bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of dietary and physical activity behaviours among women of reproductive age in urban Uganda, a qualitative study
Authors: Yiga Peter , Ogwok Patrick , Achieng Julian , Auma Mary Devota , Seghers Jan , Matthys Christophe
Published: October 2020

Objective:

To explore determinants of dietary and physical activity behaviours among women of reproductive age.

Design:

Data were collected through focus group discussions (FGD). The FGD guide was based on a modified theoretical framework; theory of planned behaviour was incorporated with constructs of health belief model, precaution adoption process model, social cognitive and social support theory. Discussions were audio recorded, transcribed verbatim and analysed thematically.

Setting:

Kampala, Uganda.

Participants:

Women were categorised into young adults; 18–34 years and adults; 35–45 years

Results:

Separate FGD with independent participants were conducted for dietary and physical activity behaviours until data saturation was achieved. Six FGD were conducted per behaviour. Determinants of dietary behaviours at intra-individual level included gaps in food skills, knowledge and self-efficacy, food safety concerns, convenience, finances and physiological satisfaction. The social-cultural norms were relationship between vegetable consumption and low social status, consideration of fruits as a snack for children and not food and habitual orientation towards carbohydrate foods. At environment level, social networks and increased availability of energy-dense, nutrient poor, street and processed foods influence dietary behaviour. For physical activity, intra-individual determinants were knowledge gaps and self-efficacy, while socio-cultural norms included gender stereotypes. Home (limited space and sedentary entertainment like social media and TV) and physical environment (cheap motorised transportation) influence physical activity.

Conclusion:

The existing cultural beliefs promote dietary and physical activity behaviours which are divergent from healthy recommendations. Therefore, a comprehensive intervention is needed to address socio-cultural misconceptions, financial and time limitations in urban Uganda.
A Factory Afield: Capitalism and Empire in John Locke's Political Economy
Authors: Pinheiro Lucas G.
Published: October 2020

Since the 1950s, interpreters of John Locke have debated whether his ideas about political economy figured among the intellectual sources of capitalist development. While some have labeled Locke a mercantile or agrarian “capitalist thinker,” others have insisted that, although a mercantilist, he was in no sense a theorist of capitalism. By reconstructing the relationship between Locke's ideas and the capitalist society of his day, this article challenges the prevailing terms through which commentators have traditionally interpreted his political economy and its place in the history of capitalism. I interpret Locke's perspectives on capital accumulation, foreign trade, and labor discipline throughout the 1690s as a reflection of the historical rise of export-oriented cycles of commodity manufacturing in the English countryside known as “proto-industrialization.” Moreover, I claim that, because proto-industrialization was tied to the expansion of England's colonial economy, this neglected context of Locke's economic doctrine sheds new light on his vision of empire. Looking to his writings on Ireland, I argue that Locke pursued proto-industrial economic reform by combining a hierarchical, stadial theory of progress with an imperial policy aimed at “improving” the colonies through decreed patterns of production and exchange that favored metropolitan trade.
The Great (Toilet) Paper Chase: Our Study of the 1979 San Francisco Bay Sewage Spill (As Motivated by Walter Cronkite and the CBS Evening News)
Authors: Oremland Ronald S. , Cloern James E.
Published: October 2020

Earth system science is boundless. There are no limits to the kinds of questions, problems, mysteries, or paradoxes that motivate our research and shape its direction. So how do we decide which directions to take, which questions to answer, what problems to solve? Sometimes our research is motivated by an unanticipated event requiring a degree of stochastic interpretive crystal ball gazing. Last year we ended our careers of more than four decades as life scientists at the USGS in Menlo Park, CA. We find ourselves in a state of reflection and want to share a story about a stochastic event that brought us together as collaborators, taught us essential lessons of life as research scientists, and seeded a friendship that endures.
Photonuclear Reactions in Lightning: 1. Verification and Modeling of Reaction and Propagation Processes
Authors: Wada Y. , Enoto T. , Nakazawa K. , Odaka H. , Furuta Y. , Tsuchiya H.
Published: October 2020

We report simulation results of photonuclear reactions in the atmosphere triggered by a downward terrestrial gamma ray flash in lightning. Possible channels of reactions in the atmosphere and their cross‐sections are verified with the ENDF/B‐VII.1 library. Monte Carlo simulations with two stages are then performed with the Geant4 framework. In the first stage, electrons following the relativistic runaway electron avalanche spectrum are produced in a mass model of the atmosphere, and production of photoneutrons and β+‐decay nuclei is calculated based on the nuclear data library. In total 1 × 1013 neutrons and 4 × 1012 β+‐decay nuclei are produced by 1018 energetic electrons above 1 MeV. In the second stage, propagation of the photoneutrons and positrons from the β+‐decay nuclei in the previous stage is calculated. As a result, we model on‐ground distributions of fluxes and energy spectra for neutrons, neutron‐related gamma rays, and annihilation ones. The simulation model is to be compared with photonuclear events detected in low‐charge‐center winter thunderstorms.
Resolving the Latitudinal Short‐Scale Gravity Field of Jupiter Using Slepian Functions
Authors: Parisi Marzia , Galanti Eli , Folkner William M. , Kaspi Yohai , Buccino Dustin R.
Published: October 2020

