bluuebunny/crossref_metadata_2025 huggingface dataset:
Linker histone dH1K27 dimethylation marks Drosophila heterochromatin independently of H3K9 methylation
Authors: Bernués Jordi , Izquierdo-Boulstridge Andrea , Reina Oscar , Castejón Lucía , Fernández-Castañer Elena , Leal Núria , Guerrero-Pepinosa Nancy , Bonet-Costa Carles , Vujatovic Olivera , Azorín Fernando
Published: June 2021

Post-translational modifications (PTMs) of histones are important epigenetic determinants and specific core histones PTMs correlate with functional chromatin states. However, despite linker histone H1s are heavily post-translationally modified, little is known about the genomic distribution of H1s PTMs and their association with epigenetic chromatin states. Here, we address this question in Drosophila that encodes a single somatic linker histone, dH1. We previously reported that dH1 is dimethylated at K27 (dH1K27me2). Here, we show that dH1K27me2 is a major PTM of Drosophila heterochromatin. At mitosis, dH1K27me2 accumulates at pericentromeric heterochromatin, while, in interphase cells, it is also detected at intercalary heterochromatin. ChIPseq experiments show that dH1K27me2 enriched regions cluster at both the assembled and unassembled heterochromatin regions of all four Drosophila chromosomes. More than 98% of the dH1K27me2 enriched regions map to heterochromatic repetitive DNA elements, including transposable elements, simple DNA repeats and satellite DNAs. We also show that dH1K27me2 is independent of H3K9 methylation, as it is equally detected in flies carrying a H3K9R mutation. Moreover, dH1K27me2 is not affected by depletion of Su(var)3-9, HP1a and Su(var)4-20. Altogether these results suggest that dH1K27me2 is a novel epigenetic mark of Drosophila heterochromatin that acts upstream of the major Su(var)3-9/HP1a pathway of heterochromatin formation.
A binocular synaptic network supports interocular response alignment in visual cortical neurons
Authors: Scholl Benjamin , Tepohl Clara , Ryan Melissa A. , Thomas Connon I. , Kamasawa Naomi , Fitzpatrick David
Published: June 2021

In the visual system, signals from the two eyes are combined to form a coherent representation through the convergence of synaptic input populations onto individual cortical neurons. As individual synapses originate from either monocular (representing one eye) or binocular (representing both eyes) cortical networks, it has been unclear how these inputs are integrated coherently. Here, we imaged dendritic spines on layer 2/3 binocular cells in ferret visual cortex with in vivo two-photon microscopy to examine how monocular and binocular synaptic networks contribute to the interocular alignment of orientation tuning. We found that binocular synapses varied in degree of ‘congruency’, namely response correlation between left and right eye visual stimulation. Binocular congruent inputs were functionally distinct from binocular noncongruent and monocular inputs, exhibiting greater tuning selectivity and connection specificity. Using correlative light and electron microscopy, we found no difference in ultrastructural anatomy and instead, observed strength in numbers using a simple model simulating aggregate synaptic input. This model demonstrated a predominate contribution of binocular congruent inputs in sculpting somatic orientation preference and interocular response alignment. Our study suggests that, in layer 2/3 cortical neurons, a binocular network is responsible for forming a coherent representation in individual neurons through recurrent intracortical interactions.
Dynamic Phosphorylation of RGS Provides Spatial Regulation of MAP Kinase and Promotes Completion of Cytokinesis during the Yeast Pheromone Response
Authors: Simke William C. , Johnson Cory P. , Hart Andrew J. , Mayhue Sari , Craig P. Lucas , Sojka Savannah , Kelley Joshua B.
Published: June 2021

Yeast use a G-protein coupled receptor (GPCR) signaling pathway to detect mating pheromone, arrest in G1, and direct polarized growth towards the potential mating partner. The primary negative regulator of this pathway is the regulator of G-protein signaling (RGS), Sst2, which induces Gα GTPase activity and subsequent inactivation of all downstream signaling including a MAPK cascade. The MAPK Fus3 phosphorylates the RGS in response to pheromone, but the role of this modification is unknown. We set out to examine the role of RGS phosphorylation during the pheromone response. We found that RGS phosphorylation peaks early in the pheromone response and diminishes RGS localization to the polarity site and focuses MAPK complexes there. At later time points, RGS is predominantly unphosphorylated, which promotes RGS localization to the polar cap and broadens the distribution of MAPK complexes relative to the Cdc42 polarity machinery. Surprisingly, we found that phosphorylation of the RGS is required for the completion of cytokinesis prior to pheromone induced growth. The completion of cytokinesis in the presence of pheromone is promoted by the formin Bnr1 and the kelch-repeat protein, Kel1, both proteins previously found to interact with the RGS.
Detection of antibodies neutralizing historical and emerging SARS-CoV-2 strains using a thermodynamically coupled de novo biosensor system
Authors: Zhang Jason Z. , Yeh Hsien-Wei , Walls Alexandra C. , Wicky Basile I.M. , Sprouse Kaiti , VanBlargan Laura A. , Treger Rebecca , Quijano-Rubio Alfredo , Pham Minh N. , Kraft John C. , Haydon Ian C. , Yang Wei , DeWitt Michelle , Chow Cameron , Carter Lauren , Wener Mark H. , Stewart Lance , Veesler David , Diamond Michael S. , Baker David
Published: June 2021

