bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of poly(A) tail length and non-A residues during the human oocyte-to-embryo transition
Authors: Liu Yusheng , Wu Keliang , Shao Fanghong , Nie Hu , Zhang Jingye , Li Cheng , Hou Zhenzhen , Wang Jiaqiang , Zhou Bing , Zhao Han , Lu Falong
Published: August 2021

Poly(A) tail-mediated post-transcriptional regulation of maternal mRNA has been shown to be vital in the oocyte-to-embryo transition (OET) in flies, fish, frogs, and mice1–8. However, nothing is known about poly(A) tail dynamics for even a single gene during the human OET, because of the limited availability of human oocytes and embryos in combination with the low sensitivity of previous methods. Here, we systematically profiled the transcriptome-wide mRNA poly(A) tails in human oocytes at the germ-vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as pre-implantation embryos at the 1-cell (1C), 2-cell (2C), 4-cell (4C), 8-cell (8C), morula (MO), and blastocyst (BL) stages using single-oocyte/embryo PAIso-seq1 and PAIso-seq2 methods. We show that poly(A) tail length is highly dynamic during the OET, with BTG4 responsible for global deadenylation. Moreover, we reveal that non-A residues occur primarily in poly(A) tails of maternal RNA, which begin to increase at the MI stage, become highly abundant after fertilization (with U residues occurring in about two thirds, G residues in about one third, and C residues in about one fifth of mRNAs), and decline at the 8C stage. Importantly, we reveal that TUT4/7 can add U residues to deadenylated mRNA, which can then be re- polyadenylated to produce 5′-end and internal U residues. In addition, the re- polyadenylated mRNA can be stabilized through the addition of G residues by TENT4A/B. Finally, we demonstrate that U residues in poly(A) tails mark the maternal transcripts for quicker degradation in 8C human embryos compared to those without U residues. Together, our results not only reveal the dynamics of poly(A) tail length and non-A residues, but also provide mechanistic insights into the regulation of the length and the role of non-A residues during human OET. These findings further scientific understanding and open a new door for studying the human OET.
nf-core/mag: a best-practice pipeline for metagenome hybrid assembly and binning
Authors: Krakau Sabrina , Straub Daniel , Gourlé Hadrien , Gabernet Gisela , Nahnsen Sven
Published: August 2021

The analysis of shotgun metagenomic data provides valuable insights into microbial communities, while allowing resolution at individual genome level. In absence of complete reference genomes, this requires the reconstruction of metagenome assembled genomes (MAGs) from sequencing reads. We present the nf-core/mag pipeline for metagenome assembly, binning and taxonomic classification. It can optionally combine short and long reads to increase assembly continuity and utilize sample-wise group-information for co-assembly and genome binning. The pipeline is easy to install - all dependencies are provided within containers -, portable and reproducible. It is written in Nextflow and developed as part of the nf-core initiative for best-practice pipeline development. All code is hosted on GitHub under the nf-core organization https://github.com/nf-core/mag and released under the MIT license.
Phylogenomics invokes the clade housing Cryptista, Archaeplastida, and Microheliella maris
Authors: Yazaki Euki , Yabuki Akinori , Imaizumi Ayaka , Kume Keitaro , Hashimoto Tetsuo , Inagaki Yuji
Published: August 2021

As-yet-undescribed branches in the tree of eukaryotes are potentially represented by some of “orphan” protists (unicellular micro-eukaryotes), of which phylogenetic affiliations have not been clarified in previous studies. By clarifying the phylogenetic positions of orphan protists, we may fill the previous gaps in the diversity of eukaryotes and further uncover the novel affiliation between two (or more) major lineages in eukaryotes. Microheliella maris was originally described as a member of the phylum Heliozoa, but a pioneering large-scale phylogenetic analysis failed to place this organism within the previously described species/lineages with confidence. In this study, we analyzed a 319-gene alignment and demonstrated that M. maris represents a basal lineage of one of the major eukaryotic lineages, Cryptista. We here propose a new clade name “Pancryptista” for Cryptista plus M. maris. The 319-gene analyses also indicated that M. maris is a key taxon to recover the monophyly of Archaeplastida and the sister relationship between Archaeplastida and Pancryptista, which is collectively called as “CAM clade” here. Significantly, Cryptophyceae tend to be attracted to Rhodophyta depending on the taxon sampling (ex., in the absence of M. maris and Rhodelphidia) and the particular phylogenetic “signal” most likely hindered the stable recovery of the monophyly of Archaeplastida in previous studies. We hypothesize that many cryptophycean genes (including those in the 319-gene alignment) recombined partially with the homologous genes transferred from the red algal endosymbiont during secondary endosymbiosis and bear a faint phylogenetic affinity to the rhodophytan genes.
Discrepancies in the detection of SARS-CoV-2 by qRT-PCR are dependent on the target gene used for its amplification: Implications in the diagnosis of clinical infection
Authors: Campos-Pardos Elena , Calvet-Seral Juan , Aguilera Antonio , Milagro-Beamonte Ana , Martínez-Sapiña Ana , Barbeito Gema , del Molino María Luisa Pérez , Gonzalo-Asensio Jesús
Published: August 2021

