bluuebunny/crossref_metadata_2025 huggingface dataset:
A genome-scale metabolic reconstruction provides insight into the metabolism of the thermophilic bacteriumRhodothermus marinus
Authors: Kristjansdottir Thordis , Hreggvidsson Gudmundur O. , Stefansson Sigmar Karl , Gudmundsdottir Elisabet Eik , Bjornsdottir Snaedis H. , Fridjonsson Olafur H. , Karlsson Eva Nordberg , Vanhalst Justine , Reynisson Birkir , Gudmundsson Steinn
Published: May 2021

The thermophilic bacteriumRhodothermus marinushas mainly been studied for its thermostable enzymes. More recently, the potential of using the species as a cell factory and in biorefinery platforms has been explored, due to the elevated growth temperature, native production of compounds such as carotenoids and EPSs, the ability to grow on a wide range of carbon sources including polysaccharides, and available genetic tools. A comprehensive understanding of the metabolism of production organisms is crucial. Here, we report a genome-scale metabolic model ofR. marinusDSM 4252T. Moreover, the genome of the genetically amenableR. marinusISCaR-493 was sequenced and the analysis of the core genome indicated that the model could be used for both strains. Bioreactor growth data was obtained, used for constraining the model and the predicted and experimental growth rates were compared. The model correctly predicted the growth rates of both strains. During the reconstruction process, different aspects of theR. marinusmetabolism were reviewed and subsequently, both cell densities and carotenoid production were investigated for strain ISCaR-493 under different growth conditions. Additionally, thedxsgene, which was not found in theR. marinusgenomes, fromThermus thermophiluswas cloned on a shuttle vector into strain ISCaR-493 resulting in a higher yield of carotenoids.

Importance

A biorefinery converting biomass into fuels and value-added chemicals is a sustainable alternative to fossil fuel-based chemical synthesis.Rhodothermus marinusis a bacterium that is potentially well suited for biorefineries. It possesses various enzymes that degrade biomass, such as macroalgae and parts of plants (e.g. starch and xylan) and grows at high temperatures (55-77°C) which is beneficial in biorefinery processes. In this study, we reviewed the metabolism ofR. marinusand constructed a metabolic model. Such a model can be used to predict phenotypes, e.g. growth under different environmental and genetic conditions. We focused specifically on metabolic features that are of interest in biotechnology, including carotenoid pigments which are used in many different industries. We described cultivations ofR. marinusand the resulting carotenoid production in different growth conditions, which aids in understanding how carotenoid yields can be increased in the bacterium.
Defining dual-axis landscape gradients of human influence for studying ecological processes
Authors: Padilla Benjamin J. , Sutherland Chris
Published: May 2021

Ecological processes are strongly shaped by human landscape modification, and understanding the reciprocal relationship between ecosystems and modified landscapes is critical for informed conservation. Single axis measures of spatial heterogeneity proliferate in the contemporary gradient ecology literature, though they are unlikely to capture the complexity of ecological responses. Here, we develop a standardized approach for defining multi-dimensional gradients of human influence in heterogeneous landscapes and demonstrate this approach to analyze landscape characteristics of ten ecologically distinct US cities. Using occupancy data of a common human-adaptive songbird collected in each of the cities, we then use our dual-axis gradients to evaluate the utility of our approach. Spatial analysis of landscapes surrounding ten US cities revealed two important axes of variation that are intuitively consistent with the characteristics of multi-use landscapes, but are often confounded in single axis gradients. These were, a hard-to-soft gradient, representing transition from developed areas to non-structural soft areas; and brown-to-green, differentiating between two dominant types of soft landscapes: agriculture (brown) and natural areas (green). Analysis of songbird data demonstrated that occupancy responds to both hard-to-soft (decreasing with development intensity) and brown-to-green gradient (increasing with more natural area). Overall, our results reveal striking consistency in the dominant sources of variation across ten geographically distinct cities and suggests that our approach advances how we relate variation in ecological responses to human influence. Our case study demonstrates this: robins show a remarkably consistent response to a gradient differentiating agricultural and natural areas, but city-specific responses to the more traditional gradient of development intensity, which would be overlooked with a single gradient approach. Managing ecological communities in human dominated landscapes is extremely challenging due to a lack of standardized approaches and a general understanding of how socio-ecological systems function, and our approach offers promising solutions.
Transcriptome-wide identification and expression profiling of the ERF gene family suggest roles as transcriptional activators and repressors of fruit ripening in durian
Authors: Khaksar Gholamreza , Sirikantaramas Supaart
Published: May 2021

