Publications by authors named "Luis Escobar"

106 Publications

Hydrolysis of Aliphatic Bis-isonitriles in the Presence of a Polar Super Aryl-Extended Calix[4]pyrrole Container.

Angew Chem Int Ed Engl 2021 Feb 17. Epub 2021 Feb 17.

Institute of Chemical Research of Catalonia (ICIQ), Supramolecular Chemistry, Avda. Paisos Catalans 16, 43007, Tarragona, SPAIN.

We report binding studies of an octa-pyridinium super aryl-extended calix[4]pyrrole receptor with neutral difunctional aliphatic guests in water. The guests have terminal isonitrile and formamide groups, and the complexes display an inclusion binding geometry and 1:1 stoichiometry. Using 1H NMR titrations and ITC experiments, we characterized the dissimilar thermodynamic and kinetic properties of the complexes. The bis-isonitriles possess independent reacting groups, however, in the presence of 1 equiv. of the receptor the hydrolysis reaction produces mixtures of non-statistical composition and a significant decrease in reaction rates. The selectivity for the mono-formamide product is specially enhanced in the case of the bis-isonitrile having a spacer with five methylene groups. The analysis of the kinetic data suggests that the observed modifications in reaction rates and selectivity are related to the formation of highly stable inclusion complexes in which the isonitrile is hidden from bulk water molecules. The concentration of the reacting substrates in the bulk solution is substantially reduced by binding to the receptor. In turn, the hydrolysis rates of the isonitrile groups for the bound substrates are slower than in the bulk solution. The receptor acts as both a sequestering and supramolecular protecting group.
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http://dx.doi.org/10.1002/anie.202101499DOI Listing
February 2021

Molecular Recognition in Water Using Macrocyclic Synthetic Receptors.

Chem Rev 2021 Feb 20;121(4):2445-2514. Epub 2021 Jan 20.

Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology (BIST), Av. Països Catalans 16, 43007 Tarragona, Spain.

Molecular recognition in water using macrocyclic synthetic receptors constitutes a vibrant and timely research area of supramolecular chemistry. Pioneering examples on the topic date back to the 1980s. The investigated model systems and the results derived from them are key for furthering our understanding of the remarkable properties exhibited by proteins: high binding affinity, superior binding selectivity, and extreme catalytic performance. Dissecting the different effects contributing to the proteins' properties is severely limited owing to its complex nature. Molecular recognition in water is also involved in other appreciated areas such as self-assembly, drug discovery, and supramolecular catalysis. The development of all these research areas entails a deep understanding of the molecular recognition events occurring in aqueous media. In this review, we cover the past three decades of molecular recognition studies of neutral and charged, polar and nonpolar organic substrates and ions using selected artificial receptors soluble in water. We briefly discuss the intermolecular forces involved in the reversible binding of the substrates, as well as the hydrophobic and Hofmeister effects operating in aqueous solution. We examine, from an interdisciplinary perspective, the design and development of effective water-soluble synthetic receptors based on cyclic, oligo-cyclic, and concave-shaped architectures. We also include selected examples of self-assembled water-soluble synthetic receptors. The catalytic performance of some of the presented receptors is also described. The latter process also deals with molecular recognition and energetic stabilization, but instead of binding ground-state species, the targets become elusive counterparts: transition states and other high-energy intermediates.
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http://dx.doi.org/10.1021/acs.chemrev.0c00522DOI Listing
February 2021

Using host traits to predict reservoir host species of rabies virus.

PLoS Negl Trop Dis 2020 12 8;14(12):e0008940. Epub 2020 Dec 8.

School of Natural Sciences, University of Tasmania, Hobart, Australia.

Wildlife are important reservoirs for many pathogens, yet the role that different species play in pathogen maintenance frequently remains unknown. This is the case for rabies, a viral disease of mammals. While Carnivora (carnivores) and Chiroptera (bats) are the canonical mammalian orders known to be responsible for the maintenance and onward transmission of rabies Lyssavirus (RABV), the role of most species within these orders remains unknown and is continually changing as a result of contemporary host shifting. We combined a trait-based analytical approach with gradient boosting machine learning models to identify physiological and ecological host features associated with being a reservoir for RABV. We then used a cooperative game theory approach to determine species-specific traits associated with known RABV reservoirs. Being a carnivore reservoir for RABV was associated with phylogenetic similarity to known RABV reservoirs, along with other traits such as having larger litters and earlier sexual maturity. For bats, location in the Americas and geographic range were the most important predictors of RABV reservoir status, along with having a large litter. Our models identified 44 carnivore and 34 bat species that are currently not recognized as RABV reservoirs, but that have trait profiles suggesting their capacity to be or become reservoirs. Further, our findings suggest that potential reservoir species among bats and carnivores occur both within and outside of areas with current RABV circulation. These results show the ability of a trait-based approach to detect potential reservoirs of infection and could inform rabies control programs and surveillance efforts by identifying the types of species and traits that facilitate RABV maintenance and transmission.
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http://dx.doi.org/10.1371/journal.pntd.0008940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748407PMC
December 2020

The 2020 report of The Lancet Countdown on health and climate change: responding to converging crises.

