bluuebunny/crossref_metadata_2025 huggingface dataset:
Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy
Authors: Alomari Ghada , Al-Trad Bahaa , Hamdan Salehhuddin , Aljabali Alaa , Al-Zoubi Mazhar , Bataineh Nesreen , Qar Janti , Tambuwala Murtaza M.
Published: October 2019

Several recent studies have reported that gold nanoparticles (AuNPs) attenuate hyperglycemia in diabetic animal models without any observed side effects. The present study was intended to provide insight into the effects of 50-nm AuNPs on diabetic kidney disease. Adult male rats were divided into three groups (n = 7/group): control (non-diabetic, ND), diabetic (D), and diabetic treated intraperitoneally with 50-nm AuNPs (AuNPs + D; 2.5 mg/kg/day) for 7 weeks. Diabetes was induced by a single-dose injection of 55 mg/kg streptozotocin. The result showed that AuNP treatment prevented diabetes-associated increases in the blood glucose level. Reduction in 24-h urinary albumin excretion rate, glomerular basement membrane thickness, foot process width, and renal oxidative stress markers was also demonstrated in the AuNP-treated group. In addition, the results showed downregulation effect of AuNPs in renal mRNA or protein expression of transforming growth factor β1 (TGF-β1), fibronectin, collagen IV, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A (VEGF-A). Moreover, the protein expression of nephrin and podocin, podocyte markers, in glomeruli was increased in the AuNPs + D group compared with the D group. These results provide evidence that 50-nm AuNPs can ameliorate renal damage in experimental models of diabetic nephropathy through improving the renal function and downregulating extracellular matrix protein accumulation, along with inhibiting renal oxidative stress and amelioration of podocyte injury.
Effects of land cover changes and slope gradient on soil quality in the Gumara watershed, Lake Tana basin of North–West Ethiopia
Authors: Wubie Mesfin Anteneh , Assen Mohammed
Published: October 2019

This study evaluated land cover change and slope gradient on selected soil quality parameters in the Gumara watershed, northwestern Ethiopia. 36 soil samples were collected from 0- to 20-cm depth under four land cover types across three slope gradients. The collected soil samples were analyzed for selected soil quality parameters. Result indicated that the bulk density of the soil is different (P < 0.001) in the watershed because of land cover change and slope gradient. Cultivated land and steeper slopes have the highest bulk density and lowest total porosity. On the other hand, the forestland and gentler slopes have lowest bulk density and high total porosity. Intensive cultivation accompanied by continuous conversion of forestland to cultivated land caused high bulk density and low total porosity. Cation exchange capacity, exchangeable magnesium total nitrogen, available phosphorus and potassium negatively correlated with slope gradient. Conversion of forestland to cultivated land contributed to changes in pH (P < 0.05) exchangeable calcium (P < 0.01), potassium (P < 0.001), available phosphorus (P < 0.01) and nitrogen (P < 0.01) content. The soil degradation index results showed that soil organic carbon, nitrogen, available phosphorus and exchangeable potassium contents declined and bulk density increased because of the land cover change. This negative effect on agricultural development and environmental health of the watershed makes an integrated land resource management approach vital for sustaining agricultural productivity and the environment health of the Gumara watershed.
Developing a university-wide academic integrity E-learning tutorial: a Canadian case
Authors: Benson Lyle , Rodier Kristin , Enström Rickard , Bocatto Evandro
Published: October 2019

Academic integrity has become a significant point of concern in the post-secondary landscape, and many institutions are now exploring ways on how to implement academic integrity training for students. This paper delineates the development of an Academic Integrity E-Learning (AIE-L) tutorial at MacEwan University, Canada. In its first incarnation, the AIE-L tutorial was intended as an education tool for students who had been found to violate the University’s Academic Integrity Policy. However, in a discourse of the academic integrity process, the University reimagined it from only emphasising the increased understanding and strengthened commitment of students found to have committed academic misconduct to a proactive focus with education for all students. The purpose of the present paper is three-fold: first, describe the development of the AIE-L tutorial as an experiential case study; second, improve the content of the AIE-L tutorial through students’ quantitative and qualitative feedback; third, calibrate the pre and post-test questions for content validity for a forthcoming large-scale measurement of the AIE-L tutorial effectiveness.
Translating innovation in biomedical research: Design and delivery of a competency-based regulatory science course
Authors: Greenberg-Worisek Alexandra J. , Cornelius Katherine E. , Cumba Garcia Luz , Enders Felicity T. , Shah Nilay D. , Windebank Anthony J.
Published: October 2019

