Metabolomics Highlights Different Life History Strategies of White and Brown Rot Wood-Degrading Fungi.

White and brown rot fungi efficiently deconstruct lignocellulose in wood, Earth's largest pool of aboveground biotic carbon and an important natural resource. Despite its vital importance, little is known about the metabolomic signatures among fungal species and nutritional modes (rot types). In this study, we used GC-MS metabolomics in solid wood substrates (in planta) to compare brown rot fungi (Rhodonia placenta and Gloeophylum trabeum) and white rot fungi (Trametes versicolor and Pleurotus ostreatus) at two decay stages (earlier and later), finding identifiable patterns for brown rot fungi at later decay stages. These patterns occurred in highly reducing environments that were not observed in white rot fungi. Metabolomes measured among the two white rot fungi were notably different, but we found a potential biomarker compound, galactitol, that was characteristic to white rot taxa. In addition, we found that white rot fungi were more efficient at catabolizing phenolic compounds that were originally present in wood. Collectively, white rot fungi were characterized by measured sugar release relative to higher carbohydrate solubilization by brown rot fungi, a distinction in soluble sugar availability that might shape success in the face of "cheater" competitors. This need to protect excess free sugars may explain the differentially high brown rot fungal production of pyranones and furanones, likely linked to an expansion of polyketide synthase genes. IMPORTANCE Despite the ecological and economic importance of wood-degrading fungi, little is known about the array of metabolites that fungi produce during wood decomposition. This study provides an in-depth insight into the wood decomposition process by analyzing and comparing the changes of >100 compounds produced by fungi with metabolic distinct nutritional modes (white and brown rot fungi) at different decay stages. We found a unique pattern of metabolites that correlated well with brown rot (carbohydrate selective mode) in later decay. These compounds were in line with some of the physiochemical and genetic features previously seen in these fungi such as a faster sugar release, lower pH, and the expansion of polyketide-synthase genes compared to white rot fungi (lignin-degrading mode). This study provides spatiotemporally resolved mechanism insights as well as critical groundwork that will be valuable for studies in basic biology and ecology, as well as applied biomass deconstruction and bioremediation.

Association between body mass index and the risk of falls: a nationwide population-based study.

The association of BMI with falls differed between men and women in Korea. Obesity was associated with a greater risk of falls in women, whereas underweight seemed to increase the risk of falls compared with normal weight in men. PURPOSE: This study examined the sex-specific association between body mass index (BMI) and falls in Korean adults using data from a large population-based survey. METHODS: We analyzed 113,805 men and women (age ≥ 50 years) who participated in the Korean Community Health Survey in 2013. Logistic regression was used to assess the relationship between BMI and falls. RESULTS: The mean (± standard deviation) age and BMI of all participants were 63.8 ± 9.6 years and 23.2 ± 2.9 kg/m2, respectively. Among the 113,805 subjects, 19.1% and 6.7% had histories of falls and recurrent falls, respectively. The association of BMI with recurrent falls differed between men and women. The multivariable-adjusted odd ratios (ORs) for recurrent falls were 0.98 (95% confidence interval [CI] 0.86-1.12), 1.23 (1.14-1.32), and 1.51 (1.26-1.81) in women with BMIs of < 18.5, 25-29.9, and ≥ 30 kg/m2, respectively, relative to those with BMIs of 18.5-24.9 kg/m2. The corresponding ORs for men were 1.20 (95% CI 1.01-1.42), 1.05 (0.96-1.14), and 0.97 (0.69-1.38), respectively. Older age and low economic level were associated independently with higher ORs of recurrent falls in men and women, respectively. In addition, comorbidities, including diabetes, stroke, arthritis, osteoporosis, and asthma, correlated significantly with an increased risk of recurrent falls (all p < 0.001). CONCLUSIONS: Obesity was associated with a greater risk of recurrent falls in women, whereas underweight seemed to be associated with a greater risk of falls in men.

