Displaying publications 1 - 20 of 80 in total

Abstract:
Sort:
  1. Clark CJ, Jussim L, Frey K, Stevens ST, Al-Gharbi M, Aquino K, et al.
    Proc Natl Acad Sci U S A, 2023 Nov 28;120(48):e2301642120.
    PMID: 37983511 DOI: 10.1073/pnas.2301642120
    Science is among humanity's greatest achievements, yet scientific censorship is rarely studied empirically. We explore the social, psychological, and institutional causes and consequences of scientific censorship (defined as actions aimed at obstructing particular scientific ideas from reaching an audience for reasons other than low scientific quality). Popular narratives suggest that scientific censorship is driven by authoritarian officials with dark motives, such as dogmatism and intolerance. Our analysis suggests that scientific censorship is often driven by scientists, who are primarily motivated by self-protection, benevolence toward peer scholars, and prosocial concerns for the well-being of human social groups. This perspective helps explain both recent findings on scientific censorship and recent changes to scientific institutions, such as the use of harm-based criteria to evaluate research. We discuss unknowns surrounding the consequences of censorship and provide recommendations for improving transparency and accountability in scientific decision-making to enable the exploration of these unknowns. The benefits of censorship may sometimes outweigh costs. However, until costs and benefits are examined empirically, scholars on opposing sides of ongoing debates are left to quarrel based on competing values, assumptions, and intuitions.
  2. Troell M, Naylor RL, Metian M, Beveridge M, Tyedmers PH, Folke C, et al.
    Proc Natl Acad Sci U S A, 2014 Sep 16;111(37):13257-63.
    PMID: 25136111 DOI: 10.1073/pnas.1404067111
    Aquaculture is the fastest growing food sector and continues to expand alongside terrestrial crop and livestock production. Using portfolio theory as a conceptual framework, we explore how current interconnections between the aquaculture, crop, livestock, and fisheries sectors act as an impediment to, or an opportunity for, enhanced resilience in the global food system given increased resource scarcity and climate change. Aquaculture can potentially enhance resilience through improved resource use efficiencies and increased diversification of farmed species, locales of production, and feeding strategies. However, aquaculture's reliance on terrestrial crops and wild fish for feeds, its dependence on freshwater and land for culture sites, and its broad array of environmental impacts diminishes its ability to add resilience. Feeds for livestock and farmed fish that are fed rely largely on the same crops, although the fraction destined for aquaculture is presently small (∼4%). As demand for high-value fed aquaculture products grows, competition for these crops will also rise, as will the demand for wild fish as feed inputs. Many of these crops and forage fish are also consumed directly by humans and provide essential nutrition for low-income households. Their rising use in aquafeeds has the potential to increase price levels and volatility, worsening food insecurity among the most vulnerable populations. Although the diversification of global food production systems that includes aquaculture offers promise for enhanced resilience, such promise will not be realized if government policies fail to provide adequate incentives for resource efficiency, equity, and environmental protection.
  3. Slik JW, Aiba S, Bastian M, Brearley FQ, Cannon CH, Eichhorn KA, et al.
    Proc Natl Acad Sci U S A, 2011 Jul 26;108(30):12343-7.
    PMID: 21746913 DOI: 10.1073/pnas.1103353108
    The marked biogeographic difference between western (Malay Peninsula and Sumatra) and eastern (Borneo) Sundaland is surprising given the long time that these areas have formed a single landmass. A dispersal barrier in the form of a dry savanna corridor during glacial maxima has been proposed to explain this disparity. However, the short duration of these dry savanna conditions make it an unlikely sole cause for the biogeographic pattern. An additional explanation might be related to the coarse sandy soils of central Sundaland. To test these two nonexclusive hypotheses, we performed a floristic cluster analysis based on 111 tree inventories from Peninsular Malaysia, Sumatra, and Borneo. We then identified the indicator genera for clusters that crossed the central Sundaland biogeographic boundary and those that did not cross and tested whether drought and coarse-soil tolerance of the indicator genera differed between them. We found 11 terminal floristic clusters, 10 occurring in Borneo, 5 in Sumatra, and 3 in Peninsular Malaysia. Indicator taxa of clusters that occurred across Sundaland had significantly higher coarse-soil tolerance than did those from clusters that occurred east or west of central Sundaland. For drought tolerance, no such pattern was detected. These results strongly suggest that exposed sandy sea-bed soils acted as a dispersal barrier in central Sundaland. However, we could not confirm the presence of a savanna corridor. This finding makes it clear that proposed biogeographic explanations for plant and animal distributions within Sundaland, including possible migration routes for early humans, need to be reevaluated.
