bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcellular localization and mitotic interactome analyses identify SIRT4 as a centrosomally localized and microtubule associated protein
Authors: Bergmann Laura , Lang Alexander , Bross Christoph , Altinoluk-Hambüchen Simone , Fey Iris , Overbeck Nina , Stefanski Anja , Wiek Constanze , Kefalas Andreas , Verhülsdonk Patrick , Mielke Christian , Sohn Dennis , Stühler Kai , Hanenberg Helmut , Jänicke Reiner U. , Scheller Jürgen , Reichert Andreas S. , Ahmadian M. Reza , Piekorz Roland P. 
Published: February 2020

AbstractThe stress-inducible and senescence-associated tumor suppressor SIRT4, a member of the family of mitochondrial sirtuins (SIRT3, SIRT4, and SIRT5), regulates bioenergetics and metabolismviaNAD+-dependent enzymatic activities. Next to the known mitochondrial location, we found that a fraction of endogenous or ectopically expressed SIRT4, but not SIRT3, is located at the mitotic spindle apparatus in the cytosol. Confocal spinning disk microscopy revealed that SIRT4 localizes during the cell cycle dynamically at centrosomes with an intensity peak in G2and early mitosis. Moreover, SIRT4 binds to microtubules and interacts with structural (α,β-tubulin, γ-tubulin, TUBGCP2, TUBGCP3) and regulatory (HDAC6) microtubule components as detected by co-immunoprecipitation and mass spectrometric analyses of the mitotic SIRT4 interactome. Overexpression of SIRT4 resulted in a pronounced decrease of acetylated α-tubulin (K40) associated with altered microtubule dynamics in mitotic cells. SIRT4 or the N-terminally truncated variant SIRT4(ΔN28), which is unable to translocate into mitochondria, delayed mitotic progression and reduced cell proliferation. This study extends the functional roles of SIRT4 beyond mitochondrial metabolism, and suggests that SIRT4 acts as a novel centrosomal / microtubule-associated protein in the regulation of cell cycle progression. Thus, stress-induced SIRT4 may exert its role as tumor suppressor through mitochondrial as well as extramitochondrial functions, the latter associated with its localization at the mitotic spindle apparatus.
Capybara: A computational tool to measure cell identity and fate transitions
Authors: Kong Wenjun , Fu Yuheng C. , Morris Samantha A. 
Published: February 2020

SummaryTransitions in cell identity are fundamental to development, reprogramming, and disease. Single-cell technologies enable the dissection of tissue composition on a cell-by-cell basis in complex biological systems. However, highly-sparse single-cell RNA-seq data poses challenges for cell-type identification algorithms based on bulk RNA-seq. Single-cell analytical tools are also limited, where they require prior biological knowledge and typically classify cells in a discrete, categorical manner. Here, we present a computational tool, ‘Capybara,’ designed to measure cell identity as a continuum, at single-cell resolution. This approach enables the classification of discrete cell entities but also identifies cells harboring multiple identities, supporting a metric to quantify cell fate transition dynamics. We benchmark the performance of Capybara against other existing classifiers and demonstrate its efficacy to annotate cells and identify critical transitions within a well-characterized differentiation hierarchy, hematopoiesis. Our application of Capybara to a range of reprogramming strategies reveals previously uncharacterized regional patterning and identifies a putativein vivocorrelate for an engineered cell type that has, to date, remained undefined. These findings prioritize interventions to increase the efficiency and fidelity of cell engineering strategies, showcasing the utility of Capybara to dissect cell identity and fate transitions. Capybara code and documentation are available athttps://github.com/morris-lab/Capybara.
Agewise mapping of genomic oxidative DNA modification demonstrates oxidative-driven reprogramming of pro-longevity genes
Authors: Aung Lynn Htet Htet , Wang Yin , Liu Zi-Qian , Li Zhe , Yu Zhongjie , Chen Xiatian , Gao Jinning , Shan Peipei , Zhou Zhixia , Li Peifeng 
Published: February 2020

