bluuebunny/crossref_metadata_2025 huggingface dataset:
The supernumerary B chromosome of maize: drive and genomic conflict
Authors: Birchler James A. , Yang Hua
Published: November 2021

The supernumerary B chromosome of maize is dispensable, containing no vital genes, and thus is variable in number and presence in lines of maize. In order to be maintained in populations, it has a drive mechanism consisting of nondisjunction at the pollen mitosis that produces the two sperm cells, and then the sperm with the two B chromosomes has a preference for fertilizing the egg as opposed to the central cell in the process of double fertilization. The sequence of the B chromosome coupled with B chromosomal aberrations has localized features involved with nondisjunction and preferential fertilization, which are present at the centromeric region. The predicted genes from the sequence have paralogues dispersed across all A chromosomes and have widely different divergence times suggesting that they have transposed to the B chromosome over evolutionary time followed by degradation or have been co-opted for the selfish functions of the supernumerary chromosome.
An accurate model for SARS-CoV-2 pooled RT-PCR test errors
Authors: Daon Yair , Huppert Amit , Obolski Uri
Published: November 2021

Pooling is a method of simultaneously testing multiple samples for the presence of pathogens. Pooling of SARS-CoV-2 tests is increasing in popularity, due to its high testing throughput. A popular pooling scheme is Dorfman pooling: test
N
individuals simultaneously, if the test is positive, each individual is then tested separately; otherwise, all are declared negative. Most analyses of the error rates of pooling schemes assume that including more than a single infected sample in a pooled test does not increase the probability of a positive outcome. We challenge this assumption with experimental data and suggest a novel and parsimonious probabilistic model for the outcomes of pooled tests. As an application, we analyse the false-negative rate (i.e. the probability of a negative result for an infected individual) of Dorfman pooling. We show that the false-negative rates under Dorfman pooling increase when the prevalence of infection decreases. However, low infection prevalence is exactly the condition when Dorfman pooling achieves highest throughput efficiency. We therefore urge the cautious use of pooling and development of pooling schemes that consider correctly accounting for tests’ error rates.
Macrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids
Authors: Brewster Richard C. , Labeaga Irati Colmenero , Soden Catriona E. , Jarvis Amanda G.
Published: November 2021

Improving the sustainability of synthesis is a major goal in green chemistry, which has been greatly aided by the development of asymmetric transition metal catalysis. Recent advances in asymmetric catalysis show that the ability to control the coordination sphere of substrates can lead to improvements in enantioselectivity and activity, in a manner resembling the operation of enzymes. Peptides can be used to mimic enzyme structures and their secondary interactions and they are easily accessible through solid-phase peptide synthesis. Despite this, cyclic peptides remain underexplored as chiral ligands for catalysis due to synthetic complications upon macrocyclization. Here, we show that the solid-phase synthesis of peptides containing metal-binding amino acids, bipyridylalanine (
1
), phenyl pyridylalanine (
2
) and
N,N-
dimethylhistidine (
3
) can be combined with peptide macrocylization using peptide cyclase 1 (PCY1) to yield cyclic peptides under mild conditions. High conversions of the linear peptides were observed (approx. 90%) and the Cu-bound cyclo(FSAS(
1
)SSKP) was shown to be a competent catalyst in the Friedel-Crafts/conjugate addition of indole. This study shows that PCY1 can tolerate peptides containing amino acids with classic inorganic and organometallic ligands as side chains, opening the door to the streamlined and efficient development of cyclic peptides as metal ligands.
Mechanics of floating bodies
Authors: Beig Robert , Schmidt Bernd G.
Published: November 2021

We introduce and study the mechanical system which describes the dynamics and statics of rigid bodies of constant density floating in a calm incompressible fluid. Since much of the standard equilibrium theory, starting with Archimedes, allows bodies with vertices and edges, we assume the bodies to be convex and take care not to assume more regularity than that implied by convexity. One main result is the (Lyapunov) stability of equilibria satisfying a condition equivalent to the standard ‘metacentric’ criterion.
Chicken gut microbiome members limit the spread of an antimicrobial resistance plasmid in
Escherichia coli
Authors: Duxbury Sarah J. N. , Alderliesten Jesse B. , Zwart Mark P. , Stegeman Arjan , Fischer Egil A. J. , de Visser J. Arjan G. M.
Published: November 2021