Hydroxychloroquine treatment during pregnancy in lupus patients is associated with lower risk of preeclampsia.

BACKGROUND: Hydroxychloroquine (HCQ) is regarded as a mainstay in the treatment of systemic lupus erythematosus (SLE) because of its efficacy in preventing flares, achieving remission, and reducing overall mortality. However, the impact of HCQ on pregnancy outcomes remains controversial. OBJECTIVE: We aimed to investigate the effect of HCQ on pregnancy outcomes in patients with SLE. METHODS: We performed a retrospective cohort study of 151 pregnancies in 122 patients with SLE (80 pregnancies in the HCQ treatment group and 71 pregnancies in the HCQ nontreatment group). We reviewed baseline characteristics including maternal comorbidities such as antiphospholipid syndrome, lupus nephritis, and autoimmune hepatitis. Pregnancy outcomes (preeclampsia, preterm delivery, and fetal growth restriction) and neonatal outcomes (gestational age at delivery and birth weight) were compared between HCQ treatment and nontreatment groups. RESULTS: Preeclampsia was significantly less complicated (7.5% vs 19.7%, p = 0.032) and neonatal birth weight was significantly greater (2757.0 ± 583.5 g vs 2542.3 ± 908.3 g, p = 0.001) in the HCQ treatment group than in the HCQ nontreatment group. Multiple logistic analysis adjusting for body mass index (BMI), lupus nephritis, serum uric acid, and estimated glomerular filtration rate revealed HCQ treatment was associated with exceedingly lower risk of preeclampsia in SLE pregnancy (odds ratio (OR) 0.106 (confidence interval (CI) 0.017-0.671)). Other independent risk factors for preeclampsia were a high prepregnancy BMI (OR 1.575 (CI 1.114-2.227)) and low eGFR level (OR 0.931 (CI 0.886-0.979)) before pregnancy. CONCLUSION: Our data showed pregnancy outcomes in SLE patients can be improved in the HCQ treatment group with about 90% reduction of preeclampsia.

Identification of small peptides and glycinamide that inhibit melanin synthesis using a positional scanning synthetic peptide combinatorial library.

BACKGROUND: Antimelanogenic peptides are potentially useful to treat hyperpigmentation, but many peptides have limited application because of high cost and/or low activity. OBJECTIVES: To identify small and potent peptide inhibitors of cellular melanin synthesis that are useful for cosmetic and medical applications. METHODS: A positional scanning synthetic tetrapeptide combinatorial library was used for screening of potentially active peptides. Antimelanogenic activities of the peptide pools and individual peptides were evaluated in B16-F10 melanoma cells and human epidermal melanocytes treated with alpha-melanocyte-stimulating hormone (α-MSH). RESULTS: Predicted active tetrapeptide sequences were R-(F/L)-(C/W)-(G/R)-NH2 . Of the individual tetrapeptides tested, D3 (RFWG-NH2 ) and D5 (RLWG-NH2 ) exhibited high antimelanogenic activities. Tetrapeptide D9 (FRWG-NH2 ) with a sequence identical to that of a portion of α-MSH also showed antimelanogenic activity. Of the tripeptides tested, E5 (FWG-NH2 ), E6 (LWG-NH2 ) and E7 (RWG-NH2 ) were relatively more active. Dipeptide F1 (WG-NH2 ) and monopeptide G1 (G-NH2 , glycinamide) retained activity, but G2 (Ac-G-NH2 ) and G3 (glycine) did not. The antimelanogenic activities of peptides D3, E5, F1 and G1 were verified in α-MSH-stimulated human epidermal melanocytes. Commercially available G-NH2 ·HCl suppressed the phosphorylation levels of cAMP-responsive element binding protein, protein levels of microphthalmia-associated transcription factor and tyrosinase, l-tyrosine hydroxylase activity of tyrosinase, and the melanin levels in stimulated cells. CONCLUSIONS: Small peptides, including glycinamide and tryptophanyl glycinamide, are potent antimelanogenic agents with potential value for the treatment of skin hyperpigmentation.

