bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation measures and protection awareness are significant for latent tuberculosis infection: a cross-sectional study based on T-SPOT.TBamong health care workers in China
Authors: Deng Yunfeng , Liu Yun , Li Yan , Jing Hui , Wang Yan , Li Xuezheng , Xu Lingzhong
Published: March 2019

This study aimed to reveal the associated risk factors for latent tuberculosis infection (LTBI) detected by T-SPOT.TBassay among health care workers (HCWs) at different working locations or job categories in China. This cross-sectional study included 934 HCWs who underwent the T-SPOT.TBassay. Demographic and social characteristics of the participants, including age, sex, job categories, department/ward and duration of healthcare service, were recorded. Among 934 HCWs, 267 (28.5867%) were diagnosed as having LTBI with positive T-SPOT.TBassay. HCWs working in inpatient tuberculosis (TB) (odds ratio (OR) 2.917; 95% confidence interval (CI) 1.852–4.596;P< 0.001) and respiratory wards (OR 1.840; 95% CI 1.124–3.011;P= 0.015), and with longer duration of healthcare service (OR 1.048; 95% CI 1.016–1.080;P= 0.003) were risk factors for positive T-SPOT.TBresult. Furthermore, longer working duration increased the positive rate of T-SPOT.TBresults for physicians and nurses, and physicians had higher risks than nurses for the same working duration. Inpatient TB and respiratory wards were high-risk working locations for HCWs with LTBI, and longer duration of healthcare service also increased the risk of LTBI among HCWs. A complete strategy for TB infection control and protection awareness among HCWs should be enhanced.
The association of cellulitis incidence and meteorological factors in Taiwan
Authors: Hsu Ren-Jun , Chou Chia-Cheng , Liu Jui-Ming , Pang See-Tong , Lin Chien-Yu , Chuang Heng-Chang , Chuang Cheng-Keng , Wang Hsiao-Wei , Chang Ying-Hsu , Lin Po-Hung
Published: March 2019

Cellulitis is a common infection of the skin and soft tissue. Susceptibility to cellulitis is related to microorganism virulence, the host immunity status and environmental factors. This retrospective study from 2001 to 2013 investigated relationships between the monthly incidence rate of cellulitis and meteorological factors using data from the Taiwanese Health Insurance Dataset and the Taiwanese Central Weather Bureau. Meteorological data included temperature, hours of sunshine, relative humidity, total rainfall and total number of rainy days. In otal, 195 841 patients were diagnosed with cellulitis and the incidence rate was strongly correlated with temperature (γS = 0.84, P < 0.001), total sunshine hours (γS = 0.65, P < 0.001) and total rainfall (γS = 0.53, P < 0.001). The incidence rate of cellulitis increased by 3.47/100 000 cases for every 1° elevation in environmental temperature. Our results may assist clinicians in educating the public of the increased risk of cellulitis during warm seasons and possible predisposing environmental factors for infection.
International coordination of environmental policies: is it always worth the effort?
Authors: Bayham Jude , Muñoz-García Félix , Espínola-Arredondo Ana
Published: March 2019

We study entry policies as an alternative form of environmental policy. Given the strong political opposition to standard output subsidies and taxes, several countries have recently used entry policies to promote renewable energy technology, such as solar panels and biofuels. We study a two-stage game in which two regulators choose an entry policy (i.e., tax, subsidy or permit) to maximize domestic welfare. Observing the policy, firms decide the region in which to enter and compete as Cournot oligopolists. We find that both domestic (uncoordinated) policies and internationally coordinated policies increase welfare relative to unregulated settings. However, the welfare gains from international policy coordination are only large when the product is extremely clean. These results indicate that the welfare gains of international policy coordination may only offset the costs of negotiation in relatively clean industries.
Variation of iodine status during pregnancy and its associations with thyroid function in women from Rio de Janeiro, Brazil
Authors: Corcino Carolina Martins , Berbara Tatiana Martins Benvenuto Louro , Saraiva Débora Ayres , Morais Nathalie Anne de Oliveira e Silva de , Schtscherbyna Annie , Gertrudes Larissa Nascimento , Teixeira Patrícia de Fátima dos Santos , Vaisman Mario
Published: March 2019

Objective

To assess iodine status and its effects on maternal thyroid function throughout pregnancy.

Design

In the present prospective cohort study, three urinary samples were requested for urinary iodine concentration (UIC) determinations in both the first and third gestational trimesters. Serum thyrotropin (TSH) and free thyroxine (FT4) were analysed in both trimesters and thyroid antibodies were assessed once.

Setting

Rio de Janeiro, Brazil.

Participants

First-trimester pregnant women (n243), of whom 100 were re-evaluated during the third trimester.

Results

Iodine sufficiency was found in the studied population (median UIC=216·7 µg/l). The first- and third-trimester median UIC was 221·0 and 208·0 µg/l, respectively. TSH levels (mean (sd)) were higher in the third trimester (1·08 (0·67)v. 1·67 (0·86) mIU/l;P<0·001), while FT4levels decreased significantly (1·18 (0·16)v. 0·88 (0·12) ng/dl;P<0·001), regardless the presence of iodine deficiency (UIC<150 µg/l) or circulating thyroid antibodies. UIC correlated (β; 95% CI) independently and negatively with age (–0·43; –0·71, –0·17) and positively with multiparity (0·15; 0·02, 0·28) and BMI (0·25; 0·00, 0·50). Furthermore, median UIC per pregnant woman tended to correlate positively with TSH (0·07; –0·01, 0·14). Women with median UIC≥250 µg/l and at least one sample ≥500 µg/l throughout pregnancy had a higher risk of subclinical hypothyroidism (OR=6·6; 95% CI 1·2, 37·4).

