bluuebunny/crossref_metadata_2025 huggingface dataset:
Arginine-rich C9ORF72 ALS Proteins Stall Ribosomes in a Manner Distinct From a Canonical Ribosome-Associated Quality Control Substrate
Authors: Kriachkov Viacheslav , McWilliam Hamish E G , Mintern Justine D , Amarasinghe Shanika L , Ritchie Matt , Furic Luc , Hatters Danny M
Published: February 2022

Hexanucleotide expansion mutations inC9ORF72are a cause of familial amyotrophic lateral sclerosis. We previously reported that long arginine-rich dipeptide repeats (DPR), mimicking abnormal proteins expressed from the hexanucleotide expansion, caused translation stalling when expressed in cell culture models. Whether this stalling provides a mechanism of pathogenicity remains to be determined. Here we explored the molecular features of DPR-induced stalling and examined whether known regulatory mechanisms of ribosome quality control (RQC) are involved to sense and resolve the stalls. We demonstrate that arginine-containing DPRs lead to stalling in a length dependent manner, with lengths longer than 40 repeats invoking severe translation arrest. Mutational screening of 40×Gly-Xxx DPRs shows that stalling is most pronounced where Xxx are positively charged amino acids (Arg or Lys). Through a genome-wide knockout screen we find that genes regulating stalling on polyadenosine mRNA coding for poly-Lys, a canonical RQC substrate, respond differently to the readthrough of arginine-rich DPRs. Indeed, we find evidence that DPR-mediated stalling has no natural regulatory responses even though the stalls may be sensed, as evidenced by an upregulation of RQC gene expression. These findings therefore implicate arginine-rich DPR-mediated stalled ribosomes as posing a particular danger to cellular health and viability.
Elasticity generates indissoluble biomolecular condensates
Authors: Meng Lingyu , Lin Jie
Published: February 2022

While biomolecular condensates are often liquid-like, many experiments found that condensates also exhibit solid-like behaviors, making them indissoluble in conditions liquid condensates dissolve. Despite the biological significance of indissoluble condensates to cellular fitness, the mechanisms underlying the indissolubility of solid-like condensates are still unclear. In this work, we study the effects of elasticity on the dissolution of biomolecular condensates. We demonstrate that the bulk stress inside condensates may prevent the condensates from dissolution and obtain a new mechanical equilibrium condition of elastic condensates. Moreover, we theoretically predict a phase diagram of indissolubility for biomolecular condensates and identify a minimum bulk modulus for the condensates to be indissoluble. To verify our theories, we simulate the two-fluid model in which the slow component corresponding to biomolecules generates elastic stress. Our theoretical predictions are nicely confirmed and independent of microscopic details. Our works show that elasticity makes biomolecular condensates less prone to dissolution.
Chromosome-scale genome assembly of the diploid oat Avena longiglumis reveals the landscape of repetitive sequences, genes and chromosome evolution in grasses
Authors: Liu Qing , Yuan Hongyu , Li Mingzhi , Wang Ziwei , Cui Dongli , Ye Yushi , Sun Zongyi , Tan Xukai , Schwarzacher Trude , Heslop-Harrison John Seymour
Published: February 2022

Background

Oat (Avena sativa, 2n=6x=42) is an important crop, and with its wild relatives including A. longiglumis (ALO, 2n=6x=14), has advantageous agronomic and nutritional traits. A de-novo chromosome-level ALO genome assembly was made to investigate diversity and structural genome variation between Avena species and other Poaceae in an evolutionary context, and develop genomic resources to identify the pangenome and economic traits within Pooideae.

Results

The 3.85 gigabase ALO genome (seven pseudo-chromosomes), contained 40,845 protein-coding genes and 87% repetitive sequences (84.21% transposable elements). An LTR retrotransposon family was abundant at all chromosome centromeres, and genes were distributed without major terminal clusters. Comparisons of synteny with A. eriantha and A. strigosa showed evolutionary translocations of terminal segments including many genes. Comparison with rice (x=12) and the ancestral grass karyotype showed synteny and features of chromosome evolution including fusions, translocations and insertions of syntenic blocks across Pooideae species. With a genome size 10 times larger than rice, ALO showed relatively uniform expansion along the chromosome arms, with few gene-poor regions along arms, and no major duplications nor deletions. Linked gene networks were identified (mixed-linkage glucans and cellulose synthase genes), and CYP450 genes may be related to salt-tolerance.

Conclusions

The high-continuity genome assembly shows gene, chromosomal structural and copy number variation, providing a reference for the Avena pangenome, defining the full spectrum of diversity. Chromosomal rearrangements and genome expansion demonstrate features of evolution across the genus and grass BOP-clade, contributing to exploitation of gene and genome diversity through precision breeding.
Eukaryotic Plankton Community Assembly and Influencing Factors Between Continental Shelf and Slope Sites in the Northern South China Sea
Authors: Li Tangcheng , Liu Guilin , Yuan Huatao , Chen Jianwei , Lin Xin , Li Hongfei , Yu Liying , Wang Cong , Li Ling , Zhuang Yunyun , Lin Senjie
Published: February 2022