Early gravity measurements performed by the Juno spacecraft determined Jupiter's low‐degree gravity harmonics, including the first estimate of the planet's north‐south asymmetric field. The retrieved information was used to infer that the strong zonal winds visible at the cloud tops must extend down a few thousand kilometers, where they are suppressed in the deep interior. The next frontier for the Juno gravity experiment includes, among other goals, the determination of Jupiter's small‐scale gravity field with high accuracy, and its relation to atmospheric circulation at shorter length scales. The geometry of the Juno closest approaches to the planet poses a challenge to this task, as they span latitudes between 4°N and 29°N over the course of the nominal mission. Since Doppler measurements are the most sensitive to gravity anomalies when the spacecraft is close to the body, observations of Jupiter's gravity field are mostly concentrated in the northern hemisphere, while the traditional spherical harmonic functions are not orthonormal over a latitudinal subdomain. Here we define customized Slepian functions, which are orthogonal in a specific latitude range and are optimized to represent Jupiter's local surface gravity at north latitudes. We show that with the new functions, the short‐scale latitudinal variability of the gravity field is resolved with high accuracy between 15°S and 45°N latitude. Furthermore, preliminary results show that the estimated values for the Slepian coefficients from the Juno data match the predictions obtained using thermal wind balance to relate the dynamical density anomalies and the winds with an optimized scale height.
Secondary research use of personal medical data: attitudes from patient and population surveys in The Netherlands and Germany
Authors: Richter Gesine , Borzikowsky Christoph , Lesch Wiebke , Semler Sebastian C. , Bunnik Eline M. , Buyx Alena , Krawczak Michael
Published: October 2020

Making routine clinical-care-data available for medical research requires adequate consent to legitimize use and exchange. While, public interest in supporting medical research is increasing, individuals often find it difficult to actively enable researchers to access their data. In addition to broad consent, the idea of (consent-free) data donation has been brought into play as another way to legitimize secondary research use of medial data. However, flanking the implementation of broad consent policies or data donation, the attitude of patients, and the general public toward different aspects of these approaches needs to be assessed. We conducted two empirical studies to this end among Dutch patients (n = 7430) and representative German citizens (n = 1006). Wide acceptance of broad consent was observed among Dutch patients (92.3%), corroborating previous findings among German patients (93.0%). Moreover, 28.8% of the Dutch patients generally approved secondary data-use for non-academic research, 42.3% would make their decision dependent upon the type of institution in question. In the German survey addressing the general population, 78.8% approved data donation without explicit consent as an alternative model of legitimization, the majority of those who approved (96.7%) would allow donated data to be used by universities and public research institutions. This willingness to support contrasted sharply with the fact that only 16.6% would allow access to the data by industry. Our findings thus not only add empirical evidence to the debate about broad consent and data donation, but also suggest that widespread public discussion and education about the role of industry in medical research is necessary in that context.
Non-invasive molecularly-specific millimeter-resolution manipulation of brain circuits by ultrasound-mediated aggregation and uncaging of drug carriers
Authors: Ozdas Mehmet S. , Shah Aagam S. , Johnson Paul M. , Patel Nisheet , Marks Markus , Yasar Tansel Baran , Stalder Urs , Bigler Laurent , von der Behrens Wolfger , Sirsi Shashank R. , Yanik Mehmet Fatih
Published: October 2020

Non-invasive, molecularly-specific, focal modulation of brain circuits with low off-target effects can lead to breakthroughs in treatments of brain disorders. We systemically inject engineered ultrasound-controllable drug carriers and subsequently apply a novel two-component Aggregation and Uncaging Focused Ultrasound Sequence (AU-FUS) at the desired targets inside the brain. The first sequence aggregates drug carriers with millimeter-precision by orders of magnitude. The second sequence uncages the carrier’s cargo locally to achieve high target specificity without compromising the blood-brain barrier (BBB). Upon release from the carriers, drugs locally cross the intact BBB. We show circuit-specific manipulation of sensory signaling in motor cortex in rats by locally concentrating and releasing a GABAA receptor agonist from ultrasound-controlled carriers. Our approach uses orders of magnitude (1300x) less drug than is otherwise required by systemic injection and requires very low ultrasound pressures (20-fold below FDA safety limits for diagnostic imaging). We show that the BBB remains intact using passive cavitation detection (PCD), MRI-contrast agents and, importantly, also by sensitive fluorescent dye extravasation and immunohistochemistry.
Redox-triggered switching in three-dimensional covalent organic frameworks
Authors: Gao Chao , Li Jian , Yin Sheng , Sun Junliang , Wang Cheng
Published: October 2020

The tuning of molecular switches in solid state toward stimuli-responsive materials has attracted more and more attention in recent years. Herein, we report a switchable three-dimensional covalent organic framework (3D COF), which can undergo a reversible transformation through a hydroquinone/quinone redox reaction while retaining the crystallinity and porosity. Our results clearly show that the switching process gradually happened through the COF framework, with an almost quantitative conversion yield. In addition, the redox-triggered transformation will form different functional groups on the pore surface and modify the shape of pore channel, which can result in tunable gas separation property. This study strongly demonstrates 3D COFs can provide robust platforms for efficient tuning of molecular switches in solid state. More importantly, switching of these moieties in 3D COFs can remarkably modify the internal pore environment, which will thus enable the resulting materials with interesting stimuli-responsive properties.
Mendelian randomization while jointly modeling cis genetics identifies causal relationships between gene expression and lipids
Authors: van der Graaf Adriaan , Claringbould Annique , Rimbert Antoine ,   BIOS Consortium, Heijmans Bastiaan T. , Hoen Peter A. C.’t , van Meurs Joyce B. J. , Jansen Rick , Franke Lude , Westra Harm-Jan , Li Yang , Wijmenga Cisca , Sanna Serena
Published: October 2020