Conclusions

In this cohort with adequate iodine status during pregnancy, excessive UIC was associated with an increased risk of subclinical hypothyroidism.
Imaging and Analysis of Cellular Locations in Three-Dimensional Tissue Models
Authors: Colomb Warren , Osmond Matthew , Durfee Charles , Krebs Melissa D. , Sarkar Susanta K.
Published: March 2019

The absence of quantitative in vitro cell–extracellular matrix models represents an important bottleneck for basic research and human health. Randomness of cellular distributions provides an opportunity for the development of a quantitative in vitro model. However, quantification of the randomness of random cell distributions is still lacking. In this paper, we have imaged cellular distributions in an alginate matrix using a multiview light sheet microscope and developed quantification metrics of randomness by modeling it as a Poisson process, a process that has constant probability of occurring in space or time. We imaged fluorescently labeled human mesenchymal stem cells embedded in an alginate matrix of thickness greater than 5 mm with $\sim\! {\rm 2}{\rm. 9} \pm {\rm 0}{\rm. 4}\,\mu {\rm m}$ axial resolution, the mean full width at half maximum of the axial intensity profiles of fluorescent particles. Simulated randomness agrees well with the experiments. Quantification of distributions and validation by simulations will enable quantitative study of cell–matrix interactions in tissue models.
Dietary and Biochemical Characteristics Associated with Normal-Weight Obesity
Authors: Amani Reza , Parohan Mohammad , Jomehzadeh Nabi , Haghighizadeh Mohammad Hossein
Published: March 2019

Abstract. Background: Inflammation and oxidative stress have been reported to be higher in subjects with normal weight obesity (NWO) syndrome [normal body mass index (BMI) (<25 kg/m2) but excessive body fat (for women ≥ 30% and for men ≥ 20%) according to World Health Organization (WHO) definitions]; however, it is unclear whether this is due to inadequate dietary antioxidant intake or the pathophysiology of NWO. The aim of present study was to assess the association between dietary factors and body antioxidant status with NWO syndrome in male university students. Methods: This study was a case-control study carried out on ninety age-matched male university students [30 normal weights (NW), 30 NWO and 30 overweight-obese (OB)]. A validated food frequency questionnaire (98 items) and 3-day 24-h recalls were used for dietary assessment. Total antioxidant capacity (TAC) of diet and serum and high-sensitive C-reactive protein (hs-CRP) concentrations were also measured. Results: Dietary intake of fruits (frequency factor (FF) = 2.3 vs 2.9, p < 0.05), legumes (FF = 0.7 vs 1.3, p < 0.01), nuts and seeds (FF = 0.4 vs 0.8, p < 0.05), beta-cryptoxanthin (p < 0.05), lycopene (p < 0.05) and serum TAC levels (p < 0.01) were significantly lower in NWO compared to the NW group. No significant differences in these parameters were observed between NWO and OB group. A significant negative correlation was observed between serum TAC levels and BMI (r = −0.57, p < 0.001) and body fat percent (r = −0.52, p < 0.001). Conclusions: This study shows that NWO male subjects consume lower amounts of dietary antioxidants and share the same low body antioxidant status as obese individuals, although they appear lean.
Vitamin D3 supplementation improves serum SFRP5 and Wnt5a levels in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial
Authors: Rezagholizadeh Farzaneh , Keshavarz Seyed Ali , Djalali Mahmoud , Rad Esmaeel Yussefi , Alizadeh Shahab , Javanbakht Mohammad Hassan
Published: March 2019

Abstract. Objective: To explore the effect of vitamin D3 on novel serum adipokines, secreted frizzled-related protein 5 (SFRP5) and Wingless-Type MMTV Integration Site Family Member 5a (Wnt5a) levels in Type 2 Diabetes Mellitus (T2DM) patients. Methods: Forty patients (16 women and 24 men) with type 2 diabetes participated in this double-blind, randomized, placebo-controlled clinical trial study. Participants were randomly assigned to receive 4000 IU vitamin D3(n = 20) or placebo (n = 20) daily for 2 months. Anthropometric indices, fasting blood glucose (FBS), hemoglobin A1c (HbA1c), insulin, serum tumor necrosis factor (TNF)-α, Wnt5a, SFRP5, physical activity, lipid profile, dietary intake, and serum calcidiol were assessed at the baseline and after 8 weeks. Results: In the group receiving Vitamin D, a significant increase in Calicidiol (15.03 ± 10.44 vs. 27.33 ± 11.2 ng/dl; P = < 0.001), SFRP5 (3.6 ± 0.46 vs. 3.98 ± 0.59 ng/ml; P = 0.01), and Wnt5a (0.33 ± 0.129 vs. 0.29 ± 0.047; P = 0.03) was observed. After two months supplementation, there were significant between-group differences in Calicidiol (27.33 ± 11.2 vs. 17.9 ± 12.95 ng/dl; P = 0.01), TNF-α (89.22 ± 34.28 vs. 164.93 ± 120.45 ng/ml; P = 0.006), Wnt5a (0.29 ± 0.047 vs. 0.33 ± 0.09; P = 0.04), and HbA1c (6.6 ± 0.96 % vs. 7.64 ± 1.15 %; p = 0.002). Moreover, the net changes (end – baseline) of Calicidiol (P = < 0.001), SFRP5 (P = 0.04), Wnt5a (P = 0.005), TNF-α (P = 0.01), insulin (P = 0.03), and QUICKI (P = 0.01) was significant between the groups. There were no significant effects on FBS and homeostasis model of assessment-estimated insulin resistance (HOMA-IR). Conclusion: 8 weeks of vitamin D3 supplementation for patients with type 2 diabetes may increase serum anti-inflammatory adipokine SFRP5 but decrease serum pro-inflammatory Wnt5a and TNF-α.
Substorm Onset Latitude and the Steadiness of Magnetospheric Convection
Authors: Milan S. E. , Walach M.‐T. , Carter J. A. , Sangha H. , Anderson B. J.
Published: March 2019