Lancet 2021 Jan 2;397(10269):129-170. Epub 2020 Dec 2.

Office of the Vice Provost for Research, University College London, London, UK.

Translations: For the Chinese, French, German, and Spanish translations of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S0140-6736(20)32290-XDOI Listing
January 2021

Ecological Niche Modeling: An Introduction for Veterinarians and Epidemiologists.

Authors:
Luis E Escobar

Front Vet Sci 2020 21;7:519059. Epub 2020 Oct 21.

Department of Fish and Wildlife Conservation, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.

Most infectious diseases in animals are not distributed randomly. Instead, diseases in livestock and wildlife are predictable in terms of the geography, time, and species affected. Ecological niche modeling approaches have been crucial to the advancement of our understanding of diversity and diseases distributions. This contribution is an introductory overview to the field of distributional ecology, with emphasis on its application for spatial epidemiology. A new, revised modeling framework is proposed for more detailed and replicable models that account for both the biology of the disease to be modeled and the uncertainty of the data available. Considering that most disease systems need at least two organisms interacting (i.e., host and pathogen), biotic interactions lie at the core of the pathogen's ecological niche. As a result, neglecting interacting organisms in pathogen dynamics (e.g., maintenance, reproduction, and transmission) may limit efforts to forecast disease distributions in veterinary epidemiology. Although limitations of ecological niche modeling are noted, it is clear that the application and value of ecological niche modeling to epidemiology will increase in the future. Potential research lines include the examination of the effects of biotic variables on model performance, assessments of protocols for model calibration in disease systems, and new tools and metrics for robust model evaluation. Epidemiologists aiming to employ ecological niche modeling theory and methods to reconstruct and forecast epidemics should familiarize themselves with ecological literature and must consider multidisciplinary collaborations including veterinarians to develop biologically sound, statistically robust analyses. This review attempts to increase the use of tools from ecology in disease mapping.
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http://dx.doi.org/10.3389/fvets.2020.519059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641643PMC
October 2020

Tracking infectious diseases in a warming world.

BMJ 2020 11 13;371:m3086. Epub 2020 Nov 13.

Institute for Global Health, University College London, London W1T 4TJ, UK.

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http://dx.doi.org/10.1136/bmj.m3086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662084PMC
November 2020

Phenotypic clustering of dilated cardiomyopathy patients highlights important pathophysiological differences.

Eur Heart J 2021 Jan;42(2):162-174

Department of Cardiology, Cardiovascular Research Institute (CARIM), Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands.

Aims: The dilated cardiomyopathy (DCM) phenotype is the result of combined genetic and acquired triggers. Until now, clinical decision-making in DCM has mainly been based on ejection fraction (EF) and NYHA classification, not considering the DCM heterogenicity. The present study aimed to identify patient subgroups by phenotypic clustering integrating aetiologies, comorbidities, and cardiac function along cardiac transcript levels, to unveil pathophysiological differences between DCM subgroups.

Methods And Results: We included 795 consecutive DCM patients from the Maastricht Cardiomyopathy Registry who underwent in-depth phenotyping, comprising extensive clinical data on aetiology and comorbodities, imaging and endomyocardial biopsies. Four mutually exclusive and clinically distinct phenogroups (PG) were identified based upon unsupervised hierarchical clustering of principal components: [PG1] mild systolic dysfunction, [PG2] auto-immune, [PG3] genetic and arrhythmias, and [PG4] severe systolic dysfunction. RNA-sequencing of cardiac samples (n = 91) revealed a distinct underlying molecular profile per PG: pro-inflammatory (PG2, auto-immune), pro-fibrotic (PG3; arrhythmia), and metabolic (PG4, low EF) gene expression. Furthermore, event-free survival differed among the four phenogroups, also when corrected for well-known clinical predictors. Decision tree modelling identified four clinical parameters (auto-immune disease, EF, atrial fibrillation, and kidney function) by which every DCM patient from two independent DCM cohorts could be placed in one of the four phenogroups with corresponding outcome (n = 789; Spain, n = 352 and Italy, n = 437), showing a feasible applicability of the phenogrouping.

