.

Background: Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality.

NUAK1 governs centrosome replication in pancreatic cancer via MYPT1/PP1β and GSK3β-dependent regulation of PLK4.

The AMP-activated protein kinase (AMPK)-related kinase NUAK1 (NUAK family SNF1-like kinase 1) has emerged as a potential vulnerability in MYC-dependent cancer but the biological roles of NUAK1 in different settings are poorly characterised, and the spectrum of cancer types that exhibit a requirement for NUAK1 is unknown. Unlike canonical oncogenes, NUAK1 is rarely mutated in cancer and appears to function as an obligate facilitator rather than a cancer driver per se. Although numerous groups have developed small-molecule NUAK inhibitors, the circumstances that would trigger their use and the unwanted toxicities that may arise as a consequence of on-target activity are thus undetermined.

Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration.

Background & Aims: Mouse models of lineage tracing have helped to describe the important subpopulations of hepatocytes responsible for liver regeneration. However, conflicting results have been obtained from different models. Herein, we aimed to reconcile these conflicting reports by repeating a key lineage-tracing study from pericentral hepatocytes and characterising this Axin2CreERT2 model in detail.

Repeat infusion of autologous bone marrow cells in progressive multiple sclerosis - A phase I extension study (SIAMMS II).

Background: During the safety and feasibility 'Study of Intravenous Autologous Marrow in Multiple Sclerosis (SIAMMS)', intravenous infusion of autologous marrow was well tolerated. The efficacy of the approach is being explored in a placebo-controlled randomised controlled trial (ACTiMuS, NCT01815632) but it is not known whether repeated infusions will be required to optimise benefit. The objective of the current study was to explore the safety and feasibility of repeat treatment with intravenous autologous bone marrow for patients with progressive multiple sclerosis (MS).

Sensory and motor electrophysiological mapping of the cerebellum in humans.

Cerebellar damage during posterior fossa surgery in children can lead to ataxia and risk of cerebellar mutism syndrome. Compartmentalisation of sensorimotor and cognitive functions within the cerebellum have been demonstrated in animal electrophysiology and human imaging studies. Electrophysiological monitoring was carried out under general anaesthesia to assess the limb sensorimotor representation within the human cerebellum for assessment of neurophysiological integrity to reduce the incidence of surgical morbidities.

Alternating Hemiplegia of Childhood in a Child Harboring a Novel TBC1D24 Mutation: Case Report and Literature Review.

Alternating Hemiplegia of Childhood (AHC) is a rare neurological disease characterized by early-onset recurrent paroxysmal events and persistent neurological deficits. gene variants have been associated with a phenotypic spectrum having epilepsy as the main clinical manifestation. Herein, we report the case of a child affected by developmental delay, polymorphic seizures, and nonepileptic episodes characterized by hemiplegia or bilateral plegia, pallor, hypotonia, and dystonic postures without loss of consciousness that resolved with sleep.

The power of national acoustic tracking networks to assess the impacts of human activity on marine organisms during the COVID-19 pandemic.

COVID-19 restrictions have led to an unprecedented global hiatus in anthropogenic activities, providing a unique opportunity to assess human impact on biological systems. Here, we describe how a national network of acoustic tracking receivers can be leveraged to assess the effects of human activity on animal movement and space use during such global disruptions. We outline variation in restrictions on human activity across Australian states and describe four mechanisms affecting human interactions with the marine environment: 1) reduction in economy and trade changing shipping traffic; 2) changes in export markets affecting commercial fisheries; 3) alterations in recreational activities; and 4) decline in tourism.

Case Study in the Design of a Surrogate Solution for Use in Biopharmaceutical Drug Product Process Development.

The use of an aqueous-based surrogate solution in at-scale process development for biopharmaceutical drug products enables significant reduction in the usage of costly drug substance and improves confidence in initial drug product production runs performed using active biotherapeutic. Strategies for the formulation design of a surrogate solution that is representative of the unit operations in a typical drug product manufacturing process for a biopharmaceutical are presented herein, and a case study for the development of a surrogate solution for an example protein drug product is discussed. The surrogate was shown to have similar physical attributes to the drug product, including viscosity, surface tension, and density.

Western gorilla space use suggests territoriality.

The evolutionary origins of how modern humans share and use space are often modelled on the territorial-based violence of chimpanzees, with limited comparison to other apes. Gorillas are widely assumed to be non-territorial due to their large home ranges, extensive range overlap, and limited inter-group aggression. Using large-scale camera trapping, we monitored western gorillas in Republic of Congo across 60 km.

A seafloor habitat map for the Australian continental shelf.

Here we outline the genesis of Seamap Australia, which integrates spatial data of the seabed of Australia's continental shelf (0-200 m depth) from multiple sources to provide a single national map layer of marine habitat. It is underpinned by a hierarchical classification scheme with registered vocabulary, enabling presentation of nationally consistent information at the highest resolution available for any point in space. The Seamap Australia website enables users to delineate particular areas of interest, overlay habitat maps with many other marine data layers, and to directly access the data and metadata underlying the maps they produce.

