bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ssdp influences Wg expression and embryonic somatic muscle identity inDrosophila melanogaster
Authors: Poovathumkadavil Preethi , Da Ponte Jean-Philippe , Jagla Krzysztof 
Published: June 2021

AbstractThe somatic muscles of theDrosophilaembryo and larvae share structural and functional similarities with vertebrate skeletal muscles and serve as a powerful model for studying muscle development. Here we show that the evolutionarily conserved Ssdp protein is required for the correct patterning of somatic muscles. Ssdp is part of the conserved Chi/LDB-Ssdp (ChiLS) complex that is a core component of the conserved Wg/Wnt enhanceosome, which responds to Wg signals to regulate gene transcription.Ssdpshows isoform specific expression in developing somatic muscles and its loss of function leads to an aberrant somatic muscle pattern due to a deregulated muscle identity program.Ssdpmutant embryos fail to maintain adequate expression levels of muscle identity transcription factors and this results in aberrant muscle morphology, innervation, attachment and fusion. We also show that the epidermal expression of Wg is downregulated inSsdpmutants and that Ssdp interacts with Wg to regulate the properties of a subset of ventral muscles. Thus, our data unveil the dual contribution of Ssdp contribution to muscle diversification by regulating the expression of muscle-intrinsic identity genes and by interacting with the extrinsic factor, Wg. The knowledge gained here about Ssdp and its interaction with Wg could be relevant to vertebrate muscle development.
HSV-1 ICP22 is a selective viral repressor of cellular RNA polymerase II-mediated transcription elongation
Authors: Isa Nur F. , Bensaude Olivier , Aziz Nadiah C. , Murphy Shona 
Published: June 2021

AbstractThe Herpes Simplex Virus (HSV-1) immediate early protein ICP22 interacts with cellular proteins to inhibit host cell gene expression and promote viral gene expression. ICP22 inhibits phosphorylation of Ser2 of the RNA polymerase II (pol II) carboxyl-terminal domain (CTD) and productive elongation of pol II. Here we show that ICP22 affects elongation of pol II through both the early-elongation checkpoint and the poly(A)-associated elongation checkpoint on a protein-coding gene model. Coimmunoprecipitation assays using tagged ICP22 expressed in human cells and pulldown assays with recombinant ICP22 in vitro coupled with mass spectrometry identify transcription elongation factors, including P-TEFb, additional CTD kinases and the FACT complex as interacting cellular factors. Using a photoreactive amino acid incorporated into ICP22, we found that L191, Y230 and C225 crosslink to both subunits of the FACT complex in cells. Our findings indicate that ICP22 physically interacts with critical elongation regulators to inhibit transcription elongation of cellular genes, which may be vital for HSV-1 pathogenesis. We also show that the HSV viral activator, VP16 has a region of structural similarity to the ICP22 region that interacts with elongation factors, suggesting a model where VP16 competes with ICP22 to deliver elongation factors to viral genes.
Epithelial-mesenchymal plasticity through loss of CTCF motif accessibility and protein expression
Authors: Johnson Kelsey S. , Hussein Shaimaa , Chakraborty Priyanka , Muruganantham Arvind , Mikhail Sheridan , Gonzalez Giovanny , Song Shuxuan , Jolly Mohit Kumar , Toneff Michael J. , Benton Mary Lauren , Lin Yin C. , Taube Joseph H. 
Published: June 2021

