bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inside Information: Systematic within-node connectivity changes observed across tasks or groups
Authors: Luo Wenjing , Constable R. Todd 
Published: July 2021

AbstractMapping the human connectome and understanding its relationship to brain function holds tremendous clinical potential. The connectome has two fundamental components: the nodes and the connections between them. While much attention has been given to deriving atlases and measuring the connections between nodes, there have been no studies examining the networks within nodes. Here we demonstrate that each node contains significant connectivity information, that varies systematically across task-induced states and subjects, such that measures based on these variations can be used to classify tasks and identify subjects. The results are not specific for any particular atlas but hold across different atlas resolutions. To date, studies examining changes in connectivity have focused on edge changes and assumed there is no useful information within nodes. Our findings illustrate that for typical atlases, within-node changes can be significant and may account for a substantial fraction of the variance currently attributed to edge changes.
Simulations of dynamically cross-linked actin networks: morphology, rheology, and hydrodynamic interactions
Authors: Maxian Ondrej , Peláez Raúl P. , Mogilner Alex , Donev Aleksandar 
Published: July 2021

AbstractCross-linked actin networks are the primary component of the cell cytoskeleton and have been the subject of numerous experimental and modeling studies. While these studies have demonstrated that the networks are viscoelastic materials, evolving from elastic solids on short timescales to viscous fluids on long ones, questions remain about the duration of each asymptotic regime, the role of the surrounding fluid, and the behavior of the networks on intermediate timescales. Here we perform detailed simulations of passively cross-linked non-Brownian actin networks to quantify the principal timescales involved in the elastoviscous behavior, study the role of nonlocal hydrodynamic interactions, and parameterize continuum models from discrete stochastic simulations. To do this, we extend our recent computational framework for semiflexible filament suspensions, which is based on nonlocal slender body theory, to actin networks with dynamic cross linkers and finite filament lifetime. We introduce a model where the cross linkers are elastic springs with sticky ends stochastically binding to and unbinding from the elastic filaments, which randomly turn over at a characteristic rate. We show that, depending on the parameters, the network evolves to a steady state morphology that is either an isotropic actin mesh or a mesh with embedded actin bundles. For different degrees of bundling, we numerically apply small-amplitude oscillatory shear deformation to extract three timescales from networks of hundreds of filaments and cross linkers. We analyze the dependence of these timescales, which range from the order of hundredths of a second to the actin turnover time of several seconds, on the dynamic nature of the links, solvent viscosity, and filament bending stiffness. We show that the network is mostly elastic on the short time scale, with the elasticity coming mainly from the cross links, and viscous on the long time scale, with the effective viscosity originating primarily from stretching and breaking of the cross links. We show that the influence of nonlocal hydrodynamic interactions depends on the network morphology: for homogeneous meshworks, nonlocal hydrodynamics gives only a small correction to the viscous behavior, but for bundled networks it both hinders the formation of bundles and significantly lowers the resistance to shear once bundles are formed. We use our results to construct three-timescale generalized Maxwell models of the networks.
Subspace alignment as a mechanism for binding
Authors: Fine Justin M. , Michael Yoo Seng Bum , Ebitz R. Becket , Hayden Benjamin Y. 
Published: July 2021

ABSTRACTTo choose between options, we must solve two important binding problems. First, the features that determine each options’ values must be appropriately combined and kept separate from the corresponding features of other options. Second, options must be associated with the specific actions needed to select them. We hypothesized that the brain solves these problems through use of aligned (for bound dimensions) and orthogonal (for separated dimensions) population subspaces. We examined responses of single neurons in six putative value-coding regions in rhesus macaques performing a risky choice task. In all areas, single neurons encode the features that define the value of each option (stakes and probability) but only very weakly encode value per se. However, the coding dimensions associated with these features are aligned on a single subspace, from which a strong emergent value signal can be read out. Moreover, all six regions use nearly orthogonal subspaces for the left and right options, thereby linking options to their position in space, implementing functional partitioning, and reducing the possibility of misbinding. These results provide a new solution to the neuroeconomic binding problems and suggest that other forms of binding may work through similar principles.
Astrocyte-secreted glypican-4 drives APOE4-dependent tau pathology
Authors: Saroja Sivaprakasam R. , Gorbachev Kirill , TCW Julia , Goate Alison M. , Pereira Ana C. 
Published: July 2021