With global vaccination efforts against SARS-CoV-2 underway, there is a need for rapid quantification methods for neutralizing antibodies elicited by vaccination and characterization of their strain dependence. Here, we describe a designed protein biosensor that enables sensitive and rapid detection of neutralizing antibodies against wild type and variant SARS-CoV-2 in serum samples. More generally, our thermodynamic coupling approach can better distinguish sample to sample differences in analyte binding affinity and abundance than traditional competition based assays.
Hierarchical control of microbial community assembly
Authors: Pontrelli Sammy , Szabo Rachel , Pollak Shaul , Schwartzman Julia , Ledezma-Tejeida Daniela , Cordero Otto X. , Sauer Uwe
Published: June 2021

Metabolic processes that fuel the growth of heterotrophic microbial communities are initiated by specialized biopolymer degraders that decompose complex forms of organic matter. It is unclear, however, to what extent degraders control the downstream assembly of the community that follows polymer breakdown. Investigating a model marine microbial community that degrades chitin, we show that chitinases secreted by different degraders produce oligomers of specific chain lengths that not only select for specialized consumers but also influence the metabolites secreted by these consumers into a shared resource pool. Each species participating in the breakdown cascade exhibits unique hierarchical preferences for substrates, which underlies the sequential colonization of metabolically distinct groups as resource availability changes over time. By identifying the metabolic underpinnings of microbial community assembly, we reveal a hierarchical crossfeeding structure that allows biopolymer degraders to shape the dynamics of community assembly.

One sentence summary

Specialized biopolymer degraders direct the trajectory of microbial community assembly through interconnected modes of nutrient crossfeeding.
A multiscale approach for computing gated ligand binding from molecular dynamics and Brownian dynamics simulations
Authors: Sadiq S. Kashif , Chicharro Abraham Muñiz , Friedrich Patrick , Wade Rebecca C.
Published: June 2021

We develop an approach to characterise the effects of gating by a multi-conformation protein consisting of macrostate conformations that are either accessible or inaccessible to ligand binding. We first construct a Markov state model of the apo-protein from atomistic molecular dynamics simulations from which we identify macrostates and their conformations, compute their relative macrostate populations and interchange kinetics, and structurally characterise them in terms of ligand accessibility. We insert the calculated first-order rate constants for conformational transitions into a multi-state gating theory from which we derive a gating factorγthat quantifies the degree of conformational gating. Applied to HIV-1 protease, our approach yields a kinetic network of three accessible (semi-open, open and wide-open) and two inaccessible (closed and a newly identified, ‘parted’) macrostate conformations. The ‘parted’ conformation sterically partitions the active site, suggesting a possible role in product release. We find that the binding kinetics of drugs and drug-like inhibitors to HIV-1 protease falls in the slow gating regime. However, becauseγ=0.75, conformational gating only modestly slows ligand binding. Brownian dynamics simulations of the diffusional association of eight inhibitors to the protease - that have a wide range of experimental association constants (~104- 1010M−1s−1) - yields gated rate constants in the range ~0.5-5.7 × 108M−1s−1. This indicates that, whereas the association rate of some inhibitors could be described by the model, for many inhibitors either subsequent conformational transitions or alternate binding mechanisms may be rate-limiting. For systems known to be modulated by conformational gating, the approach could be scaled computationally efficiently to screen association kinetics for a large number of ligands.

Graphical TOC Entry
Forward genetics combined with unsupervised classifications identified zebrafish mutants affecting biliary system formation
Authors: Singh Divya Jyoti , Tuscano Kathryn M. , Ortega Karen L. , Dimri Manali , Tae Kevin , Lee William , Muslim Muslim A. , Liu Jay L. , Pierce Lain X. , McClendon Allyson , Naegele Gregory , Gibson Isabel , Livesay Jodi , Sakaguchi Takuya F.
Published: June 2021

Impaired formation of the biliary network can lead to congenital cholestatic liver diseases; however, the genes responsible for proper biliary system formation and maintenance have not been fully identified. Combining computational network structure analysis algorithms with a zebrafish forward genetic screen, we identified 24 new zebrafish mutants that display impaired intrahepatic biliary network formation. Complementation tests suggested that these 24 mutants affect 24 different genes. We applied unsupervised clustering algorithms to classify the recovered mutants into three classes unbiasedly. Further computational analyses revealed that each of the recovered mutations in these three classes shows a unique effect on node subtype composition and connection property distribution of the intrahepatic biliary network. Besides, we found that most recovered mutations are viable. In those mutant fish, biliary network phenotypes persist into adulthood, which themselves are good animal models to study chronic cholestatic liver diseases. Altogether, this study provides unique genetic and computational toolsets that advance our understanding of the molecular pathways leading to biliary system malformation and cholestatic liver diseases.
Evidence for widespread alterations in cortical microstructure after 32 hours of sleep deprivation
Authors: Voldsbekk Irene , Bjørnerud Atle , Groote Inge , Zak Nathalia , Roelfs Daniel , Maximov Ivan I. , Geier Oliver , Due-Tønnessen Paulina , Bøen Erlend , Kuiper Yvonne S. , Løkken Lise-Linn , Strømstad Marie , Blakstvedt Taran Y. , Bjorvatn Bjørn , Malt Ulrik F. , Westlye Lars T. , Elvsåshagen Torbjørn , Grydeland Håkon
Published: June 2021