The involvement of the phytohormone ethylene as the main trigger of climacteric fruit ripening is well documented. However, our knowledge regarding the role of ethylene response factor (ERF) transcription factor in the transcriptional regulation of ethylene biosynthesis during fruit ripening remains limited. Here, comprehensive transcriptome analysis and expression profiling revealed 63 ERFs in durian pulps, termed DzERF1–DzERF63, of which 34 exhibited ripening-associated expression patterns at three stages (unripe, midripe, and ripe) during fruit ripening. Hierarchical clustering analysis classified 34 ripening-associated DzERFs into three distinct clades, among which, clade I consisted of downregulated DzERFs and clade III included those upregulated during ripening. Phylogenetic analysis predicted the functions of some DzERFs based on orthologs of previously characterized ERFs. Among downregulated DzERFs, DzERF6 functional prediction revealed its role as a negative regulator of ripening via ethylene biosynthetic gene repression, whereas among upregulated genes, DzERF9 was predicted to positively regulate ethylene biosynthesis. Correlation network analysis of 34 ripening-associated DzERFs with potential target genes revealed a strong negative correlation between DzERF6 and ethylene biosynthetic genes and a strong positive correlation between DzERF9 and ethylene biosynthesis. DzERF6 and DzERF9 showed differential expression patterns in association with different ripening treatments (natural, ethylene-induced, and 1-methylcyclopropene-delayed ripening). DzERF6 was downregulated, whereas DzERF9 was upregulated, during ripening and after ethylene treatment. The auxin-repressed and auxin-induced expression of DzERF6 and DzERF9, respectively, confirmed its dose-dependent responsiveness to exogenous auxin. We suggest ethylene- and auxin-mediated roles of DzERF6 and DzERF9 during fruit ripening, possibly through transcriptional regulation of ethylene biosynthetic genes.
Trend, Population Structure and Trait Mapping from 15 Years of National Varietal Trials of UK Winter Wheat
Authors: Shorinola Oluwaseyi , Simmonds James , Wingen Luzie U. , Gardner Keith , Uauy Cristobal
Published: May 2021

There are now a rich variety of genomic and genotypic resources available to wheat researchers and breeders. However, the generation of high-quality and field-relevant phenotyping data which is required to capture the complexities of gene x environment interactions remains a major bottleneck. Historical datasets from national variety performance trials (NVPT) provide sufficient dimensions, in terms of numbers of years and locations, to examine phenotypic trends and study gene x environment interactions. Using NVPT for winter wheat varieties grown in the UK between 2002 – 2017, we examined temporal trends for eight traits related to yield, adaptation, and grain quality performance. We show a non-stationary linear trend for yield, grain protein content, HFN and days to ripening. Our data also show high environmental stability for yield, grain protein content and specific weight in UK winter wheat varieties and high environmental sensitivity for Hagberg Falling Number. Using the historical NVPT data in a genome-wide association analysis, we uncovered a significant marker-trait association peak on wheat chromosome 6A spanning the NAM-A1 gene that have been previously associated with early senescence. Together our results show the value of utilizing the data routinely collected during variety evaluation process for examining breeding progress and the genetic architecture of important traits.
uniForest: an unsupervised machine learning technique to detect outliers and restrict variance in microbiome studies
Authors: Leigh R.J. , Murphy R.A. , Walsh F.
Published: May 2021

Isolation Forests is an unsupervised machine learning technique for detecting outliers in continuous datasets that does not require an underlying equivariant or Gaussian distribution and is suitable for use on small datasets. While this procedure is widely used across quantitative fields, to our knowledge, this is the first attempt to solely assess its use for microbiome datasets. Here we present uniForest, an interactive Python notebook (which can be run from any desktop computer using the Google Colaboratory web service) for the processing of microbiome outliers. We used uniForest to apply Isolation Forests to the Healthy Human Microbiome project dataset and imputed outliers with the mean of the remaining inliers to maintain sample size and assessed its prowess in variance reduction in both community structure and derived ecological statistics (α-diversity). We also assessed its functionality in anatomical site differentiation (pre- and postprocessing) using principal component analysis, dissimilarity matrices, and ANOSIM. We observed a minimum variance reduction of 81.17% across the entire dataset and in alpha diversity at the Phylum level. Application of Isolation Forests also separated the dataset to an extremely high specificity, reducing variance within taxa samples by a minimum of 81.33%.

It is evident that Isolation Forests are a potent tool in restricting the effect of variance in microbiome analysis and has potential for broad application in studies where high levels of microbiome variance is expected. This software allows for clean analyses of otherwise noisy datasets.
BMP signaling underlies the craniofacial heterochrony in phyllostomid bats, a hyperdiverse mammal group
Authors: Camacho Jasmin , Lin Jacky D. , McCormack Michaela , Moon Rachel , Smith Samantha K. , Rasweiler John J. , Behringer Richard R. , Tabin Clifford J. , Abzhanov Arhat
Published: May 2021

