bluuebunny/crossref_metadata_2025 huggingface dataset:
Vicariance in a generalist fish parasite driven by climate and salinity tolerance of hosts
Authors: Andreou D. , Antognazza C.M. , Williams C.F. , Bradley H. , Reading A.J. , Hardouin E.A. , Stewart J.R. , Sheath D. , Galligar A. , Johnson E. , Britton J.R.
Published: September 2020

Acanthocephalans are parasites with complex lifecycles that are important components of aquatic systems and are often model species for parasite-mediated host manipulation. Genetic characterization has recently resurrectedPomphorhynchus tereticollisas a distinct species fromPomphorhynchus laevis, with potential implications for fisheries management and host manipulation research. Morphological and molecular examinations of parasites from 7 English rivers across 9 fish species revealed thatP. tereticolliswas the onlyPomphorhynchusparasite present in Britain, rather thanP. laevisas previously recorded. Molecular analyses included two non-overlapping regions of the mitochondrial gene – cytochrome oxidase and generated 62 sequences for the shorter fragment (295 bp) and 74 for the larger fragment (583 bp). These were combined with 61 and 13 sequences respectively, from Genbank. A phylogenetic analysis using the two genetic regions and all the DNA sequences available forP. tereticollisidentified two distinct genetic lineages in Britain. One lineage, possibly associated with cold water tolerant fish, potentially spread to the northern parts of Britain from the Baltic regionviaa northern route across the estuarine area of what is now the North Sea during the last Glaciation. The other lineage, associated with temperate freshwater fish, may have arrived laterviathe Rhine/Thames fluvial connection during the last glaciation or early Holocene when sea levels were low. These results raise important questions on this generalist parasite and its variously environmentally adapted hosts, and especially in relation to the consequences for parasite vicariance.
The Economy-Wide Impact of Subsidy Reform: A CGE Analysis
Authors: Roos Elizabeth L. , Adams Philip D.
Published: September 2020

Oil prices fell from around $US110 per barrel in 2014 to less than $US50per barrel at the start of 2017. This put enormous pressure on government budgets within the Gulf Cooperation Council (GCC) region. The focus of GCC economic policies quickly shifted to fiscal reform, including the removal of domestic subsidies on energy products. In this paper, we use a dynamic Computable General Equilibrium (CGE) model to investigate the economic impact of the gradual removal of subsidies on refined petroleum and electricity, with specific reference to the Kingdom of Saudi Arabia (KSA).

Our study shows that removing subsidies eliminates a large distortion in the economy. This improves the efficiency of resource use, so that even though employment and capital in most years fall relative to baseline levels, real GDP rises. In addition, we show that fully-funded compensation payments offset the increases in energy prices, leaving economic welfare of the Saudi-national population little affected. Removing the energy subsidies leads to an improvement in the net volume of trade, while leading to a mixed outcome for industries.
Delirium at the end of life
Authors: Knoepfel Silvana , Bode Leonie , Gehrke Samuel , Spiller Tobias , Fuchs Simon , Ernst Jutta , von Känel Roland , Boettger Soenke
Published: September 2020

Background

The general in-hospital mortality and interrelationship with delirium are vastly understudied. Therefore, this study aimed to assess the rates of in-hospital mortality and terminal delirium.

Method

In this prospective cohort study of 28,860 patients from 37 services including 718 in-hospital deaths, mortality rates and prevalence of terminal delirium were determined with simple logistic regressions and their respective odds ratios (ORs).

Results

Although overall in-hospital mortality was low (2.5%), substantial variance between services became apparent: Across intensive care services the rate was 10.8% with a 5.8-fold increased risk, across medical services rates were 4.4% and 2.4-fold, whereas at the opposite end, across surgical services rates were 0.7% and 87% reduction, respectively. The highest in-hospital mortality rate occurred on the palliative care services (27.3%, OR 19.45). The general prevalence of terminal delirium was 90.7% and ranged from 83.2% to 100%. Only across intensive care services (98.1%, OR 7.48), specifically medical intensive care (98.1%, OR 7.48) and regular medical services (95.8%, OR 4.12) rates of terminal delirium were increased. In contrast, across medical services (86.4%, OR 0.32) and in particular oncology (73.9%, OR 0.25), pulmonology (72%, OR 0.31) and cardiology (63.2%, OR 0.4) rates were decreased. For the remaining services, rates of terminal delirium were the same.

Significance of results

Although in-hospital mortality was low, the interrelationship with delirium was vast: most patients were delirious at the end of life. The implications of terminal delirium merit further studies.
Metabolic and behavioural effects in offspring exposed to maternal sucrose consumption: a systematic review and meta-analysis of data from rodent models
Authors: Morahan H. L. , Leenaars C. H. C. , Boakes R. A. , Rooney K. B.
Published: September 2020