Discrepancies exist in Cycle threshold (Ct) values during detection of SARS-CoV-2 by qRT-PCR. We demonstrate that Ct values depend on the position of the target gene in the viral genome. Simultaneous detection of five genes in positive samples revealed lower Ct values as we move further to the 3’ end (orf1AB/RdRp>E>M>orf7a>N). These findings were confirmed in a retrospective analysis with 363 positive clinical samples. Our findings have key implications in clinical diagnostics of SARS-CoV-2, patient management and public health interventions.
Racism as a Leading Cause of Death: Measuring Excess Deaths in the US
Authors: Massey Daisy S. , Faust Jeremy S. , Dorsey Karen B. , Lu Yuan , Krumholz Harlan M.
Published: August 2021

Background

Excess death for Black people compared with White people is a measure of health equity. We sought to determine the excess deaths under the age of 65 (<65) for Black people in the United States (US) over the most recent 20-year period. We also compared the excess deaths for Black people with a cause of death that is traditionally reported.

Methods

We used the Center of Disease Control (CDC) WONDER’s Multiple Cause of Death 1999-2019 dataset to report age-adjusted mortality rates among non-Hispanic Black (Black) and non-Hispanic White (White) people and to calculate annual age-adjusted <65 excess deaths for Black people from 1999-2019. We measured the difference in mortality rates between Black and White people and the 20-year and 5-year trends using linear regression. We compared age-adjusted <65 excess deaths for Black people to the primary causes of death among <65 Black people in the US.

Results

From 1999 to 2019, the age-adjusted mortality rate for Black men was 1,186 per 100,000 and for White men was 921 per 100,000, for a difference of 265 per 100,000. The age-adjusted mortality rate for Black women was 802 per 100,000 and for White women was 664 per 100,000, for a difference of 138 per 100,000. While the gap for men and women is less than it was in 1999, it has been increasing among men since 2014. These differences have led to many Black people dying before age 65. In 1999, there were 22,945 age-adjusted excess deaths among Black women <65 and in 2019 there were 14,444—deaths that would not have occurred had their risks been the same as those of White women. Among Black men, 38,882 age-adjusted excess <65 deaths occurred in 1999 and 25,850 in 2019. When compared to the top 5 causes of deaths among <65 Black people, death related to disparities would be the highest mortality rate among both <65 Black men and women.

Comment

In the US, over the recent 20-year period, disparities in mortality rates resulted in between 61,827 excess deaths in 1999 and 40,294 excess deaths in 2019 among <65 Black people. The race-based disparity in the US was the leading cause of death among <65 Black people. Societal commitment and investment in eliminating disparities should be on par with those focused on other leading causes of death such as heart disease and cancer.
The impact of pausing the Oxford-AstraZeneca COVID-19 vaccine on uptake in Europe: a difference-in-differences analysis
Authors: Jain Vageesh , Lorgelly Paula
Published: August 2021

Background

Several countries paused their rollouts of the Oxford-AstraZeneca COVID-19 vaccine in mid-March 2021 due to concerns about vaccine-induced thrombosis and thrombocytopenia. Many warned that this risked damaging public confidence during a critical period of pandemic response. This study investigated whether the pause in the use of the Oxford-AstraZeneca vaccine had an impact on subsequent vaccine uptake in European countries.

Methods

We used a difference-in-differences approach capitalizing on the fact that some countries halted their rollouts whilst others did not. A longitudinal panel was constructed for European Economic Area countries spanning 15 weeks in early 2021. Media reports were used to identify countries that paused the Oxford-AstraZeneca vaccine and the timing of this. Data on vaccine uptake were available through the European Centre for Disease Control and Prevention COVID-19 Vaccine Tracker. Difference-in-differences linear regression models controlled for key confounders that could influence vaccine uptake, and country and week fixed effects. Further models and robustness checks were performed.

Results

The panel included 28 countries, with 19 in the intervention group and 9 in the control group. Pausing the Oxford-AstraZeneca vaccine was associated with a 0.52% decrease in uptake for the first dose of a COVID-19 vaccine and a 1.49% decrease in the uptake for both doses, comparing countries that paused to those that did not. These estimates are not statistically significant (p=0.86 and 0.39 respectively). For the Oxford-AstraZeneca vaccine only, the pause was associated with a 0.56% increase in uptake for the first dose and a 0.07% decrease in uptake for both doses. These estimates are also not statistically significant (p= 0.56 and 0.51 respectively). All our findings are robust to sensitivity analyses.

Conclusion

As new COVID-19 vaccines emerge, regulators should be cautious to deviate from usual protocols if further investigation on clinical or epidemiological grounds is warranted.
Genomic diversity and antimicrobial resistance of Prevotella spp. isolated from chronic lung disease airways
Authors: Webb Kasey A. , Olagoke Olusola , Baird Timothy , Neill Jane , Pham Amy , Wells Timothy J. , Ramsay Kay A. , Bell Scott C. , Sarovich Derek S. , Price Erin P.
Published: August 2021

Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are characterised by increasingly frequent acute pulmonary exacerbations that reduce life quality and length. Human airways are home to a rich polymicrobial environment, including members of the obligately anaerobic genus, Prevotella. Despite their commonness, surprisingly little is known about the prevalence, role, genomic diversity, and antimicrobial resistance (AMR) potential of Prevotella species/strains in healthy and diseased airways. Here, we used comparative genomics to develop a real-time PCR assay to permit rapid Prevotella spp. quantification from cultures and clinical specimens. Assay specificity was validated across a panel of Prevotella and non-Prevotella species, followed by PCR screening of CF and COPD respiratory-derived cultures. Next, 35 PCR-positive isolates were subjected to whole-genome sequencing. Of eight identified species, P. histicola, P. melaninogenica, P. nanceiensis, P. salivae and P. denticola overlapped between participant cohorts. Phylogenomic analysis revealed considerable interhost but limited intrahost diversity, suggesting patient-specific lineages in the lower airways, probably from oral cavity aspirations. Correlation of phenotypic AMR profiles with AMR gene presence identified excellent correlation between tetQ presence and decreased doxycycline susceptibility, and ermF presence and decreased azithromycin susceptibility and clindamycin resistance. AMR rates were higher in the CF isolates, reflecting greater antibiotic use in this cohort. All tested Prevotella isolates were tobramycin-resistant, providing a potential selection method to improve Prevotella culture retrieval rates. Our addition of 35 airway-derived Prevotella genomes to public databases will enhance ongoing efforts to unravel the role of this diverse and enigmatic genus in both chronic respiratory diseases and healthy lungs.

Data summary

Thirty-five Prevotella spp. genomes generated in this study are available in the Sequence Read Archive (SRA) and GenBank databases under BioProject accession PRJNA742126.
Microbiomes in drinking water treatment and distribution: a meta-analysis from source to tap
Authors: Thom Claire , Smith Cindy J , Moore Graeme , Weir Paul , Ijaz Umer Z
Published: August 2021

A meta-analysis of existing and available Illumina 16S rRNA datasets from drinking water source, treatment and drinking water distribution systems (DWDS) were collated to compare changes in abundance and diversity throughout. Samples from bulk water and biofilm were used to assess principles governing microbial community assembly and the value of amplicon sequencing to water utilities. Individual phyla relationships were explored to identify competitive or synergistic factors governing DWDS microbiomes. The relative importance of stochasticity in the assembly of the DWDS microbiome was considered to identify the significance of source and treatment in determining communities in DWDS. Treatment of water significantly reduces overall species abundance and richness, with chlorination of water providing the most impact to individual taxa relationships. The assembly of microbial communities in the bulk water of the source, primary treatment process and DWDS is governed by more stochastic processes, as is the DWDS biofilm. DWDS biofilm is significantly different from bulk water in terms of local contribution to beta diversity, type and abundance of taxa present. Water immediately post chlorination has a more deterministic microbial assembly, highlighting the significance of this process in changing the microbiome, although elevated levels of stochasticity in DWDS samples suggest that this may not be the case at customer taps. 16S rRNA sequencing is becoming more routine, and may have several uses for water utilities, including: detection and risk assessment of potential pathogens such as those within the genera ofLegionellaandMycobacterium;assessing the risk of nitrification in DWDS; providing improved indicators of process performance and monitoring for significant changes in the microbial community to detect contamination. Combining this with quantitative methods like flow cytometry will allow a greater depth of understanding of the DWDS microbiome.
The Retrieval-related Anterior shift is Moderated by Age and Correlates with Memory Performance
Authors: Srokova Sabina , Hill Paul F , Rugg Michael D
Published: August 2021

Recent research suggests that episodic memory is associated with systematic differences in the localization of neural activity observed during memory encoding and retrieval. The retrieval-related anterior shift is a phenomenon whereby the retrieval of a stimulus event (e.g., a scene image) is associated with a peak neural response which is localized more anteriorly than the response elicited when the stimulus is experienced directly. Here, we examine whether the magnitude of the anterior shift, i.e., the distance between encoding- and retrieval-related response peaks, is moderated by age, and also whether the shift is associated with memory performance. Younger and older human subjects of both sexes underwent fMRI as they completed encoding and retrieval tasks on word-face and word-scene pairs. We localized peak scene- and face-selectivity for each individual participant within the face-selective precuneus (PCU) and in three scene-selective (parahippocampal place area [PPA], medial place area [MPA], occipital place area [OPA]) regions of interest (ROIs). In line with recent findings, we identified an anterior shift in PPA and OPA in both age groups and, in older adults only, in MPA and PCU also. Of importance, the magnitude of the anterior shift was larger in older than in younger adults. The shift within the PPA exhibited an age-invariant across-participant negative correlation with source memory performance, such that a smaller displacement between encoding- and retrieval-related neural activity was associated with better performance. These findings provide novel insights into the functional significance of the anterior shift, especially in relation to memory decline in older age.
Filling of a water-free void explains the allosteric regulation of the β1-adrenergic receptor by cholesterol
Authors: Abiko Layara Akemi , Teixeira Raphael Dias , Engilberge Sylvain , Grahl Anne , Grzesiek Stephan
Published: August 2021