Cortical microstructure is influenced by circadian rhythm and sleep deprivation, yet the precise underpinnings of these effects remain unclear. The ratio between T1-weighted and T2-weighted magnetic resonance images (T1w/T2w ratio) has been linked to myelin levels and dendrite density and may offer novel insight into the intracortical microstructure of the sleep deprived brain. Here, we examined intracortical T1w/T2w ratio in 41 healthy young adults (26 women) before and after 32 hours of either sleep deprivation (n = 18) or a normal sleep-wake cycle (n = 23). Linear models revealed significant group differences in T1w/T2w ratio change after 32 hours in four clusters, including bilateral effects in the insular, cingulate, and superior temporal cortices, comprising regions involved in attentional, auditory and pain processing. Across clusters, the sleep deprived group showed an increased T1w/T2w ratio, while the normal sleep-wake group exhibited a reduced ratio. These changes were not explained by in-scanner head movement, and 95% of the effects across clusters remained significant after adjusting for cortical thickness and hydration. Compared with a normal sleep-wake cycle, 32 hours of sleep deprivation yields intracortical T1w/T2w ratio increases. While the intracortical changes detected by this study could reflect alterations in myelin or dendritic density, or both, histological analyses are needed to clarify the precise underlying cortical processes.
Distinct MUNC lncRNA structural domains regulate transcription of different promyogenic factors
Authors: Przanowska Roza K. , Weidmann Chase A. , Saha Shekhar , Cichewicz Magdalena A. , Jensen Kate N. , Przanowski Piotr , Irving Patrick S. , Guertin Michael J. , Weeks Kevin M. , Dutta Anindya
Published: June 2021

Many lncRNAs have been discovered using transcriptomic data, however, it is broadly unclear what fraction of lncRNAs are functional and what structural properties affect their phenotype. MUNC lncRNA, also known as DRReRNA, stimulates skeletal muscle differentiation. The prevailing hypothesis is that MUNC stimulates the Myod1 gene in cis as an enhancer RNA and stimulates expression of several other promyogenic genes in trans by recruiting the cohesin complex to their promoters. Experimental probing of the RNA structure revealed that MUNC contains multiple structural domains not detected by RNA structure prediction algorithms in the absence of experimental information. We discovered that these specific and structurally distinct domains are required for induction of different promyogenic genes, for binding at different genomic sites to regulate the expression of adjacent genes, and for binding the cohesin complex. Moreover, we found that induction of Myod1 or interaction with cohesin comprise only a subset of the broad regulatory impact of this lncRNA. Our study thus reveals unexpectedly complex, structure-driven functions for the MUNC lncRNA and emphasizes the importance of experimentally determined structures for understanding structure-function relationships in lncRNAs.
Point-of-care analyte quantification and digital readout via lysate-based cell-free biosensors interfaced with personal glucose monitors
Authors: Zhang Yan , Steppe Paige L. , Kazman Maxwell W. , Styczynski Mark P.
Published: June 2021

Field-deployable diagnostics based on cell-free systems have advanced greatly, but on-site quantification of target analytes remains a challenge. Here we demonstrate that Escherichia coli lysate-based cell-free biosensors coupled to a personal glucose monitor (PGM) can enable on-site analyte quantification, with the potential for straightforward reconfigurability to diverse types of analytes. We show that analyte-responsive regulators of transcription and translation can modulate production of the reporter enzyme β-galactosidase, which in turn converts lactose into glucose for PGM quantification. Because glycolysis is active in the lysate and would readily deplete converted glucose, we decoupled enzyme production and glucose conversion to increase endpoint signal output. This lysate metabolism did, however, allow for one-pot removal of glucose present in complex samples (like human serum) without confounding target quantification. Taken together, we show that integrating lysate-based cell-free biosensors with PGMs enables accessible target detection and quantification at the point of need.

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A method for three-dimensional single-cell chronic electrophysiology from developing brain organoids
Authors: Le Floch Paul , Li Qiang , Liu Ren , Tasnim Kazi , Zhao Siyuan , Lin Zuwan , Jiang Han , Liu Jia
Published: June 2021

Human induced pluripotent stem cell-derived brain organoids have shown great potential for studies of human brain development and neurological disorders. However, quantifying the evolution and development of electrical functions in brain organoids is currently limited by measurement techniques that cannot provide long-term stable three-dimensional (3D) bioelectrical interfaces with brain organoids during development. Here, we report a cyborg brain organoid platform, in which 2D progenitor or stem cell sheets can fold “tissue-like” stretchable mesh nanoelectronics through organogenesis, distributing stretchable electrode arrays across 3D organoids. The tissue-wide integrated stretchable electrode arrays show no interruption to neuronal differentiation, adapt to the volume and morphological changes during organogenesis, and provide long-term stable electrical contacts with neurons within brain organoids during development. The seamless and non-invasive coupling of electrodes to neurons enables a 6-month continuous recording of the same brain organoids and captures the emergence of single-cell action potentials from early-stage brain organoid development.
metaMIC: reference-free Misassembly Identification and Correction of de novo metagenomic assemblies
Authors: Lai Senying , Pan Shaojun , Coelho Luis Pedro , Chen Wei-Hua , Zhao Xing-Ming
Published: June 2021

