bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution and phylogenetic distribution ofendo-α-mannosidase
Authors: Sobala Łukasz F. 
Published: December 2022

AbstractWhile glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. One of them is the glycoproteinendo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside thecis-Golgi. It is unique as the only endo-acting mannosidase found in this organelle. Relatively little is known about its origins and evolutionary history; so far it was thought to occur only in vertebrates. Here I perform a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals. I found the endomannosidase to be vastly more widely distributed in animals than previously thought and in fact present in almost all eukaryotic clades. I tracked protein motif changes in context of the canonical animal enzyme. Additionally, my data show that the two canonical versions of endomannosidase in vertebrates, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and indicate presence of a third protein, named here CMANEAL. Finally, I describe a framework where N-glycosylation co-evolved with complex multicellularity. A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. This systematic analysis of the endomannosidase evolution is one step towards this goal.
Inverse Agonist Activity of Angiotensin II Receptor Blocker Is Crucial for Prevention of Aortic Aneurysm Formation in Marfan Syndrome
Authors: Yagi Hiroki , Akazawa Hiroshi , Liu Qing , Umei Masahiko , Kadowaki Hiroshi , Matsuoka Ryo , Shindo Akito , Okamura Shun , Saga-Kamo Akiko , Takeda Norifumi , Komuro Issei 
Published: December 2022

AbstractBackgroundMarfan syndrome (MFS), an inherited disorder caused byFBN1gene mutations, causes fatal aortic aneurysm. Selective angiotensin II (Ang II) type 1 (AT1) receptor blockade is a preventive option for patients with MFS aortopathy, and recent clinical studies demonstrated that the inhibitory effect of an AT1receptor blocker (ARB) losartan on aortic aneurysm growth is equivalent to that of β-blockers. At present, several ARBs are clinically available, and they have drug-specific differences in pharmacological properties. Especially, inverse agonism of ARBs has potential benefits for cardiovascular protection, but its impact on MFS aortopathy remains poorly understood.MethodsCandesartan-7H is a candesartan derivative which lacks the carboxyl group critical for inverse agonist activity and works as a neutral antagonist for AT1receptor. Candesartan cilexetil (1 mg/kg/day), candesartan-7H (1 mg/kg/day or 20 mg/kg/day), or vehicle was administered toFbn1C1041G/+mice, and aortic aneurysm formation was analyzed using echocardiography, histological staining, andin situMMP assay. Activation of TGF-β signaling and mechanosensitive signaling was studied using western blot and immunohistochemical analysis.ResultsCandesartan cilexetil (1 mg/kg/day) and candesartan-7H (20 mg/kg/day) lowered blood pressures equally inFbn1C1041G/+mice, but that candesartan-7H (1 mg/kg/day) did not. Aortic aneurysmal progression in association with aortic wall thickening, degeneration of elastic fibers, deposition of collagen, MMP activation, and TGF-β signaling activation inFbn1C1041G/+mice was significantly suppressed by treatment with candesartan cilexetil (1 mg/kg/day), but not by candesartan-7H even at 20 mg/kg/day. In addition, candesartan cilexetil, but not candesartan-7H, inhibited up-regulation of mechanical stress–responsive transcriptional factor Egr-1 in ascending aorta ofFbn1C1041G/+mice.ConclusionsOur findings support a crucial role of inverse agonist activity of ARB for prevention of mechanical stress-induced AT1receptor activation and aortic aneurysm formation in MFS mice.
The Tip60/Ep400 chromatin remodeling complex impacts basic cellular functions in cranial neural crest-derived tissue during early orofacial development
Authors: Gehlen-Breitbach Sebastian , Schmid Theresa , Fröb Franziska , Rodrian Gabriele , Weider Matthias , Wegner Michael , Gölz Lina 
Published: December 2022

AbstractThe cranial neural crest plays a fundamental role in orofacial development and morphogenesis. Accordingly, mutations with impact on the cranial neural crest and its development lead to orofacial malformations such as cleft lip and palate. As a pluripotent and dynamic cell population, the cranial neural crest undergoes vast transcriptional and epigenomic alterations throughout the formation of facial structures pointing to an essential role of factors regulating chromatin state or transcription levels. Using CRISPR/Cas9-guided genome editing and conditional mutagenesis in the mouse, we here show that inactivation of Kat5 and Ep400 as the two essential enzymatic subunits of the Tip60/Ep400 chromatin remodeling complexes severely affects carbohydrate and amino acid metabolism in cranial neural crest cells. The resulting decrease in protein synthesis, proliferation and survival leads to a drastic reduction of cranial neural crest cells early in fetal development and a loss of most facial structures in the absence of either protein. Following heterozygous loss of Kat5 in neural crest cells palatogenesis was impaired. These findings point to a decisive role of the Tip60/Ep400 chromatin remodeling complex in facial morphogenesis and lead us to conclude that the orofacial clefting observed in patients with heterozygous KAT5 missense mutations is at least in part due to disturbances in the cranial neural crest.
Gene regulatory network inference using mixed-norms regularized multivariate model with covariance selection
Authors: Mbebi Alain J. , Nikoloski Zoran 
Published: December 2022

