bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling variable-number tandem repeat variation across populations using repeat-pangenome graphs
Authors: Lu Tsung-Yu ,   The Human Genome Structural Variation Consortium, Chaisson Mark 
Published: August 2020

AbstractVariable number tandem repeat sequences (VNTR) are composed of consecutive repeats of short segments of DNA with hypervariable repeat count and composition. They include protein coding sequences and associations with clinical disorders. It has been difficult to incorporate VNTR analysis in disease studies that use short-read sequencing because the traditional approach of mapping to the human reference is less effective for repetitive and divergent sequences. We solve VNTR mapping for short reads with a repeat-pangenome graph (RPGG), a data structure that encodes both the population diversity and repeat structure of VNTR loci from multiple haplotype-resolved assemblies. We developed software to build a RPGG, and use the RPGG to estimate VNTR composition with short reads. We used this to discover VNTRs with length stratified by continental population, and novel expression quantitative trait loci, indicating that RPGG analysis of VNTRs will be critical for future studies of diversity and disease.
The RNA-binding protein Puf5 buffers mRNA levels against chromatin-mediated changes in nascent transcription
Authors: Kochan David Z. , Mawer Julia S. P. , Tishinov Kiril , Parekh Swati , Massen Jennifer , Graef Martin , Spang Anne , Tessarz Peter 
Published: August 2020

ABSTRACTGene expression is a dynamic process regulated at all stages, starting with opening of chromatin, transcription, and continuing with mRNA export, translation and, finally, degradation. While there are feedback mechanisms within the system, it is not clear whether these extend to crosstalk between chromatin architecture and mRNA decay. Here, we show that changes in nascent transcription, mediated by mutating H3K56 to alanine, are post-transcriptionally buffered by the Pumilio protein Puf5, which stabilizes transcripts in a context-dependent manner. Depleting Puf5 in an H3K56A background leads to synthetic lethality. This genetic interaction can be explained by a decrease in translation due to downregulation of its direct mRNA targets, largely consisting of ribosomal protein genes. Importantly, we show that this post-transcriptional buffering is not only linked to H3K56A, but may be a more widespread phenomenon that also buffers against an increase in nascent RNA transcription in order to maintain physiological mRNA levels and cellular homeostasis.
Identifying potential hosts of short-branch Microsporidia
Authors: Doliwa Annemie , Dunthorn Micah , Rassoshanska Erika , Mahé Frédéric , Bass David , Ritter Camila Duarte 
Published: August 2020

AbstractMicrosporidia are obligate parasites that are closely related to Fungi. While the widely-known “long-branch” Microsporidia infect mostly animals, the hosts of “short-branch” Microsporidia are only partially characterized or not known at all. Here, we used network analyses from Neotropical rainforest soil metabarcoding data, to infer co-occurrences between environmental lineages of short-branch microsporidians and their potential hosts. We found significant co-occurrences with several taxa, especially with Apicomplexa, Cercozoa, Fungi, as well as some Metazoa. Our results are the first step to identify potential hosts of the environmental lineages of short-branch microsporidians, which can be targeted in future molecular and microscopic studies.
Bacterial Vipp1 and PspA are members of the ancient ESCRT-III membrane-remodelling superfamily
Authors: Liu Jiwei , Tassinari Matteo , Souza Diorge P , Naskar Souvik , Noel Jeffrey K. , Bohuszewicz Olga , Buck Martin , Williams Tom A. , Baum Buzz , Low Harry H 
Published: August 2020

