bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring Burnout in Social Work
Authors: Doherty Ann S. , Mallett John , Leiter Michael P. , McFadden Paula
Published: March 2020

Abstract. Several studies challenge the three-dimensional structure of the Maslach Burnout Inventory – Human Services Survey (MBI-HSS), citing alternative measurement models including bifactor models. While bifactor models have merit, if data sampling violates assumptions of Stochastic Measurement Theory (SMT) the bifactor model requires modification prior to application. The present study compared five alternative MBI-HSS factor models using both Confirmatory Factor Analysis (CFA) and Exploratory Structural Equation Modeling (ESEM). Data from a cross-sectional survey of United Kingdom (UK) social workers were examined ( N = 1257), with validation analyses conducted in an independent sample ( N = 162). Bifactor models, re-specified to account for SMT, provided good fit. However, improved fit was observed for a bifactor-ESEM specification, in both test (χ2 = 1,112.93, df = 149, p < .001, CFI = .969, RMSEA = .072, 90% CI [.068, .076]) and validation (χ2 = 227.89, df = 149, p < .001, CFI = .978, RMSEA = .057, 90% CI [.042, .072]) samples. The results confirm the MBI-HSS possesses a bifactor structure in UK social workers when SMT is considered, and that bifactor-ESEM may provide a better framework to examine MBI-HSS.
Short Forms Do Not Fall Short
Authors: Rammstedt Beatrice , Lechner Clemens M. , Danner Daniel
Published: March 2020

Abstract. Researchers wishing to assess personality in research settings with severe time limitations typically use short-scale measures of the Big Five. Over the last decade, several such measures have been developed. To guide researchers in choosing the one best suited to their needs, we conducted the present study. Based on a large-scale sample representative of the adult population in Germany, we compared the psychometric properties of three short-scale versions assessing the Big Five: the 10-item BFI-10, the 15-item BFI-2-XS, and the 30-item BFI-2-S. To assess the psychometric quality of these measures, we investigated and compared the descriptive statistics and reliabilities of the scale scores as well as the patterns of factor loadings and the model fit of the instruments as indicators of their factorial validity. As the typical research settings in which these short measures are administered are heterogeneous population samples, we investigated to what degree the resulting Big Five estimates were comparable across major sociodemographic groups (age, gender, and educational strata). Finally, we compared the validity of the three measures for a set of external criteria. Results indicate that the latent Big Five domains can be assessed adequately with all three measures, which were found to have high psychometric quality, with coefficients of mostly comparable size.
The SMART‐s Trace Gas and Aerosol Inversions: I. Algorithm Theoretical Basis for Column Property Retrievals
Authors: Jeong Ukkyo , Tsay Si‐Chee , Giles David M. , Holben Brent N. , Swap Robert J. , Abuhassan Nader , Herman Jay R.
Published: March 2020

The SMART‐s (Spectral Measurements for Atmospheric Radiative Transfer—spectroradiometer) acquires Sun/sky observations for retrieving optimal information on trace gases and aerosols with minimal assumptions. Overall, the algorithm of SMART‐s incorporates a series of retrievals, from fundamental quantities (i.e., column abundance of trace gases and aerosol loading) to higher‐order geophysical parameters (e.g., aerosol physicochemical properties and vertical profiles), utilizing Sun/sky spectral radiance measurements. This paper describes the theoretical basis for column retrievals of trace gases and aerosols. Associated profile retrievals will be presented in follow‐up papers. The current algorithm retrieves the fine/coarse mode of the particle size distribution and spectral complex index of refraction and, thereby, the spectral aerosol single‐scattering albedo ω0. SMART‐s retrieval is unique particularly in its high spectral resolution of the complex index of refraction and ω0 from near‐ultraviolet to near‐infrared wavelengths, which is pivotal information for atmospheric chemistry, climate and other inversions. We theoretically assessed information content and retrieval accuracy of the algorithm and compared different type of measurements including the Aerosol Robotic Network (AERONET) and standard Pandora. For the same levels of radiometric accuracy, SMART‐s measurements provide the most informative aerosol retrievals based on theoretical error analyses. Higher spectral resolution measurements are particularly beneficial for particle size distribution and fine‐mode refractive index retrievals. We applied this algorithm to the AERONET Sun/sky measurements at Kanpur, India, in 2016 to assess algorithm consistency. Even with different assumptions and numerical methods for the inversion, SMART‐s retrieved aerosol parameters agreed well with the AERONET operational products (e.g., absolute mean bias errors less than 0.01 for ω0).
Hydraulic Potential Energy Model for Hydropower Operation in Mixed Reservoir Systems
Authors: Wan Wenhua , Wang Hao , Zhao Jianshi
Published: March 2020

