The 2013-2016 epidemic of Ebola virus disease in West Africa was of unprecedented magnitude and changed our perspective on this lethal but sporadically emerging virus. This outbreak also marked the ...beginning of large-scale real-time molecular epidemiology. Here, we show how evolutionary analyses of Ebola virus genome sequences provided key insights into virus origins, evolution and spread during the epidemic. We provide basic scientists, epidemiologists, medical practitioners and other outbreak responders with an enhanced understanding of the utility and limitations of pathogen genomic sequencing. This will be crucially important in our attempts to track and control future infectious disease outbreaks.
Full text
Available for:
KISLJ, NUK, SBMB, UL, UM, UPUK
COVID-19 testing: One size does not fit all Mina, Michael J; Andersen, Kristian G
Science (American Association for the Advancement of Science),
01/2021, Volume:
371, Issue:
6525
Journal Article
Peer reviewed
Open access
To control the pandemic, testing should be considered a public health tool
Tests for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed within days of the release ...of the virus genome (
1
). Multiple countries have been successful at controlling SARS-CoV-2 transmission by investing in large-scale testing capacity (
2
). Most testing has focused on quantitative polymerase chain reaction (qPCR) assays, which are capable of detecting minute amounts of viral RNA. Although powerful, these molecular tools cannot be scaled to meet demands for more extensive public health testing. To combat COVID-19, the “one-size-fits-all” approach that has dominated and confused decision-making with regard to testing and the evaluation of tests is unsuitable: Diagnostics, screening, and surveillance serve different purposes, demand distinct strategies, and require separate approval mechanisms. By supporting the innovation, approval, manufacturing, and distribution of simpler and cheaper screening and surveillance tools, it will be possible to more effectively limit the spread of COVID-19 and respond to future pandemics.
: Indole‐3‐ylcarbinol (13C) is formed during processing of cruciferous vegetables and is suggested to be one of the modulators of drug‐metabolising enzymes. Indole‐3‐ylcarbinol is a far less ...efficient inducer of hepatic enzymes after parenteral than after oral administration, due to formation of active metabolites in the gastrointestinal tract. As indole‐3‐ylcarbinol is unstable in weakly acidic aqueous solutions, non‐active condensation products may be formed from indole‐3‐ylcarbinol, that cannot be transformed to the active products when reaching the stomach. The purpose of the present study was to test the ability of the condensation products formed at a pH corresponding to that of fresh vegetable juice to modulate the metabolism of xenobiotics. Indole‐3‐ylcarbinol was incubated in vitro at room temperature in the dark at pH 5.5 and samples taken at various times, for oral administration to rats and for chemical analysis. Indole‐3‐ylcarbinol was rapidly transformed into various oligomeric products. The 7‐ethoxyresorufin O‐deethylase activities (marker of cytochrome Cytochrome P450 1A enzymes, CYP1A) in liver, kidney and colon increased with the duration of the in vitro condensation period whereas the formation of 6β‐, 15β‐ and and 2α‐hydroxytestosterone was not affected significantly, indicating no effect on CYP2C11 or CYP3A enzymes. The hepatic metabolism of the food mutagen 2‐amino‐1‐methyl‐6‐phenylimidazo4, 5‐bpyridine (PhIP), was increased by indole‐3‐ylcarbinol condensation products and the 4′‐OH‐PhIP/N‐OH‐PhIP ratio was decreased due to a significantly increased formation of the proximate genotoxic metabolite, N‐OH‐PhIP. The activities of DT‐diaphorase and glutathione S‐transferase were not changed significantly in the rat organs. These experiments clearly indicate that indole‐3‐ylcarbinol is not the definitive CYP1A inducer and that indole‐3‐ylcarbinol at near‐neutral pH, is transformed to compounds that are inducers by themselves or may be further converted into inducing compounds in the rat stomach. Also, the enzyme inducing potency of indole‐3‐ylcarbinol containing vegetable juice is apparently enhanced by incubation in vitro before the intake.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Vertical stacking of two-dimensional (2D) crystals, such as graphene and hexagonal boron nitride, has recently lead to a new class of materials known as van der Waals heterostructures (vdWHs) with ...unique and highly tunable electronic properties. Ab initio calculations should in principle provide a powerful tool for modeling and guiding the design of vdWHs, but in their traditional form such calculations are only feasible for commensurable structures with a few layers. Here we show that the dielectric properties of realistic, incommensurable vdWHs comprising hundreds of layers can be efficiently calculated using a multiscale approach where the dielectric functions of the individual layers (the dielectric building blocks) are computed ab initio and coupled together via the long-range Coulomb interaction. We use the method to illustrate the 2D–3D transition of the dielectric function of multilayer MoS2 crystals, the hybridization of quantum plasmons in thick graphene/hBN heterostructures, and to demonstrate the intricate effect of substrate screening on the non-Rydberg exciton series in supported WS2. The dielectric building blocks for a variety of 2D crystals are available in an open database together with the software for solving the coupled electrodynamic equations.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Hereditary xerocytosis is thought to be a rare genetic condition characterized by red blood cell (RBC) dehydration with mild hemolysis. RBC dehydration is linked to reduced Plasmodium infection ...in vitro; however, the role of RBC dehydration in protection against malaria in vivo is unknown. Most cases of hereditary xerocytosis are associated with gain-of-function mutations in PIEZO1, a mechanically activated ion channel. We engineered a mouse model of hereditary xerocytosis and show that Plasmodium infection fails to cause experimental cerebral malaria in these mice due to the action of Piezo1 in RBCs and in T cells. Remarkably, we identified a novel human gain-of-function PIEZO1 allele, E756del, present in a third of the African population. RBCs from individuals carrying this allele are dehydrated and display reduced Plasmodium infection in vitro. The existence of a gain-of-function PIEZO1 at such high frequencies is surprising and suggests an association with malaria resistance.