Proteins often contain cavities, which are usually assumed to be water-filled. Recent high-pressure NMR results indicate that the preactive conformation of the β1-adrenergic receptor (β1AR) contains completely empty cavities (dry voids) of about ∼100 Å3 volume, which disappear in the active conformation of the receptor. Here we have localized these cavities by X-ray crystallography on xenon-derivatized β1AR crystals. One of the cavities coincides with the binding pocket of cholesterol. Solution NMR data show that addition of the soluble cholesterol analog cholesteryl hemisuccinate (CHS) impedes the formation of the active conformation of the receptor by blocking conserved GPCR microswitches. This wedge-like action explains the function of the cellularly highly abundant cholesterol as a negative allosteric modulator of β1AR. The detailed understanding of GPCR regulation by cholesterol via filling of a dry void and the easy scouting for such voids by xenon may provide new routes for the development of allosteric drugs.
Strikingly different roles of SARS-CoV-2 fusion peptides uncovered by neutron scattering
Authors: Santamaria Andreas , Batchu Krishna C. , Matsarskaia Olga , Prévost Sylvain F. , Russo Daniela , Natali Francesca , Seydel Tilo , Hoffmann Ingo , Laux Valerie , Haertlein Michael , Darwish Tamim A. , Russell Robert A. , Corucci Giacomo , Fragneto Giovanna , Maestro Armando , Zaccai Nathan R.
Published: August 2021

Coronavirus disease-2019 (COVID-19), a lethal respiratory illness caused by the coronavirus SARS-CoV-2, emerged in the end of 2019 and has since spread aggressively across the globe. A thorough understanding of the molecular mechanisms of cellular infection by coronaviruses is therefore of utmost importance. A critical stage in infection is the fusion between viral and host membranes. Here, we present a detailed investigation of the role of the SARS-CoV-2 Spike protein, and the influence of calcium and cholesterol, in this fusion process. Structural information from specular neutron reflectometry and small angle neutron scattering, complemented by dynamics information from quasi-elastic and spin-echo neutron spectroscopy, revealed strikingly different functions encoded in the Spike fusion domain. Calcium drives the N-terminal of the Spike fusion domain to fully cross the host plasma membrane. Removing calcium however re-orients the protein to the lipid leaflet in contact with the virus, leading to significant changes in lipid fluidity and rigidity. In conjunction with other regions of the fusion domain which are also positioned to bridge and dehydrate viral and host membranes, the molecular events leading to cell entry by SARS-CoV-2 are proposed.

SIGNIFICANCE

We have recreated here important elements of the critical membrane fusion mechanism of the SARS-CoV-2 coronavirus by simplifying the system down to its core elements, amenable to experimental analysis by neutron scattering. Neutrons are well suited for the study of protein – membrane interactions under physiological conditions, since they allow structural and dynamics characterization at room temperature. Our results revealed strikingly different functions encoded in the viral Spike fusion domain and thereby provide a potential calcium-dependent cell entry mechanism for SARS-CoV-2. In particular, calcium drives the protein’s N-terminal to harpoon through the host membrane, while removing calcium re-orients the protein so that it is able to bridge and dehydrate lipid membranes, facilitating their fusion.
Physiological basis underlying antidepressant-induced activation of TrkB receptors
Authors: Alitalo Okko , Kohtala Samuel , Rosenholm Marko , Kohtala Piia , Saarreharju Roosa , Matsui Nobuaki , Hernandez Gemma Gonzalez , Müller Heidi Kaastrup , Theilmann Wiebke , Sarparanta Mirkka , Klein Anders , Kärkkäinen Olli , Rozov Stanislav , Rantamäki Tomi
Published: August 2021

We show that both pharmacological and non-pharmacological treatments of depression activate TrkB receptors—a well-established target of antidepressants—by inducing a physiological response coupled to sedation. Several rapid-acting antidepressants trigger TrkB signaling by evoking a state associated with electroencephalographic slow-wave activity, behavioral immobility, reduced cerebral glucose utilization, and lowered body temperature. Remarkably, antidepressant-induced TrkB signaling was not compromised in animals exhibiting reduced activity-dependent release of BDNF but was diminished by maintaining animals in warm ambient temperature. Most importantly, prevention of the hypothermic response attenuated the behavioral effects produced by rapid-acting antidepressant nitrous oxide. Our results suggest that the phenomenon underlying TrkB transactivation—changes in energy expenditure and thermoregulation—is essential, but not sufficient, for antidepressant responses. Indeed, regardless of differential clinical and pharmacodynamic properties, all drugs that disrupt energy metabolism and induce hypothermia activated TrkB. This study challenges pharmacology-centric hypotheses regarding antidepressant effects and highlight the role of complex changes in bioenergetics and thermoregulation.

Highlights

Rapid-acting antidepressants evoke homeostatic emergence of slow-wave sleep during which TrkB signaling becomes regulated.

Non-antidepressant metabolic inhibitors and diverse sedatives activate TrkB signaling.

Reduction in body temperature determined the ability of antidepressants to transactivate TrkB.

Drug-induced TrkB signaling was blunted by maintenance of normothermic body temperature.

Warm ambient temperature after nitrous oxide exposure blocked the antidepressant-like effects.

