bluuebunny/crossref_metadata_2025 huggingface dataset:
Redox-mediated kick-start of mitochondrial energy metabolism drives resource-efficient seed germination
Authors: Nietzel Thomas , Mostertz Jörg , Ruberti Cristina , Née Guillaume , Fuchs Philippe , Wagner Stephan , Moseler Anna , Müller-Schüssele Stefanie J. , Benamar Abdelilah , Poschet Gernot , Büttner Michael , Møller Ian Max , Lillig Christopher H. , Macherel David , Wirtz Markus , Hell Rüdiger , Finkemeier Iris , Meyer Andreas J. , Hochgräfe Falko , Schwarzländer Markus
Published: December 2019

Seeds preserve a far developed plant embryo in a quiescent state. Seed metabolism relies on stored resources and is reactivated to drive germination when the external conditions are favorable. Since the switchover from quiescence to reactivation provides a remarkable case of a cell physiological transition we investigated the earliest events in energy and redox metabolism of
Arabidopsis
seeds at imbibition. By developing fluorescent protein biosensing in intact seeds, we observed ATP accumulation and oxygen uptake within minutes, indicating rapid activation of mitochondrial respiration, which coincided with a sharp transition from an oxidizing to a more reducing thiol redox environment in the mitochondrial matrix. To identify individual operational protein thiol switches, we captured the fast release of metabolic quiescence in organello and devised quantitative iodoacetyl tandem mass tag (iodoTMT)-based thiol redox proteomics. The redox state across all Cys peptides was shifted toward reduction from 27.1% down to 13.0% oxidized thiol. A large number of Cys peptides (412) were redox switched, representing central pathways of mitochondrial energy metabolism, including the respiratory chain and each enzymatic step of the tricarboxylic acid (TCA) cycle. Active site Cys peptides of glutathione reductase 2, NADPH-thioredoxin reductase a/b, and thioredoxin-o1 showed the strongest responses. Germination of seeds lacking those redox proteins was associated with markedly enhanced respiration and deregulated TCA cycle dynamics suggesting decreased resource efficiency of energy metabolism. Germination in aged seeds was strongly impaired. We identify a global operation of thiol redox switches that is required for optimal usage of energy stores by the mitochondria to drive efficient germination.
Predator-informed looming stimulus experiments reveal how large filter feeding whales capture highly maneuverable forage fish
Authors: Cade David E. , Carey Nicholas , Domenici Paolo , Potvin Jean , Goldbogen Jeremy A.
Published: December 2019

The unique engulfment filtration strategy of microphagous rorqual whales has evolved relatively recently (<5 Ma) and exploits extreme predator/prey size ratios to overcome the maneuverability advantages of swarms of small prey, such as krill. Forage fish, in contrast, have been engaged in evolutionary arms races with their predators for more than 100 million years and have performance capabilities that suggest they should easily evade whale-sized predators, yet they are regularly hunted by some species of rorqual whales. To explore this phenomenon, we determined, in a laboratory setting, when individual anchovies initiated escape from virtually approaching whales, then used these results along with in situ humpback whale attack data to model how predator speed and engulfment timing affected capture rates. Anchovies were found to respond to approaching visual looming stimuli at expansion rates that give ample chance to escape from a sea lion-sized predator, but humpback whales could capture as much as 30–60% of a school at once because the increase in their apparent (visual) size does not cross their prey’s response threshold until after rapid jaw expansion. Humpback whales are, thus, incentivized to delay engulfment until they are very close to a prey school, even if this results in higher hydrodynamic drag. This potential exaptation of a microphagous filter feeding strategy for fish foraging enables humpback whales to achieve 7× the energetic efficiency (per lunge) of krill foraging, allowing for flexible foraging strategies that may underlie their ecological success in fluctuating oceanic conditions.
Shear force sensing of epithelial Na
+
channel (ENaC) relies on
N
-glycosylated asparagines in the palm and knuckle domains of αENaC
Authors: Knoepp Fenja , Ashley Zoe , Barth Daniel , Baldin Jan-Peter , Jennings Michael , Kazantseva Marina , Saw Eng Leng , Katare Rajesh , Alvarez de la Rosa Diego , Weissmann Norbert , Fronius Martin
Published: December 2019

Significance

The ability to sense mechanical forces is essential for all living organisms. Extracellular tethers have been proposed to mediate mechanical activation of channels belonging to the epithelial Na
+
channel (ENaC)/degenerin protein family. The nature and architecture of the tethers that link the channel protein with the extracellular matrix are unknown. Our study provides experimental evidence that glycosylated asparagines and their
N
-glycans are part of tethers for mechanical activation of ENaC by shear force. The identified asparagines are also important for arterial blood pressure regulation in vivo. These findings provide insights into how mechanical forces are sensed by mechanosensitive ENaC channels to regulate blood pressure.
Ultrasmall silica nanoparticles directly ligate the T cell receptor complex
Authors: Vis Bradley , Hewitt Rachel E. , Monie Tom P. , Fairbairn Camilla , Turner Suzanne D. , Kinrade Stephen D. , Powell Jonathan J.
Published: December 2019

