bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of nicotinamide N-methyltransferase in oral malignant melanoma and potential prognostic significance
Authors: Mascitti Marco , Santarelli Andrea , Sartini Davide , Rubini Corrado , Colella Giuseppe , Salvolini Eleonora , Ganzetti Giulia , Offidani Annamaria , Emanuelli Monica
Published: November 2018

Oral malignant melanoma (OMM) is an aggressive tumour, and shows deep tissue invasion at initial presentation. The prognosis is worse than that for cutaneous melanoma (CM), and the overall 5-year survival rate is 10–25%. A study of the molecular mechanisms involved in the development of OMM is necessary to identify new prognostic markers. In this study, we evaluated the possible role of nicotinamide N-methyltransferase (NNMT) in OMM. We carried out immunohistochemical analyses to evaluate the expression of NNMT in 15 OMM and 15 CM, measuring the percentage of positive cells and the value of NNMT expression intensity. Furthermore, we explored the relationship between NNMT levels and the prognostic parameters of patients with OMM. NNMT was significantly more expressed in CM compared with OMM, whereas higher staining intensity for NNMT was observed in OMM cases (P<0.05). In addition, a significant relationship was found between NNMT staining intensity and the presence of ulceration (P<0.05). Furthermore, univariate analysis showed a negative effect of NNMT expression on the disease-free survival rate (P<0.05). This study is the first to report the expression of NNMT in OMM and to compare OMM enzyme levels with those detected in CM. Data obtained seem to suggest the presence of potential molecular differences between these two tumours.
Obesity in relation to serum persistent organic pollutant concentrations in CHAMACOS women
Authors: Warner Marcella , Rauch Stephen , Coker Eric S. , Harley Kim , Kogut Katherine , Sjödin Andreas , Eskenazi Brenda
Published: November 2018

Background:

Environmental exposure to endocrine-disrupting chemicals (EDCs), including persistent organic pollutants (POPs), has been hypothesized to increase risk of obesity. Using data from the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, we examined the longitudinal relationship between serum concentrations of a POPs mixture and several obesity measures.

Methods:

Concentrations of 17 POPs were measured in serum collected in 2009–2011 from 468 CHAMACOS women. Anthropometry measurements and personal interviews were completed at up to three study visits between 2009 and 2014. We assessed the relationship of serum POPs concentrations with adiposity measures longitudinally using generalized estimation equation (GEE) models. We implemented Bayesian Kernel Machine Regression (BKMR) to elucidate the effects of joint exposure to the POPs mixture.

Results:

In GEE models, positive associations with body mass index were found for dichlorodiphenyltrichloroethane (Q4 vs. Q1: adjusted β = 3.2 kg/m2; 95% CI = 1.5, 4.9), β-hexachlorocyclohexane (Q4 vs. Q1: adjusted β = 3.6 kg/m2; 95% CI = 2.0, 5.2), and polybrominated diphenyl ether (PBDE)-47 (Q4 vs. Q1: adjusted β = 1.9 kg/m2; 95% CI = 0.3, 3.5), while PBDE-153 was inversely associated (Q4 vs. Q1: adjusted β = −2.8 kg/m2; 95% CI = −4.4, −1.2). BKMR results, while largely consistent with single pollutant models, revealed the shape and direction of the exposure–response relationships, as well as interactions among pollutants within the mixture, that could not be discovered by single-pollutant models.

Conclusion:

In summary, we found significant associations of serum POPs with several adiposity measures using both conventional regressions and BKMR. Our results provide support for the chemical obesogen hypothesis, that exposure to EDCs may alter risk for later obesity.
An Orally Available NLRP3 Inflammasome Inhibitor Prevents Western Diet–Induced Cardiac Dysfunction in Mice
Authors: Carbone Salvatore , Mauro Adolfo G. , Prestamburgo Andrea , Halquist Matthew S. , Narayan Pratush , Potere Nicola , Mezzaroma Eleonora , Van Tassell Benjamin W. , Abbate Antonio , Toldo Stefano
Published: November 2018

Background:

A diet rich in saturated fat and sugars (Western diet, WD) induces myocardial expression of the NLRP3 inflammasome and dysfunction in mice. We therefore hypothesized that a diet enriched with an orally available NLRP3 inflammasome inhibitor could prevent WD-induced cardiac dysfunction in mice.

Methods:

Ten-week-old CD-1 male mice were fed WD or standard diet (SD) for 8 weeks. The compound 16673-34-0, an orally active NLRP3 inhibitor, was added to the diet at a concentration of 100 mg/Kg. The plasmatic levels of the NLRP3 inflammasome inhibitor were measured. Food intake, body weight, and glucose tolerance were assessed. Cardiac systolic and diastolic functions were measured by Doppler echocardiography at baseline, 4 weeks, and 8 weeks.

Results:

WD induced a significant increase in body weight (+14%, P = 0.02), impaired glucose tolerance (+34%, P = 0.03), and a significant increase in isovolumetric relaxation time (+129%, P = 0.03) and reduction in left ventricular ejection fraction (−10%, P = 0.03), as compared to standard chow diet (SD). The treatment with NLRP3 inhibitor in the diet prevented cardiac systolic and diastolic dysfunction (P < 0.05 for left ventricular ejection fraction, isovolumetric relaxation time, and myocardial performance index in WD with drug vs. WD without drug), without significant changes in heart rate and metabolic parameters.