Inference of causality between gene expression and complex traits using Mendelian randomization (MR) is confounded by pleiotropy and linkage disequilibrium (LD) of gene-expression quantitative trait loci (eQTL). Here, we propose an MR method, MR-link, that accounts for unobserved pleiotropy and LD by leveraging information from individual-level data, even when only one eQTL variant is present. In simulations, MR-link shows false-positive rates close to expectation (median 0.05) and high power (up to 0.89), outperforming all other tested MR methods and coloc. Application of MR-link to low-density lipoprotein cholesterol (LDL-C) measurements in 12,449 individuals with expression and protein QTL summary statistics from blood and liver identifies 25 genes causally linked to LDL-C. These include the known SORT1 and ApoE genes as well as PVRL2, located in the APOE locus, for which a causal role in liver was not known. Our results showcase the strength of MR-link for transcriptome-wide causal inferences.
Local-scale Arctic tundra heterogeneity affects regional-scale carbon dynamics
Authors: Lara M. J. , McGuire A. D. , Euskirchen E. S. , Genet H. , Yi S. , Rutter R. , Iversen C. , Sloan V. , Wullschleger S. D.
Published: October 2020

In northern Alaska nearly 65% of the terrestrial surface is composed of polygonal ground, where geomorphic tundra landforms disproportionately influence carbon and nutrient cycling over fine spatial scales. Process-based biogeochemical models used for local to Pan-Arctic projections of ecological responses to climate change typically operate at coarse-scales (1km2–0.5°) at which fine-scale (<1km2) tundra heterogeneity is often aggregated to the dominant land cover unit. Here, we evaluate the importance of tundra heterogeneity for representing soil carbon dynamics at fine to coarse spatial scales. We leveraged the legacy of data collected near Utqiaġvik, Alaska between 1973 and 2016 for model initiation, parameterization, and validation. Simulation uncertainty increased with a reduced representation of tundra heterogeneity and coarsening of spatial scale. Hierarchical cluster analysis of an ensemble of 21st-century simulations reveals that a minimum of two tundra landforms (dry and wet) and a maximum of 4km2 spatial scale is necessary for minimizing uncertainties (<10%) in regional to Pan-Arctic modeling applications.
Nano polarimetry: enhanced AFM-NSOM triple-mode polarimeter tip
Authors: Karelits Matityahu , Zalevsky Zeev , Karsenty Avi
Published: October 2020

A novel application of a combined and enhanced NSOM-AFM tip-photodetector system resulted in a nanoscale Polarimeter, generated by four different holes, each sharing a different shape, and enabling that the four photonic readouts forming the tip will be the four Stokes coefficients, this in order to place the polarization state in the Poincare sphere. The new system has been built on standard Atomic Force Microscope (AFM) cantilever, in order to serve as a triple-mode scanning system, sharing complementary scanning topography, optical data analysis and polarization states. This new device, which has been designed and simulated using Comsol Multi-Physics software package, consists in a Platinum-Silicon drilled conical photodetector, sharing subwavelength apertures, and has been processed using advanced nanotechnology tools on a commercial silicon cantilever. After a comparison study of drilled versus filled tips advantages, and of several optics phenomena such as interferences, the article presents the added value of multiple-apertures scanning tip for nano-polarimetry.
Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19
Authors: Cho Junhyung , Lee Young Jae , Kim Je Hyoung , Kim Sang il , Kim Sung Soon , Choi Byeong-Sun , Choi Jang-Hoon
Published: October 2020

The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, patients with COVID-19 and comorbidities such as hypertension and cardiac diseases have a higher mortality rate. An efficient strategy in response to this issue is repurposing drugs with antiviral activity for therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases that have antiviral activity against several coronaviruses. Thus, we aimed to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentrations (IC50) of DIG and OUA were determined at a nanomolar concentration. Progeny virus titers of single-dose treatment of DIG, OUA and remdesivir were approximately 103-, 104- and 103-fold lower (> 99% inhibition), respectively, than that of non-treated control or chloroquine at 48 h post-infection (hpi). Furthermore, therapeutic treatment with DIG and OUA inhibited over 99% of SARS-CoV-2 replication, leading to viral inhibition at the post entry stage of the viral life cycle. Collectively, these results suggest that DIG and OUA may be an alternative treatment for COVID-19, with potential additional therapeutic effects for patients with cardiovascular disease.
Differential expression of miRNAs in skeletal muscles of Indian sheep with diverse carcass and muscle traits
Authors: Kaur Mandeep , Kumar Ashish , Siddaraju Naveen Kumar , Fairoze Mohamed Nadeem , Chhabra Pooja , Ahlawat Sonika , Vijh Ramesh Kumar , Yadav Anita , Arora Reena
Published: October 2020

