Reasons to Conserve Nature Pearson, Richard G.
Trends in ecology & evolution,
20/May , Letnik:
31, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Is it sufficient to base arguments for conservation on the intrinsic value of nature, regardless of the services and economic benefits that biodiversity provides for humans? This question underlies ...much recent debate that has been at times acrimonious and has led to calls for a more inclusive approach to conservation. Yet melding different ideologies within a unified conceptual framework has proven difficult. Here I describe an approach that recognizes the importance of the level of biological organization and spatial extent in determining the strength of alternative arguments for why we should conserve nature. I argue that the framework helps reconcile contrasting viewpoints and brings clarity to when different conservation management approaches (for instance, regulation versus monetary valuation) are most appropriate.
A framework is presented that can help unify diverse reasons for conserving nature.
Recognizing the utilitarian value of nature does not deny its intrinsic value.
Reconciling different viewpoints will result in better conservation practice.
β-hemoglobinopathies such as sickle cell disease (SCD) and β-thalassemia result from mutations in the adult HBB (β-globin) gene. Reactivating the developmentally silenced fetal HBG1 and HBG2 ...(γ-globin) genes is a therapeutic goal for treating SCD and β-thalassemia
. Some forms of hereditary persistence of fetal hemoglobin (HPFH), a rare benign condition in which individuals express the γ-globin gene throughout adulthood, are caused by point mutations in the γ-globin gene promoter at regions residing ~115 and 200 bp upstream of the transcription start site. We found that the major fetal globin gene repressors BCL11A and ZBTB7A (also known as LRF) directly bound to the sites at -115 and -200 bp, respectively. Furthermore, introduction of naturally occurring HPFH-associated mutations into erythroid cells by CRISPR-Cas9 disrupted repressor binding and raised γ-globin gene expression. These findings clarify how these HPFH-associated mutations operate and demonstrate that BCL11A and ZBTB7A are major direct repressors of the fetal globin gene.
Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. Here, we identify the developmental transcription factor
Grhl3 as a potent tumor suppressor of ...SCC in mice, and demonstrate that targeting of
Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Deletion of
Grhl3 in adult epidermis evokes loss of expression of PTEN, a direct GRHL3 target, resulting in aggressive SCC induced by activation of PI3K/AKT/mTOR signaling. Restoration of
Pten expression completely abrogates SCC formation. Reduced levels of
GRHL3 and
PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data define the
GRHL3-PTEN axis as a critical tumor suppressor pathway in SCC.
► Grhl3 is a potent tumor suppressor of SCC in humans and mice ► Pten is the downstream effector of Grhl3 tumor suppressor activity ► A miR-21 proto-oncogenic network synchronously targets Grhl3 and Pten ► Grhl3/PTEN-deficient SCC displays an oncogene addiction to PI3K/AKT signaling
Animal populations have undergone substantial declines in recent decades. These declines have occurred alongside rapid, human‐driven environmental change, including climate warming. An association ...between population declines and environmental change is well established, yet there has been relatively little analysis of the importance of the rates of climate warming and its interaction with conversion to anthropogenic land use in causing population declines. Here we present a global assessment of the impact of rapid climate warming and anthropogenic land use conversion on 987 populations of 481 species of terrestrial birds and mammals since 1950. We collated spatially referenced population trends of at least 5 years’ duration from the Living Planet database and used mixed effects models to assess the association of these trends with observed rates of climate warming, rates of conversion to anthropogenic land use, body mass, and protected area coverage. We found that declines in population abundance for both birds and mammals are greater in areas where mean temperature has increased more rapidly, and that this effect is more pronounced for birds. However, we do not find a strong effect of conversion to anthropogenic land use, body mass, or protected area coverage. Our results identify a link between rapid warming and population declines, thus supporting the notion that rapid climate warming is a global threat to biodiversity.
Animal populations have undergone substantial declines in recent decades. These declines have occurred alongside rapid, human‐driven environmental change, including climate warming. Here we present a global assessment of the impact of rapid climate warming and anthropogenic land conversion on 987 populations of 481 species of terrestrial birds and mammals since 1950. We found that declines in population abundance for both birds and mammals are greater in areas where mean temperature has increased more rapidly. Our results identify a link between rapid warming and population declines, thus supporting the notion that rapid climate warming is a global threat to biodiversity.