AbstractThe accumulation of unrepaired oxidatively damaged DNA can influence both the rate of ageing and life expectancy of an organism. Mapping oxidative DNA damage sites at whole-genome scale will help us to recognize the damage-prone sequence and genomic feature information, which is fundamental for ageing research. Here, we developed an algorithm to map the whole-genome oxidative DNA damage at single-base resolution using Single-Molecule Real-Time (SMRT) sequencing technology. We sequenced the genomic oxidative DNA damage landscape of C. elegans at different age periods to decipher the potential impact of genomic DNA oxidation on physiological ageing. We observed an age-specific pattern of oxidative modification in terms of motifs, chromosomal distribution, and genomic features. Integrating with RNA-Seq data, we demonstrated that oxidative modification in promoter regions was negatively associated with the expression of pro-longevity genes, denoting that oxidative modification in pro-longevity genes may exert epigenetic potential and thus affect lifespan determination. Together, our study opens up a new field for exploration of “oxigenetics,” that focuses on the mechanisms of redox-mediated ageing.SummaryWe developed an algorithm to map the oxidative DNA damage at single-base resolution.Oxidative DNA damage landscape in C. elegans illustrated an age-specific pattern in terms of motifs, chromosomal distribution, and genomic features.Oxidative modification in older worms occurred higher frequency at the sex chromosome, with the preference for promoter and exon regions.Oxidative modification in promoter regions of pro-longevity genes was negatively associated with their expression, suggesting the oxidative-driven transcript reprogramming of pro-longevity genes in physiological ageing.
Double-stranded RNA bending by AU-tract sequences
Authors: Marin-Gonzalez Alberto , Aicart-Ramos Clara , Marin-Baquero Mikel , Martín-González Alejandro , Suomalainen Maarit , Kannan Abhilash , Vilhena J. G. , Greber Urs F. , Moreno-Herrero Fernando , Pérez Rubén 
Published: February 2020

ABSTRACTSequence-dependent structural deformations of the DNA double helix (dsDNA) have been extensively studied, where adenine tracts (A-tracts) provide a striking example for global bending in the molecule. In contrast to dsDNA, much less is known about how the nucleotide sequence affects bending deformations of double-stranded RNA (dsRNA). Using all-atom microsecond long molecular dynamics simulations we found a sequence motif consisting of alternating adenines and uracils, or AU-tracts, that bend the dsRNA helix by locally compressing the major groove. We experimentally tested this prediction using atomic force microscopy (AFM) imaging of long dsRNA molecules containing phased AU-tracts. AFM images revealed a clear intrinsic bend in these AU-tracts molecules, as quantified by a significantly lower persistence length compared to dsRNA molecules of arbitrary sequence. The bent structure of AU-tracts here described might play a role in sequence-specific recognition of dsRNAs by dsRNA-interacting proteins or impact the folding of RNA into intricate tertiary and quaternary structures.
Phylogeny and distribution of Y-chromosomal haplotypes in domestic, ancient and wild goats
Authors: Nijman Isaäc J. , Rosen Benjamin D. , Zheng Zhuqing , Jiang Yu , Cumer Tristan , Daly Kevin G. , Bâlteanu Valentin A. , Berger Beate , Blichfeldt Thor , Boink Geert , Carolan Sean , Cubric-Curik Vlatka , Kantanen Juha , Martínez Amparo , Mazza Raffaele , Khayatzadeh Negar , Kim Namshin , Ouchene-Khelifi Nadjet-Amina , Pereira Filipe , da Silva Anne , Simčič Mojca , Sölkner Johann , Sutherland Alison , Tigchelaar Johannes ,   Econogene Consortium, Ajmone-Marsan Paolo , Bradley Daniel G. , Colli Licia , Pompanon François , Lenstra Johannes A. 
Published: February 2020