ABSTRACTThe aggregation of tau proteins into insoluble filaments and the spread of these filaments across brain regions are the major drivers of neurodegeneration in tauopathies, including in Alzheimer’s disease (AD). Apolipoprotein E4 (APOE4), a crucial genetic risk factor for late-onset AD, has been shown to exacerbate tau pathology in mouse models. However, the exact mechanisms through which APOE4 induces tau pathology remains unknown. Here, we report that the astrocyte-secreted protein glypican-4 (GPC-4), which we identify as a novel binding partner of APOE4, drives tau pathology. We discovered that GPC-4 preferentially interacts with APOE4 in comparison to APOE2, considered to be a protective allele to AD, and post-mortem APOE4-carrying AD brains highly express GPC-4 in neurotoxic astrocytes. The astrocyte-secreted GPC-4 induced both tau accumulation and propagation in vitro. CRISPR/dCas9 mediated activation of GPC-4 in a tauopathy mouse model robustly induced tau pathology. Using in vitro Tau FRET-biosensor cells, human iPSCs-derived astrocytes and an in vivo mouse model, we found that APOE4-induced tau pathology was greatly diminished in the absence of GPC-4. We further show that APOE4-mediated surface trafficking of APOE receptor low-density lipoprotein receptor-related protein 1 (LRP1) through GPC-4 can be a gateway to tau spreading. Together, our data comprehensively demonstrate that APOE4-induced tau pathologies are directly mediated by GPC-4.
Anti-tumor efficacy of an MMAE conjugated antibody targeting cell surface TACE/ADAM17-cleaved Amphiregulin in breast cancer
Authors: Lofgren Kristopher A. , Sreekumar Sreeja , Jenkins E. Charles , Ernzen Kyle J. , Kenny Paraic A. 
Published: July 2021

AbstractThe Epidermal Growth Factor Receptor ligand, Amphiregulin, is a key proliferative effector of estrogen receptor signaling in breast cancer and also plays a role in other malignancies. Amphiregulin is a single-pass transmembrane protein proteolytically processed by TACE/ADAM17 to release the soluble EGFR ligand, leaving a residual transmembrane stalk that is subsequently internalized. Here, we report the development of an antibody drug conjugate, GMF-1A3-MMAE, targeting an AREG neo-epitope revealed following ADAM17-mediated cleavage. The antibody does not interact with uncleaved Amphiregulin, providing a novel means of targeting cells with high rates of Amphiregulin shedding. Using fluorescent dye conjugation, we demonstrated that the antibody is internalized by cancer cells in a manner dependent on the presence of cell surface cleaved Amphiregulin. Antibodies conjugated with monomethyl auristatin E (MMAE) were cytotoxic in vitro and induced rapid regression of established breast tumor xenografts in immunocompromised mice. We further demonstrate that these antibodies recognize the Amphiregulin neo-epitope in formalin fixed paraffin embedded tumor tissue, suggesting their utility as a companion diagnostic for patient selection.
Sea Surface Temperatures Drive Historical Demography of Deep-Sea Fishes
Authors: Weber Max D. , Carter Joshua E. , Eytan Ron I. 
Published: July 2021

