bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural indicators of human gut feelings
Authors: Mayeli Ahmad , Al Zoubi Obada , White Evan J. , Chappelle Sheridan , Kuplicki Rayus , Smith Ryan , Feinstein Justin S. , Bodurka Jerzy , Paulus Martin P. , Khalsa Sahib S.
Published: February 2021

Understanding the neural processes governing the human gut-brain connection has been challenging due to the inaccessibility of the body’s interior. Here, we investigated neural responses to gastrointestinal sensation using a minimally invasive mechanosensory probe by quantifying brain, stomach, and perceptual responses following the ingestion of a vibrating capsule. Participants successfully perceived capsule stimulation under two vibration conditions (normal and enhanced), as evidenced by above chance accuracy scores. Perceptual accuracy improved significantly during the enhanced relative to normal stimulation, which was associated with a more rapid detection of the stimulation and reduced reaction time variability. Stomach stimulation induced early and late neural responses in parieto-occipital leads near the midline. Moreover, these ‘gastric evoked potentials’ showed intensity-dependent increases in amplitude and were significantly correlated with perceptual accuracy. These findings highlight a unique form of enterically-focused sensory monitoring within the human brain, with implications for understanding gut-brain interactions in healthy and clinical populations.
Mesenchymal stem cells carry and transport clusters of cancer cells
Authors: Zarubova Jana , Hasani-Sadrabadi Mohammad Mahdi , Norris Sam CP , Kasko Andrea M , Li Song
Published: February 2021

Cell clusters that collectively migrate from primary tumors appear to be far more potent in forming distant metastases than single cancer cells. A better understanding of collective cell migration phenomenon and the involvement of different cell types during this process is needed. Here, we utilize a micropatterned surface composed of a thousand of low-adhesive microwells to screen motility of spheroids containing different cell types by analyzing their ability to move from the bottom to the top of the microwells. Mesenchymal stem cells (MSCs) spheroid migration was efficient in contrast to cancer cell only spheroids. In spheroids with both cell types mixed together, MSCs were able to carry the low-motile cancer cells during migration. As the percentage of MSCs increased in the spheroids, more migrating spheroids were detected. Extracellular vesicles secreted by MSCs also contributed to the pro-migratory effect exerted by MSCs. However, the transport of cancer cells was more efficient when MSCs were physically present in the cluster. Similar results were obtained when cell clusters were encapsulated within a micropatterned hydrogel, where collective migration was guided by micropatterned matrix stiffness. These results suggest that stromal cells facilitate the migration of cancer cell clusters, which is contrary to the general belief that malignant cells metastasize independently.

Significance

During metastasis, tumor cells may migrate as a cluster, which exhibit higher metastatic capacity compared to single cells. However, whether and how non-cancer cells contained in tumor cluster regulate it’s migration is not clear. Here, we utilize two unique approaches to study collective tumor cell migration in vitro: first, in low-adhesive microwells and second, in micropatterned hydrogels to analyze migration in 3D microenvironment. Our results indicate that MSCs in tumor cell clusters could play an important role in the dissemination of cancer cells by actively transporting low-motile cancer cells. In addition, MSC-released paracrine factors also increase the motility of tumor cells. These findings reveal a new mechanism of cancer cell migration and may lead to new approaches to suppress metastases.
Natural Mucosal Barriers and COVID-19 in Children
Authors: Pierce Carl A. , Sy Sharlene , Galen Benjamin , Goldstein Doctor Y , Orner Erika , Keller Marla J. , Herold Kevan C. , Herold Betsy C.
Published: February 2021

COVID-19 is more benign in children compared to adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesized that a more robust early innate immune response to SARS-CoV-2 may protect against severe disease and compared clinical outcomes, viral copies and cellular gene and protein expression in nasopharyngeal swabs from 12 children and 27 adults upon presentation to the Emergency Department. SARS-CoV-2 copies were similar, but compared to adults, children displayed higher expression of genes associated with interferon signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1β protein were detected in nasal fluid in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected in nasal fluid from both groups and correlated negatively with mucosal IL-18. These findings suggest that a vigorous mucosal immune response in children compared to adults contributes to favorable clinical outcomes.
Sub-diagnostic effects of genetic variants associated with autism
Authors: Rolland Thomas , Cliquet Freddy , Anney Richard J.L. , Moreau Clara , Traut Nicolas , Mathieu Alexandre , Huguet Guillaume , Duan Jinjie , Warrier Varun , Portalier Swan , Dry Louise , Leblond Claire S. , Douard Elise , Amsellem Frédérique , Malesys Simon , Maruani Anna , Toro Roberto , Børglum Anders D. , Grove Jakob , Baron-Cohen Simon , Packer Alan , Chung Wendy K. , Jacquemont Sébastien , Delorme Richard , Bourgeron Thomas
Published: February 2021

