bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Heterochromatin protein 1 is a master regulator in RNA splicing precision deficient in ulcerative colitis
Authors: Mata-Garrido Jorge , Xiang Yao , Chang-Marchand Yunhua , Reisacher Caroline , Ageron-ardila Elisabeth , Guerrera Chiara , Casafont Inigo , Bruneau Aurelia , Cherbuy Claire , Treton Xavier , Dumay Anne , Ogier-Denis Eric , Batsche Eric , Costallat Mickael , Revêchon Gwladys , Eriksson Maria , Muchardt Christian , Arbibe Laurence 
Published: December 2020

AbstractDefects in RNA splicing have been linked to numerous human disorders, but remain poorly explored in inflammatory bowel disease (IBD). Here, we report that, in the gut epithelium of patients with ulcerative colitis (UC), the expression of the chromatin and alternative splicing regulator HP1γ is strongly reduced. Accordingly, inactivation of the HP1γ gene in the mouse gut triggered several IBD-like traits, including inflammation and dysbiosis. In parallel, we discovered that its loss of function broadly increased splicing noise, reducing requirement for canonical splicing consensus sequences, and favoring the usage of cryptic splice sites at numerous genes with key functions in gut biology. This notably resulted in the production of progerin, a noncanonical toxic splice variant of prelamin A mRNA, responsible for the Hutchinson Gilford Progeria Syndrome (HGPS) of premature aging. Likewise, production of progerin transcript was found to be a signature of colonic cells from UC patients. Thus, our study identifies HP1γ as a regulator of RNA metabolismin vivo, providing a unique mechanism linking anti-inflammation and accuracy of RNA splicing in the gut epithelium. HP1 defect may confer a general disturbance in RNA splicing precision to scrutinize in IBD and more generally in accelerating aging diseases.
Structural basis of meiotic chromosome synaptic elongation through hierarchical fibrous assembly of SYCE2-TEX12
Authors: Dunce James M. , Salmon Lucy J. , Davies Owen R. 
Published: December 2020

AbstractThe synaptonemal complex (SC) is a supramolecular protein assembly that mediates synapsis between homologous chromosomes during meiosis. SC elongation along the chromosome length (up to 24 μm) depends on its midline α-fibrous component SYCE2-TEX12. Here, we report X-ray crystal structures of SYCE2-TEX12 as an individual building-block and upon assembly within a fibrous lattice. We combine these structures with mutagenesis, biophysics and electron microscopy to reveal the hierarchical mechanism of SYCE2-TEX12 fibre assembly. SYCE2-TEX12’s building-blocks are 2:2 coiled-coils which dimerise into 4:4 hetero-oligomers and interact end-to-end and laterally to form 10-nm fibres, which intertwine within 40-nm bundled micrometre-long fibres that define the SC’s midline structure. This assembly mechanism bears striking resemblance with intermediate filament proteins vimentin, lamin and keratin. Thus, SYCE2-TEX12 exhibits behaviour typical of cytoskeletal proteins to provide an α-fibrous SC backbone that structurally underpins synaptic elongation along meiotic chromosomes.
Glycolysis downregulation is a hallmark of HIV-1 latency and sensitizes infected cells to oxidative stress
Authors: Shytaj Iart Luca , Procopio Francesco Andrea , Tarek Mohammad , Carlon-Andres Irene , Tang Hsin-Yao , Goldman Aaron R. , Munshi MohamedHusen , Forcato Mattia , Leskov Konstantin , Ye Fengchun , Lucic Bojana , Cruz Nicolly , Singh Amit , Bicciato Silvio , Padilla-Parra Sergi , Lusic Marina , Diaz Ricardo Sobhie , Alvarez-Carbonell David , Savarino Andrea 
Published: December 2020