  4. Tao J, Chen J, Li J, Mathurin L, Zheng JC, Li Y, et al.
    Proc Natl Acad Sci U S A, 2017 09 12;114(37):9832-9837.
    PMID: 28855335 DOI: 10.1073/pnas.1709163114
    The optimal functionalities of materials often appear at phase transitions involving simultaneous changes in the electronic structure and the symmetry of the underlying lattice. It is experimentally challenging to disentangle which of the two effects--electronic or structural--is the driving force for the phase transition and to use the mechanism to control material properties. Here we report the concurrent pumping and probing of Cu2S nanoplates using an electron beam to directly manipulate the transition between two phases with distinctly different crystal symmetries and charge-carrier concentrations, and show that the transition is the result of charge generation for one phase and charge depletion for the other. We demonstrate that this manipulation is fully reversible and nonthermal in nature. Our observations reveal a phase-transition pathway in materials, where electron-induced changes in the electronic structure can lead to a macroscopic reconstruction of the crystal structure.
  5. Slik JWF, Franklin J, Arroyo-Rodríguez V, Field R, Aguilar S, Aguirre N, et al.
    Proc Natl Acad Sci U S A, 2018 02 20;115(8):1837-1842.
    PMID: 29432167 DOI: 10.1073/pnas.1714977115
    Knowledge about the biogeographic affinities of the world's tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world's tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.
  6. Sun T, Wang D, Mirkin MV, Cheng H, Zheng JC, Richards RM, et al.
    Proc Natl Acad Sci U S A, 2019 06 11;116(24):11618-11623.
    PMID: 31127040 DOI: 10.1073/pnas.1821091116
    The catalytic activity of low-dimensional electrocatalysts is highly dependent on their local atomic structures, particularly those less-coordinated sites found at edges and corners; therefore, a direct probe of the electrocatalytic current at specified local sites with true nanoscopic resolution has become critically important. Despite the growing availability of operando imaging tools, to date it has not been possible to measure the electrocatalytic activities from individual material edges and directly correlate those with the local structural defects. Herein, we show the possibility of using feedback and generation/collection modes of operation of the scanning electrochemical microscope (SECM) to independently image the topography and local electrocatalytic activity with 15-nm spatial resolution. We employed this operando microscopy technique to map out the oxygen evolution activity of a semi-2D nickel oxide nanosheet. The improved resolution and sensitivity enables us to distinguish the higher activities of the materials' edges from that of the fully coordinated surfaces in operando The combination of spatially resolved electrochemical information with state-of-the-art electron tomography, that unravels the 3D complexity of the edges, and ab initio calculations allows us to reveal the intricate coordination dependent activity along individual edges of the semi-2D material that is not achievable by other methods. The comparison of the simulated line scans to the experimental data suggests that the catalytic current density at the nanosheet edge is ∼200 times higher than that at the NiO basal plane.
  7. Chua KB, Crameri G, Hyatt A, Yu M, Tompang MR, Rosli J, et al.
    Proc Natl Acad Sci U S A, 2007 Jul 03;104(27):11424-9.
