LifeSeeker: an interactive concept-based retrieval system for lifelog data.

Lifelogging was introduced as the process of passively capturing personal daily events via wearable devices. It ultimately creates a visual diary encoding every aspect of one's life with the aim of future sharing or recollecting. In this paper, we present LifeSeeker, a lifelog image retrieval system participating in the Lifelog Search Challenge (LSC) for 3 years, since 2019. Our objective is to support users to seek specific life moments using a combination of textual descriptions, spatial relationships, location information, and image similarities. In addition to the LSC challenge results, a further experiment was conducted in order to evaluate the power retrieval of our system on both expert and novice users. This experiment informed us about the effectiveness of the user's interaction with the system when involving non-experts.

A community-based strategy to eliminate hepatitis C among people who inject drugs in Vietnam.

Background: Towards hepatitis C elimination among people who inject drugs (PWID), we assessed the effectiveness of a strategy consisting of a community-based respondent-driven sampling (RDS) as wide screening, a simplified and integrated hospital-based care, and prevention of reinfection supported by community-based organisations (CBO), in Hai Phong, Vietnam. Methods: Adults who injected heroin were enrolled in a RDS survey implemented in two CBO premises. Rapid HIV and HCV tests were done on site, and blood was taken for HCV RNA testing. Those with detectable HCV RNA were referred with CBO support to three public hospitals for 12-week sofosbuvir/daclatasvir, plus ribavirin for patients with cirrhosis. Participants were followed-up 12 weeks post-treatment (SVR12) and 48 weeks after enrolment. The primary endpoint was the rate of undetectable HCV RNA participants at 48 weeks. Findings: Among the 1444 RDS survey participants, 875 had hepatitis C. Their median age was 41 years (IQR 36-47), 96% were males, 36% were HIV-coinfected. Overall, 686 (78.4%) started sofosbuvir/daclatasvirs, and 629 of the 647 (97.2%) patients tested at SVR12 were cured. At week 48 (581/608) 95.6% had undetectable HCV RNA, representing 66.4% of all PWID identified with hepatitis C. The reinfection rate after SVR12 was 4/100 person-years (95% CI: 2-7). Interpretation: Our strategy, involving CBO and addressing all steps from wide HCV screening to prevention of reinfection, stands as a promising approach to eliminate HCV among PWID in low and middle-income countries. Funding: France ANRS|MIE (#ANRS12380). The RDS survey was implemented with grants from the NIDA (#R01DA041978) and ANRS|MIE (#ANRS12353).

Experience of Peripheral Blood CD34+ Stem Cells Collection in Autoimmune Patients.

BACKGROUND: Autologous Hematopoietic Stem Cell Transplantation with or without CD34+ selection is being used successfully to treat patients with severe and refractory autoimmune disease. This study describes our experience of CD34+ stem cell mobilization, harvesting and selection in autoimmune patients based on conditions in Vietnam - the developing country. METHODS: Eight autoimmune patients (four patients with Myasthenia Gravis and four patients with Systemic Lupus Erythematosus) underwent PBSC mobilization with granulocyte colony-stimulating factor (G-CSF) and cyclophosphamide. The apheresis was performed on a Terumo BCT Spectra Optia machine. CD34+ hematopoetic stem cells were collected from the leukapheresis by CliniMACS Plus device using CD34 Enrichment KIT. CD34+ cells, T and B lymphocytes were counted on a FACS BD Canto II device. RESULTS: Eight patients (4 MG and 4 SLE) including 5 females and 3 males were involved in this study. The mean age of the patients was 33.13 ± 16.64 years (ranging from 13 to 58 years). The average number of days for mobilization was 7.9 ± 1.6 days, whereas the average number of days for harvesting was 1.5 ± 0.5 days. There was no difference in the number of days for mobilization and harvesting between the MG and SLE groups. The number of CD34+ cells in peripheral blood (PB) on the day of harvesting was 108.37 ± 59.64 x 106 cells/L. There was a significant difference in white blood cell (WBC), neutrophil, monocyte, and platelet cell counts between before and after mobilization. On the day of stem cell harvesting, variables such as WBC, neutrophil, lymphocyte, monocyte, platelet, CD34+ cell counts, and hemoglobin were not different between the MG and SLE groups. The CD34+ recovery percentage following the CD34+ selection procedure was 68.8%, whereas almost 99.9% of the T and B lymphocytes, and NK cells in the PBSC products were eliminated. CONCLUSIONS: Very first attempts in mobilizing, harvesting, and selecting CD34+ stem cells were successful, paving the way for autoimmune patients to have autologous hematopoietic stem cell transplantation in Vietnam.