AbstractEpithelial-mesenchymal transition (EMT) and its reversal, mesenchymal-epithelial transition (MET) drive tissue reorganization critical for early development. In carcinomas, processing through EMT, MET or partial states promotes migration, invasion, dormancy, and metastatic colonization. As a reversible process, EMT is inherently regulated at epigenetic and epigenomic levels. To understand the epigenomic nature of reversible EMT and its partial states, we characterized chromatin accessibility dynamics, transcriptomic output, protein expression, and cellular phenotypes during stepwise reversible EMT. We found that the chromatin insulating protein machinery, including CTCF, is suppressed and re-expressed, coincident with broad alterations in chromatin accessibility, during EMT/MET and is lower in triple-negative breast cancer cell lines with EMT features. Through analysis of chromatin accessibility using ATAC-seq, we identify that early phases of EMT are characterized by enrichment for AP-1 family member binding motifs but also by diminished enrichment for CTCF binding motifs. Through loss-of-function analysis we demonstrate that suppression of CTCF alters cellular plasticity, facilitating entrance into a partial EMT state. These findings are indicative of a role of CTCF and chromatin reorganization for epithelial-mesenchymal plasticity.
Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study
Authors: Iida Megan A. , Farrell Kurt , Walker Jamie M. , Richardson Timothy E. , Marx Gabe , Bryce Clare H. , Purohit Dushyant , Ayalon Gai , Beach Thomas G. , Bigio Eileen H. , Cortes Etty , Gearing Marla , Haroutunian Vahram , McMillan Corey T. , Lee Eddie B. , Dickson Dennis , McKee Ann C. , Stein Thor D. , Trojanowski John Q. , Woltjer Randall L. , Kovacs Gabor G. , Kofler Julia K. , Kaye Jeffrey , White Charles L. , Crary John F. 
Published: June 2021

AbstractPrimary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does not progress extensively to neocortical regions. Given this restricted pathoanatomical pattern and variable symptomatology, there is a need to reexamine and improve upon how PART is neuropathologically assessed and staged. We performed a retrospective autopsy study in a collection (n=174) of post-mortem PART brains and used logistic regression to determine the extent to which a set of clinical and neuropathological features predict cognitive impairment. We compared Braak staging, which focuses on hierarchical neuroanatomical progression of AD tau and Aβ pathology, with quantitative assessments of neurofibrillary burden using computer-derived positive pixel counts on digitized whole slide images of sections stained immunohistochemically with antibodies targeting abnormal hyperphosphorylated tau (p-tau) in the entorhinal region and hippocampus. We also assessed other factors affecting cognition, including aging-related tau astrogliopathy (ARTAG) and atrophy. We found no association between Braak stage and cognitive impairment when controlling for age (p=0.76). In contrast, p-tau burden was significantly correlated with cognitive impairment even when adjusting for age (p=0.03). The strongest correlate of cognitive impairment was cerebrovascular disease, a well-known risk factor (p<0.0001), but other features including ARTAG (p=0.03) and hippocampal atrophy (p=0.04) were also associated. In contrast, sex, APOE, psychiatric illness, education, argyrophilic grains, and incidental Lewy bodies were not. These findings support the hypothesis that comorbid pathologies contribute to cognitive impairment in subjects with PART. Quantitative approaches beyond Braak staging are critical for advancing our understanding of the extent to which age-related tauopathy changes impact cognitive function.
Tropical tree growth sensitivity to climate is driven by species intrinsic growth rate and leaf traits
Authors: Bauman David , Fortunel Claire , Cernusak Lucas A. , Bentley Lisa P. , McMahon Sean M. , Rifai Sami W. , Aguirre-Gutiérrez Jesús , Oliveras Imma , Bradford Matt , Laurance Susan G. W. , Delhaye Guillaume , Hutchinson Michael F. , Dempsey Raymond , McNellis Brandon E. , Santos-Andrade Paul E. , Ninantay-Rivera Hugo R. , Chambi Paucar Jimmy R. , Phillips Oliver L. , Malhi Yadvinder 
Published: June 2021

AbstractA better understanding of how climate affects growth in tree species is essential for improved predictions of forest dynamics under climate change. Long-term climate averages (mean climate) and short-term deviations from these averages (anomalies) both influence tree growth, but the rarity of long-term data integrating climatic gradients with tree censuses has so far limited our understanding of their respective role, especially in tropical systems. Here, we combined 49 years of growth data for 509 tree species across 23 tropical rainforest plots along a climatic gradient to examine how tree growth responds to both climate means and anomalies, and how species functional traits mediate these tree growth responses to climate. We showed that short-term, anomalous increases in atmospheric evaporative demand and solar radiation consistently reduced tree growth. Drier forests and fast-growing species were more sensitive to water stress anomalies. In addition, species traits related to water use and photosynthesis partly explained differences in growth sensitivity to both long-term and short-term climate variations. Our study demonstrates that both climate means and anomalies shape tree growth in tropical forests, and that species traits can be leveraged to understand these demographic responses to climate change, offering a promising way forward to forecast tropical forest dynamics under different climate trajectories.
Host phenology can select for multiple stable parasite virulence strategies
Authors: MacDonald Hannelore , Brisson Dustin 
Published: June 2021

