bluuebunny/crossref_metadata_2025 huggingface dataset:
Long Period Seismicity at Mammoth Mountain, California
Authors: Dawson Phillip , Chouet Bernard
Published: June 2019

Long period (LP) seismicity is a ubiquitous feature at Mammoth Mountain, California. Phase‐based locations exhibit source depths ranging from ∼8 to 25 km. Between September 2011 and October 2013, over 200 LP events were added to the Northern California Earthquake Data Center catalog. Three typical LP events were used as master events, and continuous waveform correlation was performed over the 2‐year period, with the results indicating that thousands of LP events were present in the continuous seismic data. Using phase‐weighted stacking, representative network stacks for the three events were produced. Full waveform inversion of the representative events using Green functions that adequately represent the topography of Mammoth Mountain and the high‐resolution velocity structure produced through local earthquake tomography suggest that all three event types are located within ∼100 m of the surface in the vicinity of the Chair 12 tree kill and CO2emission area and within ∼1 km of the Mammoth Mountain Ski Area base lodge. The source mechanisms are purely volumetric and can be attributed to a subhorizontal hydrothermal crack excited into acoustic resonance by the rapid discharge of CO2gases trapped in the crack. An accompanying vertical force that is opposite in phase to the volume change in the crack can be attributed to pressure and momentum changes in an adjacent fluid‐filled conduit linking the crack to the surface. The implication of this work is that LP seismicity at Mammoth Mountain occurs almost continuously and in direct contradiction to the traditional view—at very shallow depths.
The Effects of a 1998 Observing System Change on MERRA‐2‐Based Ozone Profile Simulations
Authors: Stauffer Ryan M. , Thompson Anne M. , Oman Luke D. , Strahan Susan E.
Published: June 2019

Model simulations of ozone (O3) driven by meteorological reanalyses are useful for filling observational gaps and interpreting observed O3 variability and trends. However, the transport circulation of reanalysis products is impacted by changes to the observing system (the data assimilated into the reanalyses). We examine the impacts of these changes on simulated O3 from two models, Global Modeling Initiative (GMI) Chemistry Transport Model (GMI CTM) and Modern‐Era Retrospective Analysis for Research Applications version 2 (MERRA‐2) GMI Replay (M2 GMI Replay) simulation, using observations from global ozonesondes (>50,000 profiles) and satellites from 1980 to 2016. Both models are constrained by meteorology from the NASA MERRA‐2 reanalysis, and both use versions of NASA's GMI chemical mechanism. We focus on an observing system change affecting simulated O3 after 1998, associated with the assimilation of temperature and humidity data from new microwave profiling satellites. A large post‐1998 O3 increase, mainly confined to 15–20‐km altitude, of ~10 Dobson units (DU) in midlatitudes occurs in the GMI CTM, worsening the bias compared to observations. In contrast, an increase in M2 GMI Replay simulation O3 of ~10 DU is observed only near −60° latitude, reducing the bias compared to observations. The GMI CTM O3 high biases display a Quasi‐Biennial Oscillation (QBO)‐like periodicity that result from excessive transport from the tropical stratosphere to the midlatitude lower stratosphere during the QBO westerly phase. We quantify O3 discontinuities caused by MERRA‐2 observing system changes and demonstrate how the MERRA‐2 Global Modeling Initiative Replay simulation dampens the effects of these changes and QBO‐driven artifacts on simulated lower stratospheric and total O3. We caution against using simulations driven by a reanalysis to derive multidecadal O3 trends, especially prior to 1998.
Wet Scavenging in WRF‐Chem Simulations of Parameterized Convection for a Severe Storm During the DC3 Field Campaign
Authors: Li Y. , Pickering K. E. , Barth M. C. , Bela M. M. , Cummings K. A. , Allen D. J.
Published: June 2019

Deep convection can transport surface moisture and pollution from the planetary boundary layer to the upper troposphere (UT) within a few minutes. The convective transport of precursors of both ozone and aerosols from the planetary boundary layer affects the concentrations of these constituents in the UT and can influence the Earth's radiation budget and climate. Some precursors of both ozone and aerosols are soluble and reactive in the aqueous phase. This study uses the Weather Research and Forecasting model coupled with Chemistry (WRF‐Chem) to simulate the wet scavenging of precursors of both ozone and aerosols including CH2O, CH3OOH, H2O2, and SO2 in a supercell system observed on 29 May 2012, during the 2012 Deep Convective Clouds and Chemistry (DC3) field campaign at cloud‐parameterized resolution. The default WRF‐Chem simulations underestimate the mixing ratios of soluble ozone precursors in the UT because the dissolved soluble trace gases are not released when the droplets freeze. In order to improve the model simulation of cloud‐parameterized wet scavenging, we added ice retention factors for various species to the cloud‐parameterized wet scavenging module and adjusted the conversion rate of cloud water to rainwater at temperatures below freezing in the cloud parameterization as well as in the subgrid‐scale wet‐scavenging calculation. The introduction of these model modifications greatly improved the model simulation of less soluble species.
Release of Perfluoroalkyl Substances From Melting Glacier of the Tibetan Plateau: Insights Into the Impact of Global Warming on the Cycling of Emerging Pollutants
Authors: Chen Mengke , Wang Chuanfei , Wang Xiaoping , Fu Jianjie , Gong Ping , Yan Juping , Yu Zhengliang , Yan Fangping , Nawab Javed
Published: June 2019

