Research on the human microbiome, the microbiota that live in, on, and around the human person, has revolutionized our understanding of the complex interactions between microbial life and human ...health and disease. The microbiome may also provide a valuable tool in forensic death investigations by helping to reveal the postmortem interval (PMI) of a decedent that is discovered after an unknown amount of time since death. Current methods of estimating PMI for cadavers discovered in uncontrolled, unstudied environments have substantial limitations, some of which may be overcome through the use of microbial indicators. In this project, we sampled the microbiomes of decomposing human cadavers, focusing on the skin microbiota found in the nasal and ear canals. We then developed several models of statistical regression to establish an algorithm for predicting the PMI of microbial samples. We found that the complete data set, rather than a curated list of indicator species, was preferred for training the regressor. We further found that genus and family, rather than species, are the most informative taxonomic levels. Finally, we developed a k-nearest- neighbor regressor, tuned with the entire data set from all nasal and ear samples, that predicts the PMI of unknown samples with an average error of ±55 accumulated degree days (ADD). This study outlines a machine learning approach for the use of necrobiome data in the prediction of the PMI and thereby provides a successful proof-of- concept that skin microbiota is a promising tool in forensic death investigations.
Abstract
Global ultraviolet (UV) surface reflectivity climatologies are all composed from daylight passive remote sensing observations of reflected UV light, generally integrated over a distribution ...of attainable reflection directions. We discovered the sensitivity of Aeolus lidar surface returns (LSR) to surface characteristics, providing the first evidence that active remote sensing can be effectively used for retrieving unidirectional UV surface reflectivity on global scales. LSR reproduces surface reflectivity monthly changes in Sahara, which are visible in the Lambertian Equivalent Reflectivity (LER) climatologies from TROPOMI and GOME-2. Very high correlations (r > 0.90) between gridded LSR and the LER climatologies are reported at global and regional scales for 36 different regions. Three clear land cover gradients are discerned from Aeolus LSR signal: (1) water/land, (2) vegetation/arid areas and (3) no snow/snow. The strongest LSR signal was retrieved over snow, while over vegetation, we found moderate negative agreement (r < − 0.60) between LSR and vegetation index proxy. Overall, the success of the first active remote sensing method for retrieving unidirectional UV surface reflectivity using Aeolus is demonstrated. Our approach can be effectively used to detect unresolved land and, especially, snow cover changes in high latitudes because, unlike passive instruments, Aeolus also provided nighttime observations.
Metagenomics uses nucleic acid sequencing to characterize species diversity in different niches such as environmental biomes or the human microbiome. Most studies have used 16S rRNA amplicon ...sequencing to identify bacteria. However, the decreasing cost of sequencing has resulted in a gradual shift away from amplicon analyses and towards shotgun metagenomic sequencing. Shotgun metagenomic data can be used to identify a wide range of species, but have rarely been applied to fungal identification. Here, we develop a sequence classification pipeline, FindFungi, and use it to identify fungal sequences in public metagenome datasets. We focus primarily on animal metagenomes, especially those from pig and mouse microbiomes. We identified fungi in 39 of 70 datasets comprising 71 fungal species. At least 11 pathogenic species with zoonotic potential were identified, including Candida tropicalis. We identified Pseudogymnoascus species from 13 Antarctic soil samples initially analyzed for the presence of bacteria capable of degrading diesel oil. We also show that Candida tropicalis and Candida loboi are likely the same species. In addition, we identify several examples where contaminating DNA was erroneously included in fungal genome assemblies.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by accumulation of extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles, leading to chronic ...activation of astrocytes and microglia and persistent neuroinflammation. Aβ-linked activation of microglia and astrocytes leads to increased intracellular calcium and production of proinflammatory cytokines, impacting the progression of neurodegeneration. An N-terminal Aβ fragment (Aβ
) and a shorter hexapeptide core sequence within the N-Aβ fragment (N-Aβcore: Aβ
) have previously been shown to protect against Aβ-induced mitochondrial dysfunction, oxidative stress and apoptosis in neurons and rescue synaptic and spatial memory deficits in an APP/PSEN1 mouse model. Here, we hypothesized that the N-Aβ fragment and N-Aβcore are protective against Aβ-induced gliotoxicity, promoting a neuroprotective environment and potentially alleviating the characteristically persistent neuroinflammation present in AD.
We treated ex vivo organotypic brain slice cultures from an aged familial AD mouse model, 5xFAD, with the N-Aβcore and used immunocytochemistry to assess the impact on astrogliosis and microgliosis and alterations in synaptophysin-positive puncta engulfed by microglia. Isolated neuron/glia cultures, mixed glial cultures or a microglial cell line were treated with oligomeric human Aβ at concentrations mimicking the pathogenic concentrations (μM) observed in AD in the absence or presence of the non-toxic N-terminal Aβ fragments. Resultant changes in synaptic density, gliosis, oxidative stress, mitochondrial dysfunction, apoptosis, and the expression and release of proinflammatory markers were then determined.