Conclusions:

An orally available NLRP3 inhibitor prevented WD-induced cardiac dysfunction in obese mice.
Mitochondrial Dysfunction and Apoptosis Are Attenuated on κ-Opioid Receptor Activation Through AMPK/GSK-3β Pathway After Myocardial Ischemia and Reperfusion
Authors: Tian Xin , Zhou Yaguang , Wang Yuanbo , Zhang Shumiao , Feng Jiahao , Wang Xu , Guo Haitao , Fan Rong , Feng Na , Jia Min , Gu Xiaoming , Li Juan , Yang Lu , Wang Yueming , Li Jun , Zheng Guoxu , Fu Feng , Pei Jianming
Published: November 2018

Previous studies have shown that κ-opioid receptor activation possesses cardioprotection against myocardial ischemia and reperfusion (MI/R) injury. The current study was designed to investigate whether mitochondrial dysfunction after MI/R is regulated by the κ-opioid receptor and to further explore the underlying mechanisms involved. MI/R rat model was established in vivo, and a hypoxia and reoxygenation cardiomyocytes model was used in vitro. Mitochondrial morphology and function as well as myocardial apoptosis were determined. Our data indicated that treatment with U50,488H (a selective κ-opioid receptor agonist) not only reduced apoptosis but also significantly improved mitochondrial morphology and function. These effects were blocked by nor-binaltorphimine (nor-BNI, a selective κ-opioid receptor antagonist), Compound C (an AMPK inhibitor), and AR-A014418 (a GSK3β inhibitor). Moreover, in cardiomyocytes, treatment with U50,488H significantly increased the expression in phosphorylation of AMPK and the phosphorylation of GSK3β. Treatment of cardiomyocytes with AMPKα siRNA decreased the phosphorylation of AMPK and GSK3β. Moreover, AMPK activation resulted in the phosphorylation of GSK3β. Our findings suggested that U50,488H exerted cardioprotective effects by improving mitochondrial morphology and function against MI/R injury through activation of the κ-opioid receptor–mediated AMPK/GSK3β pathway.
New Mass Spectrometric Approaches for the Quantitative Evaluation of Anticancer Drug Levels in Treated Patients
Authors: D'Aronco Sara , D'Angelo Edoardo , Crotti Sara , Traldi Pietro , Agostini Marco
Published: November 2018

Alternatively to the well-consolidated liquid chromatography coupled to tandem mass spectrometry approach used for the evaluation of anticancer drug concentrations in treated patients, new mass spectrometric methods have been proposed and tested recently. They exhibited faster analysis time and, at first sight, simpler instrumental approaches. However, results obtained by these methods require an in-depth evaluation, because of their strong dependence on the experimental set-up. In this short review, the quantification of irinotecan, sunitinib, and 6-α-hydroxy paclitaxel (the main metabolite of paclitaxel) by laser desorption ionization techniques (matrix-assisted laser desorption/ionization, nanostructure-assisted laser desorption/ionization, and surface-assisted laser desorption/ionization) is reported and discussed, showing the advantages but also the drawbacks of the methods. The matrix-assisted laser desorption/ionization approach led to the most reliable results, and the cross-validation for the quantitative analysis of irinotecan indicates that this method can be fruitfully used for therapeutic drug monitoring and pharmacokinetic studies. Another recently proposed technique, paper spray mass spectrometry, has been tested for the quantitative measurement of imatinib in plasma samples. Even if the approach is, at first sight, really simple, the parameterization of the analytical and instrumental aspects has required many efforts to reach satisfactory results. What it should be expected in the future is the evaluation of these methods, not only in scientific environments dedicated to instrument development, but also in clinical chemistry laboratories, to evaluate their effectiveness and to give new and valid tools for TDM and for other qualitative or quantitative measurements of biomedical interest.
Efficacy of Luliconazole Against Broad-Range Filamentous Fungi Including Fusarium solani Species Complex Causing Fungal Keratitis
Authors: Todokoro Daisuke , Suzuki Takashi , Tamura Takashi , Makimura Koichi , Yamaguchi Hideyo , Inagaki Katsuhiro , Akiyama Hideo
Published: November 2018

Purpose:

Fungal keratitis can be difficult to medically treat. Topical antifungals are usually applied empirically as the initial option in treating fungal keratitis. Natamycin (NAT) and/or voriconazole (VRCZ) have been widely used in the treatment of fungal keratitis. However, Fusarium solani species complex (FSSC), which are the dominant species of fungal keratitis, are resistant to VRCZ. This study investigated in vitro efficacy of luliconazole (LLCZ), a new imidazole antifungal, against FSSC and other filamentous fungi.

Methods:

A total of 18 Fusarium isolates and 7 others were grown on potato dextrose agar at 30 and 37°C. For Fusarium, species identification and phylogenetic tree analysis were performed based on elongation factor-1α (EF-1α) DNA sequencing. The broth microdilution method was used for antifungal susceptibility testing of 11 antifungal drugs including LLCZ.

Results:

The 18 identified Fusarium isolates belonged to FSSC (n = 13), Fusarium oxysporum species complex (FOSC; n = 2), Fusarium chlamydosporum species complex (FCSC; n = 1), Fusarium incarnatum-equiseti species complex (FIESC; n = 1), and Fusarium fujikuroi species complex (FFSC; n = 1). We further divided 13 FSSC isolates into 3 clades, FSSC5 (n = 8), FSSC3 + 4 (n = 4), and FSSC9-a (n = 1), with 8 FSSC strains growing at 37°C. LLCZ showed lowest minimum inhibitory concentrations (MICs) against all tested filamentous fungi, with a MIC90 against the Fusarium species of 0.06 μg/mL, whereas MIC90 for NAT and VRCZ were 4 and 8 μg/mL, respectively.