Evaluating the quality of metagenomic assemblies is important for constructing reliable metagenome-assembled genomes and downstream analyses. Here, we present metaMIC (https://github.com/ZhaoXM-Lab/metaMIC), a machine-learning based tool for identifying and correcting misassemblies in metagenomic assemblies. Benchmarking results on both simulated and real datasets demonstrate that metaMIC outperforms existing tools when identifying misassembled contigs. Furthermore, metaMIC is able to localize the misassembly breakpoints, and the correction of misassemblies by splitting at misassembly breakpoints can improve downstream scaffolding and binning results.
Hypothalamic effective connectivity at rest is associated with body weight and energy homeostasis
Authors: Voigt Katharina , Andrews Zane B. , Harding Ian H. , Razi Adeel , Verdejo-Garcia Antonio
Published: June 2021

Hunger and satiety states drive eating behaviours via changes in brain function. The hypothalamus is a central component of the brain networks that regulate food intake. Animal research parsed the roles of the lateral hypothalamus (LH) and the medial hypothalamus (MH) in hunger and satiety respectively. Here, we examined how hunger and satiety change information flow between human LH and MH brain networks, and how these interactions are influenced by body mass index. Forty participants (15 overweight/obese) underwent two resting-state functional MRI scans: after overnight fasting (fasted state) and following a standardised meal (sated state). The direction and valence (excitatory/inhibitory influence) of information flow between the MH and LH was modelled using spectral dynamic causal modelling. Our results revealed two core networks interacting across homeostatic state and weight status: subcortical bidirectional connections between the LH, MH and the substantia nigra pars compacta (prSN), and cortical top-down inhibition from frontoparietal and temporal areas. During fasting relative to satiety, we found higher inhibition between the LH and prSN, whereas the prSN received greater top-down inhibition from across the cortex. Individuals with higher BMI showed that these network dynamics occur irrespective of fasted or satiety states. Our findings reveal fasting affects brain dynamics over a distributed hypothalamic-midbrain-cortical network. This network is less sensitive to state-related fluctuations among people with obesity.
Ultrashort treatment with telacebec alone and with companion drugs in immunocompetent and immunosuppressed mouse footpad models of Buruli ulcer
Authors: Komm Oliver , Almeida Deepak V. , Converse Paul J. , Omansen Till F. , Nuermberger Eric L.
Published: June 2021

The antimicrobial treatment of Mycobacterium ulcerans infection, or Buruli ulcer (BU), has a long duration and is therefore burdensome and linked to indirect costs for affected patients. The new antimycobacterial drug telacebec (Q203) has previously shown promising treatment-shortening potential in mouse models of BU. In the present study, we investigated the potential of Q203 to reduce the treatment duration further. The first experiment investigated the possibility of cure by one, three or five doses of Q203 (2 mg/kg) with or without a companion drug (bedaquiline, BDQ, clofazimine, CFZ, or clarithromycin, CLR) in immunocompetent BALB/c mice. The second experiment assessed the effect of five doses of Q203 with or without BDQ or CFZ on Mycobacterium ulcerans infection of immunocompromised SCID-beige mice with the aim to evaluate the contribution of host immunity to treatment efficacy. In BALB/c mice, a treatment duration as short as 3 days was sufficient to prevent relapse in nearly all footpads and a single dose of Q203 with or without BDQ or CFZ prevented relapse in approximately 50% of footpads. Unlike in BALB/c mice, a small percentage of SCID-beige mouse footpads were culture-positive after a treatment duration of five days, highlighting an important role of host immunity for M. ulcerans clearance. Our results confirm the marked potency and prolonged bactericidal and sterilizing effects of Q203, even in immunocompromised SCID-beige mice.
A selective adenylyl cyclase 1 inhibitor relieves pain without causing tolerance
Authors: Giacoletti Gianna , Price Tatum , Hoelz Lucas V.B , Msdi Abdulwhab Shremo , Vazquez-Falto Katerina , Amorim Fernandes Tácio V. , Santos de Pontes Vinícius , Wang Hongbing , Boechat Nubia , Nornoo Adwoa , Brust Tarsis F.
Published: June 2021