While over a hundred genes are significantly associated with autism, little is known about the prevalence of variants affecting them in the general population. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Using data from more than 13,000 autistic individuals and 210,000 undiagnosed individuals, we provide a gene-level map of the odds ratio for autism associated to rare loss-of-function (LoF) variants in 185 genes robustly associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the phenotype of undiagnosed individuals heterozygous for such variants and show that they exhibit a decrease in fluid intelligence, qualification level and income, and an increase in material deprivation. These effects were larger for LoFs in autism-associated genes than in other LoF-intolerant genes and appeared largely independent of sex and polygenic scores for autism. Using brain imaging data from 21,049 UK-Biobank individuals, we provide evidence for smaller cortical surface area and volume among carriers of LoFs in genes with high odds ratios for autism. Our gene-level map is a key resource to distinguish genes with high and low odds ratio for autism, and highlights the importance of including quantitative data on both diagnosed and undiagnosed individuals to better delineate the effect of genetic variants beyond the categorical diagnosis. Data are available athttps://genetrek.pasteur.fr/.
Performance of SARS-CoV-2 rapid antigen test compared with real-time RT-PCR in asymptomatic individuals
Authors: Peña Mónica , Ampuero Manuel , Garcés Carlos , Gaggero Aldo , García Patricia , Velasquez María Soledad , Luza Ricardo , Alvarez Pía , Paredes Fabio , Acevedo Johanna , Farfán Mauricio J. , Solari Sandra , Soto-Rifo Ricardo , Valiente-Echeverría y Fernando
Published: February 2021

Screening, testing and contact tracing plays a pivotal role in the control of COVID-19 pandemic. To carry out this strategy it is necessary to increase the testing capacity. Here, we compared a SARS CoV-2 rapid antigen test (RAT) and RT-PCR in 842 asymptomatic individuals from Tarapacá, Chile. We report a sensibility of 69.86%, a specificity of 99.61%, PPV of 94.44% and NPP of 97.22% with Ct values (Ct > 27) that were significantly higher among individuals with false-negative RAT. These results support the fact that RAT might have a significant impact in the identification of asymptomatic carriers in areas that lack well-equipped laboratories to perform SARS-CoV-2 real -time RT-PCR diagnostics or the results take more than 24-48 hours, as well as zones with high traffic of individuals, such as border/customs, airports, interregional bus, train stations or in any mass testing campaign requiring rapid results.
Memory of split-belt walking endures weeks in young children and younger adults but less so in older adults
Authors: Lissinna Brittany , Smith Allison , La Kaylie , Yang Jaynie F
Published: February 2021

Adults and children modify how they move to accommodate persistent changes in their surroundings, called motor adaptation. Walking-related motor adaption can be seen when one walks on a treadmill with two belts running at different speeds, a split-belt treadmill, where a new walking pattern is slowly adopted with practice. This has been suggested as a way to improve left-right symmetry in walking after a stroke. Central to using split-belt walking for rehabilitation is whether the adapted motor pattern is retained over days and weeks, and whether this motor memory is a function of the person’s age. When first exposed to split-belt walking, the walking is asymmetric (initial error), resembling a limp. With subsequent exposure, the error is smaller than the initial error, indicating the adaptation was remembered. Here, we explored the persistence of this memory over 24 hours, one week, and two weeks, in young children (3-6 yr old), younger adults (20-30 yr old) and older adults (50-70 yr old). We found that the motor memory declines with the interval duration, but was still evident up to 2 weeks after initial exposure. Retention of the motor memory in children and younger adults was better than older adults. Further, forgetting between trials was seen on the first day of split-belt walking especially in children and older adults, but this forgetting diminished with repeated trials. The results indicate that long-term memory of motor adaptation on the split-belt treadmill is affected by age, but it may be possible to enhance the memory by more frequent and repeated exposure. This suggests that when using split-belt adaptation in rehabilitation, the sessions should ideally be less than one week apart.
A macroecological description of alternative stable states reproduces intra- and inter-host variability of gut microbiome
Authors: Zaoli Silvia , Grilli Jacopo
Published: February 2021

The most fundamental questions in microbial ecology concern the diversity and variability of communities. Their composition varies widely across space and time, as it is determined by a non-trivial combination of stochastic and deterministic processes. The interplay between non-linear community dynamics and environmental fluctuations determines the rich statistical structure of community variability, with both rapid temporal dynamics fluctuations and non-trivial correlations across habitats. Here we analyze long time-series of gut microbiome and compare intra- and inter-community dissimilarity. Under a macroecological framework we characterize their statistical properties. We show that most taxa have large but stationary fluctuations over time, while a minority is characterized by quick changes of average abundance which cluster in time, suggesting the presence of alternative stable states. We disentangle inter-individual variability in a major stochastic component and a deterministic one, the latter recapitulated by differences in the carrying capacities of taxa. Finally, we develop a model which includes environmental fluctuations and alternative stable states. This model quantitatively predicts the statistical properties of both intra- and inter-individual community variability, therefore summarizing variation in a unique macroecological framework.
Metabolic and Process Engineering for Microbial Production of Protocatechuate from Xylose withCorynebacterium glutamicum
Authors: Labib Mohamed , Görtz Jonas , Brüsseler Christian , Kallscheuer Nicolai , Gätgens Jochem , Jupke Andreas , Marienhagen Jan , Noack Stephan
Published: February 2021