AbstractHost phenology is an important driver of parasite transmission dynamics and evolution. Prior research has demonstrated that host phenology can drive monocyclic, obligate-killer parasites to evolve an intermediate virulence strategy where all parasites kill their host just before the season ends to limit the death of parasite progeny in the environment. The impact of host seasonality on parasites that are not constrained to a monocyclic life-cycle, however, cannot be inferred from these results. Here we present a mathematical model that demonstrates that many, but not all, seasonal host activity patterns support multiple evolutionarily stable parasite strategies (ESS), although these strategies cannot coexist in the same system. The specific monocyclic and polycyclic parasite evolutionarily stable strategies in each phenological pattern are interspersed with less-fit mono- and polycyclic strategies (evolutionary repellors). The ESS that dominates each system at equilibrium is a function of the strategy of the parasite introduced into the system. The results demonstrate that host phenology can, in theory, maintain diverse parasite strategies among isolated geographic locations.
Caenorhabditis elegans ETR-1/CELF has broad effects on the muscle cell transcriptome, including genes that regulate translation and neuroblast migration
Authors: Ochs Matthew E. , McWhirter Rebecca M. , Unckless Robert L. , Miller David M. , Lundquist Erik A. 
Published: June 2021

AbstractMigration of neuroblasts and neurons from their birthplace is central to the formation of neural circuits and networks. ETR-1 is the Caenorhabditis elegans homolog of the CELF1 (CUGBP, ELAV-like family 1) RNA-processing factor involved in neuromuscular disorders. etr-1 regulates body wall muscle differentiation. Our previous work showed that etr-1 in muscle has a non-autonomous role in neuronal migration, suggesting that ETR-1 is involved in the production of a signal emanating from body wall muscle that controls neuroblast migration and that interacts with Wnt signaling. etr-1 is extensively alternatively-spliced, and we identified the viable etr-1(lq61) mutant, caused by a stop codon in alternatively-spliced exon 8 and only affecting etr-1 isoforms containing exon 8. We took advantage of viable etr-1(lq61) to identify potential RNA targets of ETR-1 in body wall muscle using a combination of fluorescence activated cell sorting (FACS) of body wall muscles from wild-type and etr-1(lq61) and subsequent RNA-seq. This analysis revealed genes whose splicing and transcript levels were controlled by ETR-1 exon 8 isoforms, and represented a broad spectrum of genes involved in muscle differentiation, myofilament lattice structure, and physiology. Genes with transcripts underrepresented in etr-1(lq61) included those involved in ribosome function and translation, similar to potential CELF1 targets identified in chick cardiomyocytes. This suggests that at least some targets of ETR-1 might be conserved in vertebrates, and that ETR-1 might generally stimulate translation in muscles. As proof-of-principle, a functional analysis of a subset of ETR-1 targets revealed genes involved in AQR and PQR neuronal migration. One such gene, lev-11/tropomyosin, requires ETR-1 for alternative splicing, and another, unc-52/perlecan, requires ETR-1 for the production of long isoforms containing 3’ exons. In sum, these studies identified gene targets of ETR-1/CELF1 in muscles, which included genes involved in muscle development and physiology, and genes with novel roles in neuronal migration.
Stratified Test Accurately Identifies Differentially Expressed Genes Under Batch Effects in Single-Cell Data
Authors: Liang Shaoheng , Liang Qingnan , Chen Rui , Chen Ken 
Published: June 2021