Plasmid-mediated antimicrobial resistance is a major contributor to the spread of resistance genes within bacterial communities. Successful plasmid spread depends upon a balance between plasmid fitness effects on the host and rates of horizontal transmission. While these key parameters are readily quantified
in vitro
, the influence of interactions with other microbiome members is largely unknown. Here, we investigated the influence of three genera of lactic acid bacteria (LAB) derived from the chicken gastrointestinal microbiome on the spread of an epidemic narrow-range ESBL resistance plasmid, IncI1 carrying

bla
CTX-M-1

, in mixed cultures of isogenic
Escherichia coli
strains. Secreted products of LAB decreased
E. coli
growth rates in a genus-specific manner but did not affect plasmid transfer rates. Importantly, we quantified plasmid transfer rates by controlling for density-dependent mating opportunities. Parametrization of a mathematical model with our
in vitro
estimates illustrated that small fitness costs of plasmid carriage may tip the balance towards plasmid loss under growth conditions in the gastrointestinal tract. This work shows that microbial interactions can influence plasmid success and provides an experimental-theoretical framework for further study of plasmid transfer in a microbiome context.
Recommendations for improving statistical inference in population genomics
Authors: Johri Parul , Aquadro Charles F. , Beaumont Mark , Charlesworth Brian , Excoffier Laurent , Eyre-Walker Adam , Keightley Peter D. , Lynch Michael , McVean Gil , Payseur Bret A. , Pfeifer Susanne P. , Stephan Wolfgang , Jensen Jeffrey D.
Published: November 2021

The field of population genomics has grown rapidly in response to the recent advent of affordable, large-scale sequencing technologies. As opposed to the situation during the majority of the 20th century, in which the development of theoretical and statistical population-genetic insights out-paced the generation of data to which they could be applied, genomic data are now being produced at a far greater rate than they can be meaningfully analyzed and interpreted. With this wealth of data has come a tendency to focus on fitting specific (and often rather idiosyncratic) models to data, at the expense of a careful exploration of the range of possible underlying evolutionary processes. For example, the approach of directly investigating models of adaptive evolution in each newly sequenced population or species often neglects the fact that a thorough characterization of ubiquitous non-adaptive processes is a prerequisite for accurate inference. We here describe the perils of these tendencies, present our consensus views on current best practices in population genomic data analysis, and highlight areas of statistical inference and theory that are in need of further attention. Thereby, we argue for the importance of defining a biologically relevant baseline model tuned to the details of each new analysis, of skepticism and scrutiny in interpreting model-fitting results, and of carefully defining addressable hypotheses and underlying uncertainties.
Spatiotemporal patterns of urban mosquitoes are modulated by socioeconomic status and environmental traits in the United States
Authors: Yitbarek Senay , Chen Kelvin , Celestin Modeline , McCary Matthew
Published: November 2021

The distribution of mosquitoes and associated vector diseases (e.g., West Nile, dengue, and Zika viruses) is likely a function of environmental conditions in the landscape. Urban environments are highly heterogeneous in the amount of vegetation, standing water, and concrete structures covering the land at a given time, each having the capacity to influence mosquito abundance and disease transmission. Previous research suggests that socioeconomic status is correlated with the ecology of the landscape, with lower-income neighborhoods generally having more concrete structures and standing water via residential abandonment, garbage dumps, and inadequate sewage. Whether these socio-ecological factors affect mosquito distributions across urban environments in the United States (US) remains unclear. Here, we present a meta-analysis of 22 paired observations from 15 articles testing how socioeconomic status relates to overall mosquito burden in urban landscapes in the United States. We then analyzed a comprehensive dataset from a socioeconomic gradient in Baltimore, Maryland to model spatiotemporal patterns of Aedes albopictus using a spatial regression model with socio-ecological covariates. The meta-analysis revealed that lower-income neighborhoods (regions making less than $50,000 per year on average) are exposed to 151% greater mosquito densities and mosquito-borne illnesses compared to higher-income neighborhoods (≥$50,000 per year). Two species of mosquito (Ae. albopictus and Aedes aegypti) showed the strongest relationship with socioeconomic status, with Ae. albopictus and Ae. aegypti being 62% and 22% higher in low-income neighborhoods, respectively. In the spatial regression analysis in Baltimore, we found that Ae. albopictus spatial spread of 1.2 km per year was significantly associated with median household income, vegetation cover, tree density, and abandoned buildings. Specifically, Ae. albopictus abundance was negatively correlated with median household income, vegetation cover, and tree density. Ae. albopictus abundance and the cover of abandoned buildings were positively correlated. Together, these results indicate that socio-ecological interactions can lead to disproportionate impacts of mosquitoes on humans in urban landscapes. Thus, concerted efforts to manage mosquito populations in low-income urban neighborhoods are required to reduce mosquito burden for the communities most vulnerable to human disease.
DeepMAPS: Single-cell biological network inference using heterogeneous graph transformer
Authors: Ma Anjun , Wang Xiaoying , Wang Cankun , Li Jingxian , Xiao Tong , Wang Juexing , Li Yang , Liu Yuntao , Chang Yuzhou , Wang Duolin , Jiang Yuexu , Li Jinpu , Su Li , Gu Shaopeng , Xin Gang , Li Zihai , Liu Bingqiang , Xu Dong , Ma Qin
Published: November 2021

