Displaying publications 1 - 20 of 107 in total

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  1. Xiao L, Parolia A, Qiao Y, Bawa P, Eyunni S, Mannan R, et al.
    Nature, 2022 Jan;601(7893):434-439.
    PMID: 34937944 DOI: 10.1038/s41586-021-04246-z
    The switch/sucrose non-fermentable (SWI/SNF) complex has a crucial role in chromatin remodelling1 and is altered in over 20% of cancers2,3. Here we developed a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4, called AU-15330. Androgen receptor (AR)+ forkhead box A1 (FOXA1)+ prostate cancer cells are exquisitely sensitive to dual SMARCA2 and SMARCA4 degradation relative to normal and other cancer cell lines. SWI/SNF ATPase degradation rapidly compacts cis-regulatory elements bound by transcription factors that drive prostate cancer cell proliferation, namely AR, FOXA1, ERG and MYC, which dislodges them from chromatin, disables their core enhancer circuitry, and abolishes the downstream oncogenic gene programs. SWI/SNF ATPase degradation also disrupts super-enhancer and promoter looping interactions that wire supra-physiologic expression of the AR, FOXA1 and MYC oncogenes themselves. AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide, even inducing disease remission in castration-resistant prostate cancer (CRPC) models without toxicity. Thus, impeding SWI/SNF-mediated enhancer accessibility represents a promising therapeutic approach for enhancer-addicted cancers.
  2. Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou JJ, et al.
    Nature, 2020 07;583(7815):286-289.
    PMID: 32380510 DOI: 10.1038/s41586-020-2313-x
    The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.
  3. Wijedasa LS, Posa MR, Clements GR
    Nature, 2015 Nov 19;527(7578):305.
    PMID: 26581283 DOI: 10.1038/527305b
  4. Watson M
    Nature, 1923;112:470-471.
    BEFORE Sir Ronald Ross's epoch-making discovery, there was no more puzzling problem in medicine than the cause of malaria; no secret in Nature more cunningly hid than the malaria secret. Malaria was known to be connected with swamps, and to be reduced by drainage and cultivation. Yet, as if merely to confuse, men found that to flood some swamps actually improved health; and elsewhere that drainage and the cultivation of the soil produced the most serious and devastating outbursts of the disease. Yet again, malaria was found not only in swamps, but also often on hills and dry sandy deserts. Some jungle-covered land was singularly free from malaria: other jungle land was intensely malarial. In fact, malaria existed on soils of every conceivable variety, of every age in geological time. It was-impossible to point to any mineral, chemical, or vegetable condition essential to its presence. It was, and had been for hundreds of years, a dark, inscrutable mystery.
  5. Walton HJ
    Nature, 1922;109:334-335.
    DR. WATSON'S book shows clearly the wide range of scientific knowledge which is required by those who work in the tropics either as physicians or as sanitarians. It is unnecessary nowadays to insist upon the importance of the control of malaria in the development of those vast areas from which is derived so much of the food supplies and raw materials of manufacture of all civilised countries, but only those who have had practical experience of the methods used to deal with the disease can appreciate how many and how varied these must be.
  6. WHARTON RH
    Nature, 1951 May 26;167(4256):854-5.
    PMID: 14833440
  7. Volkov I, Banavar JR, He F, Hubbell SP, Maritan A
    Nature, 2005 Dec 1;438(7068):658-61.
    PMID: 16319890
    The recurrent patterns in the commonness and rarity of species in ecological communities--the relative species abundance--have puzzled ecologists for more than half a century. Here we show that the framework of the current neutral theory in ecology can easily be generalized to incorporate symmetric density dependence. We can calculate precisely the strength of the rare-species advantage that is needed to explain a given RSA distribution. Previously, we demonstrated that a mechanism of dispersal limitation also fits RSA data well. Here we compare fits of the dispersal and density-dependence mechanisms for empirical RSA data on tree species in six New and Old World tropical forests and show that both mechanisms offer sufficient and independent explanations. We suggest that RSA data cannot by themselves be used to discriminate among these explanations of RSA patterns--empirical studies will be required to determine whether RSA patterns are due to one or the other mechanism, or to some combination of both.
  8. VELLA F, TAVARIA D
    Nature, 1961 May 20;190:729-30.
    PMID: 13780662
  9. Usinowicz J, Chang-Yang CH, Chen YY, Clark JS, Fletcher C, Garwood NC, et al.
    Nature, 2017 10 05;550(7674):105-108.
    PMID: 28953870 DOI: 10.1038/nature24038
    The tropical forests of Borneo and Amazonia may each contain more tree species diversity in half a square kilometre than do all the temperate forests of Europe, North America, and Asia combined. Biologists have long been fascinated by this disparity, using it to investigate potential drivers of biodiversity. Latitudinal variation in many of these drivers is expected to create geographic differences in ecological and evolutionary processes, and evidence increasingly shows that tropical ecosystems have higher rates of diversification, clade origination, and clade dispersal. However, there is currently no evidence to link gradients in ecological processes within communities at a local scale directly to the geographic gradient in biodiversity. Here, we show geographic variation in the storage effect, an ecological mechanism that reduces the potential for competitive exclusion more strongly in the tropics than it does in temperate and boreal zones, decreasing the ratio of interspecific-to-intraspecific competition by 0.25% for each degree of latitude that an ecosystem is located closer to the Equator. Additionally, we find evidence that latitudinal variation in climate underpins these differences; longer growing seasons in the tropics reduce constraints on the seasonal timing of reproduction, permitting lower recruitment synchrony between species and thereby enhancing niche partitioning through the storage effect. Our results demonstrate that the strength of the storage effect, and therefore its impact on diversity within communities, varies latitudinally in association with climate. This finding highlights the importance of biotic interactions in shaping geographic diversity patterns, and emphasizes the need to understand the mechanisms underpinning ecological processes in greater detail than has previously been appreciated.
