bluuebunny/crossref_metadata_2025_split huggingface dataset:
A de novo protein structure prediction by iterative partition sampling, topology adjustment, and residue-level distance deviation optimization
Authors: Liu Jun , Zhao Kai-Long , He Guang-Xing , Wang Liu-Jing , Zhou Xiao-Gen , Zhang Gui-Jun 
Published: May 2021

AbstractMotivationWith the great progress of deep learning-based inter-residue contact/distance prediction, the discrete space formed by fragment assembly cannot satisfy the distance constraint well. Thus, the optimal solution of the continuous space may not be achieved. Designing an effective closed-loop continuous dihedral angle optimization strategy that complements the discrete fragment assembly is crucial to improve the performance of the distance-assisted fragment assembly method.ResultsIn this article, we proposed a de novo protein structure prediction method called IPTDFold based on closed-loop iterative partition sampling, topology adjustment and residue-level distance deviation optimization. First, local dihedral angle crossover and mutation operators are designed to explore the conformational space extensively and achieve information exchange between the conformations in the population. Then, the dihedral angle rotation model of loop region with partial inter-residue distance constraints is constructed, and the rotation angle satisfying the constraints is obtained by differential evolution algorithm, so as to adjust the spatial position relationship between the secondary structures. Lastly, the residue distance deviation is evaluated according to the difference between the conformation and the predicted distance, and the dihedral angle of the residue is optimized with biased probability. The final model is generated by iterating the above three steps. IPTDFold is tested on 462 benchmark proteins, 24 FM targets of CASP13, and 20 FM targets of CASP14. Results show that IPTDFold is significantly superior to the distance-assisted fragment assembly method Rosetta_D (Rosetta with distance). In particular, the prediction accuracy of IPTDFold does not decrease as the length of the protein increases. When using the same FastRelax protocol, the prediction accuracy of IPTDFold is significantly superior to that of trRosetta without orientation constraints, and is equivalent to that of the full version of trRosetta.AvailabilityThe source code and executable are freely available at https://github.com/iobio-zjut/IPTDFold.Contactzgj@zjut.edu.cn
A gene expression panel for estimating age in males and females of the sleeping sickness vector Glossina morsitans
Authors: Lucas Eric R. , Darby Alistair C. , Torr Stephen J. , Donnelly Martin J. 
Published: May 2021

AbstractMany vector-borne diseases are controlled by methods that kill the insect vectors responsible for disease transmission. Recording the age structure of vector populations provides information on mortality rates and vectorial capacity, and should form part of the detailed monitoring that occurs in the wake of control programmes, yet tools for obtaining estimates of individual age remain limited. We investigate the potential of using markers of gene expression to predict age in tsetse flies, which are the vectors of deadly and economically damaging African trypanosomiases. We use RNAseq to identify candidate expression markers, and test these markers using qPCR in laboratory-reared Glossina morstians morsitans of known age. Measuring the expression of six genes was sufficient to obtain a prediction of age with root mean squared error of less than 8 days, while just two genes were sufficient to classify flies into age categories of ≤ 15 and >15 days old. Further testing of these markers in field-caught samples and in other species will determine the accuracy of these markers in the field.
Robust detection of natural selection using a probabilistic model of tree imbalance
Authors: Dilber Enes , Terhorst Jonathan 
Published: May 2021

AbstractNeutrality tests such as Tajima’sD(Tajima, 1989) and Fay and Wu’sH(Fay and Wu, 2000) are standard implements in the population genetics toolbox. One of their most common uses is to scan the genome for signals of natural selection. However, it is well understood that deviance measures likeDandHare confounded by other evolutionary forces—in particular, population expansion—that may be unrelated to selection. Because they are not model-based, it is not clear how to deconfound these statistics in a principled way.In this paper we derive new likelihood-based methods for detecting natural selection which are robust to confounding by fluctuations in effective population size. At the core of our method is a novel proba-bilistic model of tree imbalance, which generalizes Kingman’s coales-cent to allow certain aberrant tree topologies to arise more frequently than is expected under neutrality. We derive a frequency spectrum-based estimator which can be used in place ofD, and also extend to the case where genealogies are first estimated. We benchmark our meth-ods on real and simulated data, and provide an open source software implementation.
Scale-free behavioral dynamics directly linked with scale-free cortical dynamics
Authors: Jones Sabrina A. , Barfield Jacob H. , Norman V. Kindler , Shew Woodrow L. 
Published: May 2021