Novel mutations in unrelated Vietnamese patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder (PID) due to genetic defects in the NADPH oxidase of phagocytes. Affected patients become susceptible to infections such as pneumonia, diarrhea, and skin ulcer types. The patients require life-long treatment with prophylactic antibiotics, antifungals, or hematopoietic stem cell transplantation (HSCT) therapy. Early, accurate diagnosis will contribute to the life-prolonging of patients with CGD. This study's aim is to identify the mutation related to the disease. CASE PRESENTATION: Six patients from different Vietnamese families were collected for genetic analysis at Allergy, Immunology, and Rheumatology Department, Vietnam National Hospital Pediatrics. They were diagnosed with CGD by flow cytometry test with the conversion of dihydrorhodamine (DHR) 123 to rhodamine 123. METHODS: We performed whole exome sequencing (WES) as a tool for detecting novel mutations. The mutations were confirmed by the Sanger sequencing method in patients and their families. The influence of the mutations was predicted with the in silico analysis tools: PROVEAN, SIFT, PolyPhen 2, Mutation Taster, and MaxEntScan. RESULTS: In this study, five mutations were found in six unrelated patients with CGD from different Vietnamese families. Three novel pathogenic mutations were detected including one mutation (c.45+2 T>G) in the CYBB gene and two mutations (c.187_188insA and c.289G>C) in the NCF2 gene. CONCLUSIONS: Our results of CGD-related mutations contribute to the general understanding of the etiology of the disease and emphasize that WES sequencing can be used as a tool to help to diagnose carriers as well as assist in genetic counseling and prenatal screening.

Diagnostic Value of High-Sensitivity Troponin T for Subclinical Left Ventricular Systolic Dysfunction in Patients with Sepsis.

BACKGROUND: Left ventricular systolic dysfunction (LVSD) is common in sepsis. Speckle-tracking echocardiography (STE) is a useful emerging tool for evaluating the intrinsic left ventricular systolic function. High-sensitivity cardiac troponin T (hs-cTnT) is the most sensitive biomarker of myocardial injury. However, there are limited data regarding the association between hs-cTnT level and left ventricular systolic dysfunction based on STE in septic patients. We performed this prospective study to evaluate the diagnostic value of hs-cTnT level for subclinical left ventricular systolic dysfunction measured by STE in septic patients according to the sepsis-3 definition. METHODS: Patients with sepsis based on sepsis-3 definition admitted to the intensive care unit were prospectively performed STE and hs-cTnT level within 24 hours after the onset of sepsis. Baseline clinical and echocardiographic variables were collected. Left ventricular systolic dysfunction was defined as a global longitudinal strain of ≥-15%. RESULTS: During a 19-month period, 116 patients were enrolled in the study. The elevated hs-cTnT level was seen in 86.2% of septic patients, and 43.1% of patients had LVSD on STE. The median hs-cTnT level and the proportion of elevated hs-cTnT level (>14 ng/L) were significantly higher in patients with LVSD than in patients without LVSD. The area under the ROC curves of hs-cTnT to detect LVSD was 0.73 (P < 0.001). In the multivariate analysis, hs-cTnT (HR, 1.002; 95% CI, 1.000 to 1.004; P = 0.025) and septic shock (HR, 7.6; 95% CI, 2.25 to 25.76; P = 0.001) were independent predictors of LVSD. CONCLUSION: Our study indicated that the serum hs-cTnT level might be a useful biomarker for detecting LVSD in septic patients.

Prognostic Role of Left Ventricular Systolic Function Measured by Speckle Tracking Echocardiography in Septic Shock.