    PMID: 17592121
    Respiratory infections constitute the most widespread human infectious disease, and a substantial proportion of them are caused by unknown etiological agents. Reoviruses (respiratory enteric orphan viruses) were first isolated from humans in the early 1950s and so named because they were not associated with any known disease. Here, we report a previously unknown reovirus (named "Melaka virus") isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation. Two of his family members developed similar symptoms approximately 1 week later and had serological evidence of infection with the same virus. Epidemiological tracing revealed that the family was exposed to a bat in the house approximately 1 week before the onset of the father's clinical symptoms. Genome sequence analysis indicated a close genetic relationship between Melaka virus and Pulau virus, a reovirus isolated in 1999 from fruit bats in Tioman Island, Malaysia. Screening of sera collected from human volunteers on the island revealed that 14 of 109 (13%) were positive for both Pulau and Melaka viruses. This is the first report of an orthoreovirus in association with acute human respiratory diseases. Melaka virus is serologically not related to the different types of mammalian reoviruses that were known to infect humans asymptomatically. These data indicate that bat-borne reoviruses can be transmitted to and cause clinical diseases in humans.
  8. Slik JW, Arroyo-Rodríguez V, Aiba S, Alvarez-Loayza P, Alves LF, Ashton P, et al.
    Proc Natl Acad Sci U S A, 2015 Jun 16;112(24):7472-7.
    PMID: 26034279 DOI: 10.1073/pnas.1423147112
    The high species richness of tropical forests has long been recognized, yet there remains substantial uncertainty regarding the actual number of tropical tree species. Using a pantropical tree inventory database from closed canopy forests, consisting of 657,630 trees belonging to 11,371 species, we use a fitted value of Fisher's alpha and an approximate pantropical stem total to estimate the minimum number of tropical forest tree species to fall between ∼ 40,000 and ∼ 53,000, i.e., at the high end of previous estimates. Contrary to common assumption, the Indo-Pacific region was found to be as species-rich as the Neotropics, with both regions having a minimum of ∼ 19,000-25,000 tree species. Continental Africa is relatively depauperate with a minimum of ∼ 4,500-6,000 tree species. Very few species are shared among the African, American, and the Indo-Pacific regions. We provide a methodological framework for estimating species richness in trees that may help refine species richness estimates of tree-dependent taxa.
  9. Wilkinson JL, Boxall ABA, Kolpin DW, Leung KMY, Lai RWS, Galbán-Malagón C, et al.
    Proc Natl Acad Sci U S A, 2022 Feb 22;119(8).
    PMID: 35165193 DOI: 10.1073/pnas.2113947119
    Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.
  10. Kobayashi Y, Komatsuya K, Imamura S, Nozaki T, Watanabe YI, Sato S, et al.
    Proc Natl Acad Sci U S A, 2023 Jul 11;120(28):e2214765120.
    PMID: 37406097 DOI: 10.1073/pnas.2214765120
    The malaria parasite Plasmodium falciparum has a nonphotosynthetic plastid called the apicoplast, which contains its own genome. Regulatory mechanisms for apicoplast gene expression remain poorly understood, despite this organelle being crucial for the parasite life cycle. Here, we identify a nuclear-encoded apicoplast RNA polymerase σ subunit (sigma factor) which, along with the α subunit, appears to mediate apicoplast transcript accumulation. This has a periodicity reminiscent of parasite circadian or developmental control. Expression of the apicoplast subunit gene, apSig, together with apicoplast transcripts, increased in the presence of the blood circadian signaling hormone melatonin. Our data suggest that the host circadian rhythm is integrated with intrinsic parasite cues to coordinate apicoplast genome transcription. This evolutionarily conserved regulatory system might be a future target for malaria treatment.
  11. Yan W, Ge HM, Wang G, Jiang N, Mei YN, Jiang R, et al.
    Proc Natl Acad Sci U S A, 2014 Dec 23;111(51):18138-43.
    PMID: 25425666 DOI: 10.1073/pnas.1417304111
    The Pictet-Spengler (PS) reaction constructs plant alkaloids such as morphine and camptothecin, but it has not yet been noticed in the fungal kingdom. Here, a silent fungal Pictet-Spenglerase (FPS) gene of Chaetomium globosum 1C51 residing in Epinephelus drummondhayi guts is described and ascertained to be activable by 1-methyl-L-tryptophan (1-MT). The activated FPS expression enables the PS reaction between 1-MT and flavipin (fungal aldehyde) to form "unnatural" natural products with unprecedented skeletons, of which chaetoglines B and F are potently antibacterial with the latter inhibiting acetylcholinesterase. A gene-implied enzyme inhibition (GIEI) strategy has been introduced to address the key steps for PS product diversifications. In aggregation, the work designs and validates an innovative approach that can activate the PS reaction-based fungal biosynthetic machinery to produce unpredictable compounds of unusual and novel structure valuable for new biology and biomedicine.