Increased transcription of ribosomal RNA genes (rDNA) by RNA Polymerase I is a common feature of human cancer, but whether it is required for the malignant phenotype remains unclear. We show that ...rDNA transcription can be therapeutically targeted with the small molecule CX-5461 to selectively kill B-lymphoma cells in vivo while maintaining a viable wild-type B cell population. The therapeutic effect is a consequence of nucleolar disruption and activation of p53-dependent apoptotic signaling. Human leukemia and lymphoma cell lines also show high sensitivity to inhibition of rDNA transcription that is dependent on p53 mutational status. These results identify selective inhibition of rDNA transcription as a therapeutic strategy for the cancer specific activation of p53 and treatment of hematologic malignancies.
► Hematologic cancer cell survival is dependent on activated Pol I transcription ► CX-5461, a selective inhibitor of Pol I, treats hematologic cancers in mice ► CX-5461 selectively kills tumor cells by activating p53-dependent apoptosis ► CX-5461 shows potent antiproliferative capacity in human hematologic tumor cells
The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there ...is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants' genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites' drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance.
The aim of this review is to mark the 75th anniversary of the introduction of the original corneal contact lens of Tuohy in 1948.
American documents in the public domain, such as census records and ...draft registration cards, were consulted in order to provide a more comprehensive biography of Kevin M Tuohy, inventor of the corneal contact lens, than those previously published.
Perhaps due to a failure to consult original sources concerning the Tuohy corneal lens, some historical accounts have provided incomplete or incorrect information about its design and dimensions. The back surface specification of the bi-curve Tuohy lens in its standard diameter of 11.50 mm has been tabulated and edge lift and edge clearance values calculated. A colour photograph illustrates the fluorescein pattern of a Tuohy lens.
Patients wearing Tuohy lenses were able to achieve a much longer wearing time compared to those wearing sealed scleral lenses since they eliminated corneal epithelial oedema, a frequent problem which necessitated removal of lenses after a few hours of wear due to cloudy vision. Only some of Tuohy lens wearers exhibited an adverse corneal response such as fluorescein staining after 12, or more, hours of wear.
The clinical success of the Tuohy lens and the fact that its fitting procedure was simpler and quicker than that for scleral lenses encouraged optometrists to commence contact lens practice and to implement improvements in the design of the corneal lens.
Summary Background As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong subregion, emerging resistance to partner drugs in artemisinin combination ...therapies seriously threatens global efforts to treat and eliminate this disease. Molecular markers that predict failure of artemisinin combination therapy are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in southeast Asia and beyond. Methods We did a genome-wide association study of 297 P falciparum isolates from Cambodia to investigate the relationship of 11 630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC50 s), and tested whether these genetic variants are markers of treatment failure with dihydroartemisinin–piperaquine. We then did a survival analysis of 133 patients to determine whether candidate molecular markers predicted parasite recrudescence following dihydroartemisinin–piperaquine treatment. Findings Piperaquine IC50 s increased significantly from 2011 to 2013 in three Cambodian provinces (2011 vs 2013 median IC50 s: 20·0 nmol/L IQR 13·7–29·0 vs 39·2 nmol/L 32·8–48·1 for Ratanakiri, 19·3 nmol/L 15·1–26·2 vs 66·2 nmol/L 49·9–83·0 for Preah Vihear, and 19·6 nmol/L 11·9–33·9 vs 81·1 nmol/L 61·3–113·1 for Pursat; all p≤10−3 ; Kruskal-Wallis test). Genome-wide analysis of SNPs identified a chromosome 13 region that associates with raised piperaquine IC50 s. A non-synonymous SNP (encoding a Glu415Gly substitution) in this region, within a gene encoding an exonuclease, associates with parasite recrudescence following dihydroartemisinin–piperaquine treatment. Genome-wide analysis of CNVs revealed that a single copy of the mdr1 gene on chromosome 5 and a novel amplification of the plasmepsin 2 and plasmepsin 3 genes on chromosome 14 also associate with raised piperaquine IC50 s. After adjusting for covariates, both exo-E415G and plasmepsin 2–3 markers significantly associate (p=3·0 × 10−8 and p=1·7 × 10−7 , respectively) with decreased treatment efficacy (survival rates 0·38 95% CI 0·25–0·51 and 0·41 0·28–0·53, respectively). Interpretation The exo-E415G SNP and plasmepsin 2–3 amplification are markers of piperaquine resistance and dihydroartemisinin–piperaquine failures in Cambodia, and can help monitor the spread of these phenotypes into other countries of the Greater Mekong subregion, and elucidate the mechanism of piperaquine resistance. Since plasmepsins are involved in the parasite’s haemoglobin-to-haemozoin conversion pathway, targeted by related antimalarials, plasmepsin 2–3 amplification probably mediates piperaquine resistance. Funding Intramural Research Program of the US National Institute of Allergy and Infectious Diseases, National Institutes of Health, Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, and UK Department for International Development.
