Immunity to self co-generates regulatory T cells

Immune responses to self are kept in check by tolerance mechanisms, including suppression by regulatory T cells (Tregs). The defective generation of Tregs specific for self-antigens may lead to autoimmune disease. We identified a novel population of human CD4^+^ Tregs, characterized by high surface expression of CD52, which is co-generated in response to autoantigen. Blood CD4^+^CD52^hi^ T cells were generated preferentially in response to low-dose autoantigen and suppressed proliferation and interferon-[gamma] production by other T cells. Depletion of resting CD4^+^CD52^hi^ T cells enhanced the T-cell response to autoantigen. CD4^+^CD52^hi^ Tregs were neither derived from nor distinguished by markers of conventional resting CD4^+^CD25^+^ Tregs. In response to the pancreatic islet autoantigens glutamic acid decarboxylase, the generation of CD4^+^CD52^hi^ Tregs was impaired in individuals with and at-risk for type 1 diabetes, compared to healthy controls and individuals with type 2 diabetes. CD4^+^CD52^hi^ Tregs co-generated to self-antigen may therefore contribute to immune homeostasis and protect against autoimmune disease

A photographic essay on landslides across southeastern New South Wales triggered by the rainfall events of 2022

Eastern Australia has experienced a significant magnitude rainfall event of extended duration in the first 7 months of 2022. Across the east coast of New South Wales (NSW) a series of troughs and East Coast Lows occurred during a La Nina weather cycle bringing above average rainfall to the region. As this first half of 2022 La Nina event was drawing to a close the Indian Ocean Dipole entered a negative phase which coincided with another intense East Coast Low in early July 2022 impacting the Illawarra region of NSW. These events caused widespread flooding and significant landslide damage to road and rail infrastructure across the state networks and local government infrastructure across NSW. During this extended wet period in the first 7 months of 2022 more than 200 landslides have been recorded across the Illawarra, Southern Highlands and Blue Mountains regions of NSW whilst many more have occurred across the north coast region. This paper presents a brief and albeit preliminary summary of the rainfall and provides a series of photographs with very brief descriptions of some of these landslide events within southeastern NSW. The intent of the paper is to provide early guidance to AGS members of the nature and form of landslides that have occurred across the Illawarra region. This paper does not discuss the dual fatality resulting from the Wentworth Falls area rockfall of the 5th April

Reinvestigation of the Saccharomyces cerevisiae genome annotation by comparison to the genome of a related fungus: Ashbya gossypii

BACKGROUND: The recently sequenced genome of the filamentous fungus Ashbya gossypii revealed remarkable similarities to that of the budding yeast Saccharomyces cerevisiae both at the level of homology and synteny (conservation of gene order). Thus, it became possible to reinvestigate the S. cerevisiae genome in the syntenic regions leading to an improved annotation. RESULTS: We have identified 23 novel S. cerevisiae open reading frames (ORFs) as syntenic homologs of A. gossypii genes; for all but one, homologs are present in other eukaryotes including humans. Other comparisons identified 13 overlooked introns and suggested 69 potential sequence corrections resulting in ORF extensions or ORF fusions with improved homology to the syntenic A. gossypii homologs. Of the proposed corrections, 25 were tested and confirmed by resequencing. In addition, homologs of nearly 1,000 S. cerevisiae ORFs, presently annotated as hypothetical, were found in A. gossypii at syntenic positions and can therefore be considered as authentic genes. Finally, we suggest that over 400 S. cerevisiae ORFs that overlap other ORFs in S. cerevisiae and for which no homolog can be detected in A. gossypii should be regarded as spurious. CONCLUSIONS: Although, the S. cerevisiae genome is rightly considered as one of the most accurately sequenced and annotated eukaryotic genomes, we have shown that it still benefits substantially from comparison to the completed sequence and syntenic gene map of A. gossypii, an evolutionarily related fungus. This type of approach will strongly support the annotation of more complex genomes such as the human and murine genomes

A MYC-ZNF148-ID1/3 regulatory axis modulating cancer stem cell traits in aggressive breast cancer

