bluuebunny/crossref_metadata_2025_split huggingface dataset:
LATS1 but not LATS2 represses autophagy by a kinase-independent scaffold function
Authors: Tang Fengyuan , Gao Ruize , Jeevan-Raj Beena , Wyss Christof B. , Kalathur Ravi K. R. , Piscuoglio Salvatore , Ng Charlotte K. Y. , Hindupur Sravanth K. , Nuciforo Sandro , Dazert Eva , Bock Thomas , Song Shuang , Buechel David , Morini Marco F. , Hergovich Alexander , Matthias Patrick , Lim Dae-Sik , Terracciano Luigi M. , Heim Markus H. , Hall Michael N. , Christofori Gerhard 
Published: December 2019

AbstractAutophagy perturbation represents an emerging therapeutic strategy in cancer. Although LATS1 and LATS2 kinases, core components of the mammalian Hippo pathway, have been shown to exert tumor suppressive activities, here we report a pro-survival role of LATS1 but not LATS2 in hepatocellular carcinoma (HCC) cells. Specifically, LATS1 restricts lethal autophagy in HCC cells induced by sorafenib, the standard of care for advanced HCC patients. Notably, autophagy regulation by LATS1 is independent of its kinase activity. Instead, LATS1 stabilizes the autophagy core-machinery component Beclin-1 by promoting K27-linked ubiquitination at lysine residues K32 and K263 on Beclin-1. Consequently, ubiquitination of Beclin-1 negatively regulates autophagy by promoting inactive dimer formation of Beclin-1. Our study highlights a functional diversity between LATS1 and LATS2, and uncovers a scaffolding role of LATS1 in mediating a cross-talk between the Hippo signaling pathway and autophagy.
Structural basis of nucleosome assembly by the Abo1 AAA+ ATPase histone chaperone
Authors: Cho Carol , Jang Juwon , Kang Yujin , Watanabe Hiroki , Uchihashi Takayuki , Kim Seung Joong , Kato Koichi , Lee Ja Yil , Song Ji-Joon 
Published: December 2019

AbstractThe fundamental unit of chromatin, the nucleosome, is an intricate structure that requires histone chaperones for assembly. ATAD2 AAA+ ATPases are a family of histone chaperones that regulate nucleosome density and chromatin dynamics. Here, we demonstrate that the fission yeast ATAD2 homolog, Abo1, deposits histone H3–H4 onto DNA in an ATP-hydrolysis-dependent manner by in vitro reconstitution and single-tethered DNA curtain assays. We present cryo-EM structures of an ATAD2 family ATPase to atomic resolution in three different nucleotide states, revealing unique structural features required for histone loading on DNA, and directly visualize the transitions of Abo1 from an asymmetric spiral (ATP-state) to a symmetric ring (ADP- and apo-states) using high-speed atomic force microscopy (HS-AFM). Furthermore, we find that the acidic pore of ATP-Abo1 binds a peptide substrate which is suggestive of a histone tail. Based on these results, we propose a model whereby Abo1 facilitates H3–H4 loading by utilizing ATP.
Sensitivity of the global carbonate weathering carbon-sink flux to climate and land-use changes
Authors: Zeng Sibo , Liu Zaihua , Kaufmann Georg 
Published: December 2019

AbstractThe response of carbonate weathering carbon-sink flux (CCSF) to its environmental drivers is still not well understood on the global scale. This hinders understanding of the terrestrial carbon cycle. Here, we show that there is likely to be a widespread and consistent increase in the global CCSF (ranging from + 9.8% (RCP4.5) to + 17.1% (RCP8.5)) over the period 1950–2100. In the coming years the increasing temperature might be expected to have a negative impact on carbonate weathering. However, the increasing rainfall and anticipated land-use changes will counteract this, leading to a greater CCSF. This finding has been obtained by using long-term historical (1950–2005) and modeled future (2006–2100) data for two scenarios (RCP4.5 and RCP8.5) for climate and land-use change in our CCSF equilibrium model. This study stresses the potential role that carbonate weathering may play in the evolution of the global carbon cycle over this century.
Magneto-ionic control of spin polarization in multiferroic tunnel junctions
Authors: Wei Yingfen , Matzen Sylvia , Quinteros Cynthia P. , Maroutian Thomas , Agnus Guillaume , Lecoeur Philippe , Noheda Beatriz 
Published: December 2019