The forecast‐informed hydropower operation for mixed reservoir systems, which consist of parallel and cascade reservoirs, is of considerable importance in practice; however, this operation still lacks an analytical basis in theory. From the perspective of energy, this paper introduces the concept of “hydraulic potential energy” and mathematically derives the energy transformation formula for multi‐reservoir hydropower operation. Based on this formula and the rolling single‐period forecast, a maximum hydraulic potential energy model (E1 model) is proposed. The presented rigorous proofs demonstrate the deficiencies of the commonly considered objectives or principles of minimizing the outflow‐induced energy‐cost, while the objective function of the E1 model is demonstrated to be superior. If the constraints of power output and reservoir storage are nonbinding, the derived optimal spatial principle for hydropower operation is (1) to equalize the Relative Marginal Energy (RME) among reservoirs or (2) if this status is not feasible, to release water and generate hydropower first from the reservoirs that have the largest RME values. Considering the uncertainty of future inflow, the E1 model is extended to the two‐stage hydraulic potential energy model (E2 model). A case study of a hypothetical mixed three‐reservoir system demonstrates the superior performance of the E2 model compared with the conventional K‐value principle and the minimum energy‐cost model. This paper provides an innovative spatial principle and a practical model for the realization of forecast‐informed hydropower operation, which contributes to the optimization of the large‐scale energy market.
Lipid analysis of CO2-rich subsurface aquifers suggests an autotrophy-based deep biosphere with lysolipids enriched in CPR bacteria
Authors: Probst Alexander J , Elling Felix J , Castelle Cindy J , Zhu Qingzeng , Elvert Marcus , Birarda Giovanni , Holman Hoi-Ying N , Lane Katherine R , Ladd Bethany , Ryan M Cathryn , Woyke Tanja , Hinrichs Kai-Uwe , Banfield Jillian F
Published: March 2020

Sediment-hosted CO2-rich aquifers deep below the Colorado Plateau (USA) contain a remarkable diversity of uncultivated microorganisms, including Candidate Phyla Radiation (CPR) bacteria that are putative symbionts unable to synthesize membrane lipids. The origin of organic carbon in these ecosystems is unknown and the source of CPR membrane lipids remains elusive. We collected cells from deep groundwater brought to the surface by eruptions of Crystal Geyser, sequenced the community, and analyzed the whole community lipidome over time. Characteristic stable carbon isotopic compositions of microbial lipids suggest that bacterial and archaeal CO2 fixation ongoing in the deep subsurface provides organic carbon for the complex communities that reside there. Coupled lipidomic-metagenomic analysis indicates that CPR bacteria lack complete lipid biosynthesis pathways but still possess regular lipid membranes. These lipids may therefore originate from other community members, which also adapt to high in situ pressure by increasing fatty acid unsaturation. An unusually high abundance of lysolipids attributed to CPR bacteria may represent an adaptation to membrane curvature stress induced by their small cell sizes. Our findings provide new insights into the carbon cycle in the deep subsurface and suggest the redistribution of lipids into putative symbionts within this community.
Organoid cultures of MELAS neural cells reveal hyperactive Notch signaling that impacts neurodevelopment
Authors: Winanto  , Khong Zi Jian , Soh Boon-Seng , Fan Yong , Ng Shi-Yan
Published: March 2020

Mutations in mitochondrial DNA (mtDNA), typically maternally inherited, can result in severe neurological conditions. There is currently no cure for mitochondrial DNA diseases and treatments focus on management of the symptoms rather than correcting the defects downstream of the mtDNA mutation. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is one such mitochondrial disease that affects many bodily systems, particularly the central nervous system and skeletal muscles. Given the motor deficits seen in MELAS patients, we investigate the contribution of motor neuron pathology to MELAS. Using a spinal cord organoid system derived from induced pluripotent stem cells of a MELAS patient, as well as its isogenically corrected control, we found that high levels of Notch signaling underlie neurogenesis delays and neurite outgrowth defects that are associated with MELAS neural cultures. Furthermore, we demonstrate that the gamma-secretase inhibitor DAPT can reverse these neurodevelopmental defects.
“Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis
Authors: Zhang Changping , Liu Zixuan , Zhang Yuhao , Ma Liang , Song Erqun , Song Yang
Published: March 2020

Exposure to nanomaterials (NMs) is an emerging threat to human health, and the understanding of their intracellular behavior and related toxic effects is urgently needed. Ferroptosis is a newly discovered, iron-mediated cell death that is distinctive from apoptosis or other cell-death pathways. No evidence currently exists for the effect of “iron free” engineered NMs on ferroptosis. We showed by several approaches that (1) zinc oxide nanoparticles (ZnO NPs)-induced cell death involves ferroptosis; (2) ZnO NPs-triggered ferroptosis is associated with elevation of reactive oxygen species (ROS) and lipid peroxidation, along with depletion of glutathione (GSH) and downregulation of glutathione peroxidase 4 (GPx4); (3) ZnO NPs disrupt intracellular iron homeostasis by orchestrating iron uptake, storage and export; (4) p53 largely participates in ZnO NPs-induced ferroptosis; and (5) ZnO particle remnants and dissolved zinc ion both contribute to ferroptosis. In conclusion, our data provide a new mechanistic rationale for ferroptosis as a novel cell-death phenotype induced by engineered NMs.
Interaction of 2D materials with liquids: wettability, electrochemical properties, friction, and emerging directions
Authors: Snapp Peter , Kim Jin Myung , Cho Chullhee , Leem Juyoung , Haque Md Farhadul , Nam SungWoo
Published: March 2020