AbstractThe male-specific part of the Y-chromosome is in mammalian and many other species the longest haplotype that is inherited without recombination. By its paternal transmission it has a small effective population size in species with dominant males. In several species, Y-chromosomal haplotypes are sensitive markers of population history and introgression. Previous studies have identified in domestic goats four major Y-chromosomal haplotypes Y1A, Y1B, Y2A and Y2B with a marked geographic differentiation and several regional variants. In this study we used published whole-genome sequences of 70 male goats from 16 modern breeds, 11 ancient-DNA samples and 29 samples from seven wild goat species. We identified single-copy male-specific SNPs in four scaffolds, containingSRY, ZFY, DBYwithSSX3YandUTY,andUSP9YwithUMN2001,respectively. Phylogenetic analyses indicated haplogroups corresponding to the haplotypes Y1B, Y2A and Y2B, respectively, but Y1A was split into Y1AA and Y1AB. All haplogroups were detected in ancient DNA samples from southeast Europe and, with the exception of Y1AB, in the bezoar goat, which is the wild ancestor of the domestic goats. Combining these data with those of previous studies and with genotypes obtained by Sanger sequencing or the KASP assay yielded haplogroup distributions for 132 domestic breeds or populations. The phylogeographic differentiation indicated paternal population bottlenecks on all three continents. This possibly occurred during the Neolithic introductions of domestic goats to those continents with a particularly strong influence in Europe along the Danubian route. This study illustrates the power of the Y-chromosomal haplotype for the reconstructing the history of mammalian species with a wide geographic range.
Random Forest Regression for Optimizing Variable Planting Rates for Corn and Soybean Using High-Resolution Topographical and Soil Data
Authors: Krause Margaret R. , Crossman Savanna , DuMond Todd , Lott Rodman , Swede Jason , Arliss Scott , Robbins Ron , Ochs Daniel , Gore Michael A. 
Published: February 2020

ABSTRACTIn recent years, planting machinery that enables precise control of the planting rates has become available for corn (Zea maysL.) and soybean (Glycine maxL.). With increasingly available topographical and soil information, there is a growing interest in developing variable rate planting strategies to exploit variation in the agri-landscape in order to maximize production. A random forest regression-based approach was developed to model the interactions between planting rate, topography, and soil characteristics and their effects on yield based on on-farm variable rate planting trials for corn and soybean conducted at 27 sites in New York between 2014 and 2018 (57 site-years) in collaboration with the New York Corn and Soybean Growers Association. Planting rate ranked highly in terms of random forest regression variable importance while explaining relatively minimal yield variation in the linear context, indicating that yield response to planting rate likely depends on complex interactions with agri-landscape features. Models were moderately predictive of yield within site-years and across years at a particular site, while the ability to predict yield across sites was low. Relatedly, variable importance measures for the topographical and soil features varied considerably across sites. Together, these results suggest that local testing may provide the most accurate optimized planting rate designs due to the unique set of conditions at each site. The proposed method was extended to identify the optimal variable rate planting design for maximizing yield at each site given the topographical and soil data, and empirical validation of the resulting designs is currently underway.
Identification of plant enhancers and their constituent elements by STARR-seq in tobacco leaves
Authors: Jores Tobias , Tonnies Jackson , Dorrity Michael W , Cuperus Josh T , Fields Stanley , Queitsch Christine 
Published: February 2020