We study the role of substorms and steady magnetospheric convection (SMC) in magnetic flux transport in the magnetosphere, using observations of field‐aligned currents by the Active Magnetosphere and Planetary Electrodynamics Response Experiment. We identify two classes of substorm, with onsets above and below 65° magnetic latitude, which display different nightside field‐aligned current morphologies. We show that the low‐latitude onsets develop a poleward‐expanding auroral bulge, and identify these as substorms that manifest ionospheric convection‐braking in the auroral bulge region as suggested by Grocott et al. (2009, https://doi.org/10.5194/angeo-27-591-2009). We show that the high‐latitude substorms, which do not experience braking, can evolve into SMC events if the interplanetary magnetic field remains southward for a prolonged period following onset. We conclude that during periods of ongoing driving, the magnetosphere displays repeated substorm activity or SMC depending on the rate of driving and the open magnetic flux content of the magnetosphere prior to onset. We speculate that sawtooth events are an extreme case of repeated onsets and that substorms triggered by northward‐turnings of the interplanetary magnetic field mark the cessation of periods of SMC. Our results provide a new explanation for the differing modes of response of the terrestrial system to solar wind‐magnetosphere‐ionosphere coupling by invoking friction between the ionosphere and atmosphere.
Analytic Modeling of Magnetic Field in the Magnetosheath and Outer Magnetosphere
Authors: Romashets E. P. , Vandas M.
Published: March 2019

Magnetosheath is a region surrounded by the bow shock and the magnetopause. According to statistical analysis, the boundaries can be treated as nonconfocal paraboloids of rotations. It is not easy to meet boundary conditions simultaneously on both sides. This problem is treated here and its solution is presented. A linear combination of harmonics that satisfy the condition on the magnetopause are selected in order to meet the condition on the bow shock. The method allows to calculate surface currents on the magnetopause. It is applied for typical conditions in solar wind. A modified magnetic dipole is used as a model of the magnetospheric field. Its modification is found by the method of potentials using cylindrical harmonics. Magnetopause currents are compared with results from a model with confocal paraboloids, which is commonly used in literature.
Effect of Dilatancy on the Transition From Aseismic to Seismic Slip Due to Fluid Injection in a Fault
Authors: Ciardo F. , Lecampion B.
Published: March 2019

Aseismic crack growth upon activation of fault slip due to fluid injection may or may not lead to the nucleation of a dynamic rupture depending on in situ conditions, frictional properties of the fault, and the value of overpressure. In particular, a fault is coined as unstable if its residual frictional strength τr is lower than the in situ background shear stress τo. We study here how fault dilatancy associated with slip affect shear crack propagation due to fluid injection. We use a planar bidimensional model with frictional weakening and assume that fluid flow only takes place along the fault (impermeable rock/immature fault). Dilatancy induces an undrained pore‐pressure drop locally strengthening the fault. We introduce an undrained residual fault shear strength
(function of dilatancy) and show theoretically that under the assumption of small‐scale yielding, an otherwise unstable fault (τr < τo) is stabilized when
is larger than τo. We numerically solve the complete coupled hydromechanical problem and confirm this theoretical estimate. It is important to note that the undrained residual strength is fully activated only if residual friction is reached. Dilatancy stabilizes an otherwise unstable fault if the nucleation of an unabated dynamic rupture—without dilatancy—is affected by residual friction, which is the case for sufficiently large injection pressure. We also discuss the effect of fault permeability increase due to slip. Our numerical results show that permeability increases lead to faster aseismic growth but do not impact the stabilizing effect of dilatancy with respect to dynamic rupture.
Capturing Uncertainty in Magnetospheric Ultralow Frequency Wave Models
Authors: Bentley S. N. , Watt Clare E. J. , Rae I. J. , Owens M. J. , Murphy K. , Lockwood M. , Sandhu J. K.
Published: March 2019

We develop and test an empirical model predicting ground‐based observations of ultralow frequency (ULF, 1–20 mHz) wave power across a range of frequencies, latitudes, and MLT sectors. This is parameterized by instantaneous solar wind speed vsw, variance in proton number density var(Np), and interplanetary southward magnetic field Bz. A probabilistic model of ULF wave power will allow us to address uncertainty in radial diffusion coefficients and therefore improve diffusion modeling of radial transport in Earth's outer radiation belt. Our model can be used in two ways to reproduce wave power: by sampling from conditional probability distribution functions and by using the mean (expectation) values. We derive a method for testing the quality of the parameterization and test the ability of the model to reproduce ULF wave power time series. Sampling is a better method for reproducing power over an extended time period as it retains the same overall distribution, while mean values are better for predicting the power in a time series. The model predicts each hour in a time series better than the assumption that power persists from the preceding hour. Finally, we review other sources of diffusion coefficient uncertainty. Although this wave model is designed principally for the goal of improved radial diffusion coefficients to include in outer radiation belt diffusion‐based modeling, we anticipate that our model can also be used to investigate the occurrence of ULF waves throughout the magnetosphere and hence the physics of ULF wave generation and propagation.
Amplitude Modulation of Seasonal Variability in Terrestrial Water Storage
Authors: Hamlington B. D. , Reager J. T. , Chandanpurkar H. , Kim K.‐Y.
Published: March 2019