Crepidiastrum denticulatum Extract Ameliorates Kidney Ischemia-Reperfusion Injury in Mice.

BACKGROUND: Crepidiastrum denticulatum (CD) is a well-known, traditionally consumed vegetable in Korea, which was recently reported to contain bioactive compounds with detoxification and antioxidant properties. Ischemia-reperfusion injury (IRI) is a major problem after renal transplantation. Furthermore, inflammatory responses to IRI exacerbate the resultant renal injury. In the present study, we investigated whether CD extract exhibits renoprotective effects against IR-induced acute kidney injury in mice. MATERIALS AND METHODS: Renal IRI was induced in male C57BL/6 mice by bilateral renal pedicle occlusion for 30 minutes followed by reperfusion for 48 hours. CD extract (75 mg/kg) was administered orally 5 days before IRI. RESULTS: Treatment with CD extract significantly decreased blood urea nitrogen and serum creatinine levels as well as kidney tubular injury. CD also prevented IRI-induced renal glutathione depletion and increased malondialdehyde levels. Western blotting and reverse transcriptase polymerase chain reaction indicated that CD extract significantly attenuates inducible nitric oxide synthase and toll-like receptor 2/4 protein levels 48 h after IRI. The expression of tumor necrosis factor-α and interleukin-1ß was significantly decreased in the CD extract treatment group. CONCLUSION: CD extract improved acute renal IRI through its antioxidant and anti-inflammatory effects. These findings suggest that CD extract is a potential therapeutic agent for acute ischemia-induced renal damage.

Human skin-depigmenting effects of resveratryl triglycolate, a hybrid compound of resveratrol and glycolic acid.

OBJECTIVES: Resveratryl triglycolate (RTG) is a hybrid compound derived by the esterification of resveratrol with glycolic acid. This compound has been previously shown to inhibit cellular melanin synthesis in vitro. This study aimed to examine the in vivo skin-depigmenting efficacy of RTG in human participants. METHODS: In total, 22 women aged between 25 and 49 years with Fitzpatrick skin type III or IV were enrolled. Their forearms were exposed to UV to induce artificial pigmentation. The test product containing 0.4% RTG or the control product was applied twice daily for up to 8 weeks after the artificial pigmentation. The participants visited the research centre every 2 weeks and were subjected to skin assessments. RESULTS: Visual assessment of pigmentation degree and instrumental analysis of melanin index, skin lightness (L* value) and skin colour (individual typology angle, ITAo ) indicated enhanced depigmentation of the skin in the test group, compared with the control group, in Weeks 6 and 8 (P < 0.05). No adverse skin reactions were observed in any of the participants during the entire test. CONCLUSION: This study demonstrated the skin-depigmenting effects of RTG in human participants.

Double-blind Randomized Study to Evaluate the Safety and Efficacy of Over-the-counter Tooth-whitening Agents Containing 2.9% Hydrogen Peroxide.

OBJECTIVES: In this double-blind randomized study, we evaluated the safety and efficacy of over-the-counter (OTC) bleaching products that included 2.9% hydrogen peroxide (H2O2) with two methods of application: strip and paint-on. METHODS AND MATERIALS: A commonly used product was selected for each type (strip and paint-on) of OTC bleaching agent. In total, 75 volunteers were assigned randomly into five groups: two test groups (strip and paint-on), two negative control groups (products without H2O2), and one positive control group (dentist-supervised home bleaching). The tooth shade was evaluated with a spectrophotometer and Vita shade guide at baseline and 2 weeks and 4 weeks after use. To document any adverse reactions, such as hypersensitivity or tissue irritation, all patients were examined and the Gingival Index (GI), Plaque Index (PI), and a visual analog scale (VAS) measuring the cold response were obtained. RESULTS: There were significant differences among the five groups ( p<0.001). The positive control showed the greatest color changes; then, in decreasing order, the strip-type test group, paint-on-type test group, and negative controls. The strip-type bleaching agent was significantly more effective than the paint-on-type agent and the negative control, while it was significantly less effective than the dentist-supervised home bleaching. Regardless of the treatment group, the canines showed greater color changes than did the central or lateral incisors. Some cases of gingival irritation and hypersensitivity were observed, but they were mild and reversible. GI, PI, and VAS scores were not significantly changed. CONCLUSIONS: Within the limitations of this study, the results indicated that the strip-type and paint-on-type OTC bleaching agents were significantly less efficacious than was dentist-supervised home bleaching; however, they showed acceptable safety and efficacy. The strip-type was more effective than was the paint-on-type in this study.