3,4-Dihydroxybenzoate (protocatechuate, PCA) is a phenolic compound naturally found in edible vegetables and medicinal herbs. PCA is of interest in the chemical industry as a building block for novel polymers and has wide potential for pharmaceutical applications due to its antioxidant, anti-inflammatory, and antiviral properties. In the present study, we designed and constructed a novelCorynebacterium glutamicumstrain to enable the efficient utilization ofd-xylose for microbial production of PCA. The engineered strain showed a maximum PCA titer of 62.1 ± 12.1 mM (9.6 ± 1.9 g L−1) fromd-xylose as the primary carbon and energy source. The corresponding yield was, which corresponds to 38 % of the maximum theoretical yield and is 14-fold higher compared to the parental producer strain ond-glucose. By establishing a one-pot bioreactor cultivation process followed by subsequent process optimization, the same maximum titer and a total amount of 16.5 ± 1.1 g was reached. Downstream processing of PCA from this fermentation broth was realized via electrochemically induced crystallization by taking advantage of the pH-dependent properties of PCA. Since PCA turned out to be electrochemically unstable in combination with several anode materials, a threechamber electrolysis setup was established to crystallize PCA and to avoid direct anode contact. This resulted in a maximum final purity of 95.4 %. In summary, the established PCA production process represents a highly sustainable approach, which will serve as a blueprint for the bio-based production of other hydroxybenzoic acids from alternative sugar feedstocks.
Experimental Control of a Reaction Occurring during the Interaction between Chicken Anemia Virus (CAV) and Its Corresponding Antibodies
Authors: Ivanov Ognyan , Todorov Petar , Simeonov Konstantin , Vaseashta Ashok
Published: February 2021

In our ongoing investigations, we have studied a specific interaction between electromagnetic fields and matter – the so-called Electromagnetic echo effect (EMEE). It enables rapid and contactless investigations of gases, liquids and solids to be performed, since the signal generated as a result of the effect is quite sensitive to all kinds of changes occurring within the studied samples. The effect can be considered universal for all matter and provides analysis in real time. We use this phenomenon to demonstrate the practical possibility to control reactions, occurring between Chicken anemia virus (CAV) and the corresponding antibodies. This methodology can be used for simple but reliable control of similar, otherwise hard to detect, antigen-antibody reactions, in order to confirm the presence of a certain viral species. The approach offers a high level of safety, since it enables measurements to be taken remotely, thus limiting exposure to contagion. We further discuss the possibility to register the presence of SARS-nCoV-2 in an attempt to address current global pandemic.
Tumor expressed CD95 causes suppression of anti-tumor activity of NK cells in a model of triple negative breast cancer
Authors: Qadir Abdul S. , Guégan Jean Philippe , Ginestier Christophe , Chaibi Assia , Bessede Alban , Charafe-Jauffret Emmanuelle , Macario Manon , Lavoué Vincent , de la Motte Rouge Thibault , Law Calvin , Vilker Jacob , Wang Hongbin , Stroup Emily , Schipma Matthew J. , Bridgeman Bryan , Murmann Andrea E. , Ji Zhe , Legembre Patrick , Peter Marcus E.
Published: February 2021

The apoptosis inducing receptor CD95/Fas has multiple tumorigenic activities. Stimulation by its cognate ligand CD95L on many cancer cells increases their growth, motility, ability to invade and/or their cancer stemness. Using genetically engineered mouse models of ovarian and liver cancer, we previously reported that deletion of CD95 in the tumor cells strongly reduced their ability to growin vivo[1, 2]. Using a combination of immune-deficient and immune-competent mouse models, we now establish that loss of CD95 in metastatic triple negative breast cancer cells prevents tumor growth by modulating the immune landscape. CD95 deficient but not wild-type tumors barely grow in an immune-competent environment and show an increase in immune infiltrates into the tumor. This growth reduction is caused by NK cells and does not involve CD8+T cells. On the other hand, in immune compromised mice CD95 k.o. cells are not growth inhibited, but they fail to form metastases. In summary, we demonstrate that in addition to its tumor and metastasis promoting activities, CD95 expression by tumor cells can exert immune suppressive activities providing a new target for immune therapy.
HaVoC, a bioinformatic pipeline for reference-based consensus assembly and lineage assignment for SARS-CoV-2 sequences
Authors: Nguyen Phuoc Truong , Plyusnin Ilya , Sironen Tarja , Vapalahti Olli , Kant Ravi , Smura Teemu
Published: February 2021

Background

SARS-CoV-2 related research has increased in importance worldwide since December 2019. Several new variants of SARS-CoV-2 have emerged globally, of which the most notable and concerning currently are the UK variant B.1.1.7, the South African variant B1.351 and the Brazilian variant P.1. Detecting and monitoring novel variants is essential in SARS-CoV-2 surveillance. While there are several tools for assembling virus genomes and performing lineage analyses to investigate SARS-CoV-2, each is limited to performing singular or a few functions separately.