Hierarchical social modularity in gorillas.

Modern human societies show hierarchical social modularity (HSM) in which lower-order social units like nuclear families are nested inside increasingly larger units. It has been argued that this HSM evolved independently and after the chimpanzee-human split due to greater recognition of, and bonding between, dispersed kin. We used network modularity analysis and hierarchical clustering to quantify community structure within two western lowland gorilla populations.

Surgical Outcomes of Single-Level Bilateral Selective Dorsal Rhizotomy for Spastic Diplegia in 150 Consecutive Patients.

Objectives: Selective dorsal rhizotomy (SDR) is used to improve spasticity, gait, and pain in children with spastic diplegia. There is growing evidence supporting its long-term benefits in terms of functional outcomes, independence, and quality of life. There is, however, little contemporary work describing the surgical morbidity of this irreversible procedure.

Lateral manus translation for limb-sparing surgery in 18 dogs with distal radial osteosarcoma in dogs.

Objective: To describe and report outcomes after lateral translation of the manus for limb-sparing management of distal radial osteosarcoma in dogs.

Study Design: Retrospective case series.

Study Population: Eighteen client-owned dogs.

Paediatric new-onset seizure clinic in Australia: Experience and lessons learnt.

Aim: A new-onset seizure clinic (NOSC) was established at our hospital in 2011, with the aim to provide accurate diagnosis and appropriate management to children with new-onset seizures or seizure mimics.

Methods: We report on the data analysis of the first 200 children seen in NOSC. A paediatric neurologist or paediatric/neurology trainee under supervision of a neurologist reviewed all the children.

Australian Clinical Consensus Guideline: The diagnosis and acute management of childhood stroke.

Stroke is among the top 10 causes of death in children and survivors carry resulting disabilities for decades, at substantial cost to themselves and their families. Children are not currently able to access reperfusion therapies, due to limited evidence supporting safety and efficacy and long diagnostic delays. The Australian Clinical Consensus Guideline for the Diagnosis and Acute Management of Childhood Stroke was developed to minimize unwarranted variations in care and document best evidence on the risk factors, etiologies, and conditions mimicking stroke that differ from adults.

Long-term outcome of dogs treated with ulnar rollover transposition for limb-sparing of distal radial osteosarcoma: 27 limbs in 26 dogs.

Objective: To determine outcomes in dogs with distal radial osteosarcoma treated with ulnar rollover transposition (URT) limb-sparing surgery including: viability of the ulnar graft, complications, subjective limb function, disease-free interval (DFI), and survival time (ST).

Study Design: Retrospective case series.

Animals: Twenty-six client-owned dogs with distal radial osteosarcoma and no involvement of the ulna.

Comorbid Conditions in Canadians Hospitalized Because of Diabetes.

Objectives: The number of hospital discharges involving type 1 or type 2 diabetes as the first-listed diagnosis has increased over the past few decades. Such cases are commonly associated with various comorbidities. We analyzed data collected from hospital separations in Canada to determine the number and proportion of comorbid conditions in Canadians hospitalized because of diabetes.

The Final (Oral Ebola) Vaccine Trial on Captive Chimpanzees?

Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV.

Reinforcing the association between distal 1q CNVs and structural brain disorder: A case of a complex 1q43-q44 CNV and a review of the literature.

Copy Number Variations (CNVs) comprising the distal 1q region 1q43-q44 are associated with neurological impairments, structural brain disorder, and intellectual disability. Here, we report an extremely rare, de novo case of a 1q43-q44 deletion with an adjacent duplication, associated with severe seizures, microcephaly, agenesis of the corpus callosum, and pachygyria, a consequence of defective neuronal migration disorder. We conducted a literature survey to find that our patient is only the second case of such a 1q43-q44 CNV ever to be described.

Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS): study protocol for a randomised controlled trial.

Background: We have recently completed an evaluation of the safety and feasibility of intravenous delivery of autologous bone marrow in patients with progressive multiple sclerosis (MS). The possibility of repair was suggested by improvement in the neurophysiological secondary outcome measure seen in all participants. The current study will examine the efficacy of intravenous delivery of autologous marrow in progressive MS.

Repeat infusion of autologous bone marrow cells in multiple sclerosis: protocol for a phase I extension study (SIAMMS-II).

Introduction: The 'Study of Intravenous Autologous Marrow in Multiple Sclerosis (SIAMMS)' trial was a safety and feasibility study which examined the effect of intravenous infusion of autologous bone marrow without myeloablative therapy. This trial was well tolerated and improvement was noted in the global evoked potential (GEP)--a neurophysiological secondary outcome measure recording speed of conduction in central nervous system pathways. The efficacy of intravenous delivery of autologous marrow in progressive multiple sclerosis (MS) will be examined in the phase II study the 'Assessment of Bone Marrow-Derived Cellular Therapy in Progressive Multiple Sclerosis (ACTiMuS; NCT01815632)'.