Graphical abstract
Modelling the future distribution of rare bryophytes in Scotland: is inclusion of habitat loss important?
Authors: Ferretto Anna , Smith Pete , Genney David , Matthews Robin , Brooker Rob
Published: August 2021

Species distribution models (SDMs) have been widely used to predict species ranges and their future distribution under climate change scenarios. In this study we applied Maxent, one of the most used SDMs, to project the distribution of some rare bryophyte species in Scotland in the 2050s. Most of these species are strongly linked to the blanket bog habitat, which is threatened by climate change in the near future. To assess the extent to which changes in habitat distribution leads to a different modelled distribution of the selected bryophytes, blanket bog distribution was included in the model as one of the explanatory variables for some species, and Maxent was run for three 2050s scenarios: once with the current blanket bog distribution and two other runs using the blanket bog distribution derived from two bioclimatic models (Lindsay modified and Blanket Bog Tree model) under the same climate change scenario. For seven out of nine of our studied bryophyte species, the modelled distribution in Scotland was predicted to decline, with some species retreating towards the north-west and other species almost disappearing. When the change in blanket bog distribution was also accounted for, further areas in the north/centre east of Scotland and in the south were predicted to be unfavourable for many of the species considered. Our findings suggest that when modelling species distributions, habitat distribution also needs to be considered, especially when there is a strong relationship between the species and a particular habitat.
Input zone-selective dysrhythmia in motor thalamus after dopamine depletion
Authors: Nakamura Kouichi C. , Sharott Andrew , Tanaka Takuma , Magill Peter J.
Published: August 2021

The cerebral cortex, basal ganglia and motor thalamus form circuits important for purposeful movement. In Parkinsonism, basal ganglia neurons often exhibit dysrhythmic activity during, and with respect to, the slow (∼1 Hz) and beta-band (15–30 Hz) oscillations that emerge in cortex in a brain state-dependent manner. There remains, however, a pressing need to elucidate the extent to which motor thalamus activity becomes similarly dysrhythmic after dopamine depletion relevant to Parkinsonism. To address this, we recorded single-neuron and ensemble outputs in the ‘basal ganglia-recipient zone’ (BZ) and ‘cerebellar-recipient zone’ (CZ) of motor thalamus in anesthetized male dopamine-intact rats and 6-OHDA-lesioned rats during two brain states, respectively defined by cortical slow-wave activity and activation. Two forms of thalamic input zone-selective dysrhythmia manifested after dopamine depletion: First, BZ neurons, but not CZ neurons, exhibited abnormal phase-shifted firing with respect to cortical slow oscillations prevalent during slow-wave activity; secondly, BZ neurons, but not CZ neurons, inappropriately synchronized their firing and engaged with the exaggerated cortical beta oscillations arising in activated states. These dysrhythmias were not accompanied by the thalamic hypoactivity predicted by canonical firing rate-based models of circuit organization in Parkinsonism. Complementary recordings of neurons in substantia nigra pars reticulata suggested their altered activity dynamics could underpin the BZ dysrhythmias. Finally, pharmacological perturbations demonstrated that ongoing activity in the motor thalamus bolsters exaggerated beta oscillations in motor cortex. We conclude that BZ neurons are selectively primed to mediate the detrimental influences of abnormal slow and beta-band rhythms on circuit information processing in Parkinsonism.
Do closely related species interact with similar partners? Testing for phylogenetic signal in bipartite interaction networks
Authors: Perez-Lamarque Benoît , Maliet Odile , Pichon Benoît , Selosse Marc-André , Martos Florent , Morlon Hélène
Published: August 2021

Abstract

Whether interactions between species are conserved on evolutionary time-scales has spurred the development of both correlative and process-based approaches for testing phylogenetic signal in interspecific interactions: do closely related species interact with similar partners? Here we use simulations to test the statistical performances of the two approaches that are the most widely used in the field: Mantel tests and the Phylogenetic Bipartite Linear Model (PBLM). Mantel tests investigate the correlation between phylogenetic distances and dissimilarities in sets of interacting partners, while PBLM is a process-based approach that relies on strong assumptions about how interactions evolve. We find that PBLM often detects a phylogenetic signal when it should not. Simple Mantel tests instead have infrequent false positives and moderate statistical power; however, they often artifactually detect that closely related species interact with dissimilar partners. Partial Mantel tests, which are used to partial out the phylogenetic signal in the number of partners, actually fail at correcting for this confounding effect, and we instead recommend evaluating the significance of Mantel tests with network permutations constraining the number of partners. We also explore the ability of simple Mantel tests to analyze clade-specific phylogenetic signals. We provide general guidelines and an application on an interaction network between orchids and mycorrhizal fungi.
Trace elements in grey seals from the Gulf of St. Lawrence
Authors: MacMillan Gwyneth A. , Amyot Marc , Daoust Pierre-Yves , Lemire Mélanie
Published: August 2021

We measured baseline levels of 19 trace element and mercury speciation for grey seals (Halichoerus grypus) from the Gulf of St. Lawrence (GSL), Québec, Canada. With interest growing in commercializing grey seal products for human consumption in this region, the goal of this study was to measure essential and non-essential trace elements in grey seals to evaluate health concerns and nutritional benefits. From 2015 to 2019, 120 grey seals were sampled by hunters and researchers at 4 sites in the GSL. Muscle, liver, heart and kidney samples were analyzed for 10 non-essential elements (Sb, As, Be, B, Cd, Pb, Hg, Ni, Tl, Sn) and 9 essential elements (Co, Cr, Cu, Fe, Mg, Mn, Mo, Se, Zn). Both total mercury (THg) and methylmercury (MeHg) were analysed for a subset of samples. Many elements were undetected in liver (Sb, As, Be, B, Cr, Co, Pb, Ni, Tl, Sn) and muscle tissues (same, plus Cd, Mn, Mo). Results showed lower element concentrations in the muscle (Fe, Mg, Se) and livers (Cd, Cr, Hg, Mn, Mo, Se) of young-of-the-year harvested in the winter (< 6 weeks old) compared to older animals feeding at sea. For older seals (∼ 5 months to 29 years), we did not observe progressive age-dependent bioaccumulation. Sex-specific differences were not very pronounced, but a few elements were 30 - 70% higher in the muscle (THg, MeHg) and liver (Mn, Zn) of male seals. Comparison to Canadian dietary reference intakes shows that a weekly portion of liver from young-of-the-year (< 6 weeks old) is a good source of essential elements (Cu, Fe) and that muscle and liver from this age category does not exceed reference values for toxic elements (As, Cd, Pb, MeHg). Ongoing discussions with regional public health professionals will help to develop dietary recommendations for the consumption of older grey seals.