The Tibetan Plateau (TP) has encountered rapid warming, with more than 50% of lakes expanding and 80% of glaciers retreating. Melting glaciers are known as a secondary source of pollutants, but the dynamics and release features of water‐soluble emerging chemicals have not been studied in the TP. Glacial ice and snow, meltwater runoff, rain, and lake water were collected in Nam Co basin, in the central TP. The total concentrations of perfluoroalkyl acids (PFAAs) were 1,413 pg/L for glacial ice, followed by 1,277 pg/L for meltwater runoff, 980 pg/L for lake water, and 616 pg/L for rain. Perfluorobutanoic acid is dominant in runoff and glacial ice, while lake water contained high proportions of perfluorobutane sulfonate and perfluorooctane sulfonate. During the melting season, meltwater runoff generally had greater PFAAs concentrations, and the PFAAs release fluxes were strongly related to the glacial melt intensity. Due to the direct input of PFAAs by melted glaciers, south shore of Lake Nam Co contained higher PFAAs concentrations. The estimated input fluxes of PFAAs to the lake by rain and glacial and nonglacial runoff were 1,425, 1,342, and 2,192 mg/day, respectively. Taken together, these evidences suggest that melting glaciers are sources of PFAAs, while the lake is the receptor. Given the continuity of glacial melt and high concentrations of water‐soluble emerging pollutants in glacier, the melting process will increase the risks of emerging pollutants to freshwater sources and should be of great concern.
3.5KJPNv2: an allele frequency panel of 3552 Japanese individuals including the X chromosome
Authors: Tadaka Shu , Katsuoka Fumiki , Ueki Masao , Kojima Kaname , Makino Satoshi , Saito Sakae , Otsuki Akihito , Gocho Chinatsu , Sakurai-Yageta Mika , Danjoh Inaho , Motoike Ikuko N. , Yamaguchi-Kabata Yumi , Shirota Matsuyuki , Koshiba Seizo , Nagasaki Masao , Minegishi Naoko , Hozawa Atsushi , Kuriyama Shinichi , Shimizu Atsushi , Yasuda Jun , Fuse Nobuo ,   the Tohoku Medical Megabank Project Study Group, Tamiya Gen , Yamamoto Masayuki , Kinoshita Kengo
Published: June 2019

The first step towards realizing personalized healthcare is to catalog the genetic variations in a population. Since the dissemination of individual-level genomic information is strictly controlled, it will be useful to construct population-level allele frequency panels with easy-to-use interfaces. In the Tohoku Medical Megabank Project, we sequenced nearly 4000 individuals from a Japanese population and constructed an allele frequency panel of 3552 individuals after removing related samples. The panel is called the 3.5KJPNv2. It was constructed by using a standard pipeline including the 1KGP and gnomAD algorithms to reduce technical biases and to allow comparisons to other populations. Our database is the first large-scale panel providing the frequencies of variants present on the X chromosome and on the mitochondria in the Japanese population. All the data are available on our original database at https://jmorp.megabank.tohoku.ac.jp.
How soap bubbles freeze
Authors: Ahmadi S. Farzad , Nath Saurabh , Kingett Christian M. , Yue Pengtao , Boreyko Jonathan B.
Published: June 2019

Droplets or puddles tend to freeze from the propagation of a single freeze front. In contrast, videographers have shown that as soap bubbles freeze, a plethora of growing ice crystals can swirl around in a beautiful effect visually reminiscent of a snow globe. However, the underlying physics of how bubbles freeze has not been studied. Here, we characterize the physics of soap bubbles freezing on an icy substrate and reveal two distinct modes of freezing. The first mode, occurring for isothermally supercooled bubbles, generates a strong Marangoni flow that entrains ice crystals to produce the aforementioned snow globe effect. The second mode occurs when using a cold stage in a warm ambient, resulting in a bottom-up freeze front that eventually halts due to poor conduction along the bubble. Blending experiments, scaling analysis, and numerical methods, the dynamics of the freeze fronts and Marangoni flows are characterized.
IAPP toxicity activates HIF1α/PFKFB3 signaling delaying β-cell loss at the expense of β-cell function
Authors: Montemurro Chiara , Nomoto Hiroshi , Pei Lina , Parekh Vishal S. , Vongbunyong Kenny E. , Vadrevu Suryakiran , Gurlo Tatyana , Butler Alexandra E. , Subramaniam Rohan , Ritou Eleni , Shirihai Orian S. , Satin Leslie S. , Butler Peter C. , Tudzarova Slavica
Published: June 2019

The islet in type 2 diabetes (T2D) is characterized by amyloid deposits derived from islet amyloid polypeptide (IAPP), a protein co-expressed with insulin by β-cells. In common with amyloidogenic proteins implicated in neurodegeneration, human IAPP (hIAPP) forms membrane permeant toxic oligomers implicated in misfolded protein stress. Here, we establish that hIAPP misfolded protein stress activates HIF1α/PFKFB3 signaling, this increases glycolysis disengaged from oxidative phosphorylation with mitochondrial fragmentation and perinuclear clustering, considered a protective posture against increased cytosolic Ca2+ characteristic of toxic oligomer stress. In contrast to tissues with the capacity to regenerate, β-cells in adult humans are minimally replicative, and therefore fail to execute the second pro-regenerative phase of the HIF1α/PFKFB3 injury pathway. Instead, β-cells in T2D remain trapped in the pro-survival first phase of the HIF1α injury repair response with metabolism and the mitochondrial network adapted to slow the rate of cell attrition at the expense of β-cell function.
An ultrathin conformable vibration-responsive electronic skin for quantitative vocal recognition
Authors: Lee Siyoung , Kim Junsoo , Yun Inyeol , Bae Geun Yeol , Kim Daegun , Park Sangsik , Yi Il-Min , Moon Wonkyu , Chung Yoonyoung , Cho Kilwon
Published: June 2019