We present DeepMAPS (Deep learning-based Multi-omics Analysis Platform for Single-cell data) for biological network inference from single-cell multi-omics (scMulti-omics). DeepMAPS includes both cells and genes in a heterogeneous graph to simultaneously infer cell-cell, cell-gene, and gene-gene relations. The multi-head attention mechanism in a graph transformer considers the heterogeneous relation among cells and genes within both local and global context, making DeepMAPS robust to data noise and scale. We benchmarked DeepMAPS on 18 scMulti-omics datasets for cell clustering and biological network inference, and the results showed that our method outperformed various existing tools. We further applied DeepMAPS on lung tumor leukocyte CITE-seq data and matched diffuse small lymphocytic lymphoma scRNA-seq and scATAC-seq data. In both cases, DeepMAPS showed competitive performance in cell clustering and predicted biologically meaningful cell-cell communication pathways based on the inferred gene networks. Note that we deployed a webserver using DeepMAPS implementation equipped with multiple functions and visualizations to improve the feasibility and reproducibility of scMulti-omics data analysis. Overall, DeepMAPS represents a heterogeneous graph transformer for single-cell study and may benefit the use of scMulti-omics data in various biological systems.
Generation and Culture of Cardiac Microtissues in a Microfluidic Chip with a Reversible Open Top Enables Electrical Pacing, Dynamic Drug Dosing and Endothelial Cell Co-Culture
Authors: Vivas Aisen , IJspeert Camilo , Pan Jesper Yue , Vermeul Kim , Berg Albert van den , Passier Robert , Keller Stephan Sylvest , Meer Andries D. van der
Published: November 2021

Cardiovascular disease morbidity has increased worldwide in recent years while drug development has been affected by failures in clinical trials and lack of physiologically relevant models. Organs-on-chips and human pluripotent stem cell technologies aid to overcome some of the limitations in cardiac in vitro models. Here, a bi-compartmental, monolithic heart-on-chip device that facilitates porous membrane integration in a single fabrication step is presented. Moreover, the device includes open-top compartments that allow facile co-culture of human pluripotent stem cell-derived cardiomyocytes and human adult cardiac fibroblast into geometrically defined cardiac microtissues. The device can be reversibly closed with a glass seal or a lid with fully customized 3D-printed pyrolytic carbon electrodes allowing electrical stimulation of cardiac microtissues. A subjacent microfluidic channel allowed localized and dynamic drug administration to the cardiac microtissues, as demonstrated by a chronotropic response to isoprenaline. Moreover, the microfluidic channel could also be populated with human induced pluripotent stem-derived endothelial cells allowing co-culture of heterotypic cardiac cells in one device. Overall, this study demonstrates a unique heart-on-chip model that systematically integrates the structure and electromechanical microenvironment of cardiac tissues in a device that enables active perfusion and dynamic drug dosing. Advances in the engineering of human heart-on-chip models represent an important step towards making organ-on-a-chip technology a routine aspect of preclinical cardiac drug development.
Multilineage plasticity in prostate cancer through expansion of stem–like luminal epithelial cells with elevated inflammatory signaling
Authors: Zaidi Samir , Zhao Jimmy L. , Chan Joseph M. , Roudier Martine P. , Wadosky Kristine M. , Gopalan Anuradha , Karthaus Wouter R. , Choi Jungmin , Lawrence Kayla , Chaudhary Ojasvi , Xu Tianhao , Masilionis Ignas , Mazutis Linas , Chaligné Ronan , Linkov Irina , Barlas Afsar , Jungbluth Achim , Rekhtman Natasha , Silber Joachim , Manova–Todorova Katia , Watson Philip A. , True Lawrence D. , Nelson Peter S. , Scher Howard I. , Rathkopf Dana E. , Morris Michael J. , Haffner Michael C. , Goodrich David W. , Pe’er Dana , Sawyers Charles L.
Published: November 2021

Lineage plasticity is a well–established mechanism of resistance to targeted therapies in lung and prostate cancer, where tumors transition from adenocarcinoma to small–cell or neuroendocrine carcinoma. Through single–cell analysis of a cohort of heavily–treated castration–resistant human prostate cancers (CRPC), we report a greater degree of plasticity than previously appreciated, with multiple distinct neuroendocrine (NEPC), mesenchymal (EMT–like), and other subpopulations detected within single biopsies. To explore the steps leading to this plasticity, we turned to two genetically engineered mouse models of prostate cancer that recapitulate progression from adenocarcinoma to neuroendocrine disease. Time course studies reveal expansion of stem–like luminal epithelial cells (Sca1+,Psca+, called L2) that, based on trajectories, gave rise to at least 4 distinct subpopulations, NEPC (Ascl1+), POU2F3 (Pou2f3+), TFF3 (Tff3+) and EMT–like (Vim+,Ncam1+)––these populations are also seen in human prostate and small cell lung cancers. Transformed L2–like cells express stem–like and gastrointestinal endoderm–like transcriptional programs, indicative of reemerging developmental plasticity programs, as well as elevated Jak/Stat and interferon pathway signaling. In sum, while the magnitude of multilineage heterogeneity, both within and across patients, raises considerable treatment challenges, the identification of highly plastic luminal cells as the likely source of this heterogeneity provides a target for more focused therapeutic intervention.