The emergence of two-dimensional (2D) materials as functional surfaces for sensing, electronics, mechanics, and other myriad applications underscores the importance of understanding 2D material–liquid interactions. The thinness and environmental sensitivity of 2D materials induce novel surface forces that drive liquid interactions. This complexity makes fundamental 2D material–liquid interactions variable. In this review, we discuss the (1) wettability, (2) electrical double layer (EDL) structure, and (3) frictional interactions originating from 2D material–liquid interactions. While many 2D materials are inherently hydrophilic, their wettability is perturbed by their substrate and contaminants, which can shift the contact angle. This modulation of the wetting behavior enables templating, filtration, and actuation. Similarly, the inherent EDL at 2D material–liquid interfaces is easily perturbed. This EDL modulation partially explains the wettability modulation and enables distinctive electrofluidic systems, including supercapacitors, energy harvesters, microfluidic sensors, and nanojunction gating devices. Furthermore, nanoconfinement of liquid molecules at 2D material surfaces arising from a perturbed liquid structure results in distinctive hydrofrictional behavior, influencing the use of 2D materials in microchannels. We expect 2D material–liquid interactions to inform future fields of study, including modulation of the chemical reactivity of 2D materials via tuning 2D material–liquid interactions. Overall, 2D material–liquid interactions are a rich area for research that enables the unique tuning of surface properties, electrical and mechanical interactions, and chemistry.
3D characterisation and quantification of an offshore freshened groundwater system in the Canterbury Bight
Authors: Micallef Aaron , Person Mark , Haroon Amir , Weymer Bradley A. , Jegen Marion , Schwalenberg Katrin , Faghih Zahra , Duan Shuangmin , Cohen Denis , Mountjoy Joshu J. , Woelz Susanne , Gable Carl W. , Averes Tanita , Kumar Tiwari Ashwani
Published: March 2020

Although offshore freshened groundwater (OFG) systems have been documented in numerous continental margins worldwide, their geometry, controls and emplacement dynamics remain poorly constrained. Here we integrate controlled-source electromagnetic, seismic reflection and borehole data with hydrological modelling to quantitatively characterise a previously unknown OFG system near Canterbury, New Zealand. The OFG system consists of one main, and two smaller, low salinity groundwater bodies. The main body extends up to 60 km from the coast and a seawater depth of 110 m. We attribute along-shelf variability in salinity to permeability heterogeneity due to permeable conduits and normal faults, and to recharge from rivers during sea level lowstands. A meteoric origin of the OFG and active groundwater migration from onshore are inferred. However, modelling results suggest that the majority of the OFG was emplaced via topographically-driven flow during sea level lowstands in the last 300 ka. Global volumetric estimates of OFG will be significantly revised if active margins, with steep coastal topographies like the Canterbury margin, are considered.
A signaling hub of insulin receptor, dystrophin glycoprotein complex and plakoglobin regulates muscle size
Authors: Eid Mutlak Yara , Aweida Dina , Volodin Alexandra , Ayalon Bar , Dahan Nitsan , Parnis Anna , Cohen Shenhav
Published: March 2020

Signaling through the insulin receptor governs central physiological functions related to cell growth and metabolism. Here we show by tandem native protein complex purification approach and super-resolution STED microscopy that insulin receptor activity requires association with the fundamental structural module in muscle, the dystrophin glycoprotein complex (DGC), and the desmosomal component plakoglobin (γ-catenin). The integrity of this high-molecular-mass assembly renders skeletal muscle susceptibility to insulin, because DGC-insulin receptor dissociation by plakoglobin downregulation reduces insulin signaling and causes atrophy. Furthermore, low insulin receptor activity in muscles from transgenic or fasted mice decreases plakoglobin-DGC-insulin receptor content on the plasma membrane, but not when plakoglobin is overexpressed. By masking β-dystroglycan LIR domains, plakoglobin prevents autophagic clearance of plakoglobin-DGC-insulin receptor co-assemblies and maintains their function. Our findings establish DGC as a signaling hub, and provide a possible mechanism for the insulin resistance in Duchenne Muscular Dystrophy, and for the cardiomyopathies seen with plakoglobin mutations.
A megaplasmid family driving dissemination of multidrug resistance in Pseudomonas
Authors: Cazares Adrian , Moore Matthew P. , Hall James P.  J. , Wright Laura L. , Grimes Macauley , Emond-Rhéault Jean-Guillaume , Pongchaikul Pisut , Santanirand Pitak , Levesque Roger C. , Fothergill Joanne L. , Winstanley Craig
Published: March 2020

Multidrug resistance (MDR) represents a global threat to health. Here, we used whole genome sequencing to characterise Pseudomonas aeruginosa MDR clinical isolates from a hospital in Thailand. Using long-read sequence data we obtained complete sequences of two closely related megaplasmids (>420 kb) carrying large arrays of antibiotic resistance genes located in discrete, complex and dynamic resistance regions, and revealing evidence of extensive duplication and recombination events. A comprehensive pangenomic and phylogenomic analysis indicates that: 1) these large plasmids comprise an emerging family present in different members of the Pseudomonas genus, and associated with multiple sources (geographical, clinical or environmental); 2) the megaplasmids encode diverse niche-adaptive accessory traits, including multidrug resistance; 3) the accessory genome of the megaplasmid family is highly flexible and diverse. The history of the megaplasmid family, inferred from our analysis of the available database, suggests that members carrying multiple resistance genes date back to at least the 1970s.
Tactile sensory coding and learning with bio-inspired optoelectronic spiking afferent nerves
Authors: Tan Hongwei , Tao Quanzheng , Pande Ishan , Majumdar Sayani , Liu Fu , Zhou Yifan , Persson Per O. Å. , Rosen Johanna , van Dijken Sebastiaan
Published: March 2020