Eukaryotic plankton are pivotal members of marine ecosystems playing crucial roles in food webs and biogeochemical cycles. However, understanding the patterns and drivers of their community assembly remains a grand challenge. A study was conducted in the northern South China Sea (SCS) to address this issue. Here, 49 samples were collected and size-fractionated from discrete depths at continental shelf and continental slope in the northern South China Sea over a diel cycle. From high throughput sequencing of the 18S rDNA gene V4 region, 2,463 operational taxonomic units (OTUs) were retrieved. Alveolata and Opisthokonta overwhelmingly dominated the assemblages in relative abundance (44.76%, 31.08%) and species richness (59%, 12%). Biodiversity was higher in the slope than the shelf and increased with depth. Temperature and salinity were found as the major deterministic drivers of taxon composition. Community structure was influenced by multiple factors in the importance order of: environmental factors (temperature + salinity) > spatial factor > water depth > sampling time. Furthermore, the neutral model explained more variations in the smaller-sized (0.22-3μm) community (24%) than larger-sized (3-200 μm) community (16%) but generally explained less variations than did deterministic processes. Additionally, our data indicated that the larger plankton might be more environmentally filtered and less plastic whereas the smaller plankton had stronger dispersal ability. This study provides novel insights into differential contributions of the deterministic process and stochastic process and complexities of assembly mechanisms in shaping the community assembly of micro-nano and pico-eukaryotic biospheres in a subtropical ocean.

Importance

Eukaryotic plankton are essential to the biogeochemical processes in the ocean. Understanding the plankton community and influence factors is rapidly increasing with the advances in high-throughput sequencing in recent years, especially the microbe. Our study documented the biodiversity and drivers of community assembly of eukaryotic plankton in the subtropic northern SCS. We found the community structure was influenced by multiple factors and the deterministic process was more important than the stochastic process in the assembly of the eukaryotic plankton communities. Temperture is the most important factors in deterministic factors rather the nutrients which were previously thought important in shaping the eukaryotic plankton community in this oceanic province. Furthermore, we found smaller-sized miceukaryotic plankton are less environment filtered and more plastic than the larger-sized plankton. This insight revealed the differential contributions of the deterministic process and stochastic process and complexities of assembly mechanisms in shaping the community of eukaryotic biospheres.
Differential CO2-fixation potentials and supporting roles of phagotrophy and proton pump among plankton lineages in a subtropical marginal sea
Authors: Li Hongfei , Chen Jianwei , Yu Liying , Fan Guangyi , Li Tangcheng , Li Ling , Yuan Huatao , Wang Jingtian , Wang Cong , Lin Senjie
Published: February 2022

Lineage-wise physiological activities of plankton communities in the ocean are important but challenging to characterize. Here we conducted whole-assemblage metatranscriptomic profiling at continental shelf and slope sites of South China Sea to investigate carbon fixation in different lineages. We catalogued 4.4 million unique genes, ∼37% being annotatable and mainly involved in microbial metabolism, photosynthesis, amino acid synthesis, oxidative phosphorylation, and two-component systems. With RuBisCO expression as proxy, Calvin carbon fixation (CCF) was mainly contributed by Bacillariophyta, Chlorophyta, Cyanobacteria, Haptophyta and non-diatom Stramenopiles, which was differentially affected by environmental factors among lineages. CCF exhibited positive or negative correlations with phagotrophy gene expression depending on lineages, suggesting phagotrophy enhances (Bacillariophyta, Haptophyta, and Chlorophyta) or complements (Dinophyta) CCF. Our data reveal significant potential of non-Calvin carbon fixation (NCF), mainly contributed by Flavobacteriales, Alteromonadales, Oceanospirillales and Rhodobacterales. Furthermore, in Flavobacteriales, Alteromonadales, Pelagibacterales and Rhodobacterales, NCF potential was positively correlated with proteorhodopsin expression, suggesting that NCF is energetically supported by proteorhodopsin. The novel insights into lineage-dependent potential of carbon fixation, widespread mixotrophy, and proteorhodopsin as energy source for NCF lay a methodological and informational foundation for further research to understand the carbon fixation and trophic landscape in the ocean.

Importance

Lineage-dependent physiologies are very important for understanding the contributions of different lineages to the biogeochemical processes in the oceanic plankton, but it is hardly possible using classical ecological methods. Even though metatranscriptomic methods have now been increasingly used to investigate physiologies of marine plankton, lineage-specific contribution to carbon fixation and phagotrophy has not received due research effort. Using whole-assemblage (prokaryotes + eukaryotes) plankton metatranscriptomic approach, with RNA quantity-based calibration to allow comparison across separately sequenced samples, this study reveals differential capacities of carbon fixation among lineages, widespread mixotrophy, and the potential of proteorhodopsin as energy source for non-photosynthetic carbon fixation. With these novel insights this study lays a methodological and informational foundation for further research to understand the carbon fixation and trophic landscape in the ocean.
HiFi Metagenomic Sequencing Enables Assembly of Accurate and Complete Genomes from Human Gut Microbiota
Authors: Kim Chan Yeong , Ma Junyeong , Lee Insuk
Published: February 2022

