bluuebunny/crossref_metadata_2025 huggingface dataset:
Glomus Tumor of the Toe
Authors: Sprinkle Robert L.B. , Sangueza Omar P. , Schwartz Gregory A.
Published: June 2017

A glomus tumor is an uncommon, predominantly benign, neoplastic lesion that primarily involves a thermoregulatory microvascular apparatus, the glomus body. Although these lesions can occur anywhere in the body, the subungual tissue of the hand represents the most common presentation site. Glomus tumors are not often encountered in the foot. Symptoms traditionally include the classic triad of pain, pressure, and cold sensitivity. This case report describes a variant location for a glomus tumor in the subcuticular tissue adjacent to the medial middle phalanx of the second toe. The nonsubungual location for this presentation should prompt the inclusion of glomus tumor in a digital soft-tissue lesion differential diagnosis. The lesion was excised surgically and was subsequently diagnosed histopathologically as a glomus tumor.
Posttraumatic Retronychia of the Foot with Clinical and Ultrasound Correlation
Authors: Pizarro Mariana , Pieressa Nicolás , Wortsman Ximena
Published: June 2017

Retronychia, the posterior embedding of the nail bed into the proximal nail fold, can be a complex clinical dermatologic diagnosis that may mimic other inflammatory ungual diseases or tumors of the nail. It has been related to a history of severe systemic conditions that secondarily affect the nail matrix and is commonly associated with onychomadesis. We present a case of retronychia of the foot with a purely traumatic origin, nonconcomitant with onychomadesis, that was diagnosed by color Doppler ultrasound in a long-time practitioner of martial arts who was otherwise healthy. Color Doppler ultrasound is an excellent imaging technique for supporting the diagnosis of retronychia. It provides information on the exact location and morphology of the nail plate as well as the presence of inflammatory signs in the ungual and proximal periungual regions. Additionally, this imaging technique can support the differential diagnosis with other nail conditions. Since there are many sports or activities that can potentially injure the toenails, retronychia may be an underestimated entity and the present case can raise the awareness of this condition and show the usefulness of color Doppler ultrasound.
Dissecting the variation in transcriptional circuits between naive and primed pluripotent states
Authors: Deb Aritra , Sarkar Arijita , Ghosh Zhumur
Published: June 2017

Naive and primed pluripotent states are very similar to each other, but subtle differences exist in their maintenance and differentiation programmes. Transcription factors (TFs) play a key role towards maintaining pluripotency and cellular reprogramming. However, TF expression dynamics and regulatory mechanisms in naive and primed pluripotent states are poorly understood. Here, we performed a comprehensive transcriptional analysis of both states, which revealed a gene expression pattern in mESCs (naive state) that appear to be distinct from mEpiSCs (primed state). We screened 10 TFs essential for maintenance, self‐renewal and differentiation, of which the TFs‐ Notch3, Meis1, Gli3 and Srf can act as novel markers distinguishing the two states. Furthermore, a detailed bioinformatic analysis (involving these TFs) elucidated essential transcriptional circuits between the naive and primed pluripotent states.
On the shape of sea level anomaly signal on periphery of mesoscale ocean eddies
Authors: Amores A. , Monserrat S. , Melnichenko O. , Maximenko N.
Published: June 2017

Good knowledge of mesoscale eddy properties and their spatial and temporal distribution in the world ocean is important for an accurate estimate of their role in heat, salt, and/or momentum transports. Composites of satellite sea level anomaly, used to evaluate internal eddy structure, commonly produce, at larger radii, a series of rings of alternating sign. We suggest that these secondary rings are not a part of the dynamical structure of the “central” eddy but are a rectified signature of the surrounding eddies. We show that statistical distribution of eddy polarities is not random but that an eddy of given polarity tends to be surrounded by eddies of opposite polarity. This observed spatial eddy polarity distribution, which is hypothesized to be a result of eddy self‐organization, is not only responsible for the secondary rings observed in the composite estimates but also causes a reduction of around 20% of the eddy composite amplitude and an increment of around 10% in the maximum rotational velocity, while it has negligible effect on the estimated eddy scale.
Landform features and seasonal precipitation predict shallow groundwater influence on temperature in headwater streams
Authors: Johnson Zachary C. , Snyder Craig D. , Hitt Nathaniel P.
Published: June 2017

Headwater stream responses to climate change will depend in part on groundwater‐surface water exchanges. We used linear modeling techniques to partition likely effects of shallow groundwater seepage and air temperature on stream temperatures for 79 sites in nine focal watersheds using hourly air and water temperature measurements collected during summer months from 2012 to 2015 in Shenandoah National Park, Virginia, USA. Shallow groundwater effects exhibited more variation within watersheds than between them, indicating the importance of reach‐scale assessments and the limited capacity to extrapolate upstream groundwater influences from downstream measurements. Boosted regression tree (BRT) models revealed intricate interactions among geomorphological landform features (stream slope, elevation, network length, contributing area, and channel confinement) and seasonal precipitation patterns (winter, spring, and summer months) that together were robust predictors of spatial and temporal variation in groundwater influence on stream temperatures. The final BRT model performed well for training data and cross‐validated samples (correlation = 0.984 and 0.760, respectively). Geomorphological and precipitation predictors of groundwater influence varied in their importance between watersheds, suggesting differences in spatial and temporal controls of recharge dynamics and the depth of the groundwater source. We demonstrate an application of the final BRT model to predict groundwater effects from landform and precipitation covariates at 1075 new sites distributed at 100 m increments within focal watersheds. Our study provides a framework to estimate effects of groundwater seepage on stream temperature in unsampled locations. We discuss applications for climate change research to account for groundwater‐surface water interactions when projecting future thermal thresholds for stream biota.
Single Atomically Sharp Lateral Monolayer p‐n Heterojunction Solar Cells with Extraordinarily High Power Conversion Efficiency
Authors: Tsai Meng‐Lin , Li Ming‐Yang , Retamal José Ramón Durán , Lam Kai‐Tak , Lin Yung‐Chang , Suenaga Kazu , Chen Lih‐Juann , Liang Gengchiau , Li Lain‐Jong , He Jr‐Hau
Published: June 2017