The potential for variation and the capacity to evolve in response to ecological opportunity are important aspects of an adaptive radiation. Identifying the origin of phenotypic variation, in which natural selection might act upon, is a major goal of evolutionary developmental biology. The New World leaf-nosed bats (phyllostomids) are a textbook example of an adaptive radiation. Their cranial morphology is diverse along relative facial length, which is related to their diets. We previously used geometric morphometrics to reveal peramorphosis, a type of heterochrony, in the cranial evolution among phyllostomid bats. We then demonstrated that the mechanism of peramorphic diversity in phyllostomid rostrum length resulted from altered cellular proliferation. Here, we investigate the progenitors of the face, the cranial neural crest, and a key signaling pathway related to their proliferation and differentiation into mature tissues: the bone morphogenetic protein (BMP). With geometric morphometrics, immunofluorescence, and confocal imaging—in three phyllostomid species and one outgroup bat species—we show the molecular patterns that underlie the adaptive and innovative traits seen in phyllostomid bats. Then, with mouse genetics, we mimic the BMP molecular pattern observed in nectar feeding bats and recapitulate the elongated morphological variation in mice. Surprisingly, we also observe an expansion in the nose-tip of mice, akin to the expanding leaf-nose tissue in phyllostomid bats. These data, combined with the mouse genetics literature on BMP signaling, suggest the BMP developmental pathway plays a central role in shaping the craniofacial variation necessary for adaptation in bats. Further, we speculate that the BMP signaling pathway could underlie other bizarre facial phenotypes in mammals that are derived from frontonasal mesenchyme, such as the proboscis. Overall, this study combines a comparative framework to developmental data, with a genetic approach, to directly investigate the role of development on complex morphology.
T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma
Authors: Carey Ryan M. , McMahon Derek B. , Rajasekaran Karthik , Gopallawa Indiwari , Newman Jason G. , Basu Devraj , White Elizabeth A. , Lee Robert J.
Published: May 2021

Better management of head and neck squamous cell carcinomas (HNSCCs) requires a clearer understanding of tumor biology and disease risk. Bitter taste receptors (T2Rs) have been studied in several cancers, including thyroid, salivary, and GI, but their role in HNSCC has not been explored. We found that HNSCC patient samples and cell lines expressed functional T2Rs on both the cell and nuclear membranes. Bitter compounds, including bacterial metabolites, activated T2R-mediated nuclear Ca2+ responses leading to mitochondrial depolarization, caspase activation and ultimately apoptosis. Buffering nuclear Ca2+ elevation blocked caspase activation. Furthermore, increased expression of T2Rs in HNSCCs from The Cancer Genome Atlas (TCGA) is associated with improved overall survival. This work suggests that T2Rs are potential biomarkers to predict outcomes and guide treatment selection, may be leveraged as therapeutic targets to stimulate tumor apoptosis, and may mediate tumor-microbiome crosstalk in HNSCC.
Empowering systems-guided drug target discovery with metabolic and structural analysis
Authors: Chowdhury Sourav , Zielinski Daniel C. , Dalldorf Christopher , Rodrigues Joao V , Palsson Bernhard O. , Shakhnovich Eugene I
Published: May 2021

Elucidating intracellular drug targets has been a difficult problem. While machine learning analysis of omics data has been a promising approach, going from large-scale trends to specific targets remains a challenge. Here, we developed a systems-guided hierarchic workflow that utilizes metabolic and structural analysis to narrow in on specific targets suggested by statistical and machine learning analysis of metabolomics data. Utilizing a novel multi-valent DHFR-targeting antibiotic compound, CD15-3, as a case study, we first measured global metabolomics and applied statistics and machine learning to locate broad areas of metabolic perturbation under antibiotic stress. We then tested the ability of suggested compounds to rescue growth and performed metabolic modelling to identify pathways whose inhibition was consistent with growth rescue patterns. Next, we utilized protein structural similarity to further prioritize candidate drug targets within these pathways. Overexpression and in vitro activity assays of a top candidate target, HPPK (folK), showed complete recovery from drug induced growth inhibition and with microscopy. As interest in ‘white-box’ machine learning methods continues to grow, this study demonstrates how established machine learning methods can be combined with mechanistic analyses to improve the resolution of drug target finding workflows.
High level production and characterization of truncated human angiotensin converting enzyme 2 in Nicotiana benthamiana plant as a potential therapeutic target in COVID-19
Authors: Mamedov Tarlan , Gürbüzaslan İrem , Ilgin Merve , Yuksel Damla , Mammadova Gunay , Ozkul Aykut , Hasanova Gulnara
Published: May 2021

The COVID-19 pandemic, which is caused by SARS-CoV-2 has rapidly spread to more than 222 countries and has put global public health at high risk. The world urgently needs safe, a cost-effective SARS-CoV-2 coronavirus vaccine, therapeutic and antiviral drugs to combat the COVID-19. Angiotensin-converting enzyme 2 (ACE2), as a key receptor for SARS-CoV-2 infections, has been proposed as a potential therapeutic target in COVID-19 patients. In this study, we report high level production (about ∼0.75 g /kg leaf biomass) of glycosylated and non-glycosylated forms of recombinant human truncated ACE2 in Nicotiana benthamiana plant. The plant produced recombinant human truncated ACE2s successfully bind to the SARC-CoV-2 spike protein, but deglycosylated ACE2 binds more strongly than the glycosylated counterpart. Importantly, both deglycosylated and glycosylated forms of AEC2 stable at elevated temperatures for prolonged periods and demonstrated strong anti-SARS-CoV-2 activity in vitro. The IC50 values of glycosylated and deglycosylated AEC2 were 0.4 and 24 μg/ml, respectively, for the pre-entry infection, when incubated with 100TCID50 of SARS-CoV-2. Thus, plant produced truncated ACE2s are promising cost-effective and safe candidate as a potential therapeutic targets in the treatment of COVID-19 patients.
Intrinsic timescales in the visual cortex change with selective attention and reflect spatial connectivity
Authors: Zeraati Roxana , Shi Yan-Liang , Steinmetz Nicholas A. , Gieselmann Marc A. , Thiele Alexander , Moore Tirin , Levina Anna , Engel Tatiana A.
Published: May 2021