As the pace of biomedical innovation rapidly evolves, there is a need to train researchers to understand regulatory science challenges associated with clinical translation. We describe a pilot course aimed at addressing this need delivered jointly through the Mayo Clinic Center for Clinical and Translational Science and the Yale-Mayo Center for Excellence in Regulatory Science and Innovation. Course design was informed by the Association for Clinical and Translational Science’s Regulatory Science Working Group’s competencies. The course used didactic, case-, and problem-based learning sessions to expose students to regulatory science concepts. Course evaluation focused on student satisfaction and learning. A total of 25 students enrolled in the first two course deliveries. Students represented several disciplines and career stages, from predoctoral to faculty. Students reported learning “an incredible amount” (7/19, 36.8%) or “a lot” (9/19, 47.4%); this was reflected in individual coursework and their course evaluations. Qualitative feedback indicated that assignments that challenged them to apply the content to their own research were appreciated. The heterogeneity of students enrolled, coupled with assessments and course evaluations, supports the statement that there is a growing need and desire for regulatory science-focused curricula. Future research will determine the long-term impact.
Emergency Management for the Outpatient Health Care Environment
Authors: Paras Emma , Butler Matthew
Published: October 2019

Utilization of ambulatory and outpatient services for primary, specialty, and surgical care has risen in the United States over the last decade, in parallel with the evolution of health care emergency management. Regulatory and accreditation authorities; legislature and policies; and real-life events such as hurricanes, tornadoes, and wildfires throughout the country have caused health care systems to take a more all-hazards approach for emergency management. While health care emergency management has grown tremendously in significance, outpatient settings have yet to see the same growth. However, concepts of comprehensive emergency management and the incident command system are important and valuable across all health care system settings, including outpatient facilities. The purpose of this article is to summarize regulatory requirements for outpatient health care emergency management, describe nuances of outpatient settings, and provide recommendations for how to successfully incorporate outpatient and ambulatory locations into the “Enterprise” model for comprehensive health care emergency management.
Secrecy's subjects: Special operators in the US shadow war
Authors: Van Veeren Elspeth
Published: October 2019

This article sets out a framework for studying the power of secrecy in security discourses. To date, the interplay between secrecy and security has been explored within security studies most often through a framing of secrecy and security as a ‘balancing’ act, where secrecy and revelation are binary opposites, and excesses of either produce insecurity. Increasingly, however, the co-constitutive relationship between secrecy and security is the subject of scholarly explorations. Drawing on ‘secrecy studies’, using the US ‘shadow war’ as an empirical case study, and conducting a close reading of a set of key memoirs associated with the rising practice of ‘manhunting’ in the Global War on Terrorism (GWoT), this article makes the case that to understand the complex workings of power within a security discourse, the political work of secrecy as a multilayered composition of practices (geospatial, technical, cultural, and spectacular) needs to be analysed. In particular, these layers result in the production and centring of several secrecy subjects that help to reproduce the logic of the GWoT and the hierarchies of gender, race, and sex within and beyond special operator communities (‘insider’, ‘stealthy’, ‘quiet’, and ‘alluring’ subjects) as essential to the security discourse of the US ‘shadow war’.
Knowing Full Well from Testimony?
Authors: Fricker Elizabeth
Published: October 2019

Testimony poses a challenge to systematic epistemology. I cite two kinds of testimony situation where the recipient's belief is not safe, yet intuitively counts as knowledge. Can Sosa's more sophisticated virtue reliabilism, which theorises animal knowledge as apt belief, yield the intuitively correct verdict on these cases? Sosa shows that a belief can be apt, though it is not safe, and so it may seem a quick positive answer is forthcoming. However, I explore complications in applying his AAA framework, regarding what we take as the circumstances in which the subject's attempt is made: the AAA framework does not mandate a particular choice, yet this affects whether the attempt (in particular, a believing in the endeavour to attain truth) comes out as apt or not. I conclude that Sosa's theory is subject to a familiar charge: it does not give a reductive account of knowledge, since we must deploy independent intuitions about whether knowledge is gained in a case, in order to apply it.
Easy Knowledge, Circularity, and the Puzzle of Reliability Knowledge
Authors: Steup Matthias
Published: October 2019

According to externalist reliabilism and dogmatic foundationalism, it's possible to gain knowledge through a perceptual experience without being in a position to know that the experience is reliable. As a result, both of these views face the problem of making knowledge of perceptual reliability too easy, for they permit deducing perceptual reliability from particular perceptual experience without already knowing that these experiences are trustworthy. Ernest Sosa advocates a two-stage solution to the problem. At the first stage, a rich body of perceptual animal knowledge is acquired. At the second stage, perceptual knowledge becomes reflective after deducing perceptual reliability from the initial body of perceptual animal knowledge. I defend the alternative approach of rejecting both externalist reliabilism and dogmatic foundationalism. According to the alternative view, perceptual knowledge and knowledge of perceptual reliability require each other. Such a cognitive structure seems viciously circular. I propose that the appearance of vicious circularity dissipates when the relationship in question is viewed, not as one of temporal priority, but instead as synchronic mutual dependence. At a given time, one cannot have perceptual knowledge without knowledge of perceptual reliability, and vice versa. Such mutual dependence, I argue, is benign.
Counseling students’ attitudes toward complementary and alternative medicine integration in counseling practice
Authors: Ong Lee Za , King Carrie L. , Jackson Hope A.
Published: October 2019