Advances in metagenomic assembly have led to the discovery of genomes belonging to unculturable microorganisms. Metagenome-assembled genomes (MAGs) often suffer from discontinuity and chimerism. Recently, nanopore metagenomic sequencing assembled 20 complete MAGs (cMAGs) from 13 human fecal samples, but with low nucleotide accuracy. Here, we report 102 cMAGs obtained by high-accuracy long-read (HiFi) metagenomic sequencing of five human fecal samples, whose initial circular contigs were filtered for authentic prokaryotic genomes using our bioinformatics workflow. Nucleotide accuracy of the final cMAGs was similar to that of Illumina sequencing. The cMAGs could exceed 6 Mbp and included complete genomes of diverse taxa, including entirely unculturable RF39 and TANB77 orders, whose genomes have not been characterized yet. Moreover, cMAGs revealed that regions hard to assemble by short-read sequencing comprised mostly genomic islands and rRNAs. HiFi metagenomic sequencing will facilitate cataloging accurate and complete genomes of human gut microbiota, including unculturable species.
Staphylococcus aureus nt5 gene contributes to bacterial infection ability to form kidney abscess
Authors: Ye Yang , Liu Xinpeng , Xia Zijing , Tang Min , Zhang Dan , He Fuqiang , Zhang Peng , Liang Shufang
Published: February 2022

Staphylococcus aureus (S. aureus) is a commonly conditional infection pathogen, in which several key virulence genes are responsible for bacterial infection ability. The S. aureus nt5 gene, encoding 5’-nucleotidase, mediates bacterial nucleic acid pathway, yet it is nearly unknown of nt5 function for staphylococcal infection ability. Herein we have constructed S. aureus mutant with the gene nt5C166T silence (S. aureus Δnt5) by a CRISPR RNA-guided base editing system to investigate bacterial infection ability in vitro and in vivo. As expected, several nt5-related genes are disturbed in S. aureus Δnt5, in which gene transcription level of py is decreased compared with the wild-type S. aureus. Bacterial gene nt5 is downregulated and py/adk are upregulated when S. aureus is exposed to antibiotics daptomycin, which indicates nt5-mediated nucleic acid pathway is interfered upon with daptomycin treatment. Furthermore, the mutant Δnt5 displays about a 40-fold reduction of bacterial loading in mouse kidney on a mouse sepsis model, and the infection ability of Δnt5 is reduced than the wild-type bacteria. The gene nt5 contributes to S. aureus-infected abscess formation in mouse kidney, and the silence of nt5 gene promotes phagocytosis of S. aureus by mouse and human immunocytes. In general, our findings reveal nt5 silence impedes bacterial loading in kidney to form abscess but enhances S. aureus to be phagocytosed by host cell immune system in vitro and in vivo, which indicates that nt5 gene plays an important role in bacterial infection and immune evasion.
Lineages derived from Cryptococcus neoformans type strain H99 support a link between the capacity to be pleomorphic and virulence
Authors: Fernandes Kenya E. , Fraser James A. , Carter Dee A.
Published: February 2022

The pathogenic yeast Cryptococcus neoformans causes nearly 200,000 deaths annually in immunocompromised individuals. Cryptococcus cells can undergo substantial morphological change during mammalian infection, including increased capsule and cell size, the release of shed capsule, and the production of titan (> 10 μm), micro (< 2 μm) and irregular cells. We examined phenotypic variation under conditions designed to simulate in vivo stress in a collection of nine lineages derived from the C. neoformans type strain H99. These lineages are highly genetically similar but have a range of virulence levels. Strains from hypervirulent lineages had a larger average capsule size, greater variation in cell size, and an increased production of micro cells and shed capsule. We tested whether disruption of SGF29, which encodes a component of the SAGA histone acetylation complex that has previously been implicated in the hypervirulence of some lineages, might also have a role in the production of morphological variants. Deletion of SGF29 in a lineage with intermediate virulence substantially increased its production of micro cells and released capsule, consistent with a switch to hypervirulence. We further examined SGF29 in a set of 52 clinical isolates and found loss-of-function mutations were significantly correlated with patient death. Expansion of a TA repeat in the second intron of SGF29 was positively correlated with cell and capsule size, suggesting it may also affect Sgf29 function. This study extends the evidence for a link between pleomorphism and virulence in Cryptococcus, with a likely role for epigenetic mechanisms mediated by SAGA-induced histone acetylation.

IMPORTANCE

Cryptococcosis is a devastating cause of death and disease worldwide. During infection, Cryptococcus cells can undergo substantial changes to their size and shape. In this study, we used a collection C. neoformans strains that are highly genetically similar but possess differing levels of virulence to investigate how morphological variation aligns with virulence. We found hypervirulent strains on average had larger capsules and greater variation in cell size, and also produced more micro cells and shed capsule. These hypervirulent strains possessed a mutation in SGF29, which encodes a component of the SAGA complex involved in epigenetic regulation. Analysis of the SGF29 gene in a set of clinical isolates found strains with loss-of-function mutations were associated with higher patient death rates. The capacity to vary appears to be linked with virulence in Cryptococcus, and this can occur in the absence of genetic variation via epigenetic mechanisms.
Single-cell molecular characterization to partition the human glioblastoma tumor microenvironment (TME) genetic background
Authors: Lessi Francesca , Franceschi Sara , Morelli Mariangela , Menicagli Michele , Pasqualetti Francesco , Santonocito Orazio , Gambacciani Carlo , Pieri Francesco , Aquila Filippo , Aretini Paolo , Mazzanti Chiara Maria
Published: February 2022