One Sentence Summary

Multilineage plasticity results from expansion of stem–like luminal cells with JAK/STAT activation, serving as a therapeutic target.
Optimality of extracellular enzyme production and activity in dynamic flux balance modeling
Authors: Quintin Michael , Dukovski Ilija , Bhatnagar Jennifer , Segrè Daniel
Published: November 2021

In microbial communities, many vital metabolic functions, including the degradation of cellulose, proteins and other complex macromolecules, are carried out by costly, extracellularly secreted enzymes. While significant effort has been dedicated to analyzing genome-scale metabolic networks for individual microbes and communities, little is known about the interplay between global allocation of metabolic resources in the cell and extracellular enzyme secretion and activity. Here we introduce a method for modeling the secretion and catalytic functions of extracellular enzymes using dynamic flux balance analysis. This new addition, implemented within COMETS (Computation Of Microbial Ecosystems in Time and Space), simulates the costly production and secretion of enzymes and their diffusion and activity throughout the environment, independent of the producing organism. After tuning our model based on data for a Saccharomyces cerevisiae strain engineered to produce exogenous cellulases, we explored the dynamics of the system at different cellulose concentrations and enzyme production rates. We found that there are distinct rates of constitutive enzyme secretion which maximize either growth rate or biomass yield. These optimal rates are strongly dependent on enzyme kinetic properties and environmental conditions, including the amount of cellulose substrate available. Our framework will facilitate the development of more realistic simulations of microbial community dynamics within environments rich in complex macromolecules, with applications in the study of soil and plant-associated ecosystems, and other natural and engineered microbiomes.

Importance

Many organisms - including soil, marine and human-associated bacteria and fungi - perform part of their metabolic functions outside of the boundary of the cell, through the secretion of extracellular enzymes that can diffuse and facilitate reactions independently of the organism that produced them. In order to better understand and predict microbial ecosystems, it would be helpful to create mathematical models incorporating these extracellular reactions within simulations of metabolism at the whole-cell level. In this paper we demonstrate the implementation of such a methodology and apply it to study a cellulase-secreting yeast. This work will be useful for a number of microbial ecology applications, including modeling of microbiome dynamics, engineering of bioproducts (e.g. biofuels) from plant biomass through synthetic communities or modified organisms, and testing of basic ecological hypotheses about the balance between cost and benefits of the production of common goods in microbial communities.
Natural variation in the maternal and zygotic mRNA complements of the early embryo in Drosophila melanogaster
Authors: Feitzinger Anna A. , Le Anthony , Thompson Ammon , Haseeb Mehnoor , Murugesan Mohan K. , Tang Austin M. , Lott Susan E.
Published: November 2021

Maternal gene products supplied to the egg during oogenesis drive the earliest events of development in all metazoans. After the initial stages of embryogenesis, maternal transcripts are degraded as zygotic transcription is activated, this is known as the maternal to zygotic transition (MZT). Altering the abundances of maternally deposited factors in the laboratory can have a dramatic effect on development, adult phenotypes and ultimately fitness. Zygotic transcription activation is a tightly regulated process, where the zygotic genome takes over control of development from the maternal genome, and is required for the viability of the organism. Recently, it has been shown that the expression of maternal and zygotic transcripts have evolved in the Drosophila genus over the course of 50 million years of evolution. However, the extent of natural variation of maternal and zygotic transcripts within a species has yet to be determined. We asked how the maternal and zygotic pools of mRNA vary within and between populations of D. melanogaster. In order to maximize sampling of genetic diversity, African lines of D. melanogaster originating from Zambia as well as DGRP lines originating from North America were chosen for transcriptomic analysis. Single embryo RNA-seq was performed at a stage before and a stage after zygotic genome activation in order to determine which transcripts are maternally deposited and which are zygotically expressed within and between these populations. Differential gene expression analysis has been used to quantify quantitative changes in RNA levels within populations as well as fixed expression differences between populations at both stages. Generally, we find that maternal transcripts are more highly conserved, and zygotic transcripts evolve at a higher rate. We find that there is more within population variation in transcript abundance than between populations and that expression variation is highest post-MZT between African lines. Determining the natural variation of gene expression surrounding the MZT in natural populations of D. melanogaster gives insight into the extent of how a tightly regulated process may vary within a species, the extent of developmental constraint at both stages and on both the maternal and zygotic genomes, and reveals expression changes allowing this species to adapt as it spread across the world.
Global patterns and rates of habitat transitions across the eukaryotic tree of life
Authors: Jamy Mahwash , Biwer Charlie , Vaulot Daniel , Obiol Aleix , Jing Homgmei , Peura Sari , Massana Ramon , Burki Fabien
Published: November 2021