Adenylyl cyclases (ACs) catalyze the production of the second messenger cyclic adenosine monophosphate from adenosine triphosphate. Among the ten different AC isoforms, studies with knockout animals indicate that inhibition of AC1 can relieve pain and reduce behaviors linked to opioid dependence. We previously identified ST034307 as a selective inhibitor of AC1. The development of an AC1-selective inhibitor now provides the opportunity to further study the therapeutic potential of inhibiting this protein in pre-clinical animal models of pain and related adverse reactions. In the present study we have shown that ST034307 relieves pain in mouse models of formalin-induced inflammatory pain, acid-induced visceral pain, and acid-depressed nesting. In addition, ST034307 did not cause analgesic tolerance after chronic dosing. We also show that the compound is restricted to the periphery following subcutaneous injections and report the predicted molecular interaction between ST034307 and AC1. Our results indicate that AC1 inhibitors represent a promising new class of analgesic agents that treat pain and appear to produce less adverse effects than currently-used opioids.
Cross-platform Bayesian optimization system for autonomous biological assay development
Authors: Elder Sam , Klumpp-Thomas Carleen , Yasgar Adam , Travers Jameson , Frebert Shayne , Wilson Kelli M. , Zakharov Alexey V. , Dahlin Jayme L. , Kreisbeck Christoph , Sheberla Dennis , Sittampalam Gurusingham S. , Godfrey Alexander G. , Simeonov Anton , Michael Sam
Published: June 2021

Current high-throughput screening assay optimization is often a manual and time-consuming process, even when utilizing design-of-experiment approaches. A cross-platform, Cloud-based Bayesian optimization-based algorithm was developed as part of the NCATS ASPIRE Initiative to accelerate preclinical drug discovery. A cell-free assay for papain enzymatic activity was used as proof-of-concept for biological assay development. Compared to a brute force approach that sequentially tested all 294 assay conditions to find the global optimum, the Bayesian optimization algorithm could find suitable conditions for optimal assay performance by testing only 21 assay conditions on average, with up to 20 conditions being tested simultaneously. The algorithm could achieve a seven-fold reduction in costs for lab supplies and high-throughput experimentation run-time, all while being controlled from a remote site through a secure connection. Based on this proof-of-concept, this technology is expected to be applied to more complex biological assays and automated chemistry reaction screening at NCATS, and should be transferable to other institutions.
Computational and experimental assessment of backbone templates for computational protein design
Authors: Marin Frederikke Isa , Johansson Kristoffer Enøe , O’Shea Charlotte , Lindorff-Larsen Kresten , Winther Jakob Rahr
Published: June 2021

Computational protein design has taken big strides over the recent years, however, the tools available are still not at a state where a sequence can be designed to fold into a given protein structure at will and with high probability. We have here applied a recent release of Rosetta Design to redesign a set of structurally very similar proteins belonging to the Thioredoxin fold. We determined design success using a combination of a genetic screening tool to assay folding/stability in E. coli and selecting the best hits from this for further biochemical characterization. We have previously used this set of template proteins for redesign and found that success was highly dependent on template structure, a trait which was also found in this study. Nevertheless, state of the art design software is now able to predict the best template, most likely due to the introduction of the cart_bonded energy term. The template that led to the greatest fraction of successful designs was the same (a Thioredoxin from spinach) as that identified in our previous study. Our previously described redesign of Thioredoxin, which also used the spinach protein as template, however also performed well. In the present study, both these templates yielded proteins with compact folded structures, and enforces the conclusion that any design project must carefully consider different design templates. Fortunately, selecting designs using the cart_bonded energy term appears to correctly identify such templates.
Spatial organization of face part representations within face-selective areas revealed by high-field fMRI
Authors: Zhang Jiedong , Jiang Yong , Song Yunjie , Zhang Peng , He Sheng
Published: June 2021

Regions sensitive to specific object categories as well as organized spatial patterns sensitive to different features have been found across the whole ventral temporal cortex (VTC). However, it is unclear that within each object category region, how specific feature representations are organized to support object identification. Would object features, such as object parts, be represented in fine-scale spatial organization within object category-specific regions? Here we used high-field 7T fMRI to examine the spatial organization of neural tuning to different face parts within each face-selective region. Our results show consistent spatial organization across individuals that within right posterior fusiform face area (pFFA) and right occipital face area (OFA), the posterior portion of each region was biased to eyes, while the anterior portion was biased to mouth and chin stimuli. Our results demonstrate that within the occipital and fusiform face processing regions, there exist systematic spatial organizations of neural tuning to different face parts that support further computation combining them.
Haplotype diversity and sequence heterogeneity of human telomeres
Authors: Grigorev Kirill , Foox Jonathan , Bezdan Daniela , Butler Daniel , Luxton Jared J. , Reed Jake , McKenna Miles J. , Taylor Lynn , George Kerry A. , Meydan Cem , Bailey Susan M. , Mason Christopher E.
Published: June 2021

Telomeres are regions of repetitive nucleotide sequences capping the ends of eukaryotic chromosomes that protect against deterioration, and whose lengths can be correlated with age and adverse health risk factors. Yet, given their length and repetitive nature, telomeric regions are not easily reconstructed from short-read sequencing, thus making telomere sequencing, mapping, and variant resolution challenging problems. Recently, long-read sequencing, with read lengths measuring in hundreds of kilobase pairs, has made it possible to routinely read into telomeric regions and inspect their sequence structure. Here, we describe a framework for extracting telomeric reads from whole-genome single-molecule sequencing experiments, including de novo identification of telomere repeat motifs and repeat types, and also describe their sequence variation. We find that long, complex telomeric stretches and repeats can be accurately captured with long-read sequencing, observe extensive sequence heterogeneity of human telomeres, discover and localize noncanonical telomere sequence motifs (both previously reported, as well as novel), and validate them in short-read sequence data. These data reveal extensive intra- and inter-population diversity of repeats in telomeric haplotypes, reveal higher paternal inheritance of telomeric variants, and represent the first motif composition maps of multi-kilobase-pair human telomeric haplotypes across three distinct ancestries (Ashkenazi, Chinese, and Utah), which can aid in future studies of genetic variation, aging, and genome biology.
Productivity monitoring in building construction projects: a systematic review
Authors: Alaloul Wesam Salah , Alzubi Khalid M. , Malkawi Ahmad B. , Al Salaheen Marsail , Musarat Muhammad Ali
Published: June 2021