Glioblastoma (GB) is a devastating primary brain malignancy. Recurrence of GB is inevitable despite the standard treatment of surgery, chemotherapy, and radiation, and the median survival is limited to around 15 months. Barriers to treatment include the complex interactions among the different cellular components inhabitant of the tumor microenvironment. These challenges are further compounded by extensive inter- and intra-tumor heterogeneity and by the dynamic plasticity of GB cells. The complex heterogeneous nature of GB cells is helped by the local inflammatory tumor microenvironment, which mostly induces tumor aggressiveness and drug resistance. More effective therapy development heavily depends on higher resolution molecular subtype signatures. All cellular components of a GB tumor are subjected to a continuous pressure inducing proliferation that might favor the accumulation of genetic mutations. Understanding the genetic background of several cellular component s belonging to a GB microenvironment could give insights into tumor behavior and progression. In the present study by using fluorescent multiple labeling and DEPArray cell separator, we recovered several single cells or groups of single cells from populations of different origins from IDH-WT GB samples. From each GB sample, we collected astrocytes (GFAP+), microglia (IBA+), stem cells (CD133+), and endothelial cells (CD105+) and performed Copy Number Aberration (CNA) analysis with a low sequencing depth. The same tumors were subjected to a bulk CNA analysis. The tumor partition in its single components allowed single-cell molecular subtyping which revealed new aspects of GB altered genetic background. Nowadays, single-cell approaches are leading to a new understanding of GB physiology and disease. Moreover, single-cell CNAs resource will permit new insights into genome heterogeneity, mutational processes, and clonal evolution in malignant tissues.
sgcocaller and comapr: personalised haplotype assembly and comparative crossover map analysis using single-gamete sequencing data
Authors: Lyu Ruqian , Tsui Vanessa , Crismani Wayne , Liu Ruijie , Shim Heejung , McCarthy Davis J.
Published: February 2022

Profiling gametes of an individual enables the construction of personalised haplotypes and meiotic crossover landscapes, now achievable at larger scale than ever through the availability of high-throughput single-cell sequencing technologies. However, high-throughput single-gamete data commonly have low depth of coverage per gamete, which challenges existing gametebased haplotype phasing methods. In addition, haplotyping a large number of single gametes from high-throughput singlecell DNA sequencing data and constructing meiotic crossover profiles using existing methods requires intensive processing. Here, we introduce efficient software tools for the essential tasks of generating personalised haplotypes and calling crossovers in gametes from single-gamete DNA sequencing data (sgcocaller), and constructing, visualising, and comparing individualised crossover landscapes from single gametes (comapr). With additional data pre-possessing, the tools can also be applied to bulk-sequenced samples. We demonstrate that sgcocaller is able to generate impeccable phasing results for high-coverage datasets, on which it is more accurate and stable than existing methods, and also performs well on low-coverage single-gamete sequencing datasets for which current methods fail. Our tools achieve highly accurate results with user-friendly installation, comprehensive documentation, efficient computation times and minimal memory usage.
Conformational switch in the alpha-synuclein C-terminus domain directs its fibril polymorphs
Authors: Aguirre Cesar , Miyanoiri Yohei , So Masatomo , Tamaki Hajime , Maruno Takahiro , Doi Junko , Wang Nan , Yamaguchi Keiichi , Nakajima Kichitaro , Yamamori Yu , Inoura Hiroko , Choong Chi-Jing , Kakuda Keita , Ajiki Takahiro , Kimura Yasuyoshi , Ozono Tatsuhiko , Baba Kousuke , Nagano Seiichi , Nagai Yoshitaka , Ogi Hirotsugu , Uchiyama Susumu , Matsuki Yoh , Tomii Kentaro , Goto Yuji , Ikenaka Kensuke , Mochizuki Hideki
Published: February 2022

α-Synuclein (αSyn) inclusions are a pathological hallmark of several neurodegenerative disorders. While cryo-electron microscopy studies have revealed distinct fibril polymorphs across different synucleinopathies, the molecular switches controlling polymorphism remained unveiled. In this study, we found that fibril morphology is associated with the conformational state of monomeric αSyn. Through systematic manipulation of the ionic strength and temperature, we pinpoint two distinct polymorphs: a twisted morphology at low ionic strength and temperature, and a rod-like morphology at higher ionic strength and temperature. Most strikingly, we found that a specific conformational change in the C-terminal domain of the monomeric αSyn serves as the master switch for the formation of polymorphs. Interestingly, this conformational change can be triggered by calcium binding to the C-terminus, connecting environmental factors to specific fibril architectures. Our results unmask the C-terminal domain as a key player for orchestrating αSyn fibril morphology, providing significant insights into the fibrogenesis of αSyn.