The impact of ultrasmall nanoparticles (<10-nm diameter) on the immune system is poorly understood. Recently, ultrasmall silica nanoparticles (USSN), which have gained increasing attention for therapeutic applications, were shown to stimulate T lymphocytes directly and at relatively low-exposure doses. Delineating underlying mechanisms and associated cell signaling will hasten therapeutic translation and is reported herein. Using competitive binding assays and molecular modeling, we established that the T cell receptor (TCR):CD3 complex is required for USSN-induced T cell activation, and that direct receptor complex–particle interactions are permitted both sterically and electrostatically. Activation is not limited to αβ TCR-bearing T cells since those with γδ TCR showed similar responses, implying that USSN mediate their effect by binding to extracellular domains of the flanking CD3 regions of the TCR complex. We confirmed that USSN initiated the signaling pathway immediately downstream of the TCR with rapid phosphorylation of both ζ-chain–associated protein 70 and linker for activation of T cells protein. However, T cell proliferation or IL-2 secretion were only triggered by USSN when costimulatory anti-CD28 or phorbate esters were present, demonstrating that the specific impact of USSN is in initiation of the primary, nuclear factor of activated T cells-pathway signaling from the TCR complex. Hence, we have established that USSN are partial agonists for the TCR complex because of induction of the primary T cell activation signal. Their ability to bind the TCR complex rapidly, and then to dissolve into benign orthosilicic acid, makes them an appealing option for therapies targeted at transient TCR:CD3 receptor binding.
Development of structure–function coupling in human brain networks during youth
Authors: Baum Graham L. , Cui Zaixu , Roalf David R. , Ciric Rastko , Betzel Richard F. , Larsen Bart , Cieslak Matthew , Cook Philip A. , Xia Cedric H. , Moore Tyler M. , Ruparel Kosha , Oathes Desmond J. , Alexander-Bloch Aaron F. , Shinohara Russell T. , Raznahan Armin , Gur Raquel E. , Gur Ruben C. , Bassett Danielle S. , Satterthwaite Theodore D.
Published: December 2019

The protracted development of structural and functional brain connectivity within distributed association networks coincides with improvements in higher-order cognitive processes such as executive function. However, it remains unclear how white-matter architecture develops during youth to directly support coordinated neural activity. Here, we characterize the development of structure–function coupling using diffusion-weighted imaging and
n
-back functional MRI data in a sample of 727 individuals (ages 8 to 23 y). We found that spatial variability in structure–function coupling aligned with cortical hierarchies of functional specialization and evolutionary expansion. Furthermore, hierarchy-dependent age effects on structure–function coupling localized to transmodal cortex in both cross-sectional data and a subset of participants with longitudinal data (
n
= 294). Moreover, structure–function coupling in rostrolateral prefrontal cortex was associated with executive performance and partially mediated age-related improvements in executive function. Together, these findings delineate a critical dimension of adolescent brain development, whereby the coupling between structural and functional connectivity remodels to support functional specialization and cognition.
Regulation of INF2-mediated actin polymerization through site-specific lysine acetylation of actin itself
Authors: A Mu , Fung Tak Shun , Francomacaro Lisa M. , Huynh Thao , Kotila Tommi , Svindrych Zdenek , Higgs Henry N.
Published: December 2019

Significance

Tight regulation is required to control biochemical reactions in cells so that these reactions can be activated precisely when and where needed. Our work focuses on actin, a protein that polymerizes into filaments in at least 20 distinct processes in mammalian cells. We have previously shown that lysine acetylation, a relatively minor modification on actin, is crucial for regulating a specific population of actin filaments through a protein called INF2. Here we identify key acetylated lysines that control INF2 activity. INF2 mutations link to 2 human diseases, focal segmental glomerulosclerosis (a kidney disease) and Charcot–Marie–Tooth disease (a neuropathy), and our findings further the mechanistic understanding of these diseases.
Accurate and rapid background estimation in single-molecule localization microscopy using the deep neural network BGnet
Authors: Möckl Leonhard , Roy Anish R. , Petrov Petar N. , Moerner W. E.
Published: December 2019

Significance

Single-molecule localization microscopy has developed from a specialized technique into a widely used method across biological and chemical science. However, to see one molecule, unwanted light from the sample (background) must be minimized. More importantly, nonuniform background can seriously degrade the localization process. So far, addressing this problem has been challenging. We provide a robust, general, and easy-to-implement framework rooted in deep learning to accurately and rapidly estimate arbitrarily structured background so that this interfering structure can be removed. The method works both for conventional microscopes and also for complex 3-dimensional designs based on engineering the point-spread function. Accurate background estimation is a critically useful tool for extracting maximum information from single-molecule images.
Chorea-related mutations in PDE10A result in aberrant compartmentalization and functionality of the enzyme
Authors: Tejeda Gonzalo S. , Whiteley Ellanor L. , Deeb Tarek Z. , Bürli Roland W. , Moss Stephen J. , Sheridan Eamonn , Brandon Nicholas J. , Baillie George S.
Published: December 2019

Significance

Phosphodiesterase 10A (PDE10A) is as a target of interest in Huntington’s disease (HD) as levels of the enzyme have been shown to decrease prior to the development of the hallmark motor symptoms. Clearly, a better understanding of how PDE10A protein levels change as HD develops is required. Here we show that mutations in the regulatory GAF domains of PDE10A that cause hyperkinetic syndromes in humans lead to misprocessing of the PDE10A enzyme that ultimately leads to targeted degradation by the ubiquitin proteasome system or clearance by autophagy. Both mechanisms result in a paucity of PDE10A activity that lead to a loss of movement coordination. Our research suggests that similar mechanisms may underpin PDE10A loss during HD.
B2 and ALU retrotransposons are self-cleaving ribozymes whose activity is enhanced by EZH2
Authors: Hernandez Alfredo J. , Zovoilis Athanasios , Cifuentes-Rojas Catherine , Han Lu , Bujisic Bojan , Lee Jeannie T.
Published: December 2019

