ECC–RT-PCR: a new method to determine the viability and infectivity of Giardia cysts

SummaryBackgroundGiardia sp is a major cause of diarrheal illness worldwide, and millions of people are infected each year. Rapid methods to determine the infectivity and virulence of isolates are critical for the development of intervention strategies to control the transmission of Giardia sp cysts, which occurs through contaminated surfaces, food, and water. However, determining the viability, infectivity, and virulence of Giardia sp cysts using molecular methods is a technical challenge because of the lack of a cell culture model.MethodThis study was designed to evaluate mRNA expression in trophozoites and to assess trophozoite attachment to cell monolayer and changes in transcellular resistance as an indicator of Giardia sp viability and infectivity. Heat shock mRNA in Giardia cysts and variant-specific protein (VSP) mRNA in trophozoites were quantified by reverse transcription polymerase chain reaction (RT-PCR). C2bb (Caco-2) cells were grown on transwell chambers to study the attachment of trophozoites, changes in transcellular resistance, and expression of VSP in trophozoites.ResultsThe results of these molecular and cell culture studies indicate a direct linear correlation between the viability and infectivity of fresh stocks of Giardia sp cysts. The attachment of trophozoites to cell monolayer, expression of VSP, and change in the transcellular resistance was directly correlated with their infectivity in neonatal mice. PCR was successfully combined with the electrophysiological analysis of cell culture (ECC–RT-PCR) post-trophozoite attachment.ConclusionThis study shows that the ECC–RT-PCR, a new integrated cell culture assay, can be used as a rapid and cost-effective tool for assessing the viability and infectivity of environmental isolates of Giardia sp cysts

Airborne Infectious Agents and Other Pollutants in Automobiles for Domestic Use: Potential Health Impacts and Approaches to Risk Mitigation

Theworld total of passenger cars is expected to go fromthe current one billion to \u3e2.5 billion by 2050. Cars for domestic use account for ∼74% of the world’s yearly production ofmotorized vehicles. In North America, ∼80% of the commuters use their own car with another 5.6% travelling as passengers.With the current life-expectancy of 78.6 years, the average North American spends 4.3 years driving a car! This equates to driving 101 minutes/day with a lifetime driving distance of nearly 1.3 million km inside the confined and often shared space of the car with exposure to a mix of potentially harmful pathogens, allergens, endotoxins, particulates, and volatile organics. Such risks may increase in proportion to the unprecedented upsurge in the numbers of family cars globally. Though new technologies may reduce the levels of air pollution from car exhausts and other sources, they are unlikely to impact our in-car exposure to pathogens. Can commercial in-car air decontamination devices reduce the risk from airborne infections and other pollutants?We lack scientifically rigorous protocols to verify the claims of such devices. Here we discuss the essentials of a customized aerobiology facility and test protocols to assess such devices under field-relevant conditions

Combating SARS-CoV-2: Leveraging microbicidal experiences with other emerging/re-emerging viruses

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan City, China, late in December 2019 is another example of an emerging zoonotic virus that threatens public health and international travel and commerce. When such a virus emerges, there is often insufficient specific information available on mechanisms of virus dissemination from animal to human or from person to person, on the level or route of infection transmissibility or of viral release in body secretions/excretions, and on the survival of virus in aerosols or on surfaces. The effectiveness of available virucidal agents and hygiene practices as interventions for disrupting the spread of infection and the associated diseases may not be clear for the emergent virus. In the present review, we recommend approaches for infection prevention and control for SARS-CoV-2 which can be invoked based on pre-existing data on microbicidal and hygiene effectiveness for related and unrelated enveloped viruse

Reducing antibiotic prescribing and addressing the global problem of antibiotic resistance by targeted hygiene in the home and everyday life settings: A position paper

Antimicrobial resistance (AMR) continues to threaten global health. Although global and national AMR action plans are in place, infection prevention and control is primarily discussed in the context of health care facilities with home and everyday life settings barely addressed. As seen with the recent global SARS-CoV-2 pandemic, everyday hygiene measures can play an important role in containing the threat from infectious microorganisms. This position paper has been developed following a meeting of global experts in London, 2019. It presents evidence that home and community settings are important for infection transmission and also the acquisition and spread of AMR. It also demonstrates that the targeted hygiene approach offers a framework for maximizing protection against colonization and infections, thereby reducing antibiotic prescribing and minimizing selection pressure for the development of antibiotic resistance. If combined with the provision of clean water and sanitation, targeted hygiene can reduce the circulation of resistant bacteria in homes and communities, regardless of a country\u27s Human Development Index (overall social and economic development). Achieving a reduction of AMR strains in health care settings requires a mirrored reduction in the community. The authors call upon national and international policy makers, health agencies, and health care professionals to further recognize the importance of targeted hygiene in the home and everyday life settings for preventing and controlling infection, in a unified quest to tackle AMR

Atmospheric CO₂ over the last 1000 years: A high-resolution record from the West Antarctic Ice Sheet (WAIS) Divide ice core