Significance Statement

The αSyn C-terminus domain acts as the master switch programming its fibril polymorphism.
Identification and characterization of the HERV-K (HML-8) group of human endogenous retroviruses in the genome
Authors: Liu Mengying , Jia Lei , Li Hanping , Liu Yongjian , Han Jingwan , Zhai Xiuli , Wang Xiaolin , Li Tianyi , Li Jingyun , Zhang Bohan , Yu Changyuan , Li Lin
Published: February 2022

Human endogenous retroviruses (HERV) could vertically transmit in a Mendelian fashion and stable maintenance in the human genome which are estimated to comprise about 8%. HERVs affect human physiology and pathology based on the effect of the provirus-encoded protein or LTR elements. The characterization of the genomic distribution is an essential step to understanding the relationship between endogenous retrovirus expression and diseases. However, the poorly characterization of HML-8 hinders a detailed understanding of the expression regulation of this family in human health and its actual impact on host genomes. In the light of this, the definition of a precise and updated HERV-K HML-8 genomic map is urgently needed. Here we report a comprehensive analysis of HERV-K HML-8 sequences presence and distribution within the human genome, with a detailed description of the different structural and phylogenetic aspects characterizing the group. A total of 40 proviruses and 5 solo LTR elements were characterized with a detailed description of provirus structure, integration time, potentially regulated genes, transcription factor binding sites, and primer binding site feature. The integration time results showed that the HML-8 elements found in the human genome have been integrated in the primate lineage between 23.5 and 52 million years ago (mya). Overall, the results have finally clarified the composition of HML-8, providing an exhaustive background for subsequent functional studies.

Highlights

➢

A comprehensive characterization of the HERV-K (HML-8) in human genome.

➢

There is an apparent preference of HML-8 into intergenic regions and introns.

➢

There are two distinct clusters for the env region of the HML-8 elements.

➢

The average time of HML-8 integration in human is 37.1 mya.
GFAP-directed Inactivation of Men1 Exploits Glial Cell Plasticity in Favor of Neuroendocrine Reprogramming
Authors: Duan Suzann , Sawyer Travis W. , Sontz Ricky A. , Wieland Bradley A. , Diaz Andres F. , Merchant Juanita L.
Published: February 2022

BACKGROUND & AIMS

Efforts to characterize the signaling mechanisms that underlie gastroenteropancreatic neoplasms (GEP-NENs) are precluded by a lack of comprehensive model systems that recapitulate pathogenesis. Investigation into a potential cell-of-origin for gastrin-secreting NENs revealed a role for enteric glia in neuroendocrine cell specification. Here we investigated the hypothesis that loss of menin in glial cells stimulated neuroendocrine differentiation and tumorigenesis.

METHODS

Using Cre-lox technology, we generated a conditional glial fibrillary acidic protein-directed Men1 knockout (GFAPΔMen1) mouse model. Cre specificity was confirmed using a tdTomato reporter. GFAPΔMen1 mice were evaluated for GEP-NEN development and neuroendocrine cell hyperplasia. siRNA-mediated Men1 silencing in a rat enteric glial cell line was performed in parallel.

RESULTS

GFAPΔMen1 mice developed pancreatic NENs, in addition to pituitary prolactinomas that phenocopied the human MEN1 syndrome. GFAPΔMen1 mice exhibited gastric neuroendocrine hyperplasia that coincided with a significant loss of GFAP expression. Mechanistically, Men1 deletion induced reprogramming from a mature glial phenotype toward a neuroendocrine lineage. Furthermore, blockade of Hedgehog signaling in enteric glia attenuated neuroendocrine hyperplasia by restricting the neuroendocrine cell fate.

CONCLUSIONS

GFAP-directed Men1 inactivation exploits glial cell plasticity in favor of neuroendocrine differentiation.

GRAPHICAL ABSTRACT
Modelling the spread of resistance to Varroa in Australian feral honeybee populations
Authors: Owen Robert , Scheerlinck Jean-Pierre , Stevenson Mark
Published: February 2022

Australia is the only country where Western honeybees, Apis mellifera, are not infested with the mite Varroa destructor. Hence, a collapse in the feral honeybee population, brought about by an incursion and spread of V. destructor, would have serious consequences for Australian horticulture given its dependence on managed and feral honeybees for pollination. Managing Varroa in commercial colonies is well understood and can be achieved, although at significant bee-health costs, by using miticides. Protecting the feral population in the event of a Varroa incursion is much more difficult, but nevertheless imperative. One way to mitigate against collapse of the feral population is to seed it with Varroa-resistant queens, so as to accelerate the spread of resistance. We developed a simulation model of the spread of Varroa-resistance in feral honeybee populations following the introduction of Varroa-resistant queens into the managed population.

We show that, compared with a do-nothing scenario, seeding the managed honeybee population with Varroa-resistant queens was only effective in decreasing the length of time for the feral honeybee population to recover when the size of the managed resistant population was large compared to the size of the feral population. This situation may be achievable in some urban areas where numbers of managed colonies are high and habitat for feral colonies is limited.
High sorbic acid resistance ofPenicillium roquefortiis mediated by the SORBUS gene cluster
Authors: Punt Maarten , Seekles Sjoerd J. , van Dam Jisca L. , de Adelhart Toorop Connor , Martina Raithel R , Houbraken Jos , Ram Arthur F. J. , Wösten Han A. B. , Ohm Robin A.
Published: February 2022