Conclusion: The present study identified four different DCM phenogroups associated with significant differences in clinical presentation, underlying molecular profiles and outcome, paving the way for a more personalized treatment approach.
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http://dx.doi.org/10.1093/eurheartj/ehaa841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813623PMC
January 2021

Reply to Patella et al. and Lindestam Arlehamn et al.: Complex pandemic dynamics and effect of bacillus Calmette-Guérin (BCG) vaccination on COVID-19 prevalence and mortality.

Proc Natl Acad Sci U S A 2020 10 29;117(41):25207-25208. Epub 2020 Sep 29.

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.

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http://dx.doi.org/10.1073/pnas.2017197117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568233PMC
October 2020

Epidemiology of dengue fever in Guatemala.

PLoS Negl Trop Dis 2020 08 19;14(8):e0008535. Epub 2020 Aug 19.

Centre for Drugs and Diagnostics Research, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Dengue fever occurs worldwide and about 1% of cases progress to severe haemorrhage and shock. Dengue is endemic in Guatemala and its surveillance system could document long term trends. We analysed 17 years of country-wide dengue surveillance data in Guatemala to describe epidemiological trends from 2000 to 2016.Data from the national dengue surveillance database were analysed to describe dengue serotype frequency, seasonality, and outbreaks. We used Poisson regression models to compare the number of cases each year with subsequent years and to estimate incidence ratios within serotype adjusted by age and gender. 91,554 samples were tested. Dengue was confirmed by RT-qPCR, culture or NS1-ELISA in 7097 (7.8%) cases and was IgM ELISA-positive in 19,290 (21.1%) cases. DENV1, DENV2, DENV3, and DENV4 were detected in 2218 (39.5%), 2580 (45.9%), 591 (10.5%), and 230 (4.1%) cases. DENV1 and DENV2 were the predominant serotypes, but all serotypes caused epidemics. The largest outbreak occurred in 2010 with 1080 DENV2 cases reported. The incidence was higher among adults during epidemic years, with significant increases in 2005, 2007, and 2013 DENV1 outbreaks, the 2010 DENV2 and 2003 DENV3 outbreaks. Adults had a lower incidence immediately after epidemics, which is likely linked to increased immunity.
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http://dx.doi.org/10.1371/journal.pntd.0008535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458341PMC
August 2020

Predictors of recurrence of atrial fibrillation within the first 3 months after ablation.

Europace 2020 09;22(9):1337-1344

Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Universiteitsingel 50, 6229 ER Maastricht, Netherlands.

Aims: Freedom from atrial fibrillation (AF) at 1 year can be achieved in 50-70% of patients undergoing catheter ablation. Recurrent AF early after ablation most commonly terminates spontaneously without further interventional treatment but is associated with later recurrent AF. The aim of this investigation is to identify clinical and procedural factors associated with recurrence of AF early after ablation.

Methods And Results: We retrospectively analysed data for recurrence of AF within the first 3 months after catheter ablation from the randomized controlled AXAFA-AFNET 5 trial, which demonstrated that continuous anticoagulation with apixaban is as safe and as effective compared to vitamin K antagonists in 678 patients undergoing first AF ablation. The primary outcome of first recurrent AF within 90 days was observed in 163 (28%) patients, in which 78 (48%) patients experienced an event within the first 14 days post-ablation. After multivariable adjustment, a history of stroke/transient ischaemic attack [hazard ratio (HR) 1.54, 95% confidence interval (CI) 0.93-2.6; P = 0.11], coronary artery disease (HR 1.85, 95% CI 1.20-2.86; P = 0.005), cardioversion during ablation (HR 1.78, 95% CI 1.26-2.49; P = 0.001), and an age:sex interaction for older women (HR 1.01, 95% CI 1.00-1.01; P = 0.04) were associated with recurrent AF. The P-wave duration at follow-up was significantly longer for patients with AF recurrence (129 ± 31 ms vs. 122 ± 22 ms in patients without AF, P = 0.03).

Conclusion: Half of all early AF recurrences within the first 3 months post-ablation occurred within the first 14 days post-ablation. Vascular disease and cardioversion during the procedure are strong predictors of recurrent AF. P-wave duration at follow-up was longer in patients with recurrent AF.

Trial Registration: Clinicaltrials.gov identifier NCT02227550.
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http://dx.doi.org/10.1093/europace/euaa132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478316PMC
September 2020

BCG vaccine protection from severe coronavirus disease 2019 (COVID-19).

Proc Natl Acad Sci U S A 2020 07 9;117(30):17720-17726. Epub 2020 Jul 9.