Results

Due to the lack of publicly available pipelines, which could perform fast reference-based assemblies on raw SARS-CoV-2 sequences in addition to identifying lineages to detect variants of concern, we have developed an open source bioinformatic pipeline calledHaVoC(Helsinki university Analyzer for Variants Of Concern).HaVoCcan reference assemble raw sequence reads and assign the corresponding lineages to SARS-CoV-2 sequences.

Conclusions

HaVoCis a pipeline utilizing several bioinformatic tools to perform multiple necessary analyses for investigating genetic variance among SARS-CoV-2 samples. The pipeline is particularly useful for those who need a more accessible and fast tool to detect and monitor the spread of SARS-CoV-2 variants of concern during local outbreaks.HaVoCis currently being used in Finland for monitoring the spread of SARS-CoV-2 variants.HaVoCuser manual and source code are available athttps://www.helsinki.fi/en/projects/havocandhttps://bitbucket.org/auto_cov_pipeline/havoc, respectively.
Easy multiple sequential CRISPR/Cas9 knockouts in cell lines using a Cre/LoxP re-cyclable vector
Authors: Dong Li , Etemadi Nima , Vaux David L
Published: February 2021

To easily generate cell lines lacking multiple proteins, we inserted Cre/Lox sites flanking the guide RNA, Cas9, and mCherry fluorescent protein coding regions of a CRISPR/Cas9 lentiviral vector. Cells bearing an inducible Cre recombinase construct can be transfected with the CRISPR/Cas9 lentiviral vector, and mCherry positive cells sorted by flow cytometry. Induction of Cre causes deletion of the guide RNA,Cas9, andmCherrygenes, so that mCherry negative cells can be isolated. After confirming successful targeting of the gene, the cells can be re-infected with the same vector bearing a different guide RNA, and mCherry-positive cells sorted once more. In this way, multiple genes can be mutated sequentially using the same vector and selection marker, without persistent expression of the guide RNA or Cas9. We used this system to sequentially mutate two candidate genes,Bak1andBcl2, and generated lines that lacked expression of both proteins.
AnadAmutation confers nicotinic acid auxotrophy in pro-carcinogenic intestinalEscherichia coliNC101
Authors: Lopez Lacey R. , Barlogio Cassandra J. , Broberg Christopher A. , Wang Jeremy , Arthur Janelle C.
Published: February 2021

Inflammatory bowel diseases and inflammation-associated colorectal cancer are linked to blooms of adherent-invasiveEscherichia coli(AIEC) in the intestinal microbiota. AIEC are functionally defined by their ability to adhere/invade epithelial cells and survive/replicate within macrophages. Changes in micronutrient availability can alter AIEC physiology and interactions with host cells. Thus, culturing AIEC for mechanistic investigations often involves precise nutrient formulation. We observed that the pro-inflammatory and pro-carcinogenic AIEC strain NC101 failed to grow in minimal media (MM). We hypothesized that NC101 was unable to synthesize a vital micronutrient normally found in the host gut. Through nutrient supplementation studies, we identified that NC101 is a nicotinic acid (NA) auxotroph. NA auxotrophy was not observed in the other non-toxigenicE. colior AIEC strains we tested. Sequencing revealed NC101 has a missense mutation innadA, a gene encoding quinolinate synthase A that is important forde novoNAD biosynthesis. Correcting the identifiednadApoint mutation restored NC101 prototrophy without impacting AIEC function, including motility and AIEC-defining survival in macrophages. Our findings, along with the generation of a prototrophic NC101 strain, will greatly enhance the ability to performin vitrofunctional studies that are needed for mechanistic investigations on the role of intestinalE. coliin digestive disease.

Importance

Inflammatory bowel diseases (IBD) and colorectal cancer (CRC) are significant global health concerns that are influenced by gut resident microbes, like adherent-invasiveEscherichia coli(AIEC). Nutrient availability influences specialized metabolite production, AIEC-defining functional attributes, and AIEC:host interactions. NC101 is a pro-inflammatory and pro-carcinogenic AIEC strain commonly used for studies on IBD and CRC. We identified that NC101 growthin vitrorequires a micronutrient found in the host gut. By correcting an identified mutation, we generated an NC101 strain that no longer has micronutrient restrictions. Our findings will facilitate future research that necessitates precise nutrient manipulation, enhancing AIEC functional studies and investigations on other auxotrophic intestinal microbiota members. Broadly, this will improve the study of bacterial:host interactions impacting health and disease.
A bacteriophage cocktail significantly reducesListeria monocytogeneswithout deleterious impact on the commensal gut microbiota under simulated gastro-intestinal conditions
Authors: Jakobsen Rasmus Riemer , Trinh Jimmy T. , Bomholtz Louise , Brok-Lauridsen Signe Kristine , Sulakvelidze Alexander , Nielsen Dennis Sandris
Published: February 2021