Conclusions:

LLCZ has the strongest in vitro antifungal activity among all drugs used against broad-range filamentous fungi including FSSC. LLCZ may potentially be a new medical treatment option for fungal keratitis.
Urticaria Multiforme
Authors: Maynard Kristi
Published: November 2018

Urticaria multiforme is a rare, hypersensitivity reaction that occurs in infants and small children. Because of its rare occurrence, many providers are unable to accurately identify the rash and associated symptoms to unnecessary laboratory and histological testing or misdiagnosis. This article highlights the case of an 11-month-old female infant with urticaria multiforme. It explores the identification, diagnosis, and current treatment recommendations.
Self-Management Problem-Solving Tools for Lower-Limb Prosthesis Wearers: Mobile App Usability and Acceptability Study
Authors: Lee Daniel Joseph , Veneri Diana A. , Goodworth Adam D.
Published: November 2018

Introduction

The ability to self-manage and problem solve effectively is an important component of managing chronic conditions. For individuals with limb loss, problem solving the fit of their prosthetic socket is crucial to being able to functionally ambulate with a prosthetic leg. This study evaluates and compares two innovative problem-solving tools designed to empower prosthesis wearers in self-managing their socket fit.

Materials and Methods

Fourteen paper-based problem-solving decision trees were integrated into a mobile health app displayed on an iPad. Thirty prosthesis wearers performed a total of six trials split between the two conditions (paper-based and mobile app).Technical effectiveness, efficiency, and acceptability were assessed during and after participants used each tool to problem solve real-life scenarios. Technical effectiveness was a measure of the number of errors, whereas efficiency was a measure of the amount of time needed to complete each trial. Acceptability was measured using Likert-like questionnaires and semistructured interviews.

Results

Results demonstrated significantly better efficiency (paper-based = 124.22 seconds on average, app = 108.76 seconds; P = 0.0076) and technical effectiveness (paper-based = 0.66 errors on average, app = 0.2 errors; P < 0.001) for the app. Age and education were correlated with the outcomes.

Conclusions

The mobile app demonstrated significantly better outcomes as compared with the paper-based decision trees. Both the mobile app and paper-based tool had high acceptability; however, the mobile app was found to be significantly easier to use and less confusing than the paper-based version of the decision trees. Further study is required to assess the efficacy of the decision trees to manage a prosthetic fit issue in an individual who is currently having difficult managing a prosthetic socket fit issue.
Comparison of chitinase-3-like protein 1, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 index with shear-wave elastography
Authors: Mushtaq Saadiya , Ghani Eijaz , Azam Khalid , Hussain Tabinda
Published: November 2018

Background

In the past, there has been an exponential increase in the potential biomarkers that can be used for staging of liver fibrosis. In light of intraobserver and intralobular variations, criticism has been directed at liver biopsy, and its efficacy has been challenged. Shear-wave elastography (SWE) has become a routine method for pre-assessment of liver fibrosis. Serum markers such as chitinase-3-like protein 1 (CHI3L1) also known as YKL-40, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 (Fib-4) index have been researched as potential alternates to detect liver fibrosis.

Study

A total of 150 enrolled patients with chronic hepatitis underwent serum analysis to estimate CHI3L1 or YKL-40 level, aspartate aminotransferase-to-platelet ratio index, and Fib-4 index. These patients also underwent SWE.

Results

The distribution of fibrosis grade according to SWE was F0: 46 patients, F1: 31 patients, F2: 16 patients, F3: four patients, and F4: 53 patients. Receiver operating characteristic curve analysis for F0–F1 versus F2–F3, F0–F1 versus F4, and F2–F3 versus F4 gave area under curve values of 0.56 (P>0.05), 0.76 (P<0.01), and 0.75, respectively (P<0.01) for aspartate aminotransferase-to-platelet ratio index; of 0.65 (P<0.05), 0.78 (P<0.01), and 0.7, respectively (P<0.05) for Fib-4 index; and 0.98, 0.99, and 0.95, respectively (P<0.01 for all) for CHI3L1.

Conclusion

CHI3L1 could be used as a preliminary tool to assess mild/absent fibrosis from significant fibrosis and cirrhosis.
Health Information and the Quality and Safety of Care for People With Disability: An Analysis of Australian Reports of Reviewable Deaths in Residential Care
Authors: Dahm Maria R. , Georgiou Andrew , Balandin Susan , Hill Sophie , Hemsley Bronwyn
Published: November 2018

Objective

Many Australians with disability live in residential care and require assistance to manage their health information across hybrid care settings encompassing residential care, primary and tertiary care, and allied health. In this study, we examined case study reports on people with disability living in residential care in New South Wales, Australia to (a) identify threats to the quality of care and safety for this vulnerable patient group in relation to health documentation and information infrastructure and (b) evaluate the applicability of a conceptual health information infrastructure model.

Methods

All 99 case studies were extracted from eight New South Wales Ombudsmen reports of reviewable deaths for a directed content analysis applying a conceptual model of health information infrastructure in residential care.