ABSTRACTGenetic engineering ofcis-regulatory elements in crop plants is a promising strategy to ensure food security. However, such engineering is currently hindered by our limited knowledge of plantcis-regulatory elements. Here, we adapted STARR-seq — a technology for the high-throughput identification of enhancers — for its use in transiently transformed tobacco leaves. We demonstrate that the optimal placement in the reporter construct of enhancer sequences from a plant virus, pea and wheat was just upstream of a minimal promoter, and that none of these four known enhancers was active in the 3′-UTR of the reporter gene. The optimized assay sensitively identified small DNA regions containing each of the four enhancers, including two whose activity was stimulated by light. Furthermore, we coupled the assay to saturation mutagenesis to pinpoint functional regions within an enhancer, which we recombined to create synthetic enhancers. Our results describe an approach to define enhancer properties that can be performed in potentially any plant species or tissue transformable byAgrobacteriumand that can use regulatory DNA derived from any plant genome.One-sentence summaryWe developed a high-throughput assay in transiently transformed tobacco leaves that can identify enhancers, characterize their functional elements and detect condition-specific enhancer activity.
A computational model explains and predicts substantia nigra pars reticulata responses to pallidal and striatal inputs
Authors: Phillips Ryan S. , Rosner Ian , Gittis Aryn H. , Rubin Jonathan E. 
Published: February 2020

AbstractAs a rodent basal ganglia (BG) output nucleus, the substantia nigra pars reticulata (SNr) is well positioned to impact behavior. SNr neurons receive GABAergic inputs from the striatum (direct pathway) and globus pallidus (GPe, indirect pathway). Dominant theories of action selection rely on these pathways’ inhibitory actions. Yet, experimental results on SNr responses to these inputs are limited and include excitatory effects. Our study combines experimental and computational work to characterize, explain, and make predictions about these pathways. We observe diverse SNr responses to stimulation of SNr-projecting striatal and GPe neurons, including biphasic and excitatory effects, which our modeling shows can be explained by intracellular chloride processing. Our work predicts that ongoing GPe activity could tune the SNr operating mode, including its responses in decision-making scenarios, and GPe output may modulate synchrony and low-frequency oscillations of SNr neurons, which we confirm using optogenetic stimulation of GPe terminals within the SNr.
Accelerated cell cycles enable organ regeneration under developmental time constraints in theDrosophilahindgut
Authors: Cohen Erez , Fox Donald T. 
Published: February 2020

SummaryIndividual organ development must be temporally coordinated with development of the rest of the organism. As a result, cell division in a developing organ occurs on a relatively fixed time scale. Despite this, many developing organs can regenerate cells lost to injury. How organs regenerate within the time constraints of organism development remains unclear. Here, we show the developingDrosophilahindgut regenerates by accelerating the mitotic cell cycle. This process requires JAK/STAT signaling and is achieved by decreasing G1 length during the normal period of developmental mitoses. Mitotic capacity is then terminated by the steroid hormone ecdysone receptor. This receptor activates a hindgut-specific enhancer offizzy-related, a negative regulator of mitotic cyclins. We further identify the Sox transcription factorDichaeteas an important negative regulator of injury-induced mitotic cycles. Our findings reveal how mitotic cell cycle entry mechanisms can be adapted to accomplish developmental organ regeneration.
Determination of volumetric material data from boundary measurements
Authors: Löhner Rainald , Antil Harbir 
Published: February 2020

Purpose
The purpose of this study is to determine the possibility of an accurate assessment of the spatial distribution of material properties such as conductivities or impedances from boundary measurements when the governing partial differential equation is a Laplacian.

Design/methodology/approach
A series of numerical experiments were carefully performed. The results were analyzed and compared.

Findings
The results to date show that while the optimization procedure is able to obtain spatial distributions of the conductivity k that reduce the cost function significantly, the resulting conductivity k is still significantly different from the target (or real) distribution sought. While the normal fluxes recovered are very close to the prescribed ones, the tangential fluxes can differ considerably.

Research limitations/implications
At this point, it is not clear why rigorous mathematical proofs yield results of convergence and uniqueness, while in practice, accurate distributions of the conductivity k seem to be elusive. One possible explanation is that the spatial influence of conductivities decreases exponentially with distance. Thus, many different conductivities inside a domain could give rise to very similar (infinitely close) boundary measurements.