The recent development of 2D monolayer lateral semiconductor has created new paradigm to develop p‐n heterojunctions. Albeit, the growth methods of these heterostructures typically result in alloy structures at the interface, limiting the development for high‐efficiency photovoltaic (PV) devices. Here, the PV properties of sequentially grown alloy‐free 2D monolayer WSe2‐MoS2 lateral p‐n heterojunction are explores. The PV devices show an extraordinary power conversion efficiency of 2.56% under AM 1.5G illumination. The large surface active area enables the full exposure of the depletion region, leading to excellent omnidirectional light harvesting characteristic with only 5% reduction of efficiency at incident angles up to 75°. Modeling studies demonstrate the PV devices comply with typical principles, increasing the feasibility for further development. Furthermore, the appropriate electrode‐spacing design can lead to environment‐independent PV properties. These robust PV properties deriving from the atomically sharp lateral p‐n interface can help develop the next‐generation photovoltaics.
Brief Report: Association of Elevated Adipsin Levels With Pulmonary Arterial Hypertension in Systemic Sclerosis
Authors: Korman Benjamin D. , Marangoni Roberta Goncalves , Hinchcliff Monique , Shah Sanjiv J. , Carns Mary , Hoffmann Aileen , Ramsey‐Goldman Rosalind , Varga John
Published: June 2017

Objective

Adipose tissues secrete adipokines, peptides with potent effects modulating fibrosis, inflammation, and vascular homeostasis. Dysregulated adipose tissue biology and adipokine balance have recently been implicated in systemic sclerosis (SSc). This study was undertaken to determine whether altered circulating adipokine levels correlate with SSc disease subsets or clinical manifestations.

Methods

Multiplex assays were used to measure circulating adipokine levels in 198 patients with SSc and 33 healthy controls. Data were evaluated for correlations between serum adipokine levels and demographic and clinical features, including pulmonary arterial hypertension (PAH). To assess the relevance of adipsin, an adipokine involved in complement pathway activation, in SSc, we analyzed publicly available genetic and transcriptomic data.

Results

Levels of adiponectin and adipsin differed significantly between controls and patients. Adipsin was significantly elevated in patients with limited cutaneous SSc (odds ratio [OR] 28.3 [95% confidence interval (95% CI) 7.0–113.8]; P < 0.0001), and its levels were associated with serum autoantibody status, pulmonary function and cardiovascular parameters, and PAH (OR 3.3 [95% CI 1.3–8.7]; P = 0.02). Elevated adipsin was more strongly associated with PAH than B‐type natriuretic peptide was. Moreover, in SSc patients, adipsin gene single‐nucleotide polymorphisms were associated with PAH. Transcriptome data set analysis demonstrated elevated adipsin expression in patients with SSc‐related PAH.

Conclusion

We identify adipsin as a novel adipose tissue–derived marker of SSc‐related PAH. Circulating adipsin levels might serve as predictive biomarkers in SSc. Mechanistically, adipsin might represent a pathogenic link between adipocyte dysfunction and complement pathway activation and play an important role in the pathogenesis of SSc‐related PAH.
Decomposition of terrestrial resource subsidies in headwater streams: Does consumer diversity matter?
Authors: Stoker David , Falkner Amber J. , Murray Kelly M. , Lang Ashley K. , Barnum Thomas R. , Hepinstall‐Cymerman Jeffrey , Conroy Michael J. , Cooper Robert J. , Pringle Catherine M.
Published: June 2017

Resource subsidies and biodiversity are essential for maintaining community structure and ecosystem functioning, but the relative importance of consumer diversity and resource characteristics to decomposition remains unclear. Forested headwater streams are detritus‐based systems, dependent on leaf litter inputs from adjacent riparian ecosystems, and decomposition of these resources is an important ecosystem function. Here, we examined the effects of consumer community diversity on leaf decomposition in a reciprocal transplant experiment. We asked (1) whether stream consumer communities are adapted to local resources and (2) how functional trait diversity among communities affects the leaf decomposition process. We did not find evidence that communities were adapted to locally derived resource subsidies. Instead, we found that consumer biomass and functional trait diversity as well as resource characteristics were the primary biotic drivers of decomposition. Consumer biomass was stimulated by specific resource subsidies, leading to direct and indirect effects of resource subsidies on ecosystem functioning. Contrary to current theory, we show that decomposition was higher with decreased detritivore functional diversity, suggesting dominant traits encompassing a specific niche increased decomposition. We also show that top‐down, consumer diversity effects can be equal in magnitude to the bottom‐up effects of resource characteristics during the decomposition process. Our research illustrates the importance of considering multiple biotic and abiotic drivers interacting via multiple pathways to affect a crucial ecosystem function.
China's next renewable energy revolution: goals and mechanisms in the 13th Five Year Plan for energy
Authors: Gosens Jorrit , Kåberger Tomas , Wang Yufei
Published: June 2017

