bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic lattice distortions driven by surface trapping in semiconductor nanocrystals
Authors: Guzelturk Burak , Cotts Benjamin L. , Jasrasaria Dipti , Philbin John P. , Hanifi David A. , Koscher Brent A. , Balan Arunima D. , Curling Ethan , Zajac Marc , Park Suji , Yazdani Nuri , Nyby Clara , Kamysbayev Vladislav , Fischer Stefan , Nett Zach , Shen Xiaozhe , Kozina Michael E. , Lin Ming-Fu , Reid Alexander H. , Weathersby Stephen P. , Schaller Richard D. , Wood Vanessa , Wang Xijie , Dionne Jennifer A. , Talapin Dmitri V. , Alivisatos A. Paul , Salleo Alberto , Rabani Eran , Lindenberg Aaron M. 
Published: March 2021

AbstractNonradiative processes limit optoelectronic functionality of nanocrystals and curb their device performance. Nevertheless, the dynamic structural origins of nonradiative relaxations in such materials are not understood. Here, femtosecond electron diffraction measurements corroborated by atomistic simulations uncover transient lattice deformations accompanying radiationless electronic processes in colloidal semiconductor nanocrystals. Investigation of the excitation energy dependence in a core/shell system shows that hot carriers created by a photon energy considerably larger than the bandgap induce structural distortions at nanocrystal surfaces on few picosecond timescales associated with the localization of trapped holes. On the other hand, carriers created by a photon energy close to the bandgap of the core in the same system result in transient lattice heating that occurs on a much longer 200 picosecond timescale, dominated by an Auger heating mechanism. Elucidation of the structural deformations associated with the surface trapping of hot holes provides atomic-scale insights into the mechanisms deteriorating optoelectronic performance and a pathway towards minimizing these losses in nanocrystal devices.
Quantitative characterization of extracellular vesicle uptake and content delivery within mammalian cells
Authors: Bonsergent Emeline , Grisard Eleonora , Buchrieser Julian , Schwartz Olivier , Théry Clotilde , Lavieu Grégory 
Published: March 2021

AbstractExtracellular vesicles (EVs), including exosomes, are thought to mediate intercellular communication through the transfer of cargoes from donor to acceptor cells. Occurrence of EV-content delivery within acceptor cells has not been unambiguously demonstrated, let alone quantified, and remains debated. Here, we developed a cell-based assay in which EVs containing luciferase- or fluorescent-protein tagged cytosolic cargoes are loaded on unlabeled acceptor cells. Results from dose-responses, kinetics, and temperature-block experiments suggest that EV uptake is a low yield process (~1% spontaneous rate at 1 h). Further characterization of this limited EV uptake, through fractionation of membranes and cytosol, revealed cytosolic release (~30% of the uptaken EVs) in acceptor cells. This release is inhibited by bafilomycin A1 and overexpression of IFITM proteins, which prevent virus entry and fusion. Our results show that EV content release requires endosomal acidification and suggest the involvement of membrane fusion.
Scaffolding proteins guide the evolution of algal light harvesting antennas
Authors: Rathbone Harry W. , Michie Katharine A. , Landsberg Michael J. , Green Beverley R. , Curmi Paul M. G. 
Published: March 2021

AbstractPhotosynthetic organisms have developed diverse antennas composed of chromophorylated proteins to increase photon capture. Cryptophyte algae acquired their photosynthetic organelles (plastids) from a red alga by secondary endosymbiosis. Cryptophytes lost the primary red algal antenna, the red algal phycobilisome, replacing it with a unique antenna composed of αβ protomers, where the β subunit originates from the red algal phycobilisome. The origin of the cryptophyte antenna, particularly the unique α subunit, is unknown. Here we show that the cryptophyte antenna evolved from a complex between a red algal scaffolding protein and phycoerythrin β. Published cryo-EM maps for two red algal phycobilisomes contain clusters of unmodelled density homologous to the cryptophyte-αβ protomer. We modelled these densities, identifying a new family of scaffolding proteins related to red algal phycobilisome linker proteins that possess multiple copies of a cryptophyte-α-like domain. These domains bind to, and stabilise, a conserved hydrophobic surface on phycoerythrin β, which is the same binding site for its primary partner in the red algal phycobilisome, phycoerythrin α. We propose that after endosymbiosis these scaffolding proteins outcompeted the primary binding partner of phycoerythrin β, resulting in the demise of the red algal phycobilisome and emergence of the cryptophyte antenna.
Discovery of a weak topological insulating state and van Hove singularity in triclinic RhBi2
Authors: Lee Kyungchan , Lange Gunnar F. , Wang Lin-Lin , Kuthanazhi Brinda , Trevisan Thaís V. , Jo Na Hyun , Schrunk Benjamin , Orth Peter P. , Slager Robert-Jan , Canfield Paul C. , Kaminski Adam 
Published: March 2021

