bluuebunny/crossref_metadata_2025 huggingface dataset:
The multilayered organization of water-soluble proteins
Authors: Wang Lincong
Published: July 2021

The structural analysis of proteins has focused primarily on secondary structure, three-dimensional fold and active site while whole surface has been analyzed to a lesser extent and interior has not received much attention. Here we present an analysis of both the surfaces and the interiors of a set of water-soluble monomeric proteins in terms of solvent-excluded surface (SES) and atomic partial charge. The analysis shows that the surface of a soluble monomer has a net negative charge and is much smoother than the interior. Most interestingly with regard to both atomic partial charge and SES-defined geometric property there exists a multilayered organization from the exterior to the interior of a soluble monomer. The multilayered organization is closely related to protein-solvent interaction and should be a general feature of a water-soluble protein. Particularly the multilayered organization may set an upper limit for the size of a water-soluble monomer and plays an important role in the determination of its overall shape in solution.

Significance statement

The analysis of the solvent-excluded surfaces (SESs) of a large set of water-soluble monomers with crystal structures shows that in any soluble monomer there exists a multilayered organization in terms of SES-defined electric and geometric properties. It means that the atoms in a soluble monomer are not randomly distributed but organized into successive layers to optimize its interaction with solvent molecules. The SES-derived multi-layered organization should be a general feature of a water-soluble protein and likely plays a vital role in its solvation, folding and structure.
Comparison and evaluation of statistical error models for scRNA-seq
Authors: Choudhary Saket , Satija Rahul
Published: July 2021

Heterogeneity in single-cell RNA-seq (scRNA-seq) data is driven by multiple sources, including biological variation in cellular state as well as technical variation introduced during experimental processing. Deconvolving these effects is a key challenge for preprocessing workflows. Recent work has demonstrated the importance and utility of count models for scRNA-seq analysis, but there is a lack of consensus on which statistical distributions and parameter settings are appropriate. Here, we analyze 58 scRNA-seq datasets that span a wide range of technologies, systems, and sequencing depths in order to evaluate the performance of different error models. We find that while a Poisson error model appears appropriate for sparse datasets, we observe clear evidence of overdispersion for genes with sufficient sequencing depth in all biological systems, necessitating the use of a negative binomial model. Moreover, we find that the degree of overdispersion varies widely across datasets, systems, and gene abundances, and argues for a data-driven approach for parameter estimation. Based on these analyses, we provide a set of recommendations for modeling variation in scRNA-seq data, particularly when using generalized linear models or likelihood-based approaches for preprocessing and downstream analysis.
Differential effects of high versus low linear energy transfer (LET) radiation on type-I interferon (IFNβ) and TREX1 responses
Authors: Miles Devin , Cao Ning , Sandison George , Stewart Robert D. , Moffitt Greg , Pulliam Thomas , Parvathaneni Upendra , Goff Peter , Nghiem Paul , Stantz Keith
Published: July 2021

Purpose

Cancer cells produce innate immune signals following radiation damage, with STING pathway signaling as a critical mediator. High linear energy transfer (LET) radiations create larger numbers of DNA double-strand breaks (DSBs) per unit dose than low-LET radiations and may therefore be more immunogenic. We studied the dose response characteristics of pro-immunogenic type-I interferon, interferon-beta (IFNβ), and its reported suppressor signal, three-prime repair exonuclease 1 (TREX1), in vitro with low-LET x-rays and high-LET fast neutrons.

Methods

Merkel cell carcinoma cells (MCC) were irradiated by graded doses of x-rays (1-24 Gy) or fast neutrons (1-8 Gy). IFNβ was measured as a function of dose via ELISA assay, and exonuclease TREX1 expression via immunofluorescence microscopy. The Monte Carlo damage simulation (MCDS) was used to model fast neutron relative biological effectiveness for DSB induction (RBEDSB) and compared to laboratory measurements of the RBE for IFNβ production (RBEIFNβ) and TREX1 upregulation (RBETREX1). RBEIFNβ models were also applied to radiation transport simulations to quantify the potential secretion of IFNβ in representative clinical beams.

Results

Peak IFNβ secretion occurred at 5.7 Gy for fast neutrons and at 14.0 Gy for x-rays, i.e., an effective RBEIFNβ of 2.5 ± 0.2. The amplitude (peak value) of secreted IFNβ signal did not significantly differ between x-rays and fast neutrons (P > 0.05). TREX1 signal increased linearly with absorbed dose, with a four-fold higher upregulation per unit dose for fast neutrons relative to x-rays (RBETREX1 of 4.0 ± 0.1). Monte Carlo modeling of IFNβ suggests Bragg peak-to-entrance ratios of IFNβ production of 40, 100, and 120 for proton, alpha, and carbon ion beams, respectively, a factor of 10-20-fold higher compared to their corresponding physical dose peak-to-entrance ratios. The spatial width of the Bragg peak for IFNβ production is also a factor of two smaller.