Intrinsic timescales characterize dynamics of endogenous fluctuations in neural activity. Variation of intrinsic timescales across the neocortex reflects functional specialization of cortical areas, but less is known about how intrinsic timescales change during cognitive tasks. We measured intrinsic timescales of local spiking activity within columns of area V4 while monkeys performed spatial attention tasks. The ongoing spiking activity unfolded across at least two distinct timescales, fast and slow. The slow timescale increased when monkeys attended to the receptive fields location and correlated with reaction times. By evaluating predictions of several network models, we found that spatiotemporal correlations in V4 activity were best explained by the model in which multiple timescales arise from recurrent interactions shaped by spatially arranged connectivity, and attentional modulation of timescales results from an increase in the efficacy of recurrent interactions. Our results suggest that multiple timescales arise from the spatial connectivity in the visual cortex and flexibly change with the cognitive state due to dynamic effective interactions between neurons.
A systematic comparison of fibroblasts derived from postmortem human dura mater versus dermal epithelium for neurodegenerative disease modeling
Authors: Argouarch Andrea R. , Cosme Celica G. , Garcia Kristle , Corrales Christian I. , Nana Alissa L. , Karydas Anna M. , Spina Salvatore , Grinberg Lea T. , Miller Bruce , Goodarzi Hani , Seeley William W. , Kao Aimee W.
Published: May 2021

Patient-derived cells hold great promise for precision medicine approaches in human health. Fibroblast cells have been a major source of human cells for reprogramming and differentiating into specific cell types for disease modeling. Such cells can be isolated at various stages during life (presymptomatic, symptomatic, and postmortem) and thus can potentially be used to model different phases of disease progression. In certain circumstances, however, tissues are not collected during life and only postmortem tissues are the only available source of fibroblasts. Fibroblasts cultured from postmortem human dura mater of individuals with neurodegenerative diseases have been suggested as a primary source of cells for in vitro modeling of neurodegenerative diseases. Although fibroblast-like cells from human and mouse dura mater have been previously described, their utility for reprogramming and direct differentiation protocols requires further characterization. In this study, cells derived from dermal biopsies performed in living subjects were compared to cells derived from postmortem dura mater. In two instances, we have isolated and compared dermal and dural cell lines from the same subject. Notably, striking differences between the dermis and dura mater-derived cell lines were found. Compared to dermal fibroblasts, postmortem dura mater-derived cells demonstrated different morphology, exhibited slower growth rates, failed to express fibroblast protein markers, and exhibited significant differences in gene expression profiles. In addition, dura mater-derived cells were found to exhibit a high rate of chromosomal abnormalities, particularly in the loss of the Y chromosome. Our study highlights potential limitations of postmortem human dura mater-derived cells for disease modeling, argues for rigorous karyotyping prior to reprograming, and brings into question the identity of dura mater-derived cells as belonging to a fibroblast lineage.
Rescuable effect of R-salbutamol in LPS-induced immune dysfunction of sepsis
Authors: Beng Huimin , Wang Shanping , Hu Junhua , Liang Xinglong , Qin Haolong , Tan Wen
Published: May 2021

Sepsis is a severe life-threatening condition caused by a dysregulated host response to infection. So far, there are no pharmacotherapies to stop sepsis. Salbutamol, a commonly used β2-adrenoreceptor agonist, has found to be potential in regulating immune response dysfunction and exert anti-inflammatory effect. However, salbutamol exists two isomers. R-isomer exhibits the therapeutic effect and clinical benefit, while S-isomer proves to be detrimental rather than benign. So, in this study, we investigated the preventive and therapeutic effect of R-salbutamol (R-sal), S-salbutamol (S-sal) or racemic mixture in a mouse model of lipopolysaccharide (LPS)-induced sepsis. Dexamethasone (Dex) was set as comparison. The results showed that R-sal markedly improved seven-day survival rate of septic mice both administered before or after LPS. Whereas Dex showed toxic and accelerated the death of septic mice when given before LPS injection. Lung histological examination and lung function assay revealed that LPS challenge resulted in acute lung damage, including inflammatory cell infiltration, thickened alveolar septa and congestion, and decreased minute volume in septic mice. R-sal pretreatment efficiently inhibited these changes, accompanying by markedly reduced lung MPO level, serum cytokines levels and lactate release and significantly restored the lymphocytes and suppressed the percentage of monocytes. Racemic mixture exhibited diminished effects while S-sal showed enhanced cytokines release. In addition, R-sal pretreatment showed a better improvement in prognostic pulmonary function at day4 in survived mice than that of Rac-sal. Collectively, our results indicate the potential benefit of R-sal for sepsis and sepsis-induced lung injury.
Modulating the selective utilization of carbon sources by engineering the 3rd and 4th helices of the DNA-binding domain of catabolite control protein A (CcpA) in Bacillus licheniformis
Authors: Zhang Yupeng , Li Youran , Xiao Fengxu , Wang Hanrong , Zhang Liang , Ding Zhongyang , Gu Zhenghua , Xu Sha , Shi Guiyang
Published: May 2021