BACKGROUND: Left ventricular (LV) systolic dysfunction is common in septic shock. Global longitudinal strain (GLS) measured by speckle tracking echocardiography (STE) is a useful marker of intrinsic left ventricular systolic function. However, the association between left ventricular GLS and outcome in septic patients is not well understood. We performed this prospective study to investigate the prognostic value of LV systolic function utilizing speckle tracking echocardiography in patients with septic shock. METHODS: All the patients with septic shock based on sepsis-3 definition admitted to the intensive care unit were prospectively studied with STE within 24 hours after the onset of septic shock. Baseline clinical and echocardiographic variables were collected. The primary outcome was in-hospital mortality. RESULTS: During a 19-month period, 90 consecutive patients were enrolled in the study. The in-hospital mortality rate was 43.3%. Compared with survivors, nonsurvivors exhibited significantly less negative GLS (-13.1 ± 3.3% versus -15.8 ± 2.9%; p < 0.001), which reflected worse LV systolic function. The area under the ROC curves of GLS for the prediction of mortality was 0.76 (95% CI 0.67 to 0.87). Patients with GLS > -14.1% showed a significantly higher mortality rate (67.7% versus 15.6%; p < 0.0001; log-rank = 23.3; p < 0.0001). In the multivariate analysis, GLS (HR, 1.27; 95% CI 1.07 to 1.50, p = 0.005) and SOFA scores (HR, 1.27; 95% CI 1.08 to 1.50, p = 0.004) were independent predictors of in-hospital mortality. CONCLUSIONS: Our study indicated that LV systolic function measured by STE might be associated with mortality in patients with septic shock.

Building HIV healthcare worker capacity through telehealth in Vietnam.

Development of a robust technical assistance system is an essential component of a sustainable HIV response. Vietnam's National HIV Program is transitioning from a largely donor-funded programme to one primarily supported by domestic resources. Telehealth interventions are increasingly being used for training, mentoring and expert consultation in high-resource settings and hold significant potential for use as a tool to build HIV health worker capacity in low and middle-income countries. We designed, implemented and scaled up a novel HIV telehealth programme for Vietnam, with the goal of building a sustainable training model to support the country's HIV workforce needs. Over a 4-year period, HIV telehealth programmes were initiated in 17 public institutions with participation of nearly 700 clinical sites across 62 of the 63 provinces in the country. The telehealth programme was used to deliver certificate training courses, provide clinical mentoring and case-based learning, support programme implementation, provide coaching in quality improvement and disseminate new guidelines and policies. Programme evaluation demonstrated improved health worker self-reported competence in HIV care and treatment and high satisfaction among the programme participants. Lessons learnt from Vietnam's experience with telehealth can inform country programmes looking to develop a sustainable approach to HIV technical assistance and health worker capacity building.

Delivering patient-centered care in Parkinson's disease: Challenges and consensus from an international panel.

An international panel of movement disorders specialists explored the views and perceptions of people with Parkinson's disease (PD) about their condition and its treatment, including the potential mismatch between the clinician's view of the patient's condition and their own view of what aspects of the disease most affect their daily lives. The initiative was focused on Asian countries, so participants comprised experts in the management of PD from key centers in Asia, with additional insight provided by European and the North American movement disorders experts. Analysis of peer-reviewed publications on patient perceptions of PD and the factors that they consider important to their wellbeing identified several contributing factors to the mismatch of views, including gaps in knowledge of PD and its treatment, an understanding of the clinical heterogeneity of PD, and the importance of a multidisciplinary approach to patient care. The faculty proposed options to bridge these gaps to ensure that PD patients receive the personalized treatment they need to achieve the best possible outcomes. It was considered essential to improve patient knowledge about PD and its treatment, as well as increasing the awareness of clinicians of PD heterogeneity in presentation and treatment response. A multidisciplinary and shared-care approach to PD was needed alongside the use of patient-centered outcome measures in clinical trials and clinical practice to better capture the patient experience and improve the delivery of individualized therapy.

The effectiveness of knee osteoarthritis treatment by arthroscopic microfracture technique in combination with autologous bone marrow stem cells transplantation.

OBJECTIVE: We aimed to evaluate the efficacy of the treatment of knee osteoarthritis (OA) patients by using microfracture technique in combination with autologous bone marrow stem cell transplantation. METHODS: A clinical study was conducted between November 2011 and January 2015 and involved 46 patients (aged from 46 to 69) with primary knee OA grade II and III (according to Kellgren-Lawrence classification) at the Orthopedic Trauma Department, Vietnam-Germany Friendship Hospital. Patients were randomly assigned to receive knee arthroscopy and then bone-marrow stem cells from their pelvic bones via injection. RESULTS: The mean Visual Analogue Scale (VAS) score of present pain decreased from 5.68 before surgery to 1.7 24 months after surgery. The mean preoperative Knee Injury and Osteoarthritis Outcome Score (KOOS) was 36.34 (± 3.13), which increased to 74.62 (± 2.86) 24 months after surgery. On the MRI scans, the average Noyes score decreased from 12 (± 1.46) to 7 (± 1.50). Cartilage volume increased on average from 0.4512 (± 0.26) cm3 to 0.5463 (± 0.29) cm3 12-24 months after surgery. CONCLUSION: Treatment of osteoarthritis by a combination of arthroscopic microfracture and transplantation of autologous bone-marrow stem cells was an invasive, safe and effective method which showed an improvement in the clinical symptoms (VAS score) and knee functions (KOOS points).