Variability in climate and weather in many land regions is dominated by a seasonal cycle that is typically defined by as a stable, repeated pattern. Defining the annual cycle as strictly stationary, however, precludes the possibility of changes in its amplitude from one year to the next. In this study, we target and extract the modulated annual cycle in terrestrial water storage with a statistical analysis technique specifically suited to this application. We estimate the amplitude modulation of the annual cycle in terrestrial water storage in order to assess the drivers of strength of the seasonal water cycle from year to year and identify trends in the amplitude that are persistent over the 13‐year record used here. We find that climate variability is found to be one of the dominant drivers of the strength of the annual cycle in terrestrial water storage, with El Niño‐Southern Oscillation found to play a particularly significant role, as identified in previous studies.
Coordinated Special Issues on eHealth/mHealth in Pediatric Psychology: Introduction to the Clinical Practice in Pediatric Psychology Special Issue on Development and Feasibility of eHealth/mHealth Technologies for Pediatric Psychologists in Clinical Settings
Authors: Law Emily F. , Schueller Stephen M.
Published: March 2019

Objective: To highlight and disseminate research related to clinical applications of eHealth/mHealth technologies with children, youth, and families. Method: This special issue includes articles that reflect approaches to developing eHealth/mHealth interventions for children, youth, parents, and families; evaluations of feasibility, acceptability, and preliminary efficacy of digital health assessment tools and behavioral interventions for youth; and understanding adolescent privacy perceptions related to online collection of personal health-related information. Results: This collection of articles demonstrates various approaches to the development and evaluation of eHealth/mHealth technologies in clinical practice. Conclusions: eHealth/mHealth technologies have the potential to extend the reach of pediatric psychology services that can improve the health and well-being of children, youth, and their families. Further research is needed to support their efficacy, especially research that leverages methods and analyses responsive to the unique challenges and affordances of evaluating technologies with pediatric populations.

Implications for Impact Statement

In this Special Issue, we present a collection of manuscripts demonstrating various approaches to the development and evaluation of eHealth/mHealth technologies directly relevant to pediatric psychologists in clinical settings.
Endogenous advanced glycation end products in pancreatic islets after short-term carbohydrate intervention in obese, diabetes-prone mice
Authors: Kehm Richard , Rückriemen Jana , Weber Daniela , Deubel Stefanie , Grune Tilman , Höhn Annika
Published: March 2019

Diet-induced hyperglycemia is described as one major contributor to the formation of advanced glycation end products (AGEs) under inflammatory conditions, crucial in type 2 diabetes progression. Previous studies have indicated high postprandial plasma AGE-levels in diabetic patients and after long-term carbohydrate feeding in animal models. Pancreatic islets play a key role in glucose metabolism; thus, their susceptibility to glycation reactions due to high amounts of dietary carbohydrates is of special interest. Therefore, diabetes-prone New Zealand Obese (NZO) mice received either a carbohydrate-free, high-fat diet (CFD) for 11 weeks or were additionally fed with a carbohydrate-rich diet (CRD) for 7 days. In the CRD group, hyperglycemia and hyperinsulinemia were induced accompanied by increasing plasma 3-nitrotyrosine (3-NT) levels, higher amounts of 3-NT and inducible nitric oxide synthase (iNOS) within pancreatic islets. Furthermore, N-ε-carboxymethyllysine (CML) was increased in the plasma of CRD-fed NZO mice and substantially higher amounts of arg-pyrimidine, pentosidine and the receptor for advanced glycation end products (RAGE) were observed in pancreatic islets. These findings indicate that a short-term intervention with carbohydrates is sufficient to form endogenous AGEs in plasma and pancreatic islets of NZO mice under hyperglycemic and inflammatory conditions.
Vitamin D and diabetic foot ulcer: a systematic review and meta-analysis
Authors: Dai Jiezhi , Jiang Chaoyin , Chen Hua , Chai Yimin
Published: March 2019

We aimed to evaluate the association between vitamin D deficiency and diabetic foot ulcer (DFU) in patients with diabetes. Pubmed, EMBASE, BIOSIS, the Cochrane Library, and Web of Knowledge, last updated in July 2018, were searched. We assessed eligible studies for the association between vitamin D deficiency and DFU in diabetic patients. The mean difference (MD) or the odds ratio (OR) was calculated for continuous or dichotomous data respectively. Data were analyzed by using the Cochrane Collaboration’s RevMan 5.0 software. Seven studies that involved 1115 patients were included in this study. There were significantly reduced vitamin D levels in DFU (MD −13.47 nmol/L, 95%CI −16.84 to −10.10; P  =  0.34, I2 = 12%). Severe vitamin D deficiency was significantly associated with an increased risk of DFU (OR 3.22, 95%CI 2.42−4.28; P  = 0.64, I2 = 0%). This is the first meta-analysis demonstrating the association between serum vitamin D levels and DFU. Severe vitamin D deficiency is significantly associated with an increased risk of DFU.
Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas
Authors: Liko Dritan , Mitchell Louise , Campbell Kirsteen J. , Ridgway Rachel A. , Jones Carolyn , Dudek Kate , King Ayala , Bryson Sheila , Stevenson David , Blyth Karen , Strathdee Douglas , Morton Jennifer P. , Bird Thomas G. , Knight John R. P. , Willis Anne E. , Sansom Owen J.
Published: March 2019

RNA polymerase III (Pol-III) transcribes tRNAs and other small RNAs essential for protein synthesis and cell growth. Pol-III is deregulated during carcinogenesis; however, its role in vivo has not been studied. To address this issue, we manipulated levels of Brf1, a Pol-III transcription factor that is essential for recruitment of Pol-III holoenzyme at tRNA genes in vivo. Knockout of Brf1 led to embryonic lethality at blastocyst stage. In contrast, heterozygous Brf1 mice were viable, fertile and of a normal size. Conditional deletion of Brf1 in gastrointestinal epithelial tissues, intestine, liver and pancreas, was incompatible with organ homeostasis. Deletion of Brf1 in adult intestine and liver induced apoptosis. However, Brf1 heterozygosity neither had gross effects in these epithelia nor did it modify tumorigenesis in the intestine or pancreas. Overexpression of BRF1 rescued the phenotypes of Brf1 deletion in intestine and liver but was unable to initiate tumorigenesis. Thus, Brf1 and Pol-III activity are absolutely essential for normal homeostasis during development and in adult epithelia. However, Brf1 overexpression or heterozygosity are unable to modify tumorigenesis, suggesting a permissive, but not driving role for Brf1 in the development of epithelial cancers of the pancreas and gut.
The methionine salvage pathway-involving ADI1 inhibits hepatoma growth by epigenetically altering genes expression via elevating S-adenosylmethionine
Authors: Chu Yu-De , Lai Hsin-Yu , Pai Li-Mei , Huang Ya-Hui , Lin Yang-Hsiang , Liang Kung-Hao , Yeh Chau-Ting
Published: March 2019