The gram-positive bacterium Bacillus licheniformis exhibits obvious selective utilization on carbon sources. This process is mainly governed by the global regulator catabolite control protein A (CcpA), which can recognize and bind to multiple target genes widely distributed in metabolic pathways. Although the DNA-binding domain of CcpA has been predicted, the influence of key amino acids on target gene recognition and binding remains elusive. In this study, the impact of Lys31, Ile42 and Leu56 on in vitro protein-DNA interactions and in vivo carbon source selective utilization was investigated. The results showed that alanine substitution of Lys31 and Ile42, located within the 3rd helices of the DNA-binding domain, significantly weakened the binding strength between CcpA and target genes. These mutations also lead to alleviated repression of xylose utilization in the presence of glucose. On the other hand, the Leu56Arg mutant in the 4th helices exhibited enhanced binding affinity compared with that of the wild-type one. When this mutant was used to replace the native one in B. licheniformis cells, the selective utilization of glucose over xylose increased. The above research results are helpful for a deep understanding of how microorganisms can flexibly sense and adapt to changes in the external environment. Additionally, they can provide important theoretical basis for the rational design of biomass utilization and environmental adaptability of B. licheniformis cell factories.

Importance

Bacillus licheniformis is widely used in producing various valuable products, such as α enzymes, industrial chemicals and biocides. The carbon catabolite regulation process in the utilization of raw materials is crucial to maximizing the efficiency of this microbial cell factory. CcpA plays an important role in this process. This study represents a new paradigm to investigate the structure–function relationship in CcpA by fluorescence polarization experiments in vitro. The results also uncover key amino acids in the DNA-binding domain that affect the selective utilization of carbon sources. These results provide a theoretical basis for the rational design of industrial microorganisms.
Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Authors:   RECOVERY Collaborative Group, Horby Peter W , Campbell Mark , Spata Enti , Emberson Jonathan R , Staplin Natalie , Pessoa-Amorim Guilherme , Peto Leon , Wiselka Martin , Wiffen Laura , Tiberi Simon , Caplin Ben , Wroe Caroline , Green Christopher , Hine Paul , Prudon Benjamin , George Tina , Wight Andrew , Baillie J Kenneth , Basnyat Buddha , Buch Maya H , Chappell Lucy C , Day Jeremy N , Faust Saul N , Hamers Raph L , Jaki Thomas , Juszczak Edmund , Jeffery Katie , Lim Wei Shen , Montgomery Alan , Mumford Andrew , Rowan Kathryn , Thwaites Guy , Mafham Marion , Haynes Richard , Landray Martin J
Published: May 2021

Background

Colchicine has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory actions.

Methods

In this randomised, controlled, open-label trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus colchicine twice daily for 10 days or until discharge (or one of the other treatment arms) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).

Findings

Between 27 November 2020 and 4 March 2021, 5610 patients were randomly allocated to receive colchicine and 5730 patients to receive usual care alone. Overall, 1173 (21%) patients allocated to colchicine and 1190 (21%) patients allocated to usual care died within 28 days (rate ratio 1.01; 95% confidence interval [CI] 0.93-1.10; p=0.77). Consistent results were seen in all pre-specified subgroups of patients. There was no significant difference in duration of hospitalisation (median 10 days vs. 10 days) or the proportion of patients discharged from hospital alive within 28 days (70% vs. 70%; rate ratio 0.98; 95% CI 0.94-1.03; p=0.44). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (25% vs. 25%; risk ratio 1.02; 95% CI 0.96-1.09; p=0.47).

Interpretation

In adults hospitalised with COVID-19, colchicine was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056). Wellcome Trust (Grant Ref: 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator.
Nanoscale resolution imaging of the whole mouse embryos and larval zebrafish using expansion microscopy
Authors: Sim Jueun , Park Chan E , Cho In , Min Kyeongbae , Eom Minho , Han Seungjae , Jeon Hyungju , Cho Hyun-Ju , Cho Eun-Seo , Kumar Ajeet , Chong Yosep , Kang Jeong Seuk , Piatkevich Kiryl D. , Jung Erica E. , Kang Du-Seock , Kwon Seok-Kyu , Kim Jinhyun , Yoon Ki-Jun , Lee Jeong-Soo , Boyden Edward S. , Yoon Young-Gyu , Chang Jae-Byum
Published: May 2021