AbstractNaturally occurring body movements and collective neural activity both exhibit complex dynamics, often with scale-free, fractal spatiotemporal structure. Scale-free dynamics of both brain and behavior are each associated with functional benefits to the organism. Despite their similarities, scale-free brain activity and scale-free behavior have been studied separately, without a unified explanation. Here we show that scale-free dynamics of behavior and certain subsets of cortical neurons are strongly related. Surprisingly, the scale-free neural subsets exhibit stochastic winner-take-all competition with other neural subsets. This observation is inconsistent with current theory of critical phenomena in neural systems. We develop a computational model which incorporates known cell-type-specific circuit structure, explaining our findings with a new type of criticality. Our results establish neural underpinnings of scale-free behavior and clear behavioral relevance of scale-free neural activity.Popular SummaryOver the past 2 decades many measurements of brain activity have revealed a peculiar property; the activity is statistically similar when examined at different scales. This self-similar, fractal nature of brain activity has attracted the interest of neuroscientists and physicists alike. In physics, fractal structure shows up in certain non-living systems when they are operating near the tipping point of a phase transition (e.g. liquid water turning into gaseous vapor). This led to the criticality hypothesis, which posits that the brain may also operate near the tipping point of a phase transition, i.e. near criticality.Initially the criticality hypothesis was very exciting at a basic level - physical principles of phase transitions promised to help us understand how the brain works. However, a important question naturally arose and remains unresolved. What do the scale-free, fractal fluctuations of brain activity have to do with the behavior of the organism? Is it just background noise in the brain or is there something fractal-like about how we behave and interact with the world?Here we show for the first time that scale-free fluctuations of brain activity are directly related to moment-to-moment fluctuations in behavior. In fact, we show that both the brain activity and mouse behavior have very similar fractal structure. These results take the criticality hypothesis to a new level of biological and, perhaps, psychological relevance. Scale-free brain dynamics are not just background noise; they correspond to the dynamics of behavior.
Programming large target genomic deletion and concurrent insertion via a prime editing-based method: PEDAR
Authors: Jiang Tingting , Zhang Xiao-Ou , Weng Zhiping , Xue Wen 
Published: May 2021

AbstractGenomic insertions, duplications, and insertion/deletions (indels) account for ~14% of human pathogenic mutations. Current gene editing methods cannot accurately or efficiently correct these abnormal genomic rearrangements, especially larger alterations (>100 bp). Thus, developing a method to accurately delete insertions/duplications and repair the deletion junction could improve the scope of gene therapies. Here, we engineer a novel gene editor, PE-Cas9, by conjugating Cas9 nuclease to reverse transcriptase. Combined with two prime editing guide RNAs (pegRNAs) targeting complementary DNA strands, PE-Cas9 can direct the replacement of a genomic fragment, ranging from to ~1-kb to >10-kb, with a desired sequence at the target site without requiring an exogenous DNA template. In a reporter cell line, thisPE-Cas9-baseddeletionandrepair (PEDAR) method restored mCherry expression through in-frame deletion of a disrupted GFP sequence. We further show that PEDAR efficiency could be enhanced by using pegRNAs with high cleavage activity or increasing transfection efficiency. In tyrosinemia mice, PEDAR removed a 1.38-kb pathogenic insertion within theFahgene and precisely repaired the deletion junction to restore FAH expression in liver. This study highlights PEDAR as a tool for correcting pathogenic mutations.
Fluid intelligence and naturalistic task impairments after focal brain lesions
Authors: Smith Verity , Pinasco Clara , Achterberg Jascha , Mitchell Daniel J. , Das Tilak , Roca Maria , Duncan John 
Published: May 2021