The study presents the miRNA profiles of two Indian sheep populations with divergent carcass and muscle traits. The RNA sequencing of longissimus thoracis muscles from the two populations revealed a total of 400 known miRNAs. Myomirs or miRNAs specific to skeletal muscles identified in our data included oar-miR-1, oar-miR-133b, oar-miR-206 and oar-miR-486. Comparison of the two populations led to identification of 100 differentially expressed miRNAs (p < 0.05). A total of 45 miRNAs exhibited a log2 fold change of ≥ ( ±) 3.0. Gene Ontology analysis revealed cell proliferation, epithelial to mesenchymal transition, apoptosis, immune response and cell differentiation as the most significant functions of the differentially expressed miRNAs. The differential expression of some miRNAs was validated by qRT-PCR analysis. Enriched pathways included metabolism of proteins and lipids, PI3K-Akt, EGFR and cellular response to stress. The microRNA-gene interaction network revealed miR-21, miR-155, miR-143, miR-221 and miR-23a as the nodal miRNAs, with multiple targets. MicroRNA-21 formed the focal point of the network with 42 interactions. The hub miRNAs identified in our study form putative regulatory candidates for future research on meat quality traits in Indian sheep. Our results provide insight into the biological pathways and regulatory molecules implicated in muscling traits of sheep.
STAT3 deficiency in B cells exacerbates uveitis by promoting expansion of pathogenic lymphocytes and suppressing regulatory B cells (Bregs) and Tregs
Authors: Oladipupo Favour O. , Yu Cheng-Rong , Olumuyide Ezekiel , Jittaysothorn Yingyos , Choi Jin Kyeong , Egwuagu Charles E.
Published: October 2020

STAT3 transcription factor induces differentiation of naïve T cells into Th17 cells and loss of STAT3 in T cell prevents development of CNS autoimmune diseases. However, function of STAT3 in the B lymphocyte subset is not well understood. In this study, we have generated mice lacking STAT3 in CD19+B cells (CD19-STAT3KO) and investigated intrinsic and extrinsic functions of STAT3 in B cells and its potential role in resistance or pathogenesis of organ-specific autoimmune diseases. We show that STAT3 regulates metabolic mechanisms in B cells with implications for bioenergetic and metabolic pathways that control cellular homeostasis in B cells. Thus, loss of STAT3 in CD19-STAT3KO cells perturbed growth and apoptosis by inducing rapid entry of B cells into the S-phase of the cell cycle, decreasing expression of cyclin-dependent kinase inhibitors and upregulating pro-apoptotic proteins. We further show that the CD19-STAT3KO mice develop severe experimental autoimmune uveitis (EAU), an animal model of human uveitis. Exacerbated uveitis in CD19-STAT3KO mice derived in part from enhanced expression of costimulatory molecules on B cells, marked increase of Th17 responses and increased recruitment of granulocytes into the neuroretina. The enhanced autoimmunity upon deletion of STAT3 in B cells is also recapitulated in experimental autoimmune encephalitis, a mouse model of multiple sclerosis and thus support our conclusion that STAT3 deletion in B cells enhanced inflammation and the effects observed are not model specific. Our data further indicate that STAT3 pathway modulates interactions between B and T cells during EAU resulting in alteration of lymphocyte repertoire by increasing levels of autoreactive pathogenic T cells while suppressing development and/or expansion of immune-suppressive lymphocytes (Bregs and Tregs). Taken together, STAT3 exerts diametrically opposite effects in lymphocytes, with loss of STAT3 in B cells exacerbating uveitis whereasStat3deletion in T cells confers protection.
Accuracy of endobronchial ultrasound-guided transbronchial needle aspiration in HIV-infected patients with thoracic lymphadenopathy in a tuberculosis low-burden area
Authors: Tetart Macha , Betraoui Farid , Huleux Thomas , Wallyn Frédéric , Brichet Anne , Thill Pauline , Robineau Olivier , Meybeck Agnès
Published: October 2020

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an innovative technique to explore hilar and mediastinal lymphadenopathy. We aimed to assess its diagnostic accuracy in HIV-infected patients in a tuberculosis low-burden area. A retrospective review was performed of all HIV-infected patients with thoracic lymphadenopathy referred for EBUS-TBNA between January 2012 and January 2019 in 3 Northern French Hospitals. A total of 15 patients was included during the study period. Our patients were predominantly male (80%), with a mean age of 50 ± 11 years. Six patients (43%) had a CD4 cells count of less than 200/mm3. Eleven patients (73%) were receiving antiretroviral therapy, and 7 (47%) reached undetectable viral load. Adequate lymphnode sampling was accomplished in all patients. No serious complications were reported. EBUS-TBNA led to a definitive diagnosis in 12 out of 15 patients (80%). It identified 4 neoplasia, 3 atypical mycobacterial diseases, 2 tuberculosis, 1 Castleman disease, 1 sarcoidosis, and 1 professional dustiness. In 3 cases, sampling revealed normal lymphoid tissue. Active surveillance confirmed the suspected diagnosis of HIV adenitis with regression of lymphadenopathy on antiretroviral therapy in 2 cases. In one case of negative sampling, thoracoscopy led to the diagnosis of tuberculosis. In our cohort, accuracy of EBUS-TBNA was 92%. EBUS-TBNA appeared to be a safe and accurate tool in the investigation of mediastinal lymphadenopathy in HIV-infected patients in settings of tuberculosis low-prevalence. It can avoid more invasive procedures such as mediastinoscopy.
The application of single-port laparoscopic percutaneous internal ring suture for the management of indirect inguinal hernia in female adults
Authors: Wang Shih-Hsien , Yen Ju-Bei , Hsu Sheng-Lung
Published: October 2020