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

A series of epidemiological explorations has suggested a negative association between national bacillus Calmette-Guérin (BCG) vaccination policy and the prevalence and mortality of coronavirus disease 2019 (COVID-19). However, these comparisons are difficult to validate due to broad differences between countries such as socioeconomic status, demographic structure, rural vs. urban settings, time of arrival of the pandemic, number of diagnostic tests and criteria for testing, and national control strategies to limit the spread of COVID-19. We review evidence for a potential biological basis of BCG cross-protection from severe COVID-19, and refine the epidemiological analysis to mitigate effects of potentially confounding factors (e.g., stage of the COVID-19 epidemic, development, rurality, population density, and age structure). A strong correlation between the BCG index, an estimation of the degree of universal BCG vaccination deployment in a country, and COVID-19 mortality in different socially similar European countries was observed ( = 0.88; = 8 × 10), indicating that every 10% increase in the BCG index was associated with a 10.4% reduction in COVID-19 mortality. Results fail to confirm the null hypothesis of no association between BCG vaccination and COVID-19 mortality, and suggest that BCG could have a protective effect. Nevertheless, the analyses are restricted to coarse-scale signals and should be considered with caution. BCG vaccination clinical trials are required to corroborate the patterns detected here, and to establish causality between BCG vaccination and protection from severe COVID-19. Public health implications of a plausible BCG cross-protection from severe COVID-19 are discussed.
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http://dx.doi.org/10.1073/pnas.2008410117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395502PMC
July 2020

CHRONIC WASTING DISEASE MODELING: AN OVERVIEW.

J Wildl Dis 2020 Oct;56(4):741-758

Department of Fish and Wildlife Conservation, Virginia Polytechnic Institute and State University, 310 W Campus Drive, Blacksburg, Virginia 24061, USA.

Chronic wasting disease (CWD) is an infectious and fatal prion disease occurring in the family Cervidae. To update the research community regarding the status quo of CWD epidemic models, we conducted a meta-analysis on CWD research. We collected data from peer-reviewed articles published since 1980, when CWD was first diagnosed, until December 2018. We explored the analytical methods used historically to understand CWD. We used 14 standardized variables to assess overall analytical approaches of CWD research communities, data used, and the modeling methods used. We found that CWD modeling initiated in the early 2000s and has increased since then. Connectivity of the research community was heavily reliant on a cluster of CWD researchers. Studies focused primarily on regression and compartment-based models, population-level approaches, and host species of game management concern. Similarly, CWD research focused on single populations, species, and locations, neglecting modeling using community ecology and biogeographic approaches. Chronic wasting disease detection relied on classic diagnostic methods with limited sensitivity for most stages of infection. Overall, we found that past modeling efforts generated a solid baseline for understanding CWD in wildlife and increased our knowledge on infectious prion ecology. Future analytical efforts should consider more sensitive diagnostic methods to quantify uncertainty and broader scale studies to elucidate CWD transmission beyond population-level approaches. Considering that infectious prions may not follow biological rules of well-known wildlife pathogens (i.e., viruses, bacteria, fungi), assumptions used when modeling other infectious disease may not apply for CWD. Chronic wasting disease is a new challenge in wildlife epidemiology.
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http://dx.doi.org/10.7589/2019-08-213DOI Listing
October 2020

BCG vaccine-induced protection from COVID-19 infection, wishful thinking or a game changer?

medRxiv 2020 May 12. Epub 2020 May 12.

A series of epidemiological explorations have suggested a negative association between national BCG vaccination policy and the prevalence and mortality of COVID-19. Nevertheless, these comparisons are difficult to validate due to broad differences between countries such as socioeconomic status, demographic structure, rural vs. urban settings, time of arrival of the pandemic, number of diagnostic tests and criteria for testing, and national control strategies to limit the spread of COVID-19. We review evidence for the potential biological basis of BCG cross-protection from severe COVID-19 and refine the epidemiological analysis to mitigate effects of potentially confounding factors (e.g., stage of the COVID-19 epidemic, development, rurality, population density and age structure). Results fail to confirm the null hypothesis of no-association between BCG vaccination and COVID-19 mortality, and suggest that BCG could have a protective effect. Nevertheless, the analyses are restricted to coarse-scale signals and should be considered with caution. BCG vaccination clinical trials are required to corroborate the patterns detected here and to establish causality between BCG vaccination and protection from severe COVID-19. Public health implications of a plausible BCG cross-protection from severe COVID-19 are discussed.
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http://dx.doi.org/10.1101/2020.05.05.20091975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241119PMC
May 2020

Linking Mosquito Ecology, Traits, Behavior, and Disease Transmission.

Trends Parasitol 2020 04 4;36(4):393-403. Epub 2020 Mar 4.

Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA; The Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Electronic address:

Mosquitoes are considered to be the deadliest animals on Earth because the diseases they transmit claim at least a million human lives every year globally. Here, we discuss the scales at which the effects of ecological factors cascade to influence epidemiologically relevant behaviors of adult mosquitoes. In particular, we focused our review on the environmental conditions (coarse-scale variables) that shape the life-history traits of larvae and adult mosquitoes (fine-scale traits), and how these factors and their association, in turn, modulate adult behaviors to influence mosquito-borne disease transmission. Finally, we explore the integration of physical, physiological, and behavioral information into predictive models with epidemiological applications.
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http://dx.doi.org/10.1016/j.pt.2020.02.001DOI Listing
April 2020

Kinetic Stabilities and Exchange Dynamics of Water-Soluble Bis-Formamide Caviplexes Studied Using Diffusion-Ordered NMR Spectroscopy (DOSY).

Chemistry 2020 Jul 9;26(37):8220-8225. Epub 2020 Jun 9.

Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology (BIST), Av. Països Catalans 16, 43007, Tarragona, Spain.

A deep cavitand binds long-chain trans,trans- and trans,cis-bis-formamide isomers in water solution giving a pair of caviplexes in a ca. 60:40 ratio. Both caviplexes display in/out guest exchange dynamics that are slow on the H NMR chemical shift timescale, but fast on the EXSY timescale. We apply diffusion-ordered NMR spectroscopy (DOSY) to characterize the caviplexes. On the diffusion timescale, the guest in/out exchange processes feature intermediate dynamics allowing the assessment of their kinetic stabilities. We found that the trans,cis-bis-formamide isomers form kinetically more stable caviplexes than the trans,trans-counterparts. We also show that the kinetic stabilities of the bis-formamide caviplexes relate well with their relative thermodynamic stabilities. Fortunately, the tuning of the DOSY parameters allowed the observation of the exchange dynamics as slow processes on the experiment timescale.
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http://dx.doi.org/10.1002/chem.202000781DOI Listing
July 2020

Focal Eosinophilic Myositis in the Hand: A Case Report.

J Clin Rheumatol 2020 Feb 19. Epub 2020 Feb 19.

Grupo de Investigación en Reumatología, Autoinmunidad y Medicina Traslacional, (GIRAT), Fundación Valle del Lili, Universidad Icesi Cali, Colombia Laboratorio de Inmunología, Fundación Valle del Lili, Cali, Colombia Grupo de Investigación en Reumatología, Autoinmunidad y Medicina Traslacional, (GIRAT), Fundación Valle del Lili, Universidad Icesi Cali, Colombia.

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http://dx.doi.org/10.1097/RHU.0000000000001340DOI Listing
February 2020

Synergistic China-US Ecological Research is Essential for Global Emerging Infectious Disease Preparedness.

Ecohealth 2020 03 3;17(1):160-173. Epub 2020 Feb 3.

Department of Environmental Science, Policy and Management, University of California, Berkeley, Berkeley, CA, USA.

The risk of a zoonotic pandemic disease threatens hundreds of millions of people. Emerging infectious diseases also threaten livestock and wildlife populations around the world and can lead to devastating economic damages. China and the USA-due to their unparalleled resources, widespread engagement in activities driving emerging infectious diseases and national as well as geopolitical imperatives to contribute to global health security-play an essential role in our understanding of pandemic threats. Critical to efforts to mitigate risk is building upon existing investments in global capacity to develop training and research focused on the ecological factors driving infectious disease spillover from animals to humans. International cooperation, particularly between China and the USA, is essential to fully engage the resources and scientific strengths necessary to add this ecological emphasis to the pandemic preparedness strategy. Here, we review the world's current state of emerging infectious disease preparedness, the ecological and evolutionary knowledge needed to anticipate disease emergence, the roles that China and the USA currently play as sources and solutions to mitigating risk, and the next steps needed to better protect the global community from zoonotic disease.
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http://dx.doi.org/10.1007/s10393-020-01471-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088356PMC
March 2020

The ecology of chronic wasting disease in wildlife.

Biol Rev Camb Philos Soc 2020 04 21;95(2):393-408. Epub 2019 Nov 21.

Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Medical School at Houston, Houston, TX, 77030, U.S.A.