HIGHLIGHTS

We measured baseline levels of 19 trace elements in grey seals harvested from the Gulf of St. Lawrence.

We evaluated nutritional benefits and health concerns of human consumption of grey seal products.

Once seals began feeding at sea (∼ 5 mo), many element concentrations increased, but did not bioaccumulate progressively with age afterwards.

Some elements were more concentrated in the muscle (mercury) and livers (manganese, zinc) of male seals.

Young seal (< 6 we) livers are a good dietary sources of copper and iron, while its muscle and liver were below reference values for toxic elements.

GRAPHICAL ABSTRACT
Gene drive escape from resistance depends on mechanism and ecology
Authors: Cook Forest , Bull James J. , Gomulkiewicz Richard
Published: August 2021

Gene drives can potentially be used to suppress pest populations, and the advent of CRISPR technology has made it feasible to engineer them in many species, especially insects. What remains largely unknown for implementations is whether anti-drive resistance will evolve to block the population suppression. An especially serious threat to some kinds of drive is mutations in the CRISPR cleavage sequence that block the action of CRISPR, but designs have been proposed to avoid this type of resistance. Various types of resistance at loci away from the cleavage site remain a possibility, which is the focus here. It is known that modest-effect suppression drives can essentially ‘outrun’ unlinked resistance even when that resistance is present from the start. We demonstrate here how the risk of evolving (unlinked) resistance can be further reduced without compromising overall suppression by introducing multiple suppression drives or by designing drives with specific ecological effects. However, we show that even modest-effect suppression drives remain vulnerable to the evolution of extreme levels of inbreeding, which halt the spread of the drive without actually interfering with its mechanism. The landscape of resistance evolution against suppression drives is therefore complex, but avenues exist for enhancing gene drive success.
R-loop homeostasis and cancer mutagenesis promoted by the DNA cytosine deaminase APOBEC3B
Authors: McCann Jennifer L. , Cristini Agnese , Law Emily K. , Lee Seo Yun , Tellier Michael , Carpenter Michael A. , Beghè Chiara , Kim Jae Jin , Jarvis Matthew C. , Stefanovska Bojana , Temiz Nuri A. , Bergstrom Erik N. , Salamango Daniel J. , Brown Margaret R. , Murphy Shona , Alexandrov Ludmil B. , Miller Kyle M. , Gromak Natalia , Harris Reuben S.
Published: August 2021

The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here, APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R-loops in human cells andin vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B and decreases in cells overexpressing APOBEC3B. Genome-wide analyses show major changes in the overall landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions as well as binding of APOBEC3B to many of these sites. APOBEC3 mutagenesis impacts overexpressed genes and splice factor mutant tumors preferentially, and APOBEC3-attributedkataegisare enriched in RTCW consistent with APOBEC3B deamination. Taken together with the fact that APOBEC3B binds single-stranded DNA and RNA and preferentially deaminates DNA, these results support a mechanism in which APOBEC3B mediates R-loop homeostasis and contributes to R-loop mutagenesis in cancer.

Highlights

Unbiased proteomics link antiviral APOBEC3B to R-loop regulation

Systematic alterations of APOBEC3B levels trigger corresponding changes in R-loops

APOBEC3B binds R-loops in living cells andin vitro

Bioinformatics analyses support an R-loop deamination and mutation model
Kazrin is an endosomal adaptor for dynein/dynactin
Authors: Hernandez-Perez Ines , Baumann Adrian , Rubio Javier , Girao Henrique , Rebollo Elena , Aragay Anna M. , Geli Maria Isabel
Published: August 2021

Kazrin is a protein widely expressed in vertebrates whose depletion causes a myriad of developmental defects, in part derived from altered cell adhesion, impaired cell migration and failure to undergo Epidermal to Mesenchymal Transition (EMT). However, the primary molecular role of kazrin, which might contribute to all these functions, has not been elucidated yet. We previously identified one of its isoforms, kazrin C, as a protein that potently inhibits clathrin-mediated endocytosis when overexpressed. We now generated kazrin knock out Mouse Embryonic Fibroblasts (MEFs) to investigate its endocytic function. We found that kazrin depletion delays perinuclear enrichment of internalized material, indicating a role in endocytic traffic from Early (EE) to Recycling Endosomes (REs). Consistently, we found that the C-terminal domain of kazrin C, predicted to be an Intrinsically Disordered Region (IDR), directly interacts with several components of the EEs, and that kazrin depletion impairs centripetal motility of EEs. Further, we noticed that the N-terminus of kazrin C shares homology with dynein/dynactin adaptors and that it directly interacts with the dynactin complex and the dynein Light Intermediate Chain 1 (LIC1). Altogether, the data indicate that one of the primary kazrin functions is to facilitate endocytic recycling via the perinuclear endocytic compartment, by promoting microtubule and dynein/dynactin-dependent transport of EEs or EE-derived transport intermediates to the RE.
Hexose translocation mediated by SlSWEET5b is required for pollen maturation in Solanum lycopersicum
Authors: Ko Han-Yu , Tseng Hsuan-Wei , Ho Li-Hsuan , Wang Lu , Chang Tzu-Fang , Lin Annie , Ruan Yong-Ling , Neuhaus H. Ekkehard , Guo Woei-Jiun
Published: August 2021