Consumption of sugar-sweetened beverages (SSBs) during pregnancy has been associated with childhood obesity. Research in which rodent dams have been given high-fat/high-sugar diets has consistently found metabolic alterations in their offspring. However, what remains unclear is the potential impact on the developing fetus of giving sugar in isolation at concentrations similar to SSBs to the mothers. Therefore, we conducted a systematic review and meta-analysis (Protocol No: 127115 on Prospero) to identify potential relationships between maternal sucrose consumption and metabolic outcomes in offspring of rodent (rat or mouse) models. We analysed studies that provided rodent mothers dams with access to sucrose solutions (8–20% w/v) prior to conception, during pregnancy and/or lactation and that reported offspring outcomes of body weight (BW), body composition and glycaemic control. Following a systematic search of four databases (PubMed, EMBASE, Web of Science and Scopus) performed on 15 January 2019, maternal and offspring data from 15 papers were identified for inclusion. Only rat studies were identified. Meta-analyses were performed on standardised mean differences for maternal and offspring BW and fasting glucose levels, with subgroup analyses of strain, sucrose concentration, exposure period and sex of offspring. A bias towards the inclusion of only data from male offspring was identified and this limited interpretation of potential sexually dimorphic outcomes. Maternal sucrose exposure was associated with an increased risk of obesity and poor glucose disposal in adult and aged offspring.
Das Gesundheitsverhalten von Pflegefachpersonen
Authors: Stefani Maria
Published: September 2020

Zusammenfassung. In einer qualitativen Interviewstudie untersuchte die Autorin ein widersprüchliches Phänomen: Pflegefachpersonen, eine Berufsgruppe mit hoher Gesundheitskompetenz, sind überdurchschnittlich stark von Gesundheitsstörungen betroffen. Zudem zeigen betriebliche Gesundheitsmaßnahmen wenig Wirkung. In diesem Artikel werden wesentliche Erkenntnisse der Studie vorgestellt mit dem Schwerpunkt auf das Gesundheitsverhalten der Zielgruppe, das im Zusammenhang mit Berufspezifika sowie den sozial geprägten Mustern von Deutungen und Handlungen in der Pflege analysiert wurde.
Up Close with an Active Asteroid
Authors: Wolner Catherine , Hergenrother Carl , Lauretta Dante
Published: September 2020

A new journal special collection investigates the ejection of particles from the asteroid Bennu and the implications of these observations for asteroid science.
Live biotherapeutic products: the importance of a defined regulatory framework
Authors: Cordaillat-Simmons Magali , Rouanet Alice , Pot Bruno
Published: September 2020

Probiotics have been defined as “Live microorganisms that when administered in adequate amounts confer a health benefit on the host”. This definition covers a wide range of applications, target populations and (combinations of) microorganisms. Improved knowledge on the importance of the microbiota in terms of health and disease has further diversified the potential scope of a probiotic intervention, whether intended to reach the market as a food, a food supplement or a drug, depending on the intended use. However, the increased interest in the clinical application of probiotics may require specific attention given their administration in a diseased population. In addition to safety, the impact of the type of product, in terms of quality, production method and, e.g., the acceptance of side effects, is now part of the current regulatory constraints for developers. In the European Union, foods are regulated by the European Food Safety Authority and drugs by the European Medicines Agency; in the United States, the Food and Drug Administration (FDA) deals with both categories. More recently, the FDA has defined a new “live biotherapeutic products” (LBP) category, clarifying pharmaceutical expectations. Since 2019, the quality requirements for this category of drug products have also been clarified by the European Pharmacopoeia (Ph. Eur.). Similar to all products intended to prevent or treat diseases, LBPs will have to be registered as medicinal products to reach the market in the US and in Europe. In this area, regulatory authorities and the pharmaceutical industry will routinely use guidelines of the “International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use” (ICH). Although ICH guidelines are not legally binding, they provide very important recommendations, recognized by almost all drug authorities in the world. In this review, we discuss some aspects of this regulatory framework, especially focusing on products with an intended use in a diseased or vulnerable target population.
A versatile photodetector assisted by photovoltaic and bolometric effects
Authors: Jiang Wei , Zheng Tan , Wu Binmin , Jiao Hanxue , Wang Xudong , Chen Yan , Zhang Xiaoyu , Peng Meng , Wang Hailu , Lin Tie , Shen Hong , Ge Jun , Hu Weida , Xu Xiaofeng , Meng Xiangjian , Chu Junhao , Wang Jianlu
Published: September 2020

The advent of low-dimensional materials with peculiar structure and superb band properties provides a new canonical form for the development of photodetectors. However, the limited exploitation of basic properties makes it difficult for devices to stand out. Here, we demonstrate a hybrid heterostructure with ultrathin vanadium dioxide film and molybdenum ditelluride nanoflake. Vanadium dioxide is a classical semiconductor with a narrow bandgap, a high temperature coefficient of resistance, and phase transformation. Molybdenum ditelluride, a typical two-dimensional material, is often used to construct optoelectronic devices. The heterostructure can realize three different functional modes: (i) the p–n junction exhibits ultrasensitive detection (450 nm–2 μm) with a dark current down to 0.2 pA and a response time of 17 μs, (ii) the Schottky junction works stably under extreme conditions such as a high temperature of 400 K, and (iii) the bolometer shows ultrabroad spectrum detection exceeding 10 μm. The flexible switching between the three modes makes the heterostructure a potential candidate for next-generation photodetectors from visible to longwave infrared radiation (LWIR). This type of photodetector combines versatile detection modes, shedding light on the hybrid application of novel and traditional materials, and is a prototype of advanced optoelectronic devices.
Defining the susceptibility of colorectal cancers to BH3-mimetic compounds
Authors: Luo Ming-Jie , Palmieri Michelle , Riffkin Chris D. , Sakthianandeswaren Anuratha , Djajawi Tirta Mario , Hirokawa Yumiko , Shuttleworth Victoria , Segal David H. , White Christine A. , Nhu Duong , Lessene Guillaume , Lee Margaret , Gibbs Peter , Huang David C. S. , Sieber Oliver M. , Gong Jia-nan
Published: September 2020