Nanoscale resolution imaging of whole vertebrates is required for a systematic understanding of human diseases, but this has yet to be realized. Expansion microscopy (ExM) is an attractive option for achieving this goal, but the expansion of whole vertebrates has not been demonstrated due to the difficulty of expanding hard body components. Here, we demonstrate whole-body ExM, which enables nanoscale resolution imaging of anatomical structures, proteins, and endogenous fluorescent proteins (FPs) of whole zebrafish larvae and mouse embryos by expanding them fourfold. We first show that post-digestion decalcification and digestion kinetics matching are critical steps in the expansion of whole vertebrates. Then, whole-body ExM is combined with the improved pan-protein labeling approach to demonstrate the three-dimensional super-resolution imaging of antibody- or FP-labeled structures and all major anatomical structures surrounding them. We also show that whole-body ExM enables visualization of the nanoscale details of neuronal structures across the entire body.
Urbanisation, Bird Species Richness and Abundance Within Ibadan Metropolis, Nigeria
Authors: Adegbola Festus O. , Adeyanju Taiye Adeniyi , Iwajomo Soladoye B. , Ayodele Ibukunoluwa Augustine
Published: May 2021

Urbanisation is considered as one of the most profound threat to wildlife, with habitat loss and fragmentation being predominant. This study assessed the impacts of urbanisation on richness, abundance of bird species within Ibadan metropolis, Nigeria. A uniform grid of 500 square meters was installed on the map of Ibadan Metropolis using QGIS to produce 499 grid points distributed across the five urban local governments. 100 grids were selected randomly, identified with mapinR software application and surveyed with 5 point counts within each gird, established at 200m interval to avoid double counting. Each point count was observed for 5 minutes using a pair of 8×42mm binoculars within a 50m radius. Habitat variables like number of buildings, trees, paved roads, communication masts were also recorded.

A total number of 56 species of birds were observed at the end of the assessment, classified into 30 families. The test of statistics showed that there was no statistically significant difference in bird species richness between the Local Governments. The test of statistics showed that there was no statistically significant difference in bird species abundance between the local governments. The test of between-subjects effects revealed that there were no statistical significant effects when all the habitat variables were computed in the model on species richness. The number of paved roads and number of vehicles showed a significant effect on bird species abundance while others variables in the model did not exact statistically significant effects on bird species abundance.

The study therefore concluded that habitat actions due to urbanisation have not affected the richness and abundance of birds species found in all the local governments. The only habitat variables that have currently exacted significant effect on species abundance within the metropolis are number of vehicles and paved roads.
Using machine learning to design adeno-associated virus capsids with high likelihood of viral assembly
Authors: To Cuong T. , Wirsching Christian , Marques Andrew D. , Zolotukhin Sergei
Published: May 2021

We study the application of machine learning in designing adeno-associated virus (AAV) capsid sequences with high likelihood of viral assembly, i.e. capsid viability. Specifically, we design and implement Origami, a model-based optimization algorithm, to identify highly viable capsid sequences within the vast space of 2033 possibilities. Our evaluation shows that Origami performs well in terms of optimality and diversity of model-designed sequences. Moreover, these sequences are ranked according to their viability score. This helps designing experiments given budget constraint.
Chromatin architecture transitions from zebrafish sperm through early embryogenesis
Authors: Wike Candice L. , Guo Yixuan , Tan Mengyao , Nakamura Ryohei , Shaw Dana Klatt , Díaz Noelia , Whittaker-Tademy Aneasha F. , Durand Neva C. , Aiden Erez Lieberman , Vaquerizas Juan M. , Grunwald David , Takeda Hiroyuki , Cairns Bradley R.
Published: May 2021

Chromatin architecture mapping in 3D formats has increased our understanding of how regulatory sequences and gene expression are connected and regulated in a genome. The 3D chromatin genome shows extensive remodeling during embryonic development, and although the cleavage-stage embryos of most species lack structure before zygotic genome activation (pre-ZGA), zebrafish has been reported to have structure. Here, we aimed to determine the chromosomal architecture in paternal/sperm zebrafish gamete cells to discern whether it either resembles or informs early pre-ZGA zebrafish embryo chromatin architecture. First, we assessed the higher-order architecture through advanced low-cell in situ Hi-C. The structure of zebrafish sperm, packaged by histones, lacks topological associated domains and instead displays “hinge-like” domains of ∼150 kb that repeat every 1–2 Mbs, suggesting a condensed repeating structure resembling mitotic chromosomes. The pre-ZGA embryos lacked chromosomal structure, in contrast to prior work, and only developed structure post-ZGA. During post-ZGA, we find chromatin architecture beginning to form at small contact domains of a median length of ∼90 kb. These small contact domains are established at enhancers, including super-enhancers, and chemical inhibition of Ep300a (p300) and Crebbpa (CBP) activity, lowering histone H3K27ac, but not transcription inhibition, diminishes these contacts. Together, this study reveals hinge-like domains in histone-packaged zebrafish sperm chromatin and determines that the initial formation of high-order chromatin architecture in zebrafish embryos occurs after ZGA primarily at enhancers bearing high H3K27ac.
Stop going around in circles: towards a reconceptualisation of disaster risk management phases
Authors: Bosher Lee , Chmutina Ksenia , van Niekerk Dewald
Published: May 2021

Purpose

The way that disasters are managed, or indeed mis-managed, is often represented diagrammatically as a “disaster cycle”. The cyclical aspects of the disaster (risk) management concept, comprised of numerous operational phases, have, in recent years, been criticised for conceptualising and representing disasters in an overly simplistic way that typically starts with a disaster “event” – and subsequently leads onto yet another disaster. Such cyclical thinking has been proven to not be very useful for the complexities associated with understanding disasters and their risks. This paper aims to present an alternative conceptualisation of the Disaster Risk Management phases, in a way that can better factor in the underlying root causes that create differential levels of vulnerability.