This study explored counseling students’ attitudes toward beliefs and personal experience with complementary and alternative medicine (CAM) integration in counseling practices. A total of 113 clinical mental health counseling students completed a demographic questionnaire, the CAM use, and the Complementary and Alternative Medicine Beliefs Inventory. Data were analyzed using descriptive statistics, nonparametric Chi-Square testing, Mann–Whitney U test, and logistic regression analysis to determine the prevalence of CAM use, CAM beliefs, and predictive factors of CAM integration. The results indicated differences in ethnicity, gender, and age for CAM use, CAM beliefs, and predictors of attitudes toward CAM integration. Recommendations for counseling practice and education regarding CAM use and community-based health promotion were discussed.
New proofs of certain characterisations of cyclic circumscriptible quadrilaterals
Authors: Abu-Saymeh Sadi , Hajja Mowaffaq
Published: October 2019

A convex quadrilateralABCDis calledcircumscriptibleortangentialif it admits an incircle, i.e. a circle that touches all of its sides. A typical circumscriptible quadrilateral is depicted in Figure 1, where the incircle ofABCDtouches the sides at,Aʹ,Bʹ,CʹandDʹ. Notice that labellings such asAAʹ=ADʹ=aare justified by the fact that two tangents from a point to a circle have equal lengths (a, b, canddin Figure 1 are called tangent lengths). This simple fact also implies that ifx, y, andzare the angles shown in the figure, thenx = y. In fact, ifADandBCare parallel, thenx = y= 90°. Otherwise, the extensions ofADandBCwould meet, say atQ, withQDʹ. Hencex = y. Thusx = yin all cases, and sinx= siny= sinz. We shall use this observation freely. Also we shall denote the vertices and vertex angles of a polygon by the same letters, but after making sure that no confusion may arise.
Coincidence of the barycentre and the geometric centre of weighted points
Authors: Abel Ulrich
Published: October 2019

Recently, Gerhard J. Woeginger [1] gave a survey on the interesting history of results on equiangular n-vertex polygons with edge lengths in arithmetic progression. Such a polygon exists if, and only if, n has at least two distinct prime factors.
Characterisations of the parabola
Authors: Kilner Steven J. , Farnsworth David L.
Published: October 2019

Three familiar properties of a parabola are that it is the locus of points that are equidistant from the focus and the directrix, that it can be created by an intersection of a plane and a cone, and that incoming rays parallel to the axis are reflected to a single point. The first two are often used as definitions, and the third may be used as an alternative definition or characterisation.
East West Street: Then and Now
Authors: Sands Philippe
Published: October 2019

It is a great happiness to be with you today, and I am deeply honoured to be delivering the Lionel Cohen Lecture. That we should come together at the Hebrew University in Jerusalem, which I have had the great pleasure to visit on several occasions, stretching back many years, adds to the sense of personal significance.
Population dynamics of shrimpPleoticus muelleriin an upwelling region and new implications for latitudinal gradient theories
Authors: Sancinetti Gustavo S. , Castilho Antônio L. , Wolf Milena R. , Costa Rogério C. , Azevedo Alexandre , Fransozo Adilson
Published: October 2019

The population dynamics of shrimpPleoticus muelleriwas used as a model to verify if the trend of continuous reproduction periodicity, shorter body size and longevity, and early sexual maturity found in tropical regions is corroborated in upwelling regions. Shrimps were sampled in a region under the influence of upwelling (northern coast of Rio de Janeiro State, Brazil). Characteristics of bottom water were registered, and shrimps were measured (carapace length – CL) and classified by sex and gonadal development stages. Reproduction was seasonal, from September to December, and favoured by water mass intrusions of low temperatures and high chlorophyll concentrations. The greatest number of reproductive females preceded periods with the highest chlorophyll concentrations in the water column (cross-correlation;P< 0.05, lag (month) = −3,r= 0.50), suggesting greater developmental success of larval stage due to increase of food availability. Von Bertalanffy growth models resulted in asymptotic carapace length estimates of CL∞ = 40.21 mm and CL∞ = 36.78 mm for females and males, respectively. The reproductive and growth characteristics of theP. muelleripopulation studied herein were similar to that of populations from higher latitudes, demonstrating that the latitudinal pattern rule cannot be applied in regions influenced by an upwelling phenomenon.
Historicizing media, globalizing media research: infrastructures, publics, and everyday life
Authors: Schroeder Ralph
Published: October 2019

Visions of media spanning the globe and connecting cultures have been around at least since the birth of telegraphy, yet they have always fallen short of realities. Nevertheless, with the internet, a global infrastructure has emerged, which, together with mobile and smartphones, has rapidly changed the media landscape. This far-reaching digital connectedness makes it increasingly clear that the main implications of media lie in the extent to which they reach into everyday life. This article puts this reach into historical context, arguing that, in the pre-modern period, geographically extensive media networks only extended to a small elite. With the modern print revolution, media reach became both more extensive and more intensive. Yet it was only in the late nineteenth century that media infrastructures penetrated more widely into everyday life. Apart from a comparative historical perspective, several social science disciplines can be brought to bear in order to understand the ever more globalizing reach of media infrastructures into everyday life, including its limits. To date, the vast bulk of media research is still concentrated on North America and Europe. Recently, however, media research has begun to track broader theoretical debates in the social sciences, and imported debates about globalization from anthropology, sociology, political science, and international relations. These globalizing processes of the media research agenda have been shaped by both political developments and changes in media, including the Cold War, decolonization, the development of the internet and other new media technologies, and the rise of populist leaders.
Implementing Gender Mainstreaming in Swedish Model Municipalities
Authors: Freidenvall Lenita , Ramberg Madeleine
Published: October 2019