Novel targets are required to improve the outcomes for patients with colorectal cancers. In this regard, the selective inhibitor of the pro-survival protein BCL2, venetoclax, has proven highly effective in several hematological malignancies. In addition to BCL2, potent and highly selective small molecule inhibitors of its relatives, BCLxL and MCL1, are now available, prompting us to investigate the susceptibility of colorectal cancers to the inhibition of one or more of these pro-survival proteins. While targeting BCLxL, but not BCL2 or MCL1, on its own had some impact, most (15/17) of the immortalized colorectal cancer cell lines studied were efficiently killed by the combined targeting of BCLxL and MCL1. Importantly, these in vitro findings were confirmed in a xenograft model and, interestingly, in all (5/5) patient derived tumor organoids evaluated. Our results lend strong support to the notion that BCLxL and MCL1 are highly promising targets for further evaluation in efforts to improve the treatment of colorectal cancers.
Rac1 conditional deletion attenuates retinal ganglion cell apoptosis by accelerating autophagic flux in a mouse model of chronic ocular hypertension
Authors: Zhang Meng-Lu , Zhao Guo-Li , Hou Yu , Zhong Shu-Min , Xu Lin-Jie , Li Fang , Niu Wei-Ran , Yuan Fei , Yang Xiong-Li , Wang Zhongfeng , Miao Yanying
Published: September 2020

Autophagy has a fundamental role in maintaining cell homeostasis. Although autophagy has been implicated in glaucomatous pathology, how it regulates retinal ganglion cell (RGC) injury is largely unknown. In the present work, we found that biphasic autophagy in RGCs occurred in a mouse model of chronic ocular hypertension (COH), accompanied by activation of Rac1, a member of the Rho family. Rac1 conditional knockout (Rac1 cKO) in RGCs attenuated RGC apoptosis, in addition to blocking the increase in the number of autophagosomes and the expression of autophagy-related proteins (Beclin1, LC3-II/I, and p62) in COH retinas. Electron micrograph and double immunostaining of LAMP1 and LC3B showed that Rac1 cKO accelerated autolysosome fusion in RGC axons of COH mice. Inhibiting the first autophagic peak with 3-methyladenine or Atg13 siRNA reduced RGC apoptosis, whereas inhibiting the second autophagic peak with 3-MA or blocking autophagic flux by chloroquine increased RGC apoptosis. Furthermore, Rac1 cKO reduced the number of autophagosomes and apoptotic RGCs induced by rapamycin injected intravitreally, which suggests that Rac1 negatively regulates mTOR activity. Moreover, Rac1 deletion decreased Bak expression and did not interfere with the interaction of Beclin1 and Bcl-2 or Bak in COH retinas. In conclusion, autophagy promotes RGC apoptosis in the early stages of glaucoma and results in autophagic cell death in later stages. Rac1 deletion alleviates RGC damage by regulating the cross talk between autophagy and apoptosis through mTOR/Beclin1-Bak. Interfering with the Rac1/mTOR signaling pathway may provide a new strategy for treating glaucoma.
Intratumoral generation of photothermal gold nanoparticles through a vectorized biomineralization of ionic gold
Authors: Schwartz-Duval Aaron S. , Konopka Christian J. , Moitra Parikshit , Daza Enrique A. , Srivastava Indrajit , Johnson Elyse V. , Kampert Taylor L. , Fayn Stanley , Haran Anand , Dobrucki Lawrence W. , Pan Dipanjan
Published: September 2020

Various cancer cells have been demonstrated to have the capacity to form plasmonic gold nanoparticles when chloroauric acid is introduced to their cellular microenvironment. But their biomedical applications are limited, particularly considering the millimolar concentrations and longer incubation period of ionic gold. Here, we describe a simplistic method of intracellular biomineralization to produce plasmonic gold nanoparticles at micromolar concentrations within 30 min of application utilizing polyethylene glycol as delivery vector for ionic gold. We have characterized this process for intracellular gold nanoparticle formation, which progressively accumulates proteins as the ionic gold clusters migrate to the nucleus. This nano-vectorized application of ionic gold emphasizes its potential biomedical opportunities while reducing the quantity of ionic gold and required incubation time. To demonstrate its biomedical potential, we further induce in-situ biosynthesis of gold nanoparticles within MCF7 tumor mouse xenografts which is followed by its photothermal remediation.
Exciton g-factors in monolayer and bilayer WSe2 from experiment and theory
Authors: Förste Jonathan , Tepliakov Nikita V. , Kruchinin Stanislav Yu. , Lindlau Jessica , Funk Victor , Förg Michael , Watanabe Kenji , Taniguchi Takashi , Baimuratov Anvar S. , Högele Alexander
Published: September 2020

The optical properties of monolayer and bilayer transition metal dichalcogenide semiconductors are governed by excitons in different spin and valley configurations, providing versatile aspects for van der Waals heterostructures and devices. Here, we present experimental and theoretical studies of exciton energy splittings in external magnetic field in neutral and charged WSe2 monolayer and bilayer crystals embedded in a field effect device for active doping control. We develop theoretical methods to calculate the exciton g-factors from first principles for all possible spin-valley configurations of excitons in monolayer and bilayer WSe2 including valley-indirect excitons. Our theoretical and experimental findings shed light on some of the characteristic photoluminescence peaks observed for monolayer and bilayer WSe2. In more general terms, the theoretical aspects of our work provide additional means for the characterization of single and few-layer transition metal dichalcogenides, as well as their heterostructures, in the presence of external magnetic fields.
Local heating of radiation belt electrons to ultra-relativistic energies
Authors: Allison Hayley J. , Shprits Yuri Y.
Published: September 2020