Over the past few months, China has published its development plans for the 13th Five Year Plan [FYP] period [2016–2020] for energy, and separately for the electricity sector, renewable energy, hydro, wind, solar, and biomass energy. Here, we review these policies, as well as a number of key supporting policy documents that aim at increased renewable energy use in China. Presuming that China will not overshoot its growth targets for wind and PV, annual additions over the 13th FYP period will average 16 GW for wind and 13.5 GW for PV, well below the growth levels seen in recent years. The key to success in China's continued transition to renewable energy, however, does not lie in such capacity additions alone. At least as important will be the efforts at improving grid interconnectedness, flexibility of generating capacity and the grid, market mechanisms that will reduce and spread electricity demand, and better enable renewables to compete, and efforts at increasing the level of consumption of the renewable power generated.
A Dual‐Administration Microtracer Technique to Characterize the Absorption, Distribution, Metabolism, and Excretion of [14C]Seletalisib (UCB5857) in Healthy Subjects
Authors: Helmer Eric , Nicolas Jean‐Marie , Long Jeff , Roffel Ad F. , Jones Emma , Chanteux Hugues , Diaz Nieves , Garratt Holly , Bosje Tjerk
Published: June 2017

Phosphoinositide 3 kinases are targets for development of small‐molecule inhibitors to disrupt progression of immune‐inflammatory diseases. This phase 1 open‐label study (Eudract 2014‐005353‐39) evaluated the safety and relative bioavailability of 2 new seletalisib (UCB5857) formulations (A and B) compared with a reference formulation. Absolute bioavailability (period 1a, n = 6) and disposition and metabolism (period 1b, n = 6) of the reference formulation were evaluated: healthy subjects received 30 mg orally plus ∼20 μg of a 14C‐labeled microtracer (intravenously in 1a, orally in 1b). New formulations were evaluated: subjects from periods 1a and 1b were pooled and randomly distributed to receive a single oral dose (30 mg) of formulation A (n = 6) or B (n = 6) in periods 2 and 3, using a crossover design. Absolute oral bioavailability of seletalisib was 97% (90% confidence interval 87, 107). Unchanged [14C]seletalisib was the predominant radioactive component in plasma (94.8%). After oral dosing, the radioactive dose was primarily recovered in feces (74.6%, geometric coefficient of variation [GeoCV] 18.1%), mostly as metabolites. Seletalisib demonstrated a 24‐hour terminal half‐life, volume of distribution of 60.9 L (GeoCV 23.8%), and a total plasma clearance of 1.7 L/h (GeoCV 35.4%). Formulations A and B displayed similar or even higher exposure compared with reference seletalisib (areas under the concentration‐time curves 19 337 [GeoCV 30.8%], 20 380 [GeoCV 37.7%], and 15 932 [GeoCV 36.4%] h·ng/mL, respectively). New formulations A and B were bioequivalent with each other, and all 3 formulations showed acceptable safety profiles. This radiolabeled microtracer approach successfully informed on the absorption, distribution, metabolism, and excretion of seletalisib and further guided the mechanistic pharmacokinetic modeling.
A new formula for estimation of standard liver volume using computed tomography–measured body thickness
Authors: Ma Ka Wing , Chok Kenneth S. H. , Chan Albert C. Y. , Tam Henry S. C. , Dai Wing Chiu , Cheung Tan To , Fung James Y. Y. , Lo Chung Mau
Published: June 2017

The objective of this article is to derive a more accurate and easy‐to‐use formula for finding estimated standard liver volume (ESLV) using novel computed tomography (CT) measurement parameters. New formulas for ESLV have been emerging that aim to improve the accuracy of estimation. However, many of these formulas contain body surface area measurements and logarithms in the equations that lead to a more complicated calculation. In addition, substantial errors in ESLV using these old formulas have been shown. An improved version of the formula for ESLV is needed. This is a retrospective cohort of consecutive living donor liver transplantations from 2005 to 2016. Donors were randomly assigned to either the formula derivation or validation groups. Total liver volume (TLV) measured by CT was used as the reference for a linear regression analysis against various patient factors. The derived formula was compared with the existing formulas. There were 722 patients (197 from the derivation group, 164 from the validation group, and 361 from the recipient group) involved in the study. The donor's body weight (odds ratio [OR], 10.42; 95% confidence interval [CI], 7.25‐13.60; P < 0.01) and body thickness (OR, 2.00; 95% CI, 0.36‐3.65; P = 0.02) were found to be independent factors for the TLV calculation. A formula for TLV (cm3) was derived: 2 × thickness (mm) + 10 × weight (kg) + 190 with R
2 0.48, which was the highest when compared with the 4 other most often cited formulas. This formula remained superior to other published formulas in the validation set analysis (R
2, 5.37; interclass correlation coefficient, 0.74). Graft weight/ESLV values calculated by the new formula were shown to have the highest correlation with delayed graft function (C‐statistic, 0.79; 95% CI, 0.69‐0.90; P < 0.01). The new formula (2 × thickness + 10 × weight + 190) represents the first study proposing the use of CT‐measured body thickness which is novel, easy to use, and the most accurate for ESLV. Liver Transplantation 23 1113–1122 2017 AASLD.
Migration of Mg and other interstitial metal dopants in GaN
Authors: Miceli Giacomo , Pasquarello Alfredo
Published: June 2017