Transposable elements make up half of the mammalian genome. One of the most abundant is the short interspersed nuclear element (SINE). Among their million copies, B2 accounts for ∼350,000 in the mouse genome and has garnered special interest because of emerging roles in epigenetic regulation. Our recent work demonstrated that B2 RNA binds stress genes to retard transcription elongation. Although epigenetically silenced, B2s become massively up-regulated during thermal and other types of stress. Specifically, an interaction between B2 RNA and the Polycomb protein, EZH2, results in cleavage of B2 RNA, release of B2 RNA from chromatin, and activation of thermal stress genes. Although an established RNA-binding protein and histone methyltransferase, EZH2 is not known to be a nuclease. Here, we provide evidence for the surprising conclusion that B2 is a self-cleaving ribozyme. Ribozyme activity depends on Mg+2and monovalent cations but is resistant to protease treatment. However, contact with EZH2 accelerates cleavage rate by >100-fold, suggesting that EZH2 promotes a cleavage-competent RNA conformation. B2 modification-interference analysis demonstrates that phosphorothioate changes at A and C nucleotides can substitute for EZH2. B2 nucleotides 45 to 55 and 100 to 101 are essential for activity. Finally, another family of SINEs, the human ALU element, also produces a self-cleaving RNA and is cleaved during T-cell activation as well as thermal and endoplasmic reticulum (ER) stress. Thus, B2/ALU SINEs may be classified as “epigenetic ribozymes” that function as transcriptional switches during stress. Given their high copy numbers, B2 and ALU may represent the predominant ribozyme activity in mammalian cells.
WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication
Authors: Park Elizabeth M. , Scott Phillip M. , Clutario Kevin , Cassidy Katelyn B. , Zhan Kevin , Gerber Scott A. , Holland Andrew J.
Published: December 2019

Centriole duplication occurs once in each cell cycle to maintain centrosome number. A previous genome-wide screen revealed that depletion of 14 RNA splicing factors leads to a specific defect in centriole duplication, but the cause of this deficit remains unknown. Here, we identified an additional pre-mRNA splicing factor, WBP11, as a novel protein required for centriole duplication. Loss of WBP11 results in the retention of ∼200 introns, including multiple introns in TUBGCP6, a central component of the γ-TuRC. WBP11 depletion causes centriole duplication defects, in part by causing a rapid decline in the level of TUBGCP6. Several additional splicing factors that are required for centriole duplication interact with WBP11 and are required for TUBGCP6 expression. These findings provide insight into how the loss of a subset of splicing factors leads to a failure of centriole duplication. This may have clinical implications because mutations in some spliceosome proteins cause microcephaly and/or growth retardation, phenotypes that are strongly linked to centriole defects.
Electron cryotomography of intact motile cilia defines the basal body to axoneme transition
Authors: Greenan Garrett A. , Vale Ronald D. , Agard David A.
Published: December 2019

Cells use motile cilia to generate force in the extracellular space. The structure of a cilium can be classified into three subdomains: the intracellular basal body (BB) that templates cilium formation, the extracellular axoneme that generates force, and the transition zone (TZ) that bridges them. While the BB is composed of triplet microtubules (TMTs), the axoneme is composed of doublet microtubules (DMTs), meaning the cilium must convert between different microtubule geometries. Here, we performed electron cryotomography to define this conversion, and our reconstructions reveal identifying structural features of the BB, TZ, and axoneme. Each region is distinct in terms of microtubule number and geometry, microtubule inner proteins, and microtubule linkers. TMT to DMT conversion occurs within the BB, and microtubule geometry changes to axonemal by the end of the TZ, followed by the addition of axoneme-specific components essential for cilium motility. Our results provide the highest-resolution images of the motile cilium to date and reveal how BBs template axonemes.
Don’t sugarcoat it: How glycocalyx composition influences cancer progression
Authors: Buffone Alexander , Weaver Valerie M.
Published: December 2019

Mechanical interactions between tumors and the extracellular matrix (ECM) of the surrounding tissues have profound effects on a wide variety of cellular functions. An underappreciated mediator of tumor–ECM interactions is the glycocalyx, the sugar-decorated proteins and lipids that act as a buffer between the tumor and the ECM, which in turn mediates all cell-tissue mechanics. Importantly, tumors have an increase in the density of the glycocalyx, which in turn increases the tension of the cell membrane, alters tissue mechanics, and drives a more cancerous phenotype. In this review, we describe the basic components of the glycocalyx and the glycan moieties implicated in cancer. Next, we examine the important role the glycocalyx plays in driving tension-mediated cancer cell signaling through a self-enforcing feedback loop that expands the glycocalyx and furthers cancer progression. Finally, we discuss current tools used to edit the composition of the glycocalyx and the future challenges in leveraging these tools into a novel tractable approach to treat cancer.
Stem cells in cancer initiation and progression
Authors: Bajaj Jeevisha , Diaz Emily , Reya Tannishtha
Published: December 2019