  12. Deere NJ, Guillera-Arroita G, Swinfield T, Milodowski DT, Coomes DA, Bernard H, et al.
    Proc Natl Acad Sci U S A, 2020 10 20;117(42):26254-26262.
    PMID: 32989143 DOI: 10.1073/pnas.2001823117
    Tropical forest ecosystems are facing unprecedented levels of degradation, severely compromising habitat suitability for wildlife. Despite the fundamental role biodiversity plays in forest regeneration, identifying and prioritizing degraded forests for restoration or conservation, based on their wildlife value, remains a significant challenge. Efforts to characterize habitat selection are also weakened by simple classifications of human-modified tropical forests as intact vs. degraded, which ignore the influence that three-dimensional (3D) forest structure may have on species distributions. Here, we develop a framework to identify conservation and restoration opportunities across logged forests in Borneo. We couple high-resolution airborne light detection and ranging (LiDAR) and camera trap data to characterize the response of a tropical mammal community to changes in 3D forest structure across a degradation gradient. Mammals were most responsive to covariates that accounted explicitly for the vertical and horizontal characteristics of the forest and actively selected structurally complex environments comprising tall canopies, increased plant area index throughout the vertical column, and the availability of a greater diversity of niches. We show that mammals are sensitive to structural simplification through disturbance, emphasizing the importance of maintaining and enhancing structurally intact forests. By calculating occurrence thresholds of species in response to forest structural change, we identify areas of degraded forest that would provide maximum benefit for multiple high-conservation value species if restored. The study demonstrates the advantages of using LiDAR to map forest structure, rather than relying on overly simplistic classifications of human-modified tropical forests, for prioritizing regions for restoration.
  13. Hewitt CN, MacKenzie AR, Di Carlo P, Di Marco CF, Dorsey JR, Evans M, et al.
    Proc Natl Acad Sci U S A, 2009 Nov 3;106(44):18447-51.
    PMID: 19841269 DOI: 10.1073/pnas.0907541106
    More than half the world's rainforest has been lost to agriculture since the Industrial Revolution. Among the most widespread tropical crops is oil palm (Elaeis guineensis): global production now exceeds 35 million tonnes per year. In Malaysia, for example, 13% of land area is now oil palm plantation, compared with 1% in 1974. There are enormous pressures to increase palm oil production for food, domestic products, and, especially, biofuels. Greater use of palm oil for biofuel production is predicated on the assumption that palm oil is an "environmentally friendly" fuel feedstock. Here we show, using measurements and models, that oil palm plantations in Malaysia directly emit more oxides of nitrogen and volatile organic compounds than rainforest. These compounds lead to the production of ground-level ozone (O(3)), an air pollutant that damages human health, plants, and materials, reduces crop productivity, and has effects on the Earth's climate. Our measurements show that, at present, O(3) concentrations do not differ significantly over rainforest and adjacent oil palm plantation landscapes. However, our model calculations predict that if concentrations of oxides of nitrogen in Borneo are allowed to reach those currently seen over rural North America and Europe, ground-level O(3) concentrations will reach 100 parts per billion (10(9)) volume (ppbv) and exceed levels known to be harmful to human health. Our study provides an early warning of the urgent need to develop policies that manage nitrogen emissions if the detrimental effects of palm oil production on air quality and climate are to be avoided.
  14. Raes N, Cannon CH, Hijmans RJ, Piessens T, Saw LG, van Welzen PC, et al.
    Proc Natl Acad Sci U S A, 2014 Nov 25;111(47):16790-5.