Electrically charged particles are trapped by the Earth’s magnetic field, forming the Van Allen radiation belts. Observations show that electrons in this region can have energies in excess of 7 MeV. However, whether electrons at these ultra-relativistic energies are locally accelerated, arise from betatron and Fermi acceleration due to transport across the magnetic field, or if a combination of both mechanisms is required, has remained an unanswered question in radiation belt physics. Here, we present a unique way of analyzing satellite observations which demonstrates that local acceleration is capable of heating electrons up to 7 MeV. By considering the evolution of phase space density peaks in magnetic coordinate space, we observe distinct signatures of local acceleration and the subsequent outward radial diffusion of ultra-relativistic electron populations. The results have important implications for understanding the origin of ultra-relativistic electrons in Earth’s radiation belts, as well as in magnetized plasmas throughout the solar system.
Area law of noncritical ground states in 1D long-range interacting systems
Authors: Kuwahara Tomotaka , Saito Keiji
Published: September 2020

The area law for entanglement provides one of the most important connections between information theory and quantum many-body physics. It is not only related to the universality of quantum phases, but also to efficient numerical simulations in the ground state. Various numerical observations have led to a strong belief that the area law is true for every non-critical phase in short-range interacting systems. However, the area law for long-range interacting systems is still elusive, as the long-range interaction results in correlation patterns similar to those in critical phases. Here, we show that for generic non-critical one-dimensional ground states with locally bounded Hamiltonians, the area law robustly holds without any corrections, even under long-range interactions. Our result guarantees an efficient description of ground states by the matrix-product state in experimentally relevant long-range systems, which justifies the density-matrix renormalization algorithm.
A molecular sensor to quantify the localization of proteins, DNA and nanoparticles in cells
Authors: FitzGerald Laura I. , Aurelio Luigi , Chen Moore , Yuen Daniel , Rennick Joshua J. , Graham Bim , Johnston Angus P. R.
Published: September 2020

Intracellular trafficking governs receptor signaling, pathogenesis, immune responses and fate of nanomedicines. These processes are typically tracked by observing colocalization of fluorescent markers using confocal microscopy. However, this method is low throughput, limited by the resolution of microscopy, and can miss fleeting interactions. To address this, we developed a localization sensor composed of a quenched SNAP-tag substrate (SNAPSwitch) that can be conjugated to biomolecules using click chemistry. SNAPSwitch enables quantitative detection of trafficking to locations of interest within live cells using flow cytometry. Using SNAPSwitch, we followed the trafficking of DNA complexes from endosomes into the cytosol and nucleus. We show that antibodies against the transferrin or hyaluronan receptor are initially sorted into different compartments following endocytosis. In addition, we can resolve which side of the cellular membrane material was located. These results demonstrate SNAPSwitch is a high-throughput and broadly applicable tool to quantitatively track localization of materials in cells.
A role for Biofoundries in rapid development and validation of automated SARS-CoV-2 clinical diagnostics
Authors: Crone Michael A. , Priestman Miles , Ciechonska Marta , Jensen Kirsten , Sharp David J. , Anand Arthi , Randell Paul , Storch Marko , Freemont Paul S.
Published: September 2020

The SARS-CoV-2 pandemic has shown how a rapid rise in demand for patient and community sample testing can quickly overwhelm testing capability globally. With most diagnostic infrastructure dependent on specialized instruments, their exclusive reagent supplies quickly become bottlenecks, creating an urgent need for approaches to boost testing capacity. We address this challenge by refocusing the London Biofoundry onto the development of alternative testing pipelines. Here, we present a reagent-agnostic automated SARS-CoV-2 testing platform that can be quickly deployed and scaled. Using an in-house-generated, open-source, MS2-virus-like particle (VLP) SARS-CoV-2 standard, we validate RNA extraction and RT-qPCR workflows as well as two detection assays based on CRISPR-Cas13a and RT-loop-mediated isothermal amplification (RT-LAMP). In collaboration with an NHS diagnostic testing lab, we report the performance of the overall workflow and detection of SARS-CoV-2 in patient samples using RT-qPCR, CRISPR-Cas13a, and RT-LAMP. The validated RNA extraction and RT-qPCR platform has been installed in NHS diagnostic labs, increasing testing capacity by 1000 samples per day.
Maintenance of sarcomeric integrity in adult muscle cells crucially depends on Z-disc anchored titin
Authors: Swist Sandra , Unger Andreas , Li Yong , Vöge Anja , von Frieling-Salewsky Marion , Skärlén Åsa , Cacciani Nicola , Braun Thomas , Larsson Lars , Linke Wolfgang A.
Published: September 2020

