bluuebunny/crossref_metadata_2025_split huggingface dataset:
A generative network model of neurodevelopmental diversity in structural brain organization
Authors: Akarca Danyal , Vértes Petra E. , Bullmore Edward T. ,   the CALM team, Baker Kate , Gathercole Susan E. , Holmes Joni , Kievit Rogier A. , Manly Tom , Bathelt Joe , Bennett Marc , Bignardi Giacomo , Bishop Sarah , Bottacin Erica , Bridge Lara , Brkic Diandra , Bryant Annie , Butterfield Sally , Byrne Elizabeth M. , Crickmore Gemma , Dalmaijer Edwin S. , Daly Fánchea , Emery Tina , Forde Laura , Franckel Grace , Fuhrmann Delia , Gadie Andrew , Gharooni Sara , Guy Jacalyn , Hawkins Erin , Jaroslawska Agnieszka , Joeghan Sara , Johnson Amy , Jones Jonathan , Mareva Silvana , Ng-Cordell Elise , O’Brien Sinead , O’Leary Cliodhna , Rennie Joseph P. , Simpson-Kent Ivan , Siugzdaite Roma , Smith Tess A. , Uh Stephani , Vedechkina Maria , Woolgar Francesca , Zdorovtsova Natalia , Zhang Mengya , Astle Duncan E. 
Published: July 2021

AbstractThe formation of large-scale brain networks, and their continual refinement, represent crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. But how does this organization arise, and what mechanisms drive diversity in organization? We use generative network modeling to provide a computational framework for understanding neurodevelopmental diversity. Within this framework macroscopic brain organization, complete with spatial embedding of its organization, is an emergent property of a generative wiring equation that optimizes its connectivity by renegotiating its biological costs and topological values continuously over time. The rules that govern these iterative wiring properties are controlled by a set of tightly framed parameters, with subtle differences in these parameters steering network growth towards different neurodiverse outcomes. Regional expression of genes associated with the simulations converge on biological processes and cellular components predominantly involved in synaptic signaling, neuronal projection, catabolic intracellular processes and protein transport. Together, this provides a unifying computational framework for conceptualizing the mechanisms and diversity in neurodevelopment, capable of integrating different levels of analysis—from genes to cognition.
Detection of high-valent iron species in alloyed oxidic cobaltates for catalysing the oxygen evolution reaction
Authors: Li Nancy , Hadt Ryan G. , Hayes Dugan , Chen Lin X. , Nocera Daniel G. 
Published: July 2021

AbstractIron alloying of oxidic cobaltate catalysts results in catalytic activity for oxygen evolution on par with Ni-Fe oxides in base but at much higher alloying compositions. Zero-field 57Fe Mössbauer spectroscopy and X-ray absorption spectroscopy (XAS) are able to clearly identify Fe4+ in mixed-metal Co-Fe oxides. The highest Fe4+ population is obtained in the 40–60% Fe alloying range, and XAS identifies the ion residing in an octahedral oxide ligand field. The oxygen evolution reaction (OER) activity, as reflected in Tafel analysis of CoFeOx films in 1 M KOH, tracks the absolute concentration of Fe4+. The results reported herein suggest an important role for the formation of the Fe4+ redox state in activating cobaltate OER catalysts at high iron loadings.
Improved CRISPR genome editing using small highly active and specific engineered RNA-guided nucleases
Authors: Schmidt Moritz J. , Gupta Ashish , Bednarski Christien , Gehrig-Giannini Stefanie , Richter Florian , Pitzler Christian , Gamalinda Michael , Galonska Christina , Takeuchi Ryo , Wang Kui , Reiss Caroline , Dehne Kerstin , Lukason Michael J. , Noma Akiko , Park-Windhol Cindy , Allocca Mariacarmela , Kantardzhieva Albena , Sane Shailendra , Kosakowska Karolina , Cafferty Brian , Tebbe Jan , Spencer Sarah J. , Munzer Scott , Cheng Christopher J. , Scaria Abraham , Scharenberg Andrew M. , Cohnen André , Coco Wayne M. 
Published: July 2021