The minimum energy paths for the migration of interstitial Mg in wurtzite GaN are studied through density functional calculations. The study also comprises Li, Na, and Be dopants to examine the dependence on size and charge of the dopant species. In all cases considered, the impurities diffuse like ions without any tendency of localizing charge. Li, Mg, and to some extent Na, diffuse almost isotropically in GaN, with average diffusion barriers of 1.1, 2.1, and 2.5 eV, respectively. Instead Be shows a marked anisotropy with energy barriers of 0.76 and 1.88 eV for diffusion paths perpendicular and parallel to the c‐axis. The diffusion barrier generally increases with ionic charge and ionic radius, but their interplay is not trivial. The calculated migration barrier for Mg is consistent with the values estimated in a recent emission channeling experiment.
Impact of Time Since Last Childbirth on Survival of Women with Premenopausal and Postmenopausal Breast Cancers
Authors: Balakrishnan Nanthini , Teo Soo‐Hwang , Sinnadurai Siamala , Bhoo Pathy Nanthini Thevi , See Mee‐Hoong , Taib Nur Aishah , Yip Cheng‐Har , Bhoo Pathy Nirmala
Published: June 2017

Background

Reproductive factors are associated with risk of breast cancer, but the association with breast cancer survival is less well known. Previous studies have reported conflicting results on the association between time since last childbirth and breast cancer survival. We determined the association between time since last childbirth (LCB) and survival of women with premenopausal and postmenopausal breast cancers in Malaysia.

Method

A historical cohort of 986 premenopausal, and 1123 postmenopausal, parous breast cancer patients diagnosed from 2001 to 2012 in University Malaya Medical Centre were included in the analyses. Time since LCB was categorized into quintiles. Multivariable Cox regression was used to determine whether time since LCB was associated with survival following breast cancer, adjusting for demographic, tumor, and treatment characteristics.

Results

Premenopausal breast cancer patients with the most recent childbirth (LCB quintile 1) were younger, more likely to present with unfavorable prognostic profiles and had the lowest 5‐year overall survival (OS) (66.9; 95% CI 60.2–73.6%), compared to women with longer duration since LCB (quintile 2 thru 5). In univariable analysis, time since LCB was inversely associated with risk of mortality and the hazard ratio for LCB quintile 2, 3, 4, and 5 versus quintile 1 were 0.53 (95% CI 0.36–0.77), 0.49 (95% CI 0.33–0.75), 0.61 (95% CI 0.43–0.85), and 0.64 (95% CI 0.44–0.93), respectively; Ptrend = 0.016. However, this association was attenuated substantially following adjustment for age at diagnosis and other prognostic factors. Similarly, postmenopausal breast cancer patients with the most recent childbirth were also more likely to present with unfavorable disease profiles. Compared to postmenopausal breast cancer patients in LCB quintile 1, patients in quintile 5 had a higher risk of mortality. This association was not significant following multivariable adjustment.

Conclusion

Time since LCB is not independently associated with survival in premenopausal or postmenopausal breast cancers. The apparent increase in risks of mortality in premenopausal breast cancer patients with a recent childbirth, and postmenopausal patients with longer duration since LCB, appear to be largely explained by their age at diagnosis.
Callous-unemotional Traits und aggressives Verhalten
Authors: Bleyer Nastassja , Koglin Ute , Petermann Franz
Published: June 2017

Zusammenfassung. Das Ziel der vorliegenden Studie ist es, die Bindungsqualität von Jugendlichen zu ihren Eltern und zu Gleichaltrigen als Moderator in dem Zusammenhang zwischen Callous-unemotional Traits (CU-Traits) und aggressivem Verhalten zu untersuchen. Dazu wurde eine Stichprobe von N = 292 Jugendlichen zwischen 12 und 17 Jahren befragt. Die Daten wurden mittels Korrelationen und hierarchischen Regressionen ausgewertet. Es zeigen sich signifikante positive Korrelationen zwischen CU-Traits und aggressivem Verhalten. Eine gute Qualität der Bindung an Eltern und Gleichaltrige geht hingegen mit weniger aggressivem Verhalten einher. Ein moderierender Effekt auf den Zusammenhang zwischen CU-Traits und aggressivem Verhalten kann jedoch nur durch die Qualität der Bindung an die Eltern festgestellt werden. Bei Jugendlichen mit hohen CU-Traits schwächt eine hohe Bindungsqualität an die Eltern den Zusammenhang zu aggressivem Verhalten ab. Die Rolle der Bindungsqualität an die Eltern wird im Zusammenhang mit der Entstehung von aggressivem Verhalten bei Jugendlichen mit CU-Traits diskutiert.
Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles
Authors: Guimarães Poliana Macedo , Scavuzzi Bruna Miglioranza , Stadtlober Nicole Perugini , Franchi Santos Lorena Flor da Rosa , Lozovoy Marcell Alysson Batisti , Iriyoda Tatiana Mayumi Veiga , Costa Neide Tomimura , Reiche Edna Maria Vissoci , Maes Michael , Dichi Isaias , Simão Andréa Name Colado
Published: June 2017