Conductive polymer for ultra-broadband, wide-angle, and polarization-insensitive metamaterial perfect absorber.

We numerically and experimentally investigate a broadband, polarization-independent and wide-incident-angle metamaterial perfect absorber (MPA) based on conductive polymer. By optimizing the electrical conductivity of the polymer, a 16.7 GHz broadband MPA is observed with the absorptivity greater than 80% for both transverse magnetic and electric polarization. The measurement results performed in the range 8-18 GHz show a diametrical concatenation with simulation results and theoretical analysis. The absorption mechanism is explained by demonstrating the influence of polymer conductivity on the dissipated power, the equivalent impedance, and the induced electric field. Our work may contribute to further studies on broadband MPA using for various applications.

Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis.

Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We show that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss in wild-type mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of type XVII collagen (COL17A1/BP180), a critical molecule for HFSC maintenance, to trigger HFSC aging, characterized by the loss of stemness signatures and by epidermal commitment. Aged HFSCs are cyclically eliminated from the skin through terminal epidermal differentiation, thereby causing hair follicle miniaturization. The aging process can be recapitulated by Col17a1 deficiency and prevented by the forced maintenance of COL17A1 in HFSCs, demonstrating that COL17A1 in HFSCs orchestrates the stem cell-centric aging program of the epithelial mini-organ.

Treatability assessment of polycyclic aromatic hydrocarbons contaminated marine sediments using permanganate, persulfate and Fenton oxidation processes.

Various chemical oxidation techniques, such as potassium permanganate (KMnO4), sodium persulfate (Na2S2O8), Fenton (H2O2/Fe(2+)), and the modified persulfate and Fenton reagents (activated by ferrous complexes), were carried out to treat marine sediments that were contaminated with polycyclic aromatic hydrocarbons (PAHs) and dredged from Kaohsiung Harbor in Taiwan. Experimental results revealed that KMnO4 was the most effective of the tested oxidants in PAH degradation. Owing to the high organic matter content in the sediment that reduced the efficiencies of Na2S2O8 and regular Fenton reactions, a large excess of oxidant was required. Nevertheless, KH2PO4, Na4P2O7 and four chelating agents (EDTA, sodium citrate, oxalic acid, and sodium oxalate) were utilized to stabilize Fe(II) in activating the Na2S2O8 and Fenton oxidations, while Fe(II)-citrate remarkably promoted the PAH degradation. Increasing the molecular weight and number of rings of PAH did not affect the overall removal efficiencies. The correlation between the effectiveness of the oxidation processes and the physicochemical properties of individual PAH was statistically analyzed. The data implied that the reactivity of PAH (electron affinity and ionization potential) affected its treatability more than did its hydrophobicity (Kow, Koc and Sw), particularly using experimental conditions under which PAHs could be effectively oxidized.

A drug procurement, storage and distribution model in public hospitals in a developing country.

BACKGROUND: There is growing interest in pharmaceutical supply chains and distribution of medications at national and international levels. Issues of access and efficiency have been called into question. However, evaluations of system outcomes are not possible unless there are contextual data to describe the systems in question. Available guidelines provided by international advisory bodies such as the World Health Organization and the International Pharmacy Federation may be useful for developing countries like Vietnam when seeking to describe the pharmaceutical system. OBJECTIVE: The purpose of this study was to describe a conceptual model for drug procurement, storage, and distribution in four government-owned hospitals in Vietnam. METHOD: This study was qualitative and used semi-structured interviews with key informants from within the Vietnamese pharmaceutical system. Translated transcriptions were used to conduct a content analysis of the data. RESULTS: A conceptual model for the Vietnamese pharmaceutical system was described using structural and functional components. This model showed that in Vietnam, governmental policy influences the structural framework of the system, but allows for flexibility at the functional level of practice. Further, this model can be strongly differentiated from the models described by international advisory bodies. This study demonstrates a method for health care systems to describe their own models of drug distribution to address quality assurance, systems design and benchmarking for quality improvement.

Removal of polycyclic aromatic hydrocarbons from sediments using sodium persulfate activated by temperature and nanoscale zero-valent iron.