In this study, we examined the effect of a bacteriophage cocktail (tentatively designated FOP, for Foodborne Outbreak Pill) on the levels ofListeria monocytogenesin simulated small intestine, large intestine, and Caco-2 model systems. We found that FOP survival during simulated passage of the upper gastrointestinal was dependent on stomach pH, and that FOP robustly inhibitedL. monocytogeneslevels with effectiveness comparable to antibiotic treatment (ampicillin) under simulated ilium and colon conditions. FOP did not inhibit the commensal bacteria, whereas ampicillin treatment led to dysbiosis-like conditions. FOP was also more effective than antibiotic in protecting Caco-2 cells from adhesion and invasion byL. monocytogenes, while not triggering an inflammatory response. Our data suggest that FOP may provide a robust protection againstL. monocytogenesshould the bacterium enter the human gastrointestinal tract (e.g., by consumption of contaminated food), without deleterious impact on the commensal bacteria.
Bereavement care for ethnic minority communities: A systematic review of access to, models of, outcomes from, and satisfaction with, service provision
Authors: Mayland Catriona Rachel , Powell Richard A. , Clarke Gemma , Ebenso Bassey , Allsop Matthew J
Published: February 2021

Objectives

To review and synthesize the existing evidence on bereavement care, within the United Kingdom (UK), for ethnic minority communities in terms of barriers and facilitators to access; models of care; outcomes from, and satisfaction with, service provision.

Design

A systematic review adopting a framework synthesis approach was conducted. An electronic search of the literature was undertaken in MEDLINE, Embase, PsycINFO, Social Work Abstract and CINAHL via EBSCO, Global Health, Cochrane library, the Trip database and ProQuest between 2000 and 2020. Search terms included bereavement care, ethnic minority populations and the UK setting.

Results

From 3,185 initial records, following screening for eligibility, and full-text review of 164 articles, seven studies were identified. There was no research literature outlining the role of family, friends and existing networks; and a real absence of evidence about outcomes and levels of satisfaction for those from an ethnic minority background who receive bereavement care. From the limited literature, the overarching theme for barriers to bereavement care was ‘unfamiliarity and irregularities’. Four identified subthemes were ‘lack of awareness’; ‘variability in support’; ‘type and format of support’; and ‘culturally specific beliefs’. The overarching theme for facilitators for bereavement care was ‘accessibility’ with the two subthemes being ‘readily available information’ and ‘inclusive approaches’. Three studies reported on examples of different models of care provision.

Conclusions

This review reveals a stark lack of evidence about bereavement care for ethnic minority populations. In particular, understanding more about the role of family, friends and existing support systems, alongside outcomes and satisfaction will begin to develop the evidence base underpinning current provision. Direct user-representation through proactive engagement and co-design approaches may begin to determine the most appropriate models and format of bereavement care for ethnic minority communities to inform service design and delivery.
Computational validation of clonal and subclonal copy number alterations from bulk tumour sequencing
Authors: Antonello Alice , Bergamin Riccardo , Calonaci Nicola , Househam Jacob , Milite Salvatore , Williams Marc J , Anselmi Fabio , d’Onofrio Alberto , Sundaram Vasavi , Sosinsky Alona , Cross William CH , Caravagna Giulio
Published: February 2021

Abstract

The identification of chromosome number alterations is now widespread in cancer research, but three features of genomic data hinder copy number calling and downstream analyses: the purity of the tumour sample, intra-tumour heterogeneity, and the ploidy of the tumour. To assess these features, consensus methods are often utilised, though these become onerous in projects that involve thousands of genomes. To facilitate the validation of clonal and subclonal copy number variants we present CNAqc, an evolution-inspired toolset that leverages the known quantitative relationships of purity, ploidy and heterogeneity. We validate the algorithms in CNAqc using low-pass single-cell data, as well as extensive simulations. Its application is demonstrated using over 4000 whole genomes and exomes from TCGA, and PCAWG. A real world application of CNAqc in the analysis of clinical tumour samples, has been demonstrated by its incorporation into the validation of clinically accredited bioinformatics pipeline at Genomics England. Our approach is compatible with most bioinformatic pipelines and designed to augment algorithms with automated quality control procedures for data validation.
Comprehensive metabolic engineering for fermenting glycerol efficiently inSaccharomyces cerevisiae
Authors: Khattab Sadat M. R. , Watanabe Takashi
Published: February 2021

Glycerol is an eco-friendly solvent enhancing plant-biomass decomposition through a glycerolysis process in many pretreatment methods. Nonetheless, the lack of efficient conversion of glycerol by naturalSaccharomyces cerevisiaerestrains many of these scenarios. Here we outline the complete strategy for the generation of efficient glycerol fermenting yeast by rewriting the oxidation of cytosolic nicotinamide adenine dinucleotide (NADH) by O2-dependent dynamic shuttle while abolishing both glycerol phosphorylation and biosynthesis pathways. By following a vigorous glycerol oxidative pathway, the engineered strain demonstrated augmentation in conversion efficiency (CE) reach up to 0.49g-ethanol/g-glycerol—98% of theoretical conversion—with production rate >1 g/L-1h-1when supplementing glycerol as a single fed-batch on a rich-medium. Furthermore, the engineered strain showed a new capability toward ferment a mixture of glycerol and glucose with producing >86 g/L of bioethanol with 92.8% of the CE. To our knowledge, this is the highest ever reported titer in this regard. Notably, this strategy flipped our ancestral yeast from non-growth on glycerol, on the minimal medium, to a fermenting strain with productivities 0.25-0.5 g/L-1h-1and 84-78% of CE, respectively and 90% of total conversions to the products. The findings in metabolic engineering here may release the limitations of utilizing glycerol in several eco-friendly biorefinery approaches.