AbstractDespite extensive research efforts, reconstruction of gene regulatory networks (GRNs) from transcriptomics data remains a pressing challenge in systems biology. While non-linear approaches for reconstruction of GRNs show improved performance over simpler alternatives, we do not yet have understanding if joint modelling of multiple target genes may improve performance, even under linearity assumptions. To address this problem, we propose two novel approaches that cast the GRN reconstruction problem as a blend between regularized multivariate regression and graphical models that combine the L2,1-norm with classical regularization techniques. We used data and networks from the DREAM5 challenge to show that the proposed models provide consistently good performance in comparison to contenders whose performance varies with data sets from simulation and experiments from model unicellular organismsEscherichia coliandSaccharomyces cerevisiae. Since the models’ formulation facilitates the prediction of master regulators, we also used the resulting findings to identify master regulators over all data sets as well as their plasticity across different environments. Our results demonstrate that the identified master regulators are in line with experimental evidence from the model bacteriumE. coli. Together, our study demonstrates that simultaneous modelling of several target genes results in improved inference of GRNs and can be used as an alternative in different applications.Author summaryReconstruction of cellular networks based on snapshots of molecular profiles of the network components has been one of the key challenges in systems biology. In the context of reconstruction of gene regulatory networks (GRNs), this problem translates into inferring regulatory relationships between transcription factor coding genes and their targets based on, often small, number of expression profiles. While unsupervised nonlinear machine learning approaches have shown better performance than regularized linear regression approaches, the existing modeling strategies usually do predictions of regulators for one target gene at a time. Here, we ask if and to what extent the joint modeling of regulation for multiple targets leads to improvement of the accuracy of the inferred GRNs. To address this question, we proposed, implemented, and compared the performance of models cast as a blend between regularized multivariate regression and graphical models that combine the L2,1-norm with classical regularization techniques. Our results demonstrate that the proposed models, despite relying on linearity assumptions, show consistently good performance in comparison to existing, widely used alternatives.
Functional genomic mechanisms of opioid action and opioid use disorder: a systematic review of animal models and human studies
Authors: Falconnier Camille , Caparros-Roissard Alba , Decraene Charles , Lutz Pierre-Eric 
Published: December 2022

AbstractIn the past two decades, over-prescription of opioids for pain management has driven a steep increase in opioid use disorder (OUD) and death by overdose, exerting a dramatic toll on western countries. OUD is a chronic relapsing disease associated with a lifetime struggle to control drug consumption, suggesting that opioids trigger long-lasting brain adaptations, notably through functional genomic and epigenomic mechanisms. Current understanding of these processes, however, remain scarce, and have not been previously reviewed systematically. To do so, the goal of the present work was to synthesize current knowledge on genome-wide transcriptomic and epigenetic mechanisms of opioid action, in primate and rodent species. Using a prospectively registered methodology, comprehensive literature searches were completed in PubMed, Embase, and Web of Science. Of the 2709 articles identified, 73 met our inclusion criteria and were considered for qualitative analysis. Focusing on the 5 most studied nervous system structures (nucleus accumbens, frontal cortex, whole striatum, dorsal striatum, spinal cord; 44 articles), we also conducted a quantitative analysis of differentially expressed genes, in an effort to identify a putative core transcriptional signature of opioids. Only one gene, Cdkn1a, was consistently identified in eleven studies, and globally, our results unveil surprisingly low consistency across published work, even when considering most recent single-cell approaches. Analysis of putative sources of variability detected significant contributions from species, brain structure, duration of opioid exposure, strain, time-point of analysis, and batch effects, but not type of opioid. To go beyond those limitations, we leveraged threshold-free methods to illustrate how genome-wide comparisons may generate new findings and hypotheses. Finally, we discuss current methodological development in the field, and their implication for future research and, ultimately, better care.
A quantitative and site-specific atlas of the in vivo citrullinome reveals widespread existence of citrullination
Authors: Rebak Alexandra S. , Hendriks Ivo A. , Buch-Larsen Sara C. , Elsborg Jonas D. , Kirsch Rebecca , Doncheva Nadezhda T. , Jensen Lars J. , Christophorou Maria , Nielsen Michael L. 
Published: December 2022