Conclusion

High-LET fast neutrons initiate a larger IFNβ response per unit absorbed dose than low-LET x-rays (i.e., RBEIFNβ value of 2.5). The RBE value for IFNβ is quite similar to data reported in the literature for DSB induction and cellular, post-irradiation micronucleation formation for neutrons and x-rays. The increased IFNβ release after high-LET radiation may be a contributing factor in stimulating a systemic anti-tumor, adaptive immune response (abscopal effect). However, our results indicate that TREX1 anti-inflammatory signaling in vitro for MCC cells is larger per unit dose for fast neutrons than for x-rays (RBETREX1 of 4.0). Given these competing effects, additional studies are needed to clarify whether or not high-LET radiations are therapeutically advantageous over low-LET radiation for pro-inflammatory immune signaling in other cell lines in vitro and for in vivo cancer models.
Structure of the integrin receptor αMβ2 headpiece in complex with a function-modulating nanobody
Authors: Jensen Rasmus K. , Pedersen Henrik , Lorentzen Josefine , Laursen Nick Stub , Vorup-Jensen Thomas , Andersen Gregers Rom
Published: July 2021

The integrin receptor αMβ2 mediates phagocytosis of complement-opsonized objects, adhesion to the extracellular matrix and trans-endothelial migration of leukocytes. Here we present the first atomic structure of the human αMβ2 headpiece fragment in complex with the nanobody hCD11bNb1 determined at a resolution of 3.2 Å. The receptor headpiece adopts the closed conformation expected to have low ligand affinity. The crystal structure advocates that in the R77H αM variant associated with systemic lupus erythematosus, the modified allosteric coupling between ligand coupling and integrin outside-inside signalling is due to subtle conformational effects transmitted over 40 Å. The nanobody binds to the αI domain of the αM subunit in an Mg2+ independent manner with low nanomolar affinity. Biochemical and biophysical experiments with purified proteins argue that the nanobody acts as a competitive inhibitor through steric hindrance exerted on the thioester domain of iC3b attempting to bind the αM subunit. Surprisingly, the nanobody stimulates the interaction of cell-bound αMβ2 with iC3b suggesting that it represents a novel high-affinity proteinaceous αMβ2 specific agonist. We propose a model based on the conformational spectrum of the receptor to reconcile these conflicting observations regarding the functional consequences of hCD11bNb1 binding to αMβ2. Furthermore, our data suggest that the iC3b-αMβ2 complex may be more dynamic than predicted from the crystal structure of the core complex.
EpicPCR-Directed Cultivation of a Candidatus Saccharibacteria Symbiont Reveals a Type IV Pili-dependent Epibiotic Lifestyle
Authors: Xie Bingliang , Wang Jian , Nie Yong , Chen Dongwei , Hu Beiyu , Wu Xiaolei , Du Wenbin
Published: July 2021

Candidate phyla radiations (CPR), accounting for a major microbial supergroup with remarkably small genomes and reduced sizes, are widely distributed yet mostly uncultured. Limited culture and its obligate reliance upon other bacteria hindered investigation of their lifestyles. In this work we isolated a CPR bacterium, TM7i, with its host Leucobacter aridocollis J1, by combination of Emulsion, Paired Isolation and Concatenation PCR (epicPCR) detection and filtrate co-culture. Genomic profiling of TM7 genomes and microscopic investigation of TM7i-J1 symbiosis suggest the conservation of type IV pili and a pili-dependent lifestyle of TM7. Further, we observed twitching motility of TM7i mediated by pili and its role played in the interaction with its host. Our results shed a light on the lifestyle about this enigmatic bacterial radiation, which may also be adopted by other CPR organisms. The epicPCR-directed isolation method underlines high efficiency of CPR bacteria isolation and thus may be used in other symbiotic or epibiotic microorganisms.
Kinetic characterization and thermostability ofC. eleganscytoplasmic and mitochondrial malate dehydrogenases
Authors: Thomas Matthew J. , Cassidy Emma R. , Robinson Devin S. , Walstrom Katherine M.
Published: July 2021

Malate dehydrogenase (MDH) catalyzes the conversion of NAD+and malate to NADH and oxaloacetate in the last step of the citric acid cycle. Eukaryotes have at least two MDH isozymes, one that is imported into the mitochondria and one that remains in the cytoplasm. We overexpressed and purifiedCaenorhabditis eleganscytoplasmic MDH-1 (F46E10.10) and mitochondrial MDH-2 (F20H11.3) inE. coli. Our goal was to compare the kinetic and structural properties of these enzymes becauseC. eleganscan survive adverse environmental conditions, such as lack of food and elevated temperatures. In steady-state enzyme kinetics assays, we determined that theKMvalues for oxaloacetate were 54 and 52 μM, and theKMvalues for NADH were 61 and 107 μM, for MDH-1 and MDH-2, respectively. We partially purified endogenous MDH from a mixed population of worms and separated MDH-1 from MDH-2 using anion exchange chromatography. Both endogenous enzymes had aKMfor oxaloacetate similar to that of the corresponding recombinant enzyme. The reaction velocities of the recombinant enzymes had slightly different temperature-dependencies: MDH-1 and MDH-2 had maximum activity at 40 °C and 35 °C, respectively. In a thermotolerance assay, MDH-1 was much more thermostable than MDH-2. Molecular homology modeling predicted that MDH-1 had more salt-bridges between the subunits than mammalian MDH1 enzymes, and these ionic interactions may contribute to its thermostability. In contrast, the MDH-2 homology model predicted fewer ionic interaction between the subunits compared to mammalian MDH2 enzymes. These results suggest that the increased structural stability of MDH-1 may facilitate its ability to remain active in adverse environmental conditions. In contrast, MDH-2 may use other strategies, such as protein binding partners, to function under similar conditions.
Gating mechanism of human N-type voltage-gated calcium channel
Authors: Dong Yanli , Gao Yiwei , Xu Shuai , Wang Yuhang , Yu Zhuoya , Li Yue , Li Bin , Yang Bei , Zhang Xuejun Cai , Jiang Daohua , Huang Zhuo , Zhao Yan
Published: July 2021