We demonstrate that the N-terminal Aβ fragments mitigated the phenotypic switch leading to astrogliosis and microgliosis induced by pathological concentrations of Aβ in mixed glial cultures and organotypic brain slice cultures from the transgenic 5xFAD mouse model, while protecting against Aβ-induced oxidative stress, mitochondrial dysfunction and apoptosis in isolated astrocytes and microglia. Moreover, the addition of the N-Aβcore attenuated the expression and release of proinflammatory mediators in microglial cells activated by Aβ and rescued microglia-mediated loss of synaptic elements induced by pathological levels of Aβ.
Together, these findings indicate the protective functions of the N-terminal Aβ fragments extend to reactive gliosis and gliotoxicity induced by Aβ, by preventing or reversing glial reactive states indicative of neuroinflammation and synaptic loss central to AD pathogenesis.
The formation of neuronal networks is a complex phenomenon of fundamental importance for understanding the development of the nervous system. The basic process underlying the network formation is ...axonal growth, a process involving the extension of axons from the cell body and axonal navigation toward target neurons. Axonal growth is guided by the interactions between the tip of the axon (growth cone) and its extracellular environmental cues, which include intercellular interactions, the biochemical landscape around the neuron, and the mechanical and geometrical features of the growth substrate. Here, we present a comprehensive experimental and theoretical analysis of axonal growth for neurons cultured on micropatterned polydimethylsiloxane (PDMS) surfaces. We demonstrate that closed-loop feedback is an essential component of axonal dynamics on these surfaces: the growth cone continuously measures environmental cues and adjusts its motion in response to external geometrical features. We show that this model captures all the characteristics of axonal dynamics on PDMS surfaces for both untreated and chemically modified neurons. We combine experimental data with theoretical analysis to measure key parameters that describe axonal dynamics: diffusion (cell motility) coefficients, speed and angular distributions, and cell-substrate interactions. The experiments performed on neurons treated with Taxol (inhibitor of microtubule dynamics) and Y-27632 (disruptor of actin filaments) indicate that the internal dynamics of microtubules and actin filaments plays a critical role for the proper function of the feedback mechanism. Our results demonstrate that axons follow geometrical patterns through a contact-guidance mechanism, in which high-curvature geometrical features impart high traction forces to the growth cone. These results have important implications for our fundamental understanding of axonal growth as well as for bioengineering novel substrate to guide neuronal growth and promote nerve repair.
The role of childcare educators is important given that 81% of preschoolers living in developed countries receive childcare outside their home. Since children learn by observing and imitating others, ...childcare educators may play a role in promoting healthy eating behaviours and physical activity in young children. Six databases were searched for quantitative peer‐reviewed, English or French primary studies reporting the correlates, predictors or effectiveness of childcare educators' practices on preschoolers' healthy eating and physical activity behaviours. Risk of bias was assessed using the Quality Assessment Tool for Quantitative Studies. Fifteen articles were included in this review: 10 measured physical activity levels and five assessed eating behaviours. The quality score was rated as low for eight of these articles, and as moderate for the remaining seven. Two of four cross‐sectional studies reported a positive relationship between educators and children's behaviours. Eleven intervention studies reported significant favourable effects of interventions. Educators may play a positive role in promoting healthy behaviours in children, but this is mainly based on a small number of intervention type studies of low or moderate quality. The influence of specific components of educators' practices on children's healthy eating and physical activity behaviours remains inconclusive.
The prevalence of polypharmacy increases with age, increasing the exposure of older adults to potentially inappropriate medications (PIMs). Deprescribing has been shown to reduce PIMs for older ...residents in long-term care; however, deprescribing is not universally implemented. This study aims to identify the barriers and enablers to deprescribing in Irish long-term care facilities from the healthcare professionals' (HCPs) perspective.
A qualitative descriptive approach was conducted using semi-structured interviews with HCPs working in long-term care (general practitioners, pharmacists and nurses). Purposive sampling with maximum variation was applied to select long-term care sites to identify HCPs, supplemented with convenience sampling of post-graduate HCPs from University College Cork. Data was thematically analysed and mapped to a framework of deprescribing barriers and enablers informed by the Theoretical Domains Framework.