AbstractMultiferroic tunnel junctions (MFTJs) with Hf0.5Zr0.5O2 barriers are reported to show both tunneling magnetoresistance effect (TMR) and tunneling electroresistance effect (TER), displaying four resistance states by magnetic and electric field switching. Here we show that, under electric field cycling of large enough magnitude, the TER can reach values as large as 106%. Moreover, concomitant with this TER enhancement, the devices develop electrical control of spin polarization, with sign reversal of the TMR effect. Currently, this intermediate state exists for a limited number of cycles and understanding the origin of these phenomena is key to improve its stability. The experiments presented here point to the magneto-ionic effect as the origin of the large TER and strong magneto-electric coupling, showing that ferroelectric polarization switching of the tunnel barrier is not the main contribution.
Profiling the effect of nafcillin on HA-MRSA D712 using bacteriological and physiological media
Authors: Rajput Akanksha , Poudel Saugat , Tsunemoto Hannah , Meehan Michael , Szubin Richard , Olson Connor A. , Lamsa Anne , Seif Yara , Dillon Nicholas , Vrbanac Alison , Sugie Joseph , Dahesh Samira , Monk Jonathan M. , Dorrestein Pieter C. , Knight Rob , Nizet Victor , Palsson Bernhard O. , Feist Adam M. , Pogliano Joe 
Published: December 2019

AbstractStaphylococcus aureus strains have been continuously evolving resistance to numerous classes of antibiotics including methicillin, vancomycin, daptomycin and linezolid, compounding the enormous healthcare and economic burden of the pathogen. Cation-adjusted Mueller-Hinton broth (CA-MHB) is the standard bacteriological media for measuring antibiotic susceptibility in the clinical lab, but the use of media that more closely mimic the physiological state of the patient, e.g. mammalian tissue culture media, can in certain circumstances reveal antibiotic activities that may be more predictive of effectiveness in vivo. In the current study, we use both types of media to explore antibiotic resistance phenomena in hospital-acquired USA100 lineage methicillin-resistant, vancomycin-intermediate Staphylococcus aureus (MRSA/VISA) strain D712 via multidimensional high throughput analysis of growth rates, bacterial cytological profiling, RNA sequencing, and exo-metabolomics (HPLC and LC-MS). Here, we share data generated from these assays to shed light on the antibiotic resistance behavior of MRSA/VISA D712 in both bacteriological and physiological media.
Synergistic Effects of Hyperandrogenemia and Obesogenic Western-style Diet on Transcription and DNA Methylation in Visceral Adipose Tissue of Nonhuman Primates
Authors: Carbone Lucia , Davis Brett A. , Fei Suzanne S. , White Ashley , Nevonen Kimberly A. , Takahashi Diana , Vinson Amanda , True Cadence , Roberts Charles T. , Varlamov Oleg 
Published: December 2019

AbstractPolycystic ovary syndrome (PCOS) is a major reproductive disorder that is responsible for 80% of anovulatory infertility and that is associated with hyperandrogenemia, increased risk of obesity, and white adipose tissue (WAT) dysfunction. We have previously demonstrated that the combination of chronic testosterone (T) treatment and an obesogenic Western-style diet (WSD) exerts synergistic functional effects on WAT, leading to increased lipid accumulation in visceral adipocytes by an unknown mechanism. In this study, we examined the whole-genome transcriptional response in visceral WAT to T and WSD, alone and in combination. We observed a synergistic effect of T and WSD on gene expression, resulting in upregulation of lipid storage genes concomitant with adipocyte hypertrophy. Because DNA methylation is known to be associated with body fat distribution and the etiology of PCOS, we conducted whole-genome DNA methylation analysis of visceral WAT. While only a fraction of differentially expressed genes also exhibited differential DNA methylation, in silico analysis showed that differentially methylated regions were enriched in transcription factor binding motifs, suggesting a potential gene regulatory role for these regions. In summary, this study demonstrates that hyperandrogenemia alone does not induce global transcriptional and epigenetic response in young female macaques unless combined with an obesogenic diet.
Multi-Platform Omics Analysis for Identification of Molecular Characteristics and Therapeutic Targets of Uveal Melanoma
Authors: Kim Yong Joon , Park Seo Jin , Maeng Kyung Joo , Lee Sung Chul , Lee Christopher Seungkyu 
Published: December 2019

