Summary
Most mammals are coated with pigmented hair. Melanocytes in each hair follicle produce melanin pigments for the hair during each hair cycle. The key to understanding the mechanism of cyclic ...melanin production is the melanocyte stem cell (MelSC) population, previously known as ‘amelanotic melanocytes’. The MelSCs directly adhere to hair follicle stem cells, the niche cells for MelSCs and reside in the hair follicle bulge–subbulge area, the lower permanent portion of the hair follicle, to serve as a melanocyte reservoir for skin and hair pigmentation. MelSCs form a stem cell system within individual hair follicles and provide a ‘hair pigmentary unit’ for each cycle of hair pigmentation. This review focuses on the identification of MelSCs and their characteristics and explains the importance of the MelSC population in the mechanisms of hair pigmentation, hair greying, and skin repigmentation.
As the power density and integration level of electronic devices increase, there are growing demands to improve the thermal conductivity of polymers for addressing the thermal management issues. On ...the basis of the ultrahigh intrinsic thermal conductivity, graphene has exhibited great potential as reinforcing fillers to develop polymer composites, but the resultant thermal conductivity of reported graphene-based composites is still limited. Here, an interconnected and highly ordered graphene framework (HOGF) composed of high-quality and horizontally aligned graphene sheets was developed by a porous film-templated assembly strategy, followed by a stress-induced orientation process and graphitization post-treatment. After embedding into the epoxy (EP), the HOGF/EP composite (24.7 vol %) exhibits a record-high in-plane thermal conductivity of 117 W m–1 K–1, equivalent to ≈616 times higher than that of neat epoxy. This thermal conductivity enhancement is mainly because the HOGF as a filler concurrently has high intrinsic thermal conductivity, relatively high density, and a highly ordered structure, constructing superefficient phonon transport paths in the epoxy matrix. Additionally, the use of our HOGF/EP as a heat dissipation plate was demonstrated, and it achieved 75% enhancement in practical thermal management performance compared to that of conventional alumina for cooling the high-power LED.
To assess whether smoking is a risk factor for developing rheumatoid arthritis (RA).
Meta-analysis.
were observational studies that examined the association between smoking history and the risk of ...developing RA identified through Medline and EMBASE (from 1966 to December 2006), relevant books and a reference search. Two authors independently extracted the following: authors' names, publication year, sample size, participant characteristics, odds ratios (OR) or relative risks, adjustment factors, study design and area where the study was conducted. Data syntheses were based upon random effects model. Summarised syntheses effects were expressed by OR.
Sixteen studies were selected from among 433 articles. For men, summary OR for ever, current and past smokers were 1.89 (95% CI 1.56 to 2.28), 1.87 (1.49 to 2.34) and 1.76 (1.33 to 2.31), respectively. For rheumatoid factor-positive (RF+) RA, summary OR for ever, current and past smokers were 3.02 (2.35 to 3.88), 3.91 (2.78 to 5.50) and 2.46 (1.74 to 3.47), respectively. Summary OR for 20 or more pack-years of smoking was 2.31 (1.55 to 3.41). For women, summary OR for ever, current and past smokers were 1.27 (1.12 to 1.44), 1.31 (1.12 to 1.54) and 1.22 (1.06 to 1.40), respectively. For RF+ RA, summary OR for ever, current and past smokers were 1.34 (0.99 to 1.80), 1.29 (0.94 to 1.77) and 1.21 (0.83 to 1.77). Summary OR for 20 or more pack-years of smoking was 1.75 (1.52 to 2.02).
Smoking is a risk factor for RA, especially RF+ RA men and heavy smokers.
Stem cell‐based products have clinical and industrial applications. Thus, there is a need to develop quality control methods to standardize stem cell manufacturing. Here, we report a deep ...learning‐based automated cell tracking (DeepACT) technology for noninvasive quality control and identification of cultured human stem cells. The combination of deep learning‐based cascading cell detection and Kalman filter algorithm‐based tracking successfully tracked the individual cells within the densely packed human epidermal keratinocyte colonies in the phase‐contrast images of the culture. DeepACT rapidly analyzed the motion of individual keratinocytes, which enabled the quantitative evaluation of keratinocyte dynamics in response to changes in culture conditions. Furthermore, DeepACT can distinguish keratinocyte stem cell colonies from non‐stem cell‐derived colonies by analyzing the spatial and velocity information of cells. This system can be widely applied to stem cell cultures used in regenerative medicine and provides a platform for developing reliable and noninvasive quality control technology.