This article analyzes the implementation of gender mainstreaming at the local level in Sweden by investigating implementation gaps in the operations of two municipalities, Eskilstuna and Jönköping. The study draws on the literature on policy implementation, particularly the dimensions of comprehension, capacity, and will, as well as the feminist institutional literature on resistance. The data are based on a micro-study of the implementation of gender mainstreaming in two model municipalities, comprising interviews with key actors and a document study. The study shows that the key obstacles to the implementation of gender mainstreaming are complacency—that is, the perception that work on gender mainstreaming is satisfactory and that no extra attention to the matter is needed—and the congestion of perspectives—the fact that the gender equality perspective must compete with other relevant perspectives, a process in which gender equality is often the loser. Another obstacle is lack of political will. However, lack of political will, even in model municipalities, may be compensated for by solid systems of governance. The study contributes to research on implementation theory and feminist institutionalism by demonstrating the gendered barriers and obstacles to affecting change, even in best-case scenarios.
The Quebec Newborn Twin Study at 21
Authors: Boivin Michel , Brendgen Mara , Dionne Ginette , Ouellet-Morin Isabelle , Dubois Lise , Pérusse Daniel , Robaey Philippe , Tremblay Richard E. , Vitaro Frank
Published: October 2019

This paper is a revised and updated edition of a previous description of the Quebec Newborn Twin Study (QNTS), an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early genetic and environmental determinants, as well as their putative role in later social-emotional adjustment, school, health, and occupational outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS now has 16 waves of data collected or planned, including 5 in preschool. Over the last 24 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multimethod measurements. QNTS also entails extended and detailed multilevel assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child’s environment. QNTS children and a subset of their parents have been genotyped, allowing for the computation of a variety of polygenic scores. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene–environment transactions in development.
Space Weathering‐Induced Formation of Hydrogen Sulfide (H2S) and Hydrogen Disulfide (H2S2) in the Murchison Meteorite
Authors: Zhu Cheng , Góbi Sándor , Abplanalp Matthew J. , Frigge Robert , Gillis‐Davis Jeffrey J. , Kaiser Ralf I.
Published: October 2019

Theoretical calculations and experimental simulations indicate that the surprisingly low sulfur abundance on the surfaces of spacecraft visited S‐type asteroids 433 Eros and 25143 Itokawa may be due to space weathering. Two current missions, Osiris‐Rex and Hayabusa 2, are studing asteroids 101955 Bennu (B‐type) and 162173 Ryugu (C‐type), respectively. Understanding space weathering effects related to sulfur containing species is only in the beginning stages and has not been studied from the point of view of C‐type asteroids. This laboratory study details the formation of hydrogen sulfide (H2S) and hydrogen disulfide (H2S2) from conversion of nonvolatile‐sulfuretted species in the Murchison meteorite by exposure to energetic electrons and laser processing, which mimics the synergic effect of secondary electrons generated by galactic cosmic rays and high‐energy solar wind particles plus micrometeorite impact on airless bodies. The results indicate that space weathering processes likely induce depletion of sulfur on the surface of C‐type and undifferentiated S‐type asteroids. For keeping scientific integrity of these fragile species, cold/cryogenic curation of future collected samples from asteroids might be required.
Modeling the Suspended Sediment Transport in a Very Wide, Shallow, and Microtidal Estuary, the Río de la Plata, Argentina
Authors: Moreira Diego , Simionato Claudia G.
Published: October 2019

The impact of the diverse processes responsible for the distribution of suspended sediments in the wide, shallow, and microtidal Río de la Plata estuary and the adjacent shelf is studied by means of a set of process‐oriented numerical simulations. Model results show that the large width and the geometry of the estuary play a major role in the sedimentation processes. The widening and deepening of the estuary drives a significant reduction in current speeds at (i) the confluence of the tributaries and (ii) downstream Barra del Indio Shoal. Thus, sediment deposition enhances downstream those areas. Even though tides are of small amplitude in the study area, they have a significant impact on lateral mixing and resuspension of the bottom sediments. Resuspension augments the concentration of fine sediments in the layers close to the bottom, but tidal energy is not enough to lift them to the surface. Winds (which can be quite strong over this area) enhance horizontal mixing, smoothing the pattern produced by tides. Wind waves increase the concentration of sediment by vertical mixing, and their effect is most evident along the southern coast where wind waves lift the sediments resuspended by tides to the surface. The estuarine circulations associated to the bottom salinity front acts retaining sediments upstream the Barra del Indio Shoal, where estuarine currents and flocculation play an important role in sediment deposition.
Subduction‐Induced Upwelling of a Hydrous Transition Zone: Implications for the Cenozoic Magmatism in Northeast China
Authors: Chen Lin , Faccenda Manuele
Published: October 2019