AbstractTime reversal symmetric (TRS) invariant topological insulators (TIs) fullfil a paradigmatic role in the field of topological materials, standing at the origin of its development. Apart from TRS protected strong TIs, it was realized early on that more confounding weak topological insulators (WTI) exist. WTIs depend on translational symmetry and exhibit topological surface states only in certain directions making it significantly more difficult to match the experimental success of strong TIs. We here report on the discovery of a WTI state in RhBi2 that belongs to the optimal space group P$$\bar{1}$$

1

¯

, which is the only space group where symmetry indicated eigenvalues enumerate all possible invariants due to absence of additional constraining crystalline symmetries. Our ARPES, DFT calculations, and effective model reveal topological surface states with saddle points that are located in the vicinity of a Dirac point resulting in a van Hove singularity (VHS) along the (100) direction close to the Fermi energy (EF). Due to the combination of exotic features, this material offers great potential as a material platform for novel quantum effects.
Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities
Authors: Oben Bénedith , Froyen Guy , Maclachlan Kylee H. , Leongamornlert Daniel , Abascal Federico , Zheng-Lin Binbin , Yellapantula Venkata , Derkach Andriy , Geerdens Ellen , Diamond Benjamin T. , Arijs Ingrid , Maes Brigitte , Vanhees Kimberly , Hultcrantz Malin , Manasanch Elisabet E. , Kazandjian Dickran , Lesokhin Alexander , Dogan Ahmet , Zhang Yanming , Mikulasova Aneta , Walker Brian , Morgan Gareth , Campbell Peter J. , Landgren Ola , Rummens Jean-Luc , Bolli Niccolò , Maura Francesco 
Published: March 2021

AbstractMultiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n = 15) are characterized by later initiation in the patient’s life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. This data provides evidence that WGS can be used to recognize two biologically and clinically distinct myeloma precursor entities that are either progressive or stable.
An ALYREF-MYCN coactivator complex drives neuroblastoma tumorigenesis through effects on USP3 and MYCN stability
Authors: Nagy Zsuzsanna , Seneviratne Janith A. , Kanikevich Maxwell , Chang William , Mayoh Chelsea , Venkat Pooja , Du Yanhua , Jiang Cizhong , Salib Alice , Koach Jessica , Carter Daniel R. , Mittra Rituparna , Liu Tao , Parker Michael W. , Cheung Belamy B. , Marshall Glenn M. 
Published: March 2021

AbstractTo achieve the very high oncoprotein levels required to drive the malignant state cancer cells utilise the ubiquitin proteasome system to upregulate transcription factor levels. Here our analyses identify ALYREF, expressed from the most common genetic copy number variation in neuroblastoma, chromosome 17q21-ter gain as a key regulator of MYCN protein turnover. We show strong co-operativity between ALYREF and MYCN from transgenic models of neuroblastoma in vitro and in vivo. The two proteins form a nuclear coactivator complex which stimulates transcription of the ubiquitin specific peptidase 3, USP3. We show that increased USP3 levels reduce K-48- and K-63-linked ubiquitination of MYCN, thus driving up MYCN protein stability. In the MYCN-ALYREF-USP3 signal, ALYREF is required for MYCN effects on the malignant phenotype and that of USP3 on MYCN stability. This data defines a MYCN oncoprotein dependency state which provides a rationale for future pharmacological studies.
Pili allow dominant marine cyanobacteria to avoid sinking and evade predation
Authors: Aguilo-Ferretjans Maria del Mar , Bosch Rafael , Puxty Richard J. , Latva Mira , Zadjelovic Vinko , Chhun Audam , Sousoni Despoina , Polin Marco , Scanlan David J. , Christie-Oleza Joseph A. 
Published: March 2021