    PMID: 25385612 DOI: 10.1073/pnas.1403053111
    The extent of Dipterocarp rainforests on the emergent Sundaland landmass in Southeast Asia during Quaternary glaciations remains a key question. A better understanding of the biogeographic history of Sundaland could help explain current patterns of biodiversity and support the development of effective forest conservation strategies. Dipterocarpaceae trees dominate the rainforests of Sundaland, and their distributions serve as a proxy for rainforest extent. We used species distribution models (SDMs) of 317 Dipterocarp species to estimate the geographic extent of appropriate climatic conditions for rainforest on Sundaland at the last glacial maximum (LGM). The SDMs suggest that the climate of central Sundaland at the LGM was suitable to sustain Dipterocarp rainforest, and that the presence of a previously suggested transequatorial savannah corridor at that time is unlikely. Our findings are supported by palynologic evidence, dynamic vegetation models, extant mammal and termite communities, vascular plant fatty acid stable isotopic compositions, and stable carbon isotopic compositions of cave guano profiles. Although Dipterocarp species richness was generally lower at the LGM, areas of high species richness were mostly found off the current islands and on the emergent Sunda Shelf, indicating substantial species migration and mixing during the transitions between the Quaternary glacial maxima and warm periods such as the present.
  15. Assefa S, Lim C, Preston MD, Duffy CW, Nair MB, Adroub SA, et al.
    Proc Natl Acad Sci U S A, 2015 Oct 20;112(42):13027-32.
    PMID: 26438871 DOI: 10.1073/pnas.1509534112
    Malaria cases caused by the zoonotic parasite Plasmodium knowlesi are being increasingly reported throughout Southeast Asia and in travelers returning from the region. To test for evidence of signatures of selection or unusual population structure in this parasite, we surveyed genome sequence diversity in 48 clinical isolates recently sampled from Malaysian Borneo and in five lines maintained in laboratory rhesus macaques after isolation in the 1960s from Peninsular Malaysia and the Philippines. Overall genomewide nucleotide diversity (π = 6.03 × 10(-3)) was much higher than has been seen in worldwide samples of either of the major endemic malaria parasite species Plasmodium falciparum and Plasmodium vivax. A remarkable substructure is revealed within P. knowlesi, consisting of two major sympatric clusters of the clinical isolates and a third cluster comprising the laboratory isolates. There was deep differentiation between the two clusters of clinical isolates [mean genomewide fixation index (FST) = 0.21, with 9,293 SNPs having fixed differences of FST = 1.0]. This differentiation showed marked heterogeneity across the genome, with mean FST values of different chromosomes ranging from 0.08 to 0.34 and with further significant variation across regions within several chromosomes. Analysis of the largest cluster (cluster 1, 38 isolates) indicated long-term population growth, with negatively skewed allele frequency distributions (genomewide average Tajima's D = -1.35). Against this background there was evidence of balancing selection on particular genes, including the circumsporozoite protein (csp) gene, which had the top Tajima's D value (1.57), and scans of haplotype homozygosity implicate several genomic regions as being under recent positive selection.
  16. Chisholm RA, Kristensen NP, Rheindt FE, Chong KY, Ascher JS, Lim KKP, et al.
    Proc Natl Acad Sci U S A, 2023 Dec 19;120(51):e2309034120.
    PMID: 38079550 DOI: 10.1073/pnas.2309034120
    There is an urgent need for reliable data on the impacts of deforestation on tropical biodiversity. The city-state of Singapore has one of the most detailed biodiversity records in the tropics, dating back to the turn of the 19th century. In 1819, Singapore was almost entirely covered in primary forest, but this has since been largely cleared. We compiled more than 200 y of records for 10 major taxonomic groups in Singapore (>50,000 individual records; >3,000 species), and we estimated extinction rates using recently developed and novel statistical models that account for "dark extinctions," i.e., extinctions of undiscovered species. The estimated overall extinction rate was 37% (95% CI [31 to 42%]). Extrapolating our Singapore observations to a future business-as-usual deforestation scenario for Southeast Asia suggests that 18% (95% CI [16 to 22%]) of species will be lost regionally by 2100. Our extinction estimates for Singapore and Southeast Asia are a factor of two lower than previous estimates that also attempted to account for dark extinctions. However, we caution that particular groups such as large mammals, forest-dependent birds, orchids, and butterflies are disproportionately vulnerable.