Flexible and skin-attachable vibration sensors have been studied for use as wearable voice-recognition electronics. However, the development of vibration sensors to recognize the human voice accurately with a flat frequency response, a high sensitivity, and a flexible/conformable form factor has proved a major challenge. Here, we present an ultrathin, conformable, and vibration-responsive electronic skin that detects skin acceleration, which is highly and linearly correlated with voice pressure. This device consists of a crosslinked ultrathin polymer film and a hole-patterned diaphragm structure, and senses voices quantitatively with an outstanding sensitivity of 5.5 V Pa−1 over the voice frequency range. Moreover, this ultrathin device (<5 μm) exhibits superior skin conformity, which enables exact voice recognition because it eliminates vibrational distortion on rough and curved skin surfaces. Our device is suitable for several promising voice-recognition applications, such as security authentication, remote control systems and vocal healthcare.
β-Cardiac myosin hypertrophic cardiomyopathy mutations release sequestered heads and increase enzymatic activity
Authors: Adhikari Arjun S. , Trivedi Darshan V. , Sarkar Saswata S. , Song Dan , Kooiker Kristina B. , Bernstein Daniel , Spudich James A. , Ruppel Kathleen M.
Published: June 2019

Hypertrophic cardiomyopathy (HCM) affects 1 in 500 people and leads to hyper-contractility of the heart. Nearly 40 percent of HCM-causing mutations are found in human β-cardiac myosin. Previous studies looking at the effect of HCM mutations on the force, velocity and ATPase activity of the catalytic domain of human β-cardiac myosin have not shown clear trends leading to hypercontractility at the molecular scale. Here we present functional data showing that four separate HCM mutations located at the myosin head-tail (R249Q, H251N) and head-head (D382Y, R719W) interfaces of a folded-back sequestered state referred to as the interacting heads motif (IHM) lead to a significant increase in the number of heads functionally accessible for interaction with actin. These results provide evidence that HCM mutations can modulate myosin activity by disrupting intramolecular interactions within the proposed sequestered state, which could lead to hypercontractility at the molecular level.
Regulation of CAR T cell-mediated cytokine release syndrome-like toxicity using low molecular weight adapters
Authors: Lee Yong Gu , Chu Haiyan , Lu Yingjuan , Leamon Christopher P. , Srinivasarao Madduri , Putt Karson S. , Low Philip S.
Published: June 2019

Although chimeric antigen receptor (CAR) T cell therapies have demonstrated considerable success in treating hematologic malignancies, they have simultaneously been plagued by a cytokine release syndrome (CRS) that can harm or even kill the cancer patient. We describe a CAR T cell strategy in which CAR T cell activation and cancer cell killing can be sensitively regulated by adjusting the dose of a low molecular weight adapter that must bridge between the CAR T cell and cancer cell to initiate tumor eradication. By controlling the concentration and dosing schedule of adapter administration, we document two methods that can rapidly terminate (<3 h) a pre-existing CRS-like toxicity and two unrelated methods that can pre-emptively prevent a CRS-like toxicity that would have otherwise occurred. Because all four methods concurrently enhance CAR T cell potency, we conclude that proper use of bispecific adapters could potentially avoid a life-threatening CRS while enhancing CAR T cell tumoricidal activity.
CAPRI enables comparison of evolutionarily conserved RNA interacting regions
Authors: Panhale Amol , Richter Florian M. , Ramírez Fidel , Shvedunova Maria , Manke Thomas , Mittler Gerhard , Akhtar Asifa
Published: June 2019

RNA-protein complexes play essential regulatory roles at nearly all levels of gene expression. Using in vivo crosslinking and RNA capture, we report a comprehensive RNA-protein interactome in a metazoan at four levels of resolution: single amino acids, domains, proteins and multisubunit complexes. We devise CAPRI, a method to map RNA-binding domains (RBDs) by simultaneous identification of RNA interacting crosslinked peptides and peptides adjacent to such crosslinked sites. CAPRI identifies more than 3000 RNA proximal peptides in Drosophila and human proteins with more than 45% of them forming new interaction interfaces. The comparison of orthologous proteins enables the identification of evolutionary conserved RBDs in globular domains and intrinsically disordered regions (IDRs). By comparing the sequences of IDRs through evolution, we classify them based on the type of motif, accumulation of tandem repeats, conservation of amino acid composition and high sequence divergence.
Fast genetic mapping of complex traits in C. elegans using millions of individuals in bulk
Authors: Burga Alejandro , Ben-David Eyal , Lemus Vergara Tzitziki , Boocock James , Kruglyak Leonid
Published: June 2019