The widespread Cenozoic basalts in northeast China are commonly thought to be related to the stagnation of the Pacific slab in the transition zone and its deep dehydration. By incorporating experimentally constrained phase diagrams of hydrous mantle and melting conditions at high pressures into two‐dimensional petrological‐thermomechanical models, here we model the interaction of a subducting slab with a hydrous transition zone (TZ) and examine its potential role in generating intracontinental magmatism. The model results show that descending of the oceanic slab first forces up the material in the TZ. Depending on the water content in the TZ, the upwelling hydrous material may undergo dehydration melting above the TZ. As a large slab stagnates within the TZ owing to the lower mantle resistance, the deep melting migrates progressively toward the overriding continent's interior, generating plutonic/volcanic rocks in the continental crust far away from the trench. The amount of deep melting and surface magmatism is obviously related to the amount of water stored in the TZ. In contrast, the water stored in the cold core of the subducting slab and released in the transition zone does not generate melting as it is entirely absorbed by mantle transition zone nominally anhydrous minerals. Comparing the model results with the distribution of the late Cenozoic basalts in northeast China, we suggest that the intracontinental magmatism there was likely caused by deep dehydration melting induced by the slab‐transition zone interaction.
Convection On the Edge
Authors: Windmiller J. M. , Hohenegger C.
Published: October 2019

Deep convection over tropical oceans often appears intensified at the edge of convectively active regions, both in idealized studies and in observations. This edge intensification of convection is studied in detail here, using the steady state of a radiative‐convective equilibrium study, marked by a single convective cluster with deep convection intensified at the edge of this cluster. The cause for edge intensification and its dependence on the cluster area is investigated by comparing the spatial distribution of deep convection to different variables known to be important for convection. Analysis of the simulation suggests that the edge is marked by an increased probability for the triggering of convection rather than by stronger updrafts. In particular, while the edge of the moist region is not thermodynamically more favorable, we find strong surface convergence and therefore dynamical lifting at this edge. The surface convergence is shown to result from two opposing flows. On the one hand, there is, as expected from previous radiative‐convective equilibrium simulations, a low‐level inflow directed toward the moist region. On the other hand, there is a positive density anomaly at the surface which is the result of continuously forming cold pools within the convectively active region, creating a super‐cold‐pool. As the velocity of the low‐level inflow approximately matches the potential propagation speed of the super‐cold‐pool boundary, these opposing flows explain the presence of strong convergence at the edge of this region. Whether the resulting lifting induces the formation of deep convection is shown to depend on the large‐scale instability.
Optically read Coriolis vibratory gyroscope based on a silicon tuning fork
Authors: Lavrik N. V. , Datskos P. G.
Published: October 2019

In this work, we describe the design, fabrication, and characterization of purely mechanical miniature resonating structures that exhibit gyroscopic performance comparable to that of more complex microelectromechanical systems. Compared to previous implementations of Coriolis vibratory gyroscopes, the present approach has the key advantage of using excitation and probing that do not require any on-chip electronics or electrical contacts near the resonating structure. More specifically, our design relies on differential optical readout, each channel of which is similar to the “optical lever” readout used in atomic force microscopy. The piezoelectrically actuated stage provides highly efficient excitation of millimeter-scale tuning fork structures that were fabricated using widely available high-throughput wafer-level silicon processing. In our experiments, reproducible responses to rotational rates as low as 1.8 × 103° h−1 were demonstrated using a benchtop prototype without any additional processing of the raw signal. The noise-equivalent rate, ΩNER, derived from the Allan deviation plot, was found to be <0.5° h−1 for a time of 103 s. Despite the relatively low Q factors (<104) of the tuning fork structures operating under ambient pressure and temperature conditions, the measured performance was not limited by thermomechanical noise. In fact, the performance demonstrated in this proof-of-principle study is approximately four orders of magnitude away from the fundamental limit.
HNF1B-mediated repression of SLUG is suppressed by EZH2 in aggressive prostate cancer
Authors: Wang Jianqing , He Chenxi , Gao Peng , Wang Siqing , Lv Ruitu , Zhou Huihui , Zhou Qidong , Zhang Ke , Sun Jian , Fan Caibin , Ding Guanxiong , Lan Fei
Published: October 2019