AbstractAnalyzing single-cell sequencing data from large cohorts is challenging. Discrepancies across experiments and differences among participants often lead to omissions and false discoveries in differentially expressed genes. We find that the Van Elteren test, a stratified version of the widely used Wilcoxon rank-sum test, elegantly mitigates the problem. We also modified the common language effect size to supplement this test, further improving its utility. On both simulated and real patient data we show the ability of Van Elteren test to control for false positives and false negatives. A comprehensive assessment using receiver operating characteristic (ROC) curve shows that Van Elteren test achieves higher sensitivity and specificity on simulated datasets, compared with nine state-of-the-art differential expression analysis methods. The effect size also estimates the differences between cell types more accurately.
Systematic reconstruction of the cellular trajectories of mammalian embryogenesis
Authors: Qiu Chengxiang , Cao Junyue , Li Tony , Srivatsan Sanjay , Huang Xingfan , Calderon Diego , Noble William Stafford , Disteche Christine M. , Spielmann Malte , Moens Cecilia B. , Trapnell Cole , Shendure Jay 
Published: June 2021

AbstractMammalian embryogenesis is characterized by rapid cellular proliferation and diversification. Within a few weeks, a single cell zygote gives rise to millions of cells expressing a panoply of molecular programs, including much of the diversity that will subsequently be present in adult tissues. Although intensively studied, a comprehensive delineation of the major cellular trajectories that comprise mammalian development in vivo remains elusive. Here we set out to integrate several single cell RNA-seq datasets (scRNA-seq) that collectively span mouse gastrulation and organogenesis. We define cell states at each of 19 successive stages spanning E3.5 to E13.5, heuristically connect them with their pseudo-ancestors and pseudo-descendants, and for a subset of stages, deconvolve their approximate spatial distributions. Despite being constructed through automated procedures, the resulting trajectories of mammalian embryogenesis (TOME) are largely consistent with our contemporary understanding of mammalian development. We leverage TOME to nominate transcription factors (TF) and TF motifs as key regulators of each branch point at which a new cell type emerges. Finally, to facilitate comparisons across vertebrates, we apply the same procedures to single cell datasets of zebrafish and frog embryogenesis, and nominate “cell type homologs” based on shared regulators and transcriptional states.
BROADLY NEUTRALIZING ANTI- HIV-1 ANTIBODIES DO NOT INHIBIT HIV-1 ENV-MEDIATED CELL-CELL FUSION
Authors: Düzgüneş Nejat , Yee Michael , Chau Deborah 
Published: June 2021

ABSTRACTPG9, PG16, PGT121, and PGT145 antibodies were identified from culture media of activated memory B-cells of an infected donor and shown to neutralize many HIV-1 strains. Since HIV-1 spreads via both free virions and cell-cell fusion, we examined the effect of the antibodies on HIV-1 Env-mediated cell-cell fusion. Clone69TRevEnv cells that express Env in the absence of tetracycline were labeled with Calcein-AM Green, and incubated with CD4+ SupT1 cells labeled with CellTrace™ Calcein Red-Orange, with or without antibodies. Monoclonal antibodies PG9, PG16, 2G12, PGT121, and PGT145 (at up to 50 μg/mL) had little or no inhibitory effect on fusion between HIV-Env and SupT1 cells. By contrast, Hippeastrum hybrid agglutinin completely inhibited fusion. Our results indicate that transmission of the virus or viral genetic material would not be inhibited by these broadly neutralizing antibodies. Thus, antibodies generated by HIV-1 vaccines should be screened for their inhibitory effect on Env-mediated cell-cell fusion.
Spatiotemporally flexible subnetworks reveal the quasi-cyclic nature of integration and segregation in the human brain
Authors: Strindberg Marika , Fransson Peter , Cabral Joana , Ådén Ulrika 
Published: June 2021

