bluuebunny/crossref_metadata_2025 huggingface dataset:
Telehealth Uptake into Prenatal Care and Provider Attitudes during the COVID-19 Pandemic in New York City: A Quantitative and Qualitative Analysis
Authors: Madden Nigel , Emeruwa Ukachi N. , Friedman Alexander M. , Aubey Janice J. , Aziz Aleha , Baptiste Caitlin D. , Coletta Jaclyn M. , D'Alton Mary E. , Fuchs Karin M. , Goffman Dena , Gyamfi-Bannerman Cynthia , Kondragunta Sneha , Krenitsky Nicole , Miller Russell S. , Nhan-Chang Chia-Ling , Saint Jean Ashanda M. , Shukla Hemangi P. , Simpson Lynn L. , Spiegel Erica S. , Yates Hope S. , Zork Noelia , Ona Samsiya
Published: June 2020

Objective This study aimed to (1) determine to what degree prenatal care was able to be transitioned to telehealth at prenatal practices associated with two affiliated hospitals in New York City during the novel coronavirus disease 2019 (COVID-19) pandemic and (2) describe providers' experience with this transition.

Study Design Trends in whether prenatal care visits were conducted in-person or via telehealth were analyzed by week for a 5-week period from March 9 to April 12 at Columbia University Irving Medical Center (CUIMC)-affiliated prenatal practices in New York City during the COVID-19 pandemic. Visits were analyzed for maternal-fetal medicine (MFM) and general obstetrical faculty practices, as well as a clinic system serving patients with public insurance. The proportion of visits that were telehealth was analyzed by visit type by week. A survey and semistructured interviews of providers were conducted evaluating resources and obstacles in the uptake of telehealth.

Results During the study period, there were 4,248 visits, of which approximately one-third were performed by telehealth (n = 1,352, 31.8%). By the fifth week, 56.1% of generalist visits, 61.5% of MFM visits, and 41.5% of clinic visits were performed via telehealth. A total of 36 providers completed the survey and 11 were interviewed. Accessing technology and performing visits, documentation, and follow-up using the telehealth electronic medical record were all viewed favorably by providers. In transitioning to telehealth, operational challenges were more significant for health clinics than for MFM and generalist faculty practices with patients receiving public insurance experiencing greater difficulties and barriers to care. Additional resources on the patient and operational level were required to optimize attendance at in-person and video visits for clinic patients.

Conclusion Telehealth was rapidly implemented in the setting of the COVID-19 pandemic and was viewed favorably by providers. Limited barriers to care were observed for practices serving patients with commercial insurance. However, to optimize access for patients with Medicaid, additional patient-level and operational supports were required.

Key Points
A Randomized Controlled Double-Blind Comparative Study between Bupivacaine 0.25% Plus Fentanyl and Bupivacaine 0.25% Plus Dexmedetomidine for Caudal Epidural Postoperative Analgesia in Pediatric Lower Abdominal and Urogenital Surgeries in Indian Genotype
Authors: Godbole Rajashree , Gill Jasmeet , Bhattacharya Brishnik , Shrotriya Shashank , Shrivastava Siddhartha , Bandari Abhilash
Published: June 2020

Objectives This study aimed to clinically evaluate and compare the efficacy of caudal epidural bupivacaine in prolonging the postoperative analgesia, with adjuvants like fentanyl or dexmedetomidine among children of Indian genotype.

Materials and Methods A prospective double-blind randomized comparative study. The study population of 68 patients of Indian phenotype were randomly taken from a random number table and divided into two groups with 34 patients in each group. They received single shot caudal epidural blocks, with group A receiving 0.75 mL/kg of 0.25% bupivacaine + 1 mcg/kg fentanyl, group B receiving 0.75 mL/kg of 0.25% bupivacaine + 1 mcg/kg dexmedetomidine. Global Assessment of anesthesia, defined as the time from caudal injection to the first administration of rescue analgesia, will be recorded for both the groups.

Results The addition of either fentanyl or dexmedetomidine as adjuvants in caudal block provided excellent postoperative analgesia, and sedation was significantly longer duration with dexmedetomidine (18.0 hours) than fentanyl (13.1 hours). We observed good hemodynamic stability in both the groups.

Conclusion Addition of dexmedetomidine over fentanyl to bupivacaine for caudal epidural analgesia in pediatric age group has multiple advantages like better control of intraoperative and postoperative hemodynamics, significantly longer duration of postoperative analgesia, lesser bleeding during surgery, and achieving good surgical satisfaction. As the children are pain-free, calm, quiet, and sedated but arousable, the parents’ satisfaction is rewarding. The caudal epidural dose of 0.25% bupivacaine 0.75 mL/kg with adjuvants like dexmedetomidine or fentanyl is effective for postoperative analgesia in lower abdominal surgeries and is without side effects among the Indian population.
Band offset engineering for p-SnO/n-mc-Si heterojunction solar cell
Authors: Mandal Lipika , Askari Syed Sadique Anwer , Kumar Manoj , Das Mukul Kumar
Published: June 2020

A cost-effective p-SnOx/n-multicrystalline Si heterojunction thin film solar cell with SnOx as an absorber layer is investigated by Technology Computer-Aided Design simulation using experimental values of the absorption coefficient of the SnOx-layer. Heterointerface recombination and trapping of carriers due to the band offsets are considered in the simulation. Conduction and valence band offsets, which can be engineered by varying the growth kinetics dependent bandgap and electron affinity of SnOx, play a significant role in enhancing the efficiency of the solar cell. A maximum conversion efficiency of 10.506% is obtained by a proper choice of affinity and bandgap for a particular thickness of the SnOx-layer.
Rapid quenching of melts may help explain geophysical phenomena
Authors: Bandari Anashe
Published: June 2020

A multi-anvil experimental technique can provide very fast cooling of samples, allowing for the study of silicate melts at room temperature.
Influence of interfacial magnetic ordering and field-cooling effect on perpendicular exchange bias and magnetoresistance in nanoporous IrMn/[Co/Pd] films
Authors: Wu Wen-Bin , Kasiuk Julia , Nguyen Thi Ngoc Anh , Przewoźnik Janusz , Fedotova Julia , Kapusta Czesław , Kupreeva Olga , Lazarouk Serguei , Do Khanh Tung , Nguyen Thanh Huong , Vu Hong Ky , Pham Hoai Linh , Vu Dinh Lam , Åkerman Johan
Published: June 2020

We have studied systematically the effect of field cooling on the magnetic properties of continuous and porous IrMn/[Co/Pd] films. It is found that the coexistence of two ferromagnetic (FM) phases in the porous film, namely, hard-magnetic and soft-magnetic ones, with significantly different magnetic properties relates to the role of pore edges and modifies its magnetic and magnetoresistive properties. It is shown that annealing of the films with their subsequent cooling in an external magnetic field applied for aligning the magnetic moments in the antiferromagnetic (AFM) IrMn layer improves effectively the uniaxial perpendicular anisotropy of the [Co/Pd] layer and induces unidirectional anisotropy in its hard-magnetic regions, blocking simultaneously the soft-magnetic parts by pinning their magnetic moments along the film plane. Magnetoresistance of both continuous and porous films is found to be determined mainly by electron–magnon scattering, whereas the complex morphology of the porous film providing different orientations of exchange coupling at the AFM/FM interface in different film regions modifies significantly the spin-dependent electron transport. The revealed asymmetry of the field dependences of magnetoresistance is attributed both to unidirectional magnetic anisotropy of the FM layer and its splitting into magnetically nonequivalent regions in the porous films. The origin of the observed phenomenon is associated with a local influence on the orientation of AFM magnetic moments by an adjacent ferromagnet.
Electromagnetic pulse emission from target holders during short-pulse laser interactions
Authors: Minenna Damien F. G. , Poyé Alexandre , Bradford Philip , Woolsey Nigel , Tikhonchuk Vladimir T.
Published: June 2020

For the first time, a global model of electromagnetic pulse (EMP) emission connects charge separation in the laser target to quantitative measurements of the electromagnetic field. We present a frequency-domain dipole antenna model which predicts the quantity of charge accumulated in a laser target as well as the EMP amplitude and frequency. The model is validated against measurements from several high-intensity laser facilities, providing insight into target physics and informing the design of next-generation ultra-intense laser facilities. EMP amplitude is proportional to the total charge accumulated on the target, but we demonstrate that it is not directly affected by target charging time (and therefore the laser pulse duration), provided the charging time is shorter than the antenna characteristic time. We propose two independent methods for estimating the charging time based on the laser pulse duration. We also investigate the impact of target holder geometry on EMPs using cylindrical, conical, and helical holders.
Direct numerical simulation of multiscale flow physics of binary droplet collision
Authors: Chen Xiaodong , Yang Vigor
Published: June 2020

Direct numerical simulations are performed to investigate the multiscale flow physics of binary droplet collision over a wide range of Weber numbers and impact factors. All possible collision outcomes, including bouncing (both head-on and off-center), coalescence, reflexive separation, and stretching separation, are considered. The theoretical formulation is based on a complete set of conservation equations for both the liquid and gas phases. An improved volume-of-fluid technique, which is augmented by an adaptive mesh refinement algorithm, is used to track the liquid/gas interface. Several local refinement criteria are validated and employed to improve the computational accuracy and efficiency substantially. In particular, a thickness-based refinement technique is implemented for treating cases involving extremely thin gas films between droplets. The smallest numerical grid is ∼10 nm, which is on the order of 10−5 times the initial droplet diameter. A photorealistic visualization technique is employed to gain direct insights into the detailed collision dynamics, including both the shape evolution and mass relocation. The numerical framework allows us to systematically investigate the underlying mechanisms and processes, such as gas-film drainage and energy and mass transfer, at scales sufficient to resolve the near-field dynamics during droplet collision. The nonmonotonic transition of bouncing and merging outcomes for head-on collision is identified by varying the Weber number over two orders of magnitude. A geometric relation defining the droplet interactions is developed. Analytical models are also established to predict the mass transfer between colliding droplets.
Cavity mode manipulated by single gold nanoparticles
Authors: Lun Yipeng , Zhan Ziyu , Gu Fuxing , Wang Pan , Yu Huakang , Li Zhi-yuan
Published: June 2020

The ability to manipulate microlaser performance is highly desirable so as to promote on-chip classical and quantum information-processing technology. Here, we demonstrate that mode manipulation of bottle microresonators is enabled by precise deposition of single gold nanoparticles in a reconfigurable and selective manner. Numerical investigation reveals the mechanism of introducing optical loss via single Au NP scattering. Experimental results show that the lasing action of cavity modes could be efficiently suppressed, and single mode lasing is successfully achieved with a high side mode suppression factor ∼13 dB.
Topological analysis of SARS CoV-2 main protease
Authors: Estrada Ernesto
Published: June 2020

There is an urgent necessity of effective medication against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), which is producing the COVID-19 pandemic across the world. Its main protease (Mpro) represents an attractive pharmacological target due to its involvement in essential viral functions. The crystal structure of free Mpro shows a large structural resemblance with the main protease of SARS CoV (nowadays known as SARS CoV-1). Here, we report that average SARS CoV-2 Mpro is 1900% more sensitive than SARS CoV-1 Mpro in transmitting tiny structural changes across the whole protein through long-range interactions. The largest sensitivity of Mpro to structural perturbations is located exactly around the catalytic site Cys-145 and coincides with the binding site of strong inhibitors. These findings, based on a simplified representation of the protein as a residue network, may help in designing potent inhibitors of SARS CoV-2 Mpro.
Theoretical issues in deep networks
Authors: Poggio Tomaso , Banburski Andrzej , Liao Qianli
Published: June 2020

While deep learning is successful in a number of applications, it is not yet well understood theoretically. A theoretical characterization of deep learning should answer questions about their approximation power, the dynamics of optimization, and good out-of-sample performance, despite overparameterization and the absence of explicit regularization. We review our recent results toward this goal. In approximation theory both shallow and deep networks are known to approximate any continuous functions at an exponential cost. However, we proved that for certain types of compositional functions, deep networks of the convolutional type (even without weight sharing) can avoid the curse of dimensionality. In characterizing minimization of the empirical exponential loss we consider the gradient flow of the weight directions rather than the weights themselves, since the relevant function underlying classification corresponds to normalized networks. The dynamics of normalized weights turn out to be equivalent to those of the constrained problem of minimizing the loss subject to a unit norm constraint. In particular, the dynamics of typical gradient descent have the same critical points as the constrained problem. Thus there is implicit regularization in training deep networks under exponential-type loss functions during gradient flow. As a consequence, the critical points correspond to minimum norm infima of the loss. This result is especially relevant because it has been recently shown that, for overparameterized models, selection of a minimum norm solution optimizes cross-validation leave-one-out stability and thereby the expected error. Thus our results imply that gradient descent in deep networks minimize the expected error.
Single-vesicle imaging reveals lipid-selective and stepwise membrane disruption by monomeric α-synuclein
Authors: Hannestad Jonas K. , Rocha Sandra , Agnarsson Björn , Zhdanov Vladimir P. , Wittung-Stafshede Pernilla , Höök Fredrik
Published: June 2020

Significance

Neurodegenerative diseases are increasing among the world's population, but there are no cures. These disorders all involve proteins that assemble into amyloid fibers which results in brain cell death. Evidence suggests that association of these proteins with lipid membranes is crucial for both functional and pathological roles. In Parkinson's disease, the involved protein, α-synuclein, is thought to function in trafficking of lipid vesicles in the brain. In search of mechanistic origins, increasing focus is put on identifying neurotoxic reactions induced by membrane interactions. To contribute new clues to this question, we here employed a new surface-sensitive scattering microscopy technique. With this approach, we discovered that α-synuclein perturbs vesicles in a stepwise and lipid-dependent fashion already at very low protein coverage.
ALS/FTD mutations in UBQLN2 impede autophagy by reducing autophagosome acidification through loss of function
Authors: Wu Josephine J. , Cai Ashley , Greenslade Jessie E. , Higgins Nicole R. , Fan Cong , Le Nhat T. T. , Tatman Micaela , Whiteley Alexandra M. , Prado Miguel A. , Dieriks Birger V. , Curtis Maurice A. , Shaw Christopher E. , Siddique Teepu , Faull Richard L. M. , Scotter Emma L. , Finley Daniel , Monteiro Mervyn J.
Published: June 2020

Significance

Mutations in
UBQLN2
cause amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD). UBQLN2 regulates proteostasis by clearing misfolded proteins from cells through the proteasome and autophagy degradation pathways. Here, we report on defects in autophagy that results from knockout or expression of WT and ALS/FTD mutant UBQLN2 proteins in cells and mice. We show that loss of UBQLN2 reduces expression of ATP6v1g1, a critical subunit of the ATPase pump that regulates vacuolar acidification and is required for the maturation of autophagosomes. We show that WT but not ALS/FTD mutant UBQLN2 proteins can rescue the acidification defect. Furthermore, WT but not ALS/FTD mutant UBQLN2 proteins bind and stimulate ATP6v1g1 biogenesis, suggesting an important role played by UBQLN2 in V-ATPase regulation.
Myeloid ALX/FPR2 regulates vascularization following tissue injury
Authors: Sansbury Brian E. , Li Xiaofeng , Wong Blenda , Patsalos Andreas , Giannakis Nikolas , Zhang Michael J. , Nagy Laszlo , Spite Matthew
Published: June 2020

Ischemic injury initiates a sterile inflammatory response that ultimately participates in the repair and recovery of tissue perfusion. Macrophages are required for perfusion recovery during ischemia, in part because they produce growth factors that aid in vascular remodeling. The input signals governing this pro-revascularization phenotype remain of interest. Here we found that hindlimb ischemia increases levels of resolvin D1 (RvD1), an inflammation-resolving lipid mediator that targets macrophages via its receptor, ALX/FPR2. Exogenous RvD1 enhances perfusion recovery during ischemia, and mice deficient in
Alx/Fpr2
have an endogenous defect in this process. Mechanistically, RNA sequencing revealed that RvD1 induces a transcriptional program in macrophages characteristic of a pro-revascularization phenotype. Vascularization of ischemic skeletal muscle, as well as cutaneous wounds, is impaired in mice with myeloid-specific deficiency of
Alx/Fpr2
, and this is associated with altered expression of pro-revascularization genes in skeletal muscle and macrophages isolated from skeletal muscle. Collectively, these results uncover a role of ALX/FPR2 in revascularization that may be amenable to therapeutic targeting in diseases associated with altered tissue perfusion and repair.
RIG-I regulates myeloid differentiation by promoting TRIM25-mediated ISGylation
Authors: Wu Song-Fang , Xia Li , Shi Xiao-Dong , Dai Yu-Jun , Zhang Wei-Na , Zhao Jun-Mei , Zhang Wu , Weng Xiang-Qin , Lu Jing , Le Huang-Ying , Tao Sheng-ce , Zhu Jiang , Chen Zhu , Wang Yue-Ying , Chen Saijuan
Published: June 2020

Retinoic acid-inducible gene I (RIG-I) is up-regulated during granulocytic differentiation of acute promyelocytic leukemia (APL) cells induced by all-
trans
retinoic acid (ATRA). It has been reported that RIG-I recognizes virus-specific 5′-ppp-double-stranded RNA (dsRNA) and activates the type I interferons signaling pathways in innate immunity. However, the functions of RIG-I in hematopoiesis remain unclear, especially regarding its possible interaction with endogenous RNAs and the associated pathways that could contribute to the cellular differentiation and maturation. Herein, we identified a number of RIG-I–binding endogenous RNAs in APL cells following ATRA treatment, including the tripartite motif-containing protein 25 (
TRIM25
) messenger RNA (mRNA).
TRIM25
encodes the protein known as an E3 ligase for ubiquitin/interferon (IFN)-induced 15-kDa protein (ISG15) that is involved in RIG-I–mediated antiviral signaling. We show that RIG-I could bind
TRIM25
mRNA via its helicase domain and C-terminal regulatory domain, enhancing the stability of
TRIM25
transcripts. RIG-I could increase the transcriptional expression of
TRIM25
by caspase recruitment domain (CARD) domain through an IFN-stimulated response element. In addition, RIG-I activated other key genes in the ISGylation pathway by activating signal transducer and activator of transcription 1 (STAT1), including the modifier ISG15 and several enzymes responsible for the conjugation of ISG15 to protein substrates. RIG-I cooperated with STAT1/2 and interferon regulatory factor 1 (IRF1) to promote the activation of the ISGylation pathway. The integrity of ISGylation in ATRA or RIG-I–induced cell differentiation was essential given that knockdown of TRIM25 or ISG15 resulted in significant inhibition of this process. Our results provide insight into the role of the RIG-I-TRIM25-ISGylation axis in myeloid differentiation.
H1 linker histones silence repetitive elements by promoting both histone H3K9 methylation and chromatin compaction
Authors: Healton Sean E. , Pinto Hugo D. , Mishra Laxmi N. , Hamilton Gregory A. , Wheat Justin C. , Swist-Rosowska Kalina , Shukeir Nicholas , Dou Yali , Steidl Ulrich , Jenuwein Thomas , Gamble Matthew J. , Skoultchi Arthur I.
Published: June 2020

Significance

Eukaryotic genomes harbor a vast number of “selfish” DNA elements, including transposable elements and repetitive sequences. They constitute nearly 50% of the human genome and need to be silenced to maintain the integrity of the genome. Aberrant expression of such sequences, possibly due to failure of silencing mechanisms, is associated with human diseases, including cancer. Silencing of these “selfish” DNAs involves methylation of specific lysine residues in the nucleosome core particles that help package these DNA elements into chromatin in the cell nucleus. Here we demonstrate that H1 linker histones, the most abundant chromatin-binding proteins, are critical for silencing of these sequences, by promoting repressive lysine methylation and further compacting these elements into more condensed chromatin structures.
Origin of interannual variability in global mean sea level
Authors: Hamlington Benjamin D. , Piecuch Christopher G. , Reager John T. , Chandanpurkar Hrishi , Frederikse Thomas , Nerem R. Steven , Fasullo John T. , Cheon Se-Hyeon
Published: June 2020

The two dominant drivers of the global mean sea level (GMSL) variability at interannual timescales are steric changes due to changes in ocean heat content and barystatic changes due to the exchange of water mass between land and ocean. With Gravity Recovery and Climate Experiment (GRACE) satellites and Argo profiling floats, it has been possible to measure the relative steric and barystatic contributions to GMSL since 2004. While efforts to “close the GMSL budget” with satellite altimetry and other observing systems have been largely successful with regards to trends, the short time period covered by these records prohibits a full understanding of the drivers of interannual to decadal variability in GMSL. One particular area of focus is the link between variations in the El Niño−Southern Oscillation (ENSO) and GMSL. Recent literature disagrees on the relative importance of steric and barystatic contributions to interannual to decadal variability in GMSL. Here, we use a multivariate data analysis technique to estimate variability in barystatic and steric contributions to GMSL back to 1982. These independent estimates explain most of the observed interannual variability in satellite altimeter-measured GMSL. Both processes, which are highly correlated with ENSO variations, contribute about equally to observed interannual GMSL variability. A theoretical scaling analysis corroborates the observational results. The improved understanding of the origins of interannual variability in GMSL has important implications for our understanding of long-term trends in sea level, the hydrological cycle, and the planet’s radiation imbalance.
Nanoscale co-organization and coactivation of AMPAR, NMDAR, and mGluR at excitatory synapses
Authors: Goncalves Julia , Bartol Tomas M. , Camus Côme , Levet Florian , Menegolla Ana Paula , Sejnowski Terrence J. , Sibarita Jean-Baptiste , Vivaudou Michel , Choquet Daniel , Hosy Eric
Published: June 2020

Significance

Neuron-to-neuron communication is based on synapse activity where presynapses release neurotransmitters, which activate postsynaptic neurotransmitter receptors. The various families of glutamate receptors at the excitatory synapses are responsible of the fast synaptic transmission as well as the regulation of the long-term signaling implicated in information storage and memory. The organization at the nanometer scale of these postsynaptic receptors is a key determinant for synaptic transmission efficiency. Here, we combined dual-color superresolution imaging with electrophysiology and modeling to determine how the various glutamate receptors are co-organized at the nanoscale and to what extent this organization regulates the receptor activation by a single vesicle release.
Molecular height measurement by cell surface optical profilometry (CSOP)
Authors: Son Sungmin , Takatori Sho C. , Belardi Brian , Podolski Marija , Bakalar Matthew H. , Fletcher Daniel A.
Published: June 2020

The physical dimensions of proteins and glycans on cell surfaces can critically affect cell function, for example, by preventing close contact between cells and limiting receptor accessibility. However, high-resolution measurements of molecular heights on native cell membranes have been difficult to obtain. Here we present a simple and rapid method that achieves nanometer height resolution by localizing fluorophores at the tip and base of cell surface molecules and determining their separation by radially averaging across many molecules. We use this method, which we call cell surface optical profilometry (CSOP), to quantify the height of key multidomain proteins on a model cell, as well as to capture average protein and glycan heights on native cell membranes. We show that average height of a protein is significantly smaller than its contour length, due to thermally driven bending and rotation on the membrane, and that height strongly depends on local surface and solution conditions. We find that average height increases with cell surface molecular crowding but decreases with solution crowding by solutes, both of which we confirm with molecular dynamics simulations. We also use experiments and simulations to determine the height of an epitope, based on the location of an antibody, which allows CSOP to profile various proteins and glycans on a native cell surface using antibodies and lectins. This versatile method for profiling cell surfaces has the potential to advance understanding of the molecular landscape of cells and the role of the molecular landscape in cell function.
Employing NaChBac for cryo-EM analysis of toxin action on voltage-gated Na
+
channels in nanodisc
Authors: Gao Shuai , Valinsky William C. , On Nguyen Cam , Houlihan Patrick R. , Qu Qian , Liu Lei , Pan Xiaojing , Clapham David E. , Yan Nieng
Published: June 2020

NaChBac, the first bacterial voltage-gated Na
+
(Na
v
) channel to be characterized, has been the prokaryotic prototype for studying the structure–function relationship of Na
v
channels. Discovered nearly two decades ago, the structure of NaChBac has not been determined. Here we present the single particle electron cryomicroscopy (cryo-EM) analysis of NaChBac in both detergent micelles and nanodiscs. Under both conditions, the conformation of NaChBac is nearly identical to that of the potentially inactivated Na
v
Ab. Determining the structure of NaChBac in nanodiscs enabled us to examine gating modifier toxins (GMTs) of Na
v
channels in lipid bilayers. To study GMTs in mammalian Na
v
channels, we generated a chimera in which the extracellular fragment of the S3 and S4 segments in the second voltage-sensing domain from Na
v
1.7 replaced the corresponding sequence in NaChBac. Cryo-EM structures of the nanodisc-embedded chimera alone and in complex with HuwenToxin IV (HWTX-IV) were determined to 3.5 and 3.2 Å resolutions, respectively. Compared to the structure of HWTX-IV–bound human Na
v
1.7, which was obtained at an overall resolution of 3.2 Å, the local resolution of the toxin has been improved from ∼6 to ∼4 Å. This resolution enabled visualization of toxin docking. NaChBac can thus serve as a convenient surrogate for structural studies of the interactions between GMTs and Na
v
channels in a membrane environment.
Deep rotating convection generates the polar hexagon on Saturn
Authors: Yadav Rakesh K. , Bloxham Jeremy
Published: June 2020

Numerous land- and space-based observations have established that Saturn has a persistent hexagonal flow pattern near its north pole. While observations abound, the physics behind its formation is still uncertain. Although several phenomenological models have been able to reproduce this feature, a self-consistent model for how such a large-scale polygonal jet forms in the highly turbulent atmosphere of Saturn is lacking. Here, we present a three-dimensional (3D) fully nonlinear anelastic simulation of deep thermal convection in the outer layers of gas giant planets that spontaneously generates giant polar cyclones, fierce alternating zonal flows, and a high-latitude eastward jet with a polygonal pattern. The analysis of the simulation suggests that self-organized turbulence in the form of giant vortices pinches the eastward jet, forming polygonal shapes. We argue that a similar mechanism is responsible for exciting Saturn’s hexagonal flow pattern.
Cell-size regulation in budding yeast does not depend on linear accumulation of Whi5
Authors: Barber Felix , Amir Ariel , Murray Andrew W.
Published: June 2020