AbstractCitrullination is the conversion of peptidyl-arginine into the non-coded amino acid citrulline. Despite its importance in physiology and disease, global identification of citrullinated proteins and precise modification sites has remained challenging. Here, we employed quantitative mass spectrometry-based proteomics to generate a comprehensive atlas of citrullination sites in a physiologically relevant cell type. Collectively, we identified 14.056 citrullination sites within 4.008 proteins and quantified their regulation upon inhibition of the citrullinating enzyme PADI4. Using this rich dataset, we uncover general mechanistic and cell biological principles of citrullination function, while providing site-specific and quantitative information on thousands of PAD4 substrates within cells. Our findings include signature histone marks and numerous modifications on transcriptional regulators and chromatin-related signaling effectors. Additionally, we identify precise citrullination sites on an extensive list of known autoantigens. Collectively, we describe systems attributes of the human citrullinome and provide a resource framework for understanding citrullinaiton at the mechanistic level.
The Beta secretase BACE1 drives fibroblasts activation in Systemic Sclerosis through the APP/β-catenin/Notch signalling axis
Authors: Wasson Christopher W. , Lorenzis Enrico De , Clavane Eva M. , Ross Rebecca L. , Walker Kieran A. , Caballero-Ruiz Begoña , Antinozzi Cristina , Wells Rebecca , Migneco Gemma , Brown Jane M. Y. , Riobo-Del Galdo Natalia A. , Luigi Luigi Di , McKimmie Clive S. , Del Galdo Francesco , Meakin Paul J. 
Published: December 2022

AbstractThe beta-amyloid precursor protein cleaving enzyme 1 (BACE1) is well known for its role in the development of Alzheimer’s disease. Recent publications, including our own, have demonstrated a role for this enzyme in other chronic diseases. The aim of this study was to investigate the role of BACE1 in the autoimmune disease systemic sclerosis (SSc). BACE1 protein levels were elevated in SSc patient skin. Inhibition of BACE1 with small molecule inhibitors or siRNA blocked SSc and fibrotic stimuli mediated fibroblast activation. Furthermore, we show that BACE1 regulation of dermal fibroblast activation is dependent on β-catenin and Notch signalling. The Neurotropic factor BDNF negatively regulates BACE1 expression and activity in dermal fibroblasts. Finally, sera from SSc patients show higher Aβ and lower BDNF levels compared to healthy controls. The ability of BACE1 to regulate SSc fibroblast activation reveals a new therapeutic target in SSc. Several BACE1 inhibitors have been shown to be safe in clinical trials for Alzheimer’s disease and could be repurposed to ameliorate fibrosis progression.
Anillin forms linear structures and facilitates furrow ingression after septin and formin depletion
Authors: Lebedev Mikhail , Chan Fung-Yi , Bellessem Jennifer , Osório Daniel S. , Rackles Elisabeth , Mikeladze-Dvali Tamara , Carvalho Ana X. , Zanin Esther 
Published: December 2022

AbstractDuring cytokinesis a contractile ring consisting of unbranched filamentous actin (F-actin) and myosin II filaments assembles and constricts at the cell equator. Unbranched F-actin isde novogenerated by formin and without formin cleavage furrow ingression fails. InC. elegansdepletion of septin restores cleavage furrow ingression in formin (CYK-1) mutants. How the cleavage furrow ingresses without a detectable unbranched F-actin ring is not known. We report, that in this setting anillin (ANI-1) is essential for furrow ingression and forms a meshwork of linear structures, which circumferentially align around the cell equator. Although equatorial ANI-1 recruitment is facilitated by septins, the formation of linear ANI-1 structures is septin independent. Analysis of ANI-1 deletion mutants reveals that its disordered linker region is required for linear structure formation and furrow ingression. We also found that myosin II (NMY-2) decorates linear ANI-1 structures and promotes their circumferential alignment. NMY-2 also interacts with various lipids and forms membrane localized clusters in absence of F-actin and anillin binding. This suggests that NMY-2 represents an independent link between the F-actin / ANI-1 network and the plasma membrane. Collectively, our data reveals a compensatory mechanism, mediated by ANI-1 linear structures and membrane-bound NMY-2, that promotes furrow formation and ingression when formins are depleted and therefore unbranched F-actin polymerization is compromised.
Cyber threat: its origins and consequence and the use of qualitative and quantitative methods in cyber risk assessment
Authors: Crotty James , Daniel Elizabeth 
Published: December 2022