ABSTRACTDemographic histories are largely understood to be a product of their environment, as populations expand or contract in response to major environmental changes. Deep-pelagic fishes inhabit one of the most temporally and spatially stable habitats on the planet, so they may be resistant to the demographic instability commonly reported in other marine habitats, but their demographic histories are poorly understood. We reconstructed the demographic histories of thirteen species of deep-pelagic fishes using mitochondrial and nuclear DNA sequence data. We uncovered widespread evidence of demographic expansion in our study species, a counterintuitive result bases on the nature of the deep-pelagic. The frequency-based methods detected potential demographic changes in eleven species, while the Extended Bayesian Skyline Plots were more conservative and identified population expansion in five species. The dates of expansion largely coincide with periods of warm sea-surface temperature at the northern and southern boundaries for the ranges these species inhabit. We suggest that this is the result of the pelagic larval phase shared by most deep-pelagic fishes, where the larvae inhabit the upper 200 meters. Changes in sea surface conditions likely alter the suitability of the habitat in a given region for the larval phase, affecting the species range and in turn population size. These results are critical to our understanding of how the deep-pelagic fish community will respond to future climatic changes.
Ovarian cysts and granulosa cell tumors develop after sublethal total body irradiation in mice
Authors: Xiao Shiyun , Xiao Yao , Xu Xiaohong , Zhang Wen , Murph Mandi M. , Manley Nancy R. 
Published: July 2021

AbstractBackgroundLocalized and total body irradiation are used to treat certain cancers and also used prior to transplantation of stem cells or organs. However, the use of radiation also induces collateral damage to the cells of healthy tissue. Although the acute damage of radiation to oocytes is well known, the long-term effects induced by radiation to stromal cells and their relationship with age are still unclear.MethodsA total of 206 two-month-old female mice were whole-body exposed to gamma rays at doses of 0, 0.5, 1, 2, or 4 Gy, respectively. The mice were sacrificed at 3.5, 9, 12, or 18 months of age and pathological changes including cysts and tumors were assessed in the ovary and other organs.ResultsThe overall incidence of visible pathological changes of mice receiving irradiation was 33.7% in the ovary, but much lower in the liver, spleen, lung, thymus, and skin. Among these, the ovarian cyst formation rate was 24.7%, and tumor lesions were 10.2%, respectively, compared to 5% cyst formation and no tumor lesions among control, unirradiated mice. Statistical analysis showed that cyst formation was age, but not dose-dependent, whereas the formation of tumor lesions was dependent on both age and radiation dose. Pathology analysis indicated that most ovarian cysts originated from follicles and both tumor lesions analyzed originated from granulosa cells.ConclusionOvaries are highly susceptible to the effects of radiation. Long-term damage is increased after total body irradiation in mice, manifested by higher incidences of cyst formation and tumor lesions. The ovarian stromal-derived granulosa cells might play an essential role in these changes.
Citizen-science surveillance of triazole-resistantAspergillus fumigatusin UK residential garden soils
Authors: Shelton Jennifer M. G. , Collins Roseanna , Uzzell Christopher B. , Alghamdi Asmaa , Dyer Paul S. , Singer Andrew C. , Fisher Matthew C. 
Published: July 2021

AbstractCompost is an ecological niche forAspergillus fumigatusdue to its role as a decomposer of organic matter and its ability to survive the high temperatures associated with the composting process. Subsequently, composting facilities are associated with high levels ofA. fumigatusspores that are aerosolised from compost and cause respiratory illness in workers. In the UK, gardening is an activity enjoyed by individuals of all ages and it is likely that they are being exposed toA. fumigatusspores when handling commercial compost or compost they have produced themselves. In this study, 246 citizen scientists collected 509 soil samples from locations in their garden in the UK, from which were cultured 5,174A. fumigatusisolates. Of these isolates, 736 (14%) were resistant to tebuconazole: the third most-sprayed triazole fungicide in the UK, which confers cross-resistance to the medical triazoles used to treatA. fumigatuslung infections in humans. These isolates were found to contain the common resistance mechanisms in theA. fumigatus cyp51Agene TR34/L98H or TR46/Y121F/T289A, and less common resistance mechanisms TR34, TR53, TR46/Y121F/T289A/S363P/I364V/G448S and (TR46)2/Y121F/M172I/T289A/G448S. Regression analyses found that soil samples containing compost were significantly more likely to grow susceptible and tebuconazole-resistantA. fumigatusthan those that did not, and that compost samples grew significantly higher numbers ofA. fumigatusthan other samples.ImportanceThese findings highlight compost as a potential health hazard to individuals with pre-disposing factors toA. fumigatuslung infections, and a potential health hazard to immunocompetent individuals who could be exposed to sufficiently high numbers of spores to develop infection. This raises the question of whether compost bags should carry additional health warnings regarding inhalation ofA. fumigatusspores, whether individuals should be advised to wear facemasks whilst handling compost or whether commercial producers should be responsible for sterilising compost before shipping. The findings support increasing public awareness of the hazard posed by compost and investigating measures that can be taken to reduce the exposure risk.
Allele-specific expression links diverse cis-regulatory mutations to recurrent gene dysregulation in high-risk neuroblastoma
Authors: Sen Arko , Huo Yuchen , Elster Jennifer , Zage Peter E. , McVicker Graham 
Published: July 2021

AbstractNeuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here we analyze allele-specific expression (ASE) in 96 high-risk neuroblastoma tumors to discover genes with cis-acting mutations that alter dosage. We identify 1,049 genes with recurrent, neuroblastoma-specific ASE, 68% of which lie within common SCNA regions. However, many genes exhibit ASE in copy neutral samples and are enriched for mutations that cause nonsense-mediated decay, indicating that neuroblastoma tumors select for multiple types of mutations that alter gene expression. We also find 24 genes with reduced expression in stage 4 disease that have neuroblastoma-specific ASE that is independent of SCNAs. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH. In summary, our ASE analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma.
Global analysis of the specificities and targets of endoribonucleases from E. coli toxin-antitoxin systems
Authors: Culviner Peter H. , Nocedal Isabel , Fortune Sarah M. , Laub Michael T. 
Published: July 2021

AbstractToxin-antitoxin systems are widely distributed genetic modules typically featuring toxins that can inhibit bacterial growth and antitoxins that can reverse inhibition. Although Escherichia coli encodes 11 toxins with known or putative endoribonuclease activity, the target of most of these toxins remain poorly characterized. Using a new RNA-seq pipeline that enables the mapping and quantification of RNA cleavage with single-nucleotide resolution, we characterize the targets and specificities of 9 endoribonuclease toxins from E. coli. We find that these toxins use low-information cleavage motifs to cut a significant proportion of mRNAs in E. coli, but not tRNAs or the rRNAs from mature ribosomes. However, all the toxins, including those that are ribosome-dependent and cleave only translated RNA, inhibit ribosome biogenesis. This inhibition likely results from the cleavage of ribosomal protein transcripts, which disrupts the stoichiometry and biogenesis of new ribosomes and causes the accumulation of aberrant ribosome precursors. Collectively, our results provide a comprehensive, global analysis of endoribonuclease-based toxin-antitoxin systems in E. coli and support the conclusion that, despite their diversity, each disrupts translation and ribosome biogenesis.ImportanceToxin-antitoxin systems are widespread genetic modules found in almost all bacteria that can regulate their growth and may play prominent roles in phage defense. Escherichia coli encodes 11 TA systems in which the toxin is a known or predicted endoribonuclease. The targets and cleavage specificities of these endoribonucleases have remained largely uncharacerized, precluding an understanding of how each impacts cell growth and an assessment of whether they have distinct or overlapping targets. Using a new and broadly applicable RNA-seq pipeline, we present a global analysis of 9 endoribonulease toxins from E. coli. We find that each uses a relatively low-information cleavage motif to cut a large proportion of mRNAs in E. coli, but not tRNAs or mature rRNAs. Notably, although the precise set of targets varies, each toxin efficiently disrupts ribosome biogenesis, primarily by cleaving the mRNAs of ribosomal proteins. In sum, the analyses presented provide new, comprehensive insights into the cleavage specificities and targets of almost all endoribonuclease toxins in E. coli. Despite different specificities, our work reveals a striking commonality in function as each toxin disrupts ribosome biogenesis and translation.
Are patrons using the research books? A new approach to approval plan assessment
Authors: Attebury Ramirose Ilene 
Published: July 2021

Purpose
The purpose of this study is to present findings of an approval plan assessment project, which analyzed circulation statistics for four Gobi Select designations: research essential, research recommended, basic essential and basic recommended.