Design/methodology/approach

This is a conceptual paper developed, through a review of the literature and discussions between the authors, as a counterpoint to the pervasive “disaster cycle”.

Findings

The “Disaster Risk Management (DRM) Helix” is presented as an alternative way of conceptualising the DRM phases. The helictical conceptualisation of DRM phases presented in this paper is intentionally presented to start a discussion (rather than as an end point) on how best to move away from the constraints of the “disaster cycle”.

Originality/value

It is envisaged that the helictical conceptualisation of DRM can be suitably malleable to include important factors such as temporal considerations and the underlying root causes that create differential levels of vulnerability. It is, thus, the intention that the DRM Helix can provide a catalyst for exciting discussions and future adaptations of the diagram that can better capture the dynamic (non-cyclical) nature of disasters and their root causes.
A Bayesian belief network predictive model for construction delay avoidance in the UK
Authors: Wang Peipei , Fenn Peter , Wang Kun , Huang Yunhan
Published: May 2021

Purpose

The purpose of this research is to advise on UK construction delay strategies. Critical delay factors were identified and their interrelationships were explored; in addition, a predictive model was established upon the factors and interrelationships to calculate delay potentials.

Design/methodology/approach

The critical causes were identified by a literature review, verified by an open-ended questionnaire survey and then analysed with 299 samples returned from structured questionnaire surveys. The model consisted of factors screened out by Pearson product–moment correlational coefficient, constructed by a logical reasoning process and then quantified by conducting Bayesian belief networks parameter learning.

Findings

The technical aspect of construction project management was less critical while the managerial aspect became more emphasised. Project factors and client factors present relatively weak impact on construction delay, while contractor factors, contractual arrangement factors and distinctively interaction factors present relatively strong impact.

Research limitations/implications

This research does not differentiate delay types, such as excusable vs non-excusable ones and compensable vs non-compensable ones. The model nodes have been tested to be critical to construction delay, but the model structure is mostly based on previous literature and logical deduction. Further research could be done to accommodate delay types and test the relationships.

Originality/value

This research updates critical delay factor list for the UK construction projects, suggesting general rules for resource allocation concerning delay avoidance. Besides, this research establishes a predictive model, assisting delay avoidance strategies on a case-by-case basis.
Pre-event competitiveness: exploring residents’ perceptions of place management and local impacts
Authors: Wise Nicholas , Đurkin Badurina Jelena , Perić Marko
Published: May 2021

Purpose

There is a need to rethink destination competitiveness research, which tends to overlook local impacts of events and new developments. Conducting pre-event research challenges researchers to move beyond analyzing competitiveness as an end (concerning strategy, tangible outcomes, economic deliverables and value for visitors) to assessing competitiveness as a beginning (through perceptions of place management and local impacts).

Design/methodology/approach

Survey research with local residents explores competitiveness pertinent to perceptions of place management and local impacts. Participation, enthusiasm and information availability are independent variables to assess whether statistically significant differences exist among residents’ perceptions. In total, 454 surveys were collected; the analysis involved exploratory factor analysis and t-test.

Findings

Factor analysis revealed two factors for place management (organizational competencies; managing awareness) and local impacts (awareness of social benefits; local interest and support). Enthusiasm and information availability have stronger influences on residents’ perceptions than participation in pre-event activities.

Practical implications

More emphasis needs put on ensuring information availability promotes enthusiasm, to help encourage participation. These three variables are a necessary basis for exploring residents’ pre-event perceptions – a key starting point to guide decision-making through later stages of an event life-cycle.

Originality/value

Events and competitiveness studies focusing specifically on information availability and enthusiasm of residents is little-explored. By exploring these variables and extending insight on participation, this paper contributes to the literature by assessing pre-event resident perceptions of place management and local impacts (with data collected as event developments were being realized).
Culture, Islamic capital and the entrepreneurial behaviour of family firms in Saudi Arabia
Authors: Alrubaishi Dalal , McAdam Maura , Harrison Richard
Published: May 2021

Purpose

There is a significant gap in understanding with regards to the role of cultural context in family business research. This paper aims to address this by exploring the critical and pervasive influence of culture in shaping the entrepreneurial behaviours of family businesses based in Saudi Arabia.

Design/methodology/approach

The authors adopt a qualitative interpretive case study approach, which draws upon interviews with the incumbents and successors of ten Saudi Arabian family firms.