A deep learning‐based automated cell tracking (DeepACT) technology enables the evaluation of keratinocyte culture quality and the identification of keratinocyte stem cells using quantitative cell motion analysis. DeepACT comprises two main modules: identifying human keratinocytes at single‐cell resolution from phase‐contrast images of cultures through deep learning and tracking keratinocyte motion in the colony using a state‐space model.
We consider some observational consequences of replacing all black holes (BHs) with a class of non-singular solutions that mimic BHs but with dark energy (DE) interiors; GEneric Objects of DE ...(GEODEs). We focus on the BH mass function and chirp-mass redshift distribution of mergers visible to gravitational-wave observatories. We incorporate the GEODE blueshift into an initially Salpeter stellar remnant distribution, and model the binary population by evolving synthesized binary remnant distributions, published before LIGO's first measurements. We find that a GEODE produced between 20 z 40, and observed at z ∼ 7, will have its initial mass amplified by ∼20-140×. This can relieve tension between accretion-only growth models and the inferred masses of BHs in quasars at z 6. Moreover, we find that merger rates of GEODE binaries increase by a factor of ∼2× relative to classical BHs. The resulting GEODE mass function is consistent with the most recent LIGO constraints at <0.5 . In contrast, a Salpeter stellar distribution that evolves into classical remnants is in tension at 2 . This agreement occurs without low-metallicity regions, abnormally massive progenitor stars, novel formation channels, or primordial object formation at extreme rates. In particular, we find that solar metallicity progenitors, which produce 1.1-1.8M remnants, overlap with many LIGO observations when evolved as GEODEs.
Obesity is a worldwide epidemic that predisposes individuals to many age-associated diseases, but its exact effects on organ dysfunction are largely unknown
. Hair follicles-mini-epithelial organs ...that grow hair-are miniaturized by ageing to cause hair loss through the depletion of hair follicle stem cells (HFSCs)
. Here we report that obesity-induced stress, such as that induced by a high-fat diet (HFD), targets HFSCs to accelerate hair thinning. Chronological gene expression analysis revealed that HFD feeding for four consecutive days in young mice directed activated HFSCs towards epidermal keratinization by generating excess reactive oxygen species, but did not reduce the pool of HFSCs. Integrative analysis using stem cell fate tracing, epigenetics and reverse genetics showed that further feeding with an HFD subsequently induced lipid droplets and NF-κB activation within HFSCs via autocrine and/or paracrine IL-1R signalling. These integrated factors converge on the marked inhibition of Sonic hedgehog (SHH) signal transduction in HFSCs, thereby further depleting lipid-laden HFSCs through their aberrant differentiation and inducing hair follicle miniaturization and eventual hair loss. Conversely, transgenic or pharmacological activation of SHH rescued HFD-induced hair loss. These data collectively demonstrate that stem cell inflammatory signals induced by obesity robustly represses organ regeneration signals to accelerate the miniaturization of mini-organs, and suggests the importance of daily prevention of organ dysfunction.
Hair graying is the most obvious sign of aging in humans, yet its mechanism is largely unknown. Here, we used melanocyte-tagged transgenic mice and aging human hair follicles to demonstrate that hair ...graying is caused by defective self-maintenance of melanocyte stem cells. This process is accelerated dramatically with Bcl2 deficiency, which causes selective apoptosis of melanocyte stem cells, but not of differentiated melanocytes, within the niche at their entry into the dormant state. Furthermore, physiologic aging of melanocyte stem cells was associated with ectopic pigmentation or differentiation within the niche, a process accelerated by mutation of the melanocyte master transcriptional regulator Mitf.