Genetic studies of complex traits in animals have been hindered by the need to generate, maintain, and phenotype large panels of recombinant lines. We developed a new method, C. elegans eXtreme Quantitative Trait Locus (ceX-QTL) mapping, that overcomes this obstacle via bulk selection on millions of unique recombinant individuals. We use ceX-QTL to map a drug resistance locus with high resolution. We also map differences in gene expression in live worms and discovered that mutations in the co-chaperone sti-1 upregulate the transcription of HSP-90. Lastly, we use ceX-QTL to map loci that influence fitness genome-wide confirming previously reported causal variants and uncovering new fitness loci. ceX-QTL is fast, powerful and cost-effective, and will accelerate the study of complex traits in animals.
Intracavity optical trapping of microscopic particles in a ring-cavity fiber laser
Authors: Kalantarifard Fatemeh , Elahi Parviz , Makey Ghaith , Maragò Onofrio M. , Ilday F. Ömer , Volpe Giovanni
Published: June 2019

Standard optical tweezers rely on optical forces arising when a focused laser beam interacts with a microscopic particle: scattering forces, pushing the particle along the beam direction, and gradient forces, attracting it towards the high-intensity focal spot. Importantly, the incoming laser beam is not affected by the particle position because the particle is outside the laser cavity. Here, we demonstrate that intracavity nonlinear feedback forces emerge when the particle is placed inside the optical cavity, resulting in orders-of-magnitude higher confinement along the three axes per unit laser intensity on the sample. This scheme allows trapping at very low numerical apertures and reduces the laser intensity to which the particle is exposed by two orders of magnitude compared to a standard 3D optical tweezers. These results are highly relevant for many applications requiring manipulation of samples that are subject to photodamage, such as in biophysics and nanosciences.
Publisher Correction: Direct dioxygen evolution in collisions of carbon dioxide with surfaces
Authors: Yao Yunxi , Shushkov Philip , Miller Thomas F. , Giapis Konstantinos P.
Published: June 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Aquifer systems extending far offshore on the U.S. Atlantic margin
Authors: Gustafson Chloe , Key Kerry , Evans Rob L.
Published: June 2019

Low-salinity submarine groundwater contained within continental shelves is a global phenomenon. Mechanisms for emplacing offshore groundwater include glacial processes that drove water into exposed continental shelves during sea-level low stands and active connections to onshore hydrologic systems. While low-salinity groundwater is thought to be abundant, its distribution and volume worldwide is poorly understood due to the limited number of observations. Here we image laterally continuous aquifers extending 90 km offshore New Jersey and Martha’s Vineyard, Massachusetts, on the U.S. Atlantic margin using new shallow water electromagnetic geophysical methods. Our data provide more continuous constraints on offshore groundwater than previous models and present evidence for a connection between the modern onshore hydrologic system and offshore aquifers. We identify clinoforms as a previously unknown structural control on the lateral extent of low-salinity groundwater and potentially a control on where low-salinity water rises into the seafloor. Our data suggest a continuous submarine aquifer system spans at least 350 km of the U.S. Atlantic coast and contains about 2800 km3 of low-salinity groundwater. Our findings can be used to improve models of past glacial, eustatic, tectonic, and geomorphic processes on continental shelves and provide insight into shelf geochemistry, biogeochemical cycles, and the deep biosphere.
In Vivo Water Dynamics in Shewanella oneidensis Bacteria at High Pressure
Authors: Foglia Fabrizia , Hazael Rachael , Meersman Filip , Wilding Martin C. , Sakai Victoria García , Rogers Sarah , Bove Livia E. , Koza Michael Marek , Moulin Martine , Haertlein Michael , Forsyth V. Trevor , McMillan Paul F.
Published: June 2019

Following observations of survival of microbes and other life forms in deep subsurface environments it is necessary to understand their biological functioning under high pressure conditions. Key aspects of biochemical reactions and transport processes within cells are determined by the intracellular water dynamics. We studied water diffusion and rotational relaxation in liveShewanella oneidensisbacteria at pressures up to 500 MPa using quasi-elastic neutron scattering (QENS). The intracellular diffusion exhibits a significantly greater slowdown (by −10–30%) and an increase in rotational relaxation times (+10–40%) compared with water dynamics in the aqueous solutions used to resuspend the bacterial samples. Those results indicate both a pressure-induced viscosity increase and slowdown in ionic/macromolecular transport properties within the cells affecting the rates of metabolic and other biological processes. Our new data support emerging models for intracellular organisation with nanoscale water channels threading between macromolecular regions within a dynamically organized structure rather than a homogenous gel-like cytoplasm.
A fractional diffusion random laser
Authors: Chen Yuyao , Fiorentino Alfredo , Dal Negro Luca
Published: June 2019

The goal of this letter is to introduce the concept of a non-resonant fractional random laser. This is achieved by extending the classical Letokhov model of photon diffusion through disordered gain media to fractional differential operators in space and time. Fractional transport equations effectively describe anomalous photon sub-diffusion phenomena in non-uniform random scattering media with memory and long-range spatial correlation effects. In particular, by analytically solving fractional transport equations in the one-dimensional slab geometry we obtain simple closed-form expressions for the critical amplification volumes required to initiate the laser action in both fractional-order (FO) and distributed-order (DO) space-time fractional reaction-diffusion equations. Our findings demonstrate the benefits of anomalous sub-diffusive photon transport in active media with correlated disorder and stimulate the engineering of novel non-resonant random lasers with significantly reduced footprint and amplification volumes beyond the limitations of uniform disorder and Markovian diffusion processes.
Meniscus-Derived Matrix Scaffolds Promote the Integrative Repair of Meniscal Defects
Authors: Ruprecht Jacob C. , Waanders Taylor D. , Rowland Christopher R. , Nishimuta James F. , Glass Katherine A. , Stencel Jennifer , DeFrate Louis E. , Guilak Farshid , Weinberg J. Brice , McNulty Amy L.
Published: June 2019