The 5′-methylthioadenosine (MTA) cycle-participating human acireductone dioxygenase 1 (ADI1) has been implicated as a tumor suppressor in prostate cancer, yet its role remains unclear in hepatocellular carcinoma (HCC). Here, we demonstrated a significant reduction of ADI1, either in protein or mRNA level, in HCC tissues. Additionally, higher ADI1 levels were associated with favorable postoperative recurrence-free survival in HCC patients. By altering ADI1 expression in HCC cells, a negative correlation between ADI1 and cell proliferation was observed. Cell-based and xenograft experiments were performed by using cells overexpressing ADI1 mutants carrying mutations at the metal-binding sites (E94A and H133A, respectively), which selectively disrupted differential catalytic steps, resulting in staying or leaving the MTA cycle. The results showed that the growth suppression effect was mediated by accelerating the MTA cycle. A cDNA microarray analysis followed by verification experiments identified that caveolin-1 (CAV1), a growth-promoting protein in HCC, was markedly decreased upon ADI1 overexpression. Suppression of CAV1 expression was mediated by an increase of S-adenosylmethionine (SAMe) level. The methylation status of CAV1 promoter was significantly altered upon ADI1 overexpression. Finally, a genome-wide methylation analysis revealed that ADI1 overexpression altered promoter methylation profiles in a set of cancer-related genes, including CAV1 and genes encoding antisense non-coding RNAs, long non-coding RNAs, and microRNAs, resulting in significant changes of their expression levels. In conclusion, ADI1 expression promoted MTA cycle to increase SAMe levels, which altered genome-wide promoter methylation profiles, resulting in altered gene expression and HCC growth suppression.
NAA40 contributes to colorectal cancer growth by controlling PRMT5 expression
Authors: Demetriadou Christina , Pavlou Demetria , Mpekris Fotios , Achilleos Charis , Stylianopoulos Triantafyllos , Zaravinos Apostolos , Papageorgis Panagiotis , Kirmizis Antonis
Published: March 2019

N-alpha-acetyltransferase 40 (NAA40) catalyzes the transfer of an acetyl moiety to the alpha-amino group of serine 1 (S1) on histones H4 and H2A. Our previous studies linked NAA40 and its corresponding N-terminal acetylation of histone H4 (N-acH4) to colorectal cancer (CRC). However, the role of NAA40 in CRC development was not investigated. Here, we show that NAA40 protein and mRNA levels are commonly increased in CRC primary tissues compared to non-malignant specimens. Importantly, depletion of NAA40 inhibits cell proliferation and survival of CRC cell lines and increases their sensitivity to 5-Fluorouracil (5-FU) treatment. Moreover, the absence of NAA40 significantly delays the growth of human CRC xenograft tumors. Intriguingly, we found that NAA40 knockdown and loss of N-acH4 reduce the levels of symmetric dimethylation of histone H4 (H4R3me2s) through transcriptional downregulation of protein arginine methyltransferase 5 (PRMT5). NAA40 depletion and subsequent repression of PRMT5 results in altered expression of key oncogenes and tumor suppressor genes leading to inhibition of CRC cell growth. Consistent with this, NAA40 mRNA levels correlate with those of PRMT5 in CRC patient tissues. Taken together, our results establish the oncogenic function of the epigenetic enzyme NAA40 in colon cancer and support its potential as a therapeutic target.
Protoporphyrin IX is a dual inhibitor of p53/MDM2 and p53/MDM4 interactions and induces apoptosis in B-cell chronic lymphocytic leukemia cells
Authors: Jiang Liren , Malik Natasha , Acedo Pilar , Zawacka-Pankau Joanna
Published: March 2019

p53 is a tumor suppressor, which belongs to the p53 family of proteins. The family consists of p53, p63 and p73 proteins, which share similar structure and function. Activation of wild-type p53 or TAp73 in tumors leads to tumor regression, and small molecules restoring the p53 pathway are in clinical development. Protoporphyrin IX (PpIX), a metabolite of aminolevulinic acid, is a clinically approved drug applied in photodynamic diagnosis and therapy. PpIX induces p53-dependent and TAp73-dependent apoptosis and inhibits TAp73/MDM2 and TAp73/MDM4 interactions. Here we demonstrate that PpIX is a dual inhibitor of p53/MDM2 and p53/MDM4 interactions and activates apoptosis in B-cell chronic lymphocytic leukemia cells without illumination and without affecting normal cells. PpIX stabilizes p53 and TAp73 proteins, induces p53-downstream apoptotic targets and provokes cancer cell death at doses non-toxic to normal cells. Our findings open up new opportunities for repurposing PpIX for treating lymphoblastic leukemia with wild-type TP53.
TRIAD3/RNF216 E3 ligase specifically synthesises K63-linked ubiquitin chains and is inactivated by mutations associated with Gordon Holmes syndrome
Authors: Schwintzer Lukas , Aguado Roca Eva , Broemer Meike
Published: March 2019