PurposeConsumers increasingly rely on organisations for online services and data storage while these same institutions seek to digitise the information assets they hold to create economic value. Cybersecurity failures arising from malicious or accidental actions can lead to significant reputational and financial loss which organisations must guard against. Despite having some critical weaknesses, qualitative cybersecurity risk analysis is widely used in developing cybersecurity plans. This research explores these weaknesses, considers how quantitative methods might address the constraints and seeks the insights and recommendations of leading cybersecurity practitioners on the use of qualitative and quantitative cyber risk assessment methods.Design/methodology/approachThe study is based upon a literature review and thematic analysis of in-depth qualitative interviews with 16 senior cybersecurity practitioners representing financial services and advisory companies from across the world.FindingsWhile most organisations continue to rely on qualitative methods for cybersecurity risk assessment, some are also actively using quantitative approaches to enhance their cybersecurity planning efforts. The primary recommendation of this paper is that organisations should adopt both a qualitative and quantitative cyber risk assessment approach.Originality/valueThis work provides the first insight into how senior practitioners are using and combining qualitative and quantitative cybersecurity risk assessment, and highlights the need for in-depth comparisons of these two different approaches.
Target tracking and enclosing via UAV/UGV cooperation using energy estimation pigeon-inspired optimization and switchable topology
Authors: Shen Yankai , Wei Chen 
Published: December 2022

Purpose
The research of unmanned air/ground vehicle (UAV/UGV) cooperation has attracted much attention due to its potential applications in disaster rescue and target surveillance. This paper aims to focus on the UAV/UGV cooperative target tracking and enclosing, considering the limits of detection and sensor failures.

Design/methodology/approach
The UAV/UGV cooperation structure is designed, contributing to homogeneous consistency and heterogeneous communication. The target tracking of UAVs is converted into a constraint optimization problem involving tracking cost, and the target enclosing of UGVs is modeled as formation control.

Findings
The energy estimation pigeon-inspired optimization is developed to generate control inputs for UAVs. And the controller combined with switchable topology is proposed, where the switching rule is flexible in dealing with some emergencies.

Practical implications
The proposed structure and algorithms can be easily applied to practice and help design the UAV/UGV control system.

Originality/value
The energy estimation mechanism is proposed for the target tracking of UAVs, and the rules of switching topologies ensure the target enclosing process of UGVs.
Gender differences of color preferences for interior spaces in the residential built environment in Prishtina, Kosovo
Authors: Hoxha Visar , Metin Hasan , Hasani Islam , Pallaska Elvida , Hoxha Jehona , Hoxha Dhurata 
Published: December 2022

PurposeThe overall purpose of the study is to identify the gender differences in color preferences for different types of interior space in the residential built environment in Prishtina, Kosovo. Additionally, the purpose of the study is also to identify the gender differences in the emotions that various colors trigger in occupants of the mainly residential built environment.Design/methodology/approachThe present study uses a quantitative study andχ2test to analyze whether the variables formulated by study hypotheses are dependent on gender. The data are gathered by a questionnaire to measure the color preferences of the respondents. The study uses a questionnaire with eight questions that were distributed to 303 respondents using the stratified probability sampling, using gender as the main stratum for probability sampling.FindingsThe study finds that there are no gender differences in color preferences for home lighting, living room, bedroom, study room and children’s rooms in the residential built environment. The study also finds that there is a gender difference in color preferences that trigger emotions of tranquility, stability and security and warmth and pleasure in both male and female respondents.Practical implicationsThe implications of this study are that real estate and facility management firms must conduct marketing research to identify the color preferences for both housing interior and exterior depending on the different local cultural backgrounds of clients. Firms must provide training for real estate agents on the color preferences of clients for various types of spaces and the differences that may exist based on gender but also other variables.Originality/valueThe present study is the first quantification of gender differences in color preferences of the residential built environment in the capital city of an understudied region such as Kosovo.
Integrability features of a new (3+1)-dimensional nonlinear Hirota bilinear model: multiple soliton solutions and a class of lump solutions
Authors: Wazwaz Abdul-Majid , El-Sherif Lamiaa , El-Tantawy Samir 
Published: December 2022

Purpose
This paper aims to propose a new (3+1)-dimensional integrable Hirota bilinear equation characterized by five linear partial derivatives and three nonlinear partial derivatives.

Design/methodology/approach
The authors formally use the simplified Hirota's method and lump schemes for determining multiple soliton solutions and lump solutions, which are rationally localized in all directions in space.

Findings
The Painlevé analysis shows that the compatibility condition for integrability does not die away at the highest resonance level, but integrability characteristics is justified through the Lax sense.

Research limitations/implications
Multiple-soliton solutions are explored using the Hirota's bilinear method. The authors also furnish a class of lump solutions using distinct values of the parameters via the positive quadratic function method.

Practical implications
The authors also retrieve a bunch of other solutions of distinct structures such as solitonic, periodic solutions and ratio of trigonometric functions solutions.

Social implications
This work formally furnishes algorithms for extending integrable equations and for the determination of lump solutions.

Originality/value
To the best of the authors’ knowledge, this paper introduces an original work with newly developed Lax-integrable equation and shows new useful findings.