Purpose

The unique nature of the construction sector makes it fall behind other sectors in terms of productivity. Monitoring construction productivity is crucial for the construction project's success. Current practices for construction productivity monitoring are time-consuming, manned and error prone. Although previous studies have been implemented toward reducing these limitations, a gap still exists in the automated monitoring of construction productivity.

Design/methodology/approach

This study aims to investigate and assess the different techniques used for monitoring productivity in building construction projects. Therefore, a mixed review methodology (bibliometric analysis and systematic review) was adopted. All the related publications were collected from different databases, which were further screened to get the most relevant based on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) criteria.

Findings

A detailed review was performed, and it was found that traditional methods, computer vision-based and photogrammetry are the most adopted data acquisition for productivity monitoring of building projects, respectively. Machine learning algorithms (ANN, SVM) and BIM were integrated with monitoring tools and technologies to enhance the automated monitoring performance in construction productivity. Also, it was observed that current studies did not cover all the complex construction job sites and they were applied based on a small sample of construction workers and machines separately.

Originality/value

This review paper contributes to the literature on construction management by providing insight into different productivity monitoring techniques.
Assessment of residents’ perceptions and attitudes towards the appropriation of public spaces by tourists: the case of Aveiro
Authors: Moleiro Diogo Filipe , Carneiro Maria João , Breda Zélia
Published: June 2021

Purpose

This paper aims to provide an empirical analysis of residents’ perceptions and attitudes in the city of Aveiro, Portugal, regarding the appropriation of public spaces by tourists. An analysis of how the perceptions of this appropriation influence residents’ attitudes (RA) towards tourists, and even restructuring of space considering RA, is also presented. It is intended to do this based on a theoretical framework where tourism socio-cultural impacts on urban destinations are analysed with a focus on appropriation processes. Attitudes of residents are also examined.

Design/methodology/approach

A questionnaire survey (N = 301) was carried out with residents of the city of Aveiro, using a cluster sampling approach. The aim of the empirical study is to use multiple linear regression analyses to assess the extent to which the residents’ perceptions of tourists’ appropriation of public spaces influence the attitudes of the former towards the latter.

Findings

The results show that, overall, the residents consider that tourism has more positive than negative impacts. However, it can be observed that residents already perceive some negative impacts of tourism regarding the appropriation of space. Concerning RA, these tend to be more positive than negative. It can also be observed that various perceptions of appropriation of space significantly influence these attitudes. The paper ends with some guidelines for designing policies and strategies for tourism development that promote better use of public spaces by tourists.

Originality/value

Considering the limited empirical research on perceptions of appropriation of tourism space, the study carried out in this paper analyses the impact of a comprehensive set of residents’ perceptions regarding the appropriation of public space by tourists on various types of attitudes of residents towards tourists.
Technostress in the workplace: a social network perspective
Authors: Sasidharan Sharath
Published: June 2021

Purpose

Knowledge acquired by employees from co-workers through social networks may serve to reduce technostress during the use of a new and complex information system. The role of gender-based employee preferences in forming and acquiring system-related knowledge through friendship, advice, and expertise networks, and the impact of network-embedded expertise on performance outcomes are explored.

Design/methodology/approach

The research hypotheses were empirically tested through survey data collected from employees of a large organization that had implemented an enterprise system.

Findings

The advice networks of female employees were an extension of their friendship networks, whereas that of male employees were configured to include co-workers with system-related expertise. Exposure to high quality knowledge flows resulted in lowered technostress levels among male employees compared to their female counterparts. However, there was only a marginal difference in performance outcomes. The “expertise-deficit” in the advice network of female employees was apparently compensated through their dependence on the helpdesk.

Originality/value

Research on system-related knowledge support through social networks has focused on the structural features of interaction ties with little or no emphasis on networking employees and their individual preferences. Moving away from this structural orientation, this study validates the contention that gender-driven motivations impact employee networking preferences, determine network-embedded expertise levels, and influence employee technostress. This study can help configure implementation environments that maximize network acquisition of high-quality knowledge, reduce technostress, and enhance performance outcomes.
Luxury brands join hands: building interactive alliances on social media
Authors: Zhang Lini , Zhao Haidong , Cude Brenda
Published: June 2021

Purpose

This study, which is based on the extended hierarchy of effects (HOE) model, aims to examine whether social media interactions with one or more luxury brands can affect consumers' knowledge of, affection for and purchases of as well as loyalty to luxury fashion brands as a category.

