Closely related pathogens may differ dramatically in host range, but the molecular, genetic, and evolutionary basis for these differences remains unclear. In many Gram- negative bacteria, including ...the phytopathogen Pseudomonas syringae, type III effectors (TTEs) are essential for pathogenicity, instrumental in structuring host range, and exhibit wide diversity between strains. To capture the dynamic nature of virulence gene repertoires across P. syringae, we screened 11 diverse strains for novel TTE families and coupled this nearly saturating screen with the sequencing and assembly of 14 phylogenetically diverse isolates from a broad collection of diseased host plants. TTE repertoires vary dramatically in size and content across all P. syringae clades; surprisingly few TTEs are conserved and present in all strains. Those that are likely provide basal requirements for pathogenicity. We demonstrate that functional divergence within one conserved locus, hopM1, leads to dramatic differences in pathogenicity, and we demonstrate that phylogenetics-informed mutagenesis can be used to identify functionally critical residues of TTEs. The dynamism of the TTE repertoire is mirrored by diversity in pathways affecting the synthesis of secreted phytotoxins, highlighting the likely role of both types of virulence factors in determination of host range. We used these 14 draft genome sequences, plus five additional genome sequences previously reported, to identify the core genome for P. syringae and we compared this core to that of two closely related non-pathogenic pseudomonad species. These data revealed the recent acquisition of a 1 Mb megaplasmid by a sub-clade of cucumber pathogens. This megaplasmid encodes a type IV secretion system and a diverse set of unknown proteins, which dramatically increases both the genomic content of these strains and the pan-genome of the species.
All coronaviruses known to have recently emerged as human pathogens probably originated in bats
. Here we use a single experimental platform based on immunodeficient mice implanted with human lung ...tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801-an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials-markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19.
Human activities are fundamentally altering biodiversity. Projections of declines at the global scale are contrasted by highly variable trends at local scales, suggesting that biodiversity change may ...be spatially structured. Here, we examined spatial variation in species richness and composition change using more than 50,000 biodiversity time series from 239 studies and found clear geographic variation in biodiversity change. Rapid compositional change is prevalent, with marine biomes exceeding and terrestrial biomes trailing the overall trend. Assemblage richness is not changing on average, although locations exhibiting increasing and decreasing trends of up to about 20% per year were found in some marine studies. At local scales, widespread compositional reorganization is most often decoupled from richness change, and biodiversity change is strongest and most variable in the oceans.
Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule that regulates a variety of complex processes through a diverse set of c-di-GMP receptor proteins. We have utilized a systematic ...approach to identify c-di-GMP receptors from the pathogen Vibrio cholerae using the Differential Radial Capillary Action of Ligand Assay (DRaCALA). The DRaCALA screen identified a majority of known c-di-GMP binding proteins in V. cholerae and revealed a novel c-di-GMP binding protein, MshE (VC0405), an ATPase associated with the mannose sensitive hemagglutinin (MSHA) type IV pilus. The known c-di-GMP binding proteins identified by DRaCALA include diguanylate cyclases, phosphodiesterases, PilZ domain proteins and transcription factors VpsT and VpsR, indicating that the DRaCALA-based screen of open reading frame libraries is a feasible approach to uncover novel receptors of small molecule ligands. Since MshE lacks the canonical c-di-GMP-binding motifs, a truncation analysis was utilized to locate the c-di-GMP binding activity to the N-terminal T2SSE_N domain. Alignment of MshE homologs revealed candidate conserved residues responsible for c-di-GMP binding. Site-directed mutagenesis of these candidate residues revealed that the Arg9 residue is required for c-di-GMP binding. The ability of c-di-GMP binding to MshE to regulate MSHA dependent processes was evaluated. The R9A allele, in contrast to the wild type MshE, was unable to complement the ΔmshE mutant for the production of extracellular MshA to the cell surface, reduction in flagella swimming motility, attachment to surfaces and formation of biofilms. Testing homologs of MshE for binding to c-di-GMP identified the type II secretion ATPase of Pseudomonas aeruginosa (PA14_29490) as a c-di-GMP receptor, indicating that type II secretion and type IV pili are both regulated by c-di-GMP.
