bluuebunny/crossref_metadata_2025_split huggingface dataset:
Grain structure control during metal 3D printing by high-intensity ultrasound
Authors: Todaro C. J. , Easton M. A. , Qiu D. , Zhang D. , Bermingham M. J. , Lui E. W. , Brandt M. , StJohn D. H. , Qian M. 
Published: January 2020

AbstractAdditive manufacturing (AM) of metals, also known as metal 3D printing, typically leads to the formation of columnar grain structures along the build direction in most as-built metals and alloys. These long columnar grains can cause property anisotropy, which is usually detrimental to component qualification or targeted applications. Here, without changing alloy chemistry, we demonstrate an AM solidification-control solution to printing metallic alloys with an equiaxed grain structure and improved mechanical properties. Using the titanium alloy Ti-6Al-4V as a model alloy, we employ high-intensity ultrasound to achieve full transition from columnar grains to fine (~100 µm) equiaxed grains in AM Ti-6Al-4V samples by laser powder deposition. This results in a 12% improvement in both the yield stress and tensile strength compared with the conventional AM columnar Ti-6Al-4V. We further demonstrate the generality of our technique by achieving similar grain structure control results in the nickel-based superalloy Inconel 625, and expect that this method may be applicable to other metallic materials that exhibit columnar grain structures during AM.
The role of transient resonances for ultra-fast imaging of single sucrose nanoclusters
Authors: Ho Phay J. , Daurer Benedikt J. , Hantke Max F. , Bielecki Johan , Al Haddad Andre , Bucher Maximilian , Doumy Gilles , Ferguson Ken R. , Flückiger Leonie , Gorkhover Tais , Iwan Bianca , Knight Christopher , Moeller Stefan , Osipov Timur , Ray Dipanwita , Southworth Stephen H. , Svenda Martin , Timneanu Nicusor , Ulmer Anatoli , Walter Peter , Hajdu Janos , Young Linda , Maia Filipe R. N. C. , Bostedt Christoph 
Published: January 2020

AbstractIntense x-ray free-electron laser (XFEL) pulses hold great promise for imaging function in nanoscale and biological systems with atomic resolution. So far, however, the spatial resolution obtained from single shot experiments lags averaging static experiments. Here we report on a combined computational and experimental study about ultrafast diffractive imaging of sucrose clusters which are benchmark organic samples. Our theoretical model matches the experimental data from the water window to the keV x-ray regime. The large-scale dynamic scattering calculations reveal that transient phenomena driven by non-linear x-ray interaction are decisive for ultrafast imaging applications. Our study illuminates the complex interplay of the imaging process with the rapidly changing transient electronic structures in XFEL experiments and shows how computational models allow optimization of the parameters for ultrafast imaging experiments.
DAF-16/FOXO requires Protein Phosphatase 4 to initiate transcription of stress resistance and longevity promoting genes
Authors: Sen Ilke , Zhou Xin , Chernobrovkin Alexey , Puerta-Cavanzo Nataly , Kanno Takaharu , Salignon Jérôme , Stoehr Andrea , Lin Xin-Xuan , Baskaner Bora , Brandenburg Simone , Björkegren Camilla , Zubarev Roman A. , Riedel Christian G. 
Published: January 2020

AbstractIn C. elegans, the conserved transcription factor DAF-16/FOXO is a powerful aging regulator, relaying dire conditions into expression of stress resistance and longevity promoting genes. For some of these functions, including low insulin/IGF signaling (IIS), DAF-16 depends on the protein SMK-1/SMEK, but how SMK-1 exerts this role has remained unknown. We show that SMK-1 functions as part of a specific Protein Phosphatase 4 complex (PP4SMK-1). Loss of PP4SMK-1 hinders transcriptional initiation at several DAF-16-activated genes, predominantly by impairing RNA polymerase II recruitment to their promoters. Search for the relevant substrate of PP4SMK-1 by phosphoproteomics identified the conserved transcriptional regulator SPT-5/SUPT5H, whose knockdown phenocopies the loss of PP4SMK-1. Phosphoregulation of SPT-5 is known to control transcriptional events such as elongation and termination. Here we also show that transcription initiating events are influenced by the phosphorylation status of SPT-5, particularly at DAF-16 target genes where transcriptional initiation appears rate limiting, rendering PP4SMK-1 crucial for many of DAF-16’s physiological roles.
Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow
Authors: Marina Nephtali , Christie Isabel N. , Korsak Alla , Doronin Maxim , Brazhe Alexey , Hosford Patrick S. , Wells Jack A. , Sheikhbahaei Shahriar , Humoud Ibrahim , Paton Julian F. R. , Lythgoe Mark F. , Semyanov Alexey , Kasparov Sergey , Gourine Alexander V. 
Published: January 2020