The successful colonisation of new habitats has played a fundamental role during the evolution of life. Salinity is one of the strongest barriers for organisms to cross, which has resulted in the evolution of distinct marine and terrestrial (including both freshwater and soil) communities. Although microbes represent by far the vast majority of eukaryote diversity, the role of the salt barrier in shaping the diversity across the eukaryotic tree is poorly known. Traditional views suggest rare and ancient marine-terrestrial transitions, but this view is being challenged by the discovery of several recently transitioned lineages. Here, we investigate habitat evolution across the tree of eukaryotes using a unique set of taxon-rich environmental phylogenies inferred from a combination of long-read and short-read metabarcoding data spanning the ribosomal DNA operon. Our results show that overall marine and terrestrial microbial communities are phylogenetically distinct, but transitions have occurred in both directions in almost all major eukaryotic lineages, with at least 350 transition events detected. Some groups have experienced relatively high rates of transitions, most notably fungi for which crossing the salt barrier has most likely been an important aspect of their successful diversification. At the deepest phylogenetic levels, ancestral habitat reconstruction analyses suggest that eukaryotes may have first evolved in non-saline habitats, and that the two largest known eukaryotic assemblages (TSAR and Amorphea) arose in different habitats. Overall, our findings indicate that crossing the salt barrier has played an important role in eukaryotic evolution by providing new ecological niches to fill.
Efficacy of longevity interventions in C. elegans is determined by early life activity of RNA splicing factors
Authors: Dutta Sneha , Heintz Caroline , Perez-Matos Maria C. , Mutlu Ayse Sena , Piper Mary E. , Mistry Meeta , Sharma Arpit , Smith Hannah J. , Howell Porsha , Sehgal Rohan , Lanjuin Anne , Wang Meng C. , Mair William B.
Published: November 2021

Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using in vivo mini gene reporters in isogenic C. elegans, we show that alternative splicing of mRNAs related to lipid metabolism in young animals is coupled to subsequent life expectancy. Further, activity of RNA splicing factors REPO-1 and SFA-1 early in life modulates effectiveness of specific longevity interventions via POD-2/ACC1 and regulation of lipid utilization. In addition, early inhibition of REPO-1 renders animals refractory to late onset suppression of the TORC1 pathway. Together these data suggest that activity of RNA splicing factors and the metabolic landscape early in life can modulate responsiveness to longevity interventions and may explain variance in efficacy between individuals.

One Sentence Summary

Efficacy of pro-longevity interventions in C. elegans is determined by the activity of splicing factors and the lipid metabolic landscape early in the life of the individual.
Programmable large DNA deletion, replacement, integration, and inversion with twin prime editing and site-specific recombinases
Authors: Anzalone Andrew V. , Gao Xin D. , Podracky Christopher J. , Nelson Andrew T. , Koblan Luke W. , Raguram Aditya , Levy Jonathan M. , Mercer Jaron A. M. , Liu David R.
Published: November 2021

The targeted deletion, replacement, integration, or inversion of DNA sequences at specified locations in the genome could be used to study or treat many human genetic diseases. Here, we describe twin prime editing (twinPE), a method for the programmable replacement or excision of DNA sequence at endogenous human genomic sites without requiring double-strand DNA breaks. TwinPE uses a prime editor (PE) protein and two prime editing guide RNAs (pegRNAs) that template the synthesis of complementary DNA flaps on opposing strands of genomic DNA, resulting in the replacement of endogenous DNA sequence between the PE-induced nick sites with pegRNA-encoded sequences. We show that twinPE in human cells can perform precise deletions of at least 780 bp and precise replacements of genomic DNA sequence with new sequences of at least 108 bp. By combining single or multiplexed twinPE with site-specific serine recombinases either in separate steps or in a single step, we demonstrate targeted integration of gene-sized DNA plasmids (>5,000 bp) into safe-harbor loci including AAVS1, CCR5, and ALB in human cells. To our knowledge, these results represent the first RNA-programmable insertion of gene-sized DNA sequences into targeted genomic sites of unmodified human cells without requiring double-strand breaks or homology-directed repair. Twin PE combined with recombinases also mediated a 40,167-bp inversion at IDS that corrects a common Hunter syndrome allele. TwinPE expands the capabilities of precision gene editing without requiring double-strand DNA breaks and synergizes with other tools to enable the correction or complementation of large or complex pathogenic alleles in human cells.
Behavioral context affects social signal representations within single primate prefrontal cortex neurons
Authors: Jovanovic Vladimir , Fishbein Adam R. , de la Mothe Lisa , Lee Kuo-Fen , Miller Cory T.
Published: November 2021

We tested whether social signal processing in more traditional, head-restrained contexts is representative of the putative natural analog – social communication – by comparing responses to vocalizations within individual neurons in marmoset prefrontal cortex (PFC) across a series of behavioral contexts ranging from traditional to naturalistic. Although vocalization responsive neurons were evident in all contexts, cross-context consistency was notably limited. A response to these social signals when subjects were head-restrained was not predictive of a comparable neural response to the identical vocalizations during natural communication, even within the same neuron. Neural activity at the population level followed a similar pattern, as PFC activity could be reliably decoded for the context in which vocalizations were heard. This suggests that neural representations of social signals in primate PFC are not static, but highly flexible and likely reflect how nuances of the dynamic behavioral contexts affect the perception of these signals and what they communicate.
Reconstitution of 3’-processing of mammalian pre-mRNA reveals a central role of RBBP6
Authors: Schmidt Moritz , Kluge Florian , Sandmeir Felix , Kühn Uwe , Schäfer Peter , Tüting Christian , Ihling Christian , Conti Elena , Wahle Elmar
Published: November 2021