The genus Wolbachia is an archetype of maternally inherited intracellular bacteria that infect the germline of numerous invertebrate species worldwide. They can selfishly alter arthropod sex ratios ...and reproductive strategies to increase the proportion of the infected matriline in the population. The most common reproductive manipulation is cytoplasmic incompatibility, which results in embryonic lethality in crosses between infected males and uninfected females. Females infected with the same Wolbachia strain rescue this lethality. Despite more than 40 years of research and relevance to symbiont-induced speciation, as well as control of arbovirus vectors and agricultural pests, the bacterial genes underlying cytoplasmic incompatibility remain unknown. Here we use comparative and transgenic approaches to demonstrate that two differentially transcribed, co-diverging genes in the eukaryotic association module of prophage WO from Wolbachia strain wMel recapitulate and enhance cytoplasmic incompatibility. Dual expression in transgenic, uninfected males of Drosophila melanogaster crossed to uninfected females causes embryonic lethality. Each gene additively augments embryonic lethality in crosses between infected males and uninfected females. Lethality associates with embryonic defects that parallel those of wild-type cytoplasmic incompatibility and is notably rescued by wMel-infected embryos in all cases. The discovery of cytoplasmic incompatibility factor genes cifA and cifB pioneers genetic studies of prophage WO-induced reproductive manipulations and informs the continuing use of Wolbachia to control dengue and Zika virus transmission to humans.
Humans have elevated global extinction rates and thus lowered global scale species richness. However, there is no a priori reason to expect that losses of global species richness should always, or ...even often, trickle down to losses of species richness at regional and local scales, even though this relationship is often assumed. Here, we show that scale can modulate our estimates of species richness change through time in the face of anthropogenic pressures, but not in a unidirectional way. Instead, the magnitude of species richness change through time can increase, decrease, reverse, or be unimodal across spatial scales. Using several case studies, we show different forms of scale‐dependent richness change through time in the face of anthropogenic pressures. For example, Central American corals show a homogenization pattern, where small scale richness is largely unchanged through time, while larger scale richness change is highly negative. Alternatively, birds in North America showed a differentiation effect, where species richness was again largely unchanged through time at small scales, but was more positive at larger scales. Finally, we collated data from a heterogeneous set of studies of different taxa measured through time from sites ranging from small plots to entire continents, and found highly variable patterns that nevertheless imply complex scale‐dependence in several taxa. In summary, understanding how biodiversity is changing in the Anthropocene requires an explicit recognition of the influence of spatial scale, and we conclude with some recommendations for how to better incorporate scale into our estimates of change.
Highlights • A framework for potential roles of metaplasticity in vivo is presented. • Metaplasticity can prepare synapses and networks for learning. • Metaplasticity can homeostatically keep ...synaptic plasticity within a dynamic range. • Metaplasticity mechanisms may play roles in disease and treatment.
Climate change and other anthropogenic drivers of biodiversity change are unequally distributed across the world. Overlap in the distributions of different drivers have important implications for ...biodiversity change attribution and the potential for interactive effects. However, the spatial relationships among different drivers and whether they differ between the terrestrial and marine realm has yet to be examined.
We compiled global gridded datasets on climate change, land‐use, resource exploitation, pollution, alien species potential and human population density. We used multivariate statistics to examine the spatial relationships among the drivers and to characterize the typical combinations of drivers experienced by different regions of the world.
We found stronger positive correlations among drivers in the terrestrial than in the marine realm, leading to areas with high intensities of multiple drivers on land. Climate change tended to be negatively correlated with other drivers in the terrestrial realm (e.g. in the tundra and boreal forest with high climate change but low human use and pollution), whereas the opposite was true in the marine realm (e.g. in the Indo‐Pacific with high climate change and high fishing).
We show that different regions of the world can be defined by Anthropogenic Threat Complexes (ATCs), distinguished by different sets of drivers with varying intensities. We identify 11 ATCs that can be used to test hypotheses about patterns of biodiversity and ecosystem change, especially about the joint effects of multiple drivers.