Results

Ninety-one percent of case studies (n = 90) contained information relation to documentation. Forty-seven percent of case studies (n = 47) linked failures in documentation to risk of death, and 12% (n = 12) described best practice use of documentation. Threats to quality of care and safety related to poor “coordination” of information, including information not being implemented, poor “communication” across services, and discrepancies between “policy and practice” in health management.

Conclusions

The conceptual model demonstrated how “coordination” and “communication” of health information relate to tensions between “policy and practice,” influencing the safety and quality of care for people with disability in residential care. The model was a good fit to investigate how health information infrastructure may affect the quality of residential care and could inform holistic digital solutions to deliver safer, integrated, and higher quality care for people with disability.
Asian Liver Transplant Network Clinical Guidelines on Immunosuppression in Liver Transplantation
Authors: Tan Poh Seng , Muthiah Mark D. , Koh Tsingyi , Teoh Yee Leong , Chan Albert , Kow Alfred , Zheng Qishi , Kwon Choon Hyuck David , Lee Guan Huei , Lesmana Cosmas Rinaldi A. , de Villa Vanessa , Fung James , Lim Kieron
Published: November 2018

Most management guidelines and much of the available clinical trial evidence for immunosuppressants in liver transplantation (LT) pertain to Western practice. While evidence from Western studies may not translate to Asian settings, there is a paucity of Asian randomized controlled trials of immunosuppression in liver recipients. Nonetheless, there are notable differences in the indications and procedures for LT between Western and Asian settings. The Asian Liver Transplant Network held its inaugural meeting in Singapore in November 2016 and aimed to provide an Asian perspective on aspects of immunosuppression following LT. Because of their importance to outcome following LT, the meeting focused on (1) reducing the impact of renal toxicity, (2) hepatocellular carcinoma recurrence, and (3) nonadherence with immunosuppressant therapy.
Aeroecology of a solar eclipse
Authors: Nilsson Cecilia , Horton Kyle G. , Dokter Adriaan M. , Van Doren Benjamin M. , Farnsworth Andrew
Published: November 2018

Light cues elicit strong responses from nearly all forms of life, perhaps most notably as circadian rhythms entrained by periods of daylight and darkness. Atypical periods of darkness, like solar eclipses, provide rare opportunities to study biological responses to light cues. By using a continental scale radar network, we investigated responses of flying animals to the total solar eclipse of 21 August 2017. We quantified the number of biological targets in the atmosphere at 143 weather radar stations across the continental United States to investigate whether the decrease in light and temperature at an atypical time would initiate a response like that observed at sunset, when activity in the atmosphere usually increases. Overall, biological activity decreased in the period leading to totality, followed by a short low-altitude spike of biological activity during totality in some radars. This pattern suggests that cues associated with the eclipse were insufficient to initiate nocturnal activity comparable to that occurring at sunset but sufficient to suppress diurnal activity.
Multiscale modelling of the human lumbar facet capsular ligament: analysing spinal motion from the joint to the neurons
Authors: Zarei Vahhab , Dhume Rohit Y. , Ellingson Arin M. , Barocas Victor H.
Published: November 2018

Due to its high level of innervation, the lumbar facet capsular ligament (FCL) is suspected to play a role in low back pain (LBP). The nociceptors in the lumbar FCL may experience excessive deformation and generate pain signals. As such, understanding the mechanical behaviour of the FCL, as well as that of its underlying nerves, is critical if one hopes to understand its role in LBP. In this work, we constructed a multiscale structure-based finite-element (FE) model of a lumbar FCL on a spinal motion segment undergoing physiological motions of flexion, extension, ipsilateral and contralateral bending, and ipsilateral axial rotation. Our FE model was created for a generic FCL geometry by morphing a previously imaged FCL anatomy onto an existing generic motion segment model. The fibre organization of the FCL in our models was subject-specific based on previous analysis of six dissected specimens. The fibre structures from those specimens were mapped onto the FCL geometry on the motion segment. A motion segment model was used to determine vertebral kinematics under specified spinal loading conditions, providing boundary conditions for the FCL-only multiscale FE model. The solution of the FE model then provided detailed stress and strain fields within the tissue. Lastly, we used this computed strain field and our previous studies of deformation of nerves embedded in fibrous networks during simple deformations (e.g. uniaxial stretch, shear) to estimate the nerve deformation based on the local tissue strain and fibre alignment. Our results show that extension and ipsilateral bending result in largest strains of the lumbar FCL, while contralateral bending and flexion experience lowest strain values. Similar to strain trends, we calculated that the stretch of the microtubules of the nerves, as well as the forces exerted on the nerves' membrane are maximal for extension and ipsilateral bending, but the location within the FCL of peak microtubule stretch differed from that of peak membrane force.
The future of quantum biology
Authors: Marais Adriana , Adams Betony , Ringsmuth Andrew K. , Ferretti Marco , Gruber J. Michael , Hendrikx Ruud , Schuld Maria , Smith Samuel L. , Sinayskiy Ilya , Krüger Tjaart P. J. , Petruccione Francesco , van Grondelle Rienk
Published: November 2018

Biological systems are dynamical, constantly exchanging energy and matter with the environment in order to maintain the non-equilibrium state synonymous with living. Developments in observational techniques have allowed us to study biological dynamics on increasingly small scales. Such studies have revealed evidence of quantum mechanical effects, which cannot be accounted for by classical physics, in a range of biological processes. Quantum biology is the study of such processes, and here we provide an outline of the current state of the field, as well as insights into future directions.
Cetacean citations and the covenant of iron
Authors: Bulstrode Jenny
Published: November 2018