The integration and cooperation of mechanoreceptors, neurons and synapses in somatosensory systems enable humans to efficiently sense and process tactile information. Inspired by biological somatosensory systems, we report an optoelectronic spiking afferent nerve with neural coding, perceptual learning and memorizing capabilities to mimic tactile sensing and processing. Our system senses pressure by MXene-based sensors, converts pressure information to light pulses by coupling light-emitting diodes to analog-to-digital circuits, then integrates light pulses using a synaptic photomemristor. With neural coding, our spiking nerve is capable of not only detecting simultaneous pressure inputs, but also recognizing Morse code, braille, and object movement. Furthermore, with dimensionality-reduced feature extraction and learning, our system can recognize and memorize handwritten alphabets and words, providing a promising approach towards e-skin, neurorobotics and human-machine interaction technologies.
Predicting gene expression using morphological cell responses to nanotopography
Authors: Cutiongco Marie F. A. , Jensen Bjørn Sand , Reynolds Paul M. , Gadegaard Nikolaj
Published: March 2020

Cells respond in complex ways to their environment, making it challenging to predict a direct relationship between the two. A key problem is the lack of informative representations of parameters that translate directly into biological function. Here we present a platform to relate the effects of cell morphology to gene expression induced by nanotopography. This platform utilizes the ‘morphome’, a multivariate dataset of cell morphology parameters. We create a Bayesian linear regression model that uses the morphome to robustly predict changes in bone, cartilage, muscle and fibrous gene expression induced by nanotopography. Furthermore, through this model we effectively predict nanotopography-induced gene expression from a complex co-culture microenvironment. The information from the morphome uncovers previously unknown effects of nanotopography on altering cell–cell interaction and osteogenic gene expression at the single cell level. The predictive relationship between morphology and gene expression arising from cell-material interaction shows promise for exploration of new topographies.
Thermodynamics of continuous non-Markovian feedback control
Authors: Debiossac Maxime , Grass David , Alonso Jose Joaquin , Lutz Eric , Kiesel Nikolai
Published: March 2020

Feedback control mechanisms are ubiquitous in science and technology, and play an essential role in regulating physical, biological and engineering systems. The standard second law of thermodynamics does not hold in the presence of measurement and feedback. Most studies so far have extended the second law for discrete, Markovian feedback protocols; however, non-Markovian feedback is omnipresent in processes where the control signal is applied with a non-negligible delay. Here, we experimentally investigate the thermodynamics of continuous, time-delayed feedback control using the motion of an optically levitated, underdamped microparticle. We test the validity of a generalized second law which bounds the energy extracted from the system, and study the breakdown of feedback cooling for very large time delays.
Horizontal transfer and evolution of transposable elements in vertebrates
Authors: Zhang Hua-Hao , Peccoud Jean , Xu Min-Rui-Xuan , Zhang Xiao-Gu , Gilbert Clément
Published: March 2020

Horizontal transfer of transposable elements (HTT) is an important process shaping eukaryote genomes, yet very few studies have quantified this phenomenon on a large scale or have evaluated the selective constraints acting on transposable elements (TEs) during vertical and horizontal transmission. Here we screen 307 vertebrate genomes and infer a minimum of 975 independent HTT events between lineages that diverged more than 120 million years ago. HTT distribution greatly differs from null expectations, with 93.7% of these transfers involving ray-finned fishes and less than 3% involving mammals and birds. HTT incurs purifying selection (conserved protein evolution) on all TEs, confirming that producing functional transposition proteins is required for a TE to invade new genomes. In the absence of HTT, DNA transposons appear to evolve neutrally within genomes, unlike most retrotransposons, which evolve under purifying selection. This selection regime indicates that proteins of most retrotransposon families tend to process their own encoding RNA (cis-preference), which helps retrotransposons to persist within host lineages over long time periods.
Bisphosphonate nanoclay edge-site interactions facilitate hydrogel self-assembly and sustained growth factor localization
Authors: Kim Yang-Hee , Yang Xia , Shi Liyang , Lanham Stuart A. , Hilborn Jons , Oreffo Richard O. C. , Ossipov Dmitri , Dawson Jonathan I.
Published: March 2020

Nanoclays have generated interest in biomaterial design for their ability to enhance the mechanics of polymeric materials and impart biological function. As well as their utility as physical cross-linkers, clays have been explored for sustained localization of biomolecules to promote in vivo tissue regeneration. To date, both biomolecule-clay and polymer-clay nanocomposite strategies have utilised the negatively charged clay particle surface. As such, biomolecule-clay and polymer-clay interactions are set in competition, potentially limiting the functional enhancements achieved. Here, we apply specific bisphosphonate interactions with the positively charged clay particle edge to develop self-assembling hydrogels and functionalized clay nanoparticles with preserved surface exchange capacity. Low concentrations of nanoclay are applied to cross-link hyaluronic acid polymers derivatised with a pendant bisphosphonate to generate hydrogels with enhanced mechanical properties and preserved protein binding able to sustain, for over six weeks in vivo, the localized activity of the clinically licensed growth factor BMP-2.
Non-stationary statistics and formation jitter in transient photon condensation
Authors: Walker Benjamin T. , Rodrigues João D. , Dhar Himadri S. , Oulton Rupert F. , Mintert Florian , Nyman Robert A.
Published: March 2020

