Who becomes an entrepreneur after university? Evidence from Canada.

In recent decades there has been significant interest among policy makers in supporting entrepreneurship among university students, with the goal to improve labor market outcomes and contribute to the economy through venture creation. Drawing from the 2018 National Graduate Survey in Canada, our study examines who engages in entrepreneurial activity after graduation, investigating differences among demographic groups and between those who participated in entrepreneurship education on campus and those who did not participate. We find that those graduates who participated in entrepreneurship education are more likely to be self-employed and own their own business three years after graduating than the general population of university graduates.

TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen.

For the protozoan parasite Leishmania, completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mammalian host cell phagolysosome. Transmembrane transporters are the gatekeepers of intracellular environments, controlling the flux of solutes and ions across membranes. To discover which transporters are vital for survival as intracellular amastigote forms, we carried out a systematic loss-of-function screen of the L.

Cereblon-recruiting proteolysis targeting chimeras (PROTACs) can determine the selective degradation of HDAC1 over HDAC3.

Histone deacetylase (HDAC) enzymes 1-3 exist in several corepressor complexes and are viable drug targets. To date, proteolysis targeting chimeras (PROTACs) designed to target HDAC1-3 typically exhibit the selective degradation of HDAC3. Herein, we report cereblon-recruiting PROTACs that degrade HDAC1 with selectivity over HDAC3.

Optical genome mapping of structural variants in Parkinson's disease-related induced pluripotent stem cells.

Background: Certain structural variants (SVs) including large-scale genetic copy number variants, as well as copy number-neutral inversions and translocations may not all be resolved by chromosome karyotype studies. The identification of genetic risk factors for Parkinson's disease (PD) has been primarily focused on the gene-disruptive single nucleotide variants. In contrast, larger SVs, which may significantly influence human phenotypes, have been largely underexplored.

Tapasin assembly surveillance by the RNF185/Membralin ubiquitin ligase complex regulates MHC-I surface expression.

Immune surveillance by cytotoxic T cells eliminates tumor cells and cells infected by intracellular pathogens. This process relies on the presentation of antigenic peptides by Major Histocompatibility Complex class I (MHC-I) at the cell surface. The loading of these peptides onto MHC-I depends on the peptide loading complex (PLC) at the endoplasmic reticulum (ER).

The Spherical Tokamak for Energy Production: theme issue introduction.

This theme issue collects together papers summarising the conceptual design of the Spherical Tokamak for Energy Production (STEP). In 2019, the UK government funded the first design stages of a prototype fusion powerplant based on a compact toroidal geometry, called STEP. The primary technical aims of STEP are to produce net energy, to be self-sufficient in tritium fuel and to demonstrate a maintenance regime that would extrapolate to appropriate availability for commercial powerplants.

Enhanced efficacy of BCG vaccine formulated in adjuvant is dependent on IL-17A expression.

A new, more effective vaccine against tuberculosis (TB) is urgently needed to curtail the current TB problem. The only licensed vaccine, BCG, has been shown to have highly variable protective efficacy in several clinical trials ranging from zero to 80 % against TB disease. We have previously reported that BCG formulated in dimethyl dioctadecyl-ammonium bromide (DDA) with D-(+)-Trehalose 6,6'-Dibehenate (TDB) adjuvant (BCG + Adj) is significantly more protective than BCG alone following murine aerosol Mycobacterium tuberculosis infection.

Valproic Acid Causes Redox-Regulated Post-Translational Protein Modifications That Are Dependent upon P19 Cellular Differentiation States.

Valproic acid (VPA) is a common anti-epileptic drug and known neurodevelopmental toxicant. Although the exact mechanism of VPA toxicity remains unknown, recent findings show that VPA disrupts redox signaling in undifferentiated cells but has little effect on fully differentiated neurons. Redox imbalances often alter oxidative post-translational protein modifications and could affect embryogenesis if developmentally critical proteins are targeted.

Should all patients with polymyalgia rheumatica have a vascular ultrasound assessment?