Prostate cancer is the most common malignancy in men in developed countries. Overexpression of enhancer of zeste homolog 2 (EZH2), the major histone H3 lysine 27 methyltransferase, has been connected to prostate cancer malignancy. However, its downstream genes and pathways have not been well established. Here, we show tumor suppressor Hepatocyte Nuclear Factor 1β (HNF1B) as a direct downstream target of EZH2. EZH2 binds HNF1B locus and suppresses HNF1B expression in prostate cancer cell lines, which is further supported by the reverse correlation between EZH2 and HNF1B expression in clinical samples. Consistently, restored HNF1B expression significantly suppresses EZH2-mediated overgrowth and EMT processes, including migration and invasion of prostate cancer cell lines. Mechanistically, we find that HNF1B primarily binds the promoters of thousands of target genes, and differentially regulates the expression of 876 genes. We also identify RBBP7/RbAP46 as a HNF1B interacting protein which is required for HNF1B-mediated repression of SLUG expression and EMT process. Importantly, we find that higher HNF1B expression strongly predicts better prognosis of prostate cancer, alone or together with lower EZH2 expression. Taken together, we have established a previously underappreciated axis of EZH2-HNF1B-SLUG in prostate cancer, and also provide evidence supporting HNF1B as a potential prognosis marker for metastatic prostate cancer.
BDNF genetic variants and methylation: effects on cognition in major depressive disorder
Authors: Ferrer Alex , Labad Javier , Salvat-Pujol Neus , Barrachina Marta , Costas Javier , Urretavizcaya Mikel , de Arriba-Arnau Aida , Crespo José M. , Soriano-Mas Carles , Carracedo Ángel , Menchón José M. , Soria Virginia
Published: October 2019

Brain-derived neurotrophic factor (BDNF) gene regulation has been linked to the pathophysiology of major depressive disorder (MDD). MDD patients show cognitive deficits, and alteredBDNFregulation has a relevant role in neurocognitive functions. Our goal was to explore the association betweenBDNFgenetic and epigenetic variations with neurocognitive performance in a group of MDD patients and healthy controls considering possible modulating factors. The sample included 134 subjects, 64 MDD patients, and 70 healthy controls. Clinical data, childhood maltreatment, and neurocognitive performance were assessed in all participants. Eleven single nucleotide polymorphisms (SNPs) and two promoter regions in theBDNFgene were selected for genotype and methylation analysis. The role of interactions betweenBDNFgenetic and epigenetic variations with MDD diagnosis, sex, and Childhood Trauma Questionnaire (CTQ) scores was also explored. We observed significant associations between neurocognitive performance and twoBDNFSNPs (rs908867 and rs925946), an effect that was significantly mediated by methylation values at specific promoter I sites. We identified significant associations between neurocognitive results and methylation status as well as its interactions with MDD diagnosis, sex, and CTQ scores. Our results support the hypothesis thatBDNFgene SNPs and methylation status, as well as their interactions with modulating factors, can influence cognition. Further studies are required to confirm the effect ofBDNFvariations and cognitive function in larger samples.
Region specific knockdown of Parvalbumin or Somatostatin produces neuronal and behavioral deficits consistent with those observed in schizophrenia
Authors: Perez Stephanie M. , Boley Angela , Lodge Daniel J.
Published: October 2019

The anterior hippocampus and prefrontal cortex are regions linked to symptoms of schizophrenia. The anterior hippocampus is believed to be a key regulator of the mesolimbic dopamine system and is thought to be the driving force contributing to positive symptoms, while the prefrontal cortex is involved in cognitive flexibility and negative symptoms. Aberrant activity in these regions is associated with decreases in GABAergic markers, indicative of an interneuron dysfunction. Specifically, selective decreases are observed in interneurons that contain parvalbumin (PV) or somatostatin (SST). Here, we used viral knockdown in rodents to recapitulate this finding and examine the region-specific roles of PV and SST on neuronal activity and behaviors associated with positive, negative and cognitive symptoms. We found that PV and SST had differential effects on neuronal activity and behavior when knocked down in the ventral hippocampus (vHipp) or medial prefrontal cortex (mPFC). Specifically, SST or PV knockdown in the vHipp increased pyramidal cell activity of the region and produced downstream effects on dopamine neuron activity in the ventral tegmental area (VTA). In contrast, mPFC knockdown did not affect the activity of VTA dopamine neuron activity; however, it did produce deficits in negative (social interaction) and cognitive (reversal learning) domains. Taken together, decreases in PV and/or SST were sufficient to produce schizophrenia-like deficits that were dependent on the region targeted.
Fairness norm violations in anti-social psychopathic offenders in a repeated trust game
Authors: Rosenberger Lisa A. , Pfabigan Daniela M. , Lehner Benjamin , Keckeis Katinka , Seidel Eva-Maria , Eisenegger Christoph , Lamm Claus
Published: October 2019