IMPORTANCE

With the avenues for achieving efficient lignocellulosic biorefinery scenarios, glycerol gained keen attention as an eco-friendly biomass-derived solvent for enhancing the dissociation of lignin and cell wall polysaccharides during pretreatment process. Co-fermentation of glycerol with the released sugars from biomass after the glycerolysis expands the resource for ethanol production and release from the burden of component separation. Titer productivities are one of the main obstacles for industrial applications of this process. Therefore, the generation of highly efficient glycerol fermenting yeast significantly promotes the applicability of the integrated biorefineries scenario. Besides, the glycerol is an important carbon resource for producing chemicals. Hence, the metabolic flux control of yeast from glycerol contributes to generation of cell factory producing chemicals from glycerol, promoting the association between biodiesel and bioethanol industries. Thus, this study will shed light on solving the problems of global warming and agricultural wastes, leading to establishment of the sustainable society.
Chemical ecology of an apex predator life cycle
Authors: Mucci Nicholas C. , Jones Katarina A. , Cao Mengyi , Wyatt Michael R. , Foye Shane , Kauffman Sarah , Taufer Michela , Chikaraishi Yoshito , Steffan Shawn , Campagna Shawn , Goodrich-Blair Heidi
Published: February 2021

Microbial symbiotic interactions, mediated by small molecule signaling, drive physiological processes of higher order systems. Metabolic analytic technologies advancements provide new avenues to examine how chemical ecology, or conversion of existing biomass to new forms, changes over a symbiotic lifecycle. We examine such processes using the tripartite relationship between nematode hostSteinernema carpocapsae, its obligate mutualist bacterium,Xenorhabdus nematophila, and the insects they infect together. We integrate trophic, metabolomics, and gene regulation analyses to understand insect biomass conversion to nematode or bacterium biomass. Trophic analysis established bacteria as the primary insect consumers, with nematodes at trophic position 4.37, indicating consumption of bacteria and likely other nematodes. Significant, discrete metabolic phases were distinguishable from each other, indicating the insect chemical environment changes reproducibly during bioconversion. Tricarboxylic acid cycle components and amino acids were significantly affected throughout infection. These findings contribute to an ongoing understanding of how symbiont associations shape chemical environments.

Teaser

Entomopathogenic nematodes act as an apex predator in some ecosystems through altering chemical environments of their prey.
Invadopodia enable cooperative invasion and metastasis of breast cancer cells
Authors: Perrin L. , Belova E. , Bayarmagnai B. , Tüzel E. , Gligorijevic B.
Published: February 2021

Invasive and non-invasive cancer cells can invade together during the cooperative invasion. However, the events leading to it, role of EMT and the consequences this may have on metastasis are unknown. In this study, we demonstrate that the isogenic 4T1 and 67NR breast cancer cells sort from each other in 3D spheroids, followed by cooperative invasion. By time-lapse microscopy, we show that the invasive 4T1 cells move more persistently compared to non-invasive 67NR, sorting and accumulating at the spheroid-ECM interface, a process dependent on cell-ECM adhesions and independent from E-cadherin cell-cell adhesions. Elimination of invadopodia in 4T1 cells blocks invasion, demonstrating that invadopodia requirement is limited to leader cells. Importantly, we demonstrate that cells with and without invadopodia can also engage in cooperative metastasis in preclinical mouse models. Altogether, our results suggest that a small number of cells with invadopodia can drive the metastasis of heterogeneous cell clusters.
Innate Immune sensing of Influenza A viral RNA through IFI16 promotes pyroptotic cell death
Authors: Mishra Shalabh , Raj Athira S , Kumar Akhilesh , Rajeevan Ashwathi , Kumari Puja , Kumar Himanshu
Published: February 2021

Programmed cell death pathways are triggered by various stresses or stimuli, including viral infections. The mechanism underlying the regulation of these pathways upon Influenza A virus IAV infection is not well characterized. We report that a cytosolic DNA sensor IFI16 is essential for the activation of programmed cell death pathways in IAV infected cells. We have identified that IFI16 functions as an RNA sensor for influenza A virus by binding to genomic RNA. The activation of IFI16 triggers the production of type I, III interferons, and also other pro-inflammatory cytokines via the STING-TBK1 and Pro-caspase-1 signaling axis, thereby promoting cell death (apoptosis and pyroptosis in IAV infected cells). Whereas, IFI16 knockdown cells showed reduced inflammatory responses and also prevented cell mortality during IAV infection. These results demonstrate the pivotal role of IFI16-mediated IAV sensing and its essential role in activating programmed cell death pathways.
Validation of the Crystallography Open Database using the Crystallographic Information Framework
Authors: Vaitkus Antanas , Merkys Andrius , Gražulis Saulius
Published: February 2021