AbstractThough the organization of functional brain networks is modular at its core, modularity does not capture the full range of dynamic interactions between individual brain areas nor at the level of subnetworks. In this paper we present a hierarchical model that represents both flexible and modular aspects of intrinsic brain organization across time by constructing spatiotemporally flexible subnetworks. We also demonstrate that segregation and integration are complementary and simultaneous events. The method is based on combining the instantaneous phase synchrony analysis (IPSA) framework with community detection to identify a small, yet representative set of subnetwork components at the finest level of spatial granularity. At the next level, subnetwork components are combined into spatiotemporally flexibly subnetworks where temporal lag in the recruitment of areas within subnetworks is captured. Since individual brain areas are permitted to be part of multiple interleaved subnetworks, both modularity as well as more flexible tendencies of connectivity are accommodated for in the model. Importantly, we show that assignment of subnetworks to the same community (integration) corresponds to positive phase coherence within and between subnetworks, while assignment to different communities (segregation) corresponds to negative phase coherence or orthogonality. Together with disintegration, i.e. the breakdown of internal coupling within subnetwork components, orthogonality facilitates reorganization between subnetworks. In addition, we show that the duration of periods of integration is a function of the coupling strength within subnetworks and subnetwork components which indicates an underlying metastable dynamical regime. Based on the main tendencies for either integration or segregation, subnetworks are further clustered into larger meta-networks that are shown to correspond to combinations of core resting-state networks. We also demonstrate that subnetworks and meta-networks are coarse graining strategies that captures the quasi-cyclic recurrence of global patterns of integration and segregation in the brain. Finally, the method allows us to estimate in broad terms the spectrum of flexible and/or modular tendencies for individual brain areas.
Natural resource funds for innovation in emerging countries: an assessment of the Chilean experience
Authors: Medina-Bueno José Luis , Guimón José , Cancino Christian A. 
Published: June 2021

Purpose
This study aims to explore the institutional complexities associated with the design and implementation of a natural resource fund for innovation.

Design/methodology/approach
This study examines the case of Chile's Innovation Fund for Competitiveness by means of a historical approach building on interviews with key informants.

Findings
The proper functioning of a natural resource fund for innovation requires efficient institutional and operational structures, as well as strong coordination with innovation system actors. In particular, the case of Chile highlights the challenges inherent in adopting a regional approach when implementing this type of strategy, due to the institutional voids that hamper the role of regional governments in emerging countries.

Originality/value
Natural resource funds for innovation constitute a strategic mechanism for developing the innovative capabilities necessary to enhance the competitiveness of resource-rich emerging countries. This is one of the first studies addressing the institutional challenges involved in setting up this kind of fund in practice, focusing on one of the most relevant and longstanding examples from Latin America.
An analytic method for parameter extraction of InP HBTs small-signal model
Authors: Zhang Jincan , Liu Min , Wang Jinchan , Xu Kun 
Published: June 2021

Purpose
High-speed Indium Phosphide (InP) HBTs have been widely used to design high-speed analog, digital and mixed-signal integrated circuits. The purpose of this study is to propose a new parameter extraction procedure for determining an improved T-topology small-signal equivalent circuit of InP heterojunction bipolar transistors (HBTs).

Design/methodology/approach
The alternating current crowding effect is considered through adding the intrinsic base capacitance in the small-signal equivalent circuit. All of the circuit parameters are extracted directly without using any approximation.

Findings
The extraction technique is more easily understood and clearer than other extraction methods, as the equations are derived from the S-parameters by peeling peripheral elements from small-signal models to get reduced ones and extracting each equivalent-circuit parameter using each equation.

Originality/value
To validate the presented parameter extraction technology, an n-p-n emitter-up InP HBT was analyzed adopting the method. Excellent agreement between measured and modeled S-parameters is obtained up to 40 GHz.
Memristive combinational logic circuits and stochastic computing implementation scheme
Authors: Li Tianshu , Duan Shukai , Liu Jun , Wang Lidan 
Published: June 2021

Purpose
Stochastic computing which is an alternative method of the binary calculation has key merits such as fault-tolerant capability and low hardware cost. However, the hardware response time of it is required to be very fast due to its bit-wise calculation mode. While the complementary metal oxide semiconductor (CMOS) components are difficult to meet the requirements aforementioned. For this, the stochastic computing implementation scheme based on the memristive system is proposed to reduce the response time. The purpose of this paper is to provide the implementation scheme based memristive system for the stochastic computing.

Design/methodology/approach
The hardware structure of material logic based on the memristive system is realized according to the advantages of the memristor. After that, the scheme of NOT logic, AND logic and multiplexer are designed, which are the basic units of stochastic computing. Furthermore, a stochastic computing system based on memristive combinational logic is structured and its validity is verified successfully by operating a case.

Findings
The numbers of the elements of the proposed stochastic computing system are less than the conventional stochastic computing based on CMOS circuits.

Originality/value
The paper proposed a novel implementation scheme for stochastic computing based on the memristive systems, which are different from the conventional stochastic computing based on CMOS circuits.