Psychopathic offenders have a high propensity to violate social norms, as indicated for instance by their widespread lying and cheating behaviour. The reasons for their norm violations are not well understood, though, as they are able to recognise norms in a given situation and also punish norm violators. In this study, we investigated whether psychopathic offenders would violate fairness norms during a repeated trust game because of increased profit-maximising concerns. We measured back-transfer decisions in the repeated trust game, and affective arousal by means of skin conductance responses (SCR) in violent offenders with varying degrees of psychopathy, and non-offenders with low-trait psychopathy. Psychopathy in offenders was measured with the Psychopathy Checklist–Revised (PCL-R). In the task, a participant and an interaction partner entrusted each other money for multiple rounds with the goal to earn as much money as possible. Fairness norm violations were positively associated with Factor 2 scores (the lifestyle/anti-social psychopathy subscale) of the PCL-R, but this was not accompanied by clear profit-maximising behaviour. In addition, anticipatory arousal to self-advantageous decisions was higher in all offenders, independent of their degree of psychopathy, compared with non-offenders. The results of our study widen our understanding of social decision-making in psychopathy. They also suggest treatment possibilities in offenders scoring high on Factor 2, targeting empathic concern and related prosocial intentions to overcome norm-violating behaviour.
Humanized bone facilitates prostate cancer metastasis and recapitulates therapeutic effects of zoledronic acid in vivo
Authors: Landgraf Marietta , Lahr Christoph A. , Sanchez-Herrero Alvaro , Meinert Christoph , Shokoohmand Ali , Pollock Pamela M. , Hutmacher Dietmar W. , Shafiee Abbas , McGovern Jacqui A.
Published: October 2019

Advanced prostate cancer (PCa) is known for its high prevalence to metastasize to bone, at which point it is considered incurable. Despite significant effort, there is no animal model capable of recapitulating the complexity of PCa bone metastasis. The humanized mouse model for PCa bone metastasis used in this study aims to provide a platform for the assessment of new drugs by recapitulating the human–human cell interactions relevant for disease development and progression. The humanized tissue-engineered bone construct (hTEBC) was created within NOD-scid IL2rgnull (NSG) mice and was used for the study of experimental PC3-Luc bone metastases. It was confirmed that PC3-Luc cells preferentially grew in the hTEBC compared with murine bone. The translational potential of the humanized mouse model for PCa bone metastasis was evaluated with two clinically approved osteoprotective therapies, the non-species-specific bisphosphonate zoledronic acid (ZA) or the human-specific antibody Denosumab, both targeting Receptor Activator of Nuclear Factor Kappa-Β Ligand. ZA, but not Denosumab, significantly decreased metastases in hTEBCs, but not murine femora. These results highlight the importance of humanized models for the preclinical research on PCa bone metastasis and indicate the potential of the bioengineered mouse model to closely mimic the metastatic cascade of PCa cells to human bone. Eventually, it will enable the development of new effective antimetastatic treatments.
YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways
Authors: Chen Qun , Yang Chuang , Chen Lei , Zhang Jing-Jing , Ge Wan-Li , Yuan Hao , Meng Ling-Dong , Huang Xu-Min , Shen Peng , Miao Yi , Jiang Kui-Rong
Published: October 2019

Background

Pancreatic cancer (PDAC) is a highly invasive cancer with poor prognosis. Recent research has found that the transcription factor Yin Yang 1 (YY1) plays an inhibitory role in the development of pancreatic cancer. It has been reported that tubulin polymerisation-promoting protein (TPPP) plays an indispensable role in a variety of tumours, but its expression and role in pancreatic cancer have not yet been elucidated.

Methods

In this study, we performed ChIP-sequencing and found that YY1 directly binds to the promoter region of TPPP. The expression of TPPP in pancreatic cancer was detected by western blotting and immunohistochemistry. Four-week-old male BALB/c-nude mice were used to assess the effect of TPPP on pancreatic cancer.

Results

Immunohistochemistry revealed that TPPP was expressed at low levels in pancreatic cancer tissues, and was associated with blood vessel invasion. The results from vivo experiments have showed that TPPP could enhance the migration and invasion of pancreatic cancer. Further experiments showed that YY1 could inhibit the migration, invasion and angiogenesis of pancreatic cancer cells by downregulating TPPP via p38/MAPK and PI3K/AKT pathways.

Conclusion

Our study demonstrates that TPPP may act as a promoter and may serve as a novel target for the treatment of pancreatic cancer.
Stiffness-switchable DNA-based constitutional dynamic network hydrogels for self-healing and matrix-guided controlled chemical processes
Authors: Yue Liang , Wang Shan , Wulf Verena , Willner Itamar
Published: October 2019

Constitutional dynamic networks (CDNs) attract interest as signal-triggered reconfigurable systems mimicking natural networks. The application of CDNs to control material properties is, however, a major challenge. Here we report on the design of a CDN consisting of four toehold-modified constituents, two of which act as bidentate units for chain-elongating, while the other two form a tetradentate structure acting as a crosslinking unit. Their hybridization yields a hydrogel of medium stiffness controlled by the balance between bidentate and tetradentate units. Stabilization of the tetradentate constituent by an auxiliary effector up-regulates the crosslinking unit, yielding a high-stiffness hydrogel. Conversely, stabilization of one of the bidentate constituents by an orthogonal effector enriches the chain-elongation units leading to a low-stiffness hydrogel. Using appropriate counter effectors, the hydrogels are reversibly switched across low-, medium- and high-stiffness states. The hydrogels are used to develop self-healing and controlled drug-release matrices and functional materials for operating biocatalytic cascades.
Nucleus segmentation across imaging experiments: the 2018 Data Science Bowl
Authors: Caicedo Juan C. , Goodman Allen , Karhohs Kyle W. , Cimini Beth A. , Ackerman Jeanelle , Haghighi Marzieh , Heng CherKeng , Becker Tim , Doan Minh , McQuin Claire , Rohban Mohammad , Singh Shantanu , Carpenter Anne E.
Published: October 2019