Prions are misfolded infectious proteins responsible for a group of fatal neurodegenerative diseases termed transmissible spongiform encephalopathy or prion diseases. Chronic Wasting Disease (CWD) is the prion disease with the highest spillover potential, affecting at least seven Cervidae (deer) species. The zoonotic potential of CWD is inconclusive and cannot be ruled out. A risk of infection for other domestic and wildlife species is also plausible. Here, we review the current status of the knowledge with respect to CWD ecology in wildlife. Our current understanding of the geographic distribution of CWD lacks spatial and temporal detail, does not consider the biogeography of infectious diseases, and is largely biased by sampling based on hunters' cooperation and funding available for each region. Limitations of the methods used for data collection suggest that the extent and prevalence of CWD in wildlife is underestimated. If the zoonotic potential of CWD is confirmed in the short term, as suggested by recent results obtained in experimental animal models, there will be limited accurate epidemiological data to inform public health. Research gaps in CWD prion ecology include the need to identify specific biological characteristics of potential CWD reservoir species that better explain susceptibility to spillover, landscape and climate configurations that are suitable for CWD transmission, and the magnitude of sampling bias in our current understanding of CWD distribution and risk. Addressing these research gaps will help anticipate novel areas and species where CWD spillover is expected, which will inform control strategies. From an ecological perspective, control strategies could include assessing restoration of natural predators of CWD reservoirs, ultrasensitive CWD detection in biotic and abiotic reservoirs, and deer density and landscape modification to reduce CWD spread and prevalence.
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http://dx.doi.org/10.1111/brv.12568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085120PMC
April 2020

The 2019 report of The Lancet Countdown on health and climate change: ensuring that the health of a child born today is not defined by a changing climate.

Lancet 2019 11;394(10211):1836-1878

Institute for Human Health and Performance, University College London, London, UK.

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http://dx.doi.org/10.1016/S0140-6736(19)32596-6DOI Listing
November 2019

Relative hydrophilicities of and formamides.

Proc Natl Acad Sci U S A 2019 10 16;116(40):19815-19820. Epub 2019 Sep 16.

Center for Supramolecular Chemistry and Catalysis, Shanghai University, Shanghai 200444, China;

Secondary formamides are widely encountered in biology and exist as mixtures of both and isomers. Here, we assess hydrophilicity differences between isomeric formamides through direct competition experiments. Formamides bearing long aliphatic chains were sequestered in a water-soluble molecular container having a hydrophobic cavity with an end open to the aqueous medium. NMR spectroscopic experiments reveal a modest preference (<1 kcal/mol) for aqueous solvation of the formamide terminals over the isomers. With diformamides, the supramolecular approach allows staging of intramolecular competition between short-lived species with subtle differences in hydrophobic properties.
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http://dx.doi.org/10.1073/pnas.1911331116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778222PMC
October 2019

Guest Exchange Mechanisms in Mono-Metallic Pd /Pt -Cages Based on a Tetra-Pyridyl Calix[4]pyrrole Ligand.

Angew Chem Int Ed Engl 2019 11 24;58(45):16105-16109. Epub 2019 Sep 24.

Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology (BIST), Av. Països Catalans, 16, 43007, Tarragona, Spain.

Planar pyridyl N-oxides are encapsulated in mono-metallic Pd /Pt -cages based on a tetra-pyridyl calix[4]pyrrole ligand. The exchange dynamics of the cage complexes are slow on both the NMR chemical shift and EXSY timescales, but encapsulation of the guests by the cages is fast on the human timescale. A "French doors" mechanism, involving the rotation of the meso-phenyl walls of the cages, allows the passage of the planar guests. The encapsulation of quinuclidine N-oxide, a sterically more demanding guest, is slower than pyridyl N-oxides in the Pd -cage, and does not take place in the Pt counterpart. A modification of the encapsulation mechanism for the quinuclidine N-oxide is postulated that requires the partial dissociation of the Pd -cage. The substrate binding selectivity featured by the cages is related to their different guest uptake/release mechanisms.
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http://dx.doi.org/10.1002/anie.201909685DOI Listing
November 2019

First report case with negative genetic study (array CGH, exome sequencing) in patients with vertical transmission of Zika virus infection and associated brain abnormalities.

Appl Clin Genet 2019 30;12:141-150. Epub 2019 Jul 30.

Center for Research on Congenital Anomalies and Rare Diseases (CIACER), Department of Basic Medical Sciences, Universidad Icesi, Cali, Colombia.

Introduction: Zika virus (ZIKV) is a little-known emerging mosquito-borne flavivirus. The perinatal ZIKV infection was associated with birth defects during the Brazilian outbreak. There was an increased risk of intrauterine transmission of the virus and a marked increase in the number of newborns with microcephaly. We report on two such cases.