There is a growing appreciation that both giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely interrelated conditions that have significant overlap in aetiology, clinical characteristics and treatment regimens. Subclinical GCA in PMR is becoming increasingly recognised, and there is evolving evidence that this may be a more aggressive disease phenotype than PMR. Ultrasound (US) lends itself well as a screening tool for GCA in PMR; it is inexpensive, non-invasive, widely available, lacks ionising radiation, may be performed at the bedside and is recommended by EULAR as a first-line investigation for suspected GCA.

PTCH1-mutant human cerebellar organoids exhibit altered neural development and recapitulate early medulloblastoma tumorigenesis.

Patched 1 (PTCH1) is the primary receptor for the sonic hedgehog (SHH) ligand and negatively regulates SHH signalling, an essential pathway in human embryogenesis. Loss-of-function mutations in PTCH1 are associated with altered neuronal development and the malignant brain tumour medulloblastoma. As a result of differences between murine and human development, molecular and cellular perturbations that arise from human PTCH1 mutations remain poorly understood.

MDM2 Antagonist Idasanutlin Reduces HDAC1/2 Abundance and Corepressor Partners but Not HDAC3.

Histone deacetylases 1-3 (HDAC1, HDAC2, and HDAC3) and their associated corepressor complexes play important roles in regulating chromatin structure and gene transcription. HDAC enzymes are also validated drug targets for oncology and offer promise toward new drugs for neurodegenerative diseases and cardiovascular diseases. We synthesized four novel heterobifunctional molecules designed to recruit the mouse double minute 2 homologue (MDM2) E3 ligase to degrade HDAC1-3 utilizing the MDM2 inhibitor idasanutlin, known as proteolysis targeting chimeras (PROTACs).

Empowering our First Nations workforce: evaluation of a First Nations COVID-19 vaccination training program.

Background: A COVID-19 vaccination training program was designed for Aboriginal and Torres Strait Islander (First Nations) health workers and practitioners in Queensland to expand their scope of practice to include COVID-19 immunisation. In the setting of a global pandemic, the project aimed to improve vaccination levels and show how First Nations staff are central to community-led responses to effectively address their community's health needs.

Methods: The program, consisting of an online module and face to face workshop, is described and then evaluated with the RE-AIM framework via mixed methods of participant training surveys and qualitative feedback.

Disciplinary gender balance, research productivity, and recognition of men and women in academia.

Gender disparities in science have become a salient concern for policy makers and researchers. Previous studies have documented a gender gap in research productivity and recognition in the sciences, and different reasons for this gap have been proposed. In this study, we examine four academic fields with different proportions of men and women in their population.

Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica.

Objective: The aim of the present study was to determine the clinical significance of subclinical giant cell arteritis (GCA) in polymyalgia rheumatica (PMR) and ascertain its optimal treatment approach.

Methods: Patients with PMR who fulfilled the 2012 European Alliance of Associations for Rheumatology/American College of Rheumatology Provisional Classification Criteria for PMR, did not have GCA symptoms and were routinely followed up for 2 years and were stratified into two groups, according to their ultrasound results: isolated PMR and PMR with subclinical GCA. The outcomes (relapses, glucocorticoid use and disease-modifying antirheumatic drug treatments) between groups were compared.

Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice.

Engineering human tissue with diverse cell types and architectures remains challenging. The cerebral cortex, which has a layered cellular architecture composed of layer-specific neurons organised into vertical columns, delivers higher cognition through intricately wired neural circuits. However, current tissue engineering approaches cannot produce such structures.

C9orf72-ALS human iPSC microglia are pro-inflammatory and toxic to co-cultured motor neurons via MMP9.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, with additional pathophysiological involvement of non-neuronal cells such as microglia. The commonest ALS-associated genetic variant is a hexanucleotide repeat expansion (HRE) mutation in C9orf72. Here, we study its consequences for microglial function using human iPSC-derived microglia.

Calcium dysregulation combined with mitochondrial failure and electrophysiological maturity converge in Parkinson's iPSC-dopamine neurons.

Parkinson's disease (PD) is characterized by a progressive deterioration of motor and cognitive functions. Although death of dopamine neurons is the hallmark pathology of PD, this is a late-stage disease process preceded by neuronal dysfunction. Here we describe early physiological perturbations in patient-derived induced pluripotent stem cell (iPSC)-dopamine neurons carrying the - mutation, a strong genetic risk factor for PD.