By the early decades of the nineteenth century, with surveys established as the weapon of choice for the fiscal military state, their instrumentation provided a focal point for radical attacks on political establishments. This paper considers a notorious dispute over mastery of iron in the instrumentation of magnetic surveying that took place in the 1830s between an Admiralty committee and the Reverend William Scoresby, a whaler-turned-clergyman. Scoresby staked his claim by drawing on the labour law of the whaleboats, a culture peculiarly preoccupied with the properties of bone and blubber, ink and skin, parchment and iron, where magnetism was forged in the ‘combinations’, as Scoresby put it, of such specific materials. The enterprises of his most avid reader, peer and fellow labour rights activist, Herman Melville, showcase the salience of Scoresby's struggle with Admiralty authority. The eminent Australian scholar Greg Dening's approach to ethnohistory proves the appropriate instrument with which to analyse such an encounter between traditions, negotiated through material forms. In the fraught exchange between whaler and maritime state, the combination laws that helped prompt the threat of revolution in early nineteenth-century Britain were translated into Scoresby's iron. Extant material and archival collections in Greenwich and Whitby offer traces of a battle between ways of knowing this protean metal: ‘not down in any map; true places never are’.
A probabilistic metric for the validation of computational models
Authors: Dvurecenska Ksenija , Graham Steve , Patelli Edoardo , Patterson Eann A.
Published: November 2018

A new validation metric is proposed that combines the use of a threshold based on the uncertainty in the measurement data with a normalized relative error, and that is robust in the presence of large variations in the data. The outcome from the metric is the probability that a model's predictions are representative of the real world based on the specific conditions and confidence level pertaining to the experiment from which the measurements were acquired. Relative error metrics are traditionally designed for use with a series of data values, but orthogonal decomposition has been employed to reduce the dimensionality of data matrices to feature vectors so that the metric can be applied to fields of data. Three previously published case studies are employed to demonstrate the efficacy of this quantitative approach to the validation process in the discipline of structural analysis, for which historical data were available; however, the concept could be applied to a wide range of disciplines and sectors where modelling and simulation play a pivotal role.
On the definition of Landau constants in amplitude equations away from a critical point
Authors: Pham Khanh Gia , Suslov Sergey A.
Published: November 2018

A weakly nonlinear stability analysis of shear flows based on amplitude expansion is re-examined. While it has been known that the condition required to define the coefficients of the resulting Stuart–Landau series representing the nonlinear temporal evolution of the most amplified Fourier component of a disturbance is not unique, we show that it can be formulated in a flexible generic form that incorporates different conditions used by various authors previously. The new formulation is interpreted from the point of view of low-dimensional projection of a full solution of a problem onto the space spanned by the basic flow vector and the eigenvector of the linearized problem. It is rigorously proven that the generalized condition formulated in this work reduces to a standard solvability condition at the critical point, where the basic flow first becomes unstable with respect to infinitesimal disturbances, and that it results in a well-posed problem for the determination of coefficients of Stuart–Landau series both at the critical point and a finite distance away from it. On a practical side, the generalized condition reported here enables one to choose the projection in such a way that the resulting low-dimensional approximate solution emphasizes specific physical features of interest via selecting the appropriate projection weight matrix without changing the overall asymptotic expansion procedure.
A new type of microphotoreactor with integrated optofluidic waveguide based on solid-air nanoporous aerogels
Authors: Özbakır Yaprak , Jonáš Alexandr , Kiraz Alper , Erkey Can
Published: November 2018

In this study, we developed a new type of microphotoreactor based on an optofluidic waveguide with aqueous liquid core fabricated inside a nanoporous aerogel. To this end, we synthesized a hydrophobic silica aerogel monolith with a density of 0.22 g cm
−3
and a low refractive index of 1.06 that—from the optical point of view—effectively behaves like solid air. Subsequently, we drilled an L-shaped channel within the monolith that confined both the aqueous core liquid and the guided light, the latter property arising due to total internal reflection of light from the liquid–aerogel interface. We characterized the efficiency of light guiding in liquid-filled channel and—using the light delivered by waveguiding—we carried out photochemical reactions in the channel filled with aqueous solutions of methylene blue dye. We demonstrated that methylene blue could be efficiently degraded in the optofluidic photoreactor, with conversion increasing with increasing power of the incident light. The presented optofluidic microphotoreactor represents a versatile platform employing light guiding concept of conventional optical fibres for performing photochemical reactions.
Bacterial response to graphene oxide and reduced graphene oxide integrated in agar plates
Authors: Mokkapati V. R. S. S. , Pandit Santosh , Kim Jinho , Martensson Anders , Lovmar Martin , Westerlund Fredrik , Mijakovic Ivan
Published: November 2018