N-type voltage-gated calcium (CaV) channels mediate Ca2+ influx at the presynaptic terminals in response to action potential and play vital roles in synaptogenesis, neurotransmitter releasing, and nociceptive transmission. Here we elucidate a cryo-electron microscopy (cryo-EM) structure of the human CaV2.2 complex at resolution of 2.8 Å. This complex structure reveals how the CaV2.2, β1, and α2δ1 subunits are assembled. In our structure, the second voltage-sensing domain (VSD) is stabilized at a resting-state conformation, which is distinct from the other three VSDs of CaV2.2 as well as activated VSDs observed in previous structures of CaV channels. The structure also shows that the intracellular gate formed by S6 helices is closed, and a W-helix from the DII-III linker is determined to act as a blocking-ball that causes closed-state inactivation in CaV2.2. Collectively, our structure provides previously unseen structural insights into fundamental gating mechanisms of CaV channels.
Myths and mechanisms: RecBCD and Chi hotspots as determinants of self vs. non-self
Authors: Subramaniam Suriyen , Smith Gerald R.
Published: July 2021

Bacteria face a challenge when DNA enters their cells by transformation, mating, or phage infection. Should they treat this DNA as an invasive foreigner and destroy it, or consider it one of their own and potentially benefit from incorporating new genes or alleles to gain useful functions? It is frequently stated that the short nucleotide sequence Chi (5’ GCTGGTGG 3’) recognized by RecBCD helicase-nuclease allows Escherichia coli to distinguish self (i.e., E. coli) DNA from non-self (i.e., any other) DNA and to destroy non-self DNA, and that Chi is “over-represented” in the E. coli genome. We show here that these dogmas are incorrect and apparently based on false assumptions. We note Chi’s wide-spread occurrence and activity in distantly related species. We illustrate multiple, highly non-random features of the genomes of coli and coliphage P1 that account for Chi’s high frequency and genomic position, leading us to propose that P1 selects for Chi’s enhancement of recombination, whereas E. coli selects for the preferred codons in Chi. We discuss other, substantiated mechanisms for self vs. non-self determination involving RecBCD and for RecBCD’s destruction of DNA that cannot recombine, whether foreign or domestic.
Long-range single-molecule mapping of chromatin modification in eukaryotes
Authors: Weng Zhe , Ruan Fengying , Chen Weitian , Xie Zhe , Xie Yeming , Zhang Chen , Chen Zhichao , Wang Juan , Sun Yuxin , Fang Yitong , Guo Mei , Tong Yiqin , Li Yaning , Tang Chong
Published: July 2021

The epigenetic modifications of histones are essential markers related to the development and pathogenesis of diseases, including human cancers. Mapping histone modification has emerged as the widely used tool for studying epigenetic regulation. However, existing approaches are limited by fragmentation and short-read sequencing represent the average chromatin status in samples and cannot provide information about the long-range chromatin states. We leveraged the advantage of long read sequencing to develop a method “BIND&MODIFY” for profiling the histone modification of individual DNA fibers. Our approach is based on the recombinant fused protein A-M.EcoGII, which tethers the methyltransferase M.EcoGII to the protein binding sites and locally labels the neighboring DNA regions through artificial methylations. We demonstrated that the aggregated BIND&MODIFY signal matches the bulk-level ChIP-seq and CUT&TAG, verify the single-molecule heterogenous histone modification status, and quantify the correlation between distal elements. This method could be an essential tool in future third-generation sequencing ages.
Therapeutic targeting of SETD2-deficient cancer cells with the small-molecule compound RITA
Authors: Lopez Kirsten A. , Sarkar Sovan , Seraia Elena , Toffanin Chiara , Cooper Christian , Challoumas Michalis , Okonjo Fiona A. , Jones George D. D. , Buffa Francesca , Ebner Daniel , Humphrey Timothy C.
Published: July 2021

The histone methyltransferase SETD2 and its associated histone mark H3 lysine 36 trimethylation (H3K36me3) are frequently lost in certain cancer types, identifying SETD2 as an important therapeutic target. Here we show that SETD2-deficient cancer cells are profoundly sensitive to the compound RITA, resulting in significant p53 induction and apoptosis. This is further associated with defects in DNA replication, leading to delays in S-phase progression, increased recruitment of replication stress markers, and reduced replication fork progression. RITA sensitivity is linked to the phenol sulphotransferase SULT1A1, which we find to be highly upregulated in cells that lack SETD2. Depletion of SULT1A1 or addition of the phenol sulphotransferase inhibitor DCNP abolishes these phenotypes and suppresses the sensitivity of SETD2-deficient cancer cells, identifying SULT1A1 activity to be critical in mediating the potent cytotoxicity of RITA against SETD2-deficient cells. These findings define a novel therapeutic strategy for targeting the loss of SETD2 in cancer.