The giant protein titin is thought to be required for sarcomeric integrity in mature myocytes, but direct evidence for this hypothesis is limited. Here, we describe a mouse model in which Z-disc-anchored TTN is depleted in adult skeletal muscles. Inactivation of TTN causes sarcomere disassembly and Z-disc deformations, force impairment, myocyte de-stiffening, upregulation of TTN-binding mechanosensitive proteins and activation of protein quality-control pathways, concomitant with preferential loss of thick-filament proteins. Interestingly, expression of the myosin-bound Cronos-isoform of TTN, generated from an alternative promoter not affected by the targeting strategy, does not prevent deterioration of sarcomere formation and maintenance. Finally, we demonstrate that loss of Z-disc-anchored TTN recapitulates muscle remodeling in critical illness ‘myosinopathy’ patients, characterized by TTN-depletion and loss of thick filaments. We conclude that full-length TTN is required to integrate Z-disc and A-band proteins into the mature sarcomere, a function that is lost when TTN expression is pathologically lowered.
The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia
Authors: Ham Daniel J. , Börsch Anastasiya , Lin Shuo , Thürkauf Marco , Weihrauch Martin , Reinhard Judith R. , Delezie Julien , Battilana Fabienne , Wang Xueyong , Kaiser Marco S. , Guridi Maitea , Sinnreich Michael , Rich Mark M. , Mittal Nitish , Tintignac Lionel A. , Handschin Christoph , Zavolan Mihaela , Rüegg Markus A.
Published: September 2020

With human median lifespan extending into the 80s in many developed countries, the societal burden of age-related muscle loss (sarcopenia) is increasing. mTORC1 promotes skeletal muscle hypertrophy, but also drives organismal aging. Here, we address the question of whether mTORC1 activation or suppression is beneficial for skeletal muscle aging. We demonstrate that chronic mTORC1 inhibition with rapamycin is overwhelmingly, but not entirely, positive for aging mouse skeletal muscle, while genetic, muscle fiber-specific activation of mTORC1 is sufficient to induce molecular signatures of sarcopenia. Through integration of comprehensive physiological and extensive gene expression profiling in young and old mice, and following genetic activation or pharmacological inhibition of mTORC1, we establish the phenotypically-backed, mTORC1-focused, multi-muscle gene expression atlas, SarcoAtlas (https://sarcoatlas.scicore.unibas.ch/), as a user-friendly gene discovery tool. We uncover inter-muscle divergence in the primary drivers of sarcopenia and identify the neuromuscular junction as a focal point of mTORC1-driven muscle aging.
Enhanced carbon dioxide conversion at ambient conditions via a pore enrichment effect
Authors: Zhou Wei , Deng Qi-Wen , Ren Guo-Qing , Sun Lei , Yang Li , Li Yi-Meng , Zhai Dong , Zhou Yi-Hong , Deng Wei-Qiao
Published: September 2020

Chemical fixation of carbon dioxide (CO2) may be a pathway to retard the current trend of rapid global warming. However, the current economic cost of chemical fixation remains high because the chemical fixation of CO2 usually requires high temperature or high pressure. The rational design of an efficient catalyst that works at ambient conditions might substantially reduce the economic cost of fixation. Here, we report the rational design of covalent organic frameworks (COFs) as efficient CO2 fixation catalysts under ambient conditions based on the finding of “pore enrichment”, which is concluded by a detailed investigation of the 10994 COFs. The best predicted COF, Zn-Salen-COF-SDU113, is synthesized, and its efficient catalytic performance for CO2 cycloaddition to terminal epoxide is confirmed with a yield of 98.2% and turnover number (TON) of 3068.9 under ambient conditions, which is comparable to the reported leading catalysts. Moreover, this COF achieves the cycloaddition of CO2 to 2,3-epoxybutane under ambient conditions among all porous materials. This work provides a strategy for designing porous catalysts in the economic fixation of carbon dioxide.
FastClone is a probabilistic tool for deconvoluting tumor heterogeneity in bulk-sequencing samples
Authors: Xiao Yao , Wang Xueqing , Zhang Hongjiu , Ulintz Peter J. , Li Hongyang , Guan Yuanfang
Published: September 2020

Dissecting tumor heterogeneity is a key to understanding the complex mechanisms underlying drug resistance in cancers. The rich literature of pioneering studies on tumor heterogeneity analysis spurred a recent community-wide benchmark study that compares diverse modeling algorithms. Here we present FastClone, a top-performing algorithm in accuracy in this benchmark. FastClone improves over existing methods by allowing the deconvolution of subclones that have independent copy number variation events within the same chromosome regions. We characterize the behavior of FastClone in identifying subclones using stage III colon cancer primary tumor samples as well as simulated data. It achieves approximately 100-fold acceleration in computation for both simulated and patient data. The efficacy of FastClone will allow its application to large-scale data and clinical data, and facilitate personalized medicine in cancers.
ER-mitochondria contacts promote mtDNA nucleoids active transportation via mitochondrial dynamic tubulation
Authors: Qin Jinshan , Guo Yuting , Xue Boxin , Shi Peng , Chen Yang , Su Qian Peter , Hao Huiwen , Zhao Shujuan , Wu Congying , Yu Li , Li Dong , Sun Yujie
Published: September 2020