While standard therapies can lead to an initial remission of aggressive cancers, they are often only a transient solution. The resistance and relapse that follows is driven by tumor heterogeneity and therapy-resistant populations that can reinitiate growth and promote disease progression. There is thus a significant need to understand the cell types and signaling pathways that not only contribute to cancer initiation, but also those that confer resistance and drive recurrence. Here, we discuss work showing that stem cells and progenitors may preferentially serve as a cell of origin for cancers, and that cancer stem cells can be key in driving the continued growth and  functional heterogeneity of established cancers. We also describe emerging evidence for the role of developmental signals in cancer initiation, propagation, and therapy resistance and discuss how targeting these pathways may be of therapeutic value.
Regulation of ion transport from within ion transit pathways
Authors: Hilgemann Donald W.
Published: December 2019

All cells must control the activities of their ion channels and transporters to maintain physiologically appropriate gradients of solutes and ions. The complexity of underlying regulatory mechanisms is staggering, as exemplified by insulin regulation of transporter trafficking. Simpler strategies occur in single-cell organisms, where subsets of transporters act as solute sensors to regulate expression of their active homologues. This Viewpoint highlights still simpler mechanisms by which Na transporters use their own transport sites as sensors for regulation. The underlying principle is inherent to Na/K pumps in which aspartate phosphorylation and dephosphorylation are controlled by occupation of transport sites for Na and K, respectively. By this same principle, Na binding to transport sites can control intrinsic inactivation reactions that are in turn modified by extrinsic signaling factors. Cardiac Na/Ca exchangers (NCX1s) and Na/K pumps are the best examples. Inactivation of NCX1 occurs when cytoplasmic Na sites are fully occupied and is regulated by lipid signaling. Inactivation of cardiac Na/K pumps occurs when cytoplasmic Na-binding sites are not fully occupied, and inactivation is in turn regulated by Ca signaling. Potentially, Na/H exchangers (NHEs) and epithelial Na channels (ENaCs) are regulated similarly. Extracellular protons and cytoplasmic Na ions oppose secondary activation of NHEs by cytoplasmic protons. ENaCs undergo inactivation as cytoplasmic Na rises, and small diffusible molecules of an unidentified nature are likely involved. Multiple other ion channels have recently been shown to be regulated by transiting ions, thereby underscoring that ion permeation and channel gating need not be independent processes.
Distinct antiblockade features of strongly interacting Rydberg atoms under a two-color weak excitation scheme
Authors: Bai Suying , Tian Xuedong , Han Xiaoxuan , Jiao Yuechun , Wu Jinhui , Zhao Jianming , Jia Suotang
Published: December 2019

We present distinct antiblockade features of strongly interacting 64D
5/2 Rydberg atoms employing a two-color excitation scheme. The first color (pulse A) is set to resonantly excite a few seed Rydberg atoms, each of which establishes a blockade region due to the long-range multipole interactions. The second color (pulse B) is blue detuned so that the multipole-interaction-induced shifts of certain atoms are well compensated to result in the antiblockade effect. We find in particular that a few seed atoms can lead to a remarkable difference of the Rydberg excitation in the presence of pulse B for a wide range of blue detuning. Relevant dynamics of this antiblockade excitation is also investigated by varying the pulse-B duration for a fixed blue detuning, further confirming the facilitation process of Rydberg excitation accompanied by a saturation effect. These experimental results can be well recovered by theoretical simulations based on a multilevel two-body model.
Regime shift of the hydroclimate–vegetation system in the Yellow River Delta of China from 1982 through 2015
Authors: Niu Beibei , Zhang Zixuan , Yu Xinyang , Li Xinju , Wang Zhen , Loáiciga Hugo A , Peng Sha
Published: December 2019

The Yellow River Delta (YRD) has been experiencing substantial climatic, hydrological, and anthropogenic stresses, and a sound understanding of the regime shift in its hydroclimate–vegetation system is of fundamental importance for maintaining the health and stability of its regional ecosystems. This study constructs and analyzes a 34-year-dataset (1982–2015) of hydro–climatic variables and satellite-based Normalized Difference Vegetation Index (NDVI) in the YRD. A seasonal-trend decomposition technique based on loess (STL), and a structural change analysis were coupled to detect regime shifts of regional hydroclimate and vegetation in the YRD from 1982 through to 2015. During this period the YRD exhibited a significant warmer–drier–greening trend and experienced four regime shifts of its hydroclimate–vegetation system, with the four shift periods roughly centered in 1989, 1998, 2004, and 2012. Partial correlation analysis revealed that temperature was the dominant factor promoting vegetative growth in spring and autumn (all PNDVI-TEM greater than 0.65), and streamflow impacted the NDVI mainly in summer. Temperature and precipitation were the dominant controls of vegetative growth during the growing season prior to 2002, and thereafter precipitation and streamflow alternately became the main moisture-influencing factors of vegetative growth. Streamflow played an important complementary role on vegetative growth, particularly in near riverine areas when drought exceeds a certain threshold. Additionally, climate shifts determined the changing trend of NDVI across the region, while the effect of land use change is localized and predominant in the northeastern part of the study region. These findings offer an insight into appropriate water regulation of the Yellow River and on climatic adaptation within the YRD.
Monitoring hydropower reliability in Malawi with satellite data and machine learning
Authors: Falchetta Giacomo , Kasamba Chisomo , Parkinson Simon C
Published: December 2019