Reliability and validity of the Atopic Dermatitis Symptom Score (ADSS).

BACKGROUND: We have developed the Atopic Dermatitis Symptom Score (ADSS) by which patients or parents can easily assess and record AD symptoms on a daily basis in a smartphone application. The aim of this study was to evaluate the reliability and validity of the ADSS. METHODS: We enrolled 307 children and adolescents with AD. Parents or caregivers were asked to record daily symptoms of the patients (itching, sleep disturbance, erythema, dryness, oozing, and edema) using a scale of 0-4. Statistical analyses consisted of the test-retest reliability, concurrent validity, minimal clinically important difference (MCID), responsiveness, floor or ceiling effects, and screening accuracy. Receiver-operating characteristic analyses were conducted to evaluate the ADSS cutoff point for predicting severe AD (SCORing AD [SCORAD] ≥40). RESULTS: Test-retest reliability between daytime and night-time ADSS was good (intraclass correlation coefficient, 0.82 [95% CI: 0.70-0.90]). An increase in ADSS was significantly associated with an increase in SCORAD (r = 0.64, P < .0001) (concurrent validity). The MCID was 4.1 points for the ADSS. There was a significant association between changes in ADSS and SCORAD (r = 0.56, P < .0001), indicating good responsiveness. At the optimal ADSS cutoff value of 7.0, sensitivity, specificity, and positive and negative predictive values were 88.4%, 78.6%, 21.1%, and 99.1%, respectively (screening accuracy). CONCLUSIONS: The ADSS can be a useful tool for self-assessment of skin symptoms in children with AD.

Retention Improvement in Fluoride Application with Cold Atmospheric Plasma.

This study aimed to apply fluoride formulations to enamel with cold atmospheric plasma (CAP) and analyze the fluoride uptake, retention, and acid resistance quantitatively. Human enamel specimens were divided randomly into 2 groups: group APF1, 1.23% acidulated phosphate fluoride (APF) gel; group APF2, 1.23% APF gel with CAP. Fluoride and CAP were applied to the samples 4 times at 1-wk intervals. The specimens were also stored in artificial saliva for 4 wk to evaluate the retention of fluoride. The fluoride content on the fluoride-treated enamel was measured by an electron probe microanalyzer. To detect the resistance to demineralization, the calcium-to-phosphate ratio of the enamel samples was measured after the application of APF gel with or without CAP, followed by soaking in the demineralization solution. In groups APF1 and APF2, the amount of fluoride detected increased depending on the application frequency, and more fluoride was detected in group APF2 than in group APF1. In the experiment examining the maintenance effect, fluoride was not detected in group APF1, whereas fluoride was detected in group APF2 up to the fourth week. As for the resistance to demineralization, the calcium-to-phosphate ratio of the enamel treated with APF and CAP was higher than that treated with APF alone, and it increased with the frequency of treatment. This study suggests that the combination treatment of CAP and fluoride improves retention of fluoride on the enamel and resistance to demineralization when compared with treatment with fluoride alone.

Effects of space allocations and energy levels on growth performance and nutrient digestibility in growing and finishing pigs.