AbstractCurrently, there is no effective treatment for metastatic uveal melanoma (UVM). Here, we aimed to identify the mechanism involving intrinsic chemoresistance of metastatic UVM and the relevant therapeutic targets for UVM. We analyzed cohorts of 80 and 67 patients with primary UVM and skin cutaneous melanoma (SKCM), respectively, using The Cancer Genome Atlas dataset. Mutational burdens identified by whole exome sequencing were significantly lower in UVM than in SKCM patients. COSMIC mutational signature analysis identified that most of the mutations in UVM patients (>90%) were associated with spontaneous deamination of 5-methylcytosine or defective mismatch repair. Transcriptome analysis revealed that the MYC signature was more enriched in UVM patients, as compared to SKCM patients. Fifty-nine (73.8%) of 80 UVM patients showed gains in MYC copy number, and a high MYC copy number was associated with aggressive clinicopathological features of tumors and poor survival. Kinome-wide siRNA library screening identified several therapeutic targets, reported as synthetic lethal targets for MYC-addicted cancers. Notably, UVM cell lines showed high susceptibility to a WEE1 inhibitor (MK-1775; adavosertib) at a clinically tolerable dose. Overall, our study identified high MYC activity in UVM, and suggested G2/M checkpoint inhibitors as effective therapeutic targets for UVM.
Uncovering ferroelectric polarization in tetragonal (Bi1/2K1/2)TiO3–(Bi1/2Na1/2)TiO3 single crystals
Authors: Kitanaka Yuuki , Noguchi Yuji , Miyayama Masaru 
Published: December 2019

AbstractWe report the robust ferroelectric properties of (1 − x)(Bi1/2Na1/2)TiO3–x(Bi1/2K1/2)TiO3 (x = 33%) single crystals grown by a top-seeded solution growth process under a high oxygen-pressure (0.9 MPa) atmosphere. The sample exhibit a large remanent polarization of 48 μC/cm2 and a sizeable piezoelectric strain constant of 460 pm/V. Neutron powder diffraction structural analysis combined with first-principles calculations reveals that the large ferroelectric polarization comparable to PbTiO3 stems from the hybridization between Bi-6p and O-2p orbitals at a moderately negative chemical pressure.
IL-36γ is a pivotal inflammatory player in periodontitis-associated bone loss
Authors: Cloitre Alexandra , Halgand Boris , Sourice Sophie , Caillon Jocelyne , Huck Olivier , Bugueno Isaac Maximiliano , Batool Fareeha , Guicheux Jérôme , Geoffroy Valérie , Lesclous Philippe 
Published: December 2019

AbstractPeriodontitis is a prevalent chronic inflammatory disease due to the host response (IL-1β, IL-6, TNF-α and IL-17A) to oral bacteria such as Porphyromonas gingivalis. The newer members of the IL-1 family, IL-36s (IL-36α/IL-36β/IL-36γ/IL-36Ra/IL-38) are known to be involved in host defense against P. gingivalis in oral epithelial cells (OECs) and are considered as key inflammatory mediators in chronic diseases. The aim of this study was to investigate the potential role of IL-36s in periodontitis. We showed here that IL-36γ mRNA gingival expression is higher in periodontitis patients, whereas IL-36β and IL-36Ra mRNA expression are lower compared to healthy controls. Interestingly, the elevated IL-36γ expression in patients is positively correlated with the RANKL/OPG ratio, an index of bone resorption. In vitro, IL-36γ expression was induced through TLR2 activation in primary OECs infected with P. gingivalis but not in gingival fibroblasts, the most widespread cell type in gingival connective tissue. In OECs, recombinant IL-36γ enhanced the expression of inflammatory cytokines (IL-1β, IL-6, TNF-α and IL-36γ), of TLR2 and importantly, the RANKL/OPG ratio. These findings suggest that IL-36γ could be a pivotal inflammatory player in periodontitis by perpetuating gingival inflammation and its associated alveolar bone resorption and could be a relevant therapeutic target.
Spatial Distribution of Intracranial Vessel Wall Enhancement in Hypertension and Primary Angiitis of the CNS
Authors: Song Jae W. , Shou Haochang , Obusez Emmanuel C. , Raymond Scott B. , Rafla Samuel D. , Kharal G. Abbas , Schaefer Pamela W. , Romero Javier M. 
Published: December 2019