As most of the female inguinal hernias are of indirect type, we conducted this retrospective study to evaluate whether the single port laparoscopic percutaneous internal ring suture is feasible for the management of indirect inguinal hernia in female adults. From April 2016 to August 2019, there were 31 female adults who were diagnosed with inguinal hernias and received laparoscopic inspection at our surgical department. One patient who was finally diagnosed as an encysted hydrocele was excluded from the statistic study. All the 30 cases were of indirect type with a total of 35 single port laparoscopic percutaneous internal ring sutures performed. The median age was 38 years (range 20–88 years). The number and percentage of patients with right, left and bilateral hernias were 17 (56%), 11 (37%) and 2 (7%) respectively. Three contralateral patent processi vaginalium and 1 occult femoral hernia were found during operation. The percentages of the respective classifications according to the European Hernia Society system for the 35 PIRSs were L1: 40%, L2: 49%, and L3: 11%. The average operation time was 18 min for unilateral and 30 min for bilateral hernias. There were 1 recurrence and 1 chronic postoperative inguinal pain. Both had their symptoms and signs resolved after reoperation. The mean follow-up period was 13.6 months. We concluded that the single-port laparoscopic percutaneous internal ring suture is feasible for the management of indirect inguinal hernia in female adults.
Reproductive characteristics of American bullfrogs (Lithobates catesbeianus) in their invasive range of the Pacific Northwest, USA
Authors: Urbina Jenny , Bredeweg Evan M. , Cousins Christopher , Blaustein Andrew R. , Garcia Tiffany S.
Published: October 2020

Invasive species pose a major threat to global biodiversity. The effects of invasive species can be strongly influenced and potentially mediated by their reproductive characteristics, such as fecundity, egg production, and duration and number of reproductive events. Selection for smaller body size at first reproduction can also play a role in their establishment, facilitating colonization and spread. The American bullfrog, native to the eastern U.S. (Lithobates catesbeianus), is a species that has invaded more than 40 countries across 4 continents. This species has become especially prevalent in the western United States since its introduction in the early 1900s. This study characterized reproductive characteristics of bullfrogs with emphasis on the minimum size at which males and females reach sexual maturity in the Willamette Valley, Oregon, USA invasion range. We collected and dissected 121 individuals in 2013 and 2017, quantifying characteristics of sexual maturity including snout-vent length, total length, sex, tympanum diameter, presence of distended oviducts or eggs for females, and testes length and sperm activity in males. Our results showed that the minimum reproductive size of both males and females was smaller relative to bullfrogs in their native range as well as in populations across their invasive range. Reduction in size at reproductive maturity is likely impacting the invasive success of American bullfrogs and this study gives us insight on management actions to control the invasion. Applying this insight, managers can adjust their definition of reproductively active adults, increasing the target population of culling and other control methods.
Metal ions shape α-synuclein
Authors: Moons Rani , Konijnenberg Albert , Mensch Carl , Van Elzen Roos , Johannessen Christian , Maudsley Stuart , Lambeir Anne-Marie , Sobott Frank
Published: October 2020

α-Synuclein is an intrinsically disordered protein that can self-aggregate and plays a major role in Parkinson’s disease (PD). Elevated levels of certain metal ions are found in protein aggregates in neurons of people suffering from PD, and environmental exposure has also been linked with neurodegeneration. Importantly, cellular interactions with metal ions, particularly Ca2+, have recently been reported as key for α-synuclein’s physiological function at the pre-synapse. Here we study effects of metal ion interaction with α-synuclein at the molecular level, observing changes in the conformational behaviour of monomers, with a possible link to aggregation pathways and toxicity. Using native nano-electrospray ionisation ion mobility-mass spectrometry (nESI-IM-MS), we characterize the heterogeneous interactions of alkali, alkaline earth, transition and other metal ions and their global structural effects on α-synuclein. Different binding stoichiometries found upon titration with metal ions correlate with their specific binding affinity and capacity. Subtle conformational effects seen for singly charged metals differ profoundly from binding of multiply charged ions, often leading to overall compaction of the protein depending on the preferred binding sites. This study illustrates specific effects of metal coordination, and the associated electrostatic charge patterns, on the complex structural space of the intrinsically disordered protein α-synuclein.
Reconstruction and analysis of genome-scale metabolic model of weak Crabtree positive yeast Lachancea kluyveri
Authors: Nanda Piyush , Patra Pradipta , Das Manali , Ghosh Amit
Published: October 2020

Lachancea kluyveri, a weak Crabtree positive yeast, has been extensively studied for its unique URC pyrimidine catabolism pathway. It produces more biomass than Saccharomyces cerevisiae due to the underlying weak Crabtree effect and resorts to fermentation only in oxygen limiting conditions that renders it as a suitable industrial host. The yeast also produces ethyl acetate as a major overflow metabolite in aerobic conditions. Here, we report the first genome-scale metabolic model, iPN730, of L. kluyveri comprising of 1235 reactions, 1179 metabolites, and 730 genes distributed in 8 compartments. The in silico viability in different media conditions and the growth characteristics in various carbon sources show good agreement with experimental data. Dynamic flux balance analysis describes the growth dynamics, substrate utilization and product formation kinetics in various oxygen-limited conditions. We have also demonstrated the effect of switching carbon sources on the production of ethyl acetate under varying oxygen uptake rates. A phenotypic phase plane analysis described the energetic cost penalty of ethyl acetate and ethanol production on the specific growth rate of L. kluyveri. We generated the context specific models of L. kluyveri growing on uracil or ammonium salts as the sole nitrogen source. Differential flux calculated using flux variability analysis helped us in highlighting pathways like purine, histidine, riboflavin and pyrimidine metabolism associated with uracil degradation. The genome-scale metabolic construction of L. kluyveri will provide a better understanding of metabolism behind ethyl acetate production as well as uracil catabolism (pyrimidine degradation) pathway. iPN730 is an addition to genome-scale metabolic models of non-conventional yeasts that will facilitate system-wide omics analysis to understand fungal metabolic diversity.
Pharmacokinetic prediction of an antibody in mice based on an in vitro cell-based approach using target receptor-expressing cells
Authors: Noguchi Yuki , Ozeki Kazuhisa , Akita Hidetaka
Published: October 2020