Segmenting the nuclei of cells in microscopy images is often the first step in the quantitative analysis of imaging data for biological and biomedical applications. Many bioimage analysis tools can segment nuclei in images but need to be selected and configured for every experiment. The 2018 Data Science Bowl attracted 3,891 teams worldwide to make the first attempt to build a segmentation method that could be applied to any two-dimensional light microscopy image of stained nuclei across experiments, with no human interaction. Top participants in the challenge succeeded in this task, developing deep-learning-based models that identified cell nuclei across many image types and experimental conditions without the need to manually adjust segmentation parameters. This represents an important step toward configuration-free bioimage analysis software tools.
Biomass-derived Carbon Quantum Dots for Visible-Light-Induced Photocatalysis and Label-Free Detection of Fe(III) and Ascorbic acid
Authors: Das Gouri Sankar , Shim Jong Pil , Bhatnagar Amit , Tripathi Kumud Malika , Kim TaeYoung
Published: October 2019

Visible-light-driven photocatalysts prepared using renewable resources are crucial but challenging to develop for the efficient degradation of organic pollutants, which is required to solve ever-increasing water deterioration issues. In this study, we report a visible-light-responsive photocatalyst for the efficient degradation of methylene blue (MB) as a model pollutant dye. Green-emissive carbon quantum dots (CQDs) were synthesized from pear juice via a facile, scalable, one-pot solvothermal process. The as-synthesized CQDs exhibit superior photocatalytic activity under visible-light irradiation owing to their efficient light absorption, electron transfer, and separation of photogenerated charge carriers, facilitating ~99.5% degradation of MB within 130 min. A possible mechanism for the photocatalysis is proposed on the basis of comprehensive active species trapping experiments. Furthermore, the CQDs were used in a specific sensitive assay for Fe(III) and ascorbic acid (AA), even with interference from other metal ions. The fluorescence emission of CQDs was “turned off” specifically upon binding of Fe(III) and “turned on” with AA. The prepared CQDs represent efficient photocatalysts and fluorescent probes that are not restricted by toxicity, cost, or lack of scalability.
The Psychology of Existential Risk: Moral Judgments about Human Extinction
Authors: Schubert Stefan , Caviola Lucius , Faber Nadira S.
Published: October 2019

The 21st century will likely see growing risks of human extinction, but currently, relatively small resources are invested in reducing such existential risks. Using three samples (UK general public, US general public, and UK students; total N = 2,507), we study how laypeople reason about human extinction. We find that people think that human extinction needs to be prevented. Strikingly, however, they do not think that an extinction catastrophe would be uniquely bad relative to near-extinction catastrophes, which allow for recovery. More people find extinction uniquely bad when (a) asked to consider the extinction of an animal species rather than humans, (b) asked to consider a case where human extinction is associated with less direct harm, and (c) they are explicitly prompted to consider long-term consequences of the catastrophes. We conclude that an important reason why people do not find extinction uniquely bad is that they focus on the immediate death and suffering that the catastrophes cause for fellow humans, rather than on the long-term consequences. Finally, we find that (d) laypeople—in line with prominent philosophical arguments—think that the quality of the future is relevant: they do find extinction uniquely bad when this means forgoing a utopian future.
Nitrogen-doped Carbon with Modulated Surface Chemistry and Porous Structure by a Stepwise Biomass Activation Process towards Enhanced Electrochemical Lithium-Ion Storage
Authors: Nie Zhenzhen , Huang Yewei , Ma Beibei , Qiu Xiaobin , Zhang Nan , Xie Xiuqiang , Wu Zhenjun
Published: October 2019

Controllable conversion of biomass to value-added carbon materials is attractive towards a wide variety of potential applications. Herein, hydrothermal treatment and KOH activation are successively employed to treat the cheap and abundant camellia oleifera shell as a new carbon raw material. It is shown that this stepwise activation process allows the production of porous nitrogen-doped carbon with optimized surface chemistry and porous structure compared to the counterparts prepared by a single activation procedure. Benefiting from the modulated porous structure, the as-produced porous nitrogen-doped carbon electrode delivered a high reversible capacity of 1080 mAh g−1 at a current density of 100 mA g−1, which is 3.3 and 5.8 times as high as that of the carbon materials prepared by bare hydrothermal treatment or KOH activation, respectively. Moreover, the optimized surface composition of the porous nitrogen-doped carbon endows it with a highest initial Coulombic efficiency among the three samples, showing great potentials for practical applications. This work is expected to pave a new avenue to upgrade biomass to carbon materials with tunable surface properties and microstructures for target applications.