A human cell contains hundreds to thousands of mitochondrial DNA (mtDNA) packaged into nucleoids. Currently, the segregation and allocation of nucleoids are thought to be passively determined by mitochondrial fusion and division. Here we provide evidence, using live-cell super-resolution imaging, that nucleoids can be actively transported via KIF5B-driven mitochondrial dynamic tubulation (MDT) activities that predominantly occur at the ER-mitochondria contact sites (EMCS). We further demonstrate that a mitochondrial inner membrane protein complex MICOS links nucleoids to Miro1, a KIF5B receptor on mitochondria, at the EMCS. We show that such active transportation is a mechanism essential for the proper distribution of nucleoids in the peripheral zone of the cell. Together, our work identifies an active transportation mechanism of nucleoids, with EMCS serving as a key platform for the interplay of nucleoids, MICOS, Miro1, and KIF5B to coordinate nucleoids segregation and transportation.
A moonlighting role for enzymes of glycolysis in the co-localization of mitochondria and chloroplasts
Authors: Zhang Youjun , Sampathkumar Arun , Kerber Sandra Mae-Lin , Swart Corné , Hille Carsten , Seerangan Kumar , Graf Alexander , Sweetlove Lee , Fernie Alisdair R.
Published: September 2020

Glycolysis is one of the primordial pathways of metabolism, playing a pivotal role in energy metabolism and biosynthesis. Glycolytic enzymes are known to form transient multi-enzyme assemblies. Here we examine the wider protein-protein interactions of plant glycolytic enzymes and reveal a moonlighting role for specific glycolytic enzymes in mediating the co-localization of mitochondria and chloroplasts. Knockout mutation of phosphoglycerate mutase or enolase resulted in a significantly reduced association of the two organelles. We provide evidence that phosphoglycerate mutase and enolase form a substrate-channelling metabolon which is part of a larger complex of proteins including pyruvate kinase. These results alongside a range of genetic complementation experiments are discussed in the context of our current understanding of chloroplast-mitochondrial interactions within photosynthetic eukaryotes.
Synthesis of chiral anti-1,2-diamine derivatives through copper(I)-catalyzed asymmetric α-addition of ketimines to aldimines
Authors: Gan Xu-Cheng , Zhang Cheng-Yuan , Zhong Feng , Tian Ping , Yin Liang
Published: September 2020

Chiral 1,2-diamines serve as not only common structure units in bioactive molecules but also useful ligands for a range of catalytic asymmetric reactions. Here, we report a method to access anti-1,2-diamine derivatives. By means of the electron-withdrawing nature of 2- or 4-nitro-phenyl group, a copper(I)-catalyzed asymmetric α-addition of ketimines derived from trifluoroacetophenone and 2- or 4-NO2-benzylamines to aldimines is achieved, which affords a series of chiral anti-1,2-diamine derivatives in moderate to high yields with moderate to high diastereoselectivity and high to excellent enantioselectivity. Aromatic aldimines, heteroaromatic aldimines, and aliphatic aldimines serve as suitable substrates. The nitro group is demonstrated as a synthetical handle by several transformations, including a particularly interesting Fe(acac)3-catalyzed radical hydroamination with a trisubstituted olefin. Moreover, the aryl amine moiety obtained by the reduction of the nitro group serves as a synthetically versatile group, which leads to the generation of several functional groups by the powerful Sandmeyer reaction, such as -OH, -Br, -CF3, and -BPin.
Mapping and identification of soft corona proteins at nanoparticles and their impact on cellular association
Authors: Mohammad-Beigi Hossein , Hayashi Yuya , Zeuthen Christina Moeslund , Eskandari Hoda , Scavenius Carsten , Juul-Madsen Kristian , Vorup-Jensen Thomas , Enghild Jan J. , Sutherland Duncan S.
Published: September 2020

The current understanding of the biological identity that nanoparticles may acquire in a given biological milieu is mostly inferred from the hard component of the protein corona (HC). The composition of soft corona (SC) proteins and their biological relevance have remained elusive due to the lack of analytical separation methods. Here, we identify a set of specific corona proteins with weak interactions at silica and polystyrene nanoparticles by using an in situ click-chemistry reaction. We show that these SC proteins are present also in the HC, but are specifically enriched after the capture, suggesting that the main distinction between HC and SC is the differential binding strength of the same proteins. Interestingly, the weakly interacting proteins are revealed as modulators of nanoparticle-cell association mainly through their dynamic nature. We therefore highlight that weak interactions of proteins at nanoparticles should be considered when evaluating nano-bio interfaces.
Enhancing mucosal immunity by transient microbiota depletion
Authors: Becattini Simone , Littmann Eric R. , Seok Ruth , Amoretti Luigi , Fontana Emily , Wright Roberta , Gjonbalaj Mergim , Leiner Ingrid M. , Plitas George , Hohl Tobias M. , Pamer Eric G.
Published: September 2020

Tissue resident memory CD8+ T cells (Trm) are poised for immediate reactivation at sites of pathogen entry and provide optimal protection of mucosal surfaces. The intestinal tract represents a portal of entry for many infectious agents; however, to date specific strategies to enhance Trm responses at this site are lacking. Here, we present TMDI (Transient Microbiota Depletion-boosted Immunization), an approach that leverages antibiotic treatment to temporarily restrain microbiota-mediated colonization resistance, and favor intestinal expansion to high densities of an orally-delivered Listeria monocytogenes strain carrying an antigen of choice. By augmenting the local chemotactic gradient as well as the antigenic load, this procedure generates a highly expanded pool of functional, antigen-specific intestinal Trm, ultimately enhancing protection against infectious re-challenge in mice. We propose that TMDI is a useful model to dissect the requirements for optimal Trm responses in the intestine, and also a potential platform to devise novel mucosal vaccination approaches.
Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity
Authors: Yang Wenjing , Yu Tianming , Huang Xiangsheng , Bilotta Anthony J. , Xu Leiqi , Lu Yao , Sun Jiaren , Pan Fan , Zhou Jia , Zhang Wenbo , Yao Suxia , Maynard Craig L. , Singh Nagendra , Dann Sara M. , Liu Zhanju , Cong Yingzi
Published: September 2020

