Summary
Background
Human skin has the crucial roles of maintaining homeostasis and protecting against the external environment. Skin offers protection against mechanical trauma due to the reversible ...deformation of its structure; these biomechanical properties are amenable to dynamic testing using noninvasive devices.
Objectives
To characterize the biomechanical properties of young, black African/African‐Caribbean and white Northern European skin from different anatomical sites, and to relate underlying skin architecture to biomechanical function.
Methods
Using cutometry and ballistometry, the biomechanical properties of buttock and dorsal forearm skin were determined in black African/African‐Caribbean (n = 18) and white Northern European (n = 20) individuals aged 18–30 years. Skin biopsies were obtained from a subset of the volunteers (black African/African‐Caribbean, n = 5; white Northern European, n = 6) and processed for histological and immunohistochemical detection of the major elastic fibre components and fibrillar collagens.
Results
We have determined that healthy skin from young African and white Northern European individuals has similar biomechanical properties (F3): the skin is resilient (capable of returning to its original position following deformation, R1), exhibits minimal fatigue (R4) and is highly elastic (R2, R5 and R7). At the histological level, skin with these biomechanical properties is imbued with strong interdigitation of the rete ridges at the dermoepidermal junction (DEJ) and candelabra‐like arrays of elastic fibres throughout the papillary dermis. Dramatic disruption to this highly organized arrangement of elastic fibres, effacement of the rete ridges and alterations to the alignment of the fibrillar collagens is apparent in the white Northern European forearm and coincides with a marked decline in biomechanical function.
Conclusions
Maintenance of skin architecture – both epidermal morphology and elastic fibre arrangement – is essential for optimal skin biomechanical properties. Disruption to underlying skin architecture, as observed in the young white Northern European forearm, compromises biomechanical function.
What's already known about this topic?
Human skin offers protection against the external environment via the reversible deformation of its structure: the stratum corneum and components of the dermal extracellular matrix imbue skin with these important biomechanical properties.
Skin biomechanical properties are amenable to dynamic testing in vivo using the noninvasive methods of cutometry and ballistometry.
What does this study add?
This study combines in vivo testing of black African and white Northern European skin with the histological assessment of skin biopsies in order to interrogate the relationship between underlying skin architecture and biomechanical function.
Disruption to skin architecture, particularly loss of oxytalan fibres and effacement of rete ridges, correlates with perturbation of biomechanical function.
What is the translational message?
Quantitative measurement of biomechanical properties combined with histological assessment of underlying extracellular matrix architecture are useful tools to provide us with an understanding of skin's normal functions.
These techniques may be useful to examine the clinical progression of skin conditions that affect skin elasticity and provide objective measurement of the efficacy of treatment options designed to improve skin health.
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Linked Comment: Dobrev. Br J Dermatol 2017; 177:622–623
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We report the discovery and characterisation of a super-Earth and a sub-Neptune transiting the bright (
K
= 8.8), quiet, and nearby (37 pc) M3V dwarf TOI-1266. We validate the planetary nature of ...TOI-1266 b and c using four sectors of TESS photometry and data from the newly-commissioned 1-m SAINT-EX telescope located in San Pedro Mártir (México). We also include additional ground-based follow-up photometry as well as high-resolution spectroscopy and high-angular imaging observations. The inner, larger planet has a radius of
R
= 2.37
−0.12
+0.16
R
⊕
and an orbital period of 10.9 days. The outer, smaller planet has a radius of
R
= 1.56
−0.13
+0.15
R
⊕
on an 18.8-day orbit. The data are found to be consistent with circular, co-planar and stable orbits that are weakly influenced by the 2:1 mean motion resonance. Our TTV analysis of the combined dataset enables model-independent constraints on the masses and eccentricities of the planets. We find planetary masses of
M
p
= 13.5
−9.0
+11.0
M
⊕
(<36.8
M
⊕
at 2-
σ
) for TOI-1266 b and 2.2
−1.5
+2.0
M
⊕
(<5.7
M
⊕
at 2-
σ
) for TOI-1266 c. We find small but non-zero orbital eccentricities of 0.09
−0.05
+0.06
(<0.21 at 2-
σ
) for TOI-1266 b and 0.04 ± 0.03 (< 0.10 at 2-
σ
) for TOI-1266 c. The equilibrium temperatures of both planets are of 413 ± 20 and 344 ± 16 K, respectively, assuming a null Bond albedo and uniform heat redistribution from the day-side to the night-side hemisphere. The host brightness and negligible activity combined with the planetary system architecture and favourable planet-to-star radii ratios makes TOI-1266 an exquisite system for a detailed characterisation.
Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we ...explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell.
Light transmission aggregometry (LTA) is the most common method used to assess platelet function. However, there is no universal standard for its performance. The Platelet Physiology Subcommittee of ...the Scientific and Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis formed a working party of experts with the aim of producing a series of consensus recommendations for standardizing LTA. Due to a lack of investigations that directly compared different methodologies to perform LTA studies, there were insufficient data to develop evidence-based guidelines. Therefore, the RAND method was used, which obtains a formal consensus among experts about the appropriateness of health care interventions, particularly when scientific evidence is absent, scarce and/or heterogeneous. Using this approach, each expert scored as "appropriate", "uncertain" or "inappropriate" a series of statements about the practice of LTA, which included pre-analytical variables, blood collection, blood processing, methodological details, choice of agonists and the evaluation and reporting of results. After presentation and public discussion at SSC meetings, the assessments were further refined to produce final consensus recommendations. Before delivering the recommendations, a formal literature review was performed using a series of defined search terms about LTA. Of the 1830 potentially relevant studies identified, only 14 publications were considered to be actually relevant for review. Based upon the additional information, 6 consensus statements were slightly modified. The final statements were presented and discussed at the SSC Meeting in Cairo (2010) and formed the basis of a consensus document, which is the subject of the present report. This article is protected by copyright. All rights reserved.
Intensification of grasslands is necessary to meet the increasing demand of livestock products. The application of nitrogen (N) on grasslands affects the N balance therefore the nitrogen use ...efficiency (NUE). Emissions of nitrous oxide (N2O) are produced due to N fertilisation and low NUE. These emissions depend on the type and rates of N applied. In this study we have compiled data from 5 UK N fertilised grassland sites (Crichton, Drayton, North Wyke, Hillsborough and Pwllpeiran) covering a range of soil types and climates. The experiments evaluated the effect of increasing rates of inorganic N fertiliser provided as ammonium nitrate (AN) or calcium ammonium nitrate (CAN). The following fertiliser strategies were also explored for a rate of 320 kg N ha−1: using the nitrification inhibitor dicyandiamide (DCD), changing to urea as an N source and splitting fertiliser applications. We measured N2O emissions for a full year in each experiment, as well as soil mineral N, climate data, pasture yield and N offtake. N2O emissions were greater at Crichton and North Wyke whereas Drayton, Hillsborough and Pwllpeiran had the smallest emissions. The resulting average emission factor (EF) of 1.12% total N applied showed a range of values for all the sites between 0.6 and 2.08%. NUE depended on the site and for an application rate of 320 kg N ha−1, N surplus was on average higher than 80 kg N ha−1, which is proposed as a maximum by the EU Nitrogen Expert Panel. N2O emissions tended to be lower when urea was applied instead of AN or CAN, and were particularly reduced when using urea with DCD. Finally, correlations between the factors studied showed that total N input was related to Nofftake and Nexcess; while cumulative emissions and EF were related to yield scaled emissions.
Display omitted
•N2O emissions and NUE were measured at 5 UK grassland sites.•Different fertilisation rates and strategies were tested in all sites.•Average N2O emission factor was 1.12%, but ranged from 0.60% to 2.08%.•Using urea and urea with DCD reduced N2O emission factor.•Yield scaled emissions and emissions relative to herbage N content show similar trend.
Severe falciparum malaria is a major cause of preventable child mortality in sub-Saharan Africa. Plasma concentrations of P. falciparum Histidine-Rich Protein 2 (PfHRP2) have diagnostic and ...prognostic value in severe malaria. We investigate the potential use of plasma PfHRP2 and the sequestration index (the ratio of PfHRP2 to parasite density) as quantitative traits for case-only genetic association studies of severe malaria. Data from 2198 Kenyan children diagnosed with severe malaria, genotyped for 14 major candidate genes, show that polymorphisms in four major red cell genes that lead to hemoglobin S, O blood group, α-thalassemia, and the Dantu blood group, are associated with substantially lower admission plasma PfHRP2 concentrations, consistent with protective effects against extensive parasitized erythrocyte sequestration. In contrast the known protective ATP2B4 polymorphism is associated with higher plasma PfHRP2 concentrations, lower parasite densities and a higher sequestration index. We provide testable hypotheses for the mechanism of protection of ATP2B4.