Hydro-climatic extremes can affect the reliability of electricity supply, in particular in countries that depend greatly on hydropower or cooling water and have a limited adaptive capacity. Assessments of the vulnerability of the power sector and of the impact of extreme events are thus crucial for decision-makers, and yet often they are severely constrained by data scarcity. Here, we introduce and validate an energy-climate-water framework linking remotely-sensed data from multiple satellite missions and instruments (TOPEX/POSEIDON. OSTM/Jason, VIIRS, MODIS, TMPA, AMSR-E) and field observations. The platform exploits random forests regression algorithms to mitigate data scarcity and predict river discharge variability when ungauged. The validated predictions are used to assess the impact of hydroclimatic extremes on hydropower reliability and on the final use of electricity in urban areas proxied by nighttime light radiance variation. We apply the framework to the case of Malawi for the periods 2000–2018 and 2012–2018 for hydrology and power, respectively. Our results highlight the significant impact of hydro-climatic variability and dry extremes on both the supply of electricity and its final use. We thus show that a modelling framework based on open-access data from satellites, machine learning algorithms, and regression analysis can mitigate data scarcity and improve the understanding of vulnerabilities. The proposed approach can support long-term infrastructure development monitoring and identify vulnerable populations, in particular under a changing climate.
Instability of the Kolmogorov flow in a wall-bounded domain
Authors: Chen Zhi-Min
Published: December 2019

In the magnetohydrodynamics (MHD) experiment performed by Bondarenko and his co-workers in 1979, the Kolmogorov flow loses stability and transits into a secondary steady state flow at the Reynolds number R = O(103), as Hartmann boundary layer friction dominates the energy dissipation of the fluid motion. This problem is modelled as a two-dimensional MHD flow bounded between horizontal walls under slip wall boundary condition. However, the rigorous analysis showing the existence of the secondary steady state flow was missing in earlier investigations and has now been established. The theoretical solution has a very good agreement with the flow measured in laboratory experiment at R = O(103). Further transition of the secondary flow is observed numerically. Especially, well developed turbulence arises at R = O(104) via an inverse energy cascade scenario.
FunGeCo: a web-based tool for estimation of functional potential of bacterial genomes and microbiomes using gene context information
Authors: Anand Swadha , Kuntal Bhusan K , Mohapatra Anwesha , Bhatt Vineet , Mande Sharmila S
Published: December 2019

Motivation

Functional potential of genomes and metagenomes which are inferred using homology-based methods are often subjected to certain limitations, especially for proteins with homologs which function in multiple pathways. Augmenting the homology information with genomic location of the constituent genes can significantly improve the accuracy of estimated functions. This can help in distinguishing cognate homolog belonging to a candidate pathway from its other homologs functional in different pathways.

Results

In this article, we present a web-based analysis platform ‘FunGeCo’ to enable gene-context-based functional inference for microbial genomes and metagenomes. It is expected to be a valuable resource and complement the existing tools for understanding the functional potential of microbes which reside in an environment.

Availability and implementation

https://web.rniapps.net/fungeco [Freely available for academic use].

Supplementary information

Supplementary data are available at Bioinformatics online.
Dynamic borrowing in the presence of treatment effect heterogeneity
Authors: Kotalik Ales , Vock David M , Donny Eric C , Hatsukami Dorothy K , Koopmeiners Joseph S
Published: December 2019

A number of statistical approaches have been proposed for incorporating supplemental information in randomized clinical trials. Existing methods often compare the marginal treatment effects to evaluate the degree of consistency between sources. Dissimilar marginal treatment effects would either lead to increased bias or down-weighting of the supplemental data. This represents a limitation in the presence of treatment effect heterogeneity, in which case the marginal treatment effect may differ between the sources solely due to differences between the study populations. We introduce the concept of covariate-adjusted exchangeability, in which differences in the marginal treatment effect can be explained by differences in the distributions of the effect modifiers. The potential outcomes framework is used to conceptualize covariate-adjusted and marginal exchangeability. We utilize a linear model and the existing multisource exchangeability models framework to facilitate borrowing when marginal treatment effects are dissimilar but covariate-adjusted exchangeability holds. We investigate the operating characteristics of our method using simulations. We also illustrate our method using data from two clinical trials of very low nicotine content cigarettes. Our method has the ability to incorporate supplemental information in a wider variety of situations than when only marginal exchangeability is considered.
Carbon capture and storage in the USA: the role of US innovation leadership in climate-technology commercialization
Authors: Beck Lee
Published: December 2019