The 3’ ends of almost all eukaryotic mRNAs are generated in an essential two-step processing reaction, endonucleolytic cleavage of an extended precursor followed by the addition of a poly(A) tail. By reconstituting the reaction from overproduced and purified proteins, we provide a minimal list of fourteen polypeptides essential and two stimulatory for RNA processing. In a reaction depending on the polyadenylation signal AAUAAA, the reconstituted system cleaves pre-mRNA at a single preferred site corresponding to the one usedin vivo. Among the proteins, Cleavage Factor I stimulates cleavage but is not essential, consistent with its prominent role in alternative polyadenylation. RBBP6 is required, structural data showing it to contact and presumably activate the endonuclease CPSF73 through its DWNN domain. The C-terminal domain of RNA polymerase II is dispensable. ATP, but not its hydrolysis, supports RNA cleavage by binding to the hClp1 subunit of cleavage factor II with submicromolar affinity.
The effect of acute oral galactose administration on the redox system of the rat small intestine
Authors: Homolak Jan , Perhoc Ana Babic , Knezovic Ana , Barilar Jelena Osmanovic , Virag Davor , Joja Mihovil , Salkovic-Petrisic Melita
Published: November 2021

Galactose is a ubiquitous monosaccharide with important yet incompletely understood nutritive and physiological roles. Chronic parenteral D-galactose administration is used for modeling aging-related pathophysiological processes in rodents due to its ability to induce oxidative stress (OS). Conversely, chronic oral D-galactose administration prevents and alleviates cognitive decline in a rat model of sporadic Alzheimer’s disease indicating galactose may exert beneficial health effects by acting in the gut. The present aim was to explore acute time-response of intestinal redox homeostasis following oral administration of D-galactose. Male Wistar rats were euthanized at baseline (n=6), 30 (n=6), 60 (n=6), and 120 (n=6) minutes following orogastric administration of D-galactose (200 mg/kg). The overall reductive capacity, lipid peroxidation, the concentration of low molecular weight thiols (LMWT) and protein sulfhydryls (SH), the activity of Mn and Cu/Zn superoxide dismutases (SOD), reduced and oxidized fractions of nicotinamide adenine dinucleotide phosphates (NADPH/NADP), and hydrogen peroxide dissociation rate were analyzed in duodenum and ileum. Acute oral administration of D-galactose increased the activity of SODs and decreased intestinal lipid peroxidation and nucleophilic substrates (LMWT, SH, NADPH) indicating activation of peroxidative damage defense pathways. The redox system of the small intestine can acutely tolerate even high luminal concentrations of galactose (0.55 M) and oral galactose treatment is associated with a reduction rather than the increment of the intestinal OS. The ability of oral D-galactose to modulate intestinal OS should be further explored in the context of intestinal barrier maintenance, and beneficial cognitive effects associated with long-term administration of low doses of D-galactose.
Aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) dose-dependently shifts the gut microbiome consistent with the progression of steatosis to steatohepatitis with fibrosis
Authors: Fling Russell R. , Zacharewski Tim R.
Published: November 2021

Gut dysbiosis with disrupted enterohepatic bile acid metabolism is commonly associated with non-alcoholic fatty liver disease (NAFLD) and recapitulated in a NAFLD-phenotype elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. TCDD induces hepatic fat accumulation and increases levels of secondary bile acids including taurolithocholic acid and deoxycholic acid, microbial modified bile acids involved in host bile acid regulation signaling pathways. To investigate the effects of TCDD on the gut microbiota, cecum contents of male C57BL/6 mice orally gavaged with sesame oil vehicle or 0.3, 3, or 30 µg/kg TCDD were examined using shotgun metagenomic sequencing. Taxonomic analysis identified dose-dependent increases in Lactobacillus species (i.e., Lactobacillus reuteri). Increased species were also associated with dose-dependent increases in bile salt hydrolase sequences, responsible for deconjugation reactions in secondary bile acid metabolism. Increased L. reuteri levels were further associated with mevalonate-dependent isopentenyl diphosphate (IPP) biosynthesis and menaquinone biosynthesis genes. Analysis of gut microbiomes from cirrhosis patients identified increased abundance of these pathways as identified in the mouse cecum metagenomic analysis. These results extend the association of lactobacilli with the AhR/intestinal axis in NAFLD progression and highlight the similarities between TCDD-elicited phenotypes in mice to human NAFLD.
AbDiver – A tool to explore the natural antibody landscape to aid therapeutic design
Authors: Młokosiewicz Jakub , Deszyński Piotr , Wilman Wiktoria , Jaszczyszyn Igor , Ganesan Rajkumar , Kovaltsuk Aleksandr , Leem Jinwoo , Galson Jacob , Krawczyk Konrad
Published: November 2021

Motivation

Rational design of therapeutic antibodies can be improved by harnessing the natural sequence diversity of these molecules. Our understanding of the diversity of antibodies has recently been greatly facilitated through the deposition of hundreds of millions of human antibody sequences in next-generation sequencing (NGS) repositories. Contrasting a query therapeutic antibody sequence to naturally observed diversity in similar antibody sequences from NGS can provide a mutational road-map for antibody engineers designing biotherapeutics. Because of the sheer scale of the antibody NGS datasets, performing queries across them is computationally challenging.

