澳大利亚再生医学研究所

This paper focuses on the continuities and transformations of middle-class identities, through examining Asian international graduates on temporary visas. Studies on this group have provided important insights into how middle-class youth negotiate insecurity and instability after graduation in host countries. Few, however, have considered the role of class in sustaining and shaping international graduates' experiences as well as their migration trajectories. This paper aims to address the ongoing calls of scholars studying temporary middle-class migrants to investigate how their privilege is unstable and relational, and just like other migrants; their everyday lives are shaped by identity markers such as class. The paper is divided into two parts. Part 1 focuses on the continuities of global middle-classness. It highlights similarities between the Asian middle-class and the global (often western) middle-classes through discussing how (a) their middle-class parents' socio-economic stability enables them to embrace instability; (b) despite their privilege, however, not meeting the aspirations of stable employment can have repercussions; and (c) their embrace of instability is temporary as their future migration trajectory may include returning to their home country to reclaim their class privileges. Part 2 of the paper focuses on middle-class transformations. Through examining the boundary work that Asian international graduates do, it de-universalises middle-classness. Finally, the paper suggests Asian middle-class migrants offer a productive space for further understanding middle-classness, its diverse meanings and manifestations.

The origin of paired fins was a major event in early vertebrate history that fueled the adaptive radiation of the gnathostome clade. Evidence for the conservation of ancient regulatory systems between paired and median fins supports a model in which appendage-patterning mechanisms first evolved in the midline and were later redeployed to a new embryonic context, the flank. However, while paired fins and limbs are asymmetric along the dorsoventral (DV) axis, the equivalent axis does not exist in median fins, which are symmetric across the midline, raising questions of how DV patterning evolved. Here, we combine genetic tools in zebrafish with comparative expression analyses in representative ray-finned and cartilaginous fishes to show that a subset of limb DV patterning genes are expressed during median fin development. Using genetic lineage tracing of the canonical limb dorsalizing factor lmx1bb , we further demonstrate that, although lmx1bb -derived cells occupy distinct spatial domains across fin types, a subset of this lineage is fated to differentiate into fin ray osteoblasts in both paired and median fins. To test the potential conservation of regulatory modules across fin types, we generated a series of deletion mutants for two known lmx1b mouse limb enhancers, LARM1 and LARM2, that we show are partially conserved upstream of zebrafish lmx1bb . These experiments revealed that LARM function is essential for dorsoventral patterning of the paired pectoral and pelvic fins of zebrafish but is dispensable for formation of the unpaired dorsal and anal fins. Collectively, these data support the conservation of an ancient LARM -Lmx1b dorsal determination system in the paired fins of osteichthyans, challenge models proposing simple co-option of a pre-existing median fin gene regulatory network and suggest that the acquisition of this regulatory module may have been a key early step in the evolution of the paired fin DV patterning axis.

Inherited bone marrow failure syndromes (IBMFS) are monogenic disorders characterized by single or multilineage cytopenias from hypoproliferative dyshematopoiesis. Diagnosis is challenging because of substantial clinical and pathological overlap between individual IBMFS entities and acquired diseases such as immune aplastic anemia. Conventional genetic testing using targeted panels or whole exome sequencing incompletely captures the spectrum of pathogenic variation, leaving a substantial proportion of cases undiagnosed. We evaluated the utility of upfront whole genome and transcriptome sequencing (WGTS) in 237 patients with suspected IBMFS using non-hematopoietic DNA. Median age was 29 years (range 3 months-76 years) and 34.6% were under 18 years. Clinically-accredited sequencing was performed with real-time return of results to guide patient management and familial testing. A molecular diagnosis was established in 87/237 patients (36.7%), spanning hereditary thrombocytopenia, telomere biology disorders, Diamond-Blackfan anemia, severe congenital neutropenia, Shwachman-Diamond syndrome, Fanconi anemia and other IBMFS. A further four patients were diagnosed with non-hematological genetic conditions and seven patients with secondary actionable findings. Novel pathogenic mechanisms including retrotransposon-mediated gene disruption were identified. Further, novel associations with primary IBMFS-like presentations (THRA) as well as definitive evidence of gene-disease associations (MEIS1, TUBB) were established. Acceptability of WGTS based on the established Theoretical Framework of Acceptability was high among patients and carers. Upfront WGTS in suspected IBMFS provides a high diagnostic yield when compared with other genomic approaches, identifies actionable genomic abnormalities, and expands the spectrum of disease mechanisms and gene associations in IBMFS.

Definitive hematopoietic stem cells (HSCs) arise in the dorsal aorta of the developing mammalian embryo by a process of endothelial-to-hematopoietic transition. A deep understanding of the precise number, location, and timing of HSC emergence in vivo is required to inform on signals that control definitive HSC production for therapeutical purposes. Current methods to image and quantify intra-aortic clusters in situ require extensive manual counting and a high spatio-temporal resolution reference map of this process in the mouse embryo is still missing. Using whole-mount immunofluorescence, tissue clearing, confocal and light-sheet microscopy, followed by machine learning analysis, we have developed an imaging pipeline for the segmentation and quantification of CD31+cKit+Runx1+ HSC precursors. We apply this pipeline to mouse embryos covering every 2 somites between E9.0 and E12.5 to generate the most comprehensive atlas of emerging hematopoietic stem cells across time and space. This resource provides an excellent benchmark to which future genetic and environmental manipulations affecting hematopoietic stem cell development can be compared and can further be overlayed on spatial gene expression maps to identify novel regulators of endothelial-to-hematopoietic transition.

We examine how social information about competition choices influences individuals' willingness to compete. Participants perform a real-effort task under both piece-rate and tournament incentives, and subsequently make competition choices in two rounds. Between rounds, we exogenously vary the information provided about others' choices across three treatments. We find that social information about the proportion of participants who chose to compete in the first round significantly affects the willingness to compete in the second round. This effect is not driven by the salience of the incentive schemes. Observing a lower rate of competition among peers increases an individual's propensity to enter the tournament. This evidence is consistent with predictions from a rational model of Bayesian learning, in which individuals strategically choose to compete based on their treatment-induced belief about the average ability of other participants.