AbstractMembrane remodelling and repair are essential for all cells. Proteins that perform these functions include Vipp1/IM30 in photosynthetic plastids, PspA in bacteria, CdvB in TACK archaea and ESCRT-III in eukaryotes. Here, we show that these protein families are homologous and share a common evolutionary origin. Using cryo-electron microscopy we present structures for Vipp1 rings over a range of symmetries. Each ring is built from rungs that stack and spontaneously self-organise to form domes. Rungs are assembled from a polymer that is strikingly similar in structure to ESCRT-III. A tilt between rungs generates the dome-shaped curvature with constricted open ends and an inner membrane-binding lumen. Overall, our results reveal conserved mechanistic principles that underlie Vipp1, PspA and ESCRT-III dependent membrane remodelling across all domains of life.One sentence summaryEvolutionary and structural analyses of Vipp1/IM30 rings reveal ESCRT-III-like polymers that remodel membranes in bacteria.
Assessment of Neurovascular Coupling & Cortical Spreading Depression in Mixed Models of Atherosclerosis & Alzheimer’s Disease
Authors: Shabir Osman , Pendry Ben , Lee Llywelyn , Eyre Beth , Sharp Paul , Rebollar Monica A , Howarth Clare , Heath Paul R , Wharton Stephen B , Francis Sheila E , Berwick Jason 
Published: August 2020

AbstractNeurovascular coupling is a critical brain mechanism whereby changes to blood flow accompany localised neural activity. The breakdown of neurovascular coupling is linked to the development and progression of several neurological conditions including dementia. In this study, we examined cortical haemodynamics in preparations that modelled Alzheimer’s disease (J20-AD) and atherosclerosis (PCSK9-ATH) between 9-12m of age. We report novel findings with atherosclerosis where neurovascular decline is characterised by significantly reduced blood volume, levels of oxyhaemoglobin & deoxyhaemoglobin, in addition to global neuroinflammation. In the comorbid mixed model (J20-PCSK9-MIX), we report a 3x fold increase in hippocampal amyloid-beta plaques. A key finding was that cortical spreading depression (CSD) due to electrode insertion into the brain was worse in the diseased animals and led to a prolonged period of hypoxia. These findings suggest that systemic atherosclerosis can be detrimental to neurovascular health and that having cardiovascular comorbidities can exacerbate pre-existing Alzheimer’s-related amyloid-plaques.
iModulonDB: a knowledgebase of microbial transcriptional regulation derived from machine learning
Authors: Rychel Kevin , Decker Katherine , Sastry Anand V , Phaneuf Patrick V , Poudel Saugat , Palsson Bernhard O 
Published: August 2020

ABSTRACTIndependent component analysis (ICA) of bacterial transcriptomes has emerged as a powerful tool for obtaining co-regulated, independently-modulated gene sets (iModulons), inferring their activities across a range of conditions, and enabling their association to known genetic regulators. By grouping and analyzing genes based on observations from big data alone, iModulons can provide a novel perspective into how the composition of the transcriptome adapts to environmental conditions. Here, we present iModulonDB (imodulondb.org), a knowledgebase of prokaryotic transcriptional regulation computed from high-quality transcriptomic datasets using ICA. Users select an organism from the home page and then search or browse the curated iModulons that make up its transcriptome. Each iModulon and gene has its own interactive dashboard, featuring plots and tables with clickable, hoverable, and downloadable features. This site enhances research by presenting scientists of all backgrounds with co-expressed gene sets and their activity levels, which lead to improved understanding of regulator-gene relationships, discovery of transcription factors, and the elucidation of unexpected relationships between conditions and genetic regulatory activity. The current release of iModulonDB covers three organisms (E. coli, S. aureus, andB. subtilis) with 204 iModulons, and can be expanded to cover many additional organisms.
Structural and biochemical mechanisms of NLRP1 inhibition by DPP9
Authors: Huang Menghang , Zhang Xiaoxiao , Ann Toh Gee , Gong Qin , Wang Jia , Han Zhifu , Wu Bin , Zhong Franklin , Chai Jijie 
Published: August 2020