Meniscal tears have a poor healing capacity, and damage to the meniscus is associated with significant pain, disability, and progressive degenerative changes in the knee joint that lead to osteoarthritis. Therefore, strategies to promote meniscus repair and improve meniscus function are needed. The objective of this study was to generate porcine meniscus-derived matrix (MDM) scaffolds and test their effectiveness in promoting meniscus repair via migration of endogenous meniscus cells from the surrounding meniscus or exogenously seeded human bone marrow-derived mesenchymal stem cells (MSCs). Both endogenous meniscal cells and MSCs infiltrated the MDM scaffolds. In the absence of exogenous cells, the 8% MDM scaffolds promoted the integrative repair of an in vitro meniscal defect. Dehydrothermal crosslinking and concentration of the MDM influenced the biochemical content and shear strength of repair, demonstrating that the MDM can be tailored to promote tissue repair. These findings indicate that native meniscus cells can enhance meniscus healing if a scaffold is provided that promotes cellular infiltration and tissue growth. The high affinity of cells for the MDM and the ability to remodel the scaffold reveals the potential of MDM to integrate with native meniscal tissue to promote long-term repair without necessarily requiring exogenous cells.
Severe pulmonary disease in an adult primary ciliary dyskinesia population in Brazil
Authors: Olm Mary Anne Kowal , Marson Fernando Augusto Lima , Athanazio Rodrigo Abensur , Nakagawa Naomi Kondo , Macchione Mariangela , Loges Niki Tomas , Omran Heymut , Rached Samia Zahi , Bertuzzo Carmen Sílvia , Stelmach Rafael , Saldiva Paulo Hilário Nascimento , Ribeiro José Dirceu , Jones Marcus Herbert , Mauad Thais
Published: June 2019

Primary Ciliary Dyskinesia (PCD) is underdiagnosed in Brazil. We enrolled patients from an adult service of Bronchiectasis over a two-year period in a cross-sectional study. The inclusion criteria were laterality disorders (LD), cough with recurrent infections and the exclusion of other causes of bronchiectasis. Patients underwent at least two of the following tests: nasal nitric oxide, ciliary movement and analysis of ciliary immunofluorescence, and genetic tests (31 PCD genes + CFTR gene). The clinical characterization included the PICADAR and bronchiectasis scores, pulmonary function, chronic Pseudomonas aeruginosa (cPA) colonization, exhaled breath condensate (EBC) and mucus rheology (MR). Forty-nine of the 500 patients were diagnosed with definite (42/49), probable (5/49), and clinical (2/49) PCD. Twenty-four patients (24/47) presented bi-allelic pathogenic variants in a total of 31 screened PCD genes. A PICADAR score > 5 was found in 37/49 patients, consanguinity in 27/49, LD in 28/49, and eight PCD sibling groups. FACED diagnosed 23/49 patients with moderate or severe bronchiectasis; FEV1 ≤ 50% in 25/49 patients, eight patients had undergone lung transplantation, four had been lobectomized and cPA+ was determined in 20/49. The EBC and MR were altered in all patients. This adult PCD population was characterized by consanguinity, severe lung impairment, genetic variability, altered EBC and MR.
B-mode ultrasound for the assessment of hepatic fibrosis: a quantitative multiparametric analysis for a radiomics approach
Authors: D’Souza Julia C. , Sultan Laith R. , Hunt Stephen J. , Schultz Susan M. , Brice Angela K. , Wood Andrew K. W. , Sehgal Chandra M.
Published: June 2019

Hepatic fibrosis and cirrhosis are a growing global health problem with increasing mortality rates. Early diagnosis and staging of hepatic fibrosis represent a major challenge. Currently liver biopsy is the gold standard for fibrosis assessment; however, biopsy requires an invasive procedure and is prone to sampling error and reader variability. In the current study we investigate using quantitative analysis of computer-extracted features of B-mode ultrasound as a non-invasive tool to characterize hepatic fibrosis. Twenty-two rats were administered diethylnitrosamine (DEN) orally for 12 weeks to induce hepatic fibrosis. Four control rats did not receive DEN. B-mode ultrasound scans sampling throughout the liver were acquired at baseline, 10, and 13 weeks. Computer extracted quantitative parameters representing brightness (echointensity, hepatorenal index) and variance (heterogeneity, anisotropy) of the liver were studied. DEN rats showed an increase in echointensity from 37.1 ± SD 7.8 to 53.5 ± 5.7 (10 w) to 57.5 ± 6.1 (13 w), while the control group remained unchanged at an average of 34.5 ± 4.5. The three other features studied increased similarly over time in the DEN group. Histologic analysis showed METAVIR fibrosis grades of F2-F4 in DEN rats and F0-F1 in controls. Increasing imaging parameters correlated with increasing METAVIR grades, and anisotropy showed the strongest correlation (ρ = 0.58). Sonographic parameters combined using multiparametric logistic regression were able to differentiate between clinically significant and insignificant fibrosis. Quantitative B-mode ultrasound imaging can be implemented in clinical settings as an accurate non-invasive tool for fibrosis assessment.
Functional characterization of retinal ganglion cells using tailored nonlinear modeling
Authors: Shi Qing , Gupta Pranjal , Boukhvalova Alexandra K. , Singer Joshua H. , Butts Daniel A.
Published: June 2019