AbstractHIV-1 infects lymphoid and myeloid cells, which can harbor a latent proviral reservoir responsible for maintaining lifelong infection. Glycolytic metabolism has been identified as a determinant of susceptibility to HIV-1 infection, but its role in the development and maintenance of HIV-1 latency has not been elucidated. By combining transcriptomic, proteomic and metabolomic analysis, we here show that transition to latent HIV-1 infection downregulates glycolysis, while viral reactivation by conventional stimuli reverts this effect. Decreased glycolytic output in latently infected cells is associated with downregulation of NAD+/NADH. Consequently, infected cells rely on the parallel pentose phosphate pathway and its main product, the antioxidant NADPH, fueling antioxidant pathways maintaining HIV-1 latency. Of note, blocking NADPH downstream effectors, thioredoxin and glutathione, favors HIV-1 reactivation from latency in lymphoid and myeloid cellular models. This provides a “shock and kill effect” decreasing proviral DNA in cells from people-living-with-HIV/AIDS. Overall, our data show that downmodulation of glycolysis is a metabolic signature of HIV-1 latency that can be exploited to target latently infected cells with eradication strategies.
Molecular Noise-Filtering in theβ-adrenergic Signaling Network by Phospholamban Pentamers
Authors: Koch Daniel , Alexandrovich Alexander , Funk Florian , Schmitt Joachim P. , Gautel Mathias 
Published: December 2020

AbstractPhospholamban (PLN) is an important regulator of calcium handling in cardiomyocytes due to its ability to inhibit the sarco(endo)plasmic reticulum calcium-ATPase (SERCA)β-adrenergic stimulation reverses SERCA inhibition via PLN phosphorylation and facilitates fast calcium reuptake PLN also forms pentamers whose physiological significance has remained elusive Using biochemical experiments and mathematical modeling, we show that pentamers regulate both the dynamics and steady-state levels of monomer phosphorylation Substrate competition by pentamers and a feed-forward loop involving inhibitor-can delay monomer phosphorylation by protein kinase A (PKA) Steady-state phosphorylation of PLN is predicted to be bistable due to cooperative dephosphorylation of pentamers Both effects act as complementary noise-filters which can reduce the effect of random fluctuations in PKA activity Pentamers thereby ensure consistent monomer phosphorylation and SERCA activity in spite of noisy upstream signals Preliminary analyses suggest that the PLN mutation R del could impair noise-filtering, offering a new perspective on how this mutation causes cardiac arrhythmias.
Computational quantification of global effects induced by mutations and drugs in signaling networks of colorectal cancer cells
Authors: Sommariva Sara , Caviglia Giacomo , Ravera Silvia , Frassoni Francesco , Benvenuto Federico , Tortolina Lorenzo , Castagnino Nicoletta , Parodi Silvio , Piana Michele 
Published: December 2020

SummaryColorectal cancer (CRC) is one of the most deadly and commonly diagnosed tumors worldwide. Several genes are involved in its development and progression. The most frequent mutations concern APC, KRAS, SMAD4, and TP53 genes, suggesting that CRC relies on the alteration of different pathways. However, with classic molecular approaches, it is not easy to simultaneously analyze the interconnections between these pathways. For this reason, we propose a computational model based on a huge chemical reaction network to simulate the effects induced on the global signaling associated with CRC by single or multiple concurrent mutations or by drug treatment. This approach displays several advantages. The model can quantify the alteration in the concentration of the proteins connected with the examined mutation. Moreover, working on the global signaling of CRC, it is possible to disclose unexpected interactions between the involved pathways, representing new therapeutic targets.HighlightsColorectal cancer relates to defects in many different pathways within cell signalingCell signaling is modeled as a chemical ration network with 10 interacting pathwaysGlobal effects induced by single or multiple concurrent mutations are quantifiedA possible extension of the model to account for a targeted drug is discussed
Association ofIRS1(Gly972Arg) andIRS2(Gly1057Asp) genes polymorphisms with OSA and NAFLD in Asian Indians
Authors: Bhatt Surya Prakash , Randeep Guleria DM 
Published: December 2020