Significance Statement

The histone-modifying enzyme SETD2 has emerged as an important tumour suppressor in a number of different cancer types, identifying it as a promising therapeutic target. The concept of synthetic lethality, a genetic interaction in which the simultaneous loss of two genes or pathways that regulate a common essential process renders the cell nonviable, is a valuable tool for killing cancer cells that have known mutations. In this study, we conducted a synthetic lethality screen for compounds that specifically target SETD2-deficient cancer cells. The top hit, a compound called RITA, reduces cell viability and induces cell death only in the context of SETD2 loss, thereby highlighting a potential novel therapeutic strategy for treating SETD2-deficient cancers.
CLUH interactome reveals an association to SPAG5 and a proximity to the translation of mitochondrial protein
Authors: Hémono Mickaële , Haller Alexandre , Chicher Johana , Duchêne Anne-Marie , Ngondo Richard Patryk
Published: July 2021

Mitochondria require thousands of proteins to fulfil their essential function in energy production and other fundamental biological processes. These proteins are mostly encoded by the nuclear genome, translated in the cytoplasm before being imported into the organelle. RNA binding proteins (RBPs) are central players in the regulation of this process by affecting mRNA translation, stability or localization. CLUH is an RBP recognizing specifically mRNAs coding for mitochondrial proteins, but its precise molecular function and interacting partners remain undiscovered in mammals. Here we reveal for the first time CLUH interactome in mammalian cells. Using both co-IP and BioID proximity-labeling approaches, we identify novel molecular partners interacting stably or transiently with CLUH in HCT116 cells and mouse embryonic stem cells. We reveal a stable RNA-independent interaction of CLUH with itself and with SPAG5 in cytosolic granular structures. More importantly, we uncover an unexpected proximity of CLUH to mitochondrial proteins and their cognate mRNAs in the cytosol. Additionally, our data highlight the importance of CLUH TPR domain for its interactions with both proteins and mRNAs. Overall, through the analysis of CLUH interactome, our study sheds a new light on CLUH molecular function by highlighting its association to the translation and subcellular localization of some mRNAs coding for mitochondrial proteins.
Cryo-EM structure of alpha-synuclein fibrils amplified by PMCA from PD and MSA patient brains
Authors: Burger Domenic , Fenyi Alexis , Bousset Luc , Stahlberg Henning , Melki Ronald
Published: July 2021

Synucleinopathies are neurodegenerative diseases related to the aggregation of the protein alpha-synuclein (aSyn). Among these diseases, Parkinson’s disease (PD) and multiple system atrophy (MSA) are most prevalent. aSyn can readily form different fibrillar polymorphs, if exposed to an air-water interface or by templating with pre-existing fibrils. We here report the structures of three fibrillar polymorphs that were obtained after seeding monomeric aSyn with PD and MSA patients brain homogenates using protein misfolding cyclic amplification (PMCA). Seeding with a control brain homogenate did not produce fibrils, and seeding with other in vitro generated fibrillar polymorphs as a control faithfully produced polymorphs of a different type. The here determined fibril structures from PD and MSA brain tissue represent new folds, which partly resemble that of previously reported in vitro generated fibrils from Y39 phosphorylated aSyn protein. The relevance of these fibrils for synucleinopathies in humans remains to be further investigated.

Impact Statement

Neurodegenerative diseases such as Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are suspected to be causatively related to the prion-like propagation of aggregates of the protein alpha-synuclein (aSyn). The fibril structures reported here were obtained after seeding from diseased human brain homogenate and differ from all previously published aSyn fibril arrangements. In case these fibrils would turn out to be the long sought causative agents of these diseases, their structures might lead to the development of therapeutic strategies to modify these diseases and to a better understanding of the mechanistic processes that lead to neurodegeneration and spreading of the diseases.
A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection
Authors: Li Yansheng , Xu Mingkai , Li Yongqiang , Gu Wu , Halimu Gulinare , Li Yuqi , Zhang Zhichun , Zhou Libao , Liao Hui , Yao Songyuan , Zhang Huiwen , Zhang Chenggang
Published: July 2021