AbstractStreptococcus pyogenes (Spy) Cas9 has potential as a component of gene therapeutics for incurable diseases. One of its limitations is its large size, which impedes its formulation and delivery in therapeutic applications. Smaller Cas9s are an alternative, but lack robust activity or specificity and frequently recognize longer PAMs. Here, we investigated four uncharacterized, smaller Cas9s and found three employing a “GG” dinucleotide PAM similar to SpyCas9. Protein engineering generated synthetic RNA-guided nucleases (sRGNs) with editing efficiencies and specificities exceeding even SpyCas9 in vitro and in human cell lines on disease-relevant targets. sRGN mRNA lipid nanoparticles displayed manufacturing advantages and high in vivo editing efficiency in the mouse liver. Finally, sRGNs, but not SpyCas9, could be packaged into all-in-one AAV particles with a gRNA and effected robust in vivo editing of non-human primate (NHP) retina photoreceptors. Human gene therapy efforts are expected to benefit from these improved alternatives to existing CRISPR nucleases.
Prokineticin-2 prevents neuronal cell deaths in a model of traumatic brain injury
Authors: Bao Zhongyuan , Liu Yinlong , Chen Binglin , Miao Zong , Tu Yiming , Li Chong , Chao Honglu , Ye Yangfan , Xu Xiupeng , Sun Guangchi , Zhao Pengzhan , Liu Ning , Liu Yan , Wang Xiaoming , Lam Sin Man , Kagan Valerian E. , Bayır Hülya , Ji Jing 
Published: July 2021

AbstractProkineticin-2 (Prok2) is an important secreted protein likely involved in the pathogenesis of several acute and chronic neurological diseases through currently unidentified regulatory mechanisms. The initial mechanical injury of neurons by traumatic brain injury triggers multiple secondary responses including various cell death programs. One of these is ferroptosis, which is associated with dysregulation of iron and thiols and culminates in fatal lipid peroxidation. Here, we explore the regulatory role of Prok2 in neuronal ferroptosis in vitro and in vivo. We show that Prok2 prevents neuronal cell death by suppressing the biosynthesis of lipid peroxidation substrates, arachidonic acid-phospholipids, via accelerated F-box only protein 10 (Fbxo10)-driven ubiquitination, degradation of long-chain-fatty-acid-CoA ligase 4 (Acsl4), and inhibition of lipid peroxidation. Mice injected with adeno-associated virus-Prok2 before controlled cortical impact injury show reduced neuronal degeneration and improved motor and cognitive functions, which could be inhibited by Fbxo10 knockdown. Our study shows that Prok2 mediates neuronal cell deaths in traumatic brain injury via ferroptosis.
Single-molecule, full-length transcript isoform sequencing reveals disease-associated RNA isoforms in cardiomyocytes
Authors: Zhu Chenchen , Wu Jingyan , Sun Han , Briganti Francesca , Meder Benjamin , Wei Wu , Steinmetz Lars M. 
Published: July 2021

AbstractAlternative splicing generates differing RNA isoforms that govern phenotypic complexity of eukaryotes. Its malfunction underlies many diseases, including cancer and cardiovascular diseases. Comparative analysis of RNA isoforms at the genome-wide scale has been difficult. Here, we establish an experimental and computational pipeline that performs de novo transcript annotation and accurately quantifies transcript isoforms from cDNA sequences with a full-length isoform detection accuracy of 97.6%. We generate a searchable, quantitative human transcriptome annotation with 31,025 known and 5,740 novel transcript isoforms (http://steinmetzlab.embl.de/iBrowser/). By analyzing the isoforms in the presence of RNA Binding Motif Protein 20 (RBM20) mutations associated with aggressive dilated cardiomyopathy (DCM), we identify 121 differentially expressed transcript isoforms in 107 cardiac genes. Our approach enables quantitative dissection of complex transcript architecture instead of mere identification of inclusion or exclusion of individual exons, as exemplified by the discovery of IMMT isoforms mis-spliced by RBM20 mutations. Thereby we achieve a path to direct differential expression testing independent of an existing annotation of transcript isoforms, providing more immediate biological interpretation and higher resolution transcriptome comparisons.
Fabricating polyoxometalates-stabilized single-atom site catalysts in confined space with enhanced activity for alkynes diboration
Authors: Liu Yiwei , Wu Xi , Li Zhi , Zhang Jian , Liu Shu-Xia , Liu Shoujie , Gu Lin , Zheng Li Rong , Li Jia , Wang Dingsheng , Li Yadong 
Published: July 2021