TRIAD3/RNF216 is a ubiquitin ligase of the RING-in-between-RING family. Recent publications identified TRIAD3 mutations in patients with neurological diseases, including Gordon Holmes syndrome and Huntington-like disorder. To understand the functional relevance of these disease-associated mutations, we have tested the ubiquitin ligase activity of mutated TRIAD3 in vitro. Several of these point mutations completely abrogated TRIAD3’s catalytic activity. Using mass spectrometry, we identified new TRIAD3-interacting proteins/substrates from mouse brain lysate, which provide a new link between TRIAD3 and processes involving clathrin-mediated endocytosis. Strikingly, we found that TRIAD3 synthesises specifically lysine-63 (K63)-linked poly-ubiquitin chains in vitro, a chain type that usually plays a role in mediating signalling events rather than triggering proteasomal degradation. Therefore, this finding is of great importance to further understand TRIAD3’s cellular role and loss-of-function in disease.
Molecular architecture of a cylindrical self-assembly at human centrosomes
Authors: Kim Tae-Sung , Zhang Liang , Il Ahn Jong , Meng Lingjun , Chen Yang , Lee Eunhye , Bang Jeong Kyu , Lim Jung Mi , Ghirlando Rodolfo , Fan Lixin , Wang Yun-Xing , Kim Bo Yeon , Park Jung-Eun , Lee Kyung S.
Published: March 2019

The cell is constructed by higher-order structures and organelles through complex interactions among distinct structural constituents. The centrosome is a membraneless organelle composed of two microtubule-derived structures called centrioles and an amorphous mass of pericentriolar material. Super-resolution microscopic analyses in various organisms revealed that diverse pericentriolar material proteins are concentrically localized around a centriole in a highly organized manner. However, the molecular nature underlying these organizations remains unknown. Here we show that two human pericentriolar material scaffolds, Cep63 and Cep152, cooperatively generate a heterotetrameric α-helical bundle that functions in conjunction with its neighboring hydrophobic motifs to self-assemble into a higher-order cylindrical architecture capable of recruiting downstream components, including Plk4, a key regulator for centriole duplication. Mutations disrupting the self-assembly abrogate Plk4-mediated centriole duplication. Because pericentriolar material organization is evolutionarily conserved, this work may offer a paradigm for investigating the assembly and function of centrosomal scaffolds in various organisms.
Intrinsic measurements of exciton transport in photovoltaic cells
Authors: Zhang Tao , Dement Dana B. , Ferry Vivian E. , Holmes Russell J.
Published: March 2019

Organic photovoltaic cells are partiuclarly sensitive to exciton harvesting and are thus, a useful platform for the characterization of exciton diffusion. While device photocurrent spectroscopy can be used to extract the exciton diffusion length, this method is frequently limited by unknown interfacial recombination losses. We resolve this limitation and demonstrate a general, device-based photocurrent-ratio measurement to extract the intrinsic diffusion length. Since interfacial losses are not active layer specific, a ratio of the donor- and acceptor-material internal quantum efficiencies cancels this quantity. We further show that this measurement permits extraction of additional device-relevant information regarding exciton relaxation and charge separation processes. The generality of this method is demonstrated by measuring exciton transport for both luminescent and dark materials, as well as for small molecule and polymer active materials and semiconductor quantum dots. Thus, we demonstrate a broadly applicable device-based methodology to probe the intrinsic active material exciton diffusion length.
Proteome-wide solubility and thermal stability profiling reveals distinct regulatory roles for ATP
Authors: Sridharan Sindhuja , Kurzawa Nils , Werner Thilo , Günthner Ina , Helm Dominic , Huber Wolfgang , Bantscheff Marcus , Savitski Mikhail M.
Published: March 2019

Adenosine triphosphate (ATP) plays fundamental roles in cellular biochemistry and was recently discovered to function as a biological hydrotrope. Here, we use mass spectrometry to interrogate ATP-mediated regulation of protein thermal stability and protein solubility on a proteome-wide scale. Thermal proteome profiling reveals high affinity interactions of ATP as a substrate and as an allosteric modulator that has widespread influence on protein complexes and their stability. Further, we develop a strategy for proteome-wide solubility profiling, and discover ATP-dependent solubilization of at least 25% of the insoluble proteome. ATP increases the solubility of positively charged, intrinsically disordered proteins, and their susceptibility for solubilization varies depending on their localization to different membrane-less organelles. Moreover, a few proteins, exhibit an ATP-dependent decrease in solubility, likely reflecting polymer formation. Our data provides a proteome-wide, quantitative insight into how ATP influences protein structure and solubility across the spectrum of physiologically relevant concentrations.
Efficient plasmon-hot electron conversion in Ag–CsPbBr3 hybrid nanocrystals
Authors: Huang Xinyu , Li Hongbo , Zhang Chunfeng , Tan Shijing , Chen Zhangzhang , Chen Lan , Lu Zhenda , Wang Xiaoyong , Xiao Min
Published: March 2019

Hybrid metal/semiconductor nano-heterostructures with strong exciton-plasmon coupling have been proposed for applications in hot carrier optoelectronic devices. However, the performance of devices based on this concept has been limited by the poor efficiency of plasmon-hot electron conversion at the metal/semiconductor interface. Here, we report that the efficiency of interfacial hot excitation transfer can be substantially improved in hybrid metal semiconductor nano-heterostructures consisting of perovskite semiconductors. In Ag–CsPbBr3 nanocrystals, both the plasmon-induced hot electron and the resonant energy transfer processes can occur on a time scale of less than 100 fs with quantum efficiencies of 50 ± 18% and 15 ± 5%, respectively. The markedly high efficiency of hot electron transfer observed here can be ascribed to the increased metal/semiconductor coupling compared with those in conventional systems. These findings suggest that hybrid architectures of metal and perovskite semiconductors may be excellent candidates to achieve highly efficient plasmon-induced hot carrier devices.
Overcoming the thermal regime for the electric-field driven Mott transition in vanadium sesquioxide
Authors: Giorgianni Flavio , Sakai Joe , Lupi Stefano
Published: March 2019