Practical implications
This implies that the estimation of field conductivities (or generally field data) from boundary data is far more difficult than previously assumed when the governing partial differential equation in the domain is a Laplacian. This has consequences for material parameter assessments (e.g. for routine maintenance checks of structures), electrical impedance tomography, and many other applications.

Originality/value
This is the first time such a finding has been reported in this context.
A study on the effect of ethical leadership on teachers’ moral motivation at schools in Pakistan
Authors: Khan Shazia Rehman , Bauman David C. , Javed Uzma 
Published: February 2020

PurposeThe purpose of this study was to examine the influence of ethical leadership on moral motivation of teachers in the schools of Pakistan.Design/methodology/approachScenario-based experimental design was used to collect data (N = 174 teachers) from 25 schools in the city of Islamabad. Participants included 156 females and 18 males aged 23–37 years. Ethical leadership was measured at both construct and component levels (moral person and moral manager).FindingsThe results found that the moral person component of ethical leadership style heightens the moral identity (internalization)-based moral motivation, while the moral manager component and ethical leadership at construct level style increases moral identity (symbolization)-based moral motivation. Interestingly, in the absence of reward, only the moral person component of ethical leadership style maintained participants’ moral motivation.Originality/valueThe originality of this study lies in highlighting the divergence in ethical leadership style at component level that explains the differences in moral motivation of the teachers.
A geographically disaggregated analysis of multidimensional poverty in Punjab
Authors: Iqbal Asim , Siddiqui Anjum , Zafar Maryam 
Published: February 2020

PurposeThe study seeks to examine the extent and the causes of multidimensional poverty as opposed to the traditional unidimensional headcount poverty measures to understand the true face of economic deprivation in Punjab, Pakistan.Design/methodology/approachPoverty is measured through the Alkire–Foster index at the geographically disaggregated levels of divisions and districts, and the causes of pervasive poverty are analyzed through a logit model using the Multiple Indicators Cluster Survey (MICS) comprising of 95,238 households in 9 geographical divisions and their 36 districts.FindingsIt was found that poverty in Punjab is associated with larger household size, inadequate wealth, and low levels of educational attainment, and that both matric as well as post-matric education reduced the chances of poverty of household heads by approximately 19 percent. In addition to rural poverty, the study finds evidence of urban poverty across the geographical districts of Punjab. Contrary to common belief that chances of poverty are higher in females, it was found to be more likely in males. However, the statistical significance of gender as a determinant of poverty was not observed in the majority of divisions.Practical implicationsPractical implications were for focused policy interventions in poverty alleviation.Originality/valueThe analysis of determinants of multidimensional poverty at the geographically disaggregated level of divisions is an original contribution.Peer reviewThe peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-01-2019-0037
Functional differentiation of society as a middle-range theory
Authors: Sakai Kosuke 
Published: February 2020

PurposeThis paper aimed to analyze the ways in which Niklas Luhmann's theory of the functional differentiation of society can be applied to historical studies. To achieve this, a semantic analysis of the development of modern insurance in Germany during the nineteenth century was conducted.Design/methodology/approachThrough an examination of the significant features of Luhmann's theoretical frameworks in empirical objects, Luhmann's semantic analysis was reformulated as an approach based on a middle-range theory, similar to that of Robert K. Merton, where the potential of the theory can be maximized for empirical research. This paper embodies this proposal, citing several developments within organizations that imbued insurance technology with various ideas and values.FindingsThe theory of the functional differentiation of society can be reconstructed as a working hypothesis from a methodological perspective, instead of a general theory that explains every part of society. Applying this to empirical social practices leads to progress in historical studies conducting the semantic variations connected to the institutional formation and their boundary works.Originality/valueThis paper provides a practical research perspective for historical studies in the social sciences, employing a reinterpretation of sociological theory that may be understood only as a structural presupposition of modern society. Furthermore, the increased possibility of historical-comparative studies on modern insurance is indicated by illustrating the applicability of this framework to a detailed case study of modern insurance.