Design/methodology/approach
This study approaches approval plan assessment by analyzing three years of circulation statistics to determine which, if any, of the Gobi Select designations circulated the most.

Findings
This study reveals that books designated as “basic essential” have circulated at higher rates than other designations.

Originality/value
To the best of the author’s knowledge, no other studies have made use of Gobi Select designations to analyze circulation statistics for books obtained on an approval plan.
Analytical prediction of electromagnetic performance of dual-stator consequent-pole PM machines based on subdomain model accounting for tooth-tips
Authors: Zhu Minchen , Wu Lijian , Wang Dong , Fang Youtong , Tan Ping 
Published: July 2021

Purpose
The purpose of this paper is to analytically predict the on-load field distribution and electromagnetic performance (induced voltage, electromagnetic torque, winding inductances and unbalanced magnetic force) of dual-stator consequent-pole permanent magnet (DSCPPM) machines using subdomain model accounting for tooth-tip effect. The finite element (FE) results are presented to validate the accuracy of this subdomain model.

Design/methodology/approach
During the preliminary design and optimization of DSCPPM machines, FE method requires numerous computational resources and can be especially time-consuming. Thus, a subdomain model considering the tooth-tip effect is presented in this paper. The whole field domain is divided into four different types of sub-regions, where the analytical solutions of vector potential in each sub-region can be rapidly calculated. The proposed subdomain model can accurately predict the on-load flux density distributions and electromagnetic performance of DSCPPM machines, which is verified by FE method.

Findings
The radial and tangential components of flux densities in each sub-region of DSCPPM machine can be obtained according to the vector potential distribution, which is calculated based on the boundary and interface conditions using variable separation approach. The tooth-tip effect is investigated as well. Moreover, the phase-induced voltage, winding inductances, electromagnetic torque and X-axis/Y-axis components of unbalanced magnetic forces are calculated and compared by FE analysis, where excellent agreements are consistently exhibited.

Originality/value
The on-load field distributions and electromagnetic performance of DSCPPM machines are analytically investigated using subdomain method, which can be beneficial in the process of initial design and optimization for such DSCPPM machines.
Design and mathematical analysis of a 7T SRAM cell with enhanced read SNM using PMOS as an access transistor
Authors: Mishra Alok Kumar , D. Vaithiyanathan , Pal Yogesh , Kaur Baljit 
Published: July 2021

Purpose
This work is proposed for low power energy-efficient applications like laptops, mobile phones, and palmtops. In this study, P-channel metal–oxide–semiconductor (PMOS)’s are used as access transistor in 7 transistors (7 T) Static Random Access Memory (SRAM) cell, and the theoretical Static Noise Margin (SNM) analysis for the proposed cell is also performed. A cell is designed using 7 T which consists of 4 PMOS and 3 NMOS. In this paper write and hold SNM is addressed and read SNM is also calculated for the proposed 7 T SRAM cell.

Design/methodology/approach
The authors have replaced N-channel metal–oxide–semiconductor (NMOS) access transistors with the PMOS access transistors, which results in proper data line recovery and provides the desired coupling. An error is likely to occur, if the read operation is performed too often probably by using the NMOS pass gate. It results in an improper recovery of the data line. Instead, by using PMOS as a pass gate, the time required for read operation can be brought down. As we know the mobility (µ) of the PMOS transistor is low, so the authors have used this property into the proposed design. When a low signal is applied to its control gate, the PMOS transistor come up with the desired coupling, when working as a pass gate.

Findings
Feedback switched transistor is used in the proposed circuit, which plays an important role in the write operation. This transistor is in OFF state and PMOS’s work as access transistor, when the proposed cell operating in read mode. This helps in the reduction of power. This work is simulated using UMC 40 nm technology node in the cadence virtuoso environment. The simulated result shows that, write power saving of 51.54% and 61.17%, hold power saving of 25.68% and 48.93% when compared with reported 7 T and 6 T, respectively.

Originality/value
The proposed 7 T SRAM cell provides proper data line recovery at a lower voltage when PMOS works as the access transistor. Power consumption is very less in this technique and it is best suitable for low power applications.