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Concept: Function model

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Although the time adolescents spend with digital technologies has sparked widespread concerns that their use might be negatively associated with mental well-being, these potential deleterious influences have not been rigorously studied. Using a preregistered plan for analyzing data collected from a representative sample of English adolescents ( n = 120,115), we obtained evidence that the links between digital-screen time and mental well-being are described by quadratic functions. Further, our results showed that these links vary as a function of when digital technologies are used (i.e., weekday vs. weekend), suggesting that a full understanding of the impact of these recreational activities will require examining their functionality among other daily pursuits. Overall, the evidence indicated that moderate use of digital technology is not intrinsically harmful and may be advantageous in a connected world. The findings inform recommendations for limiting adolescents' technology use and provide a template for conducting rigorous investigations into the relations between digital technology and children’s and adolescents' health.

Concepts: Critical thinking, Function, Technology, Function model, Digital, Recreation, Quadratic function

9

Microglial cells closely interact with senile plaques in Alzheimer’s disease and acquire the morphological appearance of an activated phenotype. The significance of this microglial phenotype and the impact of microglia for disease progression have remained controversial. To uncover and characterize putative changes in the functionality of microglia during Alzheimer’s disease, we directly assessed microglial behavior in two mouse models of Alzheimer’s disease. Using in vivo two-photon microscopy and acute brain slice preparations, we found that important microglial functions - directed process motility and phagocytic activity - were strongly impaired in mice with Alzheimer’s disease-like pathology compared to age-matched non-transgenic animals. Notably, impairment of microglial function temporally and spatially correlated with Aβ plaque deposition, and phagocytic capacity of microglia could be restored by interventionally decreasing amyloid burden by Aβ vaccination. These data suggest that major microglial functions progressively decline in Alzheimer’s disease with the appearance of Aβ plaques, and that this functional impairment is reversible by lowering Aβ burden, e.g. by means of Aβ vaccination.

Concepts: Alzheimer's disease, Function, Neurology, Dementia, Beta amyloid, Microglia, Function model, Senile plaques

4

The vast majority of microorganisms on Earth reside in often-inseparable environment-specific communities-microbiomes. Meta-genomic/-transcriptomic sequencing could reveal the otherwise inaccessible functionality of microbiomes. However, existing analytical approaches focus on attributing sequencing reads to known genes/genomes, often failing to make maximal use of available data. We created faser (functional annotation of sequencing reads), an algorithm that is optimized to map reads to molecular functions encoded by the read-correspondent genes. The mi-faser microbiome analysis pipeline, combining faser with our manually curated reference database of protein functions, accurately annotates microbiome molecular functionality. mi-faser’s minutes-per-microbiome processing speed is significantly faster than that of other methods, allowing for large scale comparisons. Microbiome function vectors can be compared between different conditions to highlight environment-specific and/or time-dependent changes in functionality. Here, we identified previously unseen oil degradation-specific functions in BP oil-spill data, as well as functional signatures of individual-specific gut microbiome responses to a dietary intervention in children with Prader-Willi syndrome. Our method also revealed variability in Crohn’s Disease patient microbiomes and clearly distinguished them from those of related healthy individuals. Our analysis highlighted the microbiome role in CD pathogenicity, demonstrating enrichment of patient microbiomes in functions that promote inflammation and that help bacteria survive it.

Concepts: Protein, Bacteria, Molecular biology, Function, Syndromes, Genetic disorders, Functional analysis, Function model

1

The ability to print and pattern all the components that make up a tissue (cells and matrix materials) in three dimensions to generate structures similar to tissues is an exciting prospect of bioprinting. However, the majority of the matrix materials used so far for bioprinting cannot represent the complexity of natural extracellular matrix (ECM) and thus are unable to reconstitute the intrinsic cellular morphologies and functions. Here, we develop a method for the bioprinting of cell-laden constructs with novel decellularized extracellular matrix (dECM) bioink capable of providing an optimized microenvironment conducive to the growth of three-dimensional structured tissue. We show the versatility and flexibility of the developed bioprinting process using tissue-specific dECM bioinks, including adipose, cartilage and heart tissues, capable of providing crucial cues for cells engraftment, survival and long-term function. We achieve high cell viability and functionality of the printed dECM structures using our bioprinting method.

Concepts: Function, Extracellular matrix, Dimension, Euclidean space, Tissues, Tissue, Printing, Function model

0

A “kneeling” ultralight wheelchair prototype has been developed that allows users to adjust seat position “on the fly” for different activities throughout the day. The wheelchair includes independent adjustment functions for rear seat height, front seat height (“kneeling”) and backrest angle.  Aim: This work aimed to gather feedback about the wheelchair’s functionality and performance through end user evaluation trials.  Methods: Eight manual wheelchair users evaluated the prototype Kneeling Wheelchair for a range of activities. User perspectives on parameters such as usability, comfort, stability and effectiveness were obtained through both open-ended and Likert-scale rating questions.  Results: Results indicate several potential benefits of the adjustment functions of the Kneeling Wheelchair. Rear seat height adjustment may facilitate a number of activities of daily living, as well as provide benefits for comfort and social interactions. Back rest adjustment may increase comfort and stability on slopes. Front seat height adjustment may be beneficial for transfers and conducting sustained low-to-the-ground activities. While benefits of this adjustment function were described by many participants, some struggled with usability of the kneeling mechanism and rated this function less favourably than the other two.  Conclusion: The findings of this study will inform future iterations of the Kneeling Wheelchair design and may spur future developments in wheeled mobility. In the long-term, it is anticipated that novel wheelchair solutions, such as the one described in this paper, may support improved health, quality of life and community participation for people with mobility impairments. Implications for rehabilitation Wheelchairs that allow users to easily adjust seat and backrest position “on the fly” to better suit different tasks throughout the day may provide benefits such as facilitating activities of daily living. A front seat height adjustment feature on a new wheelchair prototype may be beneficial for transfers and conducting sustained low-to-the ground activities. End user evaluations can provide valuable insight to direct future design modifications and innovation.