Data curation practices of the Crystallography Open Database (COD) are described with additional focus being placed on the formal validation using the Crystallographic Information Framework (CIF). The cif_validate program, capable of validating CIF files against both the DDL1 and the DDLm dictionaries, is presented and used to process the entirety of the COD. Validation results collected from over 450 000 CIF files are demonstrated to be a useful resource in the data maintenance process as well as the development of the underlying ontologies. A set of programs intended to aid in the dictionary migration from DDL1 to DDLm is also presented.
Finding the best-fit background function for whole-powder-pattern fitting using LASSO combined with tree search
Authors: Toraya Hideo
Published: February 2021

A new linear function for modelling the background in whole-powder-pattern fitting has been derived by applying LASSO (least absolute shrinkage and selection operator) and the technique of tree search. The background function (BGF) consists of termsbnL(2θ/180)−n/2 andbnH(1 − 2θ/180)−n/2for the low- and high-angle sides, respectively. Some variable parameters of the BGF should be fixed at zero while others should be varied in order to find the best fit for a given data set without inducing overfitting. The LASSO algorithm can automatically select the variables in linear regression analysis. However, it finds the best-fit BGF with a set of adjustable parameters for a given data set while it derives a different set of parameters for a different data set. Thus, LASSO derives multiple solutions depending on the data set used. By regarding the individual solutions from LASSO as nodes of trees, tree structures were constructed from these solutions. The root node has the maximum number of adjustable parameters,P.Pdecreases with descending levels of the tree one by one, and leaf nodes have just one parameter. By evaluating individual solutions (nodes) by their χ2index, the best-fit single path from a root node to a leaf node was found. The present BGF can be used simply by varyingPin the range 1–10. The BGF thus derived as a final single solution was incorporated into computer programs for Pawley-based whole-powder-pattern decomposition and Rietveld refinement, and the performance of the BGF was tested in comparison with the polynomials currently widely used as the BGF. The present BGF has been demonstrated to be stable and to give an excellent fit, comparable to polynomials but with a smaller number of adjustable parameters and without introducing undulation into the calculated background curve. Basic algorithms used in statistics and machine learning have been demonstrated to be useful in developing an analytical model in X-ray crystallography.
Recognizing nonmonotonicity of exogenous determinants in a stochastic profit efficiency framework: have banks overinvested in IT capital?
Authors: Prakash Navendu , Singh Shveta , Sharma Seema
Published: February 2021

Purpose

The purpose of this study is to explore and evaluate potential nonmonotonicity in the determinants of profit efficiency, specifically IT and R&D investments in the Indian commercial banking sector.

Design/methodology/approach

The study employs an alternative stochastic profit efficiency framework and introduces nonmonotonic effects by parameterizing the location and scale parameters of the inefficiency component on an unbalanced panel data set of 72 commercial banks in the 2008–2019 period. Marginal effects across quartiles are calculated using a bias-corrected and accelerated bootstrap procedure of 500 simulations. The study disaggregates across ownership and size for gauging the impact of structure on the associations between determinants of profit efficiency.

Findings

The study partially rejects the productivity paradox as it discovers a negative association of IT and R&D with profit inefficiency. However, the observed nonmonotonicity of IT is of significance for bank managers, as the study concludes that overinvestment in IT is detrimental to a bank’s profit-maximizing interests. Further, bank size, loan default and credit risk depict a nonmonotonic relationship across the sample with large banks, high NPAs and high credit risk associated with reducing profit efficiency. In addition, higher margins and greater diversification are related positively to efficiency, and banks with cost-heavy structures or having high liquidity risk associated negatively with efficiency.

Originality/value

To the best knowledge of the authors, the study is perhaps the first to acknowledge and incorporate nonmonotonic associations of IT investments amidst other exogenous determinants under a stochastic profit efficiency framework.
Measuring national intellectual capital: a novel approach
Authors: Vo Duc Hong , Tran Ngoc Phu
Published: February 2021

Purpose

A very few studies have been conducted to measure a degree of national intellectual capital for selected groups of countries. This paper is conducted to construct a new index of national intellectual capital (INIC) which is simple, quantifiable, relevant and comparable for countries around the globe.

Design/methodology/approach

The styudy’s new INIC uses various indicators which are proxies for fundamental aspects of intellectual capital, including (1) human capital, (2) structural capital and (3) relational capital. These indicators are publicly available for many countries. The principal component analysis is utilized to derive the INIC. Various tests have also been conducted to ensure that the new index is appropriate and fit for purpose.

Findings

Findings from this paper confirm that the new INIC has a strong correlation of 0.80 with an index developed by Lin et al. (2014) (the LECB index), an advanced INIC to date. The LECB index has been infrequently updated and covered selected countries due to data and information unavailability. In addition, the study’s tests indicate that a high correlation of 0.75 is observed between the study’s index and GDP per capita. The new INIC represents an advancement in relation to its simplicity, quantification, relevance and international comparison across nations.

Practical implications

The estimates of national intellectual capital using the approach in this study will open a new strand of theoretical and empirical studies in relation to national intellectual capital and other economic and social issues of interests. This novel and innovative approach will provide policymakers with a valuable framework to formulate and implement relevant policies to enhance and improve national intellectual capital.

