scholarly journals Deep behavioural phenotyping reveals divergent trajectories of ageing and quantifies health state in C. elegans

2019 ◽  
Author(s):  
Céline N. Martineau ◽  
Bora Baskaner ◽  
Renée I. Seinstra ◽  
William R. Schafer ◽  
André E. X. Brown ◽  
...  
Keyword(s):  
Health Risks ◽  
Early Onset ◽  
Disease Model ◽  
High Accuracy ◽  
Health State ◽  
Large Set ◽  
Physiological Ageing ◽  
C Elegans ◽  
Behavioural Phenotyping ◽  
Specific Health

AbstractNeurodegenerative diseases may be the cause or the consequence of an acceleration of physiological ageing. Evidence for this concept is lacking due to practical limitations of human studies. Here, we compared the processes of physiological and pathological ageing of individual C. elegans over their lifespan. Using multi-parametric phenotyping, trajectories of ageing can be defined within a phenotypic landscape made of a large set of phenotypical features. Rather than an acceleration of ageing, a model for synucleinopathy showed a divergent trajectory of ageing. The pathological progression in individual animals can be predicted from early phenotypes with high accuracy. Despite of similar lifespans, disease-model worms display an early onset of decline in their phenotypic range of ability. This loss of flexibility provides an index of health valid for physiological and pathological contexts. Finally, we demonstrate the power of multi-parametric dataset to describe ageing, to quantify health and to predict specific health risks.

Deep Behavioural Phenotyping Reveals Divergent Trajectories of Ageing and Quantifies Health in  C. elegans

2019 ◽  
Author(s):  
Céline N. Martineau ◽  
Bora Baskaner ◽  
Renée I. Seinstra ◽  
William R. Schafer ◽  
André EX Brown ◽  
...  
Keyword(s):  
C Elegans ◽  
Behavioural Phenotyping

Discrete differential operators for periodic and two-periodic time functions

2019 ◽  
Vol 38 (1) ◽  
pp. 325-347 ◽  
Author(s):  
Tadeusz Sobczyk ◽  
Michał Radzik ◽  
Natalia Radwan-Pragłowska
Keyword(s):  
Differential Operators ◽  
High Accuracy ◽  
Large Set ◽  
Periodic Functions ◽  
Content Type ◽  
Second Derivatives ◽  
Non Linear ◽  
Discrete Operators ◽  
Linear Differential ◽  
Very High

Purpose To identify the properties of novel discrete differential operators of the first- and the second-order for periodic and two-periodic time functions. Design/methodology/approach The development of relations between the values of first and second derivatives of periodic and two-periodic functions, as well as the values of the functions themselves for a set of time instants. Numerical tests of discrete operators for selected periodic and two-periodic functions. Findings Novel discrete differential operators for periodic and two-periodic time functions determining their first and the second derivatives at very high accuracy basing on relatively low number of points per highest harmonic. Research limitations/implications Reduce the complexity of creation difference equations for ordinary non-linear differential equations used to find periodic or two-periodic solutions, when they exist. Practical implications Application to steady-state analysis of non-linear dynamic systems for solutions predicted as periodic or two-periodic in time. Originality/value Identify novel discrete differential operators for periodic and two-periodic time functions engaging a large set of time instants that determine the first and second derivatives with very high accuracy.

scholarly journals Sex-specific DNA methylation differences in people exposed to polybrominated biphenyl

Epigenomics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 757-770
Author(s):  
Sarah W Curtis ◽  
Sabrina A Gerkowicz ◽  
Dawayland O Cobb ◽  
Varun Kilaru ◽  
Metrecia L Terrell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Health Risks ◽  
Binding Sites ◽  
Adverse Health Outcomes ◽  
Functional Regions ◽  
Specific Effects ◽  
False Discovery ◽  
Polybrominated Biphenyls ◽  
Polybrominated Biphenyl ◽  
Specific Health

Aim: Michigan residents were exposed to polybrominated biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate <0.05). No CpGs were associated in both sexes. These CpGs were enriched in different functional regions and transcription factor binding sites in each sex. Conclusion: Exposure to PBBs may have sex-specific effects on the epigenome that may underlie sex-specific adverse health outcomes.

scholarly journals PMI’s heated tobacco products marketing claims of reduced risk and reduced exposure may entice youth to try and continue using these products