Two experiments were conducted to investigate effects of different space allocations and different dietary metabolizable energy (ME) levels on growth performance and nutrient digestibility in growing and finishing pigs. In experiment 1, a total of 84 growing pigs [(Yorkshire × Landrace) × Duroc] with an initial body weight (BW) of 27.10 ± 1.60 kg were used in a 5-week trial. Pigs were blocked based on initial BW into a 2 × 2 factorial design with the following factors: (i) 0.60 or 0.80 m2 /pig space allocations; and (ii) 3,400 or 3,550 kcal/kg ME of diets. In experiment 2, a total of 84 finishing pigs with an initial BW of 67.43 ± 1.97 kg were used in a 10-week trial. Pigs were allotted based on initial BW into a 2 × 2 factorial design with the following factors: (i) 0.81 or 1.08 m2 /pig space allocations; and (ii) 3,300 or 3,450 kcal/kg ME of diet. In experiment 1, high ME diet improved gain-to-feed ratio (G:F) in pigs with low space allocation but not in pigs in high space allocation (p < .05). Additionally, high ME diet increased apparent total tract digestibility (ATTD) of nitrogen in low space allocation but decreased ATTD of nitrogen in high space allocation (p < .05). In experiment 2, high ME diet improved average daily gain (ADG) and G:F in early-finishing pigs with low space allocation but not in pigs with high space allocation (p < .05). In conclusion, the provision of high ME diets was not enough to overcome the reduction in growth performance due to low space allocation but can improve feed efficiency in growing pigs and daily gain and feed efficiency early-finishing pigs.

Revision anatomical reconstruction of the lateral ligaments of the ankle augmented with suture tape for patients with a failed Broström procedure.

AIMS: The aim of this prospective study was to evaluate the intermediate-term outcomes after revision anatomical ankle ligament reconstruction augmented with suture tape for a failed modified Broström procedure. PATIENTS AND METHODS: A total of 30 patients with persistent instability of the ankle after a Broström procedure underwent revision augmented with suture tape. Of these, 24 patients who were followed up for more than two years were included in the study. There were 13 men and 11 women. Their mean age was 31.8 years (23 to 44). The mean follow-up was 38.5 months (24 to 56) The clinical outcome was assessed using the Foot and Ankle Outcome Score (FAOS) and the Foot and Ankle Ability Measure (FAAM) score. The stability of the ankle was assessed using stress radiographs. RESULTS: The mean FAOS and FAAM scores improved significantly to 87.5 (73 to 94) and 85.1 (70 to 95) points at final follow-up, respectively (p < 0.001). The mean angle of talar tilt and anterior talar translation improved significantly to 2.8° (0° to 6°) and 4.1 mm (2 to 7) at final follow-up, respectively (p < 0.001). Side to side comparison in stress radiographs at final follow-up showed no significant difference. The revision failed in one patient who underwent a further revision using allograft tendon. CONCLUSION: The revision modified Broström procedure augmented with suture tape is an effective form of treatment for recurrent instability of the ankle following a failed Broström procedure. This technique provides reliable stability and satisfactory clinical outcomes at intermediate-term follow-up. Cite this article: Bone Joint J 2017;99-B:1183-9.

Technical note: Induction of pluripotent stem cell-like cells from chicken feather follicle cells.

Pluripotent stem cells including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) are regarded as representative tools for conservation of animal genetic resources. Although ESC have been established from chicken, it is very difficult to obtain enough embryos for isolation of stem cells for avian conservation in most wild birds. Therefore, the high feasibility of obtaining the pluripotent cell is most important in avian conservation studies. In this study, we generated induced pluripotent stem cell-like cells (iPSLC) from avian Feather Follicular cells (FFC). Avian FFC are one of the most easily accessible cell sources in most avian species, and their reprogramming into pluripotent stem cells can be an alternative system for preservation of avian species. Intriguingly, FFC had mesenchymal stromal cells (MSC)-like characteristics with regard to gene expression, protein expression, and adipocyte differentiation. Subsequently, we attempted to generate iPSLC from FFC using retroviral vectors. The FFC-iPSLC can proliferate with the stem pluripotent property and differentiate into several types of cells in vitro. Our results suggest that chicken FFC are an alternative cell source for avian cell reprogramming into pluripotent stem cells. This experimental strategy should be useful for conservation and restoration of endangered or high-value avian species without sacrificing embryos.