  10. Tan DS, Smith CE, McMahon DA, Bowen ET
    Nature, 1967 Jun 10;214(5093):1154-5.
    PMID: 4964058
  11. Swinbanks D
    Nature, 1997 Sep 25;389(6649):321.
    PMID: 9311764
  12. Stephenson NL, Das AJ, Condit R, Russo SE, Baker PJ, Beckman NG, et al.
    Nature, 2014 Mar 6;507(7490):90-3.
    PMID: 24429523 DOI: 10.1038/nature12914
    Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.
  13. Snaddon JL, Willis KJ, Macdonald DW
    Nature, 2013 Oct 10;502(7470):170-1.
    PMID: 24108039 DOI: 10.1038/502170d
  14. Singh R, Ong-Abdullah M, Low ET, Manaf MA, Rosli R, Nookiah R, et al.
    Nature, 2013 Aug 15;500(7462):335-9.
    PMID: 23883927 DOI: 10.1038/nature12309
    Oil palm is the most productive oil-bearing crop. Although it is planted on only 5% of the total world vegetable oil acreage, palm oil accounts for 33% of vegetable oil and 45% of edible oil worldwide, but increased cultivation competes with dwindling rainforest reserves. We report the 1.8-gigabase (Gb) genome sequence of the African oil palm Elaeis guineensis, the predominant source of worldwide oil production. A total of 1.535 Gb of assembled sequence and transcriptome data from 30 tissue types were used to predict at least 34,802 genes, including oil biosynthesis genes and homologues of WRINKLED1 (WRI1), and other transcriptional regulators, which are highly expressed in the kernel. We also report the draft sequence of the South American oil palm Elaeis oleifera, which has the same number of chromosomes (2n = 32) and produces fertile interspecific hybrids with E. guineensis but seems to have diverged in the New World. Segmental duplications of chromosome arms define the palaeotetraploid origin of palm trees. The oil palm sequence enables the discovery of genes for important traits as well as somaclonal epigenetic alterations that restrict the use of clones in commercial plantings, and should therefore help to achieve sustainability for biofuels and edible oils, reducing the rainforest footprint of this tropical plantation crop.
  15. Singh R, Low ET, Ooi LC, Ong-Abdullah M, Ting NC, Nagappan J, et al.
    Nature, 2013 Aug 15;500(7462):340-4.
    PMID: 23883930 DOI: 10.1038/nature12356
    A key event in the domestication and breeding of the oil palm Elaeis guineensis was loss of the thick coconut-like shell surrounding the kernel. Modern E. guineensis has three fruit forms, dura (thick-shelled), pisifera (shell-less) and tenera (thin-shelled), a hybrid between dura and pisifera. The pisifera palm is usually female-sterile. The tenera palm yields far more oil than dura, and is the basis for commercial palm oil production in all of southeast Asia. Here we describe the mapping and identification of the SHELL gene responsible for the different fruit forms. Using homozygosity mapping by sequencing, we found two independent mutations in the DNA-binding domain of a homologue of the MADS-box gene SEEDSTICK (STK, also known as AGAMOUS-LIKE 11), which controls ovule identity and seed development in Arabidopsis. The SHELL gene is responsible for the tenera phenotype in both cultivated and wild palms from sub-Saharan Africa, and our findings provide a genetic explanation for the single gene hybrid vigour (or heterosis) attributed to SHELL, via heterodimerization. This gene mutation explains the single most important economic trait in oil palm, and has implications for the competing interests of global edible oil production, biofuels and rainforest conservation.
  16. Seibold S, Rammer W, Hothorn T, Seidl R, Ulyshen MD, Lorz J, et al.
    Nature, 2021 Sep;597(7874):77-81.
    PMID: 34471275 DOI: 10.1038/s41586-021-03740-8
    The amount of carbon stored in deadwood is equivalent to about 8 per cent of the global forest carbon stocks1. The decomposition of deadwood is largely governed by climate2-5 with decomposer groups-such as microorganisms and insects-contributing to variations in the decomposition rates2,6,7. At the global scale, the contribution of insects to the decomposition of deadwood and carbon release remains poorly understood7. Here we present a field experiment of wood decomposition across 55 forest sites and 6 continents. We find that the deadwood decomposition rates increase with temperature, and the strongest temperature effect is found at high precipitation levels. Precipitation affects the decomposition rates negatively at low temperatures and positively at high temperatures. As a net effect-including the direct consumption by insects and indirect effects through interactions with microorganisms-insects accelerate the decomposition in tropical forests (3.9% median mass loss per year). In temperate and boreal forests, we find weak positive and negative effects with a median mass loss of 0.9 per cent and -0.1 per cent per year, respectively. Furthermore, we apply the experimentally derived decomposition function to a global map of deadwood carbon synthesized from empirical and remote-sensing data, obtaining an estimate of 10.9 ± 3.2 petagram of carbon per year released from deadwood globally, with 93 per cent originating from tropical forests. Globally, the net effect of insects may account for 29 per cent of the carbon flux from deadwood, which suggests a functional importance of insects in the decomposition of deadwood and the carbon cycle.
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