In vivo pharmacokinetics (PK) studies using mice and monkeys are the main approaches for evaluating and predicting the PK of antibodies, and there is a strong demand for methods that do not require animal experiments. In this work, we focused on quantitatively predicting the nonlinear PK of an antibody based on cell-based assays. An anti-mouse Fc gamma receptor IIB antibody was used as a model antibody. To determine the PK parameters related to nonspecific elimination in vivo, the plasma concentration profile at 100 mg/kg, at which target-specific clearance is saturated, was analyzed by a 2-compartment model. To estimate the parameters related to target-specific elimination, the Michaelis–Menten constant (Km) and the maximum elimination rate (Vmax) were determined by an uptake assay using Chinese hamster ovary (CHO) cells expressing the target receptor. Finally, the integration of all of these parameters permitted the PK to be predicted at doses ranging from 1 to 100 mg/kg regardless of whether target-specific clearance was saturated or nonsaturated. The findings presented herein show that in vitro assays using target-expressing cells are useful tools for obtaining PK parameters and predicting PK profiles and, in some cases, eliminate the need for in vivo PK studies using experimental animals.
Integrated transcriptomic and metabolomic data reveal the flavonoid biosynthesis metabolic pathway in Perilla frutescens (L.) leaves
Authors: Jiang Tao , Guo Kunyuan , Liu Lingdi , Tian Wei , Xie Xiaoliang , Wen Saiqun , Wen Chunxiu
Published: October 2020

Perilla frutescens (L.) is an important medicinal and edible plant in China with nutritional and medical uses. The extract from leaves of Perilla frutescens contains flavonoids and volatile oils, which are mainly used in traditional Chinese medicine. In this study, we analyzed the transcriptomic and metabolomic data of the leaves of two Perilla frutescens varieties: JIZI 1 and JIZI 2. A total of 9277 differentially expressed genes and 223 flavonoid metabolites were identified in these varieties. Chrysoeriol, apigenin, malvidin, cyanidin, kaempferol, and their derivatives were abundant in the leaves of Perilla frutescens, which were more than 70% of total flavonoid contents. A total of 77 unigenes encoding 15 enzymes were identified as candidate genes involved in flavonoid biosynthesis in the leaves of Perilla frutescens. High expression of the CHS gene enhances the accumulation of flavonoids in the leaves of Perilla frutescens. Our results provide valuable information on the flavonoid metabolites and candidate genes involved in the flavonoid biosynthesis pathways in the leaves of Perilla frutescens.
Candidate gene mapping identifies genomic variations in the fire blight susceptibility genes HIPM and DIPM across the Malus germplasm
Authors: Tegtmeier Richard , Pompili Valerio , Singh Jugpreet , Micheletti Diego , Silva Katchen Julliany Pereira , Malnoy Mickael , Khan Awais
Published: October 2020

Development of apple (Malus domestica) cultivars resistant to fire blight, a devastating bacterial disease caused by Erwinia amylovora, is a priority for apple breeding programs. Towards this goal, the inactivation of members of the HIPM and DIPM gene families with a role in fire blight susceptibility (S genes) can help achieve sustainable tolerance. We have investigated the genomic diversity of HIPM and DIPM genes in Malus germplasm collections and used a candidate gene-based association mapping approach to identify SNPs (single nucleotide polymorphisms) with significant associations to fire blight susceptibility. A total of 87 unique SNP variants were identified in HIPM and DIPM genes across 93 Malus accessions. Thirty SNPs showed significant associations (p < 0.05) with fire blight susceptibility traits, while two of these SNPs showed highly significant (p < 0.001) associations across two different years. This research has provided knowledge about genetic diversity in fire blight S genes in diverse apple accessions and identified candidate HIPM and DIPM alleles that could be used to develop apple cultivars with decreased fire blight susceptibility via marker-assisted breeding or biotechnological approaches.
Distinct phenolic, alkaloid and antioxidant profile in betel quids from four regions of Indonesia
Authors: Sari Elizabeth Fitriana , Prayogo Grace Puspita , Loo Yit Tao , Zhang Pangzhen , McCullough Michael John , Cirillo Nicola
Published: October 2020