The MYC proto-oncogene (MYC) is one of the most frequently overexpressed genes in breast cancer that drives cancer stem cell-like traits, resulting in aggressive disease progression and poor prognosis. In this study, we identified zinc finger transcription factor 148 (ZNF148, also called Zfp148 and ZBP-89) as a direct target of MYC. ZNF148 suppressed cell proliferation and migration and was transcriptionally repressed by MYC in breast cancer. Depletion of ZNF148 by short hairpin RNA (shRNA) and CRISPR/Cas9 increased triple-negative breast cancer (TNBC) cell proliferation and migration. Global transcriptome and chromatin occupancy analyses of ZNF148 revealed a central role in inhibiting cancer cell de-differentiation and migration. Mechanistically, we identified the Inhibitor of DNA binding 1 and 3 (ID1, ID3), drivers of cancer stemness and plasticity, as previously uncharacterized targets of transcriptional repression by ZNF148. Silencing of ZNF148 increased the stemness and tumorigenicity in TNBC cells. These findings uncover a previously unknown tumor suppressor role for ZNF148, and a transcriptional regulatory circuitry encompassing MYC, ZNF148, and ID1/3 in driving cancer stem cell traits in aggressive breast cancer

Conservation status of Brachycephalus toadlets (Anura Brachycephalidae) from the Brazilian Atlantic rainforest.

Made available in DSpace on 2019-10-06T15:56:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-09-01The number of described anurans has increased continuously, with many newly described species determined to be at risk. Most of these new species inhabit hotspots and are under threat of habitat loss, such as Brachycephalus, a genus of small toadlets that inhabits the litter of the Brazilian Atlantic Rainforest. Of 36 known species, 22 were described in the last decade, but only 11 have been assessed according to the IUCN Red List categories, with just one currently listed as Critically Endangered. All available data on occurrence, distribution, density, and threats to Brachycephalus were reviewed. The species extent of occurrence was estimated using the Minimum Convex Polygon method for species with three or more records and by delimiting continuous areas within the altitudinal range of species with up to two records. These data were integrated to assess the conservation status according to the IUCN criteria. Six species have been evaluated as Critically Endangered, five as Endangered, 10 as Vulnerable, five as Least Concern, and 10 as Data Deficient. Deforestation was the most common threat to imperiled Brachycephalus species. The official recognition of these categories might be more readily adopted if the microendemic nature of their geographical distribution is taken into account.Instituto de Biociências Universidade Estadual Paulista (UNESP), Praça Infante Dom Henrique s/noMater Natura-Instituto de Estudos Ambientais, Rua Lamenha Lins 1080Departamento de Zoologia Universidade Federal do ParanáInstituto de Biociências Universidade Estadual Paulista (UNESP), Praça Infante Dom Henrique s/n

The BINGO Project IV: Simulations for mission performance assessment and preliminary component separation steps

The large-scale distribution of neutral hydrogen (HI) in the Universe is luminous through its 21 cm emission. The goal of the Baryon Acoustic Oscillations from Integrated Neutral Gas Observations -- BINGO -- radio telescope is to detect baryon acoustic oscillations (BAOs) at radio frequencies through 21 cm intensity mapping (IM). The telescope will span the redshift range 0.127 $< z <$ 0.449 with an instantaneous field-of-view of $14.75^{\circ} \times 6.0^{\circ}$. In this work we investigate different constructive and operational scenarios of the instrument by generating sky maps as they would be produced by the instrument. In doing this we use a set of end-to-end IM mission simulations. The maps will additionally be used to evaluate the efficiency of a component separation method (GNILC). We have simulated the kind of data that would be produced in a single-dish IM experiment such as BINGO. According to the results obtained, we have optimized the focal plane design of the telescope. In addition, the application of the GNILC method on simulated data shows that it is feasible to extract the cosmological signal across a wide range of multipoles and redshifts. The results are comparable with the standard principal component analysis method.Comment: 16 pages. Version to appear in A&

Improving Social Justice in COVID-19 Health Research: Interim guidelines for reporting health equity in observational studies

The COVID-19 pandemic has highlighted the global imperative to address health inequities. Observational studies are a valuable source of evidence for real-world effects and impacts of implementing COVID-19 policies on the redistribution of inequities. We assembled a diverse global multi-disciplinary team to develop interim guidance for improving transparency in reporting health equity in COVID-19 observational studies. We identified 14 areas in the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist that need additional detail to encourage transparent reporting of health equity. We searched for examples of COVID-19 observational studies that analysed and reported health equity analysis across one or more social determinants of health. We engaged with Indigenous stakeholders and others groups experiencing health inequities to co-produce this guidance and to bring an intersectional lens. Taking health equity and social determinants of health into account contributes to the clinical and epidemiological understanding of the disease, identifying specific needs and supporting decision-making processes. Stakeholders are encouraged to consider using this guidance on observational research to help provide evidence to close the inequitable gaps in health outcomes

(Not) being at home: Hsu Ming Teo's Behind the Moon (2005) and Michelle de Kretser's Questions of Travel (2012)

