In response to the emergence of SARS-CoV-2 variants of concern, the global scientific community, through unprecedented effort, has sequenced and shared over 11 million genomes through GISAID, as of ...May 2022. This extraordinarily high sampling rate provides a unique opportunity to track the evolution of the virus in near real-time. Here, we present outbreak.info , a platform that currently tracks over 40 million combinations of Pango lineages and individual mutations, across over 7,000 locations, to provide insights for researchers, public health officials and the general public. We describe the interpretable visualizations available in our web application, the pipelines that enable the scalable ingestion of heterogeneous sources of SARS-CoV-2 variant data and the server infrastructure that enables widespread data dissemination via a high-performance API that can be accessed using an R package. We show how outbreak.info can be used for genomic surveillance and as a hypothesis-generation tool to understand the ongoing pandemic at varying geographic and temporal scales.
Despite the well-established role of the human serotonin transporter (hSERT) in the treatment of depression, the molecular details of antidepressant drug binding are still not fully understood. Here ...we utilize amber codon suppression in a membrane-bound transporter protein to encode photocrosslinking unnatural amino acids (UAAs) into 75 different positions in hSERT. UAAs are incorporated with high specificity, and functionally active transporters have similar transport properties and pharmacological profiles compared with wild-type transporters. We employ ultraviolet-induced crosslinking with p-azido-L-phenylalanine (azF) at selected positions in hSERT to map the binding site of imipramine, a prototypical tricyclic antidepressant, and vortioxetine, a novel multimodal antidepressant. We find that the two antidepressants crosslink with azF incorporated at different positions within the central substrate-binding site of hSERT, while no crosslinking is observed at the vestibular-binding site. Taken together, our data provide direct evidence for defining the high-affinity antidepressant binding site in hSERT.
Understanding the circumstances that lead to pandemics is important for their prevention. We analyzed the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in ...the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted "A" and "B." Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October to 8 December), and the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans before November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.
Advances in genomics and computing are transforming the capacity for the characterization of biological systems, and researchers are now poised for a precision-focused transformation in the way they ...prepare for, and respond to, infectious diseases. This includes the use of genome-based approaches to inform molecular diagnosis and individual-level treatment regimens. In addition, advances in the speed and granularity of pathogen genome generation have improved the capability to track and understand pathogen transmission, leading to potential improvements in the design and implementation of population-level public health interventions. In this Perspective, we outline several trends that are driving the development of precision epidemiology of infectious disease and their implications for scientists' ability to respond to outbreaks.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Maritime surveillance of the Arctic region is of growing importance as shipping, fishing and tourism are increasing due to the sea ice retreat caused by global warming. Ships that do not identify ...themselves with a transponder system, so-called dark ships, pose a security risk. They can be detected by SAR satellites, which can monitor the vast Arctic region through clouds, day and night, with the caveat that the abundant icebergs in the Arctic cause false alarms. We collect and analyze 200 Sentinel-1 horizontally polarized SAR scenes from areas with high maritime traffic and from the Arctic region with a high density of icebergs. Ships and icebergs are detected using a continuous wavelet transform, which is optimized by correlating ships to known AIS positions. Globally, we are able to assign 72% of the AIS signals to a SAR ship and 32% of the SAR ships to an AIS signal. The ships are used to construct an annotated dataset of more than 9000 ships and ten times as many icebergs. The dataset is used for training several convolutional neural networks, and we propose a new network which achieves state of the art performance compared to previous ship–iceberg discrimination networks, reaching 93% validation accuracy. Furthermore, we collect a smaller test dataset consisting of 424 ships from 100 Arctic scenes which are correlated to AIS positions. This dataset constitutes an operational Arctic test scenario. We find these ships harder to classify with a lower test accuracy of 83%, because some of the ships sail near icebergs and ice floes, which confuses the classification algorithms.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, ...and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate an array of antiviral functions including neutralization as well as engagement of Fc-domain receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing of infected cells. Thus, to understand the antibody features mediating EBOV protection, we examined specific Fc features associated with protection using a library of EBOV-specific mAbs. Neutralization was strongly associated with therapeutic protection against EBOV. However, several neutralizing mAbs failed to protect, while several non-neutralizing or weakly neutralizing mAbs could protect. Antibody-mediated effector functions, including phagocytosis and NK cell activation, were associated with protection, particularly for antibodies with moderate neutralizing activity. This framework identifies functional correlates that can inform therapeutic and vaccine design strategies against EBOV and other pathogens.
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•Fc-effector profiles of 168 Ebola virus-specific monoclonal antibodies were defined•Effector function correlated with protection for partially neutralizing antibodies•Non-protective, strongly neutralizing antibodies fail to induce phagocytosis•Profiles of protective antibodies may aid in design of future immunotherapeutics
While antibodies provide protection against Ebola virus, the mechanism is unclear. Gunn et al. dissect the contribution of Fc-functions to protection using a library of Ebola virus-specific antibodies. Fc function was a critical predictor of protection across neutralizing and non-neutralizing antibodies, pointing to synergy between Fc- and Fab-mediated antibody-functions against Ebola.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Outbreak.info Research Library is a standardized, searchable interface of coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) publications, clinical ...trials, datasets, protocols and other resources, built with a reusable framework. We developed a rigorous schema to enforce consistency across different sources and resource types and linked related resources. Researchers can quickly search the latest research across data repositories, regardless of resource type or repository location, via a search interface, public application programming interface (API) and R package.
Urinary tract infection (UTI) is one of the most common bacterial infections worldwide. Experimental models that accurately reflect the high susceptibility to UTI in humans have, however, been ...lacking. This situation has limited detailed research into the early bladder colonization by uropathogens and the early innate defence mechanisms elicited to prevent this. We recently presented a model of urinary tract infection in pigs, animals that are naturally susceptible to UTI and have greater similarity to the physiology and anatomy of the human urinary tract than traditional rodent UTI models. In the current study, we used the pig model to investigate the minimal infectious inoculum of uropathogenic
, the most common cause of urinary tract infection. We show that in this animal a few individual bacteria that come into contact with the urothelium can give rise to fulminant cystitis, indicating the high infectious potential of uropathogenic
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Immunocorrelates of CAF family adjuvants Pedersen, Gabriel Kristian; Andersen, Peter; Christensen, Dennis
Seminars in immunology,
October 2018, 2018-10-00, 20181001, Volume:
39
Journal Article
Peer reviewed
Open access
The development of the CAF family adjuvant was initiated around 20 years ago when Statens Serum Institut was preparing its first generation protein based recombinant subunit vaccine against ...tuberculosis for clinical testing, but realized that there were no clinically relevant adjuvants available that would support the strong CMI response needed. Since then the aim for the adjuvant research at Statens Serum Institut has been to provide adjuvants with distinct immunogenicity profiles correlating with protection for any given infectious disease. Two of the adjuvants CAF01 and CAF09 are currently being evaluated in human clinical trials. The purpose of this review is to give an overview of the immunocorrelates of those CAF adjuvants furthest in development. We further aim at giving an overview of the mechanism of action of the CAF adjuvants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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