We report a decadally resolved record of atmospheric CO₂ concentration for the last 1000 years, obtained from the West Antarctic Ice Sheet (WAIS) Divide shallow ice core. The most prominent feature of the pre-industrial period is a rapid ∼7 ppm decrease of CO₂ in a span of ∼20–50 years at ∼1600 A.D. This observation confirms the timing of an abrupt atmospheric CO₂ decrease of ∼10 ppm observed for that time period in the Law Dome ice core CO₂ records, but the true magnitude of the decrease remains unclear. Atmospheric CO₂ variations over the time period 1000–1800 A.D. are statistically correlated with northern hemispheric climate and tropical Indo-Pacific sea surface temperature. However, the exact relationship between CO₂ and climate remains elusive due to regional climate variations and/or uneven geographical data density of paleoclimate records. We observe small differences of 0 ∼ 2% (0 ∼ 6 ppm) among the high-precision CO₂ records from the Law Dome, EPICA Dronning Maud Land and WAIS Divide Antarctic ice cores. However, those records share common trends of CO₂ change on centennial to multicentennial time scales, and clearly show that atmospheric CO₂ has been increasing above preindustrial levels since ∼1850 A.D

Virucidal action mechanism of alcohol and divalent cations against human adenovirus

Hygiene and disinfection practices play an important role at preventing spread of viral infections in household, industrial and clinical settings. Although formulations based on >70% ethanol are virucidal, there is a currently a need to reformulate products with much lower alcohol concentrations. It has been reported that zinc can increase the virucidal activity of alcohols, although the reasons for such potentiation is unclear. One approach in developing virucidal formulations is to understand the mechanisms of action of active ingredients and formulation excipients. Here, we investigated the virucidal activity of alcohol (40% w/v) and zinc sulfate (0.1% w/v) combinations and their impact on a human adenovirus (HAdV) using, nucleic acid integrity assays, atomic force microscopy (AFM) and transmission electron microscopy (TEM). We observed no difference in virucidal activity (5 log10 reduction in 60 min) against between an ethanol only based formulation and a formulation combining ethanol and zinc salt. Furthermore, TEM imaging showed that the ethanol only formulation produced gross capsid damage, whilst zinc-based formulation or formulation combining both ethanol and zinc did not affect HAdV DNA. Unexpectedly, the addition of nickel salt (5 mM NiCl2) to the ethanol-zinc formulation contributed to a weakening of the capsid and alteration of the capsid mechanics exemplified by AFM imaging, together with structural capsid damage. The addition of zinc sulfate to the ethanol formulation did not add the formulation efficacy, but the unexpected mechanistic synergy between NiCl2 and the ethanol formulation opens an interesting perspective for the possible potentiation of an alcohol-based formulation. Furthermore, we show that AFM can be an important tool for understanding the mechanistic impact of virucidal formulation

Genetic history from the Middle Neolithic to present on the Mediterranean island of Sardinia

The island of Sardinia has been of particular interest to geneticists for decades. The current model for Sardinia's genetic history describes the island as harboring a founder population that was established largely from the Neolithic peoples of southern Europe and remained isolated from later Bronze Age expansions on the mainland. To evaluate this model, we generate genome-wide ancient DNA data for 70 individuals from 21 Sardinian archaeological sites spanning the Middle Neolithic through the Medieval period. The earliest individuals show a strong affinity to western Mediterranean Neolithic populations, followed by an extended period of genetic continuity on the island through the Nuragic period (second millennium BCE). Beginning with individuals from Phoenician/Punic sites (first millennium BCE), we observe spatially-varying signals of admixture with sources principally from the eastern and northern Mediterranean. Overall, our analysis sheds light on the genetic history of Sardinia, revealing how relationships to mainland populations shifted over time.Joseph H. Marcus ... Wolfgang Haak ... et al

Frontotemporal dementia and its subtypes: a genome-wide association study

SummaryBackground Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with {FTD} and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with {FTD} and 4308 controls), we did separate association analyses for each {FTD} subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and {FTD} overlapping with motor neuron disease FTD-MND), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, \{HLA\} locus (immune system), for rs9268877 (p=1·05 × 10−8; odds ratio=1·204 95% \{CI\} 1·11–1·30), rs9268856 (p=5·51 × 10−9; 0·809 0·76–0·86) and rs1980493 (p value=1·57 × 10−8, 0·775 0·69–0·86) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural \{FTD\} subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10−7; 0·814 0·71–0·92). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Exploring Cosmic Origins with CORE: Cosmological Parameters

We forecast the main cosmological parameter constraints achievable with theCORE space mission which is dedicated to mapping the polarisation of the CosmicMicrowave Background (CMB). CORE was recently submitted in response to ESA'sfifth call for medium-sized mission proposals (M5). Here we report the resultsfrom our pre-submission study of the impact of various instrumental options, inparticular the telescope size and sensitivity level, and review the great,transformative potential of the mission as proposed. Specifically, we assessthe impact on a broad range of fundamental parameters of our Universe as afunction of the expected CMB characteristics, with other papers in the seriesfocusing on controlling astrophysical and instrumental residual systematics. Inthis paper, we assume that only a few central CORE frequency channels areusable for our purpose, all others being devoted to the cleaning ofastrophysical contaminants. On the theoretical side, we assume LCDM as ourgeneral framework and quantify the improvement provided by CORE over thecurrent constraints from the Planck 2015 release. We also study the jointsensitivity of CORE and of future Baryon Acoustic Oscillation and Large ScaleStructure experiments like DESI and Euclid. Specific constraints on the physicsof inflation are presented in another paper of the series. In addition to thesix parameters of the base LCDM, which describe the matter content of aspatially flat universe with adiabatic and scalar primordial fluctuations frominflation, we derive the precision achievable on parameters like thosedescribing curvature, neutrino physics, extra light relics, primordial heliumabundance, dark matter annihilation, recombination physics, variation offundamental constants, dark energy, modified gravity, reionization and cosmicbirefringence. (ABRIDGED