Influenza pandemic poses public health threats annually for lacking vaccine which provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens inducing cross-protective antibody response with epitopes activating cross-protective cytotoxic T-cells would offer an attractive strategy for developing universal vaccine. In this study, we constructed a recombinant protein NMHC consisting of influenza viral conserved epitopes and superantigen fragment. NMHC promoted the mature of bone marrow-derived dendritic cells and induced CD4+T cells to differentiate into Th1, Th2 and Th17 subtypes. Mice vaccinated with NMHC produced high level of immunoglobulins which cross-bound to HA fragments from six influenza virus subtypes with high antibody titers. Anti-NMHC serum showed potent hemagglutinin inhibition effects to highly divergent group 1 (H1 subtypes) and group 2 (H3 subtype) influenza virus strains. And purified anti-NMHC antibodies could bind to multiple HAs with high affinities. NMHC vaccination effectively protected the mice from infection and lung damage challenged by two subtypes of H1N1 influenza virus. Moreover, NMHC vaccination elicited CD4+and CD8+T-cell responses to clear the virus from infected tissue and prevent virus spreading. In conclusion, this study provided proof of concept for triggering both B cells and T cells immune responses against multiple influenza virus infection, and NMHC may be a potential candidate of universal broad-spectrum vaccine for various influenza virus prevention and therapy.
Protein kinase signalling at the Leishmania kinetochore captured by XL-BioID
Authors: Geoghegan Vincent , Jones Nathaniel G. , Dowle Adam , Mottram Jeremy C.
Published: July 2021

Elucidating protein kinase signaling pathways is an important but challenging problem in cell biology. Phosphoproteomics has been used to identify many phosphorylation sites, however the spatial context of these sites within the cell is mostly unknown, making it difficult to reconstruct signalling pathways. To address this problem an in vivo proximity capturing workflow was developed, consisting of proximity biotinylation followed by protein cross-linking (XL-BioID). This was applied to protein kinases of the Leishmania kinetochore, leading to the discovery of a novel essential kinetochore protein, KKT26. XL-BioID enabled the quantification of proximal phosphosites at the kinetochore through the cell cycle, allowing the phosphorylation state of the kinetochore to be followed during assembly. A specific inhibitor of kinetochore protein kinases KKT10/KKT19 was used to show that XL-BioID provides a spatially focussed view of protein kinase inhibition, identifying 16 inhibitor-responsive proximal phosphosites, including 3 on KKT2, demonstrating the potential of this approach for discovery of in vivo kinase signalling pathways.
Mosaic cis-regulatory evolution drives transcriptional partitioning of HERVH endogenous retrovirus in the human embryo
Authors: Carter Thomas A. , Singh Manvendra , Dumbović Gabrijela , Chobirko Jason D. , Rinn John L. , Feschotte Cédric
Published: July 2021

The human endogenous retrovirus type-H (HERVH) family is expressed in the preimplantation embryo. A subset of these elements are specifically transcribed in pluripotent stem cells where they appear to exert regulatory activities promoting self-renewal and pluripotency. How HERVH elements achieve such transcriptional specificity remains poorly understood. To uncover the sequence features underlying HERVH transcriptional activity, we performed a phyloregulatory analysis of the long terminal repeats (LTR7) of the HERVH family, which harbor its promoter, using a wealth of regulatory genomics data. We found that the family includes at least 8 previously unrecognized subfamilies that have been active at different timepoints in primate evolution and display distinct expression patterns during human embryonic development. Notably, nearly all HERVH elements transcribed in ESCs belong to one of the youngest subfamilies we dubbed LTR7up. LTR7 sequence evolution was driven by complex mutational processes, including multiple recombination events between subfamilies, that led to transcription factor binding motif modules characteristic of each subfamily. Using a reporter assay, we show that one such motif, a predicted SOX2/3 binding site unique to LTR7up, is essential for robust promoter activity in induced pluripotent stem cells. Together these findings illuminate the mechanisms by which HERVH diversified its expression pattern during evolution to colonize distinct cellular niches within the human embryo.
Positive selection and enhancer evolution shaped lifespan and body mass in great apes
Authors: Tejada-Martinez Daniela , Avelar Roberto A. , Lopes Inês , Zhang Bruce , Novoa Guy , de Magalhães João Pedro , Trizzino Marco
Published: July 2021

Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on ~1,550 genes previously described as tumor suppressors, oncogenes, ageing genes in addition to a novel Build of the CellAge database of cell-senescence genes (version 2), herein presented for the first time. Specifically, we analyzed dN/dS rates, positive selection, gene expression (RNA-seq) and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan and body mass we identified 67 genes that in primates co-evolved with those traits. Further, we identified 6 genes, important for immunity, neurodevelopment and telomere maintenance (includingTERF2), under positive selection in the great ape ancestor. RNA-seq data, generated from the liver of six species representing all the primate lineages, revealed that ~8% of the longevity genes are differentially expressed in apes relative to other primates. Importantly, by integrating RNA-seq with ChIP-seq for H3K27ac (which marks active enhancers), we show that the differentially expressed longevity genes are significantly more likely than expected to be located near a novel “ape-specific” enhancer. Moreover, these particular ape-specific enhancers are enriched for young transposable elements, and specifically SINE-Vntr-Alus (SVAs). In summary, we demonstrate that multiple evolutionary forces have contributed to the evolution of lifespan and body size in primates.
Insights into the mutation T1117I in the spike and the lineage B.1.1.389 of SARS-CoV-2 circulating in Costa Rica
Authors: Molina-Mora Jose Arturo
Published: July 2021

Emerging mutations and genotypes of the SARS-CoV-2 virus, responsible for the COVID-19 pandemic, have been reported globally. In Costa Rica during the year 2020, a predominant genotype carrying the mutation T1117I in the spike (S:T1117I) was previously identified. To investigate the possible effects of this mutation on the function of the spike, i.e. the biology of the virus, different bioinformatic pipelines based on phylogeny, natural selection and co-evolutionary models, molecular docking and epitopes prediction were implemented.