Major Histocompatibilty Complex-Restricted Adaptive Immune Responses to CT26 Colon Cancer Cell Line in Mixed Allogeneic Chimera.

BACKGROUND: Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. METHODS: We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells. The protocol involves challenging 1 × 105 cells of CT26 cells intra-hepatically on day 50 after bone marrow transplantation, and, by use of CT26 lysates and an H-2Ld-restricted AH1 pentamer, flow cytometric analysis was performed to detect the generation of cancer-specific CD4+ and CD8+ T cells at various time points. RESULTS: We found that immunocompetence against tumors depends heavily on cancer-specific CD8+ T-cell responses in a major histocompatibility complex-restricted manner; the evidence was further supported by the increase of interferon-γ-secreting CD4+ T cells. Moreover, we demonstrated that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62LhiCCR7+) as well as effector memory cells (CD62LloCCR7-). Moreover, mixed allogeneic chimeras (BALB/c to C56BL/6 or vice versa) showed similar or heightened immune responses to CT26 cells compared with that of wild-type mice. CONCLUSIONS: Our results suggest that the responses of primary immunocompetency and of pre-existing memory T cells against allogeneic cancer are sustained and preserved long-term in a mixed allogeneic chimeric environment.

Detecting selection signatures between Duroc and Duroc synthetic pig populations using high-density SNP chip.

The development of high throughput genotyping techniques has facilitated the identification of selection signatures of pigs. The detection of genomic selection signals in a population subjected to differential selection pressures may provide insights into the genes associated with economically and biologically important traits. To identify genomic regions under selection, we genotyped 488 Duroc (D) pigs and 155 D × Korean native pigs (DKNPs) using the Porcine SNP70K BeadChip. By applying the FST and extended haplotype homozygosity (EHH-Rsb) methods, we detected genes under directional selection associated with growth/stature (DOCK7, PLCB4, HS2ST1, FBP2 and TG), carcass and meat quality (TG, COL14A1, FBXO5, NR3C1, SNX7, ARHGAP26 and DPYD), number of teats (LOC100153159 and LRRC1), pigmentation (MME) and ear morphology (SOX5), which are all mostly near or at fixation. These results could be a basis for investigating the underlying mutations associated with observed phenotypic variation. Validation using genome-wide association analysis would also facilitate the inclusion of some of these markers in genetic evaluation programs.

Effects of dietary methyl sulfonyl methane (MSM) supplementation on growth performance, nutrient digestibility, meat quality, excreta microbiota, excreta gas emission, and blood profiles in broilers.

A 29-d trial was conducted to evaluate the effects of dietary methyl sulfonyl methane (MSM) supplementation on growth performance, meat quality, nutrient digestibility, excreta microbiota, excreta gas emission, and blood profiles in broilers. A total of 816 1-day-old male Ross 308 broilers (44 ± 0.44 g) were assigned to 4 dietary treatments, composed of 12 replicates with 17 birds per replicate. The 4 treatments were: 1) CON, basal diet; 2) S1, CON + 0.05% MSM; 3) S2, CON + 0.10% MSM; 4) S3, CON + 0.20% MSM. In the current study, body weight (BW) on d 14 and 29 showed significant improvement as dietary MSM increased from 0.05% to 0.20% (P < 0.05). During d 1 to 14 and overall, higher (P < 0.05) body weight gain (BWG) and lower feed conversion ratio (FCR) were observed in broilers fed MSM diets. Between d 15 and 29, higher (P < 0.05) BWG was observed in broilers fed MSM diets. Redness (a*) was increased linearly (P < 0.05) in broilers fed MSM diets. On d 3, 5, and 7, drip loss was decreased linearly (P < 0.05) in broilers fed MSM diets. Lactobacillus and E. coli were effected linearly (P < 0.05) in broilers fed MSM diets. Alanine aminotransferase (ALT), white blood cells (WBC) and lymphocytes were improved linearly (P < 0.05) in broilers fed MSM diets. In conclusion, dietary supplementation MSM has positive effects on growth performance, meat quality, excreta microbiota, and blood profiles in broilers.