Originality/value

To the best knowledge of the authors, this is the first study of its type, which is conducted to measure national intellectual capital based on publicly available data. Required data cover an extended period of years and a majority of countries. As such, an INIC will enhance transparency and feasibility for international comparison across countries.
The moderation effect of gender on accepting electronic payment technology: a study on United Arab Emirates consumers
Authors: Alshurideh Muhammad Turki , Al Kurdi Barween , Masa’deh Ra’ed , Salloum Said A.
Published: February 2021

Purpose

This paper aims to investigate if perceived security, trust and perceived privacy affect both perceived usefulness and perceived ease of use. Also, the study explores if trust, perceived usefulness and perceived ease of use influence consumers’ intentions to use the e-payment system which is supported by testing the moderation effect of gender on the intention to use such systems in the higher education institutes.

Design/methodology/approach

In total, 850 participants from United Arab Emirates (UAE) universities have filled an online questionnaire prepared for these aims. The survey instrument is composed of 22 items. The primary data was used to test the study model, proposed constructs and the study hypotheses using the Smart PLS Software.

Findings

The research confirmed that perceived security, trust and perceived privacy affect both perceived usefulness and perceived ease of use. Also, the study found that trust, perceived usefulness and perceived ease of use have anticipated the significance of consumers’ intention to use e-payment system which is found also moderated by gender. Research outcomes indicated an important contribution towards the acceptance of e-payment systems and the common design of e-commerce systems.

Originality/value

Research outcomes have indicated an important contribution toward the acceptance of e-payment systems and the common design of e-commerce systems. Additionally, this study helped in increasing the reader’s understanding of various aspects of e-commerce, specifically consumers’ trust and privacy protection which consequently allows the online sellers to formulate appropriate strategies and actions imperative to serve the online purchasers and target the internet users.
A ‘How to’ guide for interpreting parameters in habitat‐selection analyses
Authors: Fieberg John , Signer Johannes , Smith Brian , Avgar Tal
Published: February 2021

Habitat‐selection analyses allow researchers to link animals to their environment via habitat‐selection or step‐selection functions, and are commonly used to address questions related to wildlife management and conservation efforts. Habitat‐selection analyses that incorporate movement characteristics, referred to as integrated step‐selection analyses, are particularly appealing because they allow modelling of both movement and habitat‐selection processes.

Despite their popularity, many users struggle with interpreting parameters in habitat‐selection and step‐selection functions. Integrated step‐selection analyses also require several additional steps to translate model parameters into a full‐fledged movement model, and the mathematics supporting this approach can be challenging for many to understand.

Using simple examples, we demonstrate how weighted distribution theory and the inhomogeneous Poisson point process can facilitate parameter interpretation in habitat‐selection analyses. Furthermore, we provide a ‘how to’ guide illustrating the steps required to implement integrated step‐selection analyses using the amt package

By providing clear examples with open‐source code, we hope to make habitat‐selection analyses more understandable and accessible to end users.
Low resilience at the early stages of recovery of the semi‐arid Chaco forest—Evidence from a field experiment
Authors: Lipoma M. Lucrecia , Cabrol Diego A. , Cuchietti Aníbal , Enrico Lucas , Gorné Lucas D. , Díaz Sandra
Published: February 2021

Resilience—the capacity of an ecosystem to recover from disturbance—is a popular concept but quantitative empirical studies are still uncommon. This lack of empirical evidence is especially true for semi‐arid ecosystems in the face of the combined and often confounding impacts of land use and climate changes.

We designed a methodology to disentangle vegetation responses to land‐use exclusion and weather variability, and piloted it at the southern extreme of the Gran Chaco forest, the most extensive seasonally dry forest in South America. We established 16 pairs of neighbouring fenced and unfenced plots in four ecosystem types resulting from different long‐term land‐use regimes under the same climate and on highly similar soil parental material. From lower to higher land‐use intensity, related with logging and livestock grazing and trampling, these types were: primary forest (no land use in the last 50 years), secondary forest, closed species‐rich shrubland and open shrubland. In each plot we monitored plant species composition during the first 5 years following land‐use exclusion, and evaluated the resilience as the rate of change of vegetation towards the primary forest, considered as the reference ecosystem.

We found that during the first 5 years of exclusion and despite the high rainfall, only grass cover in the secondary forest showed positive resilience (recovery towards the reference ecosystem). The rest of the variables in the other ecosystem types showed either no significant change (null resilience) or even transitioned away from the reference state (negative resilience).

Synthesis. The lack of detectable recovery after 5 years of exclusion suggests that (a) long‐term land use, even at lower intensities, has affected the sources of resilience of this ecosystem; (b) rainy periods do not necessarily speed up recovery as suggested in the literature; and (c) study designs should incorporate the variation of the reference ecosystem in order to differentiate the effect of land use from other factors in a context of climate change. Although still confined to the early post‐disturbance stages, our findings suggest that recovery of these systems may be slower and more complicated than predicted in the literature on the basis of space‐for‐time substitutions.