AbstractClassical executive tasks, such as Wisconsin card-sorting and verbal fluency, are widely used as tests of frontal lobe control functions. Since the pioneering work of Shallice and Burgess (1991), it has been known that complex, naturalistic tasks can capture deficits that are missed in these classical tests. Matching this finding, deficits in several classical tasks are predicted by loss of fluid intelligence, linked to damage in a specific cortical “multiple-demand” (MD) network, while deficits in a more naturalistic task are not. To expand on these previous results, we examined the effect of focal brain lesions on three new tests – a modification of the previously-used Hotel task, a new test of task switching after extended delays, and a test of decision-making in imagined real-life scenarios. As potential predictors of impairment we measured volume of damage to a priori MD and default mode (DMN) networks, as well as cortical damage outside these networks. Deficits in the three new tasks were substantial, but were not explained by loss of fluid intelligence, or by volume of damage to either MD or DMN networks. Instead, deficits were associated with diverse lesions, and not strongly correlated with one another. The results confirm that naturalistic tasks capture cognitive deficits beyond those measured by fluid intelligence. We suggest, however, that these deficits may not arise from specific control operations required by complex behaviour. Instead, like everyday activities, complex tasks combine a rich variety of interacting cognitive components, bringing many opportunities for processing to be disturbed.
Common neural bases for processing speech prosody and music: An integrated model
Authors: Proverbio Alice Mado , Piotti Elisabetta 
Published: May 2021

ABSTRACTIt is shared notion that speech and music processing share some commonalities. Brain bioelectrical activity was recorded in healthy participants listening to music obtained by digitally transforming real speech into melodies played by viola. Sentences were originally pronounced with a positive or negative affective prosody. The research’s aim was to investigate if the emotional content of music was extracted similarly to how the affective prosody of speech is processed.EEG was recorded from 128 electrodes in 20 healthy students. Participants had to detect rare neutral piano sounds while ignoring viola melodies. Stimulus negative valence increased the amplitude of frontal P300 and N400 ERP components while a late inferior frontal positivity was enhanced in response to positive melodies. Similar ERP markers were previously found for processing positive and negative music, vocalizations and speech. Source reconstruction applied to N400 showed that negative melodies engaged the right superior temporal gyrus and right anterior cingulate cortex, while positive melodies engaged the left middle and inferior temporal gyrus and the inferior frontal cortex. An integrated model is proposed depicting a possible common circuit for processing the emotional content of music, vocalizations and speech, which might explain some universal and relatively innate brain reaction to music.
A behavioral screen for mediators of age-dependent TDP-43 neurodegeneration identifies SF2/SRSF1 among a group of potent suppressors in both neurons and glia
Authors: Azpurua Jorge , El-Karim Enas Gad , Tranquille Marvel , Dubnau Josh 
Published: May 2021

AbstractCytoplasmic aggregation of Tar-DNA/RNA binding protein 43 (TDP-43) occurs in 97 percent of amyotrophic lateral sclerosis (ALS), about 40 percent of frontotemporal dementia (FTD) and in many cases of Alzheimer’s disease (AD). Cytoplasmic TDP-43 inclusions are seen in both sporadic and familial forms of these disorders, including those cases that are caused by repeat expansion mutations in the C9orf72 gene. To identify downstream mediators of TDP-43 toxicity, we expressed human TDP-43 in a subset of Drosophila motor neurons. Such expression causes age-dependent deficits in negative geotaxis behavior. Using this behavioral readout of locomotion, we conducted an shRNA suppressor screen and identified 32 transcripts whose knockdown was sufficient to ameliorate the neurological phenotype. The majority of these suppressors also substantially suppressed the negative effects on lifespan seen with glial TDP-43 expression. In addition to identification of a number of genes whose roles in neurodegeneration were not previously known, our screen also yielded genes involved in chromatin regulation and nuclear/import export-pathways that were previously identified in the context of cell based or neurodevelopmental suppressor screens. A notable example is SF2, a conserved orthologue of mammalian SRSF1, an RNA binding protein with roles in splicing and nuclear export. Our identification SF2/SRSF1 as a potent suppressor of both neuronal and glial TDP-43 toxicity also provides a convergence with C9orf72 expansion repeat mediated neurodegeneration, where this gene also acts as a downstream mediator.Author SummaryLoss of nuclear function of TDP-43 and its mislocalization into cytoplasmic inclusions are central features to a suite of neurodegenerative disorders. We screened 2700 Drosophila genes to identify downstream mediators that suppress an age-dependent motor dysfunction phenotype when they are knocked down by RNA interference. We identified both previously implicated pathways and several novel genes whose knock down is sufficient to dramatically and robustly rescue TDP-43 toxicity both in neuronal and glial contexts. Notably, we report that SF2/SRSF1, which was previously reported as a suppressor of C9orf72 hexanucleotide expansion repeat toxicity, also is a potent suppressor of TDP-43 mediated neurodegeneration.
Structural and cellular transcriptome foundations of human brain disease
Authors: Zeighami Yashar , Bakken Trygve E. , Nickl-Jockschat Thomas , Peterson Zeru , Jegga Anil G. , Miller Jeremy A. , Evans Alan C. , Lein Ed S. , Hawrylycz Michael 
Published: May 2021