Case Report: The first case was a 25-year-old pregnant woman from Colombia who became acutely ill with general symptoms during the tenth week of gestation, followed by severe generalized itching and maculopapular rash for approximately five days. This case was reported during the epidemic stage of the ZIKV infection in Colombia. At 23.3 gestational weeks, ultrasonography showed abnormal intracranial anatomy with cerebral ventriculomegaly, microcephaly, and parenchymal calcification. Given the grave prognosis, the patient elected to terminate the pregnancy at 25 gestational weeks. The second case was a 24-year-old pregnant woman who became acutely ill during the 17th week of gestation, which corresponded with the ZIKV epidemic in Colombia. At 30.5 gestational weeks, ultrasonography showed isolated fetal cerebral ventriculomegaly. We detected ZIKV in the amniotic fluid; however, the virus was not detected in the urine or serum of the mother or fetus. Tests for dengue virus, chikungunya virus, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, HIV, hepatitis B and C, and parvovirus B19 were all negative. Different samples obtained from the placenta, amniotic liquid, and cerebrospinal fluid were positive for viral isolation of ZIKV RNA using TaqMan RT-PCR. Additionally, the parents and fetuses were tested for genetic diseases using whole exome sequencing and array CGH to rule out possible genetic syndromes that produce these congenital abnormalities.

Conclusion: These were the first cases in Colombia to show early vertical transmission of ZIKV and the first cases associated with congenital cerebral abnormalities in which molecular, infectious, and genomic tests were performed.
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http://dx.doi.org/10.2147/TACG.S190661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679697PMC
July 2019

Spatial distribution and spread potential of sixteen Leptospira serovars in a subtropical region of Brazil.

Transbound Emerg Dis 2019 Nov 17;66(6):2482-2495. Epub 2019 Aug 17.

Department of Population Health and Pathobiology, North Carolina State University, Raleigh, North Carolina, USA.

Leptospirosis is a bacterial disease that represents a major problem in animal and public health due to its high prevalence and widespread distribution. This zoonotic disease is most prevalent in tropical environments where conditions favour pathogen survival. The ecological preferences of Leptospira serovars are poorly understood, limiting our knowledge of where and when outbreaks can occur, which may result in misinformed prevention and control plans. While the disease can occur consistently in time and space in tropical regions, research on the ecology of leptospirosis remains limited in subtropical regions. This research gap regarding Leptospira ecology brings public and veterinary health problems, impacting local economies. To fill this gap of knowledge, we suggest to assess geographic and ecological features among Leptospira serovars in a subtropical area of Brazil where leptospirosis is endemic to (a) highlight environmental conditions that facilitate or limit Leptospira spread and survival and (b) reconstruct its geographic distribution. An ecological niche modelling framework was used to characterize and compare Leptospira serovars in both geographic and environmental space. Our results show that despite the geographic overlap exhibited by the different serovars assessed, we found ecological divergence among their occupied ecological niches. Ecological divergences were expressed as ranges of potential distributions and environmental conditions found suitably by serovar, Sejroe being the most asymmetric (<0.15). Most important predictors for the potential distribution of most serovars were soil pH (31.7%) and landscape temperature (24.2%). Identification of environmental preferences will allow epidemiologists to better infer the presence of a serovar based on the environmental characteristics of regions rather than inferences based solely on historical epidemiological records. Including geographic and ecological ranges of serovars also may help to forecast transmission potential of Leptospira in public health and the food animal practice.
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http://dx.doi.org/10.1111/tbed.13306DOI Listing
November 2019

Cohesin complex-associated holoprosencephaly.

Brain 2019 09;142(9):2631-2643

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

Marked by incomplete division of the embryonic forebrain, holoprosencephaly is one of the most common human developmental disorders. Despite decades of phenotype-driven research, 80-90% of aneuploidy-negative holoprosencephaly individuals with a probable genetic aetiology do not have a genetic diagnosis. Here we report holoprosencephaly associated with variants in the two X-linked cohesin complex genes, STAG2 and SMC1A, with loss-of-function variants in 10 individuals and a missense variant in one. Additionally, we report four individuals with variants in the cohesin complex genes that are not X-linked, SMC3 and RAD21. Using whole mount in situ hybridization, we show that STAG2 and SMC1A are expressed in the prosencephalic neural folds during primary neurulation in the mouse, consistent with forebrain morphogenesis and holoprosencephaly pathogenesis. Finally, we found that shRNA knockdown of STAG2 and SMC1A causes aberrant expression of HPE-associated genes ZIC2, GLI2, SMAD3 and FGFR1 in human neural stem cells. These findings show the cohesin complex as an important regulator of median forebrain development and X-linked inheritance patterns in holoprosencephaly.
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http://dx.doi.org/10.1093/brain/awz210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245359PMC
September 2019

Genetic variants in the KDM6B gene are associated with neurodevelopmental delays and dysmorphic features.

Am J Med Genet A 2019 07 23;179(7):1276-1286. Epub 2019 May 23.

Greenwood Genetic Center, Greenwood, South Carolina.