Betel quid (BQ) is a chewing mixed package that mainly contains areca nut (AN), betel leaf (Leaf) or betel stem inflorescence (SI), and slaked lime, and is consumed with or without tobacco BQ chewing is common in South East Asia and has been strongly associated with malignant and potentially malignant diseases of the oral cavity. Alkaloids such as arecoline are often accounted for the carcinogenic potential of BQ, however the chemical composition of BQ has not been studied in detail. In the current study, we investigated the total phenolic content (TPC), antioxidant activity (by mean of ferric reducing antioxidant power, FRAP), radical scavenging activity (DPPH test), polyphenolic profile and arecoline content in different components of BQ, namely AN, Leaf or SI, Husk, and blended BQ (BQ mix, containing AN, Leaf or SI and slaked lime). Samples were imported from 4 major regions of Indonesia, namely: Banda Aceh (BA), North Sumatra (NS), West Kalimantan (WK) and West Papua (WP). The highest TPC, FRAP, and DPPH values were detected in AN samples compared to other BQ components, while samples from WP region were of higher values compared to the other regions. High performance liquid chromatography—Mass Spectrometry (LC–MS) analysis showed that Husk contains the widest range of polyphenols, including hydroxybenzoic acids, hydroxycinnamic acids, flavanols, flavonols and stilbenes. Catechin and epicatechin were the main polyphenols detected in BQ, and they were present at the highest concentrations in WP–AN sample. Arecoline was detected in all AN and BQ mix samples and was significantly correlated with catechin and epicatechin, and significantly negatively correlated withp-hydroxybenzoic acid. Notably, arecoline concentration changed significantly when AN was blended in BQ mixtures. The current study is the first to extensively characterise the chemical composition of BQ and provides insight for a better understanding of the interactions of BQ alkaloids and phenolics in the development of oral submucous fibrosis and oral cancer.
Tunneling-induced optical limiting in quantum dot molecules
Authors: Veisi Mohadeseh , Kazemi Seyedeh Hamideh , Mahmoudi Mohammad
Published: October 2020

We present a convenient way to obtain an optical power limiting behavior in a quantum dot molecule system, induced by an interdot tunneling. Also, the effect of system parameters on the limiting performance is investigated; interestingly, the tunneling rate can affect the limiting performance of the system so that the threshold of the limiting behavior can be a function of the input voltage, allowing the optimization of the limiting action. Furthermore, by investigating the absorption of the probe field, it is demonstrated that the optical limiting is due to a reverse saturable absorption mechanism; indeed, analytical results show that this mechanism is based on a cross-Kerr optical nonlinearity induced by the tunneling. Additionally, the limiting properties of the system are studied by using a Z-scan technique.
Midterm outcomes of LAA occlusion with the AMPLATZER Cardiac Plug and AMPLATZER Amulet devices in a high-risk cohort
Authors: Tichelbäcker Tobias , Scherner L. , Puls M. , Schillinger W. , Adler C. , Baldus S. , Jacobshagen C. , Hünlich M.
Published: October 2020

LAA occlusion has become a favourable option in patients with atrial fibrillation not eligible for oral anticoagulation therapy. Proof of effectiveness of LAA closure devices in a midterm follow-up period. This retrospective single-center cohort study analysed outcome in patients treated with AMPLATZER Cardiac Plug or AMPLATZER Amulet device. A standardized follow-up by phone call focusing on data of death, stroke and bleeding events was performed. Routine antiplatelet strategy was DAPT for 3 months post procedural. 212 patients (mean age 77 ± 6 years) were included. Follow up was performed in 197 (93%) patients. Patients were at high risk for thromboembolic or bleeding events (prior stroke/TIA 29%; prior bleeding 54%. Overall, there was a mean follow-up period of 1244.2 days (± 756.7) and a total of 674 patient years. We observed 25 events later than day 8 post procedure. We were able to demonstrate a high effectiveness of the AMPLATZER Cardiac Plug/AMPLATZER Amulet devices regarding the prevention of stroke and bleedings in a high-risk real-world cohort during a midterm follow-up period. Overall, we observed remarkably lower rates of stroke and bleedings as predicted with CHA2DS2–VASc and HASBLED scores.
Study in circular auxetic structures for efficiency enhancement in piezoelectric vibration energy harvesting
Authors: Eghbali Pejman , Younesian Davood , Moayedizadeh Armin , Ranjbar Mostafa
Published: October 2020

Piezoelectric (PZT) components are one of the most popular elements in vibration sensing and also energy harvesting. They are very well established, cost effective and available in different geometries however there are still several challenges in their application particularly in vibration energy harvesting. They are normally narrow-band elements and work in high-frequency range. Their efficiency and power extraction density are also generally low compared with different electromagnetic techniques. Auxetic structures are proposed here to enhance efficiency of the piezoelectric circular patches in vibration energy harvesting. These kinds of patches namely PZT buzzers are inexpensive (less than 10 USD) elements and easily available. Two novel circular auxetic substrates are proposed to improve power extraction capacity of the conventional piezoelectric buzzers. Negative Poison’s ratio of the proposed meta-structure helps in efficiency enhancement. The concept is introduced, analyzed and verified through the finite element modeling and experimental testing. The idea is proved to work by comparing the harvested electrical power in the auxetic design against the conventional plain system. A parametric study is then carried out and effects of important electrical and geometrical parameters as well as the material property on the power extraction efficiency are assessed to arrive at optimum parameters. It is shown that by employing the auxetic design, a remarkable improvement in the harvested power is achievable. It is shown that for the two proposed auxetic designs, at the resonance frequency, we could reach to 10.2 and 13.3 magnification factor with respect to the plain energy harvester. Another important feature is that the resonant frequency in these new designs is very much lower than the conventional resonators. Results of this study can open a new path to application of inexpensive PZT buzzers in large-scale vibration energy harvesting.
A novel and convenient method to evaluate bone cement distribution following percutaneous vertebral augmentation
Authors: Liu Jin , Tang Jing , Liu Hao , Gu Zuchao , Zhang Yu , Yu Shenghui
Published: October 2020