There are contradictory reports in the literature regarding the anti-bacterial activity of graphene, graphene oxide (GO) and reduced graphene oxide (rGO). This controversy is mostly due to variations in key parameters of the reported experiments, like: type of substrate, form of graphene, number of layers, type of solvent and most importantly, type of bacteria. Here, we present experimental data related to bacterial response to GO and rGO integrated in solid agar-based nutrient plates—a standard set-up for bacterial growth that is widely used by microbiologists.
Bacillus subtilis
and
Pseudomonas aeruginosa
strains were used for testing bacterial growth. We observed that plate-integrated rGO showed strong anti-bacterial activity against both bacterial species. By contrast, plate-integrated GO was harmless to both bacteria. These results reinforce the notion that the response of bacteria depends critically on the type of graphene material used and can vary dramatically from one bacterial strain to another, depending on bacterial physiology.
Resveratrol-loaded PLGA nanoparticles: enhanced stability, solubility and bioactivity of resveratrol for non-alcoholic fatty liver disease therapy
Authors: Wan Shuqian , Zhang Long , Quan Yunyun , Wei Kun
Published: November 2018

Resveratrol (3, 4′, 5-trihydroxy-
trans
-stilbene, RSV), a nutraceutical, has recently attracted lots of attention because of its outstanding pharmacological potential. The effects of RSV on non-alcoholic fatty liver disease (NAFLD) remain inconclusive, although a wealth of research has been done. The major obstacle presented was RSV's poor bioavailability due to its poor aqueous solubility, chemical instability and intestinal metabolism. In this study, nanotechnology was used to encapsulate RSV to enhance its stability, water solubility and bioactivity, which can be used to treat NAFLD by HepG2 hepatocytes-induced
in vitro
. RSV-loaded poly (
d
,
l
-lactide-co-glycolide acid) (PLGA) nanoparticles (RSV-PLGA-NPs) were prepared according to an oil/water (O/W) emulsion technique. The RSV-PLGA-NPs were of spherical morphology with an average size of 176.1 nm and a negative charge of −22.6 mV. These nanoparticles exhibited remarkable encapsulation efficiency (EE%) (97.25%) and drug loading (14.9%) for RSV. A sustained RSV release from RSV-PLGA-NPs could be achieved especially in acidic conditions when simulating transporting through the gastrointestinal tract. In addition, these nanoparticles were stable enough to store at 4°C for a least six months with unchanged EE%. Moreover, RSV-PLGA-NPs were more efficient in alleviating lipogenesis, promoting lipolysis and reducing hepatocellular proliferation than free RSV due to its improved stability, water solubility and bioactivity. These findings indicated that the RSV-PLGA-NPs provided superb and stable drug delivery with small particle size, high capsulation efficiency, well-controlled drug release, which greatly enhanced the stability, water solubility and bioactivity. Besides, the discovery that the inhibitory effect of RSV-PLGA-NPs on hepatocellular proliferation and lipid accumulation in steatotic HepG2 cells may provide a new way to study the mechanism of NAFLD. Therefore, RSV-PLGA-NPs have a promising potential for NAFLD therapy.
Real or fake? Natural and artificial social stimuli elicit divergent behavioural and neural responses in mangrove rivulus,
Kryptolebias marmoratus
Authors: Li Cheng-Yu , Hofmann Hans A. , Harris Melissa L. , Earley Ryan L.
Published: November 2018

Understanding how the brain processes social information and generates adaptive behavioural responses is a major goal in neuroscience. We examined behaviour and neural activity patterns in socially relevant brain nuclei of hermaphroditic mangrove rivulus fish (
Kryptolebias marmoratus
) provided with different types of social stimuli: stationary model opponent, regular mirror, non-reversing mirror and live opponent. We found that: (i) individuals faced with a regular mirror were less willing to interact with, delivered fewer attacks towards and switched their orientation relative to the opponent more frequently than fish exposed to a non-reversing mirror image or live opponent; (ii) fighting with a regular mirror image caused higher expression of immediate-early genes (IEGs:
egr-1
and
c-Fos
) in the teleost homologues of the basolateral amygdala and hippocampus, but lower IEG expression in the preoptic area, than fighting with a non-reversing mirror image or live opponent; (iii) stationary models elicited the least behavioural and IEG responses among the four stimuli; and (iv) the non-reversing mirror image and live opponent drove similar behavioural and neurobiological responses. These results suggest that the various stimuli provide different types of information related to conspecific recognition in the context of aggressive contests, which ultimately drive different neurobiological responses.
Multiple paternity and number of offspring in mammals
Authors: Dobson F. Stephen , Abebe Ash , Correia Hannah E. , Kasumo Christian , Zinner Bertram
Published: November 2018

Many cooperative social attributes are being linked to characteristics of mating systems, particularly to the rate of multiple paternity that typifies a population. Under the logic that greater offspring production by females should engender greater competition among males to mate with females, it is predicted that multiple paternity should increase with litter sizes. We tested the predicted positive association of multiple paternity and litter size with a meta-analysis of 59 species of mammals. The probability of multiple paternity and mean litter size were positively correlated, but not significantly (
Zr
= 0.202). Also, the mean number of sires of litters increased with mean litter size, but not significantly (
Zr
= 0.235). We developed a combinatorial formula for the influence of number of male mates and litter size on the probability of multiple paternity. We used Bayesian Markov chain Monte Carlo simulations to generate an expectation for the form of the relationship between the probability of multiple paternity and mean litter size. Under the assumption of random samplings of numbers of mates, the expected association of the probability of multiple paternity and mean litter sizes among species was positive, curvilinear and relatively high. However, the empirical probabilities of multiple paternities were much less than expected, suggesting that behavioural factors (such as mating-associated behaviours) or ecological characteristics (such as population density) probably limit the number of male mates for reproductive females. The probability of multiple paternity in a population is an estimate of mating patterns that does not closely reflect the number of sires of individual litters. We suggest use of the estimated probability of mating success for males as an alternative measure of their contribution to the mating system.
Metrics matter: the effect of parasite richness, intensity and prevalence on the evolution of host migration
Authors: Shaw Allison K. , Sherman Julie , Barker F. Keith , Zuk Marlene
Published: November 2018