Design/methodology/approach

SoJump (a leading data collection company in China) launched an online survey to collect data from Chinese luxury fashion brand consumers. Structural equation modeling (SEM) was conducted to analyze data from the random sample of 308 Chinese luxury fashion brand consumers.

Findings

The findings of this study demonstrated that social media interaction had direct positive influences on three stages of the luxury fashion brand decision-making process – knowledge, affection and loyalty – but not purchases. The results also empirically confirmed that consumers' response to social media interaction follows the cognition-affect-conation sequential process presented in the HOE model.

Practical implications

This study not only provides a new perspective for researchers to investigate the impacts of interactive social media marketing on purchase decision-making in the luxury fashion brand category but also underpins the importance of building interactive alliances for luxury brands to increase consumers' knowledge of, affection for, purchases in and loyalty to the luxury fashion brand category.

Originality/value

This study is among the first to investigate whether social media interactions with luxury fashion brands as a category influence consumers' knowledge of, affection for and loyalty to that category. In addition, this study is the first attempt to explore whether social media interactions can directly influence consumers' luxury fashion brand purchases.
Functional diversity and redundancy of tropical forests shift with elevation and forest‐use intensity
Authors: Monge‐González María Leticia , Guerrero‐Ramírez Nathaly , Krömer Thorsten , Kreft Holger , Craven Dylan
Published: June 2021

Change and intensification of forest use alter tropical ecosystems, influencing biodiversity and, subsequently, ecosystem functioning. The implications of eroding biodiversity may go beyond decreases in species diversity, resulting in changes of functional diversity, that is, the diversity of ecological strategies present in the community, and functional redundancy, that is, how redundant these strategies are to biodiversity loss. However, how environmental conditions and anthropogenic influences shape functional diversity and redundancy in tropical forests remains poorly understood.

Here, we examine how tropical forests respond to forest‐use intensity along an extensive elevational gradient in Mexico from the tropical lowlands to high‐elevational mountain forests (0–3,500 m), in terms of functional diversity and functional redundancy, and how these biodiversity facets are related to forest structure. In our study, elevation was crossed with three levels of forest‐use intensity: old‐growth, degraded and secondary forests. At eight elevational sites, five replicate plots were inventoried for each level of forest‐use intensity (total n = 120 plots). Functional diversity and redundancy were calculated using leaf and wood traits of 144 tree species for Hill numbers zero, one and two.

Interactive effects between elevation and forest‐use intensity significantly affected biodiversity facets. However, interactive effects resulted from forest‐use intensity influencing biodiversity facets at only a few elevations, and not from a consistent, negative impact of forest‐use intensity. Forest structure, specifically stem density and the Gini coefficient, explained variation across biodiversity facets when these facets gave equal weight to common and rare species.

Synthesis and applications. High functional diversity and functional redundancy from lowland to mid‐elevation tropical forests suggest that these ecosystems can be resilient to future disturbances. Our results indicate that the ability of high‐elevation forests may be particularly susceptible to climate change and increasing forest‐use intensity. For these high‐elevation forests, we recommend that forest managers implement enrichment plantings with native species that can tolerate future environmental conditions. Finally, our study shows that efforts to conserve structurally heterogeneous forests and actively managing forests to increase structural heterogeneity will enhance the resilience of tropical forests while conserving their biodiversity.
Bacillus cereus food intoxication and toxicoinfection
Authors: Jovanovic Jelena , Ornelis Vincent F. M. , Madder Annemieke , Rajkovic Andreja
Published: June 2021

Bacillus cereus is one of the leading etiological agents of toxin‐induced foodborne diseases. Its omnipresence in different environments, spore formation, and its ability to adapt to varying conditions and produce harmful toxins make this pathogen a health hazard that should not be underestimated. Food poisoning by B. cereus can manifest itself as an emetic or diarrheal syndrome. The former is caused by the release of the potent peptide toxin cereulide, whereas the latter is the result of proteinaceous enterotoxins (e.g., hemolysin BL, nonhemolytic enterotoxin, and cytotoxin K). The final harmful effect is not only toxin and strain dependent, but is also affected by the stress responses, accessory virulence factors, and phenotypic properties under extrinsic, intrinsic, and explicit food conditions and host‐related environment. Infamous portrait of B. cereus as a foodborne pathogen, as well as a causative agent of nongastrointestinal infections and even nosocomial complications, has inspired vast volumes of multidisciplinary research in food and clinical domains. As a result, extensive original data became available asking for a new, both broad and deep, multifaceted look into the current state‐of‐the art regarding the role of B. cereus in food safety. In this review, we first provide an overview of the latest knowledge on B. cereus toxins and accessory virulence factors. Second, we describe the novel taxonomy and some of the most pertinent phenotypic characteristics of B. cereus related to food safety. We link these aspects to toxin production, overall pathogenesis, and interactions with its human host. Then we reflect on the prevalence of different toxinotypes in foods opening the scene for epidemiological aspects of B. cereus foodborne diseases and methods available to prevent food poisoning including overview of the different available methods to detect B. cereus and its toxins.
The role of bile acid subtypes in the diagnosis of cholangiocarcinoma
Authors: Wang Wei , Tian Shi‐Lin , Jin Die , Liu Bin , Wang Wujie , Chang Haiyang , Chen Chao , Yu Zhe , Wang Yong‐Zheng , Li Yu‐Liang
Published: June 2021

Objectives

To find the potential biomarkers of cholangiocarcinoma, form a biomarker package, evaluate its efficiency, and validate it.