A convenient method to evaluate bone cement distribution following vertebral augmentation is lacking, and therefore so is our understanding of the optimal distribution. To address these questions, we conducted a retrospective study using data from patients with a single-segment vertebral fracture who were treated with vertebral augmentation at our two hospitals. Five evaluation methods based on X-ray film were compared to determine the best evaluation method and the optimal cement distribution. Of the 263 patients included, 49 (18.63%) experienced re-collapse of treated vertebrae and 119 (45.25%) experienced new fractures during follow-up. A 12-score evaluation method (kappa value = 0.652) showed the largest area under the receiver operating characteristic curve for predicting new fractures (0.591) or re-collapse (0.933). In linear regression with the 12-score method, the bone cement distribution showed a negative correlation with the re-collapse of treated vertebra, but it showed a weak correlation with new fracture. The two prediction curves intersected at a score of 10. We conclude that an X-ray-based method for evaluation of bone cement distribution can be convenient and practical, and it can reliably predict risk of new fracture and re-collapse. The 12-score method showed the strongest predictive power, with a score of 10 suggesting optimal bone cement distribution.
Ultraviolet-B acclimation is supported by functionally heterogeneous phenolic peroxidases
Authors: Rácz Arnold , Czégény Gyula , Csepregi Kristóf , Hideg Éva
Published: October 2020

Tobacco plants were grown in plant chambers for four weeks, then exposed to one of the following treatments for 4 days: (1) daily supplementary UV-B radiation corresponding to 6.9 kJ m−2 d−1 biologically effective dose (UV-B), (2) daily irrigation with 0.1 mM hydrogen peroxide, or (3) a parallel application of the two treatments (UV-B + H2O2). Neither the H2O2 nor the UV-B treatments were found to be damaging to leaf photosynthesis. Both single factor treatments increased leaf H2O2 contents but had distinct effects on various H2O2 neutralising mechanisms. Non-enzymatic H2O2 antioxidant capacities were increased by direct H2O2 treatment only, but not by UV-B. In contrast, enzymatic H2O2 neutralisation was mostly increased by UV-B, the responses showing an interesting diversity. When class-III peroxidase (POD) activity was assayed using an artificial substrate (ABTS, 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)), both treatments appeared to have a positive effect. However, only UV-B-treated leaves showed higher POD activities when phenolic compounds naturally occurring in tobacco leaves (chlorogenic acid or quercetin) were used as substrates. These results demonstrate a substrate-dependent, functional heterogeneity in POD and further suggest that the selective activation of specific isoforms in UV-B acclimated leaves is not triggered by excess H2O2 in these leaves.
BRAF status modulates Interelukin-8 expression through a CHOP-dependent mechanism in colorectal cancer
Authors: Conciatori Fabiana , Bazzichetto Chiara , Amoreo Carla Azzurra , Sperduti Isabella , Donzelli Sara , Diodoro Maria Grazia , Buglioni Simonetta , Falcone Italia , Shirasawa Senji , Blandino Giovanni , Ferretti Gianluigi , Cognetti Francesco , Milella Michele , Ciuffreda Ludovica
Published: October 2020

Inflammation might substantially contribute to the limited therapeutic success of current systemic therapies in colorectal cancer (CRC). Amongst cytokines involved in CRC biology, the proinflammatory chemokine IL-8 has recently emerged as a potential prognostic/predictive biomarker. Here, we show that BRAF mutations and PTEN-loss are associated with high IL-8 levels in CRC models in vitro and that BRAF/MEK/ERK, but not PI3K/mTOR, targeting controls its production in different genetic contexts. In particular, we identified a BRAF/ERK2/CHOP axis affecting IL-8 transcription, through regulation of CHOP subcellular localization, and response to targeted inhibitors. Moreover, RNA Pol II and an open chromatin status in the CHOP-binding region of the IL-8 gene promoter cooperate towards increased IL-8 expression, after a selective BRAF inhibition. Overall, our data show that IL-8 production is finely and differentially regulated depending on the tumor genetic context and might be targeted for therapeutic purposes in molecularly defined subgroups of CRC patients.
The first ring-expanded NHC–copper(i) phosphides as catalysts in the highly selective hydrophosphination of isocyanates
Authors: Horsley Downie Thomas M. , Hall Jonathan W. , Collier Finn Thomas P. , Liptrot David J. , Lowe John P. , Mahon Mary F. , McMullin Claire L. , Whittlesey Michael K.
Published: October 2020

The first copper(i) phosphides supported by ring-expanded N-heterocyclic carbenes have been synthesised and react readily with heterocumulenes. These copper(i) phosphides are highly active and selective in the hydrophosphination of isocyanates.
Electro-elastic features of Nd-doped YAl3(BO3)4single crystal
Authors: Fan Mengdi , Wu Guangda , Chen Feifei , Yu Fapeng , Cheng Xiufeng , Zhao Xian
Published: October 2020

The NYAB crystal shows relatively high resistivity and good temperature stability of piezoelectric activity, potential for high temperature piezoelectric applications.