Parasites have long been thought to influence the evolution of migration, but precisely determining the conditions under which this occurs by quantifying costs of infection remains a challenge. Here we developed a model that demonstrates how the metric used to describe infection (richness/diversity, prevalence or intensity) shapes the prediction of whether migration will evolve. The model shows that predictions based on minimizing richness yield opposite results compared to those based on minimizing prevalence, with migration only selected for when minimizing prevalence. Consistent with these findings, empirical studies that measure parasite diversity typically find that migrants are worse off than residents, while those measuring prevalence or intensity find the opposite. Our own empirical analysis of fish parasite data finds that migrants (of all types) have higher parasite richness than residents, but with no significant difference in either prevalence or intensity.
Pseudomonas syringae: enterprising epiphyte and stealthy parasite
Authors: Arnold Dawn L. , Preston Gail M.
Published: November 2018

Pseudomonas syringae

is best known as a plant pathogenic bacterium that causes diseases in a multitude of hosts, and it has been used as a model organism to understand the biology of plant disease. Pathogenic and non-pathogenic isolates of

P. syringae

are also commonly found living as epiphytes and in the wider environment, including water sources such as rivers and precipitation. Ice-nucleating strains of

P. syringae

are associated with frost damage to crops. The genomes of numerous strains of

P. syringae

have been sequenced and molecular genetic studies have elucidated many aspects of this pathogen’s interaction with its host plants.
Phenome-wide Investigation of Health Outcomes Associated with Genetic Predisposition to Loneliness
Authors: Abdellaoui Abdel , Sanchez-Roige Sandra , Sealock Julia , Treur Jorien L. , Dennis Jessica , Fontanillas Pierre , Elson Sarah ,   The 23andme Research Team, Nivard Michel , Fung Ip Hill , der Zee Matthijs van , Baselmans Bart , Hottenga Jouke Jan , Willemsen Gonneke , Mosing Miriam , Yu Li , Pedersen Nancy L. , Amin Najaf , van Duijn Cornelia M , Szilagyi Ingrid , Tiemeier Henning , Neumann Alexander , Verweij Karin , Cacioppo Stephanie , Cacioppo John T. , Davis Lea K. , Palmer Abraham A. , Boomsma Dorret I.
Published: November 2018

Abstract

Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. While the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. While it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition towards loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we conducted a genome-wide association (GWAS) meta-analysis of loneliness (N=475,661), report 12 associated loci (two novel) and significant genetic correlations with 34 other complex traits. The polygenic basis for loneliness was significantly enriched for evolutionary constrained genes and genes expressed in specific brain tissues: (frontal) cortex, cerebellum, anterior cingulate cortex, and substantia nigra. We built polygenic scores based on this GWAS meta-analysis to explore the genetic association between loneliness and health outcomes in an independent sample of 18,498 individuals for whom electronic health records were available. A genetic predisposition towards loneliness predicted cardiovascular, psychiatric, and metabolic disorders, and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, effect of body fat on loneliness, and a similar weaker causal effect of BMI. Our results provide a framework for ongoing studies of the genetic basis of loneliness and its role in mental and physical health.
Drop-In Biofuel production by using fatty acid photodecarboxylase from Chlorella variabilis in the oleaginous yeast Yarrowia lipolytica
Authors: Bruder Stefan , Moldenhauer Eva Johanna , Lemke Robert Denis , Ledesma-Amaro Rodrigo , Kabisch Johannes
Published: November 2018

Background

Oleaginous yeasts are potent hosts for the renewable production of lipids and harbor great potential for derived products, such as biofuels. Several promising processes have been described that produce hydrocarbon drop-in biofuels based on fatty acid decarboxylation and fatty aldehyde decarbonylation. Unfortunately, besides fatty aldehyde toxicity and high reactivity, the most investigated enzyme, aldehyde-deformylating oxygenase, shows unfavorable catalytic properties which hindered high yields in previous metabolic engineering approaches.

Results

To demonstrate an alternative alkane production pathway for oleaginous yeasts, we describe the production of diesel-like, odd-chain alkanes and alkenes, by heterologously expressing a recently discovered light-driven oxidase from Chlorella variabilis (CvFAP) in Yarrowia lipolytica. Initial experiments showed that only strains engineered to have an increased pool of free fatty acids showed to be susceptible to sufficient decarboxylation. Providing these strains with glucose and light in a synthetic medium resulted in titers of 10.9 mg/L of hydrocarbons. Using custom 3D printed labware for lighting bioreactors, and an automated pulsed glycerol fed-batch strategy, intracellular titers of 58.7 mg/L were achieved.

Conclusions

Oleaginous yeasts such as Yarrowia lipolytica can transform renewable resources such as glycerol into fatty acids and lipids. By heterologously expressing a fatty acid photodecarboxylase from the algae Chlorella variabilis hydrocarbons were produced in several scales from microwell plate to 400 ml bioreactors. The developed bioprocess shows a route to the renewable production of hydrocarbons for a variety of applications ranging from representing a substrate for further enzymatic or chemical modification or as a drop-in biofuel blend.