Innate lymphoid cells (ILCs) and CD4+ T cells produce IL-22, which is critical for intestinal immunity. The microbiota is central to IL-22 production in the intestines; however, the factors that regulate IL-22 production by CD4+ T cells and ILCs are not clear. Here, we show that microbiota-derived short-chain fatty acids (SCFAs) promote IL-22 production by CD4+ T cells and ILCs through G-protein receptor 41 (GPR41) and inhibiting histone deacetylase (HDAC). SCFAs upregulate IL-22 production by promoting aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α (HIF1α) expression, which are differentially regulated by mTOR and Stat3. HIF1α binds directly to the Il22 promoter, and SCFAs increase HIF1α binding to the Il22 promoter through histone modification. SCFA supplementation enhances IL-22 production, which protects intestines from inflammation. SCFAs promote human CD4+ T cell IL-22 production. These findings establish the roles of SCFAs in inducing IL-22 production in CD4+ T cells and ILCs to maintain intestinal homeostasis.
Microenvironment-responsive immunoregulatory electrospun fibers for promoting nerve function recovery
Authors: Xi Kun , Gu Yong , Tang Jincheng , Chen Hao , Xu Yun , Wu Liang , Cai Feng , Deng Lianfu , Yang Huilin , Shi Qin , Cui Wenguo , Chen Liang
Published: September 2020

The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury.
Modulating electrolyte structure for ultralow temperature aqueous zinc batteries
Authors: Zhang Qiu , Ma Yilin , Lu Yong , Li Lin , Wan Fang , Zhang Kai , Chen Jun
Published: September 2020

Rechargeable aqueous batteries are an up-and-coming system for potential large-scale energy storage due to their high safety and low cost. However, the freeze of aqueous electrolyte limits the low-temperature operation of such batteries. Here, we report the breakage of original hydrogen-bond network in ZnCl2 solution by modulating electrolyte structure, and thus suppressing the freeze of water and depressing the solid-liquid transition temperature of the aqueous electrolyte from 0 to –114 °C. This ZnCl2-based low-temperature electrolyte renders polyaniline||Zn batteries available to operate in an ultra-wide temperature range from –90 to +60 °C, which covers the earth surface temperature in record. Such polyaniline||Zn batteries are robust at –70 °C (84.9 mA h g−1) and stable during over 2000 cycles with ~100% capacity retention. This work significantly provides an effective strategy to propel low-temperature aqueous batteries via tuning the electrolyte structure and widens the application range of temperature adaptation of aqueous batteries.
Dislocation and oxygen-release driven delithiation in Li2MnO3
Authors: Nakayama Kei , Ishikawa Ryo , Kobayashi Shunsuke , Shibata Naoya , Ikuhara Yuichi
Published: September 2020

Lithium-excess layered cathode materials such as Li2MnO3 have attracted much attention owing to their high energy densities. It has been proposed that oxygen-release and cation-mixing might be induced by delithiation. However, it is still unclear as to how the delithiated-region grows. Here, by using atomic-resolution scanning transmission electron microscopy combined with electron energy-loss spectroscopy, we directly observe the atomic structures at the interface between pristine and delithiated regions in the partially delithiated Li2MnO3 single crystal. We elucidate that the delithiated regions have extensive amounts of irreversible defects such as oxygen-release and Mn/Li cation-mixing. At the interface, a partially cation disordered structure is formed, where Mn migration occurred only in the specific Mn/Li layers. Besides, a number of dislocations are formed at the interface to compensate the lattice mismatch between the pristine and delithiated regions. The observed oxygen-release and dislocations could govern the growth of delithiated-regions and performance degradation in Li2MnO3.
Antibiotic susceptibility signatures identify potential antimicrobial targets in the Acinetobacter baumannii cell envelope
Authors: Geisinger Edward , Mortman Nadav J. , Dai Yunfei , Cokol Murat , Syal Sapna , Farinha Andrew , Fisher Delaney G. , Tang Amy Y. , Lazinski David W. , Wood Stephen , Anthony Jon , van Opijnen Tim , Isberg Ralph R.
Published: September 2020

A unique, protective cell envelope contributes to the broad drug resistance of the nosocomial pathogen Acinetobacter baumannii. Here we use transposon insertion sequencing to identify A. baumannii mutants displaying altered susceptibility to a panel of diverse antibiotics. By examining mutants with antibiotic susceptibility profiles that parallel mutations in characterized genes, we infer the function of multiple uncharacterized envelope proteins, some of which have roles in cell division or cell elongation. Remarkably, mutations affecting a predicted cell wall hydrolase lead to alterations in lipooligosaccharide synthesis. In addition, the analysis of altered susceptibility signatures and antibiotic-induced morphology patterns allows us to predict drug synergies; for example, certain beta-lactams appear to work cooperatively due to their preferential targeting of specific cell wall assembly machineries. Our results indicate that the pathogen may be effectively inhibited by the combined targeting of multiple pathways critical for envelope growth.
A role for annexin A2 in scaffolding the peroxiredoxin 2–STAT3 redox relay complex
Authors: Talwar Deepti , Messens Joris , Dick Tobias P.
Published: September 2020