AbstractHow oligotrophic marine cyanobacteria position themselves in the water column is currently unknown. The current paradigm is that these organisms avoid sinking due to their reduced size and passive drift within currents. Here, we show that one in four picocyanobacteria encode a type IV pilus which allows these organisms to increase drag and remain suspended at optimal positions in the water column, as well as evade predation by grazers. The evolution of this sophisticated floatation mechanism in these purely planktonic streamlined microorganisms has important implications for our current understanding of microbial distribution in the oceans and predator–prey interactions which ultimately will need incorporating into future models of marine carbon flux dynamics.
SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition
Authors: Mullen Peter J. , Garcia Gustavo , Purkayastha Arunima , Matulionis Nedas , Schmid Ernst W. , Momcilovic Milica , Sen Chandani , Langerman Justin , Ramaiah Arunachalam , Shackelford David B. , Damoiseaux Robert , French Samuel W. , Plath Kathrin , Gomperts Brigitte N. , Arumugaswami Vaithilingaraja , Christofk Heather R. 
Published: March 2021

AbstractViruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters host cell metabolism may lead to potential treatments for COVID-19. Here we profile metabolic changes conferred by SARS-CoV-2 infection in kidney epithelial cells and lung air-liquid interface (ALI) cultures, and show that SARS-CoV-2 infection increases glucose carbon entry into the TCA cycle via increased pyruvate carboxylase expression. SARS-CoV-2 also reduces oxidative glutamine metabolism while maintaining reductive carboxylation. Consistent with these changes, SARS-CoV-2 infection increases the activity of mTORC1 in cell lines and lung ALI cultures. Lastly, we show evidence of mTORC1 activation in COVID-19 patient lung tissue, and that mTORC1 inhibitors reduce viral replication in kidney epithelial cells and lung ALI cultures. Our results suggest that targeting mTORC1 may be a feasible treatment strategy for COVID-19 patients, although further studies are required to determine the mechanism of inhibition and potential efficacy in patients.
Natural product fragment combination to performance-diverse pseudo-natural products
Authors: Grigalunas Michael , Burhop Annina , Zinken Sarah , Pahl Axel , Gally José-Manuel , Wild Niklas , Mantel Yannik , Sievers Sonja , Foley Daniel J. , Scheel Rebecca , Strohmann Carsten , Antonchick Andrey P. , Waldmann Herbert 
Published: March 2021

AbstractNatural product structure and fragment-based compound development inspire pseudo-natural product design through different combinations of a given natural product fragment set to compound classes expected to be chemically and biologically diverse. We describe the synthetic combination of the fragment-sized natural products quinine, quinidine, sinomenine, and griseofulvin with chromanone or indole-containing fragments to provide a 244-member pseudo-natural product collection. Cheminformatic analyses reveal that the resulting eight pseudo-natural product classes are chemically diverse and share both drug- and natural product-like properties. Unbiased biological evaluation by cell painting demonstrates that bioactivity of pseudo-natural products, guiding natural products, and fragments differ and that combination of different fragments dominates establishment of unique bioactivity. Identification of phenotypic fragment dominance enables design of compound classes with correctly predicted bioactivity. The results demonstrate that fusion of natural product fragments in different combinations and arrangements can provide chemically and biologically diverse pseudo-natural product classes for wider exploration of biologically relevant chemical space.
Coagulase-negative staphylococci release a purine analog that inhibits Staphylococcus aureus virulence
Authors: Chin Denny , Goncheva Mariya I. , Flannagan Ronald S. , Deecker Shayna R. , Guariglia-Oropeza Veronica , Ensminger Alexander W. , Heinrichs David E. 
Published: March 2021

AbstractCoagulase-negative staphylococci and Staphylococcus aureus colonize similar niches in mammals and conceivably compete for space and nutrients. Here, we report that a coagulase-negative staphylococcus, Staphylococcus chromogenes ATCC43764, synthesizes and secretes 6-thioguanine (6-TG), a purine analog that suppresses S. aureus growth by inhibiting de novo purine biosynthesis. We identify a 6-TG biosynthetic gene cluster in S. chromogenes and other coagulase-negative staphylococci including S. epidermidis, S. pseudintermedius and S. capitis. Recombinant S. aureus strains harbouring this operon produce 6-TG and, when used in subcutaneous co-infections in mice with virulent S. aureus USA300, protect the host from necrotic lesion formation. Used prophylactically, 6-TG reduces necrotic skin lesions in mice infected with USA300, and this effect is mediated by abrogation of toxin production. RNAseq analyses reveal that 6-TG downregulates expression of genes coding for purine biosynthesis, the accessory gene regulator (agr) and ribosomal proteins in S. aureus, providing an explanation for its effect on toxin production.
Dissection of two routes to naïve pluripotency using different kinase inhibitors
Authors: Martinez-Val Ana , Lynch Cian J. , Calvo Isabel , Ximénez-Embún Pilar , Garcia Fernando , Zarzuela Eduardo , Serrano Manuel , Munoz Javier 
Published: March 2021