To limit global warming and mitigate climate change, the global economy needs to decarbonize and reduce emissions to net-zero by mid-century. The asymmetries of the global energy system necessitate the deployment of a suite of decarbonization technologies and an all-of-the-above approach to deliver the steep CO2-emissions reductions necessary. Carbon capture and storage (CCS) technologies that capture CO2 from industrial and power-plant point sources as well as the ambient air and store them underground are largely seen as needed to address both the flow of emissions being released and the stock of CO2 already in the atmosphere. Despite the pressing need to commercialize the technologies, their large-scale deployment has been slow. Initial deployment, however, could lead to near-term cost reduction and technology proliferation, and lowering of the overall system cost of decarbonization. As of November 2019, more than half of global large-scale CCS facilities are in the USA, thanks to a history of sustained government support for the technologies. Recently, the USA has seen a raft of new developments on the policy and project side signaling a reinvigorated push to commercialize the technology. Analysing these recent developments using a policy-priorities framework for CCS commercialization developed by the Global CCS Institute, the paper assesses the USA’s position to lead large-scale deployment of CCS technologies to commercialization. It concludes that the USA is in a prime position due to the political economic characteristics of its energy economy, resource wealth and innovation-driven manufacturing sector.
Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Rapid-Initiation Model of Care for Human Immunodeficiency Virus Type 1 Infection: Primary Analysis of the DIAMOND Study
Authors: Huhn Gregory D , Crofoot Gordon , Ramgopal Moti , Gathe Joseph , Bolan Robert , Luo Donghan , Simonson Richard Bruce , Nettles Richard E , Benson Carmela , Dunn Keith
Published: December 2019

Background

Most guidelines recommend rapid treatment initiation for patients with newly diagnosed human immunodeficiency virus type 1 (HIV-1) infection, but prospective US data are limited. The DIAMOND (NCT03227861) study using darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a phase 3 prospective study evaluating efficacy/safety of a single-tablet regimen in a rapid-initiation model of care.

Methods

Adults aged ≥18 years began D/C/F/TAF ≤14 days from diagnosis without screening/baseline results; as results became available, participants not meeting predefined safety/resistance stopping rules continued. Primary endpoint was virologic response (HIV-1 RNA <50 copies/mL; intent-to-treat; US Food and Drug Administration [FDA] snapshot) at week 48; participant satisfaction was measured via the HIV Treatment Satisfaction Questionnaire status version (HIVTSQs).

Results

Of 109 participants, 87% were male, 32% black/African American, median (range) age was 28 (range, 19–66) years, 25% of participants had HIV-1 RNA ≥100 000 copies/mL, 21% had CD4+ cell count <200 cells/µL, and 31% enrolled ≤48 hours from diagnosis. At week 48, 97 (89%) participants completed the study and 92 (84%) achieved HIV-1 RNA <50 copies/mL (FDA snapshot). There were no protocol-defined virologic failures; incidences of adverse events (AEs) and adverse drug reactions (33%) were low, no serious AEs were study drug related, and 1 (<1%) participant discontinued due to study drug related AE(s). The overall HIVTSQs score at week 48 was 58 (maximum: 60).

Conclusions

At week 48, a high proportion of participants starting D/C/F/TAF achieved HIV-1 RNA <50 copies/mL and very few discontinued therapy. D/C/F/TAF was well tolerated, no participants discontinued due to baseline resistance stopping criteria, and high treatment satisfaction among participants was recorded.

Clinical Trials Registration

NCT03227861.
Hepatitis C Virus (HCV) Care Continuum Outcomes and HCV Community Viral Loads Among Patients in an Opioid Treatment Program
Authors: Jordan Ashly E , Cleland Charles M , Schackman Bruce R , Wyka Katarzyna , Perlman David C , Nash Denis
Published: December 2019

Background

Hepatitis C virus (HCV) remains endemic among people who use drugs (PWUD). Measures of HCV community viral load (CVL) and HCV care continuum outcomes may be valuable for ascertaining unmet treatment need and for HCV surveillance and control.

Methods

Data from patients in an opioid treatment program during 2013–2016 were used to (1) identify proportions of antibody and viral load (VL) tested, linked-to-care, and treated, in 2013–2014 and 2015–2016, and pre- and postimplementation of qualitative reflex VL testing; (2) calculate engaged-in-care HCV CVL and “documented” and “estimated” unmet treatment need; and (3) examine factors associated with linkage-to-HCV-care.

Results

Among 11 267 patients, proportions of HCV antibody tested (52.5% in 2013–2014 vs 73.3% in 2015–2016), linked-to-HCV-care (15.7% vs 51.8%), and treated (12.0% vs 44.7%) all increased significantly. Hispanic ethnicity was associated with less linkage-to-care, and Manhattan residence was associated with improved linkage-to-care. The overall engaged-in-care HCV CVL was 4 351 079 copies/mL (standard deviation = 7 149 888); local HCV CVLs varied by subgroup and geography. Documented and estimated unmet treatment need decreased but remained high.

Conclusions

After qualitative reflex VL testing was implemented, care continuum outcomes improved, but gaps remained. High rates of unmet treatment need suggest that control of the HCV epidemic among PWUD will require expansion of HCV treatment coverage.
Bidirectional communication between neural and immune systems
Authors: Kamimura Daisuke , Tanaka Yuki , Hasebe Rie , Murakami Masaaki
Published: December 2019

The immune and nervous systems share many features, including receptor and ligand expression, enabling efficient communication between the two. Accumulating evidence suggests that the communication is bidirectional, with the neural system regulating immune cell functions and vice versa. Steroid hormones from the hypothalamus–pituitary–adrenal gland axis are examples of systemic regulators for this communication. Neural reflexes describe regional regulation mechanisms that are a historically new concept that helps to explain how the neural and body systems including immune system communicate. Several recently identified neural reflexes, including the inflammatory reflex and gateway reflex, significantly impact the activation status of the immune system and are associated with inflammatory diseases and disorders. Either pro-inflammatory or anti-inflammatory effects can be elicited by these neural reflexes. On the other hand, the activities of immune cells during inflammation, for example the secretion of inflammatory mediators, can affect the functions of neuronal systems via neural reflexes and modulate biological outputs via specific neural pathways. In this review article, we discuss recent advances in the understanding of bidirectional neuro-immune interactions, with a particular focus on neural reflexes.
Heparin induces neutrophil elastase-dependent vital and lytic NET formation
Authors: Lelliott Patrick M , Momota Masatoshi , Shibahara Takayuki , Lee Michelle S J , Smith Nicholas I , Ishii Ken J , Coban Cevayir
Published: December 2019