Findings

The authors’ empirical evidence reveals the importance of family ties and culture on the entrepreneurial behaviour of family firms in general, and the influence of “Islamic capital” on the intergenerational transfer of family legacy in particular.

Originality/value

The authors provide critical insights on how Islamic capital motivates Saudi family firms to maintain harmony, avoid disputes and create a legacy for future generations by engaging in entrepreneurial behaviours.
Examining the adoption of emergency remote teaching and virtual learning during and after COVID-19 pandemic
Authors: Anthony Jnr Bokolo , Noel Selwyn
Published: May 2021

Purpose

The Coronavirus 2019 (COVID-19) pandemic has already had a significant disruptive impact on the society, posing challenges to the provision of education across the world. Due to this crises governments over the world have temporarily closed educational institutions to help reduce the spread of COVID-19. Accordingly, educational institutions are deploying innovative emergency remote teaching (ERT) and virtual learning (VL) approaches for students to study at home. Digital technologies are being employed as a positive response to COVID-19 pandemic. Therefore, this study draws on existing literature and theories of online learning and change management to provide evidence on the state of art of ERT and VL.

Design/methodology/approach

This current study employs a systemic review of 53 sources to provide descriptive analysis leveraging on secondary sources from the literature and document reports on theories of online learning and change management, COVID-19, pandemic, emergency remote teaching and virtual learning.

Findings

Findings from this study present the theories of online learning and change management and significance and challenges of adopting ERT and VL during the COVID-19 pandemic. Also, our findings present application platforms that are being deployed for the adoption of ERT and VL during and after COVID-19 pandemic. Lastly, the findings explore potential strategies as recommendations to be employed to improve current and future adoption of ERT and VL in educational institutions.

Originality/value

This study draws on existing literature and adds to existing body of knowledge by exploring the adoption of emergency remote teaching and virtual learning during and after COVID-19 pandemic. This study provides a timely guide on the potential of emergency remote teaching and virtual learning in higher education as a response to COVID-19 crises now and into the future. This study discusses the theories of online learning and change management and also offers recommendations to educationalists and policymakers in educational institutions on addressing the crisis.
Financial impact of high land prices on the viability of winery startup projects
Authors: Santos Michael , Richman Vincent , Hu Aidong
Published: May 2021

Purpose

Does it make economic sense to invest in winery startups with high land prices? This paper aims to apply a capital budgeting analysis for a startup project to investigate the role of land prices in the decision-making of a wine entrepreneur.

Design/methodology/approach

This paper uses a capital budgeting analysis to evaluate the value of a winery project using the six investment criteria: net present value (NPV), internal rate of return (IRR), modified IRR, profitability index, payback period (PB) and discounted PB.

Findings

This study finds that high land prices are economically justifiable (NPV is greater or equal to zero) when the weighted average capital cost is sufficiently low for investors who are able to diversify risks and with access to a cheap source of funds. Additionally, this study demonstrates that wine entrepreneurs need a long-term investment horizon because the recovery of the initial investment in winery startup projects takes many years.

Research limitations/implications

The startup winery projects are heavily influenced by wine pricing, production and cost assumptions. As a result, different assumptions made at other wine regions may result in slightly different outcomes for the acceptability of the wine startup projects.

Practical implications

High land prices are economically justified for investors and entrepreneurs with the ability to diversify risk and access to cheap financial resources. As such, land prices can be a critical obstacle for individual entrepreneurs who experience a lack of capital.

Social implications

In the famous wine regions of the world, high land prices may result in more wineries being owned by the capital rich wine conglomerates.

Originality/value

This paper provides estimations of land prices based on financial methods to discuss the justification of observed prices and the implications regarding the ability of investors and entrepreneurs to access capital.
Policy and practical implications for workforce nationalization in the Gulf Cooperation Council (GCC) countries
Authors: Elbanna Said
Published: May 2021

Purpose

This study aims to advance practice and research on workforce nationalization in the Gulf Cooperation Council (GCC) countries through identifying relevant policy and practical implications needed to implement nationalization initiatives effectively.

Design/methodology/approach

The author followed a two-stage approach. Stage 1 reviewed the literature to identify relevant papers on workforce nationalization in the GCC region. Stage 2 used a thematic analysis to propose relevant implications for both policy makers and employers.

Findings

Through the lens of four perspectives at different levels, i.e. legal, organizational, human development and socio-cultural perspectives, the author has identified ten policy and practical implications. Both governments and employers need to consider these when developing holistic strategies for effective workforce nationalization.

Originality/value

Over several decades, the GCC countries have been implementing several nationalization initiatives to increase the percentage and qualifications of their national employees. The significance of these initiatives stems from the fact that the GCC countries lack adequately trained citizens. Moreover, regardless of political attitudes toward foreigners, development plans for modernization, industrialization or urbanization heavily relies on foreign employees. This is because nationals represent the minority of employees and are largely employed in the public sector. This phenomenon needs the attention of scholars to discuss different aspects of nationalization and how to effectively implement it.