Our global analysis highlights the broad conservation priorities needed to mitigate the impacts of anthropogenic change, with different priorities emerging on land and in the ocean, and in different parts of the world.
Abstrakt
Der Klimawandel und andere anthropogene Faktoren, die die biologische Vielfalt verändern, betreffen nicht alle Teile der Erde in gleicher Weise. Während unsere Kenntnisse zu jedem einzelnen Gefährdungsfaktor ständig wachsen, ist unser Verständnis zu den räumlichen Beziehungen zwischen den verschiedenen Faktoren und ihr Zusammenwirken noch sehr mangelhaft. Das betrifft z.B. auch die Unterschiede zwischen terrestrischen und marinen Lebensräumen, die sehr unterschiedlichen Bedrohungen ausgesetzt sein können, selbst wenn sie eng benachbart sind.
In der vorliegenden Studie haben wir globale Datensätze über Klimawandel, Landnutzung, Ressourcenausbeutung, Umweltverschmutzung, biologische Invasionen und Bevölkerungsdichte zusammengestellt. Mit Hilfe multivariater Statistiken haben wir die räumlichen Beziehungen zwischen diesen Ursachen des globalen Biodiversitätswandels und deren Kombinationen untersucht, um deren Einfluss auf verschiedene Regionen der Welt zu charakterisieren.
Insbesondere in den terrestrischen Regionen wirken die genannten Gefährdungsfaktoren häufig in der gleichen Richtung, vor allem solche, die zum Teil besonders hohe Belastungen darstellen. Regionen mit stärker ausgeprägtem Klimawandel sind tendenziell solche Gebiete, in denen die Gefährdung durch andere Faktoren eher geringer ist, wie z.B. in der Tundra und im borealen Nadelwald, die stark vom Klimawandel, aber weniger von hoher Nutzungsintensität und Verschmutzung betroffen sind. Dagegen treten in den Meeresregionen gegenteilige Muster auf, wo z.B. im Indopazifik ein sehr ausgeprägter Klimawandel einer hoher Ressourcenausbeutung durch Fischerei zusammenfällt.
Die Regionen der Welt lassen sich in Klassen unterschiedlicher Interaktionen und Intensitäten dieser anthropogenen Gefährungsfaktoren unterteilen. Diese insgesamt 11 verschiedene Faktorenklassen können nun dazu verwendet werden, Auswirkungen auf Biodiversität zu untersuchen und die Gefährdungs‐Hotspots zu identifizieren. Diese Hotspots sind diejenigen großräumigen Meeres‐ und Festlandsregionen, in denen prioritär Naturschutzmaßnahmen angewendet werden müssen, um den Auswirkungen des anthropogenen Biodiversitätswandels entgegenzutreten.
A free Plain Language Summary can be found within the Supporting Information of this article.
A free Plain Language Summary can be found within the Supporting Information of this article.
The interplay of genetically driven biological processes and environmental factors is a key driver of research questions spanning multiple areas of psychology. A nascent area of research focuses on ...the utility of epigenetic marks in capturing this intersection of genes and environment, as epigenetic mechanisms are both tightly linked to the genome and environmentally responsive. Advances over the past 10 years have allowed large-scale assessment of one epigenetic mark in particular, DNA methylation, in human populations, and the examination of DNA methylation is becoming increasingly common in psychological studies. In this review, we briefly outline some principles of epigenetics, focusing on highlighting important considerations unique to DNA methylation studies to guide psychologists in incorporating DNA methylation into a project. We discuss study design and biological and analytical considerations and conclude by discussing interpretability of epigenetic findings and how these important factors are currently being applied across areas of psychology.
In 2020, UNLV Special Collections and Archives conducted an internal audit of collections, strategic plans, and programming in order to assess how well it is meeting strategic goals of being more ...inclusive and increasing diversity and representation. In a data-driven institution, how can assessment be used to advocate for resources focused on diversity, equity, and inclusion? In conducting this analysis, UNLV hoped to answer the following query: how is progress measured if the goal is to preserve stories outside the traditional narrative (white, male, cisgender, heteronormative, etc.)? This article discusses strategies for assessing diversity in special collections and archives.
PDF