Concepts: Function, Activity, Wheelchair, Function model, Mobility device, Car seat, Wheelchairs, User

0

One of the many functions of melatonin in vertebrates is seasonal reproductive timing. Longer nights in winter correspond to an extended duration of melatonin secretion. The purpose of this review is to discuss melatonin synthesis, receptor subtypes, and function in the context of seasonality across vertebrates. We conclude with Tinbergen’s Four Questions to create a comparative framework for future melatonin research in the context of seasonal reproduction.

Concepts: Function, Season, Ethology, Function model, Winter, Melatonin, Tinbergen's four questions

0

Dynamic Contrast-Enhanced Cardiovascular Magnetic Resonance Imaging may quantitatively assess the Myocardial Blood Flow (MBF), recovering the tissue impulse-response function to transit of gadolinium bolus through myocardium. Several deconvolution techniques are available, using various models for the impulse-response. The method choice may influence the results, producing differences that have not been deeply investigated yet. Three methods for quantifying myocardial perfusion were compared: Fermi Function Modeling (FFM), Tofts Model ™, and Gamma Function model (GF), the latter traditionally used in brain perfusion MRI. 30 human subjects were studied at rest, and Cold Pressor Test stress (submerging hands in ice-cold water), injecting a single-bolus of gadolinium of 0.1±0.05 mmol/kg. Perfusion estimate differences among methods were analysed by paired comparisons with Student’s t-test, linear regression analysis, and Bland-Altman plots, and using also the two-way ANOVA, considering the MBF values of all patients grouped according to two categories: calculation method and rest/stress conditions. Perfusion estimates obtained by various methods in both rest and stress conditions were not significantly different, and in a good agreement with the published results. Results obtained during the first-pass transit time (20 s) yielded p-values in the range 0.20-0.28 for the Student’s t-test, slopes from the linear regression analysis between 0.98-1.03, and R values between 0.92-1.01. With the two-way ANOVA, the results were p=0.20 for the method effect (not significant), p<0.0001 for the rest/stress condition effect (highly significant, as expected), whereas no interaction resulted between rest/stress condition and method (p=0.70, not significant). Considering a wider time-frame (60 s), the estimates for both rest and stress conditions were 25-30% higher (p in the range 0.016-0.025) than those obtained in the 20 s time-frame. MBF estimates obtained by various methods at rest/stress condition were not significantly different in the first-pass transit time, encouraging quantitative perfusion estimates in DCE-CMRI with the used methods.

Concepts: Regression analysis, Linear regression, Statistics, Sociology, Magnetic resonance imaging, Normal distribution, Function model, F-test

0

Regaining the ability to independently ambulate following a physical disability can increase functional ability and participation of patients in daily life. Gait trainers are assistive devices that enable body support and provide safety during gait. However, most conventional gait trainers are pre-configured to a constant position, therefore not suitable for practicing sit-to-stand function, and require assistance from a caregiver in order to mount the device from a sitting position. We therefore evaluated the effectiveness of a dynamically-adjusting gait trainer, designed to provide independence and safety during gait and various activities, in both lab setting and at home in 4 subjects (1 female, 3 males, ages 32-79 years) with limited ambulation. Spatiotemporal parameters and gait symmetry were recorded, as well as activity levels, actual use of device and satisfaction. Although, gait parameters and physical activity levels were not notably improved, and in one case were worsened, three subjects reported positive experience with the gait trainer. The new gait trainer may have advantages in supporting users with limited mobility during walking and various functions and decrease the risk for falls. A longer practice time and individual fitting process are recommended for better accommodation to the new possibilities.

Concepts: Male, Function, Disability, Walking, Function model, Automobile, Sustainable transport

0

It is generally accepted that protein function depends on a defined 3D structure, with unfolding and aggregation dealing a final blow to functionality. A study now shows that the regulated exposure of an unstructured region in yeast pyruvate kinase triggers reversible aggregation to preserve protein function under stress.

Concepts: Enzyme, Function, Glycolysis, Pyruvate kinase, Function model

0

Leaching of hazardous trace elements from excavated urban soils during construction of cities has received considerable attention in recent years in Japan. A new concept, the pollution potential leaching index (PPLI), was applied to assess the risk of arsenic (As) leaching from excavated soils. Sequential leaching tests (SLT) with two liquid-to-solid (L/S) ratios (10 and 20Lkg(-1)) were conducted to determine the PPLI values, which represent the critical cumulative L/S ratios at which the average As concentrations in the cumulative leachates are reduced to critical values (10 or 5µgL(-1)). Two models (a logarithmic function model and an empirical two-site first-order leaching model) were compared to estimate the PPLI values. The fractionations of As before and after SLT were extracted according to a five-step sequential extraction procedure. Ten alkaline excavated soils were obtained from different construction projects in Japan. Although their total As contents were low (from 6.75 to 79.4mgkg(-1)), the As leaching was not negligible. Different L/S ratios at each step of the SLT had little influence on the cumulative As release or PPLI values. Experimentally determined PPLI values were in agreement with those from model estimations. A five-step SLT with an L/S of 10Lkg(-1) at each step, combined with a logarithmic function fitting was suggested for the easy estimation of PPLI. Results of the sequential extraction procedure showed that large portions of more labile As fractions (non-specifically and specifically sorbed fractions) were removed during long-term leaching and so were small, but non-negligible, portions of strongly bound As fractions.

Concepts: Mathematics, Estimator, Estimation, Extraction, Logarithmic scale, Construction, Logarithm, Function model