AbstractThe nucleotide-binding domain (NBD) and leucine-rich repeat (LRR)-containing receptors (NLRs) mediate innate immunity by forming inflammasomes. Activation of the NLR protein NLRP1 requires auto-cleavage within its FIIND domain1–7. In resting cells, the dipeptidyl peptidase DPP9 interacts with NLRP1-FIIND and together with a related enzyme DPP8, suppresses spontaneous NLRP1 activation8,9. The mechanisms of DPP8/9-mediated NLRP1 inhibition, however, remain elusive. Here we provide structural and biochemical evidence demonstrating that rat NLRP1 (rNLRP1) interacts with rDPP9 in a stepwise manner to form a 2:1 complex. An auto-inhibited rNLRP1 molecule first interacts with rDPP9 via its ZU5 domain. This 1:1 rNLRP1-rDPP9 complex then captures the UPA domain of a second rNLRP1 molecule via a UPA-interacting site on DPP9 and dimeric UPA-UPA interactions with the first rNLRP1. The 2:1 rNLRP1-rDPP9 complex prevents NLRP1 UPA-mediated higher order oligomerization and maintains NLRP1 in the auto-inhibited state. Structure-guided biochemical and functional assays show that both NLRP1-binding and its enzymatic activity are required for DPP9 to suppress NLRP1, supporting guard-type activation of the NLR. Together, our data reveal the mechanism of DPP9-mediated inhibition of NLRP1 and shed light on activation of the NLRP1 inflammasome.
Changes in Cell Size and Shape During 50,000 Generations of Experimental Evolution withEscherichia coli
Authors: Grant Nkrumah A. , Magid Ali Abdel , Franklin Joshua , Dufour Yann , Lenski Richard E. 
Published: August 2020

AbstractBacteria adopt a wide variety of sizes and shapes, with many species exhibiting stereotypical morphologies. How morphology changes, and over what timescales, is less clear. Previous work examining cell morphology in an experiment withEscherichia colishowed that populations evolved larger cells and, in some cases, cells that were less rod-like. That experiment has now run for over two more decades. Meanwhile, genome sequence data are available for these populations, and new computational methods enable high-throughput microscopic analyses. Here, we measured stationary-phase cell volumes for the ancestor and 12 populations at 2,000, 10,000, and 50,000 generations, including measurements during exponential growth at the last timepoint. We measured the distribution of cell volumes for each sample using a Coulter counter and microscopy, the latter of which also provided data on cell shape. Our data confirm the trend toward larger cells, while also revealing substantial variation in size and shape across replicate populations. Most populations first evolved wider cells, but later reverted to the ancestral length-to-width ratio. All but one population evolved mutations in rod-shape maintenance genes. We also observed many ghost-like cells in the only population that evolved the novel ability to grow on citrate, supporting the hypothesis that this lineage struggles with maintaining balanced growth. Lastly, we show that cell size and fitness remain correlated across 50,000 generations. Our results suggest larger cells are beneficial in the experimental environment, while the reversion toward ancestral length-to-width ratios suggests partial compensation for the less favorable surface area-to-volume ratios of the evolved cells.ImportanceBacteria exhibit great morphological diversity, yet we have only a limited understanding of how their cell sizes and shapes evolve, and of how these features affect organismal fitness. This knowledge gap reflects, in part, the paucity of the fossil record for bacteria. Here, we revive and analyze samples extending over 50,000 generations from 12 populations of experimentally evolvingEscherichia colito investigate the relation between cell size, shape, and fitness. Using this “frozen fossil record” we show that all 12 populations evolved larger cells concomitant with increased fitness, with substantial heterogeneity in cell size and shape across the replicate lines. Our work demonstrates that cell morphology can readily evolve and diversify, even among populations living in identical environments.
Phase-field modeling of multicomponent and multiphase flows in microfluidic systems: a review
Authors: Santra Somnath , Mandal Shubhadeep , Chakraborty Suman 
Published: August 2020

Purpose
The purpose of this study is to perform a detailed review on the numerical modeling of multiphase and multicomponent flows in microfluidic system using phase-field method. The phase-field method is of emerging importance in numerical computation of transport phenomena involving multiple phases and/or components. This method is not only used to model interfacial phenomena typical to multiphase flows encountered in engineering and nature but also turns out to be a promising tool in modeling the dynamics of complex fluid-fluid interfaces encountered in physiological systems such as dynamics of vesicles and red blood cells). Intrinsically, a priori unknown topological evolution of interfaces offers to be the most concerning challenge toward accurate modeling of moving boundary problems. However, the numerical difficulties can be tackled simultaneously with numerical convenience and thermodynamic rigor in the paradigm of the phase field method.