Heparin is used extensively as an anticoagulant in a broad range of diseases and procedures; however, its biological effects are not limited to coagulation and remain incompletely understood. Heparin usage can lead to the life-threatening complication known as heparin-induced thrombocytopenia (HIT), caused by the development of antibodies against heparin/PF4 complexes. Here, we demonstrate the ability of heparin to induce neutrophil extracellular traps (NETs). NETs occurred with cell lysis and death, but live neutrophils releasing extracellular DNA strands, known as vital NETs, also occurred abundantly. Formation of NETs was time and dose dependent, and required reactive oxygen species and neutrophil elastase. Other compounds related to heparin such as low molecular weight heparin, fondaparinux and heparan sulfate either failed to induce NETs, or did so to a much lesser extent. Our findings suggest the ability of heparin to directly induce NET formation should be considered in the context of heparin treatment and HIT pathogenesis.
Blinkered Learning, Blinkered Theory: How Histories in Textbooks Parochialize IR
Authors: Powel Brieg
Published: December 2019

Calls for a more “global” international relations (IR) based on theories grounded in world rather than Western histories have highlighted the Eurocentrism of history within the discipline. Global IR literature, however, neglects the role of tempocentrism in fostering that Eurocentrism. Tempocentric IR portrays the past as an extrapolation of the (Eurocentric) present, suggesting an inevitability and normality to Western dominance of international relations and obscuring non-Western significance. It also deprives IR theory-building of a broader pool of examples to inform existing theories. This article locates those centrisms in the textbooks of the discipline, while drawing on interdisciplinary research to reveal the disproportionate influence of the first years of higher education on students’ future worldviews. It is here that students are exposed to a historical grand narrative that establishes the boundaries of their inquiries and outlines what is, and what is not, significant. For a more “global” IR, therefore, it is suggested that textbook historical narratives require reconstructing in two ways. First, textbook history should be presented through connections and relations rather than substances. Second, historical chapters should reveal the multiple layers of time, including the deeper past, that have been instrumental in constituting the international relations of today.
Diagnostic Accuracy of Laser Doppler Imaging for the Assessment of Burn Depth: A Meta-analysis and Systematic Review
Authors: Wang Ru , Zhao Juan , Zhang Zhenyu , Cao Chang , Zhang Yange , Mao Yu
Published: December 2019

An overall assessment of the diagnostic value of laser Doppler imaging (LDI) to assess burn depth in patients is presented based on relevant studies. Both eligible research and relevant articles were identified through specific index searches of Embase, Cochrane, and PubMed databases. The latest study included was published in March 2019 and all eligible publications reported on cohort or cross-sectional research. All articles were tested for heterogeneity by using a suitable effect model to calculate amalgamative values of sensitivity, specificity, and the diagnostic odds ratio (DOR). Analyses of summary receiver operating characteristic (SROC) are given for burn depth values. After rigorous screening, 14 studies with a total cohort of 1,818 patients were chosen for the meta-analysis to explore the validity of LDI diagnosis to assess the depth of burns. The burn depth overall sensitivity for LDI was 91% (95% CI: 86–95%) and global specificity was 96% (95% CI: 92–98%). The overall positive likelihood ratio of LDI was 20.35 (95% CI: 10.71–38.69) and the overall negative likelihood ratio was 0.09 (95% CI: 0.05–0.15). The overall DOR was 152.93 (95% CI: 69.44–336.81) of LDI. The acreage under the SROC was not low for LDI (AUC = 0.98; 95% CI: 0.96–0.99). In conclusion, the present analysis reviewed the literature and meta-analysis of studies to validate LDI for the diagnosis of burn depth. The results indicated that LDI has a high accuracy for this diagnostic function.
Flying Away From the Bolshevik Winter: Soviet Refugees across the Southern Borders (1917–30)
Authors: Atabaki Touraj , Volkov Denis V
Published: December 2019

Methodologically drawing on the most recent works in Migration Studies and Russian Emigré Studies, the article studies migration from the USSR into Turkey, Iran and Afghanistan (1917–1930). Using various hitherto untapped archival sources, research looks into the phenomena, such as displaced statehood, political activism and cross-cultural interaction in the context of the migration/refugee policies of the relevant states (Britain, the USSR and the host countries).
Overexpression of soybean DREB1 enhances drought stress tolerance of transgenic wheat in the field
Authors: Zhou Yongbin , Chen Ming , Guo Jinkao , Wang Yanxia , Min Donghong , Jiang Qiyan , Ji Hutai , Huang Chengyan , Wei Wei , Xu Huijun , Chen Xiao , Li Liancheng , Xu Zhaoshi , Cheng Xianguo , Wang Chunxiao , Wang Chengshe , Ma Youzhi
Published: December 2019