Results

To facilitate harnessing antibody NGS data, we developed AbDiver (http://naturalantibody.com/abdiver), a free portal allowing users to compare their query sequences to those observed in the natural repertoires. AbDiver offers three antibody-specific use-cases: 1) compare a query antibody to positional variability statistics precomputed from multiple independent studies 2) retrieve close full variable sequence matches to a query antibody and 3) retrieve CDR3 or clonotype matches to a query antibody. We applied our system to a set of 742 therapeutic antibodies, demonstrating that for each use-case our system can retrieve relevant results for most sequences. AbDiver facilitates the navigation of vast antibody mutation space for the purpose of rational therapeutic antibody design and engineering.

Availability

AbDiver is freely accessible at http://naturalantibody.com/abdiver.
Improving poultry meat and sales channels to address food safety concerns: consumers' preferences on poultry meat attributes
Authors: Indrawan Dikky , Christy Accesstia , Hogeveen Henk
Published: November 2021

Purpose

This study explains Indonesian consumers' choice of poultry meat attributes and the willingness to pay (WTP) for these attributes using a discrete choice experiment.

Design/methodology/approach

The survey was conducted for the traditional and modern channels and involved a sample of 440 respondents in the Greater Jakarta area. A discrete choice experiment was employed as the study framework and in designing the questionnaire. A multinomial logistic regression analysis was used to evaluate consumers' preference for poultry attributes in modern and traditional channels.

Findings

Consumers preferred warm poultry meat, government certification and product information labeling on poultry meat. The WTP for warm poultry meat was the highest, which is indicating that freshness is crucial for consumers to ensure quality. Moreover, consumers had more trust in government certification than private certification for food safety and were willing to pay more for product information labeling on poultry meat.

Practical implications

The government can use the model as a decision support to improve poultry meat quality at sales channels in Indonesia including to close sales channels where sick poultry are sold and thus address food safety concerns caused by the avian influenza outbreak.

Originality/value

This study shows that understanding the WTP for poultry meat attributes enables the government to control the poultry sales channels and stimulates producers to supply the market with a safer poultry meat quality using the price mechanism.
Talent management in hospitality and tourism: a systematic literature review and research agenda
Authors: Kravariti Foteini , Voutsina Katerina , Tasoulis Konstantinos , Dibia Chianu , Johnston Karen
Published: November 2021

Purpose

This study aims to provide a systematic literature review (SLR) of extant research on talent management (TM) in hospitality and tourism (H&T). The objectives are first, to offer an empirical mapping analysis of TM research in H&T; second, to identify and discuss key research topics; and third, to recommend avenues for future research.

Design/methodology/approach

The authors conducted a SLR of TM literature in the context of H&T by analysing peer-reviewed papers published between January 2000 and October 2020. Following the preferred reporting items for systematic reviews and meta-analysis process, three independent coders undertook a content analysis of 74 papers for the SLR.

Findings

The authors found that TM in H&T offers contextualised evidence consistent on five key research topics: TM practices; conceptualisation of talent and TM; TM antecedents and outcomes; key TM stakeholders; and talent education and graduate careers. The analysis indicated that most studies are qualitative, focussed on Europe and North America and that primarily examine hotels. The small number of TM studies in H&T along with the lack of strong theoretical groundings show that the field is at the early stages of the growing stage, yet the sharp increase demonstrates an exponential growth in interest.

Practical implications

This study highlights the importance of TM and indicates that businesses in the sector need to reconsider the definition of talent, their approaches to TM and the bundling of TM practices to improve their effectiveness. It also calls for partnerships among the industry’s key stakeholders and a revisiting of agendas for educators.

Originality/value

To the best of the authors’ knowledge, this is the first study that offers a holistic examination of research on a wide range of TM topics within various H&T sectors over the past 20 years. It clarifies the conceptualisation of talent and TM in this field and provides insights, as well as context-specific evidence on the management of H&T talent. This study is the first to argue that the research stream is moving towards a growth stage and offers recommendations on advancing the field.
The meaning of open-water swimming for adults in Ireland: a qualitative study
Authors: Murray Edel , Fox Jackie
Published: November 2021

Purpose

There has been an increase in swimming in natural bodies of water as reported in personal qualitative accounts. However, limited academic research has explored the meaning of this occupation. Engaging with nature, exercising and being part of a community contribute to better mental and physical health. The purpose of this research was to explore the meaning that adults attribute to open-water swimming in natural bodies of water.