The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation.

The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure. Through loss of function studies, we showed BCL11B, a transcription factor recurrently mutated T-ALL, is essential for T-lineage commitment, particularly the repression of NK and myeloid potentials, and the induction of T-lineage genes, during the initial stages of human T-cell differentiation. In gain of function studies, BCL11B inhibited growth of and induced a T-lineage transcriptional program in T-ALL cells. We found previously unknown differentiation stage-specific DNA binding of BCL11B at multiple T-lineage genes; target genes showed BCL11B-dependent expression, suggesting a transcriptional activator role for BCL11B at these genes. Transcriptional analyses revealed differences in the regulatory actions of BCL11B between human and murine thymopoiesis. Our studies show BCL11B is a key regulator of the initial stages of human T-cell differentiation and delineate the BCL11B transcriptional program, enabling the dissection of the underpinnings of normal T-cell differentiation and providing a resource for understanding dysregulations in T-ALL.

Field-free switching of perpendicular magnetization through spin-orbit torque in antiferromagnet/ferromagnet/oxide structures.

Spin-orbit torques arising from the spin-orbit coupling of non-magnetic heavy metals allow electrical switching of perpendicular magnetization. However, the switching is not purely electrical in laterally homogeneous structures. An extra in-plane magnetic field is indeed required to achieve deterministic switching, and this is detrimental for device applications. On the other hand, if antiferromagnets can generate spin-orbit torques, they may enable all-electrical deterministic switching because the desired magnetic field may be replaced by their exchange bias. Here we report sizeable spin-orbit torques in IrMn/CoFeB/MgO structures. The antiferromagnetic IrMn layer also supplies an in-plane exchange bias field, which enables all-electrical deterministic switching of perpendicular magnetization without any assistance from an external magnetic field. Together with sizeable spin-orbit torques, these features make antiferromagnets a promising candidate for future spintronic devices. We also show that the signs of the spin-orbit torques in various IrMn-based structures cannot be explained by existing theories and thus significant theoretical progress is required.

Variations in fat mass contribution to bone mineral density by gender, age, and body mass index: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2011.

UNLABELLED: The relationship of body composition and bone mineral density is complex and controversial. When classifying Korean population based on gender, age, and body mass index, fat mass had varying contributions to bone mineral density. INTRODUCTION: The relationship between body composition and bone mineral density (BMD) is complex, and it is uncertain how components of body mass variably affect BMD. METHODS: This cross-sectional observational study was performed in subjects ≥20 years based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2008 to 2011. Among 17,583 subjects, the mean ages were 49.1 ± 16.0 years (M, n = 7495) and 49.3 ± 16.3 years (F, n = 10,088). Subjects were divided into age groups, either <50 or ≥50 years for males, or menopausal state, either premenopausal or postmenopausal, for females. A further classification used BMI, either <25 or ≥25 kg/m(2). Anthropometric and body composition parameters were compared and evaluated to look for correlations with BMD. Further, appendicular lean mass (ALM), fat mass (FM), fat percentage (FP), and waist circumference (WC) were included for multivariate analysis with BMD, controlling for covariates in each age group and BMI subgroup. RESULTS: Anthropometric and body composition parameters significantly correlated with BMD in all age groups for both genders. After adjusting for covariates, ALM strongly affected BMD in all age groups for both genders. FM, FP, and WC significantly affected BMD in both age groups of women and in older men, but they did not affect BMD in younger men. Fat indices positively affected BMD of all sites in all non-obese women and in non-obese older men. However, little contribution was found in obese subgroups of both genders and in non-obese younger men. CONCLUSION: Considering different weights of covariates, ALM strongly contributed to BMD in all gender, age, and BMI groups. On the other hand, fat indices positively affected BMD of both age groups in women and older men with normal BMI, but they showed little contribution to BMD within the same age groups with high BMI or any BMI subgroups of younger men.