AbstractEffecting the synergistic function of single metal atom sites and their supports is of great importance to achieve high-performance catalysts. Herein, we successfully fabricate polyoxometalates (POMs)-stabilized atomically dispersed platinum sites by employing three-dimensional metal-organic frameworks (MOFs) as the finite spatial skeleton to govern the accessible quantity, spatial dispersion, and mobility of metal precursors around each POM unit. The isolated single platinum atoms (Pt1) are steadily anchored in the square-planar sites on the surface of monodispersed Keggin-type phosphomolybdic acid (PMo) in the cavities of various MOFs, including MIL-101, HKUST-1, and ZIF-67. In contrast, either the absence of POMs or MOFs yielded only platinum nanoparticles. Pt1-PMo@MIL-101 are seven times more active than the corresponding nanoparticles in the diboration of phenylacetylene, which can be attributed to the synergistic effect of the preconcentration of organic reaction substrates by porous MOFs skeleton and the decreased desorption energy of products on isolated Pt atom sites.
Observation of negative capacitance in antiferroelectric PbZrO3 Films
Authors: Qiao Leilei , Song Cheng , Sun Yiming , Fayaz Muhammad Umer , Lu Tianqi , Yin Siqi , Chen Chong , Xu Huiping , Ren Tian-Ling , Pan Feng 
Published: July 2021

AbstractNegative capacitance effect in ferroelectric materials provides a solution to the energy dissipation problem induced by Boltzmann distribution of electrons in conventional electronics. Here, we discover that besides ferroelectrics, the antiferroelectrics based on Landau switches also have intrinsic negative capacitance effect. We report both the static and transient negative capacitance effect in antiferroelectric PbZrO3 films and reveal its possible physical origin. The capacitance of the capacitor of the PbZrO3 and paraelectric heterostructure is demonstrated to be larger than that of the isolated paraelectric capacitor at room temperature, indicating the existence of the static negative capacitance. The opposite variation trends of the voltage and charge transients in a circuit of the PbZrO3 capacitor in series with an external resistor demonstrate the existence of transient negative capacitance effect. Strikingly, four negative capacitance effects are observed in the antiferroelectric system during one cycle scan of voltage pulses, different from the ferroelectric counterpart with two negative capacitance effects. The polarization vector mapping, electric field and free energy analysis reveal the rich local regions of negative capacitance effect with the negative dP/dE and (δ2G)⁄(δD2), producing stronger negative capacitance effect. The observation of negative capacitance effect in antiferroelectric films significantly extends the range of its potential application and reduces the power dissipation further.
Anomalous and anisotropic nonlinear susceptibility in the proximate Kitaev magnet α-RuCl3
Authors: Holleis Ludwig , Prestigiacomo Joseph C. , Fan Zhijie , Nishimoto Satoshi , Osofsky Michael , Chern Gia-Wei , van den Brink Jeroen , Shivaram B. S. 
Published: July 2021

AbstractThe leading order nonlinear (NL) susceptibility, χ3, in a paramagnet is negative and diverges as T → 0. This divergence is destroyed when spins correlate and the NL response provides unique insights into magnetic order. Dimensionality, exchange interaction, and preponderance of quantum effects all imprint their signatures in the NL magnetic response. Here, we study the NL susceptibilities in the proximate Kitaev magnet α-RuCl3, which differs from the expected antiferromagnetic behavior. For T < Tc = 7.5 K and field B in the ab-plane, we obtain contrasting NL responses in low (<2 T) and high field regions. For low fields, the NL behavior is dominated by a quadratic response (positive χ2), which shows a rapid rise below Tc. This large χ2 > 0 implies a broken sublattice symmetry of magnetic order at low temperatures. Classical Monte Carlo (CMC) simulations in the standard K − H − Γ model secure such a quadratic B dependence of M, only for T ≈ Tc with χ2 being zero as T → 0. It is also zero for all temperatures in exact diagonalization calculations. On the other hand, we find an exclusive cubic term (χ3) that describes the high field NL behavior well. χ3 is large and positive both below and above Tc crossing zero only for T > 50 K. In contrast, for B ∥ c-axis, no separate low/high field behaviors are measured and only a much smaller χ3 is apparent.
Perpetrator pose reinstatement during a lineup test increases discrimination accuracy
Authors: Colloff Melissa F. , Seale-Carlisle Travis M. , Karoğlu Nilda , Rockey James C. , Smith Harriet M. J. , Smith Lisa , Maltby John , Yaremenko Sergii , Flowe Heather D. 
Published: July 2021