AbstractWe hypothesized a difference in the spatial distribution of intracranial vessel wall enhancement between CNS vasculitis and risk factors for intracranial atherosclerotic disease (ICAD). Fifty-five vessel wall MR imaging (VWI) exams were included in this retrospective observational study. Intracranial arteries were evaluated for vessel wall enhancement by branching pattern (e.g., primary, secondary, and tertiary segments). Demographic and laboratory data as well as ICAD risk factors, including a diagnosis of hypertension, were collected. A diagnosis of primary angiitis of the CNS (PACNS) was confirmed by biopsy or clinical assessment by a stroke neurologist. Univariate and multivariate Poisson regression models were fit for the outcomes. In multivariate analyses, hypertension showed significant associations with primary (β = 1.31, 95% CI 0.78–1.88, p < 0.0001) and secondary (β = 1.15, 95% CI 0.29–2.18, p = 0.05) segments, contrasting with PACNS which showed a distal spatial distribution with significant associations with secondary (β = 0.77, 95% CI 0.14–1.39, p = 0.05) and tertiary (β = 1.34, 95% CI 0.68–2.01, p < 0.0001) segments. Our results suggest the spatial distribution of vessel wall enhancement is an important consideration when interpreting VWI exams, particularly in patients with a comorbid diagnosis of hypertension. Given the global prevalence of hypertension, these results are impactful and may improve image interpretation of VWI in stroke patients.
Provitamin D3 modulation through prebiotics supplementation: simulation based assessment
Authors: Gokhale Sucheta , Bhaduri Anirban 
Published: December 2019

AbstractVitamin D is important in multiple health conditions. Vitamin D deficiency is prevalent globally even with exposure to adequate sunlight. Reduction in provitamin D3 (7-dehydrocholesterol, 7-DHC) is an important cause of vitamin D3 deficiency. Vitamin supplementation, food fortification, and use of probiotics are some approaches to reduce vitamin D3 deficiency. This study investigates plausibility of 7-DHC biosynthesis through dietary prebiotics supplementation. Furthermore, it reports mechanistic details and constraints for the biosynthesis using flux balance analysis (FBA) simulations. The FBA simulations using co-metabolism models comprising human host and a resident bacterium (Faecalibacterium prausnitzii or Bacteroides thetaiotamicron) indicated increased flux of 7-DHC with short-chain fructooligosaccharide (scFOS) or inulin supplementation. We observed around 2-fold increase in flux compared to the baseline. Biosynthesis of 7-DHC was primarily modulated through acetate, pyruvate and lactate secreted by the bacterium. We observed diverse mechanisms and dose dependent responses. We extended this assessment to 119 resident bacteria and investigated the metabolites profiles with prebiotics supplementation. In summary, the current study suggests the potential use of applying prebiotics in enhancing 7-DHC biosynthesis. Furthermore, performance of the different gut bacteria with prebiotic supplementation for secreted metabolites profile is reported. These results may be useful to design future clinical studies.
Information can be stored in the human skin memristor which has non-volatile memory
Authors: Pabst Oliver , Martinsen Ørjan G. , Chua Leon 
Published: December 2019

AbstractMuch is already understood about the anatomical and physiological mechanisms behind the linear, electrical properties of biological tissues. Studying the non-linear electrical properties, however, opens up for the influence from other processes that are driven by the electric field or movement of charges. An electrical measurement that is affected by the applied electrical stimulus is non-linear and reveals the non-linear electrical properties of the underlying (biological) tissue; if it is done with an alternating current (AC) stimulus, the corresponding voltage current plot may exhibit a pinched hysteresis loop which is the fingerprint of a memristor. It has been shown that human skin and other biological tissues are memristors. Here we performed non-linear electrical measurements on human skin with applied direct current (DC) voltage pulses. By doing so, we found that human skin exhibits non-volatile memory and that analogue information can actually be stored inside the skin at least for three minutes. As demonstrated before, human skin actually contains two different memristor types, one that originates from the sweat ducts and one that is based on thermal changes of the surrounding tissue, the stratum corneum; and information storage is possible in both. Finally, assuming that different physiological conditions of the skin can explain the variations in current responses that we observed among the subjects, it follows that non-linear recordings with DC pulses may find use in sensor applications.
A comparison between observed and DFT calculations on structure of 5-(4-chlorophenyl)-2-amino-1,3,4-thiadiazole
Authors: Kerru Nagaraju , Gummidi Lalitha , Bhaskaruni Sandeep V. H. S. , Maddila Surya Narayana , Singh Parvesh , Jonnalagadda Sreekantha B. 
Published: December 2019