Design/methodology/approach

This study used phenomenological interviews to explore the meaning that five adults attribute to open-water swimming.

Findings

Open-water swimming contributes to meaning-making in many ways. Participants reported swimming as necessary for maintaining mental and emotional well-being and forming meaningful connections with the social environment, nature and their true selves.

Research limitations/implications

This study contributes to the understanding of the meaning of open-water swimming for adults in Ireland. Understanding the meaning of this occupation may add to the body of evidence exploring blue-space to promote health.

Originality/value

Open-water swimming is an occupation growing in popularity. This is the first paper to explore open-water swimming from an occupational perspective. This may provide an alternative perspective for viewing blue-space engagement and understanding the relationship between health, blue-space occupations and our oceans.
Critical skills for infrastructure procurement: insights from developing country contexts
Authors: Asiedu Richard Ohene , Manu Patrick , Mahamadu Abdul-Majeed , Booth Colin Anthony , Olomolaiye Paul , Agyekum Kofi , Abadi Mohamed
Published: November 2021

Purpose

Effective procurement of infrastructure is partly dependent on infrastructure procurement personnel having the skills that are important for the discharge of their role. Addressing the infrastructure deficits in developing countries, therefore, calls for an understanding of the skills that are important for the discharge of the roles of public personnel that are involved in infrastructure procurement. This study aims to investigate these skills from the perspective of public infrastructure procurement personnel in the sub-Saharan African region.

Design/methodology/approach

A questionnaire survey of procurement personnel yielded 590 useable responses, which were analysed using t-tests and exploratory factor analysis (EFA).

Findings

EFA established eight key components of important infrastructure procurement skills to include skills related to: project success factors; social and environmental sustainability; marketing and e-procurement; project phase management, the application of procurement laws and procedures; soft skills, ICT and communication; and data analysis and team building.

Originality/value

The findings are crucial in developing infrastructure procurement capacity building programmes that would be appropriate for infrastructure procurement personnel in developing country contexts. Infrastructure procurement personnel ought to engage more in capacity development training that is aligned to enhancing skills within the eight components.
Knowledge-oriented leadership and technology standard innovation: a temporary-team perspective
Authors: Jiang Hong , Motohashi Kazuyuki , Liu Wentao , Zhang Xu
Published: November 2021

Purpose

This study aims to investigate the relevance of knowledge-oriented leadership (KOL) to technology standard innovation (TSI) from a temporary-team perspective. The mediating and moderating effect on knowledge integration (KI) and leader–member exchange (LMX) is emphasized.

Design/methodology/approach

The conceptual model is built based on an exhaustive literature review and is empirically tested in terms of a sample of 341 Chinese individuals with TSI experience. Quantitative analysis was performed using a questionnaire with the bootstrapping method used to demonstrate the mediating effect of KI.

Findings

The empirical results of this study prove that KI mediates the relationship between KOL and TSI. The authors deduce that LMX moderates the positive relation between KOL and KI.

Originality/value

Few studies have investigated the innovation activities of technology standards from a temporary-team perspective. To the best of the authors’ knowledge, this is the first study to look into the underlying mechanism of KOL in TSI. This research deepens the analysis by introducing LMX’s moderating role in the innovation process of technology standards, thereby providing valuable insights for leaders of innovation activities of technology standards and illuminating new aspects of knowledge-intensive temporary-team management.
Multicultural teaching competence among undergraduate faculty: a convergent mixed methods study
Authors: Puhy Chandler , Prakash Nalini , Lacson Clarissa , Bradt Joke
Published: November 2021

Purpose

Increased student diversity in universities across the USA has increased the need for post-secondary educators to develop multicultural teaching competence (MTC). Most studies of MTC focus on educators teaching grades K-12. The purpose of this study is to determine how faculty members rate themselves in terms of MTC, what multicultural knowledge and skills faculty report and how they integrate these skills into their teaching practice and what barriers exist to developing and implementing MTC. The purpose of this study was to examine the factors that impact undergraduate faculty integration of multicultural awareness and attitudes into their teaching practices to enhance student learning.

Design/methodology/approach

A convergent mixed methods study used survey and interview data from undergraduate faculty. Select items from the MTC Inventory (MTCI) and social justice scales (SJS) were administered. Interviews (N = 7) were transcribed and analyzed using thematic analysis. Quantitative and qualitative data were compared to examine convergence and divergence.

Findings

Quantitative results revealed undergraduate faculty’s awareness, knowledge and skills as indicated by percent agreement with items from the MTCI and SJS instruments. Qualitative findings included the following four themes: knowledge building, addressing diversity in the classroom, barriers and challenges, and needs and recommendations. Qualitative data corroborated or explained many of the quantitative results and provided insight into these trends and barriers that impact MTC.

Originality/value

This is the first study of its kind, to our knowledge, that has used a mixed methods research design to examine factors that impact MTCs and associated barriers among a sample of undergraduate faculty across disciplines in one urban university.