The aims of this study were to delineate cytokine profiles of systemic lupus erythematosus (SLE), construct prediction models for diagnosis and disease activity using those profiles, and to examine the associations between TNFB Ncol polymorphism, body mass index (BMI) and vitamin D levels with cytokine levels. Two hundred SLE patients and 196 healthy controls participated in this case–control study. Plasma cytokines levels of tumor necrosis factor (TNF)‐α, interferon (IFN)‐γ, interleukin (IL)‐1β, IL‐ 4, IL‐6, IL‐10, IL‐12 and IL‐17 were measured and cytokines profiles were computed. IL‐6, IL‐12, IL‐17, IFN‐γ and IL‐10 levels were significantly higher in SLE, while IL‐4 was lower in SLE. The Th1/Th2 and Th1+Th17/Th2 profiles were significantly higher in SLE than in healthy controls, whereas there were no significant differences in the proinflammatory cytokine profile (TNFα+IL‐6+IL‐1β). In total, 90.4% of all subjects were correctly classified using Th1+Th17 profile and IL‐10 (positively associated) and IL‐4 (negatively associated) as predictor variables (sensitivity=66.7% and specificity=96.9%). In all, 20.9% of the variance in the SLE Disease Activity Index was predicted by the Th1+Th17/Th2 ratio, IL‐10 and BMI (all positively) and proinflammatory profile (inversely associated). B1/B1 genotype is accompanied by increased IL‐17 and Th17/Th2 ratio, while B1/B2 genotype is accompanied by higher IL‐4 and IFNγ values. 25‐OH vitamin D was inversely associated with IFN‐γ levels. SLE is accompanied by Th1, Th17 and Treg profile and lowered IL‐4 production. Lowered vitamin D levels and B1/B1 genotype, but not BMI, contribute to changes in cytokines profiles. Future treatments should target Th1, Th2 and Th17 profiles rather than inflammatory cytokines.
Ultra-large-scale phase-field simulation study of ideal grain growth
Authors: Miyoshi Eisuke , Takaki Tomohiro , Ohno Munekazu , Shibuta Yasushi , Sakane Shinji , Shimokawabe Takashi , Aoki Takayuki
Published: June 2017

Grain growth, a competitive growth of crystal grains accompanied by curvature-driven boundary migration, is one of the most fundamental phenomena in the context of metallurgy and other scientific disciplines. However, the true picture of grain growth is still controversial, even for the simplest (or ‘ideal’) case. This problem can be addressed only by large-scale numerical simulation. Here, we analyze ideal grain growth via ultra-large-scale phase-field simulations on a supercomputer for elucidating the corresponding authentic statistical behaviors. The performed simulations are more than ten times larger in time and space than the ones previously considered as the largest; this computational scale gives a strong indication of the achievement of true steady-state growth with statistically sufficient number of grains. Moreover, we provide a comprehensive theoretical description of ideal grain growth behaviors correctly quantified by the present simulations. Our findings provide conclusive knowledge on ideal grain growth, establishing a platform for studying more realistic growth processes.
Integrative analysis of pathway deregulation in obesity
Authors: Font-Clos Francesc , Zapperi Stefano , La Porta Caterina A.M.
Published: June 2017

Obesity is a pandemic disease, linked to the onset of type 2 diabetes and cancer. Transcriptomic data provides a picture of the alterations in regulatory and metabolic activities associated with obesity, but its interpretation is typically blurred by noise. Here, we solve this problem by collecting publicly available transcriptomic data from adipocytes and removing batch effects using singular value decomposition. In this way we obtain a gene expression signature of 38 genes associated to obesity and identify the main pathways involved. We then show that similar deregulation patterns can be detected in peripheral markers, in type 2 diabetes and in breast cancer. The integration of different data sets combined with the study of pathway deregulation allows us to obtain a more complete picture of gene-expression patterns associated with obesity, breast cancer, and diabetes.
Post-secretional activation of Protease IV by quorum sensing in Pseudomonas aeruginosa
Authors: Oh Jungmin , Li Xi-Hui , Kim Soo-Kyong , Lee Joon-Hee
Published: June 2017

Protease IV (PIV), a key virulence factor of Pseudomonas aeruginosa is a secreted lysyl-endopeptidase whose expression is induced by quorum sensing (QS). We found that PIV expressed in QS mutant has severe reduction of activity in culture supernatant (CS), even though it is overexpressed to high level. PIV purified from the QS mutant (M-PIV) had much lower activity than the PIV purified from wild type (P-PIV). We found that the propeptide cleaved from prepro-PIV was co-purified with M-PIV, but never with P-PIV. Since the activity of M-PIV was restored by adding the CS of QS-positive and PIV-deficient strain, we hypothesized that the propeptide binds to and inhibits PIV, and is degraded to activate PIV by a QS-dependent factor. In fact, the CS of the QS-positive and PIV-deficient strain was able to degrade the propeptide. Since the responsible factor should be a QS-dependently expressed extracellular protease, we tested QS-dependent proteases of P. aeruginosa and found that LasB (elastase) can degrade the propeptide and activate M-PIV. We purified the propeptide of PIV and confirmed that the propeptide can bind to and inhibit PIV. We suggest that PIV is post-secretionally activated through the extracellular degradation of the propeptide by LasB, a QS-dependent protease.
Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern
Authors: Huo Ying-Yi , Li Suhua , Huang Jing , Rong Zhen , Wang Zhao , Li Zhengyang , Ji Rui , Kuang Siyun , Cui Heng-Lin , Li Jixi , Xu Xue-Wei
Published: June 2017