AbstractAstrocytes provide neurons with essential metabolic and structural support, modulate neuronal circuit activity and may also function as versatile surveyors of brain milieu, tuned to sense conditions of potential metabolic insufficiency. Here we show that astrocytes detect falling cerebral perfusion pressure and activate CNS autonomic sympathetic control circuits to increase systemic arterial blood pressure and heart rate with the purpose of maintaining brain blood flow and oxygen delivery. Studies conducted in experimental animals (laboratory rats) show that astrocytes respond to acute decreases in brain perfusion with elevations in intracellular [Ca2+]. Blockade of Ca2+-dependent signaling mechanisms in populations of astrocytes that reside alongside CNS sympathetic control circuits prevents compensatory increases in sympathetic nerve activity, heart rate and arterial blood pressure induced by reductions in cerebral perfusion. These data suggest that astrocytes function as intracranial baroreceptors and play an important role in homeostatic control of arterial blood pressure and brain blood flow.
Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection
Authors: Li Bo , Clohisey Sara M. , Chia Bing Shao , Wang Bo , Cui Ang , Eisenhaure Thomas , Schweitzer Lawrence D. , Hoover Paul , Parkinson Nicholas J. , Nachshon Aharon , Smith Nikki , Regan Tim , Farr David , Gutmann Michael U. , Bukhari Syed Irfan , Law Andrew , Sangesland Maya , Gat-Viks Irit , Digard Paul , Vasudevan Shobha , Lingwood Daniel , Dockrell David H. , Doench John G. , Baillie J. Kenneth , Hacohen Nir 
Published: January 2020

AbstractHost dependency factors that are required for influenza A virus infection may serve as therapeutic targets as the virus is less likely to bypass them under drug-mediated selection pressure. Previous attempts to identify host factors have produced largely divergent results, with few overlapping hits across different studies. Here, we perform a genome-wide CRISPR/Cas9 screen and devise a new approach, meta-analysis by information content (MAIC) to systematically combine our results with prior evidence for influenza host factors. MAIC out-performs other meta-analysis methods when using our CRISPR screen as validation data. We validate the host factors, WDR7, CCDC115 and TMEM199, demonstrating that these genes are essential for viral entry and regulation of V-type ATPase assembly. We also find that CMTR1, a human mRNA cap methyltransferase, is required for efficient viral cap snatching and regulation of a cell autonomous immune response, and provides synergistic protection with the influenza endonuclease inhibitor Xofluza.
Identification of distinct maturation steps involved in human 40S ribosomal subunit biosynthesis
Authors: Nieto Blanca , Gaspar Sonia G. , Moriggi Giulia , Pestov Dimitri G. , Bustelo Xosé R. , Dosil Mercedes 
Published: January 2020

AbstractTechnical problems intrinsic to the purification of preribosome intermediates have limited our understanding of ribosome biosynthesis in humans. Addressing this issue is important given the implication of this biological process in human disease. Here we report a preribosome purification and tagging strategy that overcomes some of the existing technical difficulties. Using these tools, we find that the pre-40S precursors go through two distinct maturation phases inside the nucleolus and follow a regulatory step that precedes late maturation in the cytoplasm. This regulatory step entails the intertwined actions of both PARN (a metazoan-specific ribonuclease) and RRP12 (a phylogenetically conserved 40S biogenesis factor that has acquired additional functional features in higher eukaryotes). Together, these results demonstrate the usefulness of this purification method for the dissection of ribosome biogenesis in human cells. They also identify distinct maturation stages and metazoan-specific regulatory mechanisms involved in the generation of the human 40S ribosomal subunit.
Cardiac muscle thin filament structures reveal calcium regulatory mechanism
Authors: Yamada Yurika , Namba Keiichi , Fujii Takashi 
Published: January 2020