Results of the phylogeny of sequences carrying the S:T1117I worldwide showed a polyphyletic group, with the emergency of local lineages. In Costa Rica, the mutation is found in the lineage B.1.1.389 and it is suggested to be a product of positive/adaptive selection. Different changes in the function of the spike protein and more stable interaction with a ligand (nelfinavir drug) were found. Only one epitope out 742 in the spike was affected by the mutation, with some different properties, but suggesting scarce changes in the immune response and no influence on the vaccine effectiveness.

Jointly, these results suggest a partial benefit of the mutation for the spread of the virus with this genotype during the year 2020 in Costa Rica, although possibly not strong enough with the introduction of new lineages during early 2021 which became predominant later. In addition, the bioinformatics pipeline offers an integrative and exhaustive in silico strategy to eventually study other mutations of interest for the SARS-CoV-2 virus and other pathogens.

Highlights

In Costa Rica during the year 2020, a predominant SARS-CoV-2 genotype carrying the mutation T1117I in the spike (S:T1117I) was identified.

The S:T1117I was assessed for possible effects of this mutation on the function of the spike with a in silico approach.

Phylogeny revealed that sequences carrying the S:T1117I worldwide define a polyphyletic group, with the emergency of local lineages, including the lineage B.1.1.389 in Costa Rica.

A positive/adaptive selection was identified for S:T1117I, with different changes in the function of the spike protein, more stable interaction with ligands and scarce changes in the immune response.

The bioinformatics pipeline can be eventually used to study other mutations of the SARS-CoV-2 virus and other pathogens.
The disease associated Tau35 fragment has an increased propensity to aggregate compared to full-length tau
Authors: Lyu Chen , Da Vela Stefano , Al-Hilaly Youssra , Marshall Karen E. , Thorogate Richard , Svergun Dmitri , Serpell Louise , Pastore Annalisa , Hanger Diane
Published: July 2021

Tau35 is a truncated form of tau found in human brain in a subset of tauopathies. Tau35 expression in mice recapitulates key features of human disease, including progressive increase in tau phosphorylation, along with cognitive and motor dysfunction. The appearance of aggregated tau suggests that Tau35 may have structural properties distinct from those of other tau species that could account for its pathological role in disease. To address this hypothesis, we performed a structural characterization of monomeric and aggregated Tau35 and compared the results to those of two longer isoforms, 2N3R and 2N4R tau. We used small angle X-ray scattering to show that Tau35, 2N3R and 2N4R tau all behave as disordered monomeric species but Tau35 exhibits higher rigidity. In the presence of the poly-anion heparin, Tau35 increases thioflavin T fluorescence significantly faster and to a greater extent than full-length tau, demonstrating a higher propensity to aggregate. We used atomic force microscopy, transmission electron microscopy and X-ray fiber diffraction to demonstrate that Tau35 aggregates are morphologically similar to previously reported tau fibrils but they are more densely packed. These data increase our understanding of the aggregation inducing properties of clinically relevant tau fragments and their potentially damaging role in the pathogenesis of human tauopathies.
Genomic and functional characterization of Pseudomonas aeruginosa-targeting bacteriophages isolated from hospital wastewater
Authors: Nordstrom Hayley R. , Evans Daniel R. , Finney Amanda G. , Westbrook Kevin J. , Zamora Paula F. , Iovleva Alina , Yassin Mohamed H. , Bomberger Jennifer M. , Shields Ryan K. , Doi Yohei , Van Tyne Daria
Published: July 2021

Pseudomonas aeruginosa infections can be difficult to treat and new therapeutic approaches are needed. Bacteriophage therapy is a promising alternative to traditional antibiotics, but large numbers of isolated and characterized phages are lacking. We collected 23 genetically and phenotypically diverse P. aeruginosa isolates from people with cystic fibrosis (CF) and clinical infections, and characterized their genetic, phenotypic, and prophage diversity. We then used these isolates to screen and isolate 14 new P. aeruginosa-targeting phages from hospital wastewater. Phages were characterized with genome sequencing, comparative genomics, and lytic activity screening against all 23 bacterial host isolates. For four different phages, we evolved bacterial mutants that were resistant to phage infection. We then used genome sequencing and functional analysis of the resistant mutants to study their mechanisms of phage resistance as well as changes in virulence factor production and antibiotic resistance, which differed from corresponding parent bacterial isolates. Finally, we tested two phages for their ability to kill P. aeruginosa grown in biofilms in vitro, and observed that both phages reduced viable bacteria in biofilms by least one order of magnitude. One of these phages also showed activity against P. aeruginosa biofilms grown on CF airway epithelial cells. Overall, this study demonstrates how systematic genomic and phenotypic characterization can be deployed to develop bacteriophages as precision antibiotics.
Genome-wide mapping reveals R-loops associated with centromeric repeats in maize
Authors: Liu Yang , Liu Qian , Su Handong , Liu Kunpeng , Xiao Xue , Li Wei , Sun Qianwen , Birchler James A. , Han Fangpu
Published: July 2021