Pollen fertility is critical for successful fertilization and, accordingly, for crop yield. While sugar unloading affects growth and development of all types of sink organs, the molecular nature for sugar import to tomato pollen is poorly understood. However, SWEET transporters have been proposed to function in pollen development. Here, qRT-PCR revealed that SlSWEET5b was markedly expressed in flowers when compared to the remaining tomato SlSWEETs; particularly, in the stamens of maturing flower buds undergoing mitosis. Distinct accumulation of SlSWEET5b-GUS fusion proteins was present in mature flower buds, especially in anther vascular and inner cells, symplasmic isolated pollen cells and styles. The demonstration that GFP fusion proteins located to the plasma membrane support the idea that the SlSWEET5b carrier functions in apoplasmic sugar translocation during pollen maturation. Such function is in line with data from yeast complementation experiments and radiotracer uptakes, showing that SlSWEET5b operates as a low affinity hexose-specific passive facilitator, with a KM of ~36 mM. Most importantly, RNAi-mediated suppression of SlSWEET5b expression resulted in shrunken nucleus-less pollen cells, impaired germination and low seed yield. Interestingly, stamens from SlSWEET5b-silenced tomato mutants contained significantly lower amounts of sucrose and increased invertase activity, pointing to reduced carbon supply and perturbed sucrose homeostasis in this tissue. Taken together, our findings reveal an essential role of SlSWEET5b in mediating apoplasmic hexose import into phloem unloading cells and into developing pollen cells to support pollen mitosis and maturation in tomato flowers.

One-sentence Summary

Plasma-membrane-localized SlSWEET5b facilitates a sequential hexose flux, from phloem to anther cells and from anther locule to pollen, to support pollen maturation and fertility in tomato flowers.
Towards a molecular mechanism underlying mitochondrial protein import through the TOM and TIM23 complexes
Authors: Ford Holly C. , Allen William J. , Pereira Gonçalo C. , Liu Xia , Dillingham Mark S. , Collinson Ian
Published: August 2021

Nearly all mitochondrial proteins need to be targeted for import from the cytosol. For the majority, the first port of call is the translocase of the outer membrane (TOM complex), followed by a procession of alternative molecular machines, conducting transport to their final destination. The pre-sequence translocase of the inner-membrane (TIM23-complex) imports proteins with cleavable pre-sequences, and comes in two flavours: the TIM23SORT complex mediates inner mitochondrial membrane (IMM) protein insertion and the TIM23MOTOR complex delivers proteins to the matrix. Progress in understanding these transport mechanisms has been hampered by the poor sensitivity and time-resolution of import assays. However, with the development of an assay based on split NanoLuc luciferase, we can now explore this process in greater detail. Here, we apply this new methodology to understand how Δψ and ATP hydrolysis, the two main driving forces for import through the TIM23MOTOR complex, contribute to the import of pre-sequence-containing precursors (PCPs) with varying properties. Notably, we found that two major rate-limiting steps define PCP import time: passage of PCP across the OMM and initiation of IMM transport by the pre-sequence. The rates of these steps are influenced by PCP properties such as size and net charge, but not total amount of PCP imported – emphasising the importance of collecting rapid kinetic data, achieved here, to elucidate mechanistic detail. The apparent distinction between transport through the two membranes (passage through TOM is substantially complete before PCP-TIM engagement) is in contrast with the current view that import occurs through TOM and TIM in a single continuous step. Our results also indicate that PCPs spend very little time in the TIM23 channel – presumably rapid success or failure of import is critical for maintaining mitochondrial fitness.
Comparative assessment of genes driving cancer and somatic evolution in noncancer tissues: an update of the NCG resource
Authors: Dressler Lisa , Bortolomeazzi Michele , Keddar Mohamed Reda , Misetic Hrvoje , Sartini Giulia , Acha-Sagredo Amelia , Montorsi Lucia , Wijewardhane Neshika , Repana Dimitra , Nulsen Joel , Goldman Jacki , Pollit Marc , Davis Patrick , Strange Amy , Ambrose Karen , Ciccarelli Francesca D.
Published: August 2021