AbstractContraction of striated muscles is driven by cyclic interactions of myosin head projecting from the thick filament with actin filament and is regulated by Ca2+ released from sarcoplasmic reticulum. Muscle thin filament consists of actin, tropomyosin and troponin, and Ca2+ binding to troponin triggers conformational changes of troponin and tropomyosin to allow actin-myosin interactions. However, the structural changes involved in this regulatory mechanism remain unknown. Here we report the structures of human cardiac muscle thin filament in the absence and presence of Ca2+ by electron cryomicroscopy. Molecular models in the two states built based on available crystal structures reveal the structures of a C-terminal region of troponin I and an N-terminal region of troponin T in complex with the head-to-tail junction of tropomyosin together with the troponin core on actin filament. Structural changes of the thin filament upon Ca2+ binding now reveal the mechanism of Ca2+ regulation of muscle contraction.
ASCOT identifies key regulators of neuronal subtype-specific splicing
Authors: Ling Jonathan P. , Wilks Christopher , Charles Rone , Leavey Patrick J. , Ghosh Devlina , Jiang Lizhi , Santiago Clayton P. , Pang Bo , Venkataraman Anand , Clark Brian S. , Nellore Abhinav , Langmead Ben , Blackshaw Seth 
Published: January 2020

AbstractPublic archives of next-generation sequencing data are growing exponentially, but the difficulty of marshaling this data has led to its underutilization by scientists. Here, we present ASCOT, a resource that uses annotation-free methods to rapidly analyze and visualize splice variants across tens of thousands of bulk and single-cell data sets in the public archive. To demonstrate the utility of ASCOT, we identify novel cell type-specific alternative exons across the nervous system and leverage ENCODE and GTEx data sets to study the unique splicing of photoreceptors. We find that PTBP1 knockdown and MSI1 and PCBP2 overexpression are sufficient to activate many photoreceptor-specific exons in HepG2 liver cancer cells. This work demonstrates how large-scale analysis of public RNA-Seq data sets can yield key insights into cell type-specific control of RNA splicing and underscores the importance of considering both annotated and unannotated splicing events.
Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
Authors: Berdugo-Vega Gabriel , Arias-Gil Gonzalo , López-Fernández Adrian , Artegiani Benedetta , Wasielewska Joanna M. , Lee Chi-Chieh , Lippert Michael T. , Kempermann Gerd , Takagaki Kentaroh , Calegari Federico 
Published: January 2020

AbstractFunctional plasticity of the brain decreases during ageing causing marked deficits in contextual learning, allocentric navigation and episodic memory. Adult neurogenesis is a prime example of hippocampal plasticity promoting the contextualisation of information and dramatically decreases during ageing. We found that a genetically-driven expansion of neural stem cells by overexpression of the cell cycle regulators Cdk4/cyclinD1 compensated the age-related decline in neurogenesis. This triggered an overall inhibitory effect on the trisynaptic hippocampal circuit resulting in a changed profile of CA1 sharp-wave ripples known to underlie memory consolidation. Most importantly, increased neurogenesis rescued the age-related switch from hippocampal to striatal learning strategies by rescuing allocentric navigation and contextual memory. Our study demonstrates that critical aspects of hippocampal function can be reversed in old age, or compensated throughout life, by exploiting the brain’s endogenous reserve of neural stem cells.
A large calibrated database of hand movements and grasps kinematics
Authors: Jarque-Bou Néstor J. , Atzori Manfredo , Müller Henning 
Published: January 2020