This article examines some interventions of Asian Australian writing into the debate over multiculturalism, and the shift from negative stereotyping of Asian migrants, to reification of racial divisions and propagation of a masked racism, to the creation of new alignments and the revival of pre-existing affiliations by migrant and second generation subjects. It compares the practices of not-at-homeness by Asian migrants and their descendants and white Australians in Hsu Ming Teo’s Behind the Moon with those of a Sri Lankan refugee and a white Australian traveller in Michelle de Kretser’s Questions of Travel. The changing concepts of belonging in the novels show a realignment of core and periphery relations within the nation state under the pressures of multiculturalism and globalization: where home is and how it is configured are questions as important for white Australians whose sense of territory is challenged as they are for Asian migrants who seek to establish a new belonging

Socio-economic impact of ecological agriculture at the territorial level

This deliverable investigates the socio-economic effects of ecological approaches to farming through implementing two participatory approaches, namely Delphi exercise and Q-method, at the level of a case study area (CSA). The focus is on how people and other productive assets are employed and remunerated by ecological approaches to agriculture, particularly those aspects that can influence employment, and drive the prosperity and vitality of local communities and some rural businesses. It is based on the collaborative research on Task 4.2 ‘Socio-economic impact of ecological agriculture at the territorial level’ of the LIFT project between UNIKENT (United Kingdom-UK) (Task Leader), BOKU (Austria), INRAE (France), VetAgro Sup (France), DEMETER (Greece), MTA KRTK (Hungary), UNIBO (Italy), IRWiR PAN (Poland), IAE-AR (Romania), SLU (Sweden), SRUC (UK). Beginning with the Delphi exercise, this deliverable presents qualitative information extracted from stakeholders in the following four steps. First, the researchers build a presentation of differences between ecological and conventional farming approaches in each CSA. Second, stakeholders elaborate on how they understand ecological farming approaches to exist in each CSA. Third, stakeholders develop a scenario of adoption of ecological approaches to farming depending on two factors: pattern (ecological farms forming clusters or randomly spread within the territory) and rate of adoption 10 years in the future. After establishing this scenario across two rounds, the stakeholders explore the socio-economic effects of their adoption scenario. The Q-methodology then presents a Q-set of statements that the Delphi has developed and, through factor analysis,studies the key stakeholder perspectives of the socio-economic effects of the perceived adoption of ecological practices in 10 years in the future. Four key results can be derived from the Delphi exercise and the Q-methodology. First, a higher adoption of ecological farming approaches, especially so at a 50% adoption rate, is mostly thought by stakeholders in the Delphi Exercise to lead to an increase in skill level and quality of life in on-farm employment. This is as a result of an increased diversity of farming enterprises on farms using ecological farming approaches, the interest generated from this, the knowledge of natural processes and biology required, engagement with nature and change in machinery that is coming into the industry. Strongly related to this need for skills is a predicted increase in the number of advisers and civil servants to deal with more complicated farms and incentives as well as monitoring of ecological effects on farm. An increase in required skill level is repeated across all Q-studies. Second, especially where farms are clustered together, Delphi Exercise respondents predict an increase in the trade of inputs such as manure and compost replacing synthetic fertiliser, as well as more sharing of capital and labour. Q-methodology highlights that these clusters may support a stronger social movement, more consumers buying local food and increase collaboration between farmers. Supply chains are expected to become shorter as farmers sell more directly and there are fewer intermediaries upstream of the farming sector. As farmers collaborate more with each other on environmental objectives, trading inputs and sharing best practices, farmer relationships should improve in rural communities. Third, Delphi exercise finds that contracting, machinery purchasers, and machinery traders and dealers could increase, decrease or display no change – the anticipated effects are mixed. Stakeholders are in no doubt that machinery use will change and therefore new skills will need to be learnt, but the wider effect on machinery purchase is uncertain. However, stakeholders conclude that a greater specialisation in machinery will occur leading to changes in farm management as well as the suppliers of this machinery. Q-methodology highlights that ecological practices will not mean the end of machinery and a lot more labour – often machinery will be useful in weeding and reducing physical labour as technology has significantly improved and skills are improving too in order to use these technologies. Fourth, Delphi respondents argued that although rural populations might be little affected by ecological farming, a shift in people moving from urban to rural settlements, and thereby a higher rural population density, seeking a more attractive rural environment, might contribute to higher local consumer demand. The Q-methodology highlights that where there is high adoption, rural areas are expected to become more attractive, as landscapes will have a much greater variety of crops instead of fields of monocrops. This variety of crops may include agroforestry (farmers interested in ecological approaches to farming may also be interested in agroforestry as a way of boosting their yields and protecting crops and livestock from the elements) as well as intercropping

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy