bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK
Authors: Deng Sunbin , McTiernan Nina , Wei Xuepeng , Arnesen Thomas , Marmorstein Ronen 
Published: February 2020

AbstractThe human N-terminal acetyltransferase E (NatE) contains NAA10 and NAA50 catalytic, and NAA15 auxiliary subunits and associates with HYPK, a protein with intrinsic NAA10 inhibitory activity. NatE co-translationally acetylates the N-terminus of half the proteome to mediate diverse biological processes, including protein half-life, localization, and interaction. The molecular basis for how NatE and HYPK cooperate is unknown. Here, we report the cryo-EM structures of human NatE and NatE/HYPK complexes and associated biochemistry. We reveal that NAA50 and HYPK exhibit negative cooperative binding to NAA15 in vitro and in human cells by inducing NAA15 shifts in opposing directions. NAA50 and HYPK each contribute to NAA10 activity inhibition through structural alteration of the NAA10 substrate-binding site. NAA50 activity is increased through NAA15 tethering, but is inhibited by HYPK through structural alteration of the NatE substrate-binding site. These studies reveal the molecular basis for coordinated N-terminal acetylation by NatE and HYPK.
Precise timing of transcription by c-di-GMP coordinates cell cycle and morphogenesis in Caulobacter
Authors: Kaczmarczyk Andreas , Hempel Antje M. , von Arx Christoph , Böhm Raphael , Dubey Badri N. , Nesper Jutta , Schirmer Tilman , Hiller Sebastian , Jenal Urs 
Published: February 2020

AbstractBacteria adapt their growth rate to their metabolic status and environmental conditions by modulating the length of their G1 period. Here we demonstrate that a gradual increase in the concentration of the second messenger c-di-GMP determines precise gene expression during G1/S transition in Caulobacter crescentus. We show that c-di-GMP stimulates the kinase ShkA by binding to its central pseudo-receiver domain, activates the TacA transcription factor, and initiates a G1/S-specific transcription program leading to cell morphogenesis and S-phase entry. Activation of the ShkA-dependent genetic program causes c-di-GMP to reach peak levels, which triggers S-phase entry and promotes proteolysis of ShkA and TacA. Thus, a gradual increase of c-di-GMP results in precise control of ShkA-TacA activity, enabling G1/S-specific gene expression that coordinates cell cycle and morphogenesis.
Genome-wide meta-analysis identifies eight new susceptibility loci for cutaneous squamous cell carcinoma
Authors: Sarin Kavita Y. , Lin Yuan , Daneshjou Roxana , Ziyatdinov Andrey , Thorleifsson Gudmar , Rubin Adam , Pardo Luba M. , Wu Wenting , Khavari Paul A. , Uitterlinden Andre , Nijsten Tamar , Toland Amanda E. , Olafsson Jon H. , Sigurgeirsson Bardur , Thorisdottir Kristin , Jorgensen Eric , Whittemore Alice S. , Kraft Peter , Stacey Simon N. , Stefansson Kari , Asgari Maryam M. , Han Jiali 
Published: February 2020

AbstractCutaneous squamous cell carcinoma (SCC) is one of the most common cancers in the United States. Previous genome-wide association studies (GWAS) have identified 14 single nucleotide polymorphisms (SNPs) associated with cutaneous SCC. Here, we report the largest cutaneous SCC meta-analysis to date, representing six international cohorts and totaling 19,149 SCC cases and 680,049 controls. We discover eight novel loci associated with SCC, confirm all previously associated loci, and perform fine mapping of causal variants. The novel SNPs occur within skin-specific regulatory elements and implicate loci involved in cancer development, immune regulation, and keratinocyte differentiation in SCC susceptibility.
Serum neurofilament light levels in normal aging and their association with morphologic brain changes
Authors: Khalil Michael , Pirpamer Lukas , Hofer Edith , Voortman Margarete M. , Barro Christian , Leppert David , Benkert Pascal , Ropele Stefan , Enzinger Christian , Fazekas Franz , Schmidt Reinhold , Kuhle Jens 
Published: February 2020

AbstractNeurofilament light (NfL) protein is a marker of neuro-axonal damage and can be measured not only in cerebrospinal fluid but also in serum, which allows for repeated assessments. There is still limited knowledge regarding the association of serum NfL (sNfL) with age and subclinical morphologic brain changes and their dynamics in the normal population. We measured sNfL by a single molecule array (Simoa) assay in 335 individuals participating in a population-based cohort study and after a mean follow-up time of 5.9 years (n = 103). Detailed clinical examination, cognitive testing and 3T brain MRI were performed to assess subclinical brain damage. We show that rising and more variable sNfL in individuals >60 years indicate an acceleration of neuronal injury at higher age, which may be driven by subclinical comorbid pathologies. This is supported by a close association of sNfL with brain volume changes in a cross-sectional and especially longitudinal manner.
Supersymmetry in the time domain and its applications in optics
Authors: García-Meca Carlos , Ortiz Andrés Macho , Sáez Roberto Llorente 
Published: February 2020

AbstractSupersymmetry is a conjectured symmetry between bosons and fermions aiming at solving fundamental questions in string and quantum field theory. Its subsequent application to quantum mechanics led to a ground-breaking analysis and design machinery, later fruitfully extrapolated to photonics. In all cases, the algebraic transformations of quantum-mechanical supersymmetry were conceived in the space realm. Here, we demonstrate that Maxwell’s equations, as well as the acoustic and elastic wave equations, also possess an underlying supersymmetry in the time domain. We explore the consequences of this property in the field of optics, obtaining a simple analytic relation between the scattering coefficients of numerous time-varying systems, and uncovering a wide class of reflectionless, three dimensional, all-dielectric, isotropic, omnidirectional, polarisation-independent, non-complex media. Temporal supersymmetry is also shown to arise in dispersive media supporting temporal bound states, which allows engineering their momentum spectra and dispersive properties. These unprecedented features may enable the creation of novel reconfigurable devices, including invisible materials, frequency shifters, isolators, and pulse-shape transformers.
High resolution 3D mapping of grain kinematics during high temperature sequestration of SO2 from flue gas by carbonate aggregates
Authors: Saadatfar Mohammad , Brink Frank , Latham Shane , King Penelope , Middleton Jill , Troitzsch Ulrike , Turner Michael , Henley Richard W. 
Published: February 2020

AbstractSulphur dioxide (SO2) is removed from flue gases prior to discharge into the atmosphere by high temperature sulphation reactions with the mineral calcite (CaCO3) in the form of calcite aggregates such as limestone. The efficiency of this industrial-scale process is constrained by the self-inhibiting growth of anhydrite (CaSO4) along calcite grain boundaries. Using very high resolution X-ray μCT and Scanning Electron Microscopy we show, for the first time, how the sulphation reaction is initiated by the anisotropic thermal expansion of calcite grains to produce high inter-grain permeability. In turn fast gas-solid reaction occurs to produce a network of porous anhydrite layers between grains. Individual calcite grains are then free to rotate and translate with respect to each other as the sulphation reaction proceeds. Grain translations of up to 24 μm and rotations of up to 0.64 degrees have been tracked in samples of a highly compacted calcite aggregate (Carrara Marble) across up to 600,000 grains through heating and cooling cycles during exposure to SO2 gas flow at temperatures from 600 to 750 °C at one atmosphere. Such grain kinematics help to maintain gas phase permeability in the solid reactant and mitigate the inhibitory growth of porous anhydrite on grain boundaries.
REP-X: An Evolution-guided Strategy for the Rational Design of Cysteine-less Protein Variants
Authors: Dalton Kevin , Lopez Tom , Pande Vijay , Frydman Judith 
Published: February 2020

AbstractSite-specific labeling of proteins is often a prerequisite for biophysical and biochemical characterization. Chemical modification of a unique cysteine residue is among the most facile methods for site-specific labeling of proteins. However, many proteins have multiple reactive cysteines, which must be mutated to other residues to enable labeling of unique positions. This trial-and-error process often results in cysteine-free proteins with reduced activity or stability. Herein we describe a general methodology to rationally engineer cysteine-less proteins. Briefly, natural variation across orthologues is exploited to identify suitable cysteine replacements compatible with protein activity and stability. As a proof-of-concept, we recount the successful engineering of a cysteine-less mutant of the group II chaperonin from methanogenic archaeon Methanococcus maripaludis. A webapp, REP-X (Replacement at Endogenous Positions from eXtant sequences), which enables users to design their own cysteine-less protein variants, will make this rational approach widely available.
Association between myopia and peripapillary hyperreflective ovoid mass-like structures in children
Authors: Lyu In Jeong , Park Kyung-Ah , Oh Sei Yeul 
Published: February 2020

AbstractWe investigated the characteristics of children with peripapillary hyperreflective ovoid mass-like structures (PHOMS) and evaluated the associated risk factors. This cross-sectional study included 132 eyes of 66 children with PHOMS and 92 eyes of 46 children without PHOMS (controls) who were assessed by disc enhanced-depth image spectral-domain (SD) optical coherence tomography (OCT). Univariable and multivariable logistic analyses were performed to evaluate risk factors associated with presence of PHOMS. Among the 66 children with PHOMS, 53 (80.3%) had bilateral and 13 (19.7%) had unilateral PHOMS. The mean age of the PHOMS group was 11.7 ± 2.6 years, and that of the control group was 11.4 ± 3.1 years. The mean spherical equivalent (SE) as determined by cycloplegic refraction was −3.13 ± 1.87 diopters (D) in the PHOMS group and −0.95 ± 2.65 D in the control group. Additionally, mean astigmatism was 0.67 ± 0.89 D and 0.88 ± 1.02 D in the PHOMS group and the control group, respectively. Mean disc size was 1,735 ± 153 µm in the PHOMS group and 1,741 ± 190 µm in the control group, while mean optic nerve head (ONH) tilt angle was 9.84 ± 5.38 degrees in the PHOMS group and 3.71 ± 4.41 degrees in the control group. SE and ONH tilt angle were significantly associated with PHOMS according to both univariable [odds ratio (OR): 1.59; p < 0.001 and OR: 1.35; p < 0.001, respectively] and multivariable (OR: 1.71; p = 0.001 and OR: 1.29; p = 0.001, respectively) logistic regression analyses. There was a significant correlation between SE and ONH tilt (r = −0.46; p < 0.001). In conclusion, PHOMS is associated with myopic shift in children, and optic disc tilt may be a mediator between myopia and PHOMS.
Soil properties explain tree growth and mortality, but not biomass, across phosphorus-depleted tropical forests
Authors: Soong Jennifer L. , Janssens Ivan A. , Grau Oriol , Margalef Olga , Stahl Clément , Van Langenhove Leandro , Urbina Ifigenia , Chave Jerome , Dourdain Aurelie , Ferry Bruno , Freycon Vincent , Herault Bruno , Sardans Jordi , Peñuelas Josep , Verbruggen Erik 
Published: February 2020

AbstractWe observed strong positive relationships between soil properties and forest dynamics of growth and mortality across twelve primary lowland tropical forests in a phosphorus-poor region of the Guiana Shield. Average tree growth (diameter at breast height) increased from 0.81 to 2.1 mm yr−1 along a soil texture gradient from 0 to 67% clay, and increasing metal-oxide content. Soil organic carbon stocks in the top 30 cm ranged from 30 to 118 tons C ha−1, phosphorus content ranged from 7 to 600 mg kg−1 soil, and the relative abundance of arbuscular mycorrhizal fungi ranged from 0 to 50%, all positively correlating with soil clay, and iron and aluminum oxide and hydroxide content. In contrast, already low extractable phosphorus (Bray P) content decreased from 4.4 to <0.02 mg kg−1 in soil with increasing clay content. A greater prevalence of arbuscular mycorrhizal fungi in more clayey forests that had higher tree growth and mortality, but not biomass, indicates that despite the greater investment in nutrient uptake required, soils with higher clay content may actually serve to sustain high tree growth in tropical forests by avoiding phosphorus losses from the ecosystem. Our study demonstrates how variation in soil properties that retain carbon and nutrients can help to explain variation in tropical forest growth and mortality, but not biomass, by requiring niche specialization and contributing to biogeochemical diversification across this region.
An assessment of oil palm plantation aboveground biomass stocks on tropical peat using destructive and non-destructive methods
Authors: Lewis Kennedy , Rumpang Elisa , Kho Lip Khoon , McCalmont Jon , Teh Yit Arn , Gallego-Sala Angela , Hill Timothy Charles 
Published: February 2020

AbstractThe recent expansion of oil palm (OP, Elaeis guineensis) plantations into tropical forest peatlands has resulted in ecosystem carbon emissions. However, estimates of net carbon flux from biomass changes require accurate estimates of the above ground biomass (AGB) accumulation rate of OP on peat. We quantify the AGB stocks of an OP plantation on drained peat in Malaysia from 3 to 12 years after planting using destructive harvests supported by non-destructive surveys of a further 902 palms. Peat specific allometric equations for palm (R2 = 0.92) and frond biomass are developed and contrasted to existing allometries for OP on mineral soils. Allometries are used to upscale AGB estimates to the plantation block-level. Aboveground biomass stocks on peat accumulated at ~6.39 ± 1.12 Mg ha−1 per year in the first 12 years after planting, increasing to ~7.99 ± 0.95 Mg ha−1 yr−1 when a ‘perfect’ plantation was modelled. High inter-palm and inter-block AGB variability was observed in mature classes as a result of variations in palm leaning and mortality. Validation of the allometries defined and expansion of non-destructive inventories across alternative plantations and age classes on peat would further strengthen our understanding of peat OP AGB accumulation rates.
Phylogenetic analysis of small ruminant lentiviruses in Germany and Iran suggests their expansion with domestic sheep
Authors: Molaee Vahid , Bazzucchi Moira , De Mia Gian Mario , Otarod Vahid , Abdollahi Darab , Rosati Sergio , Lühken Gesine 
Published: February 2020

AbstractSmall ruminant lentiviruses (SRLVs) are found in sheep in Germany and Iran. SRLVs have been classified into four genotypes: A–C and E. Genotype A has been subdivided into 20 subtypes. Previous studies suggested that, first, the ancestors of genotype A are those SRLVs found in Turkey, second, the evolution of SRLVs is related to the domestication process, and, third, SRLV infection was first observed in sheep in Iceland and the source of that infection was a flock imported from Germany. This study generated, for the first time, partial SRLV sequence data from German and Iranian sheep, enhancing our knowledge of the genetic and evolutionary relationships of SRLVs, and their associations with the domestication process. Based on 54 SRLV sequences from German and Iranian sheep, our results reveal: (1) SRLV subtypes A4, A5, A11, A16 and A21 (new) are found in German sheep and A22 (new) in Iranian sheep. (2) Genotype A has potentially an additional ancestor (A22), found in Iran, Lebanon and Jordan. (3) Subtype A22 is likely an old version of SRLVs. (4) The transmission routes of some SRLVs are compatible with domestication pathways. (5) This study found no evidence of Icelandic subtype A1 in German sheep.
Differences in Transcriptional Dynamics Between T-cells and Macrophages as Determined by a Three-State Mathematical Model
Authors: DeMarino Catherine , Cowen Maria , Pleet Michelle L. , Pinto Daniel O. , Khatkar Pooja , Erickson James , Docken Steffen S. , Russell Nicholas , Reichmuth Blake , Phan Tin , Kuang Yang , Anderson Daniel M. , Emelianenko Maria , Kashanchi Fatah 
Published: February 2020

AbstractHIV-1 viral transcription persists in patients despite antiretroviral treatment, potentially due to intermittent HIV-1 LTR activation. While several mathematical models have been explored in the context of LTR-protein interactions, in this work for the first time HIV-1 LTR model featuring repressed, intermediate, and activated LTR states is integrated with generation of long (env) and short (TAR) RNAs and proteins (Tat, Pr55, and p24) in T-cells and macrophages using both cell lines and infected primary cells. This type of extended modeling framework allows us to compare and contrast behavior of these two cell types. We demonstrate that they exhibit unique LTR dynamics, which ultimately results in differences in the magnitude of viral products generated. One of the distinctive features of this work is that it relies on experimental data in reaction rate computations. Two RNA transcription rates from the activated promoter states are fit by comparison of experimental data to model predictions. Fitting to the data also provides estimates for the degradation/exit rates for long and short viral RNA. Our experimentally generated data is in reasonable agreement for the T-cell as well macrophage population and gives strong evidence in support of using the proposed integrated modeling paradigm. Sensitivity analysis performed using Latin hypercube sampling method confirms robustness of the model with respect to small parameter perturbations. Finally, incorporation of a transcription inhibitor (F07#13) into the governing equations demonstrates how the model can be used to assess drug efficacy. Collectively, our model indicates transcriptional differences between latently HIV-1 infected T-cells and macrophages and provides a novel platform to study various transcriptional dynamics leading to latency or activation in numerous cell types and physiological conditions.
Diamond lateral FinFET with triode-like behavior
Authors: Huang Biqin , Bai Xiwei , Lam Stephen K. , Kim Samuel J. 
Published: February 2020

AbstractIn this letter we report a diamond lateral FinFET fabricated using an ohmic regrowth technique. The use of ohmic regrowth separates the source/drain and gate fabrication, providing a viable means to improve ohmic contact resistance while protecting the top surface of the diamond channel from dry etch damage. Enabled by high channel quality, the diamond transistor behavior was shown to transit from a pentode-like to a triode-like characteristic when channel length decreased. For the first time, space charge limited transport in diamond FinFETs with a short channel length was demonstrated. We have analyzed the space charge limited transport from room temperature to 150 °C. This space charge limited transport, in combination with improved ohmic contacts, will enable diamond FinFETs for various high-power applications.
Physical performances show conflicting associations in aged manual workers
Authors: Norheim Kristoffer L. , Samani Afshin , Bønløkke Jakob H. , Omland Øyvind , Madeleine Pascal 
Published: February 2020

AbstractAgeing is associated with a decrease in physical performance implying that aged manual workers may be unable to match the physical requirements of their jobs. In this cross-sectional study, 96 male manual workers aged 51–72 years were recruited. Outcomes included handgrip strength (HGS), fat-free mass (FFM), fat percentage, cardiorespiratory fitness ($$\dot{{\rm{V}}}$$V̇O2max), forced vital capacity (FVC), forced expiratory volume after 1 s (FEV1), spinal flexibility, sit-to-stand test performance and static balance. Covariates included height, smoking habits, leisure-time physical activity and systemic inflammation from blood samples. Outcomes were also compared with general populations. Age was negatively related to FFM and FEV1, whereas static balance (velocity of displacement) was positively associated with age. Greater HGS, but poorer $$\dot{{\rm{V}}}$$V̇O2max and FEV1/FEV ratio were found compared with general populations. Age was negatively related with physical performances although a large part of the variance in performance could be explained by factors other than age such as smoking and systemic inflammation. The manual workers had greater muscle strength but had poorer cardiorespiratory fitness and lung function when compared with general populations. Specific health interventions targeting specifically cardiorespiratory fitness, lung function, and balance may be needed to maintain physical performances among manual workers.
SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells
Authors: Hassan Nourhan , Rutsch Niklas , Győrffy Balázs , Espinoza-Sánchez Nancy Adriana , Götte Martin 
Published: February 2020

AbstractIn several carcinomas, the SET Domain Containing 3, Actin Histidine Methyltransferase (SETD3) is associated with oncogenesis. However, there is little knowledge about the role of SETD3 in the progression and prognosis of breast cancer. In this study, we first analyzed the prognostic value of SETD3 in breast cancer patients using the database of the public Kaplan-Meier plotter. Moreover, in vitro assays were performed to assess the role of SETD3 in the viability and capacity of invasion of human breast cancer cell lines. We observed that the high expression of SETD3 was associated with better relapse-free survival (RFS) of the whole collective of 3,951 patients, of Estrogen Receptor-positive, and of Luminal A-type breast cancer patients. However, in patients lacking expression of estrogen-, progesterone- and HER2-receptor, and those affected by a p53-mutation, SETD3 was associated with poor RFS. In vitro analysis showed that SETD3 siRNA depletion affects the viability of triple-negative cells as well as the cytoskeletal function and capacity of invasion of highly invasive MDA-MB-231 cells. Interestingly, SETD3 regulates the expression of other genes associated with cancer such as β-actin, FOXM1, FBXW7, Fascin, eNOS, and MMP-2. Our study suggests that SETD3 expression can act as a subtype-specific biomarker for breast cancer progression and prognosis.
Sting nematodes modify metabolomic profiles of host plants
Authors: Willett Denis S. , Filgueiras Camila C. , Benda Nicole D. , Zhang Jing , Kenworthy Kevin E. 
Published: February 2020

AbstractPlant-parasitic nematodes are devastating pathogens of many important agricultural crops. They have been successful in large part due to their ability to modify host plant metabolomes to their benefit. Both root-knot and cyst nematodes are endoparasites that have co-evolved to modify host plants to create sophisticated feeding cells and suppress plant defenses. In contrast, the ability of migratory ectoparasitic nematodes to modify host plants is unknown. Based on global metabolomic profiling of sting nematodes in African bermudagrass, ectoparasites can modify the global metabolome of host plants. Specifically, sting nematodes suppress amino acids in susceptible cultivars. Upregulation of compounds linked to plant defense have negative impacts on sting nematode population densities. Pipecolic acid, linked to systemic acquired resistance induction, seems to play a large role in protecting tolerant cultivars from sting nematode feeding and could be targeted in breeding programs.