While equilibrium phase transitions are easily described by order parameters and free-energy landscapes, for their non-stationary counterparts these quantities are usually ill-defined. Here, we probe transient non-equilibrium dynamics of an optically pumped, dye-filled microcavity. We quench the system to a far-from-equilibrium state and find delayed condensation close to a critical excitation energy, a transient equivalent of critical slowing down. Besides number fluctuations near the critical excitation energy, we show that transient phase transitions exhibit timing jitter in the condensate formation. This jitter is a manifestation of the randomness associated with spontaneous emission, showing that condensation is a stochastic, rather than deterministic process. Despite the non-equilibrium character of this phase transition, we construct an effective free-energy landscape that describes the formation jitter and allows, in principle, its generalization to a wider class of processes.
A highly CMOS compatible hafnia-based ferroelectric diode
Authors: Luo Qing , Cheng Yan , Yang Jianguo , Cao Rongrong , Ma Haili , Yang Yang , Huang Rong , Wei Wei , Zheng Yonghui , Gong Tiancheng , Yu Jie , Xu Xiaoxin , Yuan Peng , Li Xiaoyan , Tai Lu , Yu Haoran , Shang Dashan , Liu Qi , Yu Bing , Ren Qiwei , Lv Hangbing , Liu Ming
Published: March 2020

Memory devices with high speed and high density are highly desired to address the ‘memory wall’ issue. Here we demonstrated a highly scalable, three-dimensional stackable ferroelectric diode, with its rectifying polarity modulated by the polarization reversal of Hf0.5Zr0.5O2 films. By visualizing the hafnium/zirconium lattice order and oxygen lattice order with atomic-resolution spherical aberration-corrected STEM, we revealed the correlation between the spontaneous polarization of Hf0.5Zr0.5O2 film and the displacement of oxygen atom, thus unambiguously identified the non-centrosymmetric Pca21 orthorhombic phase in Hf0.5Zr0.5O2 film. We further implemented this ferroelectric diode in an 8 layers 3D array. Operation speed as high as 20 ns and robust endurance of more than 109 were demonstrated. The built-in nonlinearity of more than 100 guarantees its self-selective property that eliminates the need for external selectors to suppress the leakage current in large array. This work opens up new opportunities for future memory hierarchy evolution.
The RNA-binding protein DAZL functions as repressor and activator of mRNA translation during oocyte maturation
Authors: Yang Cai-Rong , Rajkovic Gabriel , Daldello Enrico Maria , Luong Xuan G. , Chen Jing , Conti Marco
Published: March 2020

Deleted in azoospermia-like (DAZL) is an RNA-binding protein critical for gamete development. In full-grown oocytes, the DAZL protein increases 4-fold during reentry into the meiotic cell cycle. Here, we have investigated the functional significance of this accumulation at a genome-wide level. Depletion of DAZL causes a block in maturation and widespread disruption in the pattern of ribosome loading on maternal transcripts. In addition to decreased translation, DAZL depletion also causes translational activation of a distinct subset of mRNAs both in quiescent and maturing oocytes, a function recapitulated with YFP-3′UTR reporters. DAZL binds to mRNAs whose translation is both repressed and activated during maturation. Injection of recombinant DAZL protein in DAZL-depleted oocytes rescues the translation and maturation to MII. Mutagenesis of putative DAZL-binding sites in these mRNAs mimics the effect of DAZL depletion. These findings demonstrate that DAZL regulates translation of maternal mRNAs, functioning both as the translational repressor and activator during oocyte maturation.
Multi-level and lineage-specific interactomes of the Hox transcription factor Ubx contribute to its functional specificity
Authors: Carnesecchi Julie , Sigismondo Gianluca , Domsch Katrin , Baader Clara Eva Paula , Rafiee Mahmoud-Reza , Krijgsveld Jeroen , Lohmann Ingrid
Published: March 2020

Transcription factors (TFs) control cell fates by precisely orchestrating gene expression. However, how individual TFs promote transcriptional diversity remains unclear. Here, we use the Hox TF Ultrabithorax (Ubx) as a model to explore how a single TF specifies multiple cell types. Using proximity-dependent Biotin IDentification in Drosophila, we identify Ubx interactomes in three embryonic tissues. We find that Ubx interacts with largely non-overlapping sets of proteins with few having tissue-specific RNA expression. Instead most interactors are active in many cell types, controlling gene expression from chromatin regulation to the initiation of translation. Genetic interaction assays in vivo confirm that they act strictly lineage- and process-specific. Thus, functional specificity of Ubx seems to play out at several regulatory levels and to result from the controlled restriction of the interaction potential by the cellular environment. Thereby, it challenges long-standing assumptions such as differential RNA expression as determinant for protein complexes.
An engineered oncolytic virus expressing PD-L1 inhibitors activates tumor neoantigen-specific T cell responses
Authors: Wang Guan , Kang Xi , Chen Katherine S. , Jehng Tiffany , Jones Lindsey , Chen Jie , Huang Xue F. , Chen Si-Yi
Published: March 2020