Display omitted
•Expression of a gain-of-function Piezo1 allele models hereditary xerocytosis in mice•Mice expressing gain-of-function Piezo1 allele are protected from cerebral malaria•A third of the African population carry a PIEZO1 gain-of-function allele (E756del)•RBCs from E756del carriers are dehydrated and show reduced susceptibility to Plasmodium
A gain-of-function mutation in the mechanically activated channel PIEZO1 is associated with resistance to the malaria parasite Plasmodium falciparum.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The proximal origin of SARS-CoV-2 Andersen, Kristian G; Rambaut, Andrew; Lipkin, W Ian ...
Nature medicine,
04/2020, Volume:
26, Issue:
4
Journal Article
Peer reviewed
Open access
Full text
Available for:
FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
It has been 20 years since West Nile virus first emerged in the Americas, and since then, little progress has been made to control outbreaks caused by this virus. After its first detection in New ...York in 1999, West Nile virus quickly spread across the continent, causing an epidemic of human disease and massive bird die-offs. Now the virus has become endemic to the United States, where an estimated 7 million human infections have occurred, making it the leading mosquito-borne virus infection and the most common cause of viral encephalitis in the country. To bring new attention to one of the most important mosquito-borne viruses in the Americas, we provide an interactive review using Nextstrain: a visualization tool for real-time tracking of pathogen evolution (nextstrain.org/WNV/NA). Nextstrain utilizes a growing database of more than 2,000 West Nile virus genomes and harnesses the power of phylogenetics for students, educators, public health workers, and researchers to visualize key aspects of virus spread and evolution. Using Nextstrain, we use virus genomics to investigate the emergence of West Nile virus in the U S, followed by its rapid spread, evolution in a new environment, establishment of endemic transmission, and subsequent international spread. For each figure, we include a link to Nextstrain to allow the readers to directly interact with and explore the underlying data in new ways. We also provide a brief online narrative that parallels this review to further explain the data and highlight key epidemiological and evolutionary features (nextstrain.org/narratives/twenty-years-of-WNV). Mirroring the dynamic nature of outbreaks, the Nextstrain links provided within this paper are constantly updated as new West Nile virus genomes are shared publicly, helping to stay current with the research. Overall, our review showcases how genomics can track West Nile virus spread and evolution, as well as potentially uncover novel targeted control measures to help alleviate its public health burden.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Since the first reports of a novel severe acute respiratory syndrome (SARS)-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how severe acute ...respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the human population. Recent debate has coalesced around two competing ideas: a “laboratory escape” scenario and zoonotic emergence. Here, we critically review the current scientific evidence that may help clarify the origin of SARS-CoV-2.
A review of the current literature supports a zoonotic origin for SARS-CoV-2 and emphasizes the need to focus on identifying the exact animal host through collaborative and carefully coordinated studies. This will enable the community to understand the roots of the COVID-19 pandemic as well as better prepare us for future pandemics
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
How viruses evolve within hosts can dictate infection outcomes; however, reconstructing this process is challenging. We evaluate our multiplexed amplicon approach, PrimalSeq, to demonstrate how virus ...concentration, sequencing coverage, primer mismatches, and replicates influence the accuracy of measuring intrahost virus diversity. We develop an experimental protocol and computational tool, iVar, for using PrimalSeq to measure virus diversity using Illumina and compare the results to Oxford Nanopore sequencing. We demonstrate the utility of PrimalSeq by measuring Zika and West Nile virus diversity from varied sample types and show that the accumulation of genetic diversity is influenced by experimental and biological systems.
PDF