The complex interplay among electronic, magnetic and lattice degrees of freedom in Mott-Hubbard materials leads to different types of insulator-to-metal transitions (IMT) which can be triggered by temperature, pressure, light irradiation and electric field. However, several questions remain open concerning the quantum or thermal nature of electric field-driven transition process. Here, using intense terahertz pulses, we reveal the emergence of an instantaneous purely-electronic IMT in the Mott-Hubbard vanadium sequioxide (V2O3) prototype material. While fast electronics allow thermal-driven transition involving Joule heating, which takes place after tens of picoseconds, terahertz electric field is able to induce a sub-picosecond electronic switching. We provide a comprehensive study of the THz induced Mott transition, showing a crossover from a fast quantum dynamics to a slower thermal dissipative evolution for increasing temperature. Strong-field terahertz-driven electronic transition paves the way to ultrafast electronic switches and high-harmonic generation in correlated systems.
The genome of the jellyfish Clytia hemisphaerica and the evolution of the cnidarian life-cycle
Authors: Leclère Lucas , Horin Coralie , Chevalier Sandra , Lapébie Pascal , Dru Philippe , Peron Sophie , Jager Muriel , Condamine Thomas , Pottin Karen , Romano Séverine , Steger Julia , Sinigaglia Chiara , Barreau Carine , Quiroga Artigas Gonzalo , Ruggiero Antonella , Fourrage Cécile , Kraus Johanna E. M. , Poulain Julie , Aury Jean-Marc , Wincker Patrick , Quéinnec Eric , Technau Ulrich , Manuel Michaël , Momose Tsuyoshi , Houliston Evelyn , Copley Richard R.
Published: March 2019

Jellyfish (medusae) are a distinctive life-cycle stage of medusozoan cnidarians. They are major marine predators, with integrated neurosensory, muscular and organ systems. The genetic foundations of this complex form are largely unknown. We report the draft genome of the hydrozoan jellyfishClytia hemisphaericaand use multiple transcriptomes to determine gene use across life-cycle stages. Medusa, planula larva and polyp are each characterized by distinct transcriptome signatures reflecting abrupt life-cycle transitions and all deploy a mixture of phylogenetically old and new genes. Medusa-specific transcription factors, including many with bilaterian orthologues, associate with diverse neurosensory structures. Compared toClytia, the polyp-only hydrozoanHydrahas lost many of the medusa-expressed transcription factors, despite similar overall rates of gene content evolution and sequence evolution. Absence of expression and gene loss amongClytiaorthologues of genes patterning the anthozoan aboral pole, secondary axis and endomesoderm support simplification of planulae and polyps in Hydrozoa, including loss of bilateral symmetry. Consequently, although the polyp and planula are generally considered the ancestral cnidarian forms, inClytiathe medusa maximally deploys the ancestral cnidarian–bilaterian transcription factor gene complement.
Nutraceutical profile and evidence of alleviation of oxidative stress by Spirogyra porticalis (Muell.) Cleve inhabiting the high altitude Trans-Himalayan Region
Authors: Kumar Jatinder , Khan Shahanshah , Mandotra S. K. , Dhar Priyanka , Tayade Amol B. , Verma Sheetal , Toppo Kiran , Arora Rajesh , Upreti Dalip K. , Chaurasia Om P.
Published: March 2019

The high altitude trans-Himalayan region indeed is hostile domain for survival. Algae inhabiting  this  hostile terrain have evolutionarily developed mechanisms to produce unique adaptogenic molecules against climatic stressors. The present study has focused on the high altitude alga Spirogyra porticalis (Muell.) Cleve- a filamentous Charophyte, and reports the estimation of amino acids (AAs), fatty acids (FAs), vitamins and their efficacy against oxidative stress. Reverse phase-HPLC, GC-FID and rapid resolution-LC/tandem mass spectrometry were used for analysis of AAs, FAs and vitamins. Analysis of the alga  revealed the presence of 19 AAs (239.51 ± 8.57 to 13102.40 ± 11.08 µg/g), dominated by alanine, proline and lysine. Enriched phenylalanine, cysteine-HCl and high lysine:arginine ratio could also have beneficial impact against hypoxia -induced cognitive impairment. A total of 9 FAs were detected (0.43 ± 0.00% to 34.76 ± 0.52%). Polyunsaturated and monounsaturated FAs were found to be dominant. The alga showed the presence of 8 vitamins within the range of 39.654 ± 3.198 to 5468.184 ± 106.859 µg/Kg, wherein Vitamin B5, B3 and B2 were dominant. 600 µg/ml of methanolic extract showed recovery of GSH and trolox equivalent antioxidants in rat blood/hemolysate, while 400 µg/ml of extract showed revival in superoxide dismutase (SOD) activity. The present study concludes that the alga S. porticalis has immense potential to counter oxidative stress as a nutraceutical supplement.
Graphene Oxide Quantum Dots Derived from Coal for Bioimaging: Facile and Green Approach
Authors: Kang Sukhyun , Kim Kang Min , jung Kyunghwan , Son Yong , Mhin Sungwook , Ryu Jeong Ho , Shim Kwang Bo , Lee Byoungsoo , Han HyukSu , Song Taeseup
Published: March 2019

Graphene oxide quantum dots (GOQDs) are usually prepared using expensive carbon precursors such as carbon nanotubes (CNT) or graphene under the strong acidic condition, which requires an additional purifying process. Here, we first develop a facile pulsed laser ablation in liquid (PLAL) technique for preparing GOQDs using earth-abundant and low-cost coal as a precursor. Only ethanol and coal are used to produce GOQDs with excellent optical properties. The prepared GOQDs exhibit excellent optoelectronic properties which can be successfully utilized in bioimaging applications.
Flexible Mid-infrared Photonic Circuits for Real-time and Label-Free Hydroxyl Compound Detection
Authors: Jin Tiening , Lin Hao-Yu Greg , Tiwald Tom , Lin Pao Tai
Published: March 2019