AbstractWe examined how encoding view influences the information that is stored in and retrieved from memory during an eyewitness identification task. Participants watched a mock crime and we varied the angle from which they viewed the perpetrator. In Experiment 1, participants (N = 2904) were tested with a static photo lineup; the viewing angle of the lineup members was the same or different from the perpetrator at encoding. In Experiment 2, participants (N = 1430) were tested with a novel interactive lineup in which they could rotate the lineup faces into any angle. In both experiments, discrimination accuracy was greater when the viewing angle at encoding and test matched. Participants reinstated the angle of the interactive faces to match their encoding angle. Our results highlight the importance of encoding specificity for eyewitness identification, and show that people actively seek out information in the testing environment that matches the study environment to aid memory retrieval.
Untargeted metabolomics approach to discriminate mistletoe commercial products
Authors: Vanhaverbeke Cécile , Touboul David , Elie Nicolas , Prévost Martine , Meunier Cécile , Michelland Sylvie , Cunin Valérie , Ma Ling , Vermijlen David , Delporte Cédric , Pochet Stéphanie , Le Gouellec Audrey , Sève Michel , Van Antwerpen Pierre , Souard Florence 
Published: July 2021

AbstractMistletoe (Viscum albumL.) is used in German-speaking European countries in the field of integrative oncology linking conventional and complementary medicine therapies to improve quality of life. Various companies sell extracts, fermented or not, for injection by subcutaneous or intra-tumoral route with a regulatory status of anthroposophic medicinal products (European Medicinal Agency (EMA) assessment status). These companies as well as anthroposophical physicians argue that complex matrices composed of many molecules in mixture are necessary for activity and that the host tree of the mistletoe parasitic plant is the main determining factor for this matrix composition. The critical point is that parenteral devices of European mistletoe extracts do not have a standard chemical composition regulated by EMA quality guidelines, because they are not drugs, regulatory speaking. However, the mechanism of mistletoe’s anticancer activity and its effectiveness in treating and supporting cancer patients are not fully understood. Because of this lack of transparency and knowledge regarding the matrix chemical composition, we undertook an untargeted metabolomics study of several mistletoe extracts to explore and compare their fingerprints by LC-(HR)MS(/MS) and1H-NMR. Unexpectedly, we showed that the composition was primarily driven by the manufacturer/preparation method rather than the different host trees. This differential composition may cause differences in immunostimulating and anti-cancer activities of the different commercially available mistletoe extracts as illustrated by structure–activity relationships based on LC–MS/MS and1H-NMR identifications completed by docking experiments. In conclusion, in order to move towards an evidence-based medicine use of mistletoe, it is a priority to bring rigor and quality, chemically speaking.
A new approach to precise mapping of local temperature fields in submicrometer aqueous volumes
Authors: Romshin Alexey M. , Zeeb Vadim , Martyanov Artem K. , Kudryavtsev Oleg S. , Pasternak Dmitrii G. , Sedov Vadim S. , Ralchenko Victor G. , Sinogeykin Andrey G. , Vlasov Igor I. 
Published: July 2021

AbstractNanodiamonds hosting temperature-sensing centers constitute a closed thermodynamic system. Such a system prevents direct contact of the temperature sensors with the environment making it an ideal environmental insensitive nanosized thermometer. A new design of a nanodiamond thermometer, based on a 500-nm luminescent nanodiamond embedded into the inner channel of a glass submicron pipette is reported. All-optical detection of temperature, based on spectral changes of the emission of “silicon-vacancy” centers with temperature, is used. We demonstrate the applicability of the thermometric tool to the study of temperature distribution near a local heater, placed in an aqueous medium. The calculated and experimental values of temperatures are shown to coincide within measurement error at gradients up to 20 °C/μm. Until now, temperature measurements on the submicron scale at such high gradients have not been performed. The new thermometric tool opens up unique opportunities to answer the urgent paradigm-shifting questions of cell physiology thermodynamics.
Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan
Authors: Khan Anwar Sheed , Phelan Jody E. , Khan Muhammad Tahir , Ali Sajid , Qasim Muhammad , Napier Gary , Campino Susana , Ahmad Sajjad , Cabral-Marques Otavio , Zhang Shulin , Rahman Hazir , Wei Dong-Qing , Clark Taane G. , Khan Taj Ali 
Published: July 2021