Penicillium roquefortiis a major food-spoilage fungus known for its high resistance to the food preservative sorbic acid. Here, we demonstrate that the minimum inhibitory concentration of undissociated sorbic acid (MICu) ranges between 4.2 and 21.2 mM when 34P. roquefortistrains were grown on malt extract broth. A genome-wide association study revealed that the six most resistant strains contained the 180 kbp gene cluster SORBUS, which was absent in the other 28 strains. In addition, a SNP analysis revealed five genes outside the SORBUS cluster that may be linked to sorbic acid resistance. A partial SORBUS knock-out (>100 of 180 kbp) in a resistant strain reduced sorbic acid resistance to similar levels as observed in the sensitive strains. Whole genome transcriptome analysis revealed a small set of genes present in both resistant and sensitiveP. roquefortistrains that were differentially expressed in the presence of the weak acid. These genes could explain whyP. roquefortiis more resistant to sorbic acid when compared to other fungi, even in the absence of the SORBUS cluster. Together, the MICuof 21.2 mM makesP. roquefortiamong the most sorbic acid-resistant fungi, if not the most resistant fungus, which is mediated by the SORBUS gene cluster.

Author summary

Chemical preservatives, such as sorbic acid, are often used in food to prevent spoilage by fungi, yet some fungi are particularly well-suited to deal with these preservatives. First, we investigated the resistance of 34Penicillium roquefortistrains to various food preservatives. This revealed that some strains were highly resistant to sorbic acid, while others are more sensitive. Next, we used DNA sequencing to compare the genetic variation between these strains and discovered a specific genetic region (SORBUS) that is unique to the resistant strains. Through comparative analysis with other fungal species the SORBUS region was studied in more detail and with the use of genetic engineering tools we removed this unique region. Finally, the mutant lacking the SORBUS region was confirmed to have lost its sorbic acid resistance. This finding is of particular interest as it suggests that only some, not all,P. roquefortistrains are potent spoilers and that specific genetic markers could help in the identification of resistant strains.
Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis
Authors: Mijnheer Gerdien , Servaas Nila H. , Leong Jing Yao , Boltjes Arjan , Spierings Eric , Chen Phyllis , Lai Liyun , Petrelli Alessandra , Vastert Sebastiaan , de Boer Rob J. , Albani Salvatore , Pandit Aridaman , van Wijk Femke
Published: February 2022

Autoimmune inflammation is characterized by tissue infiltration and expansion of antigen-specific T cells. Although this inflammation is often limited to specific target tissues, it remains yet to be explored whether distinct affected sites are infiltrated with the same, persistent T cell clones. Here we performed CyTOF analysis and T cell receptor (TCR) sequencing to study immune cell composition and (hyper-)expansion of circulating and joint-derived Tregs and non-Tregs in Juvenile Idiopathic Arthritis (JIA). We studied different joints affected at the same time, as well as over the course of relapsing-remitting disease. We found that the composition and functional characteristics of immune infiltrates are strikingly similar between joints within one patient, and observed a strong overlap between dominant T cell clones, especially Treg, of which some could also be detected in circulation and persisted over the course of relapsing remitting disease. Moreover, these T cell clones were characterized by a high degree of sequence similarity, indicating the presence of TCR clusters responding to the same antigens. These data suggest that in localized autoimmune disease there is auto-antigen driven expansion of both Teffector and Treg clones, that are highly persistent and are (re)circulating. These dominant clones might represent interesting therapeutic targets.
Generating Functional Cells Through Enhanced Interspecies Chimerism with Human Pluripotent Stem Cells
Authors: Zhu Yanling , Zhang Zhishuai , Fan Nana , Huang Ke , Li Hao , Gu Jiaming , Zhang Quanjun , Ouyang Zhen , Zhang Tian , Tang Jun , Zhang Yanqi , Suo Yangyang , Lai Chengdan , Wang Jiaowei , Wang Junwei , Shan Yongli , Wang Mingquan , Chen Qianyu , Zhou Tiancheng , Lai Liangxue , Pan Guangjin
Published: February 2022

Obtaining functional human cells through interspecies chimerism with human pluripotent stem cells (hPSCs) remains unsuccessful due to its extreamly low efficiency. Here, we show that hPSCs failed to differentiate and contribute teratoma in presence of mouse PSCs (mPSCs). While, MYCN, a pro-growth factor dramatically promotes hPSC contribution in teratoma co-formation by hPSCs/mPSCs. MYCN combined with BCL2 (M/B) greatly enhanced conventional hPSCs to integrate into preimplantation embryos of different species, such as mice, rabbits and pigs and substrantially contributed to mouse post-implantation chimera in embryonic and extra-embyonic tissues. Strikingly, M/B-hPSCs injected into preimplantation Flk-1+/- mouse embryos show further enhanced chimerism that allows obtaining live human CD34+ blood progenitor cells from chimeras through cell sorting. The chimera derived human CD34+ cells further gave rise to various subtype blood cells in typical colony forming unit(CFU) assay. Thus, we proof the concept to obtain functional human cells through enchanced interspecies chimerism with hPSCs.
Mitonuclear interactions produce extreme differences in response to redox stress
Authors: Camus M. Florencia , Kotiadis Vassilios , Carter Hugh , Rodriguez Enrique , Lane Nick
Published: February 2022