Short abstract

Oleaginous yeasts are potent hosts for the renewable production of lipids, fatty acids and derived products such as biofuels. Here, we describe, the production of odd-numbered alkanes and alkenes with a length of 17 and 15 carbons by expression of a fatty acid photodecarboxylase (CvFAP) from Chlorella variabilis in different Yarrowia lipolytica strains under different regimes of blue light exposure in several scales from microwell plate to 400 ml bioreactors.
Cell-intrinsic Wnt4 controls early cDC1 commitment and suppresses development of pathogen-specific Type 2 immunity
Authors: Hung Li-Yin , Ji Yingbiao , Christian David A. , Herbine Karl R. , Pastore Christopher F. , Herbert De’Broski R.
Published: November 2018

Whether conventional dendritic cell (cDC) precursors acquire lineage-specific identity under direction of regenerative secreted glycoproteins within bone marrow niches is entirely unknown. Herein, we demonstrate that Wnt4, a beta-catenin independent Wnt ligand, is both necessary and sufficient for necessary for the full extent of pre-cDC1 specification within bone marrow. Cell-intrinsic Wnt4 deficiency in CD11c+ cells reduced mature cDC1 numbers in BM, spleen, lung, and intestine and, reciprocally, rWnt4 treatment promoted pJNK activation and cDC1 expansion. Lack of cell-intrinsic Wnt4 in mice CD11cCreWnt4flox/flox impaired stabilization of IRF8/cJun complexes in BM and increased the basal frequency of both cDC2 and ILC2 populations in the periphery. Accordingly, CD11c-restricted Wnt4 augmented Type 2 immunity against the hookworm parasite Nippostrongylus brasiliensis accompanied by increased interleukin 5 production relative to CD11cCre controls. Collectively, these data show previously unappreciated role for Wnt4 in DC commitment and pathogen-specific immunity.
A Scube2-Shh feedback loop links morphogen release and spread to morphogen signaling to enable scale invariant patterning of the ventral neural tube
Authors: Collins Zachary M. , Cha Anna , Qin Albert , Ishimatsu Kana , Tsai Tony Y.C. , Swinburne Ian A. , Li Pulin , Megason Sean G.
Published: November 2018

To enable robust patterning, morphogen systems should be resistant to variations in gene expression and tissue size. Here we explore how the Sonic Hedgehog (Shh) morphogen gradient in the ventral neural tube enables scaled patterning in embryos of varying sizes. Using zebrafish eggs that have been surgically reduced in size, we find that ventral neural tube patterning remains proportional in smaller embryos. Intriguingly, a secreted protein implicated in Shh release, Scube2, is expressed in the dorsal-intermediate neural tube far from Shh producing cells. Overexpression ofscube2expands the Shh gradient whereas loss ofscube2causes gradient contraction. Conversely, upregulation of Shh repressesscube2expression while Shh downregulation increasesscube2expression thus establishing a negative feedback loop. This regulatory feedback is necessary for scaling, as demonstrated by its loss inscube2overexpressing embryos. Using mathematical modeling, we show that feedback control on diffusion and release rates of Shh allows the morphogen gradient to be robust to differences in field length and Shh gene dosage. We conclude that Scube2 promotes release and diffusion of Shh to allow gradient scaling in an extension to the expander-repressor model.

Summary Statement

The Shh morphogen gradient can scale to different size tissues by feedback between Scube2 mediated release and diffusion of Shh and Shh based inhibition of Scube2 expression
The stem rust fungus Puccinia graminis f. sp. tritici induces centromeric small RNAs during late infection that direct genome-wide DNA methylation
Authors: Sperschneider Jana , Jones Ashley W. , Nasim Jamila , Xu Bo , Jacques Silke , Upadhyaya Narayana M. , Mago Rohit , Figueroa Melania , Singh Karam B. , Stone Eric A. , Schwessinger Benjamin , Wang Ming-Bo , Taylor Jennifer M. , Dodds Peter N.
Published: November 2018

Background

Silencing of transposable elements (TEs) is essential for maintaining genome stability. Plants use small RNAs (sRNAs) to direct DNA methylation to TEs (RNA-directed DNA methylation; RdDM). Similar mechanisms of epigenetic silencing in the fungal kingdom have remained elusive.

Results

We use sRNA sequencing and methylation data to gain insight into epigenetics in the dikaryotic fungus Puccinia graminis f. sp. tritici (Pgt), which causes the devastating stem rust disease on wheat. We use Hi-C data to define the Pgt centromeres and show that they are repeat-rich regions (∼250 kb) that are highly diverse in sequence between haplotypes and, like in plants, are enriched for young TEs. DNA cytosine methylation is particularly active at centromeres but also associated with genome-wide control of young TE insertions. Strikingly, over 90% of Pgt sRNAs and several RNAi genes are differentially expressed during infection. Pgt induces waves of functionally diversified sRNAs during infection. The early wave sRNAs are predominantly 21 nts with a 5’ uracil derived from genes. In contrast, the late wave sRNAs are mainly 22 nt sRNAs with a 5’ adenine and are strongly induced from centromeric regions. TEs that overlap with late wave sRNAs are more likely to be methylated, both inside and outside the centromeres, and methylated TEs exhibit a silencing effect on nearby genes.

Conclusions

We conclude that rust fungi use an epigenetic silencing pathway that resembles RdDM in plants. The Pgt RNAi machinery and sRNAs are under tight temporal control throughout infection and might ensure genome stability during sporulation.