UNLABELLED: The oxidation of 16 polycyclic aromatic hydrocarbons (PAHs) compounds in sediments by sodium persulfate (Na2S2O8) simultaneously activated by temperature and nano zero-valent iron (nZVI) as the source of catalytic ferrous iron was investigated. The effect of various controlling factors, including S2O8(2-) (0.017-170 g/L), nZVI (0.01-1 g/L), and temperature (50-70 °C) were performed. The efficiency to remove PAHs was 10.7-39.1% for unactivated persulfate. The treated sample had over 50% of the persulfate still remaining from an initial persulfate dose of 170 g/L, whereas less than 1% of the persulfate remained from an initial persulfate dose of 0.017, 0.17, and 1.7 g/L. Adequate persulfate (170 g/L) must be present because it is the source of the sulfate radicals responsible for the degradation of PAHs. Results indicated that increasing temperature and the addition of nZVI into a persulfate-slurry system could enhance the persulfate oxidation process. The best removal efficiency (90%) was achieved after 24 hr while adding nZVI (0.01 g/L) to persulfate (170 g/L) at temperature of 70 °C. The results suggested that nZVI assisted persulfate oxidation without elevating temperature may be a suitable and economic alternative for the ex situ treatment of PAH-contaminated sediments. IMPLICATIONS: Nano zero-valent iron (nZVI) has been successfully applied to transform/degrade contaminants in soils and water. Additionally, nZVI has been used as a catalyst to activate persulfate for the treatment of various contaminants. In this study, with the support of temperature, nZVI-persulfate oxidation system for treatment of PAH-contaminated sediments was improved significantly and the treated sediment could meet remediation goals.

Genetic link between Cabeza, a Drosophila homologue of Fused in Sarcoma (FUS), and the EGFR signaling pathway.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive muscular weakness. Fused in Sarcoma (FUS) that has been identified in familial ALS is an RNA binding protein that is normally localized in the nucleus. However, its function in vivo is not fully understood. Drosophila has Cabeza (Caz) as a FUS homologue and specific knockdown of Caz in the eye imaginal disc and pupal retina using a GMR-GAL4 driver was here found to induce an abnormal morphology of the adult compound eyes, a rough eye phenotype. This was partially suppressed by expression of the apoptosis inhibitor P35. Knockdown of Caz exerted no apparent effect on differentiation of photoreceptor cells. However, immunostaining with an antibody to Cut that marks cone cells revealed fusion of these and ommatidia of pupal retinae. These results indicate that Caz knockdown induces apoptosis and also inhibits differentiation of cone cells, resulting in abnormal eye morphology in adults. Mutation in EGFR pathway-related genes, such as rhomboid-1, rhomboid-3 and mirror suppressed the rough eye phenotype induced by Caz knockdown. Moreover, the rhomboid-1 mutation rescued the fusion of cone cells and ommatidia observed in Caz knockdown flies. The results suggest that Caz negatively regulates the EGFR signaling pathway required for determination of cone cell fate in Drosophila.

"In their perception we are addicts": social vulnerabilities and sources of support for men released from drug treatment centers in Vietnam.

BACKGROUND: Amid the global transition to treat opioid addiction as an illness, many people who inject drugs (PWID) face heterogeneous legal environments that include both punitive and harm reduction measures. In Vietnam, many PWID, who have a high burden of HIV, are sent to drug treatment centers, or "06 centers", for compulsory detoxification, vocational training, and labor for up to four years. This study investigates the challenges and facilitators of reentry into community and family life among men who are released from "06 centers" and provides insights and recommendations for developing policies and interventions that address special needs of this vulnerable population. METHODS: In-depth interviews were conducted in 2011 by trained interviewers among a sample of 43 male PWID released within the past 2 years from "06 centers" in Hanoi, Vietnam to investigate the above issues and to recommend potential interventions. Participants were recruited from outpatient HIV clinics that serve PWID (n=22) and through peer referral from self-help groups for PWID (n=21). Interviews were audiotaped, transcribed, translated, entered into Atlas.TI qualitative data analysis software and analyzed for key themes. RESULTS: The interviews revealed persistent drug-related stigmatization, frequently paired with HIV-related stigmatization and discrimination, which hindered employment, increased participants' social isolation and exacerbated their struggles with addiction. Families were participants' primary source of financial, employment, and emotional support, but addiction-related family tensions also had negative psychological effects. Participants identified methadone maintenance treatment as an effective means of overcoming addiction, yet few could fully benefit from this treatment due to its limited availability. CONCLUSION: Our study suggests that PWID released from "06 centers" would greatly benefit from the scale-up of community-based harm reduction measures that include addiction and HIV treatment, coupled with employment-support and family centered mental health services.