Lysophospholipase_carboxylesterase (LPCE) has highly conserved homologs in many diverse species ranging from bacteria to humans, as well as substantial biological significance and potential therapeutic implications. However, its biological function and catalytic mechanism remain minimally investigated because of the lack of structural information. Here, we report the crystal structure of a bacterial esterase PE8 belonging to the LPCE family. The crystal structure of PE8 was solved with a high resolution of 1.66 Å. Compared with other homologs in the family, significant differences were observed in the amino acid sequence, three-dimensional structure, and substrate-binding pattern. Residue Arg79 undergoes configuration switching when binding to the substrate and forms a unique wall, leading to a relatively closed cavity in the substrate-binding pocket compared with the relatively more open and longer clefts in other homologs. Moreover, the mutant Met122Ala showed much stronger substrate affinity and higher catalytic efficiency because less steric repulsion acted on the substrates. Taken together, these results showed that, in PE8, Arg79 and Met122 play important roles in substrate binding and the binding pocket shaping, respectively. Our study provides new insight into the catalytic mechanism of LPCE, which may facilitate the development of structure-based therapeutics and other biocatalytic applications.
Quantity of alcohol drinking positively correlates with serum levels of endotoxin and markers of monocyte activation
Authors: Liangpunsakul Suthat , Toh Evelyn , Ross Ruth A. , Heathers Laura E. , Chandler Kristina , Oshodi AdePeju , McGee Breann , Modlik Elizabeth , Linton Tobyn , Mangiacarne Darrin , Jimenez Claudie , Dong X. Charlie , Wang Li , Tu Wanzhu , Nelson David E.
Published: June 2017

It is unknown if LPS (lipopolysaccharides) and markers of immune activation, soluble CD14 (sCD14) and CD163 (sCD163) are associated with the quantity of alcohol consumption. 148 subjects were enrolled (97 excessive drinkers (ED) and 51 controls). Time Line Follow-Back questionnaire was used to quantify the amount of alcohol consumed. Serum LPS, sCD14, and sCD163 were measured. Peripheral blood mononuclear cells (PBMCs) were also isolated. Compared to controls, ED had higher total drinks in the past 30 days, higher levels of LPS, sCD14 and sCD163. The levels of serum LPS, sCD14, and sCD163 were higher among ED with recent alcohol consumption (last drink <10 days before enrollment) compared to those without recent drinking. Similar bacterial genome copy numbers were detected in control and ED groups. We found that ethanol primed PBMCs for LPS-induced inflammatory responses. A positive correlation between serum LPS, sCD14, sCD163 and the quantity of alcohol drinking was observed after adjusting for covariates and that abstinence was associated with decline in the levels of LPS, sCD14 and sCd163. We found an increase in the levels of LPS and markers of monocyte activations in ED. Further studies are needed to determine whether these can be used as the biomarkers for excessive alcohol use.
Maintaining ecosystem resilience: functional responses of tree cavity nesters to logging in temperate forests of the Americas
Authors: Ibarra José Tomás , Martin Michaela , Cockle Kristina L. , Martin Kathy
Published: June 2017

Logging often reduces taxonomic diversity in forest communities, but little is known about how this biodiversity loss affects the resilience of ecosystem functions. We examined how partial logging and clearcutting of temperate forests influenced functional diversity of birds that nest in tree cavities. We used point-counts in a before-after-control-impact design to examine the effects of logging on the value, range, and density of functional traits in bird communities in Canada (21 species) and Chile (16 species). Clearcutting, but not partial logging, reduced diversity in both systems. The effect was much more pronounced in Chile, where logging operations removed critical nesting resources (large decaying trees), than in Canada, where decaying aspenPopulus tremuloideswere retained on site. In Chile, logging was accompanied by declines in species richness, functional richness (amount of functional niche occupied by species), community-weighted body mass (average mass, weighted by species densities), and functional divergence (degree of maximization of divergence in occupied functional niche). In Canada, clearcutting did not affect species richness but nevertheless reduced functional richness and community-weighted body mass. Although some cavity-nesting birds can persist under intensive logging operations, their ecosystem functions may be severely compromised unless future nest trees can be retained on logged sites.
E2F1-regulated long non-coding RNA RAD51-AS1 promotes cell cycle progression, inhibits apoptosis and predicts poor prognosis in epithelial ovarian cancer
Authors: Zhang Xiaodan , Liu Guoping , Qiu Junjun , Zhang Ning , Ding Jingxin , Hua Keqin
Published: June 2017

Long non-coding RNA RAD51 antisense RNA 1 (RAD51-AS1, also known as TODRA) has been shown to be down-regulated by E2F1, a key cell cycle and apoptosis regulator, in breast cancer. Little is known regarding the role of RAD51-AS1 in disease. Here, we investigate the role of RAD51-AS1 in epithelial ovarian cancer (EOC). Using luciferase reporter and chromatin immunoprecipitation experiments, we verified RAD51-AS1 as a target of E2F1 under negative regulation in EOC. We then examined RAD51-AS1 expression in EOC samples using in situ hybridization (ISH). RAD51-AS1 was localized to the nucleus and found to be a critical marker for clinical features that significantly correlated with poor survival in EOC patients. RAD51-AS1 was also an independent prognostic factor for EOC. Overexpression of RAD51-AS1 promoted EOC cell proliferation, while silencing of RAD51-AS1 inhibited EOC cell proliferation, delayed cell cycle progression and promoted apoptosis in vitro and in vivo. RAD51-AS1 may participate in carcinogenesis via regulation of p53 and p53-related genes. Our study highlights the role of RAD51-AS1 as a prognostic marker of EOC. Based on its regulation of the tumor suppressor p53, RAD51-AS1-based therapy may represent a viable therapeutic option for EOC in the near future.
Contrasting dynamics of leaf potential and gas exchange during progressive drought cycles and recovery in Amorpha fruticosa and Robinia pseudoacacia
Authors: Yan Weiming , Zheng Shuxia , Zhong Yangquanwei , Shangguan Zhouping
Published: June 2017