AbstractEmbryonic stem cells (ESCs) can be maintained in the naïve state through inhibition of Mek1/2 and Gsk3 (2i). A relevant effect of 2i is the inhibition of Cdk8/19, which are negative regulators of the Mediator complex, responsible for the activity of enhancers. Inhibition of Cdk8/19 (Cdk8/19i) stimulates enhancers and, similar to 2i, stabilizes ESCs in the naïve state. Here, we use mass spectrometry to describe the molecular events (phosphoproteome, proteome, and metabolome) triggered by 2i and Cdk8/19i on ESCs. Our data reveal widespread commonalities between these two treatments, suggesting overlapping processes. We find that post-transcriptional de-repression by both 2i and Cdk8/19i might support the mitochondrial capacity of naive cells. However, proteome reprogramming in each treatment is achieved by different mechanisms. Cdk8/19i acts directly on the transcriptional machinery, activating key identity genes to promote the naïve program. In contrast, 2i stabilizes the naïve circuitry through, in part, de-phosphorylation of downstream transcriptional effectors.
Predicting treatment response from longitudinal images using multi-task deep learning
Authors: Jin Cheng , Yu Heng , Ke Jia , Ding Peirong , Yi Yongju , Jiang Xiaofeng , Duan Xin , Tang Jinghua , Chang Daniel T. , Wu Xiaojian , Gao Feng , Li Ruijiang 
Published: March 2021

AbstractRadiographic imaging is routinely used to evaluate treatment response in solid tumors. Current imaging response metrics do not reliably predict the underlying biological response. Here, we present a multi-task deep learning approach that allows simultaneous tumor segmentation and response prediction. We design two Siamese subnetworks that are joined at multiple layers, which enables integration of multi-scale feature representations and in-depth comparison of pre-treatment and post-treatment images. The network is trained using 2568 magnetic resonance imaging scans of 321 rectal cancer patients for predicting pathologic complete response after neoadjuvant chemoradiotherapy. In multi-institution validation, the imaging-based model achieves AUC of 0.95 (95% confidence interval: 0.91–0.98) and 0.92 (0.87–0.96) in two independent cohorts of 160 and 141 patients, respectively. When combined with blood-based tumor markers, the integrated model further improves prediction accuracy with AUC 0.97 (0.93–0.99). Our approach to capturing dynamic information in longitudinal images may be broadly used for screening, treatment response evaluation, disease monitoring, and surveillance.
A rationally engineered decoder of transient intracellular signals
Authors: Lormeau Claude , Rudolf Fabian , Stelling Jörg 
Published: March 2021

AbstractCells can encode information about their environment by modulating signaling dynamics and responding accordingly. Yet, the mechanisms cells use to decode these dynamics remain unknown when cells respond exclusively to transient signals. Here, we approach design principles underlying such decoding by rationally engineering a synthetic short-pulse decoder in budding yeast. A computational method for rapid prototyping, TopoDesign, allowed us to explore 4122 possible circuit architectures, design targeted experiments, and then rationally select a single circuit for implementation. This circuit demonstrates short-pulse decoding through incoherent feedforward and positive feedback. We predict incoherent feedforward to be essential for decoding transient signals, thereby complementing proposed design principles of temporal filtering, the ability to respond to sustained signals, but not to transient signals. More generally, we anticipate TopoDesign to help designing other synthetic circuits with non-intuitive dynamics, simply by assembling available biological components.
Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial
Authors: DeCensi Andrea , Johansson Harriet , Helland Thomas , Puntoni Matteo , Macis Debora , Aristarco Valentina , Caviglia Silvia , Webber Tania Buttiron , Briata Irene Maria , D’Amico Mauro , Serrano Davide , Guerrieri-Gonzaga Aliana , Bifulco Ersilia , Hustad Steinar , Søiland Håvard , Boni Luca , Bonanni Bernardo , Mellgren Gunnar 
Published: March 2021