AbstractAim and ObjectiveThe aim of the study was to investigate the relationships between insulin receptor substrate (IRS) 1 (Gly972Arg) andIRS2(Gly1057Asp) genes with obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in Asian Indians.MethodA total of 410 overweight/obese subjects (130 with OSA with NAFLD, 100 with OSA without NAFLD, 95 without OSA and with NAFLD and 85 without OSA and without NAFLD) were recruited. Degree of NAFLD was based on liver ultrasound and of OSA on overnight polysomnography.ResultInIRS1gene, the genotype frequency (%) of Arg/Arg was significantly higher in NAFLD and OSA subjects. In addition, Gly/Arg genotype ofIRS1gene was associated with significantly higher body mass index, fat mass, %body fat, triglycerides, cholesterol, alkaline phosphate, aspartate transaminase, fasting insulin and HOMA-IR levels in OSA and NAFLD subjects. No significant difference in genotype frequencies ofIRS2was observed between four groups. Further we found that subjects carryingIRS1Gly/Arg (OR 4.49, 95% C.I. 1.06-12.52, p=0.002) genotype possess a much higher risk of OSA and NAFLD compared toIRS2Gly/Asp (OR 1.01, 95% C.I. 0.8-2.56, p=0.05).ConclusionWe concluded that Asian Indian subject carrying the allele Gly972Arg polymorphism ofIRS1is predisposed to develop OSA and NAFLD.
Complete mitochondrial genome sequence of Bos frontalis (Gayal) from Bangladesh
Authors: Deb GK , Khatun R , Hossain SMJ , Rahman SS , Bhuiyan MAB , Mobassirin S , Afrin S , Billah M , Baten A , Sarker NR , Bhuyian MSA , Siddiki AMAMZ 
Published: December 2020

AbstractThe Gayal is a large-sized endangered semi-domesticated bovine species belonging to the family Bovidae, tribe Bovini, group Bovina, genus Bos, and species Bos frontalis. It is also called the Mithan or Mithun. Mitochondrial genome is considered as an important tool for species identification and monitoring the populations of conservation concern and therefore it becomes an obligation to sequence the mitochondrial genome of Bagladeshi gayal. We want to identify some important genes related to a particular trait such as those associated with adaptation, muscle strength, or prolificacy. The data will help explore evolutionary relationships with closely related species. The mitogenome ofBos frontalisis 16,347 bp in length and nucleotide composition is AT-based (60.21%), contains 37 genes including 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control region.
Exploring Fayol's management process in a traditional Mayan dance (Pochó Dance): an ethnographic study
Authors: Suarez-Barraza Manuel F. , Miguel Davila Jose Angel 
Published: December 2020

PurposeWell into the 21st century, it is difficult to deny the contribution that Mayan culture has made to the history of the world, and not only because of its contribution to universal culture with its architecture, astronomy and mathematics. Understanding the management practices of a Mayan dance (the dance of the Pochó) that has transcended over the years can give us an idea of the management practices carried out by an ancestral culture such as the Maya. The purpose of this article is to establish an initial conceptual relationship between the management process proposed by Henry Fayol (1916) and the management of a Mayan dance that has survived to the present day.Design/methodology/approachA specific ethnographic study was carried out in the municipality of Tenosique, Tabasco (Mexico) for two consecutive years. Research methods such as direct observation, researcher diaries, in-depth interviews and photographs were utilized that allowed a study of management practices.FindingsThanks to the cross-checking of the data obtained, it was possible to determine a theoretical-conceptual relationship between Fayol's management process and the Mayan dance studied. In fact, 12 specific management practices found in the four phases of the process were identified. In addition, with the ethnographic study it was possible to determine the levels of intensity and impact regarding the satisfaction of those attending and performing the dance.Research limitations/implicationsResearch limitations are due to result from the fact that the analysis corresponds to a single Mayan dance in a specific place (Tenosique) in the state of Tabasco, Mexico.Practical implicationsTo understand the management practices of the Mayan culture through the study of a dance that has remained alive until our days; this might be useful for the management practices of today's companies.Originality/valueIt is a pioneering study that analyzes a Mayan dance through the optics of management sciences.
The informal city and the future of our cities: towards a manifesto
Authors: Mostafa Magda 
Published: December 2020