The mammalian retina encodes the visual world in action potentials generated by 20–50 functionally and anatomically-distinct types of retinal ganglion cell (RGC). Individual RGC types receive synaptic input from distinct presynaptic circuits; therefore, their responsiveness to specific features in the visual scene arises from the information encoded in synaptic input and shaped by postsynaptic signal integration and spike generation. Unfortunately, there is a dearth of tools for characterizing the computations reflected in RGC spike output. Therefore, we developed a statistical model, the separable Nonlinear Input Model, to characterize the excitatory and suppressive components of RGC receptive fields. We recorded RGC responses to a correlated noise (“cloud”) stimulus in an in vitro preparation of mouse retina and found that our model accurately predicted RGC responses at high spatiotemporal resolution. It identified multiple receptive fields reflecting the main excitatory and suppressive components of the response of each neuron. Significantly, our model accurately identified ON-OFF cells and distinguished their distinct ON and OFF receptive fields, and it demonstrated a diversity of suppressive receptive fields in the RGC population. In total, our method offers a rich description of RGC computation and sets a foundation for relating it to retinal circuitry.
Differences in the constituent fiber types contribute to the intermuscular variation in the timing of the developmental synapse elimination
Authors: Lee Young il
Published: June 2019

The emergence of a mature nervous system requires a significant refinement of the synaptic connections initially formed during development. Redundant synaptic connections are removed in a process known as synapse elimination. Synapse elimination has been extensively studied at the rodent neuromuscular junction (NMJ). Although several axons initially converge onto each postsynaptic muscle fiber, all redundant inputs are removed during early postnatal development until a single motor neuron innervates each NMJ. Neuronal activity as well as synaptic glia influence the course of synapse elimination. It is, however, unclear whether target muscle fibers are more than naïve substrates in this process. I examined the influence of target myofiber contractile properties on synapse elimination. The timing of redundant input removal in muscles examined correlates strongly with their proportion of slow myofibers: muscles with more slow fibers undergo elimination more slowly. Moreover, this intermuscular difference in the timing of synapse elimination appears to result from local differences in the rate of elimination on fast versus slow myofibers. These results, therefore, imply that differences in the constituent fiber types help account for the variation in the timing of the developmental synapse elimination between muscles and show that the muscle plays a role in the process.
Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response
Authors: Canto Luisa Matos do , Cury Sarah Santiloni , Barros-Filho Mateus Camargo , Kupper Bruna Elisa Catin , Begnami Maria Dirlei Ferreira de Souza , Scapulatempo-Neto Cristovam , Carvalho Robson Francisco , Marchi Fabio Albuquerque , Olsen Dorte Aalund , Madsen Jonna Skov , Havelund Birgitte Mayland , Aguiar Samuel , Rogatto Silvia Regina
Published: June 2019

Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. We performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between complete (pCR) and incomplete responders to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome, and Plasma Proteome). Seventeen potentially secreted candidates (pCR = 1, pIR = 13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC and association with nCRT response (GSE68204). The expression of circulating amphiregulin and cMET proteins was confirmed in serum from 14 LARC patients. Future studies in liquid biopsies could confirm the utility of these proteins for personalized treatment in LARC patients.
Redox balance, metabolic fingerprint and physiological characterization in contrasting North East Indian rice for Aluminum stress tolerance
Authors: Awasthi Jay Prakash , Saha Bedabrata , Panigrahi Jogeswar , Yanase Emiko , Koyama Hiroyuki , Panda Sanjib Kumar
Published: June 2019

Aluminum (Al) toxicity is a serious problem for rice crop productivity in acidic soils worldwide. The present work was conducted to look out for the alteration in ROS homeostasis; metabolic fingerprint; and morphology in two contrasting Indica rice cultivars of North East India (NE India) to Al toxicity. Al stress led to excess accumulation of ROS (H2O2 and O2−), and this in turn induced ROS mediated cellular damage, as indicated by lipid peroxidation both qualitatively as well as quantitatively. This excessive ROS production also led to significant reduction in chlorophyll content and stomatal conductance. This was followed by the loss of photosynthetic efficiency as detected by chlorophyll fluorescence. This excessive damage due to ROS prompted us to check the anti-oxidative machinery. Antioxidants, especially enzymes (SOD, APX, POX, GR, CAT, DHAR, MDHAR) are very important players in maintenance of ROS homeostasis. In tolerant variety Disang, higher activity of these enzymes and vice versa in sensitive variety, was observed in response to Al treatment. The non-enzymatic antioxidants (proline, ascorbate and glutathione) also showed similar trend. Though the tolerant variety showed strong anti-oxidative machinery, it was unable to completely nullify the stress experienced by the seedlings. Organic acids are also important players in detoxification of Al stress through efflux in the rhizosphere. In tolerant genotype, citrate exudate was found to be more when compared to sensitive genotypes on exposure to high dose of Al. This is supported by higher abundance of FRDL4, a citrate transporter. Not only FRDL4, other stakeholders for Al stress response like ART1 and ALS1 depicted prominent transcript abundance in the tolerant variety. In conclusion, through this study detailed physiological and metabolic characterisation of two contrasting Indica rice varieties Disang and Joymati, native to NE India for Al tolerance was performed for the very first time.
Rosmarinic acid suppresses Alzheimer’s disease development by reducing amyloid β aggregation by increasing monoamine secretion
Authors: Hase Tomoki , Shishido Syun , Yamamoto So , Yamashita Rei , Nukima Haruka , Taira Shu , Toyoda Tsudoi , Abe Keiko , Hamaguchi Tsuyoshi , Ono Kenjiro , Noguchi-Shinohara Moeko , Yamada Masahito , Kobayashi Shoko
Published: June 2019