AbstractModelling hand kinematics is a challenging problem, crucial for several domains including robotics, 3D modelling, rehabilitation medicine and neuroscience. Currently available datasets are few and limited in the number of subjects and movements. The objective of this work is to advance the modelling of hand kinematics by releasing and validating a large publicly available kinematic dataset of hand movements and grasp kinematics. The dataset is based on the harmonization and calibration of the kinematics data of three multimodal datasets previously released (Ninapro DB1, DB2 and DB5, that include electromyography, inertial and dynamic data). The novelty of the dataset is related to the high number of subjects (77) and movements (40 movements, each repeated several times) for which we release for the first time calibrated kinematic data, resulting in the largest available kinematic dataset. Differently from the previous datasets, the data are also calibrated to avoid sensor nonlinearities. The validation confirms that the data are not affected by experimental procedures and that they are similar to data acquired in real-life conditions.
Rapid and cost-effective generation of single specimen multilocus barcoding data from whole arthropod communities by multiple levels of multiplexing
Authors: de Kerdrel Guillemette A. , Andersen Jeremy C. , Kennedy Susan R. , Gillespie Rosemary , Krehenwinkel Henrik 
Published: January 2020

AbstractIn light of the current biodiversity crisis, molecular barcoding has developed into an irreplaceable tool. Barcoding has been considerably simplified by developments in high throughput sequencing technology, but still can be prohibitively expensive and laborious when community samples of thousands of specimens need to be processed. Here, we outline an Illumina amplicon sequencing approach to generate multilocus data from large collections of arthropods. We reduce cost and effort up to 50-fold, by combining multiplex PCRs and DNA extractions from pools of presorted and morphotyped specimens and using two levels of sample indexing. We test our protocol by generating a comprehensive, community wide dataset of barcode sequences for several thousand Hawaiian arthropods from 14 orders, which were collected across the archipelago using various trapping methods. We explore patterns of diversity across the Archipelago and compare the utility of different arthropod trapping methods for biodiversity explorations on Hawaii, highlighting undergrowth beating as highly efficient method. Moreover, we show the effects of barcode marker, taxonomy and relative biomass of the targeted specimens and sequencing coverage on taxon recovery. Our protocol enables rapid and inexpensive explorations of diversity patterns and the generation of multilocus barcode reference libraries across whole ecosystems.
Increased stiffness of the tumor microenvironment in colon cancer stimulates cancer associated fibroblast-mediated prometastatic activin A signaling
Authors: Bauer Jessica , Emon Md Abul Bashar , Staudacher Jonas J. , Thomas Alexandra L. , Zessner-Spitzenberg Jasmin , Mancinelli Georgina , Krett Nancy , Saif M. Taher , Jung Barbara 
Published: January 2020

AbstractColorectal cancer (CRC) is the second deadliest cancer in the US due to its propensity to metastasize. Stromal cells and especially cancer-associated fibroblasts (CAF) play a critical biophysical role in cancer progression, but the precise pro-metastatic mechanisms are not clear. Activin A, a TGF-β family member, is a strong pro-metastatic cytokine in the context of CRC. Here, we assessed the link between biophysical forces and pro-metastatic signaling by testing the hypothesis that CAF-generated mechanical forces lead to activin A release and associated downstream effects. Consistent with our hypothesis, we first determined that stromal activin A secretion increased with increasing substrate stiffness. Then we found that stromally-secreted activin A induced ligand-dependent CRC epithelial cell migration and epithelial to mesenchymal transition (EMT). In addition, serum activin A levels are significantly increased in metastatic (stage IV) CRC patients (1.558 ng/ml versus 0.4179 ng/ml, p < 0.05). We propose that increased tumor microenvironment stiffness leads to stromal cell-mediated TGF-β family signaling relying on the induction and utilization of activin A signaling.
Long-term epilepsy-associated tumors: transcriptional signatures reflect clinical course
Authors: Delev Daniel , Daka Karam , Heynckes Sabrina , Gaebelein Annette , Franco Pamela , Pfeifer Dietmar , Prinz Marco , Schnell Oliver , Urbach Horst , Mader Irina , Beck Jürgen , Grote Alexander , Becker Albert J. , Heiland Dieter Henrik 
Published: January 2020