PurposeThe New Urban Agenda has catalyzed discussion across academia and practice on how to responsibly position ourselves as key players in the making of the future of our cities. With questions such as what is the right to the city? Who has those rights? What is a city? What is formal and who defines informal? These questions may prompt a need for departure from, or at least a reconsideration of the narrative surrounding formal and informal urbanism. This paper presents a pedagogical approach to addressing these and other questions within the framework of the new agenda. It reviews pedagogical approaches to understanding and learning to design within an informal context. It also foregrounds the process with the theoretical framing of Christopher Alexander's Pattern Language and Timeless way of Building as lenses through which to understand and identify common languages and intersections across the global spectrum of representations of informal urbanism. It then outlines the resultant process and products of a one-week intensive master-class and design charette of international scholars and students focusing on the Informal City.Design/methodology/approachIt reviews pedagogical approaches to understanding and learning to design within an informal context. It also foregrounds the process with the theoretical framing of Christopher Alexander's Pattern Language and Timeless way of Building as lenses through which to understand and identify common languages and intersections across the global spectrum of representations of informal urbanism. It then outlines the resultant process and products of a one-week intensive master-class and design charette of international scholars and students focusing on the Informal City.FindingsThe paper conclusively presents new nomenclature for informality that strives to shift the semantic lens from its current negative connotations to more productive, proactive and positive ones. It also presents an Informal City Manifesto, a call to arms of theoretical framing of how we think about the formal informal divide.Research limitations/implicationsThe paper, in part, outlines the results of a single studio with a small student number. Although diverse in its composition the student body is small.Originality/valueThis new framing could potentially allow us to best leverage lessons and mitigate challenges of the informal city condition, as our human settlements continue to urbanize.
Impact of COVID-19 on undergraduate business students: a longitudinal study on academic motivation, engagement and attachment to university
Authors: Pasion Rita , Dias-Oliveira Eva , Camacho Ana , Morais Catarina , Campos Franco Raquel 
Published: December 2020

Purpose
This study aims to explore whether the COVID-19-related circumstances hindered these academic-related variables.

Design Methodology Approach
The authors surveyed two groups of undergraduate business students (42% male) who completed the questionnaires at the beginning and at the end of the semester. One group of students attended only face-to-face classes in the 2018/2019 academic year (n = 126) and the other group transitioned to online classes because of the COVID-19 outbreak in the 2019/2020 academic year (n = 99).

Findings
The findings show no statistically significant group differences between the pre- and post-test in students’ intrinsic and extrinsic motivation, feelings of attachment to the university and engagement dimensions of absorption and vigour. Nevertheless, a moderate negative effect was found in the dedication engagement dimension.

Practical Implications
The authors discuss the main results in terms of some practices that may contribute towards attenuating the effects of future emerging pandemics in the higher education setting.

Originality Value
The COVID-19 pandemic imposed a rapid transition to online instruction in education institutions worldwide. However, it remains unclear to date how students’ engagement, motivation and attachment to the university were negatively affected by the first COVID-19 outbreak.
How trust was maintained in Scandinavia through the first crisis of modernity
Authors: Dahlen Øystein Pedersen , Skirbekk Helge 
Published: December 2020