Design/methodology/approach
The phase-field method replaces the macroscopically sharp interfaces separating the fluids by a diffuse transition layer where the interfacial forces are smoothly distributed. As against the moving mesh methods (Lagrangian) for the explicit tracking of interfaces, the phase-field method implicitly captures the same through the evolution of a phase-field function (Eulerian). In contrast to the deployment of an artificially smoothing function for the interface as used in the volume of a fluid or level set method, however, the phase-field method uses mixing free energy for describing the interface. This needs the consideration of an additional equation for an order parameter. The dynamic evolution of the system (equation for order parameter) can be described by Allen–Cahn or Cahn–Hilliard formulation, which couples with the Navier–Stokes equation with the aid of a forcing function that depends on the chemical potential and the gradient of the order parameter.

Findings
In this review, first, the authors discuss the broad motivation and the fundamental theoretical foundation associated with phase-field modeling from the perspective of computational microfluidics. They subsequently pinpoint the outstanding numerical challenges, including estimations of the model-free parameters. They outline some numerical examples, including electrohydrodynamic flows, to demonstrate the efficacy of the method. Finally, they pinpoint various emerging issues and futuristic perspectives connecting the phase-field method and computational microfluidics.

Originality/value
This paper gives unique perspectives to future directions of research on this topic.
Investigating risk of bridge construction project: exploring Suramadu strait-crossing cable-stayed bridge in Indonesia
Authors: Ongkowijoyo Citra S. , Gurmu Argaw , Andi Andi 
Published: August 2020

Purpose
The complexities in strait-crossing cable-stayed bridge project are increasing the risks. This study aims to identify and analyze the significant and worth-considered construction risks of the first, biggest and longest spanned strait-crossing bridge project in Indonesia.

Design/methodology/approach
As many as 32 risk events were identified and determined as the risks that exist and can be represented in the Suramadu bridge project context. Data was collected through a design-based questionnaire disseminated to experts involved in the project as well as semi-formal interviews. Several quantitative methods were applied to analyze the significant risks, such as relative importance index, Spearman’s rank correlation test and Mann–Whitney U test.

Findings
The analyses reveal that “unexpected natural behavior” confirmed by both contractor and consultant parties is the most significant and crucial risk event. Another risk event found to be significant is the “delayed payment.” On the other hand, it is also found that several risks within the legal category are found to be less significant compared to other major risk events.

Research limitations/implications
The results of the present research should be interpreted in the context of several limitations. Given these possible concerns regarding the generalizability of the findings, along with the relatively low rate of participants in the current research, additional studies are needed to provide a more complete picture of stakeholder perceptions who are involved directly in the construction environment as well as to identify more construction risks specifically in the large-scale bridge project.

Practical implications
This study has provided fundamental contributions to the body of knowledge and practical implication to promote and assist decision-makers toward developing a comprehensive risk assessment of a large-scale bridge project.

Originality/value
The analyses of outcomes and discussion, as well as the findings of this research, have shed light on the construction risks understanding, which contributes to delivering a theoretical framework for achieving large-scale bridge project success.
Psychosocial treatment for incarcerated methamphetamine users: the Philippines experience
Authors: Hechanova Ma. Regina M. , Reyes Jennel C. , Acosta Avegale C. , Tuliao Antover P. 
Published: August 2020

Purpose
The purpose of this study is to evaluate a psychosocial treatment program for prisoners incarcerated because of methamphetamine use. It compared the outcomes of prisoners who received the program while incarcerated, those who were released and received the treatment as part of community-based drug recovery program and a waitlist-control group (WC) with no treatment.

Design/methodology/approach
A quasi-experimental design was use with pre- and post-test surveys administered to three groups: a WC group, a pre-release treatment-while-incarcerated (TWI) group, and a post-release outpatient treatment group (OP). Surveys measured recovery skills, life skills and substance use disorder (SUD) symptoms were administered before and after the intervention.

Findings
Results revealed that at baseline OP and TWI had significant higher recovery skills compared to WC group. However, in terms of life skills, there was no significant difference observed among the WC, OP and TWI group at baseline. TWI had a significantly lower number of SUD symptoms compared to the WC group at baseline. As hypothesized, findings revealed significant changes in recovery and life skills among the OP and TWI group compared to the WC group. No significant change in SUD scores were observed for all groups.