AbstractTuberculosis (TB), caused by Mycobacterium tuberculosis, is endemic in Pakistan. Resistance to both firstline rifampicin and isoniazid drugs (multidrug-resistant TB; MDR-TB) is hampering disease control. Rifampicin resistance is attributed to rpoB gene mutations, but rpoA and rpoC loci may also be involved. To characterise underlying rifampicin resistance mutations in the TB endemic province of Khyber Pakhtunkhwa, we sequenced 51 M. tuberculosis isolates collected between 2016 and 2019; predominantly, MDR-TB (n = 44; 86.3%) and lineage 3 (n = 30, 58.8%) strains. We found that known mutations in rpoB (e.g. S405L), katG (e.g. S315T), or inhA promoter loci explain the MDR-TB. There were 24 unique mutations in rpoA, rpoB, and rpoC genes, including four previously unreported. Five instances of within-host resistance diversity were observed, where two were a mixture of MDR-TB strains containing mutations in rpoB, katG, and the inhA promoter region, as well as compensatory mutations in rpoC. Heteroresistance was observed in two isolates with a single lineage. Such complexity may reflect the high transmission nature of the Khyber Pakhtunkhwa setting. Our study reinforces the need to apply sequencing approaches to capture the full-extent of MDR-TB genetic diversity, to understand transmission, and to inform TB control activities in the highly endemic setting of Pakistan.
Low testosterone and cardiometabolic risks in a real-world study of US male firefighters
Authors: Ranadive Sushant M. , Lofrano-Porto Adriana , Soares Edgard M. K. V. K. , Eagan Lauren , Porto Luiz Guilherme Grossi , Smith Denise L. 
Published: July 2021

AbstractLow serum total testosterone (TT) is associated with increased cardiovascular risk and metabolic derangements, with fatty liver (FL) emerging as an additional cardiometabolic threat. We investigated the associations between TT and cardiometabolic (CM) health in 298 US male firefighters. Cross-sectional data from occupational health examination were analyzed. TT was categorized as low (< 264 ng/dL), borderline (264–399 ng/dL), and reference (400–916 ng/dL). Conventional CM risk factors were compared among TT categories, and between firefighters with and without FL. 81% of firefighters were obese/overweight; almost 40% had FL. In the low-TT group, only 3.1% had normal BMI, while 78.1% had FL. The low-TT group had a worse CM profile, independently of age and BMI, and a fourfold higher adjusted odds of having FL. FL was associated with lower TT, regardless of age, BMI and HbA1c. Having a FL, HbA1c ≥ 5.7% or triglycerides ≥ 150 mg/dL increased the odds for low-TT by 4.1, 2.7 and 6.6 times, respectively. These real-world data reveal strong associations between low-TT and CM risk factors and support a call for action towards screening for low-TT and FL, regardless of age, BMI or dysmetabolic conditions in firefighters. Recognizing cardiometabolic risks in firefighters provides an opportunity to lessen cardiovascular diseases burden.
Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer
Authors: Tozuka Katsunori , Wongsirisin Pattama , Nagai Shigenori E. , Kobayashi Yasuhito , Kanno Miki , Kubo Kazuyuki , Takai Ken , Inoue Kenichi , Matsumoto Hiroshi , Shimizu Yoshihito , Suganuma Masami 
Published: July 2021

AbstractTo understand the mechanism underlying metastasis, identification of a mechanism-based and common biomarker for circulating tumour cells (CTCs) in heterogenous breast cancer is needed. SET, an endogenous inhibitor of protein phosphatase 2A, was overexpressed in all subtypes of invasive breast carcinoma tissues. Treatment with SET-targeted siRNAs reduced the motility of MCF-7 and MDA-MB-231 cells in transwell assay. SET knockdown reduced the number of mammospheres by 60–70% in MCF-7 and MDA-MB-231 cells, which was associated with the downregulation of OCT4 and SLUG. Hence, we analysed the presence of SET-expressing CTCs (SET-CTCs) in 24 breast cancer patients. CTCs were enriched using a size-based method and then immunocytochemically analysed using an anti-SET antibody. SET-CTCs were detected in 6/6 (100%) patients with recurrent breast cancer with a median value of 12 (12 cells/3 mL blood), and in 13/18 (72.2%) patients with stage I–III breast cancer with a median value of 2.5, while the median value of healthy controls was 0. Importantly, high numbers of SET-CTCs were correlated with lymph node metastasis in patients with stage I–III disease. Our results indicate that SET contributes to breast cancer progression and can act as a potential biomarker of CTCs for the detection of metastasis.