Drought-response-element binding (DREB)-like transcription factors can significantly enhance plant tolerance to water stress. However, most research on DREB-like proteins to date has been conducted in growth chambers or greenhouses, so there is very little evidence available to support their practical use in the field. In this study, we overexpressed GmDREB1 from soybean in two popular wheat varieties and conducted drought-tolerance experiments across a range of years, sites, and drought-stress regimes. We found that the transgenic plants consistently exhibited significant improvements in yield performance and a variety of physiological traits compared with wild-type plants when grown under limited water conditions in the field, for example showing grain yield increases between 4.79–18.43%. Specifically, we found that the transgenic plants had reduced membrane damage and enhanced osmotic adjustment and photosynthetic efficiency compared to the non-transgenic controls. Three enzymes from the biosynthetic pathway of the phytohormone melatonin were up-regulated in the transgenic plants, and external application of melatonin was found to improve drought tolerance. Together, our results demonstrate the utility of transgenic overexpression of GmDREB1 to improve the drought tolerance of wheat in the field.
Performance of the new ID-fungi plate using two types of reference libraries (Bruker and MSI) to identify fungi with the Bruker MALDI Biotyper
Authors: Heireman Laura , Patteet Sofie , Steyaert Sophia
Published: December 2019

During the last decade, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized the diagnosis of fungal infections. Recently, a new Conidia ID-fungi plate (IDFP) medium was introduced to facilitate growth and sampling of fungi. This study aimed to evaluate the IDFP for fungal MALDI-TOF MS identification by comparison with a standard fungal growth medium using two reference libraries. A total of 75 filamentous fungal isolates (including 32 dermatophytes) were inoculated on IDFP and Sabouraud-gentamicin-chloramphenicol (SGC) agar and identified by MALDI-TOF MS using formic acid/acetonitrile extraction. Both the commercially available Bruker library (version 2.0) and the public available MSI web application (version 2018) were applied. For 15% of the isolates, a faster growth was noticed on IDFP compared to SGC. IDFP enhanced the performance of fungal identification compared to SGC for both MSI (increase of 16% identifications to genus and 5% to species level) and Bruker library (increase of 22% identifications to genus and 8% to species level). In total, only 73% of the tested isolates were present in the Bruker library compared to 92% for MSI library. No significant difference (P = 0.46) in MALDI score between IDFP and SGC was observed for the MSI library, but scores were significantly (P = 0.03) higher for IDFP when using Bruker library, potentially explained by the prevention of agar contamination by using IDFP since the Bruker database was created from liquid media. IDFP is a promising alternative growth medium for MALDI-TOF MS fungal identification which would strongly benefit from optimizing the Bruker reference library.
The Ep,i–Eiso correlation: type I gamma-ray bursts and the new classification method
Authors: Minaev P Y , Pozanenko A S
Published: December 2019

We present the most extensive sample of 45 type I (short) and 275 type II (long) gamma-ray bursts (GRBs) with known redshift to investigate the correlation between the rest-frame peak energy, Ep,i and the total isotropic equivalent energy, Eiso of the prompt emission (Amati relation). The Ep,i–Eiso correlation for type I bursts is found to be well distinguished from the one constructed for type II bursts and has a similar power-law index value, Ep,i$\propto E_\text{iso}^{~0.4}$, which possibly indicates the same emission mechanism of both GRB types. We show that the initial pulse complex (IPC) of type I bursts with an extended emission and regular type I bursts follow the same correlation. We obtain similar results for type II bursts associated with Ic supernovae and for regular type II bursts. Three possible outliers from the Ep,i–Eiso correlation for type II subsample are detected. Significant evolution of the Ep,i–Eiso correlation with redshift for type II bursts is not found. We suggest the new classification method, based on the Ep,i–Eiso correlation and introduce two parameters, $EH = E_\text{p,i,2} ~ E_\text{iso,51}^{~-0.4}$ and $EHD = E_\text{p,i,2} ~ E_\text{iso,51}^{~-0.4} ~ T_\text{90,i}^{~-0.5}$, where Ep,i,2 is the value of Ep,i parameter in units of 100 keV, Eiso,51 is the value of Eiso parameter in units of 1051 erg, and T90,i is the rest-frame duration in units of seconds. EHD is found to be the most reliable parameter for the blind type I/type II classification, which can be used to classify GRBs with no redshift.
Beyond Antibiotics: A Practical Guide for the Infectious Disease Physician to Treat Opioid Use Disorder in the Setting of Associated Infectious Diseases
Authors: Seval Nikhil , Eaton Ellen , Springer Sandra A
Published: December 2019

Infections are a common cause of hospitalization for patients with opioid use disorder (OUD), and hospital admissions are rising in the context of the worsening US opioid crisis. Infectious disease (ID) physicians are frequently the first point of medical contact for these patients. In this article, we discuss the integration of evidence-based management of OUD and patient-centered care of hospitalized persons with acute injection-related infections. We describe the following components of a comprehensive approach for OUD with inpatient ID consultations: (1) how to screen for OUD; (2) how to initiate the 3 US Food and Drug Administration-approved medications for OUD (buprenorphine, methadone, and extended-release naltrexone); (3) how to manage acute pain and opioid-related conditions; and (4) how to link and integrate ID and OUD treatment after hospital discharge. These strategies reduce unplanned discharges and increase completion of recommended antimicrobial regimens.