With COVID-19, there is urgency for policymakers to understand and respond to the health needs of slum communities. Lockdowns for pandemic control have health, social and economic consequences. We ...consider access to healthcare before and during COVID-19 with those working and living in slum communities.
In seven slums in Bangladesh, Kenya, Nigeria and Pakistan, we explored stakeholder perspectives and experiences of healthcare access for non-COVID-19 conditions in two periods: pre-COVID-19 and during COVID-19 lockdowns.
Between March 2018 and May 2020, we engaged with 860 community leaders, residents, health workers and local authority representatives. Perceived common illnesses in all sites included respiratory, gastric, waterborne and mosquitoborne illnesses and hypertension. Pre-COVID, stakeholders described various preventive, diagnostic and treatment services, including well-used antenatal and immunisation programmes and some screening for hypertension, tuberculosis, HIV and vectorborne disease. In all sites, pharmacists and patent medicine vendors were key providers of treatment and advice for minor illnesses. Mental health services and those addressing gender-based violence were perceived to be limited or unavailable. With COVID-19, a reduction in access to healthcare services was reported in all sites, including preventive services. Cost of healthcare increased while household income reduced. Residents had difficulty reaching healthcare facilities. Fear of being diagnosed with COVID-19 discouraged healthcare seeking. Alleviators included provision of healthcare by phone, pharmacists/drug vendors extending credit and residents receiving philanthropic or government support; these were inconsistent and inadequate.
Slum residents' ability to seek healthcare for non-COVID-19 conditions has been reduced during lockdowns. To encourage healthcare seeking, clear communication is needed about what is available and whether infection control is in place. Policymakers need to ensure that costs do not escalate and unfairly disadvantage slum communities. Remote consulting to reduce face-to-face contact and provision of mental health and gender-based violence services should be considered.
We define phylosystemics, a multidisciplinary strategy uniting short timescale interaction studies from systems biologists and ecologists with the longer timescale studies familiar to evolutionary ...biologists, taking advantage of methods from network sciences. Phylosystemics superimposes evolutionary information on entities/edges forming interaction networks produced by systems biology and ecology. At the molecular level, phylosystemics could provide evidence to infer and to time the evolution of molecular processes within a single branch of a phylogeny, in particular between the first and last common ancestors of a group arising during a major evolutionary transition. At the ecosystemic level, phylosystemics could culminate with the development of multilayer temporal networks encompassing biotic and abiotic interactions, whose analyses could unravel ecological interactions with evolutionary consequences.
To fully understand biological interactions and evolution, they must be studied together.There are few generic models and approaches able to unite the short timescales of interactions unraveled by systems biologists and ecologists, with the longer timescale of evolution.We propose an approach to incorporate short timescale interaction networks with longer timescale evolutionary studies, by superimposing evolutionary information on interaction networks, which we name phylosystemics.Applications of phylosystemics have the potential to enhance knowledge of major evolutionary transitions and the evolution of ecosystems.
The acquisition of genes by horizontal transfer can impart entirely new biological functions and provide an important route to major evolutionary innovation. Here we have used ancient gene ...reconstruction and functional assays to investigate the impact of a single horizontally transferred nucleotide transporter into the common ancestor of the Microsporidia, a major radiation of intracellular parasites of animals and humans. We show that this transporter provided early microsporidians with the ability to steal host ATP and to become energy parasites. Gene duplication enabled the diversification of nucleotide transporter function to transport new substrates, including GTP and NAD
, and to evolve the proton-energized net import of nucleotides for nucleic acid biosynthesis, growth and replication. These innovations have allowed the loss of pathways for mitochondrial and cytosolic energy generation and nucleotide biosynthesis that are otherwise essential for free-living eukaryotes, resulting in the highly unusual and reduced cells and genomes of contemporary Microsporidia.
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