Leaf gas exchange is closely associated with water relations; however, less attention has been given to this relationship over successive drought events. Dynamic changes in gas exchange and water potential in the seedlings of two woody species, Amorpha fruticosa and Robinia pseudoacacia, were monitored during recurrent drought. The pre-dawn leaf water potential declined in parallel with gas exchange in both species, and sharp declines in gas exchange occurred with decreasing water potential. A significant correlation between pre-dawn water potential and gas exchange was observed in both species and showed a right shift in R. pseudoacacia in the second drought. The results suggested that stomatal closure in early drought was mediated mainly by elevated foliar abscisic acid (ABA) in R. pseudoacacia, while a shift from ABA-regulated to leaf-water-potential-driven stomatal closure was observed in A. fruticosa. After re-watering, the pre-dawn water potential recovered quickly, whereas stomatal conductance did not fully recover from drought in R. pseudoacacia, which affected the ability to tightly control transpiration post-drought. The dynamics of recovery from drought suggest that stomatal behavior post-drought may be restricted mainly by hydraulic factors, but non-hydraulic factors may also be involved in R. pseudoacacia.
Differential Membrane Dipolar Orientation Induced by Acute and Chronic Cholesterol Depletion
Authors: Sarkar Parijat , Chakraborty Hirak , Chattopadhyay Amitabha
Published: June 2017

Cholesterol plays a crucial role in cell membrane organization, dynamics and function. Depletion of cholesterol represents a popular approach to explore cholesterol-sensitivity of membrane proteins. An emerging body of literature shows that the consequence of membrane cholesterol depletion often depends on the actual process (acute or chronic), although the molecular mechanism underlying the difference is not clear. Acute depletion, using cyclodextrin-type carriers, is faster relative to chronic depletion, in which inhibitors of cholesterol biosynthesis are used. With the overall goal of addressing molecular differences underlying these processes, we monitored membrane dipole potential under conditions of acute and chronic cholesterol depletion in CHO-K1 cells, using a voltage-sensitive fluorescent dye in dual wavelength ratiometric mode. Our results show that the observed membrane dipole potential exhibits difference under acute and chronic cholesterol depletion conditions, even when cholesterol content was identical. To the best of our knowledge, these results provide, for the first time, molecular insight highlighting differences in dipolar reorganization in these processes. A comprehensive understanding of processes in which membrane cholesterol gets modulated would provide novel insight in its interaction with membrane proteins and receptors, thereby allowing us to understand the role of cholesterol in cellular physiology associated with health and disease.
Tuberculosis infection in rural labor migrants in Shenzhen, China: Emerging challenge to tuberculosis control during urbanization
Authors: Li Xiangwei , Yang Qianting , Feng Boxuan , Xin Henan , Zhang MingXia , Deng Qunyi , Deng Guofang , Shan Wanshui , Yue Jianrong , Zhang Haoran , Li Mufei , Li Hengjing , Jin Qi , Chen Xinchun , Gao Lei
Published: June 2017

During China’s urbanization process, rural labor migrants have been suggested to be one important bridge population to change urban-rural distribution on tuberculosis (TB) burden. Aiming to estimate the prevalence of TB infection and to track the active disease development in rural labor migrants, a prospective study was conducted in Shenzhen city, southern China. TB infection was detected using interferon-γ release assay (IGRA). Here we mainly report the characteristics of TB infection in the study population based on the baseline survey. A total of 4,422 eligible participants completed baseline survey in July 2013. QuantiFERON (QFT) positivity rates 17.87% (790/4,422) and was found to be consistent with the local TB epidemic of the areas where the participants immigrated from. Age, smoking, residence registered place, and present of BCG scars were found to be independently associated with QFT positivity. Additionally, evidence for interaction between smoking and age was observed (p for likelihood ratio test < 0.001). Our results suggested that the development of TB control strategy including latent TB infection management should pay more attention to the rural flowing population due to their high mobility and higher prevalence of TB infection.
Imipramine blue sensitively and selectively targets FLT3-ITD positive acute myeloid leukemia cells
Authors: Metts Jonathan , Bradley Heath L. , Wang Zhengqi , Shah Neil P. , Kapur Reuben , Arbiser Jack L. , Bunting Kevin D.
Published: June 2017

Aberrant cytokine signaling initiated from mutant receptor tyrosine kinases (RTKs) provides critical growth and survival signals in high risk acute myeloid leukemia (AML). Inhibitors to FLT3 have already been tested in clinical trials, however, drug resistance limits clinical efficacy. Mutant receptor tyrosine kinases are mislocalized in the endoplasmic reticulum (ER) of AML and play an important role in the non-canonical activation of signal transducer and activator of transcription 5 (STAT5). Here, we have tested a potent new drug called imipramine blue (IB), which is a chimeric molecule with a dual mechanism of action. At 200–300 nM concentrations, IB is a potent inhibitor of STAT5 through liberation of endogenous phosphatase activity following NADPH oxidase (NOX) inhibition. However, at 75–150 nM concentrations, IB was highly effective at killing mutant FLT3-driven AML cells through a similar mechanism as thapsigargin (TG), involving increased cytosolic calcium. IB also potently inhibited survival of primary human FLT3/ITD+ AML cells compared to FLT3/ITDneg cells and spared normal umbilical cord blood cells. Therefore, IB functions through a mechanism involving vulnerability to dysregulated calcium metabolism and the combination of fusing a lipophilic amine to a NOX inhibiting dye shows promise for further pre-clinical development for targeting high risk AML.
Hidden defensive morphology in rotifers: benefits, costs, and fitness consequences
Authors: Yin Xuwang , Jin Wen , Zhou Yanchun , Wang Peipei , Zhao Wen
Published: June 2017