A new mechanism is revealed by which a polyphenol, rosmarinic acid (RA), suppresses amyloid β (Aβ) accumulation in mice. Here we examined the brains of mice (Alzheimer’s disease model) using DNA microarray analysis and revealed that the dopamine (DA)-signaling pathway was enhanced in the group fed RA versus controls. In the cerebral cortex, the levels of monoamines, such as norepinephrine, 3,4-dihydroxyphenylacetic acid, DA, and levodopa, increased after RA feeding. The expression of DA-degrading enzymes, such as monoamine oxidase B (Maob), was significantly downregulated in the substantia nigra and ventral tegmental area, both DA synthesis regions. Followingin vitrostudies showing that monoamines inhibited Aβ aggregation, thisin vivostudy, in which RA intake increased concentration of monoamine by reducingMaobgene expression, builds on that knowledge by demonstrating that monoamines suppress Aβ aggregation. In conclusion, RA-initiated monoamine increase in the brain may beneficially act against AD.
Quantification of fixed adherent cells using a strong enhancer of the fluorescence of DNA dyes
Authors: Ligasová Anna , Koberna Karel
Published: June 2019

Cell quantification is widely used in basic or applied research. The current sensitive methods of cell quantification are exclusively based on the analysis of non-fixed cells and do not allow the simultaneous detection of various cellular components. A fast, sensitive and cheap method of the quantification of fixed adherent cells is described here. It is based on the incubation of DAPI- or Hoechst 33342-stained cells in a solution containing SDS. The presence of SDS results in the quick de-staining of DNA and simultaneously, in an up-to-1,000-fold increase of the fluorescence intensity of the used dyes. This increase can be attributed to the micelle formation of SDS. The method is sufficiently sensitive to reveal around 50–70 human diploid cells. It is compatible with immunocytochemical detections, the detection of DNA replication and cell cycle analysis by image cytometry. The procedure was successfully tested for the analysis of cytotoxicity. The method is suitable for the quantification of cells exhibiting low metabolic activity including senescent cells. The developed procedure provides high linearity and the signal is high for at least 20 days at room temperature. Only around 90 to 120 minutes is required for the procedure’s completion.
Coordination between vapor pressure deficit and CO2 on the regulation of photosynthesis and productivity in greenhouse tomato production
Authors: Jiao Xiao-Cong , Song Xiao-Ming , Zhang Da-Long , Du Qing-Jie , Li Jian-Ming
Published: June 2019

The high vapor pressure deficit (VPD) in some arid and semi-arid climates creates undesirable conditions for the growth of tomato plants (Solanum lycopersicumL., cv. Jinpeng). The global CO2concentration ([CO2]) has also risen in recent years to levels above 400 μmol·mol−1. However, the coordinated effect of VPD and [CO2] on tomato plant growth remains unclear, especially at VPDs of 5–6 kPa or even higher that are extremely detrimental to plant growth. Here, we explore the interaction of VPD and [CO2] on plant water status, stomatal characteristics, and gas exchange parameters in summer greenhouses in a semi-arid area. Plants were grown in four adjacent glass greenhouses with different environmental conditions: (i) high VPD + low [CO2] representing natural/control conditions; (ii) high VPD + high [CO2] representing enriched CO2; (iii) low VPD + low [CO2] representing reduced VPD; and (iv) low VPD + high [CO2] representing reduced VPD and enriched CO2. Reducing the VPD alleviated the water stress of the plant and increased the gas exchange area of the leaf, which was beneficial to the entry of CO2into the leaf. At this time, the increase of [CO2] was more beneficial to promote the photosynthetic rate and then improve the water use efficiency and yield.
The SRP signal sequence of KdpD
Authors: Pross Eva , Kuhn Andreas
Published: June 2019

KdpD is a four-spanning membrane protein that has two large cytoplasmic domains at the amino- and at the carboxyterminus, respectively. During its biogenesis KdpD binds to the signal recognition particle (SRP) of Escherichia coli that consists of a 48-kDa protein Ffh and a 4.5S RNA. The protein is targeted to the inner membrane surface and is released after contacting the SRP receptor protein FtsY. The information within the KdpD protein that confers SRP interaction was found in the amino-terminal cytoplasmic domain of KdpD, particularly at residues 22–48. Within this sequence a Walker A motif is present at residues 30–38. To determine the actual sequence specificity to SRP, a collection of mutants was constructed. When the KdpD peptides (residues 22–48) were fused to sfGFP the targeting to the membrane was observed by fluorescence microscopy. Further, nascent chains of KdpD bound to ribosomes were purified and their binding to SRP was analysed by microscale thermophoresis. We found that the amino acid residues R22, K24 and K26 are important for SRP interaction, whereas the residues G30, G34 and G36, essential for a functional Walker A motif, can be replaced with alanines without affecting the affinity to SRP-FtsY and membrane targeting.
Publisher Correction: Insight into the microbial world of Bemisia tabaci cryptic species complex and its relationships with its host
Authors: Wang Hua-Ling , Lei Teng , Xia Wen-Qiang , Cameron Stephen L. , Liu Yin-Quan , Zhang Zhen , Gowda Maruthi M. N. , De Barro Paul , Navas-Castillo Jesús , Omongo Christopher A. , Delatte Hélène , Lee Kyeong-Yeoll , Patel Mitulkumar V. , Krause-Sakate Renate , Ng James , Wu San-Ling , Fiallo-Olivé Elvira , Liu Shu-Sheng , Colvin John , Wang Xiao-Wei
Published: June 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Ancient introgression drives adaptation to cooler and drier mountain habitats in a cypress species complex
Authors: Ma Yazhen , Wang Ji , Hu Quanjun , Li Jialiang , Sun Yongshuai , Zhang Lei , Abbott Richard J. , Liu Jianquan , Mao Kangshan
Published: June 2019