Hydrogen peroxide (H2O2) is recognized to act as a signaling molecule. Peroxiredoxins (Prxs) have the ability to transfer H2O2-derived oxidizing equivalents to redox-regulated target proteins, thus facilitating the transmission of H2O2 signals. It has remained unclear how Prxs and their target proteins are brought together to allow for target-specific protein thiol oxidation. Addressing the specific case of Prx2-dependent STAT3 oxidation, we here show that the association of the two proteins occurs prior to Prx oxidation and depends on a scaffolding protein, the membrane chaperone annexin A2. Deletion or depletion of annexin A2 interrupts the transfer of oxidizing equivalents from Prx2 to STAT3, which is observed to take place on membranes. These findings support the notion that the Prx2-STAT3 redox relay is part of a highly organized membrane signaling domain.
Rapid and dynamic processing of face pareidolia in the human brain
Authors: Wardle Susan G. , Taubert Jessica , Teichmann Lina , Baker Chris I.
Published: September 2020

The human brain is specialized for face processing, yet we sometimes perceive illusory faces in objects. It is unknown whether these natural errors of face detection originate from a rapid process based on visual features or from a slower, cognitive re-interpretation. Here we use a multifaceted approach to understand both the spatial distribution and temporal dynamics of illusory face representation in the brain by combining functional magnetic resonance imaging and magnetoencephalography neuroimaging data with model-based analysis. We find that the representation of illusory faces is confined to occipital-temporal face-selective visual cortex. The temporal dynamics reveal a striking evolution in how illusory faces are represented relative to human faces and matched objects. Illusory faces are initially represented more similarly to real faces than matched objects are, but within ~250 ms, the representation transforms, and they become equivalent to ordinary objects. This is consistent with the initial recruitment of a broadly-tuned face detection mechanism which privileges sensitivity over selectivity.
Fonio millet genome unlocks African orphan crop diversity for agriculture in a changing climate
Authors: Abrouk Michael , Ahmed Hanin Ibrahim , Cubry Philippe , Šimoníková Denisa , Cauet Stéphane , Pailles Yveline , Bettgenhaeuser Jan , Gapa Liubov , Scarcelli Nora , Couderc Marie , Zekraoui Leila , Kathiresan Nagarajan , Čížková Jana , Hřibová Eva , Doležel Jaroslav , Arribat Sandrine , Bergès Hélène , Wieringa Jan J. , Gueye Mathieu , Kane Ndjido A. , Leclerc Christian , Causse Sandrine , Vancoppenolle Sylvie , Billot Claire , Wicker Thomas , Vigouroux Yves , Barnaud Adeline , Krattinger Simon G.
Published: September 2020

Sustainable food production in the context of climate change necessitates diversification of agriculture and a more efficient utilization of plant genetic resources. Fonio millet (Digitaria exilis) is an orphan African cereal crop with a great potential for dryland agriculture. Here, we establish high-quality genomic resources to facilitate fonio improvement through molecular breeding. These include a chromosome-scale reference assembly and deep re-sequencing of 183 cultivated and wildDigitariaaccessions, enabling insights into genetic diversity, population structure, and domestication. Fonio diversity is shaped by climatic, geographic, and ethnolinguistic factors. Two genes associated with seed size and shattering showed signatures of selection. Most known domestication genes from other cereal models however have not experienced strong selection in fonio, providing direct targets to rapidly improve this crop for agriculture in hot and dry environments.
Three-dimensional imaging through scattering media based on confocal diffuse tomography
Authors: Lindell David B. , Wetzstein Gordon
Published: September 2020

Optical imaging techniques, such as light detection and ranging (LiDAR), are essential tools in remote sensing, robotic vision, and autonomous driving. However, the presence of scattering places fundamental limits on our ability to image through fog, rain, dust, or the atmosphere. Conventional approaches for imaging through scattering media operate at microscopic scales or require a priori knowledge of the target location for 3D imaging. We introduce a technique that co-designs single-photon avalanche diodes, ultra-fast pulsed lasers, and a new inverse method to capture 3D shape through scattering media. We demonstrate acquisition of shape and position for objects hidden behind a thick diffuser (≈6 transport mean free paths) at macroscopic scales. Our technique, confocal diffuse tomography, may be of considerable value to the aforementioned applications.
Natural emotion vocabularies as windows on distress and well-being
Authors: Vine Vera , Boyd Ryan L. , Pennebaker James W.
Published: September 2020

To date we know little about natural emotion word repertoires, and whether or how they are associated with emotional functioning. Principles from linguistics suggest that the richness or diversity of individuals’ actively used emotion vocabularies may correspond with their typical emotion experiences. The current investigation measures active emotion vocabularies in participant-generated natural speech and examined their relationships to individual differences in mood, personality, and physical and emotional well-being. Study 1 analyzes stream-of-consciousness essays by 1,567 college students. Study 2 analyzes public blogs written by over 35,000 individuals. The studies yield consistent findings that emotion vocabulary richness corresponds broadly with experience. Larger negative emotion vocabularies correlate with more psychological distress and poorer physical health. Larger positive emotion vocabularies correlate with higher well-being and better physical health. Findings support theories linking language use and development with lived experience and may have future clinical implications pending further research.