To cope with predation, many prey species have developed inducible defenses in terms of morphology, behavior, and life history. Rotifers were the first model organisms used to evaluate the ecology and evolution of inducible defenses in aquatic ecosystems. Since the middle of last century, only visible morphological defenses, such as spine development, have been found and only in a few rotifer species. Given the development of ultrastructural defenses is taxonomically widespread in aquatic ecosystems, we hypothesize that rotifer prey, particularly small-sized species, can develop such inducible defenses. We evaluated morphological response of two common Brachionus herbivores (B. calyciflorus and B. angularis) to predatory rotifer Asplanchna brightwellii. Results confirmed existence of predator-induced ultrastructural defenses, which are expressed as increased lorica thickness and enhanced lorica hardness. Such inducible defenses are more evident and effective in the smaller sized B. angularis, leading to higher fitness of B. angularis in predator-prey interactions. As anticipated, development of defenses has inevitable fitness costs manifested as decreased reproduction or reduced sex investment. Our results not only extend understanding of inducible ultrastructural defense to other planktonic taxa that were previously observed only in cladocerans, but also verify effective mechanical protection of such hidden defensive morphology.
Triplex DNA-based Bioanalytical Platform for Highly Sensitive Homogeneous Electrochemical Detection of Melamine
Authors: Liu Xiaojuan , Song Mengmeng , Li Feng
Published: June 2017

Melamine detection has attracted much attention since the discovery of the damage of melamine to human health. Herein, we have developed a sensitive homogeneous electroanalytical platform for melamine detection, which is relied on the formation of triplex molecular beacon integrated with exonuclease III (Exo III)-mediated signal amplification. The formation of triplex molecular beacon was triggered by the recognition and incorporation of melamine to the abasic (AP) site contained in the triplex stem. The stem of the triplex molecular beacon was designed to have a protruding double-strand DNA, which can be recognized and hydrolyzed by Exo III for releasing methylene blue (MB)-labeled mononucleotide. These released MB molecules exhibit high diffusivity toward indium tin oxide electrode with negative charge, thus producing a significantly increased electrochemical response. Taking advantages of the high binding affinity of the DNA triplex structure containing AP sites towards melamine and the unique features of Exo III, this sensing platform is capable for sensitive and selective melamine assay with a detection limit as low as 8.7 nM. Furthermore, this strategy shows good applicability for melamine assay in real samples. Therefore, this strategy broadens the application of triplex DNA and presents a new method for sensitive detection of melamine.
Anisotropically biaxial strain in non-polar (112–0) plane In
x
Ga1−x
N/GaN layers investigated by X-ray reciprocal space mapping
Authors: Zhao Guijuan , Li Huijie , Wang Lianshan , Meng Yulin , Ji Zesheng , Li Fangzheng , Wei Hongyuan , Yang Shaoyan , Wang Zhanguo
Published: June 2017

In this study, the indium composition x as well as the anisotropically biaxial strain in non-polar a-plane In
x
Ga1−x
N on GaN is studied by X-ray diffraction (XRD) analysis. In accordance with XRD reciprocal lattice space mapping, with increasing indium composition, the maximum of the In
x
Ga1−x
N reciprocal lattice points progressively shifts from a fully compressive strained to a fully relaxed position, then to reversed tensile strained. To fully understand the strain in the ternary alloy layers, it is helpful to grow high-quality device structures using a-plane nitrides. As the layer thickness increases, the strain of In
x
Ga1−x
N layer releases through surface roughening and the 3D growth-mode.
Somatosensory lateral inhibition processes modulate motor response inhibition - an EEG source localization study
Authors: Friedrich Julia , Mückschel Moritz , Beste Christian
Published: June 2017

Motor inhibitory control is a central executive function, but only recently the importance of perceptual mechanisms for these processes has been focused. It is elusive whether basic mechanisms governing sensory perception affect motor inhibitory control. We examine whether sensory lateral inhibition (LI) processes modulate motor inhibitory control using a system neurophysiological approach combining EEG signal decomposition with source localization methods in a somatosensory GO/NOGO task. The results show that inter-individual variations in the strength of LI effects predominantly affect processes when information needs to be integrated between cerebral hemispheres. If information needs to be integrated between hemispheres, strong sensory suppression will lead to more impulsive errors. Importantly, the neurophysiological data suggest that not purely perceptual or motor processes are affected. Rather, LI affects the response selection level and modulates processes of stimulus categorization. This is associated with activity modulations in the posterior parietal cortex. The results suggest that when sensory suppression is high and when information needs to be integrated across hemispheres, these processes are less efficient, which likely leads to worse motor inhibitory control. The results show how basis principles modulating perceptual processes affect subsequent motor inhibitory control processes.
Erratum: Direct and accurate measurement of size dependent wetting behaviors for sessile water droplets
Authors: Park Jimin , Han Hyung-Seop , Kim Yu-Chan , Ahn Jae-Pyeong , Ok Myoung-Ryul , Lee Kyung Eun , Lee Jee-Wook , Cha Pil-Ryung , Seok Hyun-Kwang , Jeon Hojeong
Published: June 2017

Scientific Reports 5: Article number: 18150; published online: 14 December 2015; updated: 26 June 2017. This Article contains errors. In the ‘Results’ section, under the subheading ‘Size-dependent wettability of the droplets’. “The contact angle value varied dramatically with an RLSV value of less than 5 μm, whereas RLSV values of more than 80 μm approached a saturated value of 58.
Fast quantitation of pyrazole fungicides in wine by ambient ionization mass spectrometry
Authors: Pu Fan , Zhang Wenpeng , Han Chao , Ouyang Zheng
Published: June 2017

Paper capillary used for fast quantitation of pyrazole fungicides in wines.