PurposeThe aim of this article is to explain why there is a higher degree of trust in some countries compared to others – and which are the main historical factors that explain these differences. The main focus is on how governments relate to and communicate with its citizens in the times of crises.Design/methodology/approachThe analysis is based on comparative historical sociology with a modernity perspective with a special focus on Norway and Scandinavia. The authors do a parallel demonstration of history to confirm and expand the theories that could explain the high level of trust in these countries. The authors also bring in the Spanish experience in order to testify how governmental reactions affected the different levels of trust.FindingsScandinavian governments allowed open communication between different social classes on difficult and important issues, in contrast to Spain in the same period. These two factors therefore expand the understanding of the development of trust: (1) The establishment of the nation state as the organising concept and all-encompassing container of the other institutions (democracy, parliamentarism, trade unions, etc.); (2) The open hand strategy in dealing with deviant opinions, based on democratic compromises and a policing of consent ideology.Originality/valueThe article combines the understanding of the first crisis of modernity and the development of trust and contain a comparative analysis of the development of trust in four different countries. The investigation thus clarifies the correlation between specific historical factors and the levels of trust.
Image reconstruction by solving the inverse problem in ultrasonic transmission tomography system
Authors: Rymarczyk Tomasz , Kania Konrad , Gołąbek Michał , Sikora Jan , Maj Michał , Adamkiewicz Przemysław 
Published: December 2020

PurposeThe purpose of this study is to develop a reconstruction and measurement system for data analysis using ultrasonic transmission tomography. The problem of reconstruction from the projection is encountered in practical implementation, which consists in reconstructing an image that is an estimation of an unknown object from a finite set of projection data. Reconstructive algorithms used in transmission tomography are based on linear mathematical models, which makes it necessary to process non-linear data into estimates for a finite number of projections. The application of transformation methods requires building a mathematical model in which the projection data forming the known and unknown quantities are functions with arguments from a continuous set of real numbers, determining the function describing the unknown quantities sought in the form of inverse relation and adapting it to operate on discrete and noisy data. This was done by designing a tomographic device and proprietary algorithms capable of reconstructing two-dimensional images regardless of the size, shape, location or number of inclusions hidden in the examined object.Design/methodology/approachThe application consists of a device and measuring sensors, as well as proprietary algorithms for image reconstruction. Ultrasonic transmission tomography makes it possible to analyse processes occurring in an object without interfering with the examined object. The proposed solution uses algorithms based on ray integration, the Fermat principle and deterministic methods. Two applications were developed, one based on C and implemented on the embedded device, while the other application was made in Matlab.FindingsResearch shows that ultrasonic transmission tomography provides an effective analysis of tested objects in closed tanks.Research limitations/implicationsIn the presented technique, the use of ultrasonic absorption wave has been limited. Nevertheless, the effectiveness of such a solution has been confirmed.Practical implicationsThe presented solution can be used for research and monitoring of technological processes.Originality/valueAuthor’s tomographic system consisting of a measuring system and image reconstruction algorithms.
Development of mathematical model and circuit emulators for four lobe memristive behaviour
Authors: Bhardwaj Kapil , Srivastava Mayank 
Published: December 2020

Purpose
This paper aims to develop a mathematical model for four-lobe memristor (FLM) element. The four-lobe memristive behaviour can be used in realization of hyperchaotic oscillators and implementation of multi-bit memories. For verification of the developed mathematical framework, two FLM circuit emulators have been presented using VDCC and IC LM13700, respectively.

Design/methodology/approach
A mathematical model for FLM has been developed in which, the condition for the existence of symmetrical four lobes, instances and coordinates of the end points of lobes has been derived and presented. Using this mathematical framework, a FLM emulator based on VDCC has been developed. To validate the possibility of practical implementation of FLM concept, an IC LM13700-based circuit has also been developed. The workability of VDCC based circuit has been verified by running simulations in PSPICE environment using CMOS VDCC model. Similarly, the behaviour of LM13700 IC-based circuit has been confirmed by SPICE model of LM13700 IC.

Findings
It has been shown mathematically that under certain conditions, third-order flux dependent equation of memductance can be used to generate four lobes on the transient v-i plane. Also, two FLM emulators without using any voltage multiplier circuit/IC have been reported.

Originality/value
From the best knowledge of the authors, there are no such FLM emulators that have been reported in literature so far, which operates at practical operating frequencies.