Cells must couple cell-cycle progress to their growth rate to restrict the spread of cell sizes present throughout a population. Linear, rather than exponential, accumulation of Whi5, was proposed to provide this coordination by causing a higher Whi5 concentration in cells born at a smaller size. We tested this model using the inducible
GAL1
promoter to make the Whi5 concentration independent of cell size. At an expression level that equalizes the mean cell size with that of wild-type cells, the size distributions of cells with galactose-induced Whi5 expression and wild-type cells are indistinguishable. Fluorescence microscopy confirms that the endogenous and
GAL1
promoters produce different relationships between Whi5 concentration and cell volume without diminishing size control in the G1 phase. We also expressed Cln3 from the GAL1 promoter, finding that the spread in cell sizes for an asynchronous population is unaffected by this perturbation. Our findings indicate that size control in budding yeast does not fundamentally originate from the linear accumulation of Whi5, contradicting a previous claim and demonstrating the need for further models of cell-cycle regulation to explain how cell size controls passage through Start.
Global impact of atmospheric arsenic on health risk: 2005 to 2015
Authors: Zhang Lei , Gao Yang , Wu Shiliang , Zhang Shaoqing , Smith Kirk R. , Yao Xiaohong , Gao Huiwang
Published: June 2020

Significance

Exposure to arsenic, a toxic pollutant widespread in air and water, has detrimental impacts on human health. Previous studies on arsenic pollution have primarily focused on groundwater arsenic, leaving the influence of atmospheric arsenic largely ignored. In this study, we have successfully simulated the distribution of atmospheric arsenic around the world and thoroughly examined the health impacts from atmospheric arsenic on a global scale. We find that the combined effect from arsenic in both atmosphere and groundwater may substantially aggravate both the carcinogenic and noncarcinogenic risks associated with arsenic pollution. Our results have important implications for developing effective strategies to mitigate the impacts on public health from arsenic pollution.
How a raindrop gets shattered on biological surfaces
Authors: Kim Seungho , Wu Zixuan , Esmaili Ehsan , Dombroskie Jason J. , Jung Sunghwan
Published: June 2020

Many biological surfaces of animals and plants (e.g., bird feathers, insect wings, plant leaves, etc.) are superhydrophobic with rough surfaces at different length scales. Previous studies have focused on a simple drop-bouncing behavior on biological surfaces with low-speed impacts. However, we observed that an impacting drop at high speeds exhibits more complicated dynamics with unexpected shock-like patterns: Hundreds of shock-like waves are formed on the spreading drop, and the drop is then abruptly fragmented along with multiple nucleating holes. Such drop dynamics result in the rapid retraction of the spreading drop and thereby a more than twofold decrease in contact time. Our results may shed light on potential biological advantages of hypothermia risk reduction for endothermic animals and spore spreading enhancement for fungi via wave-induced drop fragmentation.
cGMP via PKG activates 26S proteasomes and enhances degradation of proteins, including ones that cause neurodegenerative diseases
Authors: VerPlank Jordan J. S. , Tyrkalska Sylwia D. , Fleming Angeleen , Rubinsztein David C. , Goldberg Alfred L.
Published: June 2020

Significance

Most studies of the regulation of proteolysis by the ubiquitin proteasome system have focused on the control of ubiquitination. However, it is now clear that the activity of the 26S proteasome and rates of protein degradation in cells are also tightly regulated through proteasome phosphorylation. Here we demonstrate that agents that raise cGMP and activate cGMP-dependent protein kinase (e.g., widely used phosphodiesterase 5 inhibitors) stimulate proteasome activities and intracellular proteolysis without affecting autophagy. Furthermore, we showed that raising cGMP reduced the levels of the disease-causing mutant tau in a zebrafish model by increasing its degradation, and also decreased the associated morphological abnormalities. Thus, activating the proteasome via cGMP is a promising strategy to prevent the progression of neurodegenerative diseases.
Hepatocyte-specific TAK1 deficiency drives RIPK1 kinase-dependent inflammation to promote liver fibrosis and hepatocellular carcinoma
Authors: Tan Shuixia , Zhao Jing , Sun Ziyu , Cao Shuangyi , Niu Kongyan , Zhong Yedan , Wang Han , Shi Linyu , Pan Heling , Hu Junhao , Qian Lihui , Liu Nan , Yuan Junying
Published: June 2020

Transforming growth factor β-activated kinase1 (TAK1) encoded by the gene MAP3K7 regulates multiple important downstream effectors involved in immune response, cell death, and carcinogenesis. Hepatocyte-specific deletion of TAK1 inTak1ΔHEPmice promotes liver fibrosis and hepatocellular carcinoma (HCC) formation. Here, we report that genetic inactivation of RIPK1 kinase using a kinase dead knockin D138N mutation inTak1ΔHEPmice inhibits the expression of liver tumor biomarkers, liver fibrosis, and HCC formation. Inhibition of RIPK1, however, has no or minimum effect on hepatocyte loss and compensatory proliferation, which are the recognized factors important for liver fibrosis and HCC development. Using single-cell RNA sequencing, we discovered that inhibition of RIPK1 strongly suppresses inflammation induced by hepatocyte-specific loss of TAK1. Activation of RIPK1 promotes the transcription of key proinflammatory cytokines, such as CCL2, and CCR2+macrophage infiltration. Our study demonstrates the role and mechanism of RIPK1 kinase in promoting inflammation, both cell-autonomously and cell-nonautonomously, in the development of liver fibrosis and HCC, independent of cell death, and compensatory proliferation. We suggest the possibility of inhibiting RIPK1 kinase as a therapeutic strategy for reducing liver fibrosis and HCC development by inhibiting inflammation.
New perspective of fracture mechanics inspired by gap test with crack-parallel compression
Authors: Nguyen Hoang , Pathirage Madura , Rezaei Masoud , Issa Mohsen , Cusatis Gianluca , Bažant Zdeněk P.
Published: June 2020