Skin regenerative capacity declines with age, but the underlying mechanisms are largely unknown. Here we demonstrate a functional link between epidermal growth factor receptor (EGFR) signaling and ...type XVII collagen (COL17A1) proteolysis on age-associated alteration of keratinocyte stem cell dynamics in skin regeneration. Live-imaging and computer simulation experiments predicted that human keratinocyte stem cell motility is coupled with self-renewal and epidermal regeneration. Receptor tyrosine kinase array identified the age-associated decline of EGFR signaling in mouse skin wound healing. Culture experiments proved that EGFR activation drives human keratinocyte stem cell motility with increase of COL17A1 by inhibiting its proteolysis through the secretion of tissue inhibitor of metalloproteinases 1 (TIMP1). Intriguingly, COL17A1 directly regulated keratinocyte stem cell motility and collective cell migration by coordinating actin and keratin filament networks. We conclude that EGFR-COL17A1 axis-mediated keratinocyte stem cell motility drives epidermal regeneration, which provides a novel therapeutic approach for age-associated impaired skin regeneration.
Background
Co‐occurring attention deficit hyperactivity disorder (ADHD) is a challenge to characterise in the presence of other medical conditions commonly present in children with Down syndrome ...(DS). The current study examined differences among children with DS with or without ADHD symptomatology in terms of demographics, developmental level, co‐occurring medical conditions, and parent and teacher ratings of behaviour and executive functioning.
Methods
Parents and teachers of 108 school‐age children with DS provided ratings of ADHD symptoms, behaviour problems and executive functioning skills. Children with DS and ADHD symptom presentation, as identified by a scoring algorithm, were compared with those without ADHD symptom presentation on demographic characteristics, developmental level, co‐occurring medical conditions and parent‐report and teacher‐report measures of behaviours and executive functioning.
Results
Sleep disorders, disruptive behaviour disorder, allergies and seizures were more common in children with DS and ADHD symptom presentation than in children without ADHD symptom presentation. After controlling for ADHD medication use, children with DS and ADHD symptom presentation had poorer performance than those without ADHD symptom presentation on parent behaviour ratings, teacher behaviour ratings and parent but not teacher ratings of executive functioning. No significant group differences in demographic characteristics or developmental level were identified.
Conclusions
Higher rates of co‐occurring medical conditions present in children with DS and ADHD symptom presentation support the need for thorough differential diagnoses. The different pattern of group differences between parent‐report and teacher‐report has implications for diagnostic practices across settings as well as for treatment.
Hematopoietic stem cells (HSCs) maintain quiescence by activating specific metabolic pathways, including glycolysis. We do not yet have a clear understanding of how this metabolic activity changes ...during stress hematopoiesis, such as bone marrow transplantation. Here, we report a critical role for the p38MAPK family isoform p38α in initiating hematopoietic stem and progenitor cell (HSPC) proliferation during stress hematopoiesis in mice. We found that p38MAPK is immediately phosphorylated in HSPCs after a hematological stress, preceding increased HSPC cycling. Conditional deletion of p38α led to defective recovery from hematological stress and a delay in initiation of HSPC proliferation. Mechanistically, p38α signaling increases expression of inosine-5′-monophosphate dehydrogenase 2 in HSPCs, leading to altered levels of amino acids and purine-related metabolites and changes in cell-cycle progression in vitro and in vivo. Our studies have therefore uncovered a p38α-mediated pathway that alters HSPC metabolism to respond to stress and promote recovery.
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•Conditional deletion of p38α disrupts the hematopoietic stem cell stress response•Induction of p38α after stress promotes hematopoietic stem cell cycling•p38α promotes proliferation by activating purine metabolism•Mitf acts downstream of p38α to regulate the purine metabolism pathway gene
Karigane et al. characterize a regulatory pathway involved in hematopoietic stem cell stress responses. They show that p38α, which is activated by hematopoietic stress, promotes purine metabolism through Mitf-mediated Impdh2 upregulation. Activated purine metabolism promotes hematopoietic stem/progenitor cell cycling and maintains repopulation capacity after transplantation.
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