Identification and Characterization of the SnTox6-Snn6 Interaction in the Parastagonospora nodorum-Wheat Pathosystem.

Parastagonospora nodorum is a necrotrophic fungal pathogen that causes Septoria nodorum blotch (SNB) (formerly Stagonospora nodorum blotch) on wheat. P. nodorum produces necrotrophic effectors (NE) that are recognized by dominant host sensitivity gene products resulting in disease development. The NE-host interaction is critical to inducing NE-triggered susceptibility (NETS). To date, seven NE-host sensitivity gene interactions, following an inverse gene-for-gene model, have been identified in the P. nodorum-wheat pathosystem. Here, we used a wheat mapping population that segregated for sensitivity to two previously characterized interactions (SnTox1-Snn1 and SnTox3-Snn3-B1) to identify and characterize a new interaction involving the NE designated SnTox6 and the host sensitivity gene designated Snn6. SnTox6 is a small secreted protein that induces necrosis on wheat lines harboring Snn6. Sensitivity to SnTox6, conferred by Snn6, was light-dependent and was shown to underlie a major disease susceptibility quantitative trait locus (QTL). No other QTL were identified, even though the P. nodorum isolate used in this study harbored both the SnTox1 and SnTox3 genes. Reverse transcription-polymerase chain reaction showed that the expression of SnTox1 was not detectable, whereas SnTox3 was expressed and, yet, did not play a significant role in disease development. This work expands our knowledge of the wheat-P. nodorum interaction and further establishes this system as a model for necrotrophic specialist pathosystems.

Reduced expression of the epidermal growth factor signaling system in preeclampsia.

INTRODUCTION: The epidermal growth factor (EGF) signaling system regulates trophoblast differentiation, and its disruption could contribute to perinatal disease. We hypothesized that this pathway is altered in preeclampsia, a disorder associated with trophoblast apoptosis and failure to invade and remodel the uterine spiral arteries. METHODS: Six EGF family peptides and a truncated EGF receptor splice variant (p110/EGFR) were examined using immunohistochemistry in the trophoblast of placentas (N = 76) from women with preeclampsia, and compared to placentas from women of similar gestational age (GA) with preterm labor (PTL) or small for gestational age (SGA) fetuses, as well as normal term placentas. EGF, transforming growth factor-α (TGFA), and heparin-binding EGF-like growth factor (HBEGF) were evaluated using ELISA in maternal plasma from another 20 pregnancies with or without preeclampsia. Cell death was evaluated in the HTR-8/SVneo human cytotrophoblast cell line using TUNEL to evaluate the protective effects of EGF peptides. RESULTS: Trophoblast HBEGF, TGFA, and EGF were significantly reduced in preeclampsia compared to PTL and SGA, while p110/EGFR accumulated significantly on the surface of the chorionic villi (p < 0.05). Plasma EGF levels were significantly decreased in preeclamptic patients, compared to non-preeclamptic patients (p < 0.05). HBEGF, EGF, TGFA, epiregulin, and betacellulin each blocked cytotrophoblast cell death in vitro (p < 0.05). DISCUSSION: Three members of the EGF family are dysregulated in placentas with preeclampsia, whereas p110/EGFR, a potential EGF receptor antagonist, is overexpressed. These findings are consistent with the concept that disruption of the EGF signaling system contributes to aberrant trophoblast development associated with preeclampsia.