Research limitations/implications
A major limitation of the study was the use of a quasi-experimental design because legal issues did not allow a randomized control trial. Future research using randomized controlled trial designs would provide more robust conclusions on the impact of the intervention. The study design was also limited to pre- and post-evaluation. Further studies are encouraged to look at longitudinal outcomes of appears on SUD symptoms and possibility of relapse.

Practical implications
Given that there were no significant differences in outcomes between OP and TWI groups, results suggest that the program may serve either as a pre- or post-release program for incarcerated drug users. However, results also suggest that completion is higher when the program is used as a pre-release program. Delivering the program prior to release also reduces challenges related to attrition including conflict in schedules and the lack of resources for transportation.

Social implications
The study suggests the value of psychosocial treatment as opposed to punitive approaches in dealing with drug use. In particular, delivering interventions prior to release can prepare participants for problems they may encounter during reintegration and prevent recidivism. In a country where drug-related killings are on the rise, the study presents an alternate and restorative justice approach.

Originality/value
The study addresses a dearth in the literature on psychosocial intervention for methamphetamine users. It also fills a vacuum in studies from developing countries such as the Philippines.
A failed success: the Barlinnie Special Unit
Authors: Wilson David , Brookes Michael 
Published: August 2020

Purpose
This paper aims to explore the reasons for and the subsequent longer-term impact of the closure of the Barlinnie Special Unit (BSU).

Design/methodology/approach
The paper is both descriptive, providing an overview of the work of the BSU, and conceptual in that it argues that the limits of “prisoner rehabilitation” are observed in the closure of the BSU, which sounds a warning for other penal therapeutic communities and what it means to operate effectively.

Findings
The BSU which assisted long-term, difficult and violent prisoners moderate their prison behaviour and then to live non-offending lives, lost the confidence of government ministers and officials, as well as senior prison managers and, seemingly, the public, so closed after being in operation for 21 years. The impact of this has been that the Scottish Prison Service has not introduced, or attempted to introduce, a similar regime for managing and treating violent and disruptive prisoners.

Practical implications
There are important lessons to be learned from the BSU experience for all who manage and work in specialist, prison therapeutic units or within prison therapeutic regimes. This includes balancing the therapeutic elements of the regime, which may involve engaging in practices which are outside the norm for custodial establishments, with those establishments’ security and operational requirements, so as to not to create a disconnect between addressing offending behaviour and maintaining expected standards of wider prison conduct.

Originality/value
While there have been previous evaluations of the BSU, the longer-term impact has neither been previously considered and nor has the unit’s closure been considered from a penal philosophical perspective.
The COVID-19 pandemic and the growing need to train engineers aligned to the sustainable development goals
Authors: Anholon Rosley , Rampasso Izabela Simon , Silva Diogo A.L. , Leal Filho Walter , Quelhas Osvaldo Luiz Gonçalves 
Published: August 2020

PurposeConsidering the requirements of sustainable development regarding professionals training and the challenges evidenced during Coronavirus disease (COVID-19) pandemic, this study aims to contribute to the debates regarding the need to insert sustainability into engineering education in the current context.Design/methodology/approachFor this, the literature about sustainability in engineering education was considered, and the need for sustainability insertion in the context of the COVID-19 pandemic was debated. It is important to emphasize that this debate was based on the authors’ experience regarding sustainability research and teaching.FindingsThe current moment unveiled companies’ financial management problems, constantly evidenced by media. In this sense, the interest of engineering students in business management may lead them to believe that companies’ survival depends only on financial aspects, neglecting environmental and social aspects. This study is characterized as a reminder to academic staff in the field of engineering to continue valuing the principles of sustainable development with their students during the COVID-19 pandemic.Originality/valueThe need to make engineering students understand the importance of social projects in the current period is emphasized. The training of professionals to consider all the sustainability aspects even during crisis moments is evidenced now and should be used as a learning lesson for the future.