The line crack models, including linear elastic fracture mechanics (LEFM), cohesive crack model (CCM), and extended finite element method (XFEM), rest on the century-old hypothesis of constancy of materials’ fracture energy. However, the type of fracture test presented here, named the gap test, reveals that, in concrete and probably all quasibrittle materials, including coarse-grained ceramics, rocks, stiff foams, fiber composites, wood, and sea ice, the effective mode I fracture energy depends strongly on the crack-parallel normal stress, in-plane or out-of-plane. This stress can double the fracture energy or reduce it to zero. Why hasn’t this been detected earlier? Because the crack-parallel stress in all standard fracture specimens is negligible, and is, anyway, unaccountable by line crack models. To simulate this phenomenon by finite elements (FE), the fracture process zone must have a finite width, and must be characterized by a realistic tensorial softening damage model whose vectorial constitutive law captures oriented mesoscale frictional slip, microcrack opening, and splitting with microbuckling. This is best accomplished by the FE crack band model which, when coupled with microplane model M7, fits the test results satisfactorily. The lattice discrete particle model also works. However, the scalar stress–displacement softening law of CCM and tensorial models with a single-parameter damage law are inadequate. The experiment is proposed as a standard. It represents a simple modification of the three-point-bend test in which both the bending and crack-parallel compression are statically determinate. Finally, a perspective of various far-reaching consequences and limitations of CCM, LEFM, and XFEM is discussed.
Recognition of nonproline N-terminal residues by the Pro/N-degron pathway
Authors: Dong Cheng , Chen Shun-Jia , Melnykov Artem , Weirich Sara , Sun Kelly , Jeltsch Albert , Varshavsky Alexander , Min Jinrong
Published: June 2020

Eukaryotic N-degron pathways are proteolytic systems whose unifying feature is their ability to recognize proteins containing N-terminal (Nt) degradation signals called N-degrons, and to target these proteins for degradation by the 26S proteasome or autophagy. GID4, a subunit of the GID ubiquitin ligase, is the main recognition component of the proline (Pro)/N-degron pathway. GID4 targets proteins through their Nt-Pro residue or a Pro at position 2, in the presence of specific downstream sequence motifs. Here we show that human GID4 can also recognize hydrophobic Nt-residues other than Pro. One example is the sequence Nt-IGLW, bearing Nt-Ile. Nt-IGLW binds to wild-type human GID4 with aKdof 16 μM, whereas the otherwise identical Nt-Pro–bearing sequence PGLW binds to GID4 more tightly, with aKdof 1.9 μM. Despite this difference in affinities of GID4 for Nt-IGLW vs. Nt-PGLW, we found that the GID4-mediated Pro/N-degron pathway of the yeastSaccharomyces cerevisiaecan target an Nt-IGLW–bearing protein for rapid degradation. We solved crystal structures of human GID4 bound to a peptide bearing Nt-Ile or Nt-Val. We also altered specific residues of human GID4 and measured the affinities of resulting mutant GID4s for Nt-IGLW and Nt-PGLW, thereby determining relative contributions of specific GID4 residues to the GID4-mediated recognition of Nt-Pro vs. Nt-residues other than Pro. These and related results advance the understanding of targeting by the Pro/N-degron pathway and greatly expand the substrate recognition range of the GID ubiquitin ligase in both human and yeast cells.
The semantics, syntax and prosody of adverbs in English
Authors: Keizer Evelien
Published: June 2020

In the extensive literature on parenthetical (non-propositional, disjunctive) adverbs, it is often assumed that, on the basis of their semantic, syntactic and prosodic properties, a binary distinction can be made between integrated (non-parenthetical) and non-integrated (parenthetical) adverbs. This paper aims to demonstrate that such a dualistic view is oversimplified, since semantic, syntactic and prosodic (non-)integration need not coincide. On the basis of a detailed analysis of the adverbs frankly (as an illocutionary and manner adverb) and cleverly, stupidly etc. (as subject-oriented and manner adverbs), it is argued that the distinctive features of Functional Discourse Grammar make it possible to capture both the differences and the interaction between these three dimensions of (non-)integration in an insightful and consistent manner.
English why don’t you X as a formulaic
expression
Authors: Thompson Sandra A. , Couper-Kuhlen Elizabeth
Published: June 2020

In this chapter we examine a formulaic expression in
English, why don’t you + action verb/predicate (=
WDY). We show that WDY is used in
everyday conversation to carry out the social work of giving advice, as in
why don't you try taking it again? We argue that this
construction is a formulaic expression because it is not understood
compositionally: the WDY format does not ask a question,
but proposes a future action that the speaker is recommending that the
recipient undertake. Our chapter explores the implicativeness of
WDY for subsequent talk, and reveals the intricate
relationship between the grammar of WDY and the social work
that it is used to do.
When an expression becomes fixed
Authors: Laury Ritva , Helasvuo Marja-Liisa , Rauma Janica
Published: June 2020