Ribosome biogenesis and protein synthesis are fundamental rate-limiting steps for cell growth and proliferation. The ribosomal proteins (RPs), comprising the structural parts of the ribosome, are ...essential for ribosome assembly and function. In addition to their canonical ribosomal functions, multiple RPs have extra-ribosomal functions including activation of p53-dependent or p53-independent pathways in response to stress, resulting in cell cycle arrest and apoptosis. Defects in ribosome biogenesis, translation, and the functions of individual RPs, including mutations in RPs have been linked to a diverse range of human congenital disorders termed ribosomopathies. Ribosomopathies are characterized by tissue-specific phenotypic abnormalities and higher cancer risk later in life. Recent discoveries of somatic mutations in RPs in multiple tumor types reinforce the connections between ribosomal defects and cancer. In this article, we review the most recent advances in understanding the molecular consequences of RP mutations and ribosomal defects in ribosomopathies and cancer. We particularly discuss the molecular basis of the transition from hypo- to hyper-proliferation in ribosomopathies with elevated cancer risk, a paradox termed "Dameshek's riddle." Furthermore, we review the current treatments for ribosomopathies and prospective therapies targeting ribosomal defects. We also highlight recent advances in ribosome stress-based cancer therapeutics. Importantly, insights into the mechanisms of resistance to therapies targeting ribosome biogenesis bring new perspectives into the molecular basis of cancer susceptibility in ribosomopathies and new clinical implications for cancer therapy.
Antimalarial resistance is rapidly spreading across parts of southeast Asia where dihydroartemisinin–piperaquine is used as first-line treatment for Plasmodium falciparum malaria. The first published ...reports about resistance to antimalarial drugs came from western Cambodia in 2013. Here, we analyse genetic changes in the P falciparum population of western Cambodia in the 6 years before those reports.
We analysed genome sequence data on 1492 P falciparum samples from 11 locations across southeast Asia, including 464 samples collected in western Cambodia between 2007 and 2013. Different epidemiological origins of resistance were identified by haplotypic analysis of the kelch13 artemisinin resistance locus and the plasmepsin 2–3 piperaquine resistance locus.
We identified more than 30 independent origins of artemisinin resistance, of which the KEL1 lineage accounted for 140 (91%) of 154 parasites resistant to dihydroartemisinin–piperaquine. In 2008, KEL1 combined with PLA1, the major lineage associated with piperaquine resistance. By 2013, the KEL1/PLA1 co-lineage had reached a frequency of 63% (24/38) in western Cambodia and had spread to northern Cambodia.
The KEL1/PLA1 co-lineage emerged in the same year that dihydroartemisinin–piperaquine became the first-line antimalarial drug in western Cambodia and spread rapidly thereafter, displacing other artemisinin-resistant parasite lineages. These findings have important implications for management of the global health risk associated with the current outbreak of multidrug-resistant malaria in southeast Asia.
Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, UK Department for International Development, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases.
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