Oncolytic viruses offer an in situ vaccination approach to activate tumor-specific T cell responses. However, the upregulation of PD-L1 expression on tumor cells and immune cells leads to tumor resistance to oncolytic immunotherapy. In this study, we generate an engineered oncolytic virus that coexpresses a PD-L1 inhibitor and GM-CSF. We find that the oncolytic virus is able to secrete the PD-L1 inhibitor that systemically binds and inhibits PD-L1 on tumor cells and immune cells. Importantly, the intratumoral injection with the oncolytic virus overcomes PD-L1-mediated immunosuppression during both the priming and effector phases, provokes systemic T cell responses against dominant and subdominant neoantigen epitopes derived from mutations, and leads to an effective rejection of both virus-injected and distant tumors. In summary, this engineered oncolytic virus is able to activate tumor neoantigen-specific T cell responses, providing a potent, individual tumor-specific oncolytic immunotherapy for cancer patients, especially those resistant to PD-1/PD-L1 blockade therapy.
Plant Raf-like kinases regulate the mRNA population upstream of ABA-unresponsive SnRK2 kinases under drought stress
Authors: Soma Fumiyuki , Takahashi Fuminori , Suzuki Takamasa , Shinozaki Kazuo , Yamaguchi-Shinozaki Kazuko
Published: March 2020

SNF1-related protein kinases 2 (SnRK2s) are key regulators governing the plant adaptive responses to osmotic stresses, such as drought and high salinity. Subclass III SnRK2s function as central regulators of abscisic acid (ABA) signalling and orchestrate ABA-regulated adaptive responses to osmotic stresses. Seed plants have acquired other types of osmotic stress-activated but ABA-unresponsive subclass I SnRK2s that regulate mRNA decay and promote plant growth under osmotic stresses. In contrast to subclass III SnRK2s, the regulatory mechanisms underlying the rapid activation of subclass I SnRK2s in response to osmotic stress remain elusive. Here, we report that three B4 Raf-like MAP kinase kinase kinases (MAPKKKs) phosphorylate and activate subclass I SnRK2s under osmotic stress. Transcriptome analyses reveal that genes downstream of these MAPKKKs largely overlap with subclass I SnRK2-regulated genes under osmotic stress, which indicates that these MAPKKKs are upstream factors of subclass I SnRK2 and are directly activated by osmotic stress.
GIS- Based Screening Model of Coastal City Karachi for Plantation of Biofuel Source
Authors: Khan Muhammad Jahangir , Hasan Syeda Ailya
Published: March 2020

Geospatial techniques are mediating in decision making, diversified data management and critical analysis. Jatropha Curcas. is a biodiesel crop and friendly to the regions of saline water environment. This study focuses to map the suitable plantation sites for biodiesel energy crop by using meteorological parameters and satellite imageries of ASTER GDEM and Landsat 8. The thematic layers of soil adjacent to existing vegetation, topographical elevation, slope, land surface temperature, and humidity are created and analyzed with soil types, bareness index and stream orders. Suitability of sites for plantation is a function of these variables which are found to be favorable in the study area. It should be taken into consideration that Jatropha Curcas plantation in Karachi which may contribute in local economic prosperity and support in maintaining heat-sink for the industrialized city.
LC-HRMS based approach to identify novel sphingolipid biomarkers in breast cancer patients
Authors: Bhadwal Priyanka , Dahiya Divya , Shinde Dhananjay , Vaiphei Kim , Math Raviswamy G. H. , Randhawa Vinay , Agnihotri Navneet
Published: March 2020

Perturbations in lipid metabolic pathways to meet the bioenergetic and biosynthetic requirements is a principal characteristic of cancer cells. Sphingolipids (SPLs) are the largest class of bioactive lipids associated to various aspects of tumorigenesis and have been extensively studied in cancer cell lines and experimental models. The clinical relevance of SPLs in human malignancies however is still poorly understood and needs further investigation. In the present study, we adopted a UHPLC-High resolution (orbitrap) Mass spectrometry (HRMS) approach to identify various sphingolipid species in breast cancer patients. A total of 49 SPLs falling into 6 subcategories have been identified. Further, integrating the multivariate analysis with metabolomics enabled us to identify an elevation in the levels of ceramide phosphates and sphingosine phosphates in tumor tissues as compared to adjacent normal tissues. The expression of genes involved in the synthesis of reported metabolites was also determined in local as well as TCGA cohort. A significant upregulation in the expression of CERK and SPHK1 was observed in tumor tissues in local and TCGA cohort. Sphingomyelin levels were found to be high in adjacent normal tissues. Consistent with the above findings, expression of SGMS1 in tumor tissues was downregulated in TCGA cohort only. Clinical correlations of the selected metabolites and their performance as biomarkers was also evaluated. Significant ROC and positive correlation with Ki67 index highlight the diagnostic potential and clinical relevance of ceramide phosphates in breast cancer.
Bubble-mediated transport of benthic microorganisms into the water column: Identification of methanotrophs and implication of seepage intensity on transport efficiency
Authors: Jordan Sebastian F. A. , Treude Tina , Leifer Ira , Janßen René , Werner Johannes , Schulz-Vogt Heide , Schmale Oliver
Published: March 2020

Benthic microorganisms transported into the water column potentially influence biogeochemical cycles and the pelagic food web structure. In the present study six gas-releasing vent sites in the Coal Oil Point seep field (California) were investigated, and the dislocation of microorganisms from the sediment into the water column via gas bubbles released from the seabed was documented. It was found that the methanotrophs transport efficiency was dependent on the volumetric gas flow, with the highest transport rate of 22.7 × 103 cells mLgas−1 at a volumetric gas flow of 0.07 mLgas s−1, and the lowest rate of 0.2 × 103 cells mLgas−1 at a gas flow of 2.2 mLgas s−1. A simple budget approach showed that this bubble-mediated transport has the potential to maintain a relevant part of the water-column methanotrophs in the seep field. The bubble-mediated link between the benthic and pelagic environment was further supported by genetic analyses, indicating a transportation of methanotrophs of the family Methylomonaceae and oil degrading bacteria of the genus Cycloclasticus from the sediment into the water column. These findings demonstrate that the bubble-mediated transport of microorganisms influences the pelagic microbial abundance and community composition at gas-releasing seep sites.
Comparison of surgery versus observation for small angle intermittent exotropia
Authors: Sung Jae Yun , Yang Hee Kyung , Hwang Jeong-Min
Published: March 2020