Genetic alterations of somatic cells can drive nonmalignant clone formation and promote cancer initiation. However, the link between these processes remains unclear hampering our understanding of tissue homeostasis and cancer development. Here we collect a literature-based repertoire of 3355 well-known or predicted drivers of cancer and noncancer somatic evolution in 122 cancer types and 12 noncancer tissues. Mapping the alterations of these genes in 7953 pancancer samples reveals that, despite the large size, the known compendium of drivers is still incomplete and biased towards frequently occurring coding mutations. High overlap exists between drivers of cancer and noncancer somatic evolution, although significant differences emerge in their recurrence. We confirm and expand the unique properties of drivers and identify a core of evolutionarily conserved and essential genes whose germline variation is strongly counter-selected. Somatic alteration in even one of these genes is sufficient to drive clonal expansion but not malignant transformation. Our study offers a comprehensive overview of our current understanding of the genetic events initiating clone expansion and cancer revealing significant gaps and biases that still need to be addressed. The compendium of cancer and noncancer somatic drivers, their literature support and properties are accessible at http://www.network-cancer-genes.org/.
Predicting user personality with social interactions in Weibo
Authors: Jiang Yuting , Deng Shengli , Li Hongxiu , Liu Yong
Published: August 2021

Purpose

The purposes of this paper are to (1) explore how personality traits pertaining to the dominance influence steadiness compliance model manifest themselves in terms of user interaction behavior on social media and (2) examine whether social interaction data on social media platforms can predict user personality.

Design/methodology/approach

Social interaction data was collected from 198 users of Sina Weibo, a popular social media platform in China. Their personality traits were also measured via questionnaire. Machine learning techniques were applied to predict the personality traits based on the social interaction data.

Findings

The results demonstrated that the proposed classifiers had high prediction accuracy, indicating that our approach is reliable and can be used with social interaction data on social media platforms to predict user personality. “Reposting,” “being reposted,” “commenting” and “being commented on” were found to be the key interaction features that reflected Weibo users' personalities, whereas “liking” was not found to be a key feature.

Originality/value

The findings of this study are expected to enrich personality prediction research based on social media data and to provide insights into the potential of employing social media data for the purpose of personality prediction in the context of the Weibo social media platform in China.
Investigating the causal complexity of corruption in project-based organizations: a scenario analysis of bidding activity in the Chinese construction sector
Authors: Wang Zhixiu , Liu Junying , Guan Xinya
Published: August 2021

Purpose

Although the global construction industry has made great contributions to economic development, industry corruption is a challenge for governments all over the world. This paper aims to investigate the causal complexity of organizational corruption by exploring the configuration effect of multiple induced conditions of corruption in the construction sector.

Design/methodology/approach

This study is focused on bribery, a specific form of corrupt behavior through a scenario-based survey role-playing game in which participants encounter bribery. A total of 400 Chinese construction sector participants were randomly recruited to complete this survey.

Findings

Compared with studies that have identified a number of factors associated with corruption in the construction sector, this study found asymmetry and complexity in the causality of organizational corruption. That is, when a variable causing corruption changes from one condition to its opposite – for example, from fierce to mild competition – the degree of corruption is not necessarily reduced as one may expect.

Practical implications

Anti-corruption measures should not rely solely on the net effects of discrete conditions and the interactions between multiple factors should not be ignored. In other words, anti-corruption strategies should not be implemented in isolation of their context, and pairing control measures with configurations is critical in controlling corruption. Finally, multiple configuration paths should be reconsidered when considering the degree of corruption reduction.

Originality/value

This study proposes a comprehensive analysis framework for addressing organizational corruption in the construction sector by investigating configuration effects of multiple induced conditions and offers a useful method for addressing corruption.
Reimagining the post-pandemic industry of arts in the Arab world: fast-tracked digital uplift or back to business as usual?
Authors: Bodolica Virginia , Kasih Bilal
Published: August 2021

Learning outcomes

The learning outcomes of this paper are as follows: to assess the extent to which a new business concept or entrepreneurial idea represents a commercial success or practical failure, to estimate the complexities associated with the management of a partnership-based venture in the context of emerging markets, to demonstrate understanding of entrepreneurial action and strategic adaptation under the condition of uncontrollable external shocks (e.g. COVID-19) and to evaluate the pros and cons of different strategic options and provide viable recommendations for the future.

Case overview/synopsis

Startup entrepreneurship constitutes the backbone of the socioeconomic activity of any nation and a driver of innovation, industrial diversification and wealth generation, particularly in emerging market settings. Drawing upon narrative storytelling techniques, this case study immerses the reader into the intricacies of entrepreneurial venture creation within the dynamic startup ecosystem in the Middle East. It follows the story of a young serial entrepreneur, Omar, who decided to launch a business in the creative industry of arts in the United Arab Emirates in partnership with his friend, Ahmed. Their common venture, Mont8, showcased and promoted the artwork of budding and well-known Arab talents and was on track to become a recognizable brand in the Middle Eastern business of arts until the COVID-19 crisis shook the world taking everyone by surprise. In an attempt to build a successful post-pandemic future, Omar was convinced that Mont8 needed to fast-track its digital transformation. He envisioned an e-commerce marketplace that would empower Arab artists, designers and photographers to create customized virtual galleries on their own web-stores through the Mont8’s digital platform. Yet, Omar’s vision diverged drastically from the very conservative mindset of Ahmed, who did not want to disrupt tradition and argued in favor of a back-to-business-as-usual approach. It remains unclear whose option would be selected and whether the two partners would stay in this makeover together or rather part ways.

Complexity academic level

Upper-level undergraduate courses.

Supplementary materials

Teaching notes are available for educators only.

Subject Code

CSS 3: Entrepreneurship.