Lysine-specific demethylase 6B (KDM6B) demethylates trimethylated lysine-27 on histone H3. The methylation and demethylation of histone proteins affects gene expression during development. Pathogenic alterations in histone lysine methylation and demethylation genes have been associated with multiple neurodevelopmental disorders. We have identified a number of de novo alterations in the KDM6B gene via whole exome sequencing (WES) in a cohort of 12 unrelated patients with developmental delay, intellectual disability, dysmorphic facial features, and other clinical findings. Our findings will allow for further investigation in to the role of the KDM6B gene in human neurodevelopmental disorders.
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http://dx.doi.org/10.1002/ajmg.a.61173DOI Listing
July 2019

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

Am J Hum Genet 2019 06 9;104(6):1210-1222. Epub 2019 May 9.

Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.
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http://dx.doi.org/10.1016/j.ajhg.2019.03.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556837PMC
June 2019

An Ecological Framework for Modeling the Geography of Disease Transmission.

Trends Ecol Evol 2019 07 8;34(7):655-668. Epub 2019 May 8.

EcoHealth Alliance, 460 W. 34th Street, New York, NY, USA. Electronic address:

Ecological niche modeling (ENM) is widely employed in ecology to predict species' potential geographic distributions in relation to their environmental constraints and is rapidly becoming the gold-standard method for disease risk mapping. However, given the biological complexity of disease systems, the traditional ENM framework requires reevaluation. We provide an overview of the application of ENM to disease systems and propose a theoretical framework based on the biological properties of both hosts and parasites to produce reliable outputs resembling disease system distributions. Additionally, we discuss the differences between biological considerations when implementing ENM for distributional ecology and epidemiology. This new framework will help the field of disease ecology and applications of biogeography in the epidemiology of infectious diseases.
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http://dx.doi.org/10.1016/j.tree.2019.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114676PMC
July 2019

Alternative reproductive adaptations predict asymmetric responses to climate change in lizards.

Sci Rep 2019 03 25;9(1):5093. Epub 2019 Mar 25.

MacroBiodiversity Lab, School of Science and Technology, Department of Biosciences, Nottingham Trent University, Nottingham, NG11 8NS, United Kingdom.

Anthropogenic climate change ranks among the major global-scale threats to modern biodiversity. Extinction risks are known to increase via the interactions between rapid climatic alterations and environmentally-sensitive species traits that fail to adapt to those changes. Accumulating evidence reveals the influence of ecophysiological, ecological and phenological factors as drivers underlying demographic collapses that lead to population extinctions. However, the extent to which life-history traits influence population responses to climate change remains largely unexplored. The emerging 'cul-de-sac hypothesis' predicts that reptilian viviparity ('live-bearing' reproduction), a 'key innovation' facilitating historical invasions of cold climates, increases extinction risks under progressively warming climates compared to oviparous reproduction - as warming advances polewards/mountainwards, historically cold-climates shrink, leading viviparous species to face demographic collapses. We present the first large-scale test of this prediction based on multiple lizard radiations and on future projections of climate-based ecological niche models. Viviparous species were found to experience stronger elevational range shifts (and potentially increased extinctions) in coming decades, compared to oviparous lizards. Therefore, our analyses support the hypothesis's fundamental prediction that elevational shifts are more severe in viviparous species, and highlight the role that life-history adaptations play in the responses of biodiversity to ongoing climate change.
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http://dx.doi.org/10.1038/s41598-019-41670-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433898PMC
March 2019

Variants in TCF20 in neurodevelopmental disability: description of 27 new patients and review of literature.

Genet Med 2019 09 11;21(9):2036-2042. Epub 2019 Feb 11.

GeneDx, Gaithersburg, MD, USA.

Purpose: To define the clinical characteristics of patients with variants in TCF20, we describe 27 patients, 26 of whom were identified via exome sequencing. We compare detailed clinical data with 17 previously reported patients.

Methods: Patients were ascertained through molecular testing laboratories performing exome sequencing (and other testing) with orthogonal confirmation; collaborating referring clinicians provided detailed clinical information.

Results: The cohort of 27 patients all had novel variants, and ranged in age from 2 to 68 years. All had developmental delay/intellectual disability. Autism spectrum disorders/autistic features were reported in 69%, attention disorders or hyperactivity in 67%, craniofacial features (no recognizable facial gestalt) in 67%, structural brain anomalies in 24%, and seizures in 12%. Additional features affecting various organ systems were described in 93%. In a majority of patients, we did not observe previously reported findings of postnatal overgrowth or craniosynostosis, in comparison with earlier reports.

Conclusion: We provide valuable data regarding the prognosis and clinical manifestations of patients with variants in TCF20.
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http://dx.doi.org/10.1038/s41436-019-0454-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171701PMC
September 2019