Chip-scale chemical detections were demonstrated by mid-Infrared (mid-IR) integrated optics made by aluminum nitride (AlN) waveguides on flexible borosilicate templates. The AlN film was deposited using sputtering at room temperature, and it exhibited a broad infrared transmittance up to λ = 9 µm. The AlN waveguide profile was created by microelectronic fabrication processes. The sensor is bendable because it has a thickness less than 30 µm that significantly decreases the strain. A bright fundamental mode was obtained at λ = 2.50–2.65 µm without mode distortion or scattering observed. By spectrum scanning at the -OH absorption band, the waveguide sensor was able to identify different hydroxyl compounds, such as water, methanol, and ethanol, and the concentrations of their mixtures. Real-time methanol monitoring was achieved by reading the intensity change of the waveguide mode at λ = 2.65 μm, which overlap with the stretch absorption of the hydroxyl bond. Due to the advantages of mechanical flexibility and broad mid-IR transparency, the AlN chemical sensor will enable microphotonic devices for wearables and remote biomedical and environmental detection.
RNAi-based bioinsecticide for Aedes mosquito control
Authors: Lopez Sheila Barbara G. , Guimarães-Ribeiro Victor , Rodriguez João Victor G. , Dorand Fernando A. P. S. , Salles Tiago S. , Sá-Guimarães Thayane E. , Alvarenga Evelyn S. L. , Melo Ana Claudia A. , Almeida Rodrigo V. , Moreira Monica F.
Published: March 2019

Zika virus infection and dengue and chikungunya fevers are emerging viral diseases that have become public health threats. Their aetiologic agents are transmitted by the bite of genus Aedes mosquitoes. Without effective therapies or vaccines, vector control is the main strategy for preventing the spread of these diseases. Increased insecticide resistance calls for biorational actions focused on control of the target vector population. The chitin required for larval survival structures is a good target for biorational control. Chitin synthases A and B (CHS) are enzymes in the chitin synthesis pathway. Double-stranded RNA (dsRNA)-mediated gene silencing (RNAi) achieves specific knockdown of target proteins. Our goal in this work, a new proposed RNAi-based bioinsecticide, was developed as a potential strategy for mosquito population control. DsRNA molecules that target five different regions in the CHSA and B transcript sequences were produced in vitro and in vivo through expression in E. coli HT115 and tested by direct addition to larval breeding water. Mature and immature larvae treated with dsRNA targeting CHS catalytic sites showed significantly decreased viability associated with a reduction in CHS transcript levels. The few larval and adult survivors displayed an altered morphology and chitin content. In association with diflubenzuron, this bioinsecticide exhibited insecticidal adjuvant properties.
Phased Patagonian Ice Sheet response to Southern Hemisphere atmospheric and oceanic warming between 18 and 17 ka
Authors: Bendle Jacob M. , Palmer Adrian P. , Thorndycraft Varyl R. , Matthews Ian P.
Published: March 2019

The onset of deglaciation in the Southern Hemisphere mid-latitudes has been attributed to the southward transmission of climate anomalies in response to slow-down of Atlantic meridional overturning circulation (AMOC) during Heinrich Stadial 1 (HS-1; 18–14.6 ka). However, inferences on the response of former ice sheets to sub-millennial palaeoclimate shifts are limited by a shortage of high-resolution terrestrial archives. Here we use a ~1000-year duration, annually-resolved lake sediment record to investigate the deglacial retreat dynamics of the Lago General Carrera–Buenos Aires ice lobe (46.5°S) of the former Patagonian Ice Sheet. We attribute the onset of glacier retreat at 18.0 ± 0.14 cal ka BP to abrupt southward migration of the Southern Westerly Winds that enhanced solar radiation receipt (and ablation) at the ice sheet surface. We infer that accelerated retreat from 17.77 ± 0.13 cal ka BP represents a lagged Southern Hemisphere response to gradual ocean-atmosphere warming associated with the centennial-scale transmission of Northern Hemisphere climate anomalies through the oceanic bipolar seesaw. By 17.38 ± 0.12 cal ka BP, the glacier margin had receded into a deepening proglacial lake, instigating sustained calving losses and more rapid ice recession.
R. nukuhivensis acts by reinforcing skin barrier function, boosting skin immunity and by inhibiting IL-22 induced keratinocyte hyperproliferation
Authors: Abdallah Florence , Lecellier Gaël , Raharivelomanana Phila , Pichon Chantal
Published: March 2019

Rauvolfia nukuhivensis is a well-known plant used for its wide range of beneficial effects in Marquesas islands. It is made up of diverse indole alkaloids and is used as traditional medicine for skin application. The actual mechanism behind the virtue of this plant is still unknown. Hence, in this study we aimed at deciphering the impact of R. nukuhivensis on skin immune system in context of (1) homeostasis, (2) pathogen infection and (3) inflammation. Here we show that R. nukuhivensis enhances cellular metabolic activity and wound healing without inducing cellular stress or disturbing cellular homeostasis. It reinforces the epithelial barrier by up-regulating hBD-1. Nevertheless, in pathogenic stress, R. nukuhivensis acts by preparing the immune system to be reactive and effective directly. Indeed, it enhances the innate immune response by increasing pathogens sensors such as TLR5. Finally, R. nukuhivensis blocks IL-22 induced hyperproliferation via PTEN and Filaggrin up-regulation as well as BCL-2 downregulation. In conclusion, this study provides evidence on the several cutaneous application potentials of R. nukuhivensis such as boosting the immune response or in restoring the integrity of the epithelial barrier.