AbstractGenes associated with risk for brain disease exhibit characteristic expression patterns that reflect both anatomical and cell type relationships. Brain-wide transcriptomic patterns of disease risk genes provide a molecular based signature for identifying disease association, often differing from common phenotypic classification. Analysis of adult brain-wide transcriptomic patterns associated with 40 human brain diseases identified five major transcriptional patterns, represented by tumor-related, neurodegenerative, psychiatric and substance abuse, and two mixed groups of diseases. Brain disease risk genes exhibit unique anatomic transcriptomic signatures, based on differential co-expression, that often uniquely identify the disease. For cortical expressing diseases, single nucleus data in the middle temporal gyrus reveals cell type expression gradients separating neurodegenerative, psychiatric, and substance abuse diseases. By homology mapping of cell types across mouse and human, transcriptomic disease signatures are found largely conserved, but with psychiatric and substance abuse related diseases showing important specific species differences. These results describe the structural and cellular transcriptomic landscape of disease in the adult brain, highlighting significant homology with the mouse yet indicating where human data is needed to further refine our understanding of disease-associated genes.
Multiple brace root phenotypes promote anchorage and limit root lodging in maize
Authors: Hostetler Ashley N. , Erndwein Lindsay , Reneau Jonathan W. , Stager Adam , Tanner Herbert G. , Cook Douglas , Sparks Erin E. 
Published: May 2021

AbstractPlant mechanical failure (lodging) causes global yield losses of 7-66% in cereal crops. We have previously shown that the above-ground nodal roots (brace roots) in maize are critical for anchorage. However, it is unknown how brace root phenotypes vary across genotypes and the functional consequence of this variation. This study quantifies the contribution of brace roots to anchorage, brace root traits, plant height, and root lodging susceptibility in 52 maize inbred lines. We show that the contribution of brace roots to anchorage and root lodging susceptibility varies among genotypes and this contribution can be explained by plant architectural variation. Additionally, supervised machine learning models were developed and show that multiple plant architectural phenotypes can predict the contribution of brace roots to anchorage and root lodging susceptibility. Together these data define the plant architectures that are important in lodging resistance and show that the contribution of brace roots to anchorage is a good proxy for root lodging susceptibility.
A Trio of Ubiquitin Ligases Sequentially Drive Ubiquitylation and Autophagic Degradation of Dysfunctional Yeast Proteasomes
Authors: Marshall Richard S. , Vierstra Richard D. 
Published: May 2021