Incompatibilities between mitochondrial and nuclear genes can perturb respiration, biosynthesis, signalling and gene expression. Here we investigate whether mild mitonuclear incompatibilities alter response to redox stress induced by N-acetyl cysteine (NAC). We studied threeDrosophila melanogasterlines with mitochondrial genomes either coevolved (WT) or mildly mismatched (BAR, COX) to an isogenic nuclear background. Responses to NAC varied substantially with mitonuclear genotype, sex, tissue and dose. NAC caused infertility and high mortality in some groups but not others. Using tissue-specific fluorespirometry, we show that NAC did not alter H2O2flux but suppressed complex I-linked respiration in female flies, maintaining a reduced glutathione pool. High mortality in BAR females was associated with severe suppression of complex I-linked respiration, rising H2O2flux in ovaries and oxidation of the glutathione pool. Our results suggest that redox stress is attenuated by suppression of complex-I linked respiration, to the point of death in some mitonuclear lines.
Selective effects of a short transient environmental fluctuation on a natural population
Authors: Pfenninger Markus , Foucault Quentin , Waldvogel Ann-Marie , Feldmeyer Barbara
Published: February 2022

Natural populations experience continuous and often transient changes of environmental conditions. These in turn may result in fluctuating selection pressures leading to variable demographic and evolutionary population responses. Rapid adaptation as short-term response to a sudden environmental change has in several cases been attributed to polygenic traits, but the underlying genomic dynamics and architecture are poorly understood. In this study, took advantage of a natural experiment in an insect population by monitoring genome-wide allele frequencies before and after a cold snap event. Whole genome pooled sequencing of time series samples revealed ten selected haplotypes carrying ancient polymorphisms, partially with signatures of balancing selection. By constantly cold exposing genetically variable individuals in the laboratory, we could demonstrate with whole genome resequencing i) among the survivors, the same alleles rose in frequency as in the wild and ii) that the identified variants additively predicted fitness (survival time) of its bearers. Finally, by simultaneously sequencing the genome and the transcriptome of cold exposed individuals we could tentatively link some of the selected SNPs to thecis- andtrans-regulation of genes and pathways known to be involved in cold response of insects, likeCytochrome P450and fatty acid metabolism. Altogether, our results shed light on the strength and speed of selection in natural populations and the genomic architecture of its underlying polygenic trait. Population genomic time series data thus appear as promising tool for measuring the selective tracking of fluctuating selection in natural populations.
Distinct structural bases for sequence-specific DNA binding by mammalian BEN domain proteins
Authors: Zheng Luqian , Liu Jingjing , Niu Lijie , Kamran Mohammad , Yang Ally W.H. , Jolma Arttu , Dai Qi , Hughes Timothy R. , Patel Dinshaw J. , Zhang Long , Prasanth Supriya G. , Yu Yang , Ren Aiming , Lai Eric C.
Published: February 2022

The BEN domain is a recently recognized DNA binding module that is present in diverse metazoans and certain viruses. Several BEN domain factors are known as transcriptional repressors, but, overall, relatively little is known of how BEN factors identify their targets in humans. In particular, X-ray structures of BEN domain:DNA complexes are only known forDrosophilafactors bearing a single BEN domain, which lack direct vertebrate orthologs. Here, we characterize several mammalian BEN domain (BD) factors, including from two NACC family BTB-BEN proteins and from BEND3, which has four BDs. In vitro selection data revealed sequence-specific binding activities of isolated BEN domains from all of these factors. We conducted detailed functional, genomic, and structural studies of BEND3. We show that BD4 is a major determinant for in vivo association and repression of endogenous BEND3 targets. We obtained a high-resolution structure of BEND3-BD4 bound to its preferred binding site, which reveals how BEND3 identifies cognate DNA targets and shows differences with one of its non-DNA-binding BEN domains (BD1). Finally, comparison with our previous invertebrate BEN structures, along with additional structural predictions using AlphaFold2 and RoseTTAFold, reveal distinct strategies for target DNA recognition by different types of BEN domain proteins. Together, these studies expand the DNA recognition activities of BEN factors and provide structural insights into sequence-specific DNA binding by mammalian BEN proteins.
Disconnectedness in a connected world: why people ignore messages and calls
Authors: Agarwal Naresh Kumar , Mitiku Tenbit , Lu Wenqing
Published: February 2022

Purpose

People are living in a world where they maintain connectivity through sending and receiving messages and calls. Yet, almost daily, people choose not to respond to certain messages or calls, which can make the sender anxious, and adversely affect their communication. The aim of this study was to investigate the receivers' reasons for not responding.

Design/methodology/approach

The authors used theories related to information avoidance, power, interpersonal deception and emotions and conducted interviews of smartphone users.

Findings

The study found that the receiver’s physical and psychological state, the time of the day and the content of the message impacted non-response. The findings suggest that the non-response behavior is moderated by the power relationship between the sender and the receiver. The receiver’s state of mind will determine the likelihood of non-response, while the sender’s state of mind will determine how the sender deals with non-response.

Research limitations/implications

The study contributes to research in mobile information behavior, and the wider fields of information science, sociology and communication.

Practical implications

The process of interviewing itself helped raise awareness about these issues with the people who were interviewed.