R-loops are stable chromatin structures comprising a DNA:RNA hybrid and a displaced single-stranded DNA. R-loops have been implicated in gene expression and chromatin structure, as well as in replication blocks and genome instability. Here, we conducted a genome-wide identification of R-loops and identified more than 700,000 R-loop peaks in the maize (Zea mays) genome. We found that sense R-loops were mainly enriched in promoters and transcription termination sites and relatively less enriched in gene bodies, which is different from the main gene-body localization of sense R-loops in Arabidopsis and Oryza sativa. At the chromosome scale, maize R-loops were enriched in pericentromeric heterochromatin regions, and a significant portion of R-loops were derived from transposable elements. In centromeres, R-loops preferentially formed within the binding regions of the centromere-specific histone CENH3, and centromeric retrotransposons were strongly associated with R-loop formation. Furthermore, centromeric retrotransposon R-loops were observed by applying the single-molecule imaging technique of atomic force microscopy. These findings elucidate the fundamental character of R-loops in the maize genome and reveal the potential role of R-loops in centromeres.
Financial literacy and financial well-being of Australian consumers: a moderated mediation model of impulsivity and financial capability
Authors: Tahir Muhammad S. , Ahmed Abdullahi D. , Richards Daniel W.
Published: July 2021

Purpose

This study aims to test a moderated mediation model for a twofold purpose. First, to examine the mediating role of financial capability (FC) in the association between financial literacy (FL) and financial well-being (FW). Second, to analyze if non-impulsive future-oriented behavior (NIB) moderates the associations of FL with FC and FL with FW.

Design/methodology/approach

The authors use the PROCESS macros in IBM SPSS Statistics to test the moderated mediation model and analyze the 2016 wave of the Household, Income and Labor Dynamics in Australia Survey.

Findings

The empirical analysis shows that FC partially mediates the association between FL and FW. Furthermore, the moderated mediation analysis shows that NIB strengthens the associations of FL with FC and FL with FW. Specifically, the positive associations of FL with FC and FL with FW significantly increase for those consumers who score high on NIB.

Practical implications

The findings have implications for the financial services industry. Professional financial planners can positively improve the ability of consumers to deal with their financial matters by highlighting the importance of FL and NIB.

Social implications

The study findings suggest educating consumers to discourage impulsive behavior and encourage them to create financial plans as it will enhance their ability to conduct financial tasks efficiently, improving their FW.

Originality/value

To the authors’ knowledge, this is the first study to assess a moderated mediation model, which examines the role of FC as a mediator variable and NIB as a moderator variable in the association between FL and FW.
Oil price and exchange rate nexus in Algeria: evidence from nonlinear asymmetric and frequency domain approach
Authors: Chekouri Sidi Mohammed , Sahed Abdelkader , Chibi Abderrahim
Published: July 2021

Purpose

This paper aims to examine the relationship between exchange rate and oil prices in Algeria over the period 2004Q1–2019Q4.

Design/methodology/approach

The nonlinear autoregressive distributed lag method is used to capture the potential asymmetric relationship among oil prices and the exchange rate. Frequency domain spectral Granger causality test is also applied to investigate the causal linkage between the two variables. The wavelet coherence is applied to analyze the evolution of this relationship both in time and frequency domains.

Findings

The empirical results reveal evidence of long-run asymmetric effects of oil price on Algeria’s real effective exchange rate (REER), implying that an increase in oil price causes a real exchange rate to appreciate, while a decrease in oil price leads to a real exchange rate to depreciate. More specifically, it is found that the impact of negative oil price shocks is higher than the one associated with positive shocks. The spectral Granger causality results further indicate that there is unidirectional causality running from oil price to REER in both medium and long run. The wavelet coherence findings provide evidence of some co-movement between the REER and oil price and point out that the oil price is leading real exchange rate in the medium and long terms.

Originality/value

This study contributes to the literature by investigating the asymmetric impact and the time domain causal linkage between oil price fluctuations and real exchange rate in Algeria.
Trait emotional intelligence and job performance evaluations: evidence from self, manager, team and peer ratings
Authors: Furnham Adrian , Treglown Luke , Topic Daria
Published: July 2021

Purpose

The study aims to look at whether trait emotional intelligence (EI) was related to the job performance level of a manager, their immediate team and their peers.

Design/methodology/approach

This study looked at the relationship between trait EI and performance appraisals, as evaluated by the person themselves, their peers, manager and team. Trait EI facets of 903 employees were compared to evaluated performance appraisals of the different groups four months later.

Findings

All 15 of the correlations (20 < r < 0.42) between the emotional intelligence facets and self-ratings were significantly positive whilst for managers 10, peers 6 and team only 4 were significant, though all were positive. In line with affective primacy theory, structural equation modelling revealed performance was rated higher by non-manager colleagues when employees exhibited traits associated with positive interpersonal interactions.