Methods

R software was used to analyze the differential expression of mRNAs between cholangiocarcinoma and adjacent nontumorous tissues, obtained from The Cancer Genome Atlas (TCGA), and enrich the KEGG pathway. Metabo‐Profile Inc. performed the comprehensive bile acid profiling and quantitation. The training set concluded 20 cholangiocarcinoma and 20 nontumorous volunteers. Receiver operating characteristic (ROC) curve and accompanying area under the curve (AUC) was calculated. The top four bile acids formed a new biomarker package. The validation set included 15 cholangiocarcinoma and 15 nontumorous, and the sensitivity and specificity of the new biomarker package were tested.

Results

Gene expression of 36 cholangiocarcinoma and nine adjacent nontumorous tissues was obtained in January 2020. Totally 9887 differential genes were eligible (logFC ≥ 1 or ≤ –1, P < 0.05, and adjust P < 0.01). GO analysis showed that 20 KEGG pathways were enriched, including primary bile acid biosynthesis and bile secretion. Comprehensive bile acid profiling and quantitation showed 15 differential bile acid types, and the ROC‐AUC was between 0.953 and 0.750. HDCA, isoLCA, bCDCA, and DCA were selected to form a biomarker package. The Logit (p = cholangiocarcinoma) = 7.898 – 3.70*(1isoLCA) – 0.444*(bCDCA) + 0.415*(HDCA) + 0.041*DCA. Its ROC‐AUC was 0.944. In the validation set, the sensitivity was 0.933 and the specificity was 0.867.

Conclusion

Bile acid types package was efficient to distinguish nontumorous population and cholangiocarcinoma. The difference might be associated to the downregulation of primary bile acid biosynthesis and bile secretion pathway of cholangiocarcinoma.
68Ga‐prostate‐specific membrane antigen (PSMA) PET/CT as a clinical decision‐making tool in biochemically recurrent prostate cancer
Authors: Davies Amy , Foo Marcus , Gan Chun Loo , Kourambas John , Redgrave Nicholas , Donnellan Scott , Appu Sree , Williams Scott , Coleman Andrew , Segelov Eva , Bradley Jason , Soo Geoffrey , Ramdave Shakher , Kwan Edmond M. , Azad Arun A.
Published: June 2021

Objective

PSMA PET/CT has demonstrated superior sensitivity over conventional imaging in the detection of local and distant recurrence in biochemically relapsed (BCR) prostate cancer. We prospectively investigated the management impact of68Ga‐PSMA PET/CT imaging in men with BCR, with the aim of identifying baseline clinicopathological predictors for management change.

Patients and methods

Men with BCR who met eligibility criteria underwent68Ga‐PSMA‐11 PET/CT at Monash Health (Melbourne, Australia). Intended management plans were prospectively documented before and after68Ga‐PSMA PET/CT imaging. Binary logistic regression analysis was performed to identify potential clinicopathological predictors of management change. Descriptive statistics were used to characterize the nature of these changes.

Results

Seventy men underwent68Ga‐PSMA‐11 PET/CT imaging. Median age was 67 years (IQR 63–72) and median PSA was 0.48 ng/ml (IQR 0.21–1.9). PSMA‐avid disease was observed in 56% (39/70) of patients. Pre‐scan management plan was altered following scanning in 43% (30/70) of patients. Management changes were significantly more common in patients with higher baseline PSA levels (PSA≥2 ng/ml,p = 0.01). 18/36 (50%) of the patients initially planned for watchful waiting had their management changed, including the use of salvage pelvic radiotherapy (n = 7) and stereotactic ablative body radiotherapy to oligometastatic disease (n = 6).

Conclusion

Management change after68Ga‐PSMA PET/CT for BCR is common and typically resulted in treatment intensification strategies in those planned for a watchful waiting approach. This study adds to the growing pool of evidence supporting the clinical utility of PSMA PET/CT imaging in the care of patients with BCR after definitive therapy.
Oil Cities in Africa: Beyond Just Transition
Authors: Obeng‐Odoom Franklin
Published: June 2021

Nations and NGOs are promoting the idea of a transition from a petroleum‐based civilization to one fueled by renewable energy. But there are many questions about how to proceed. The solution usually proposed is to develop “clean energy” as the underlying basis of a transition. Analysts tend to be concerned with climate change and land use change, with a focus on technical developments. Socio‐ecological issues receive scant attention, especially if they relate to oil cities. This article starts from the perspective that progress in saving the planet from destruction can only be achieved by taking seriously past and present injustices and taking measures to rectify them. I use the situation in Port Harcourt, Nigeria to illustrate this proposition. I focus on three interrelated concepts: rent theft, social costs, and just transition. The central problem is rent theft because it is at the root of the “crime of poverty” and the social costs of plundering the land for energy sources. Until they addressproblems arising from historical injustice, campaigns for a just transition that promote clean energy in a bioeconomy will merely reproduce the central problem. Thus, reparations and land equity must be an integral part of any solution.