2020 ◽  
pp. tobaccocontrol-2019-055318 ◽  
Author(s):  
Karma McKelvey ◽  
Michael Baiocchi ◽  
Bonnie Halpern-Felsher
Keyword(s):  
Health Risks ◽  
Risk Group ◽  
Tobacco Product ◽  
Philip Morris ◽  
Randomised Controlled ◽  
Tobacco Initiation ◽  
Consumer Marketing ◽  
Reduced Risk ◽  
Tobacco Packaging ◽  
Specific Health

ImportancePhilip Morris International (PMI) is seeking Food and Drug Administration’s (FDA) authorisation to market IQOS as a modified risk tobacco product and to make marketing claims of reduced risk and reduced exposure. Such claims may be misunderstood by youth, thereby increasing their risk for tobacco initiation.ObjectiveTo assess youth (mean age 19.3, SD=1.7) understanding and perceptions of PMI’s proposed consumer marketing claims of reduced risk and reduced exposure, we embedded a randomised controlled experiment into a survey of 450 California youth (April to August 2018). Participants were randomised to see ‘reduced exposure’, ‘reduced risk’ or neither claim. Perceptions of IQOS-related health risks and general harm and understanding of the term ‘switching completely’ as used in PMI’s proposed claims were compared.ResultsMean expectancies to experience specific health risks did not differ by claim exposure. The reduced exposure group’s perceptions of general harm did not differ from those of controls nor from the reduced risk group. The reduced risk group had the largest proportion who perceived IQOS as moderately/less harmful (n=78, 52%); controls the largest proportion perceiving IQOS as quite/extremely harmful (n=91, 63%). While 71% of the sample understood the term ‘switch completely’ correctly as used in the reduced risk (n=194, 71%) and reduced exposure (n=206, 72%) claims, more than 1 in 4 did not.ConclusionsFDA and other regulators must use caution when considering allowing claims of reduced risk or reduced exposure to appear on retail tobacco packaging. Youth misunderstand such claims, and misperceptions of harm are known to lead to tobacco-use initiation.

scholarly journals Deducing high-accuracy protein contact-maps from a triplet of coevolutionary matrices through deep residual convolutional networks

2021 ◽  
Vol 17 (3) ◽  
pp. e1008865
Author(s):  
Yang Li ◽  
Chengxin Zhang ◽  
Eric W. Bell ◽  
Wei Zheng ◽  
Xiaogen Zhou ◽  
...  
Keyword(s):  
Long Range ◽  
3D Structure ◽  
High Accuracy ◽  
Large Set ◽  
Contact Map ◽  
Homologous Proteins ◽  
Convolutional Networks ◽  
Contact Maps ◽  
Model Training ◽  
Protein Contact Maps

The topology of protein folds can be specified by the inter-residue contact-maps and accurate contact-map prediction can help ab initio structure folding. We developed TripletRes to deduce protein contact-maps from discretized distance profiles by end-to-end training of deep residual neural-networks. Compared to previous approaches, the major advantage of TripletRes is in its ability to learn and directly fuse a triplet of coevolutionary matrices extracted from the whole-genome and metagenome databases and therefore minimize the information loss during the course of contact model training. TripletRes was tested on a large set of 245 non-homologous proteins from CASP 11&12 and CAMEO experiments and outperformed other top methods from CASP12 by at least 58.4% for the CASP 11&12 targets and 44.4% for the CAMEO targets in the top-L long-range contact precision. On the 31 FM targets from the latest CASP13 challenge, TripletRes achieved the highest precision (71.6%) for the top-L/5 long-range contact predictions. It was also shown that a simple re-training of the TripletRes model with more proteins can lead to further improvement with precisions comparable to state-of-the-art methods developed after CASP13. These results demonstrate a novel efficient approach to extend the power of deep convolutional networks for high-accuracy medium- and long-range protein contact-map predictions starting from primary sequences, which are critical for constructing 3D structure of proteins that lack homologous templates in the PDB library.

scholarly journals Development of a Sleep Apnea–Specific Health State Utility Algorithm

2020 ◽  
Vol 146 (3) ◽  
pp. 270
Author(s):  
Jonathan R. Skirko ◽  
Kathryn T. James ◽  
Louis P. Garrison ◽  
Edward M. Weaver
Keyword(s):  
Sleep Apnea ◽  
Health State Utility ◽  
Health State ◽  
Specific Health State ◽  
Specific Health
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