SUMMARYAs central effectors of ubiquitin (Ub)-mediated proteolysis, proteasomes are regulated at multiple levels, including degradation of unwanted or dysfunctional particles via autophagy (termed proteaphagy). In yeast, inactive proteasomes are exported from the nucleus, sequestered into cytoplasmic aggresomes via the Hsp42 chaperone, extensively ubiquitylated, and then tethered to the expanding phagophore by the autophagy receptor Cue5. Here, we demonstrate the need for ubiquitylation driven by the trio of Ub ligases (E3s) San1, Rsp5 and Hul5, which, together with their corresponding E2s, work sequentially to promote nuclear export and Cue5 recognition. Whereas San1 functions prior to nuclear export, Rsp5 and Hul5 likely decorate aggresome-localized proteasomes in concert. Ultimately, topologically complex Ub chain(s) containing both K48 and K63 Ub-Ub linkages are assembled, mainly on the regulatory particle, to generate autophagy-competent substrates. As San1, Rsp5, Hul5, Hsp42, and Cue5 also participate in general proteostasis, proteaphagy likely engages an essential mechanism for eliminating inactive/misfolded proteins.HIGHLIGHTSUbiquitylation is essential for the autophagic turnover of dysfunctional proteasomes.The San1, Rsp5 and Hul5 E3s act sequentially to drive proteaphagy.The E2s Ubc1, Ubc4 and Ubc5 are collectively required.Both K48- and K63-mediated Ub-Ub linkages are assembled for efficient proteaphagy.
MHD and nonlinear thermal radiation effects on hybrid nanofluid past a wedge with heat source and entropy generation
Authors: Mabood Fazle , Shafiq Anum , Khan Waqar Ahmed , Badruddin Irfan Anjum 
Published: May 2021

Purpose
This study aims to investigate the irreversibility associated with the Fe3O4–Co/kerosene hybrid-nanofluid past a wedge with nonlinear radiation and heat source.

Design/methodology/approach
This study reports the numerical analysis of the hybrid nanofluid model under the implications of the heat source and magnetic field over a static and moving wedge with slips. The second law of thermodynamics is applied with nonlinear thermal radiation. The system that comprises differential equations of partial derivatives is remodeled into the system of differential equations via similarity transformations and then solved through the Runge–Kutta–Fehlberg with shooting technique. The physical parameters, which emerges from the derived system, are discussed in graphical formats. Excellent proficiency in the numerical process is analyzed by comparing the results with available literature in limiting scenarios.

Findings
The significant outcomes of the current investigation are that the velocity field uplifts for higher velocity slip and magnetic strength. Further, the heat transfer rate is reduced with the incremental values of the Eckert number, while it uplifts with thermal slip and radiation parameters. An increase in Brinkmann’s number uplifts the entropy generation rate, while that peters out the Bejan number. The results of this study are of importance involving in the assessment of the effect of some important design parameters on heat transfer and, consequently, on the optimization of industrial processes.

Originality/value
This study is original work that reports the hybrid nanofluid model of Fe3O4–Co/kerosene.
Strategic supply chains: a configurational perspective
Authors: Feizabadi Javad , Gligor David , Alibakhshi Somayeh 
Published: May 2021

PurposeDrawing on configuration theory and adopting a holistic perspective, the authors aim to explore strategic supply chain elements' interaction with internal and external contextual conditions. Specifically, they evaluate multivariate co-alignment of supply chain's capabilities (agility, adaptability, alignment), adhocracy organizational structure and environmental uncertainty (dynamism, munificence and complexity) that lead to superior performance outcomes (supply chain cycle time, financial performance, market performance).Design/methodology/approachA survey research design is adopted to collect primary and secondary data from 182 international firms. Cluster analysis and profile deviation techniques are employed first to derive a taxonomy of strategic supply chains and then examine multivariate co-alignment.FindingsThe analysis reveals that four groups of triple-A supply chains could emerge. It is found that strategic supply chains exhibit a flexible/organic/fluid organizational structure and a high level of triple-As in their processes. These supply chains perform superior to a higher level of environmental complexity, munificence and dynamism.Practical implicationsThis study's results provide insights for practitioners by informing their investment decisions for developing strategic supply chains. Specifically, this research highlights the contextuality of triple-A supply chains and offers best practices to capitalize on strategic supply chains.Originality/valueExecutives in organizations require a holistic understanding of various elements to ensure that the organizational system as a whole performs effectively. This research offers insights into the interdependencies of triple-A supply chains with other organizational and external environmental elements. Noteworthy implications for scholarship in operations/supply chain management and supply chain practitioners are presented.