  17. Liu PP, Caricchi L, Chung SL, Li XH, Li QL, Zhou MF, et al.
    Proc Natl Acad Sci U S A, 2021 11 09;118(45).
    PMID: 34725149 DOI: 10.1073/pnas.2101695118
    The Toba volcanic system in Indonesia has produced two of the largest eruptions (>2,000 km3 dense-rock equivalent [DRE] each) on Earth since the Quaternary. U-Pb crystallization ages of zircon span a period of ∼600 ky before each eruptive event, and in the run-up to each eruption, the mean and variance of the zircons' U content decrease. To quantify the process of accumulation of eruptible magma underneath the Toba caldera, we integrated these observations with thermal and geochemical modeling. We show that caldera-forming eruptions at Toba are the result of progressive thermal maturation of the upper crustal magma reservoir, which grows and chemically homogenizes, by sustained magma influx at average volumetric rates between 0.008 and 0.01 km3/y over the past 2.2 My. Protracted thermal pulses related to magma-recharge events prime the system for eruption without necessarily requiring an increased magma-recharge rate before the two supereruptions. If the rate of magma input was maintained since the last supereruption of Toba at 75 ka, eruptible magma is currently accumulating at a minimum rate of ∼4.2 km3 per millennium, and the current estimate of the total volume of potentially eruptible magma available today is a minimum of ∼315 km3 Our approach to evaluate magma flux and the rate of eruptible magma accumulation is applicable to other volcanic systems capable of producing supereruptions and thereby could help in assessing the potential of active volcanic systems to feed supereruptions.
  18. Dejea CM, Wick EC, Hechenbleikner EM, White JR, Mark Welch JL, Rossetti BJ, et al.
    Proc Natl Acad Sci U S A, 2014 Dec 23;111(51):18321-6.
    PMID: 25489084 DOI: 10.1073/pnas.1406199111
    Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC.
  19. Nett RS, Dho Y, Low YY, Sattely ES
    Proc Natl Acad Sci U S A, 2021 06 15;118(24).
    PMID: 34112718 DOI: 10.1073/pnas.2102949118
    Plants synthesize many diverse small molecules that affect function of the mammalian central nervous system, making them crucial sources of therapeutics for neurological disorders. A notable portion of neuroactive phytochemicals are lysine-derived alkaloids, but the mechanisms by which plants produce these compounds have remained largely unexplored. To better understand how plants synthesize these metabolites, we focused on biosynthesis of the Lycopodium alkaloids that are produced by club mosses, a clade of plants used traditionally as herbal medicines. Hundreds of Lycopodium alkaloids have been described, including huperzine A (HupA), an acetylcholine esterase inhibitor that has generated interest as a treatment for the symptoms of Alzheimer's disease. Through combined metabolomic profiling and transcriptomics, we have identified a developmentally controlled set of biosynthetic genes, or potential regulon, for the Lycopodium alkaloids. The discovery of this putative regulon facilitated the biosynthetic reconstitution and functional characterization of six enzymes that act in the initiation and conclusion of HupA biosynthesis. This includes a type III polyketide synthase that catalyzes a crucial imine-polyketide condensation, as well as three Fe(II)/2-oxoglutarate-dependent dioxygenase (2OGD) enzymes that catalyze transformations (pyridone ring-forming desaturation, piperidine ring cleavage, and redox-neutral isomerization) within downstream HupA biosynthesis. Our results expand the diversity of known chemical transformations catalyzed by 2OGDs and provide mechanistic insight into the function of noncanonical type III PKS enzymes that generate plant alkaloid scaffolds. These data offer insight into the chemical logic of Lys-derived alkaloid biosynthesis and demonstrate the tightly coordinated coexpression of secondary metabolic genes for the biosynthesis of medicinal alkaloids.
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links