In young children with small angle exotropia, making decisions for the individual patient whether to perform surgery or not, and choosing the optimal time for surgical intervention are quite difficult. We aimed to compare the long-term outcomes of small angle intermittent exotropia of 20 prism diopters (PD) or less after observation versus strabismus surgery. A retrospective study was performed on 164 patients aged 3 to 13 who underwent surgical intervention or observation with or without conservative management for intermittent exotropia of 14 to 20 PD. The minimum follow-up period was 2 years. The average follow-up period was 3.9 ± 2.2 years in the observation group and 4.5 ± 2.3 years in the surgery group. At the final examination, the mean angle of deviation at distance was 11.1 ± 8.9 PD in the observation group and 9.0 ± 7.5 PD in the surgery group, which was not significantly different (P = 0.121). Changes in sensory outcome and fusional control were not significantly different between both groups (P = 0.748 and P = 0.968). Subgroup analysis including patients with poor fusional control also showed similar results. By multivariate analysis, the type of surgery, unilateral recess-resect procedure, was the only predictive factor of good motor outcome in the surgery group. In conclusion, long-term surgical outcomes in small angle exotropia did not appear to be more satisfying than observation in terms of motor and sensory outcomes.
Growth of single crystalline films on lattice-mismatched substrates through 3D to 2D mode transition
Authors: Itagaki Naho , Nakamura Yuta , Narishige Ryota , Takeda Keigo , Kamataki Kunihiro , Koga Kazunori , Hori Masaru , Shiratani Masaharu
Published: March 2020

Regarding crystalline film growth on large lattice-mismatched substrates, there are two primary modes by which thin films grow on a crystal surface or interface. They are Volmer-Weber (VW: island formation) mode and Stranski-Krastanov (SK: layer-plus-island) mode. Since both growth modes end up in the formation of three-dimensional (3D) islands, fabrication of single crystalline films on lattice-mismatched substrates has been challenging. Here, we demonstrate another growth mode, where a buffer layer consisting of 3D islands initially forms and a relaxed two-dimensional (2D) layer subsequently grows on the buffer layer. This 3D-2D mode transition has been realized using impurities. We observed the 3D-2D mode transition for the case of ZnO film growth on 18%-lattice-mismatched sapphire substrates. First, nano-sized 3D islands grow with the help of nitrogen impurities. Then, the islands coalesce to form a 2D layer after cessation of the nitrogen supply, whereupon an increase in the surface energy may provide a driving force for the coalescence. Finally, the films grow in 2D mode, forming atomically flat terraces. We believe that our findings will offer new opportunities for high-quality film growth of a wide variety of materials that have no lattice-matched substrates.
Left ventricular global function index by magnetic resonance imaging — a novel marker for differentiating cardiac amyloidosis from hypertrophic cardiomyopathy
Authors: Huang Shan , Xu Hua-yan , Diao Kai-yue , Shi Ke , He Yong , He Sen , Zhang Yi , Gao Yue , Shen Meng-ting , Guo Ying-kun , Yang Zhi-gang
Published: March 2020

Differentiating cardiac amyloidosis (CA) from hypertrophic cardiomyopathy (HCM) remains a clinical challenge, particularly in those with preserved left ventricular ejection fraction (LVEF) and similar hypertrophy. This study aimed to use left ventricular global function index (LVGFI) and myocardial contraction fraction (MCF) to discriminate CA from HCM without using contrast agents on cardiovascular magnetic resonance imaging (CMR). In total, we included 68 CA patients, 90 HCM patients, and 35 healthy controls. We found that LVGFI had excellent diagnostic performance in differentiating CA from HCM (area under the curve (AUC) = 0.91, 95% CI [0.86–0.95]), even in the challenging conditions of similar hypertrophy (AUC = 0.92, 95% CI [0.87–0.97]) and preserved LVEF (AUC = 0.90, 95% CI [0.84–0.96]). LVGFI also had significant correlations with LGE extent, NT-proBNP and troponin T (all p < 0.001). Multiple logistic regression analysis revealed that LVGFI was an independent predictor of CA (odds ratio: 1.11, 95% CI: 1.01–1.23; p = 0.034). In conclusion, LVGFI is a novel and clinically useful parameters with excellent ability in determining myocardial function and differentiating cardiac amyloidosis from hypertrophic cardiomyopathy.
Routine, ensemble characterisation of electrophoretic mobility in high and saturated ionic dispersions
Authors: Austin Jake , Fernandes Diogo , Ruszala Matthew J. A. , Hill Natalie , Corbett Jason
Published: March 2020

