The heat is on: climate change, extreme heat and bushfires in WA

Climate change is increasing the intensity and frequency of heatwaves in Western Australia and driving up the likelihood of very high fire danger weather. Western Australia is experiencing a long-term increase in average temperatures and in 2014 the state recorded its highest ever annual average maximum temperature. The number of heatwave days in Perth has increased by 50% since 1950. Nine of Western Australia’s hottest Januarys on record have occurred in the last 10 years. The number of days per year with severe fire danger weather is projected to almost double in south west Western Australia by 2090 if global carbon emissions are not drastically reduced. Recent fires in Western Australia have been influenced by record hot dry conditions. The long-term trend to hotter weather in Western Australia has worsened fire weather and contributed to an increase in the frequency and severity of bushfires. The concept of a normal bushfire season is rapidly changing as bushfires increase in number, burn for longer and affect larger areas of land. By 2030, the number of professional firefighters in WA will need to more than double to meet the increasing risk of bushfires. 3. The economic, social and environmental costs of increased extreme heat and bushfire activity is likely to be immense. In Perth, from 1994-2006, there were over 20 heat attributable deaths per year. If average maximum temperatures were 2°C warmer, this number would almost double to 40 deaths. Some of Western Australia’s most fire-prone regions may become unlivable as the risks to lives and property caused by bushfires continue to increase. Without effective action on climate change, there will be 20 times the number of dangerous days for outdoor workers by 2070, reducing productivity. 4. Tackling climate change is critical to protecting Western Australia’s prosperity. As a nation we must join the global effort to substantially reduce emissions and rapidly move away from fossil fuels to renewable energy if we are to limit the severity of extreme heat and bushfires both in Western Australia and nationally

Long-term treatment of cancer-prone germline PTEN mutant mice with low-dose rapamycin extends lifespan and delays tumour development

PTEN is one of the most commonly inactivated tumour suppressor genes in sporadic cancer. Germline heterozygous PTEN gene alterations also underlie PTEN hamartoma tumour syndrome (PHTS), a rare human cancer-predisposition condition. A key feature of systemic PTEN deregulation is the inability to adequately dampen PI3-kinase (PI3K)/mTORC1 signalling. PI3K/mTORC1 pathway inhibitors such as rapamycin are therefore expected to neutralise the impact of PTEN loss, rendering this a more druggable context compared with those of other tumour suppressor pathways such as loss of TP53. However, this has not been explored in cancer prevention in a model of germline cancer predisposition, such as PHTS. Clinical trials of short-term treatment with rapamycin have recently been initiated for PHTS, focusing on cognition and colon polyposis. Here, we administered a low dose of rapamycin from the age of 6 weeks onwards to mice with heterozygous germline Pten loss, a mouse model that recapitulates most characteristics of human PHTS. Rapamycin was well tolerated and led to a highly significant improvement of survival in both male and female mice. This was accompanied by a delay in, but not full blockade of, the development of a range of proliferative lesions, including gastro-intestinal and thyroid tumours and endometrial hyperplasia, with no impact on mammary and prostate tumours, and no effect on brain overgrowth. Our data indicate that rapamycin may have cancer prevention potential in human PHTS. This might also be the case for sporadic cancers in which genetic PI3K pathway activation is an early event in tumour development, such as endometrial cancer and some breast cancers. To the best of our knowledge, this is the first report of a long-term treatment of a germline cancer predisposition model with a PI3K/mTOR pathway inhibitor. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Sex, age, deprivation and patterns in life expectancy in Quebec, Canada: a population-based study

<p>Abstract</p> <p>Background</p> <p>Little research has evaluated disparities in life expectancy according to material deprivation taking into account differences across the lifespan between men and women. This study investigated age- and sex-specific life expectancy differentials related to area-level material deprivation for the province of Québec, Canada from 1989-2004.</p> <p>Methods</p> <p>Age- and sex-specific life expectancy across the lifespan was calculated for three periods (1989-1992, 1995-1998, and 2001-2004) for the entire Québec population residing in 162 community groupings ranked according to decile of material deprivation. Absolute and relative measures were calculated to summarize differences between the most and least deprived deciles.</p> <p>Results</p> <p>Life expectancy differentials between the most and least deprived deciles were greatest for men. Over time, male differentials increased for age 20 or more, with little change occurring at younger ages. For women, differentials increased across the lifespan and were comparable to men at advanced ages. Despite gains in life expectancy among men relative to women, differentials between men and women were greater for most deprived relative to least deprived deciles.</p> <p>Conclusions</p> <p>Similar to the US, differentials in life expectancy associated with area-level material deprivation increased steadily in Québec from 1989-2004 for males and females of all ages. Differentials were comparable between men and women at advanced ages. Previous research indicating that life expectancy differentials between most and least deprived areas are greater in men may be due to a focus on younger age groups.</p

FIDEL—a retrovirus-like retrotransposon and its distinct evolutionary histories in the A- and B-genome components of cultivated peanut

In this paper, we describe a Ty3-gypsy retrotransposon from allotetraploid peanut (Arachis hypogaea) and its putative diploid ancestors Arachis duranensis (A-genome) and Arachis ipaënsis (B-genome). The consensus sequence is 11,223 bp. The element, named FIDEL (Fairly long Inter-Dispersed Euchromatic LTR retrotransposon), is more frequent in the A- than in the B-genome, with copy numbers of about 3,000 (±950, A. duranensis), 820 (±480, A. ipaënsis), and 3,900 (±1,500, A. hypogaea) per haploid genome. Phylogenetic analysis of reverse transcriptase sequences showed distinct evolution of FIDEL in the ancestor species. Fluorescent in situ hybridization revealed disperse distribution in euchromatin and absence from centromeres, telomeric regions, and the nucleolar organizer region. Using paired sequences from bacterial artificial chromosomes, we showed that elements appear less likely to insert near conserved ancestral genes than near the fast evolving disease resistance gene homologs. Within the Ty3-gypsy elements, FIDEL is most closely related with the Athila/Calypso group of retrovirus-like retrotransposons. Putative transmembrane domains were identified, supporting the presence of a vestigial envelope gene. The results emphasize the importance of FIDEL in the evolution and divergence of different Arachis genomes and also may serve as an example of the role of retrotransposons in the evolution of legume genomes in general

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Be prepared: climate change, security and Australia&#039;s Defence Force

The Climate Council has brought together climate scientists and defence experts to create a report on climate change, security and what this means for Australia’s Defence Force. Preface The science is in and defence forces are resolute. Climate change will increase sea-level rise, drive up global temperatures and increase the frequency and intensity of extreme weather events. These impacts will limit the availability of food and water, undermine human health and devastate infrastructure and economies. This, in turn, could exacerbate existing tensions, increase societal instability, drive large scale migration and be a trigger for violent conflict. This is why military forces, and the security sector more broadly, are labelling climate change a “threat multiplier”. Extreme weather events have direct implications for military preparedness and the ability of the military to sustain itself, whilst greater instability, conflict and climate-induced migration will shape the types of roles and missions that militaries will conduct in the future. &nbsp