AbstractThe crystal and molecular structure of 5-(4-chlorophenyl)-2-amino-1,3,4-thiadiazole 3 was reported, which was characterized by various spectroscopic techniques (FT-IR, NMR and HRMS) and single-crystal X-ray diffraction. The crystal structure 3 (C8H6ClN3S) crystallized in the orthorhombic space group Pna21 and the unit cell consisted of 8 asymmetric molecules. The unit cell parameters were a = 11.2027(2) Å, b = 7.6705(2) Å, c = 21.2166(6) Å, α = β = γ = 90°, V = 1823.15(8) Å3, Z = 8. In addition, the structural geometry (bond lengths, bond angles, and torsion angles), the electronic properties of mono and dimeric forms of compound 3 were calculated by using the density functional theory (DFT) method at B3LYP level 6-31+ G(d,p), 6-31++ G(d,p) and 6-311+ G(d,p) basis sets in ground state. A good correlation was found (R2 = 0.998) between the observed and theoretical vibrational frequencies. Frontier molecular orbitals (HOMO and LUMO) and Molecular Electrostatic Potential map of the compound was produced by using the optimized structures. The NBO analysis was suggested that the molecular system contains N-H…N hydrogen bonding, strong conjugative interactions and the molecule become more polarized owing to the movement of π-electron cloud from donor to acceptor. The calculated structural and geometrical results were in good rational agreement with the experimental X-ray crystal structure data of 1,3,4-thiadiazol-2-amine, 3. The compound 3 exhibited n→π* UV absorption peak of UV cutoff edge, and great magnitude of the first-order hyperpolarizability was observed. The obtained results suggest that compound 3 could have potential application as NLO material. Therefore, this study provides valuable insight experimentally and theoretically, for designing new chemical entities to meet the demands of specific applications.
PRIMEval: Optimization and screening of multiplex oligonucleotide assays
Authors: Conzemius Rick , Hendling Michaela , Pabinger Stephan , Barišić Ivan 
Published: December 2019

AbstractThe development of multiplex polymerase chain reaction and microarray assays is challenging due to primer dimer formation, unspecific hybridization events, the generation of unspecific by-products, primer depletion, and thus lower amplification efficiencies. We have developed a software workflow with three underlying algorithms that differ in their use case and specificity, allowing the complete in silico evaluation of such assays on user-derived data sets. We experimentally evaluated the method for the prediction of oligonucleotide hybridization events including resulting products and probes, self-dimers, cross-dimers and hairpins at different experimental conditions. The developed method allows explaining the observed artefacts through in silico WGS data and thermodynamic predictions. PRIMEval is available publicly at https://primeval.ait.ac.at.
Age-dependency in binocular rivalry is reflected by exclusive percepts, not mixed percepts
Authors: Arani Elahe , van Ee Raymond , van Wezel Richard 
Published: December 2019

AbstractSome aspects of decision-making are known to decline with normal aging. One of the known perceptual decision-making processes which is vastly studied is binocular rivalry. It is well-established that the older the person, the slower the perceptual dynamics. However, the underlying neurobiological cause is unknown. So, to understand how age affects visual decision-making, we investigated age-related changes in perception during binocular rivalry. In binocular rivalry, the image presented to one eye competes for perceptual dominance with the image presented to the other eye. Perception during binocular rivalry consists of alternations between exclusive percepts. However, frequently, mixed percepts with combinations of the two monocular images occur. The mixed percepts reflect a transition from the percept of one eye to the other but frequently the transitions do not complete the full cycle and the previous exclusive percept becomes dominant again. The transitional idiosyncrasy of mixed percepts has not been studied systematically in different age groups. Previously, we have found evidence for adaptation and noise, and not inhibition, as underlying neural factors that are related to age-dependent perceptual decisions. Based on those conclusions, we predict that mixed percepts/inhibitory interactions should not change with aging. Therefore, in an old and a young age group, we studied binocular rivalry dynamics considering both exclusive and mixed percepts by using two paradigms: percept-choice and percept-switch. We found a decrease in perceptual alternation Probability for older adults, although the rate of mixed percepts did not differ significantly compared to younger adults. Interestingly, the mixed percepts play a very similar transitional idiosyncrasy in our different age groups. Further analyses suggest that differences in synaptic depression, gain modulation at the input level, and/or slower execution of motor commands are not the determining factors to explain these findings. We then argue that changes in perceptual decisions at an older age are the result of changes in neural adaptation and noise.