Negative correlation between Per1 and Sox6 expression during chondrogenic differentiation in pre-chondrocytic ATDC5 cells.

Pre-chondrocytes undergo cellular differentiation stages during chondrogenesis under the influence by different transcription factors such as sry-type high mobility group box-9 (Sox9) and runt-related transcription factor-2 (Runx2). We have shown upregulation by parathyroid hormone (PTH) of the clock gene Period-1 (Per1) through the cAMP/protein kinase A signaling pathway in pre-chondrocytic ATDC5 cells. Here, we investigated the role of Per1 in the suppression of chondrogenic differentiation by PTH. In ATDC5 cells exposed to 10 nM PTH, a drastic but transient increase in Per1 expression was seen only 1 h after addition together with a prolonged decrease in Sox6 levels. However, no significant changes were induced in Sox5 and Runx2 levels in cells exposed to PTH. In stable Per1 transfectants, a significant decrease in Sox6 levels was seen, with no significant changes in Sox5 and Sox9 levels, in addition to the inhibition of gene transactivation by Sox9 allies. Knockdown of Per1 by siRNA significantly increased the Sox6 and type II collagen levels in cells cultured for 24 - 60 h. These results suggest that Per1 plays a role in the suppressed chondrocytic differentiation by PTH through a mechanism relevant to negative regulation of transactivation of the Sox6 gene during chondrogenesis.

Married men's first time experiences of early childbearing and their role in sexual and reproductive decision making: a qualitative study from rural Vietnam.

Male partners' involvement in women's sexual and reproductive health has been increasingly emphasised in international health. A qualitative approach with open-ended qualitative interviews was used to explore young, married men's first time experiences of early childbearing, their sexual and reproductive decision making and the meanings they make of their role as husbands and fathers. The results offer a nuanced picture of the men's vulnerability in becoming young fathers and having to assume their role as family decision-makers, while still being inexperienced in matters related to the health of their wives and newborn child. Constraints to gender equality and traditional norms and values continue to pose barriers to both young men and women making independent decisions in relation to marriage and childbearing. Men's involvement is necessary in healthcare programmes designed to improve women's sexual and reproductive health and the health of the newborn. Young, first-time fathers, in particular, need support and empowerment.

Hair follicle stem cells provide a functional niche for melanocyte stem cells.

In most stem cell systems, the organization of the stem cell niche and the anchoring matrix required for stem cell maintenance are largely unknown. We report here that collagen XVII (COL17A1/BP180/BPAG2), a hemidesmosomal transmembrane collagen, is highly expressed in hair follicle stem cells (HFSCs) and is required for the maintenance not only of HFSCs but also of melanocyte stem cells (MSCs), which do not express Col17a1 but directly adhere to HFSCs. Mice lacking Col17a1 show premature hair graying and hair loss. Analysis of Col17a1-null mice revealed that COL17A1 is critical for the self-renewal of HFSCs through maintaining their quiescence and immaturity, potentially explaining the mechanism underlying hair loss in human COL17A1 deficiency. Moreover, forced expression of COL17A1 in basal keratinocytes, including HFSCs, in Col17a1-null mice rescues MSCs from premature differentiation and restores TGF-ß signaling, demonstrating that HFSCs function as a critical regulatory component of the MSC niche.

Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation.

Somatic stem cell depletion due to the accumulation of DNA damage has been implicated in the appearance of aging-related phenotypes. Hair graying, a typical sign of aging in mammals, is caused by the incomplete maintenance of melanocyte stem cells (MSCs) with age. Here, we report that irreparable DNA damage, as caused by ionizing radiation, abrogates renewal of MSCs in mice. Surprisingly, the DNA-damage response triggers MSC differentiation into mature melanocytes in the niche, rather than inducing their apoptosis or senescence. The resulting MSC depletion leads to irreversible hair graying. Furthermore, deficiency of Ataxia-telangiectasia mutated (ATM), a central transducer kinase of the DNA-damage response, sensitizes MSCs to ectopic differentiation, demonstrating that the kinase protects MSCs from their premature differentiation by functioning as a "stemness checkpoint" to maintain the stem cell quality and quantity.