Introgression may act as an important source of new genetic variation to facilitate the adaptation of organisms to new environments, yet how introgression might enable tree species to adapt to higher latitudes and elevations remains unclear. Applying whole-transcriptome sequencing and population genetic analyses, we present an example of ancient introgression from a cypress species (Cupressus gigantea) that occurs at higher latitude and elevation on the Qinghai-Tibet Plateau into a related species (C. duclouxiana), which has likely aided the latter species to extend its range by colonizing cooler and drier mountain habitats during postglacial periods. We show that 16 introgressed candidate adaptive loci could have played pivotal roles in response to diverse stresses experienced in a high-elevation environment. Our findings provide new insights into the evolutionary history of Qinghai-Tibet Plateau plants and the importance of introgression in the adaptation of species to climate change.
Functional annotation and Bayesian fine-mapping reveals candidate genes for important agronomic traits in Holstein bulls
Authors: Jiang Jicai , Cole John B. , Freebern Ellen , Da Yang , VanRaden Paul M. , Ma Li
Published: June 2019

A hundred years of data collection in dairy cattle can facilitate powerful studies of complex traits. Cattle GWAS have identified many associated genomic regions. With increasing numbers of cattle sequenced, fine-mapping of causal variants is becoming possible. Here we imputed selected sequence variants to 27,214 Holstein bulls that have highly reliable phenotypes for 35 production, reproduction, and body conformation traits. We performed single-marker scans for the 35 traits and multi-trait tests of the three trait groups, revealing 282 candidate QTL for fine-mapping. We developed a Bayesian Fine-MAPping approach (BFMAP) to integrate fine-mapping with functional enrichment analysis. Our fine-mapping identified 69 promising candidate genes, including ABCC9, VPS13B, MGST1, SCD, MKL1, CSN1S1 for production, CHEK2, GC, KALRN for reproduction, and TMTC2, ARRDC3, ZNF613, CCND2, FGF6 for conformation traits. Collectively, these results demonstrated the utility of BFMAP, identified candidate genes, and enhanced our understanding of the genetic basis of cattle complex traits.
Picosecond timescale tracking of pentacene triplet excitons with chemical sensitivity
Authors: Costantini R. , Faber R. , Cossaro A. , Floreano L. , Verdini A. , Hӓttig C. , Morgante A. , Coriani S. , Dell’Angela M.
Published: June 2019

Singlet fission is a photophysical process in which an optically excited singlet exciton is converted into two triplet excitons. Singlet fission sensitized solar cells are expected to display a greatly enhanced power conversion efficiency compared to conventional single-junction cells, but the efficient design of such devices relies on the selection of materials capable of harvesting triplets generated in the fission chromophore. To this aim, the possibility of measuring triplet exciton dynamics with chemical selectivity paves the way for the rational design of complex heterojunctions, with optimized triplet conversion. Here we exploit the chemical sensitivity of X-ray absorption spectroscopy to track triplet exciton dynamics at the picosecond timescale in multilayer films of pentacene, the archetypal singlet fission material. We experimentally identify the signature of the triplet exciton in the Carbon K-edge absorption spectrum and measure its lifetime of about 300 ps. Our results are supported by state-of-the-art ab initio calculations.
Multiple Sclerosis: Epidemiology, Genetics, Symptoms, and Unmet Needs
Authors: Moreno-Torres Irene , Sabín-Muñoz Julia , García-Merino Antonio
Published: June 2019

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that affects the central nervous system. MS is more prevalent in women and is estimated to affect some 2.3 million people across the world. There is unequivocal genetic susceptibility in MS. The most consistent genetic determinant identified is the major histocompatibility complex (MHC). The haplotypes more strongly related to susceptibility and protection for MS are HLA-DR2 and HLA-DR11, respectively. Some genes outside the MHC, such as IL2RA, IL7R and TNFRSF1A, have also been related to MS. There is a latitudinal gradient of MS prevalence, probably due to environmental factors on the genetic susceptibility. The most important MS risk factors are seropositivity against Epstein–Barr virus, infectious mononucleosis, and smoking. Other factors such as vitamin D or parasitic infections require further investigation. The clinical manifestations of relapsing forms of MS in initial stages are related to demyelination of the susceptible structures such as the optic nerves or spinal cord. In established MS, the clinical symptoms are related to the multisystemic affectation and neurodegeneration such as cognitive impairment or sphincter disorders. An unmet need exists for highly effective medications with low risk for deep immunosuppression and for the symptomatic relief of MS.