With the industrialisation of nanoparticle manufacture, the pervasive incursion of nanoparticles into the environment, the need to characterise nano-scale pharmaceuticals and living systems in replicated in vivo conditions, the continuing development of new theories to describe the electro-kinetic behaviour of nano-particles in representative ionic strengths and numerous other applications, there is an urgent requirement to provide simple and effective experimental tools to validate these models and explore new systems. Micro-electrophoresis implemented with a diffusion barrier, which isolates the dispersed phase from the electrode surface, is demonstrated as enabling such measurements for the first time, preventing the catastrophic outgassing, precipitation and sample degradation observed when the dispersed phase is in close proximity to the electrode surface. Using a measurement of a few minute’s duration in a standard laboratory light scattering instrument we reproduce the theoretically predicted phenomena of asymptotic, non-zero electrophoretic mobility with increasing ionic strength, the cationic Hofmeister series dependency, charge inversion and a continuously decreasing variation in mobility with pH as molarity increases. Standard operating procedures are developed and included to encourage further work.
Circular manufacturing of chitinous bio-composites via bioconversion of urban refuse
Authors: Sanandiya Naresh D. , Ottenheim Christoph , Phua Jun Wei , Caligiani Augusta , Dritsas Stylianos , Fernandez Javier G.
Published: March 2020

Bioinspired manufacturing, in the sense of replicating the way nature fabricates, may hold great potential for supporting a socioeconomic transformation towards a sustainable society. Use of unmodified ubiquitous biological components suggests for a fundamentally sustainable manufacturing paradigm where materials are produced, transformed into products and degraded in closed regional systems with limited requirements for transport. However, adoption is currently limited by the fact that despite their ubiquitous nature, these biopolymers are predominantly harvested as industrial and agricultural products. In this study, we overcome this limitation by developing a link between bioinspired manufacturing and urban waste bioconversion. This result is paramount for the development of circular economic models, effectively connecting the organic by-products of civilization to locally decentralized, general-purpose manufacturing.
The role of Ca2+/NFAT in Dysfunction and Inflammation of Human Coronary Endothelial Cells induced by Sera from patients with Kawasaki disease
Authors: Wang Ying , Hu Jian , Liu Jingjing , Geng Zhimin , Tao Yijing , Zheng Fenglei , Wang Yujia , Fu Songling , Wang Wei , Xie Chunhong , Zhang Yiying , Gong Fangqi
Published: March 2020

Ca2+/nuclear factor of activated T-cells (Ca2+/NFAT) signaling pathway may play a crucial role in the pathogenesis of Kawasaki disease (KD). We investigated the poorly understood Ca2+/NFAT regulation of coronary artery endothelial cells and consequent dysfunction in KD pathogenesis. Human coronary artery endothelial cells (HCAECs) stimulated with sera from patients with KD, compared with sera from healthy children, exhibited significant increases in proliferation and angiogenesis, higher levels of NFATc1 and NFATc3 and some inflammatory molecules, and increased nuclear translocation of NFATc1 and NFATc3. HCAECs stimulated with sera from patients with KD treated with cyclosporine A (CsA) showed decreased proliferation, angiogenesis, NFATc1 and inflammatory molecules levels as compared with results for untreated HCAECs. In conclusion, our data reveal that KD sera activate the Ca2+/NFAT in HCAECs, leading to dysfunction and inflammation of endothelial cells. CsA has cytoprotective effects by ameliorating endothelial cell homeostasis via Ca2+/NFAT.
Near infrared readouts offer sensitive and rapid assessments of intestinal permeability and disease severity in inflammatory bowel disease models
Authors: Zhang Liang , Wallace Craig D. , Erickson Jamie E. , Nelson Christine M. , Gaudette Stephanie M. , Pohl Calvin S. , Karsen Samuel D. , Simler Gricelda H. , Peng Ruoqi , Stedman Christopher A. , Laroux F. Stephen , Wurbel Marc A. , Kamath Rajesh V. , McRae Bradford L. , Schwartz Sterman Annette J. , Mitra Soumya
Published: March 2020

Intestinal permeability and neutrophil activity are closely linked to inflammatory bowel disease (IBD) pathophysiology. Here we discuss two techniques for assessing permeability and neutrophil activity in mouse IBD models using near infrared (NIR) detection. To address the limitation of visible light readouts—namely high background—IRDye 800CW was used to enable rapid, non-terminal measurements of intestinal permeability. The increased sensitivity of NIR readouts for colon permeability is shown using dextran sulfate sodium (DSS) and anti-CD40 murine colitis models in response to interleukin-22 immunoglobulin Fc (IL22Fc) fusion protein and anti-p40 monoclonal antibody treatments, respectively. In addition to enhanced permeability, elevated levels of neutrophil elastase (NE) have been reported in inflamed colonic mucosal tissue. Activatable NIR fluorescent probes have been extensively used for disease activity evaluation in oncologic animal models, and we demonstrate their translatability using a NE-activatable reagent to evaluate inflammation in DSS mice. Confocal laser endomicroscopy (CLE) and tissue imaging allow visualization of spatial NE activity throughout diseased colon as well as changes in disease severity from IL22Fc treatment. Our findings with the 800CW dye and the NE probe highlight the ease of their implementation in preclinical IBD research.
Solvent-controlled self-assembly of tetrapodal [4 + 4] phosphate organic molecular cage
Authors: Feng Gen-Feng , Geng Jiao , Feng Fan-Da , Huang Wei
Published: March 2020

Two flexible subcomponents, namely tris(4-formylphenyl)phosphate and tris(2-aminoethyl)amine, are assembled into a tetrapodal [4 + 4] cage depending on the solvent effect. Single-crystal structure analysis reveals that the caivity is surrounded by four phosphate uints. Good selectivity of CO2 adsorption over CH4 is demonstrated by the gas adsorption experiment.