AbstractLong-term epilepsy-associated tumors (LEATs) represent mostly benign brain tumors associated with drug-resistant epilepsy. The aim of the study was to investigate the specific transcriptional signatures of those tumors and characterize their underlying oncogenic drivers. A cluster analysis of 65 transcriptome profiles from three independent datasets resulted in four distinct transcriptional subgroups. The first subgroup revealed transcriptional activation of STAT3 and TGF-signaling pathways and contained predominantly dysembryoplastic neuroepithelial tumors (DNTs). The second subgroup was characterized by alterations in the MAPK-pathway and up-stream cascades including FGFR and EGFR-mediated signaling. This tumor cluster exclusively contained neoplasms with somatic BRAFV600E mutations and abundance of gangliogliomas (GGs) with a significantly higher recurrence rate (42%). This finding was validated by examining recurrent tumors from the local database exhibiting BRAFV600E in 90% of the cases. The third cluster included younger patients with neuropathologically diagnosed GGs and abundance of the NOTCH- and mTOR-signaling pathways. The transcript signature of the fourth cluster (including both DNTs and GGs) was related to impaired neural function. Our analysis suggests distinct oncological pathomechanisms in long-term epilepsy-associated tumors. Transcriptional activation of MAPK-pathway and BRAFV600E mutation are associated with an increased risk for tumor recurrence and malignant progression, therefore the treatment of these tumors should integrate both epileptological and oncological aspects.
MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction
Authors: Cisilotto Júlia , do Amaral Alex Evangelista , Rosolen Daiane , Rode Michele Patrícia , Silva Adny Henrique , Winter Evelyn , da Silva Telma Erotides , Fischer Josiane , Matiollo Camila , Rateke Elayne Cristina de Morais , Narciso-Schiavon Janaína Luz , Schiavon Leonardo de Lucca , Creczynski-Pasa Tânia Beatriz 
Published: January 2020

AbstractAcute-on-chronic liver failure (ACLF) is a condition characterized by acute decompensation of cirrhosis, associated with organ failure(s), and high short-term mortality. The microRNAs or miRNAs are small non-coding RNA molecules, stable in circulating samples such as biological fluids, and the difference in expression levels may indicate the presence, absence and/or stage of the disease. We analyzed here the miRNA profiling to identify potential diagnostic or prognostic biomarkers for ACLF. The major miRNAs discovered were validated in a cohort of patients with acute decompensation of cirrhosis grouped in no ACLF or ACLF according to EASL-CLIF definition. Relationship between serum miRNAs and variables associated with liver-damage and survival outcomes were verified to identify possible prognostic markers. Our results showed twenty altered miRNAs between no ACLF and ACLF patients, and twenty-seven in patients who died in 30 days compared with who survived. In validation phase, miR-223-3p and miR-25-3p were significantly altered in ACLF patients and in those who died in 30 days. miR-223-3p and miR-25-3p expression were associated with the lowest survival in 30 days. The decrease in miR-223-3p and miR-25-3p expression was associated with the presence of ACLF and poor prognosis. Of these, miR-25-3p was independently related to ACLF and 30-day mortality.
Optical absorption in array of Ge/Al-shell nanoparticles in an Alumina matrix
Authors: Despoja Vito , Basioli Lovro , Parramon Jordi Sancho , Mičetić Maja 
Published: January 2020

AbstractThe absorption spectra in array of Ge, Al and Ge/Al-shell nanoparticles immersed in alumina (Al2O3) matrix is calculated in framework ofab initiomacroscopic dielectric model. It is demonstrated that absorption is strongly enhanced when germanium nanospheres are encapsulated by Al-shell. Two absorption peaks, appearing in the spectra, correspond to low energyω+and high energyω−plasmons which lie in visible and ultraviolet frequency range, respectively. It is demonstrated that in Ge/Al-shell composite theω+plasmon exists only because quantum confinement effect which provides larger Ge band gap (Δ ~ 1.5 eV) and thus prevent decay ofω+plasmon to continuum of interband electron-hole excitation in semiconducting core. Absorption in visible frequency range enhances additional 3 times when alumina is replaced by large dielectric constant insulator, such as SiC, and additional 6 times when Ge core is replaced by wide band-gap insulator, such as Si3N4. Strong enhancement of optical absorption in visible frequency range make this composites suitable for optoelectronic application, such as solar cells or light emitting devices. The simulated plasmon peaks are brought in connection with peaks appearing in ellipsometry measurements.