This chapter concerns the first person past tense
form of the verb ajatella ‘to think’ as a semi-fixed
expression in spoken Finnish. We examine this expression in present-day
conversation and in older dialect interviews, focusing on its interactional
functions, the types of complements it takes, and its patterns of
morphosyntactic fixedness and morphophonetic erosion in our two datasets. We
show that the verb ajatella is most frequently used in its
first person past tense form, mä ajattelin että
[1sg + think-pst-1sg + comp] ‘I
thought that’, and as has been shown for ‘think’ verbs in many other
languages, it is commonly used to frame stance expressions, but another
frequent use in our Finnish data is in prefacing the speaker’s expression of
her own plans as well as proposals of joint action. Most commonly,
mä ajattelin että is followed by clausal complements in
our older data, while the complements are more diverse in the newer data,
and the expression can also occur without any complements. We also show that
while mä ajattelin että ‘I thought that’ occurs in our data
in drastically reduced form and shows signs of morphosyntactic fixedness
especially in the newer data, it cannot yet be said to have become an
epistemic particle.
Mixotrophic scrippsielloid dinoflagellates prey on tintinnid ciliates
Authors: Coats D. Wayne , Choi Jungmin , Jung Jae Ho , Kim Young Ok , Lu Yameng , Nielsen Lasse Tor
Published: June 2020

Dinoflagellates can serve as predators or parasites of tintinnid ciliates. Known predators feed on the ciliate from outside the tintinnid lorica, while parasites either grow in the host cytoplasm or feed inside in the lorica while attached to the outside of the host cell. Here we report mixotrophic species of Scrippsiella that enter the lorica to consume the ciliate zooid of Helicostomella subulata from Denmark and multiple tintinnid species from Korea. We contrast morphology and life-history stages of these mixotrophic predators with dinokaryote parasites of tintinnids and address phylogenetic relationships based on rDNA sequences. Mixotrophic Scrippsiella species sometimes attack tintinnids that are simultaneously infected by syndinean dinoflagellates, complicating study of life histories and potentially leading to confusion about trophic status and taxonomy.
Ciliate ecology in the eutrophic Bay of Quinte, Lake Ontario: Community structure and feeding characteristics
Authors: Munawar M. , Niblock H. , Fitzpatrick M. , Lorimer J.
Published: June 2020

The ciliate community of the Bay of Quinte, Lake Ontario was assessed over a six year period from 2003 – 2008. One eutrophic site in the upper bay (Belleville) and one more oligotrophic site in the lower bay (Conway), were included in the survey. Both sites contained a mixture of Haptoria, Strobilidium, Halteria, Strombidium, and Vorticella, although the relative proportions varied among sites resulting in different community structures. Ciliate biomass was found to be significantly higher at Belleville (mean: 100.2 ± 14.1 mg m−3) compared to Conway (mean: 37.1 ± 3.5 mg m−3), but could be explained by sudden pulses of Haptoria, primarily species of Mesodinium, which peaked as high as 678.1 mg m−3. Canonical Correspondence Analysis showed a clustering of Halteria, Strobilidium, Tintinnina, Urotricha and Vorticella with surface temperature along with autotrophic picoplankton as a potential prey item. The results suggest that autotrophic picoplankton may be an important food resource for the ciliate community and that there is a strong seasonal gradient to community structure. Future research should be directed at understanding how ciliates influence the transfer of both primary and secondary production to higher trophic levels.
Morphological and molecular phylogeny of the polycytopharyngeal ciliate Pycnothrix monocystoides Schubotz, 1908
Authors: Foissner Wilhelm , Al-Rasheid Khaled A. S. , Strüder-Kypke Michaela C. , Lynn Denis H.
Published: June 2020

We reinvestigated Pycnothrix monocystoides Schubotz, 1908 from the intestine of the African Rock Hyrax (Procavia capensis) collected from Saudi Arabia, using protargol impregnation and electron microscopy. Pycnothrix is a unique, up to 5 mm long intestinal ciliate with about two million cilia and many cytostomes (i.e. actual cytostome plus cytopharynx; polycytopharyngy) in the oral furrow (∼vestibulum) that extends on both sides of the cell. Both walls of the furrow are covered by adoral membranelle-like ciliary polymerizations. To the right of the furrow and the cytostomes there are small ciliary fields, very likely homologous to the “dorsal brush” found in free-living litostomateans. The molecular investigations show Pycnothrix as sister to Balantidium and endemic Australian intestinal ciliates, e.g. the genus Bandia. We propose that the common ancestor had both an oral furrow and a special ciliary field both similar to that found in Balantidium. The unique morphology (polycytopharyngy) and the rather distinct molecular separation suggest maintenance of the family status given by Poche (1913).
ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimer
Authors: Shi Xiaoshan , Yokom Adam L. , Wang Chunxin , Young Lindsey N. , Youle Richard J. , Hurley James H.
Published: June 2020

The autophagy-initiating human ULK complex consists of the kinase ULK1/2, FIP200, ATG13, and ATG101. Hydrogen-deuterium exchange mass spectrometry was used to map their mutual interactions. The N-terminal 640 residues (NTD) of FIP200 interact with the C-terminal IDR of ATG13. Mutations in these regions abolish their interaction. Negative stain EM and multiangle light scattering showed that FIP200 is a dimer, while a single molecule each of the other subunits is present. The FIP200NTD is flexible in the absence of ATG13, but in its presence adopts the shape of the letter C ∼20 nm across. The ULK1 EAT domain interacts loosely with the NTD dimer, while the ATG13:ATG101 HORMA dimer does not contact the NTD. Cryo-EM of the NTD dimer revealed a structural similarity to the scaffold domain of TBK1, suggesting an evolutionary similarity between the autophagy-initiating TBK1 kinase and the ULK1 kinase complex.