Twenty-six HCPs participated from 13 long-term care facilities. The main barriers and enablers identified mapped to five domains. Barriers included insufficient resources, lack of co-ordination between healthcare settings and negative social influences. Additional barriers exist in private settings including deprescribing awareness, commitment and the need for incentives. Deprescribing enablers included interprofessional support and patient social influence. To encourage deprescribing, potential enablers include HCP education, pharmacist role expansion and tailored deprescribing guidelines within a structured process.
Interventions to support deprescribing should build on existing systems, involve stakeholders and utilise guidelines within a structured process. Any intervention must account for the nuanced barriers and enablers which exist in both public and private settings.
THE EARTHCARE SATELLITE Illingworth, A. J.; Barker, H. W.; Beljaars, A. ...
Bulletin of the American Meteorological Society,
08/2015, Volume:
96, Issue:
8
Journal Article
Peer reviewed
Open access
The collective representation within global models of aerosol, cloud, precipitation, and their radiative properties remains unsatisfactory. They constitute the largest source of uncertainty in ...predictions of climatic change and hamper the ability of numerical weather prediction models to forecast high-impact weather events. The joint European Space Agency (ESA)–Japan Aerospace Exploration Agency (JAXA) Earth Clouds, Aerosol and Radiation Explorer (EarthCARE) satellite mission, scheduled for launch in 2018, will help to resolve these weaknesses by providing global profiles of cloud, aerosol, precipitation, and associated radiative properties inferred from a combination of measurements made by its collocated active and passive sensors. EarthCARE will improve our understanding of cloud and aerosol processes by extending the invaluable dataset acquired by the A-Train satellitesCloudSat, Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO), andAqua. Specifically, EarthCARE’s cloud profiling radar, with 7 dB more sensitivity thanCloudSat, will detect more thin clouds and its Doppler capability will provide novel information on convection, precipitating ice particle, and raindrop fall speeds. EarthCARE’s 355-nm high-spectral-resolution lidar will measure directly and accurately cloud and aerosol extinction and optical depth. Combining this with backscatter and polarization information should lead to an unprecedented ability to identify aerosol type. The multispectral imager will provide a context for, and the ability to construct, the cloud and aerosol distribution in 3D domains around the narrow 2D retrieved cross section. The consistency of the retrievals will be assessed to within a target of ±10 W m−2on the (10 km)² scale by comparing the multiview broadband radiometer observations to the top-of-atmosphere fluxes estimated by 3D radiative transfer models acting on retrieved 3D domains.
Direct evidence in humans for the impact of the microbiome on nutrient absorption is lacking. We conducted an extended inpatient study using two interventions that we hypothesized would alter the gut ...microbiome and nutrient absorption. In each, stool calorie loss, a direct proxy of nutrient absorption, was measured. The first phase was a randomized cross-over dietary intervention in which all participants underwent in random order 3 d of over- and underfeeding. The second was a randomized, double-blind, placebo-controlled pharmacologic intervention using oral vancomycin or matching placebo (NCT02037295). Twenty-seven volunteers (17 men and 10 women, age 35.1 ± 7.3, BMI 32.3 ± 8.0), who were healthy other than having impaired glucose tolerance and obesity, were enrolled and 25 completed the entire trial. The primary endpoints were the effects of dietary and pharmacological intervention on stool calorie loss. We hypothesized that stool calories expressed as percentage of caloric intake would increase with underfeeding compared with overfeeding and increase during oral vancomycin treatment. Both primary endpoints were met. Greater stool calorie loss was observed during underfeeding relative to overfeeding and during vancomycin treatment compared with placebo. Key secondary endpoints were to evaluate the changes in gut microbial community structure as evidenced by amplicon sequencing and metagenomics. We observed only a modest perturbation of gut microbial community structure with under- versus overfeeding but a more widespread change in community structure with reduced diversity with oral vancomycin. Increase in Akkermansia muciniphila was common to both interventions that resulted in greater stool calorie loss. These results indicate that nutrient absorption is sensitive to environmental perturbations and support the translational relevance of preclinical models demonstrating a possible causal role for the gut microbiome in dietary energy harvest.
The ESX (or Type VII) secretion systems are protein export systems in mycobacteria and many Gram-positive bacteria that mediate a broad range of functions including virulence, conjugation, and ...metabolic regulation. These systems translocate folded dimers of WXG100-superfamily protein substrates across the cytoplasmic membrane. We report the cryo-electron microscopy structure of an ESX-3 system, purified using an epitope tag inserted with recombineering into the chromosome of the model organism
. The structure reveals a stacked architecture that extends above and below the inner membrane of the bacterium. The ESX-3 protomer complex is assembled from a single copy of the EccB
, EccC
, and EccE
and two copies of the EccD
protein. In the structure, the protomers form a stable dimer that is consistent with assembly into a larger oligomer. The ESX-3 structure provides a framework for further study of these important bacterial transporters.
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