Social implications

The findings shed light on the current communicative practices and ways to overcome the disconnectedness and stress suffered by people regularly using smartphones.

Originality/value

The study provides recommendations for healthy communication between the sender and the receiver using their smartphones.
Control flow versus communication: comparing two approaches to process modelling
Authors: Moattar Haleh , Bandara Wasana , Kannengiesser Udo , Rosemann Michael
Published: February 2022

Purpose

Business process modelling integrates and visualizes relevant information essential for managing day-to-day business operations. It plays a critical role in the design and execution of business transformations. Recognizing the role of process modelling, a large number of modelling languages, methods and techniques have been developed, each offering diverse advantages and having inherent limitations. Traditional and popular process modelling approaches focus on the exact specification of the control flow of business processes, whereas more recent approaches like Subject-oriented Business Process Management (S-BPM) are focused on the communication between process participants. This study aims to provide comparative insights about these two approaches through their experimental application. This study does so by comparing Business Process Model and Notation (BPMN); a control flow approach, with S-BPM; a communication approach, with a specific focus on their suitability for novice modellers.

Design/methodology/approach

This paper reports on an exploratory experiment that compares BPMN to S-BPM. Applying cognitive load theory, this study compares the experiences and outcomes of novice process modellers, assessing perceived ease of use, model quality (syntactic and semantic) and modelling efficiency (time to model) across the two approaches.

Findings

Study results show that S-BPM (a communication approach) led to significantly better user performances for process modelling than BPMN (a control flow approach). This study points to how a different modelling approach such as S-BPM could be either considered as an alternative or to complement the more popular control flow approach BPMN. This observation was especially relevant for modelling contexts where domain experts are novice process modellers.

Originality/value

This study provides the first empirical evidence that communication approaches like S-BPM could outperform modelling approaches which are control-flow based (i.e. BPMN), especially when being used by novice process modellers who hold the domain and process knowledge. This study uses this as a springboard to present important considerations for practice and guide future process modelling research.
Do political connections shape the nexus between board attributes and corporate cash holdings?
Authors: T.F. Abuhijleh Sara , A.A. Zaid Mohammad
Published: February 2022

Purpose

Motivated by the agency theory, this paper primarily intends to empirically investigate the impact of board attributes on corporate cash holdings and how the mentioned nexus is moderated by the level of corporate political connections in a developing country, namely, Palestine during the period of 2011–2018.

Design/methodology/approach

Multiple regression analysis on a panel data was employed. Moreover, the authors applied three different approaches of static panel data “pooled OLS, fixed effect and random effect”. Fixed-effects estimator was selected as the optimal and most appropriate model. In addition, to control for the potential endogeneity problem and to profoundly analyze the study data, the authors perform the one-step system generalized method of moment estimator.

Findings

The results of this study provide support for the agency theory ideology, which considers that sturdy and well-established corporate governance (CG) paradigms minify the magnitude of cash held by companies. Furthermore, the findings distinctly unveil that the impact of board attributes is more positive under a high level of political connections.

Research limitations/implications

This study was solely restricted to one institutional context “Palestine”; therefore, the results reflect the attributes of the Palestinian business environment. In this vein, it is possible to generate different findings in other countries, particularly in developed markets.

Practical implications

The findings of this study can draw responsible parties, top management and policymakers' attention in developing countries to introduce and contextualize new mechanisms that can lead to better managing of corporate cash holdings.

Originality/value

Empirical evidence on the moderating role of political connection on the effect of board attributes on corporate cash holdings something that was predominantly neglected by the earlier research and has not yet examined by ancestors. Hence, to protrude nuanced understanding of this novel idea, this study minutely bridges this research gap and contributes practically and theoretically to the existing CG–cash holdings literature.
A scientometric analysis and review of construction labour productivity research
Authors: Adebowale Oluseyi Julius , Agumba Justus Ngala
Published: February 2022

Purpose

Labour productivity in construction has fallen behind other industries in most of the world and has declined continuously for decades. Although several scholarly research projects have been conducted to salvage the prevalent low labour productivity in construction, contractors in the construction industry have continued to grapple with the devastating impact of low productivity. The purpose of this study is to determine key areas of focus necessary to promote productivity growth in construction.

Design/methodology/approach

Bibliometric and scientometric assessments were conducted to map the existing construction labour productivity (CLP) studies and establish key focus areas in the research domain. The keywords “Construction Productivity” OR “Construction Labour Productivity” OR “Construction Labor Productivity” OR “Construction Worker Productivity”.

Findings

Emerging trends in the CLP research field are reported. The study also determined the most productive authors and collaboration among authors, most productive journals, most active regions and publications with the highest impact in CLP research.

Research limitations/implications

Documents published in the Scopus database were considered for analysis because of the wider coverage of the database. Journal and conference articles written in English language represent the inclusion criteria, while articles in press, review, book chapters, editorial, erratum, note, short survey and data paper were excluded from analysis. The study is also limited to documents published from 2012 to 2021.

Practical implications

The study brought to the awareness of the industry practitioners and other construction stakeholders, the key knowledge areas that are critical to promoting productivity growth in construction.

Originality/value

Except bibliometric analysis, previous research studies have used different approaches to investigate productivity in construction. The study presented future research directions through the emerging knowledge areas identified in the study.