Originality/value

There are very few studies using multi-source ratings to explore the consequences of EI on a manager’s team and peers.
Statistical analysis of wind resource and energy potential assessment of Quaidabad site, Sindh Pakistan
Authors: Hulio Zahid Hussain , Yousufzai Gm , Jiang Wei
Published: July 2021

Purpose

Pakistan is an energy starving country that needs continuous supply of energy to keep up its economic speed. The aim of this paper is to assess the wind resource and energy potential of Quaidabad site for minimizing the dependence on fuels and improving the environment.

Design/methodology/approach

The Quaidabad site wind shear coefficient and turbulence intensity factor are investigated. The two-parameter k and c Weibull distribution function is used to analyze the wind speed of site. The standard deviation of the site is also assessed for a period of a year. The wind power density and energy density are assessed for a period of a year. The economic assessment of energy/kWh is investigated for selection of appropriate wind turbine.

Findings

The mean wind shear coefficient was observed to be 0.2719, 0.2191 and 0.1698 at 20, 40 and 60 m, respectively, for a period of a year. The mean wind speed is found to be 2.961, 3.563, 3.907 and 4.099 m/s at 20, 40, 60 and 80 m, respectively. The mean values of k parameters were observed to be 1.563, 2.092, 2.434 and 2.576 at 20, 40, 60 and 80 m, respectively, for a period of a year. The mean values of c m/s parameter were found to be 3.341, 4.020, 4.408 and 4.625 m/s at 20, 40, 60 and 80 m, respectively, for a period of a year. The major portion of values of standard deviation was found to be in between 0.1 and 2.00 at 20, 40, 60 and 80 m. The wind power density (W/m2) sum total values were observed to be 351, 597, 792 and 923 W/m2 at 20, 40, 60 and 80 m, respectively, for a period of a year. The mean coefficient of variation was found to be 0.161, 0.130, 0.115 and 0.105 at 20, 40, 60 and 80 m, respectively. The sum total energy density was observed to be 1,157, 2,156, 2,970 and 3,778 kWh/m2 at 20, 40, 60 and 80 m, respectively. The economic assessment is showing that wind turbine E has the minimum cost US$0.049/kWh.

Originality/value

The Quaidabad site is suitable for installing the utility wind turbines for energy generation at the lowest cost.
Sports effects on ethical judgement skills of successful entrepreneurs: adaptation of interpretative phenomenological analysis
Authors: van Rensburg Nico , Kanayo Ogujiuba
Published: July 2021

Purpose

This paper aims to identify how entrepreneurs’ active involvement in sports/athletic training affects and adds to their overall ethical judgement skills within and outside the workplace.

Design/methodology/approach

This study adopted a qualitative approach and included a combination of 12 male and female entrepreneurs who were purposively selected based on the study’s requirements. The primary data was collected through semi-structured one-on-one interviews, and interpretative phenomenological analysis served as the primary method of data analysis.

Findings

Findings from this study suggest that entrepreneurs’ active involvement in sports/athletic training does indeed influence their ethical judgement skills all-round. Arising from a combination of sports involvement factors, a unique group of underlying elements surfaced that proves valuable accustomed relationships concerning the significant impact sports/athletic training have on successful entrepreneurs’ ethical judgement skills.

Research limitations/implications

The active involvement in sports/athletic training undoubtedly plays a vital role in achieving entrepreneurs’ daily ethical judgement ability. However, this study was limited to the opinion of a small sample of participants in a specific field. Also, this study’s phenomenological nature requires the researcher’s interpretation of the results to be viewed as the truth.

Practical implications

This study provides a new perspective and validates how purposeful involvement in sports/athletic training regimens can boost the ethical judgement skills of entrepreneurs all-round. This study also proves powerful and new insight into the unique relationships among the accustomed factors and the underlying elements thereto – contributing beyond existing theory.

Originality/value

This study is novel and provides new and powerful insight into the ethical judgement skills and benefits derived thereof that can be developed by entrepreneurs from the active involvement in sports/athletic training.
Sustainability reporting and market value growth of quoted companies in Nigeria
Authors: Taiwo Oluwasikemi Janet , Owowlabi Babatunde Ayodeji , Adedokun Yemisi , Ogundajo Grace
Published: July 2021

Purpose

This study aims to examine the effect of sustainability reporting on market value growth (MVG) of quoted companies in Nigeria. The corporate reporting system has evolved, and this study examined how it influences the perception of investors.

Design/methodology/approach

This study adopted an ex post facto research design with 167 listed firms as the population. A total of 28 quoted firms were chosen with the use of purposive sampling. Data from 2009 to 2018 were obtained from secondary sources. Content analysis was used as a tool to analyse the disclosures in sustainability reports. The model was estimated using pooled ordinary least square (multivariate regression). Company age and financial leverage were used as control variables.

Findings

This study found that the compliance level of the sampled firms with sustainability reporting requirements for the four dimensions are below average, and sustainability reporting does not have a significant effect on MVG with Prob. (F-stat) of 0.7212 > 0.05. Therefore, this study recommends that management should intensify efforts in ensuring maximum compliance with the sustainability reporting guideline of Global Reporting Initiative to reflect in their market value and ensure its growth.

Originality/value

To the best of the authors’ knowledge, this study is the original idea of the authors, although references were made to previous related study but it is a unique research work of its own. The work contained in this paper (in full and part) has not been previously submitted to any other journal for publication.