AbstractLow-dose tamoxifen halves recurrence in non-invasive breast cancer without significant adverse events. Some adjuvant trials with tamoxifen 20 mg/day had shown an association between low endoxifen levels (9–16 nM) and recurrence, but no association with CYP2D6 was shown in the NSABP P1 and P2 prevention trials. We studied the association of CYP2D6 genotype and tamoxifen metabolites with tumor biomarkers and recurrence in a randomized phase III trial of low-dose tamoxifen. Median (IQR) endoxifen levels at year 1 were 8.4 (5.3–11.4) in patients who recurred vs 7.5 (5.1–10.2) in those who did not recur (p = 0.60). Tamoxifen and metabolites significantly decreased C-reactive protein (CRP, p < 0.05), and a CRP increase after 3 years was associated with higher risk of recurrence (HR = 4.37, 95% CI, 1.14–16.73, P = 0.03). In conclusion, endoxifen is below 9 nM in most subjects treated with 5 mg/day despite strong efficacy and there is no association with recurrence, suggesting that the reason for tamoxifen failure is not poor drug metabolism. Trial registration: ClinicalTrials.gov, Identifier: NCT01357772.
Thermodynamics of order and randomness in dopant distributions inferred from atomically resolved imaging
Authors: Vlcek Lukas , Yang Shize , Gong Yongji , Ajayan Pulickel , Zhou Wu , Chisholm Matthew F. , Ziatdinov Maxim , Vasudevan Rama K. , Kalinin Sergei V. 
Published: March 2021

AbstractExploration of structure-property relationships as a function of dopant concentration is commonly based on mean field theories for solid solutions. However, such theories that work well for semiconductors tend to fail in materials with strong correlations, either in electronic behavior or chemical segregation. In these cases, the details of atomic arrangements are generally not explored and analyzed. The knowledge of the generative physics and chemistry of the material can obviate this problem, since defect configuration libraries as stochastic representation of atomic level structures can be generated, or parameters of mesoscopic thermodynamic models can be derived. To obtain such information for improved predictions, we use data from atomically resolved microscopic images that visualize complex structural correlations within the system and translate them into statistical mechanical models of structure formation. Given the significant uncertainties about the microscopic aspects of the material’s processing history along with the limited number of available images, we combine model optimization techniques with the principles of statistical hypothesis testing. We demonstrate the approach on data from a series of atomically-resolved scanning transmission electron microscopy images of MoxRe1-xS2 at varying ratios of Mo/Re stoichiometries, for which we propose an effective interaction model that is then used to generate atomic configurations and make testable predictions at a range of concentrations and formation temperatures.
Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders
Authors: Martinez-Granero Francisco , Blanco-Kelly Fiona , Sanchez-Jimeno Carolina , Avila-Fernandez Almudena , Arteche Ana , Bustamante-Aragones Ana , Rodilla Cristina , Rodríguez-Pinilla Elvira , Riveiro-Alvarez Rosa , Tahsin-Swafiri Saoud , Trujillo-Tiebas Maria Jose , Ayuso Carmen , Rodríguez de Alba Marta , Lorda-Sanchez Isabel , Almoguera Berta 
Published: March 2021

AbstractMost consensus recommendations for the genetic diagnosis of neurodevelopmental disorders (NDDs) do not include the use of next generation sequencing (NGS) and are still based on chromosomal microarrays, such as comparative genomic hybridization array (aCGH). This study compares the diagnostic yield obtained by aCGH and clinical exome sequencing in NDD globally and its spectrum of disorders. To that end, 1412 patients clinically diagnosed with NDDs and studied with aCGH were classified into phenotype categories: global developmental delay/intellectual disability (GDD/ID); autism spectrum disorder (ASD); and other NDDs. These categories were further subclassified based on the most frequent accompanying signs and symptoms into isolated forms, forms with epilepsy; forms with micro/macrocephaly and syndromic forms. Two hundred and forty-five patients of the 1412 were subjected to clinical exome sequencing. Diagnostic yield of aCGH and clinical exome sequencing, expressed as the number of solved cases, was compared for each phenotype category and subcategory. Clinical exome sequencing was superior than aCGH for all cases except for isolated ASD, with no additional cases solved by NGS. Globally, clinical exome sequencing solved 20% of cases (versus 5.7% by aCGH) and the diagnostic yield was highest for all forms of GDD/ID and lowest for Other NDDs (7.1% versus 1.4% by aCGH) and ASD (6.1% versus 3% by aCGH). In the majority of cases, diagnostic yield was higher in the phenotype subcategories than in the mother category. These results suggest that NGS could be used as a first-tier test in the diagnostic algorithm of all NDDs followed by aCGH when necessary.