bluuebunny/crossref_metadata_2025 huggingface dataset:
B cell response six months after SARS-CoV-2 mRNA vaccination in people living with HIV under antiretroviral therapy
Authors: Polvere Jacopo , Fabbiani Massimiliano , Pastore Gabiria , Rancan Ilaria , Rossetti Barbara , Durante Miriam , Zirpoli Sara , Morelli Enrico , Pettini Elena , Lucchesi Simone , Fiorino Fabio , Tumbarello Mario , Ciabattini Annalisa , Montagnani Francesca , Medaglini Donata
Published: July 2022

Background

SARS-CoV-2 mRNA vaccines have demonstrated high immunogenicity in healthy subjects and preliminary results for people living with HIV (PLWHIV) are promising too. We have previously reported the persistence of spike-specific circulating IgG and memory B cells in healthy adults up to six months after mRNA SARS-CoV-2 vaccination. Unfortunately, limited longitudinal data are available for PLWHIV and no evidence of persistent spike-specific B cells have been reported yet.

Methods

We investigated the humoral response and the persistence of spike-specific memory B cells up to six months after vaccination with two doses of mRNA vaccines in 84 PLWHIV under ART and compared them to healthy controls (HCs). Humoral response was analyzed with enzyme-linked immunosorbent assay and with an angiotensin-converting enzyme 2 (ACE2) and receptor binding domain (RBD) inhibition assay. PBMCs were analyzed with a cytofluorimetric approach for B cell phenotyping.

Findings

Spike-specific IgG peaked 1 month after second dose and persisted up to six months after vaccination with no significant differences compared to HCs. The stratification of patients according to CD4+ T cell count showed a significantly lower IgG response in case of CD4<350/µl, remarking the relevance of immune reconstitution. The ability of IgG of blocking the binding between ACE2 and RBD was detected in 58·4% of PLWHIV, compared to 86·2% in HCs. The amount of circulating spike-specific memory B cells detected in PLWHIV six months after vaccination was not significantly different from HCs, while there was prevalence of antigen-specific double negative (IgD-/CD27-) cells, compared to controls.

Interpretation

In conclusion, the majority of PLWHIV developed spike-specific humoral and B cell responses that persist for at least six months after SARS-CoV-2 mRNA vaccination. However, hints of HIV-dependent immune impairment were revealed by altered spike-specific B cell phenotypes and by reduced spike-specific humoral response in patients with low CD4+ T cell count (<350/µl).
CovidOutcome2: a tool for SARS-CoV2 mutation identification and for disease severity prediction
Authors: Kalcsevszki Regina , Horváth András , Győrffy Balázs , Pongor Sándor , Ligeti Balázs
Published: July 2022

Our goal was to develop a platform, CovidOutcome2, capable of predicting disease severity from viral mutation profiles using automated machine learning (autoML) and deep neural networks applied to the available large corpus of sequenced SARS-CoV2 genomes. CovidOutcome2 accepts either user-submitted genomes or user defined mutation combinations as the input. The output is a predicted severity score plus a list of identified, annotated mutations and their functional effects in VCF format. The best model performance is a ROC-AUC 0.899 for the model including patient age and ROC-AUC 0.83 for the model without patient age.

Availability

CovidOutcome is freely available online under the URL https://www.covidoutcome.bio-ml.com as well as in a standalone version https://github.com/bio-apps/covid-outcome.
Anellovirus Structure Reveals a Mechanism for Immune Evasion
Authors: Liou Shu-hao , Cohen Noah , Zhang Yue , Acharekar Nidhi Mukund , Rodgers Hillary , Islam Saadman , Zeheb Lynn , Pitts Jared , Arze Cesar , Swaminathan Harish , Yozwiak Nathan , Ong Tuyen , Hajjar Roger J. , Chang Yong , Swanson Kurt A. , Delagrave Simon
Published: July 2022

The significant impact of the human virome on human physiology is beginning to emerge thanks to modern sequencing methods and bioinformatic tools1. Anelloviruses, the principal constituent of the commensal human virome, are universally acquired in infancy and found throughout the body2,3,4. Since the discovery of the original torque teno virus in 19975, three genera of the Anelloviridae family, each extremely diverse genetically, have been found in humans. These viruses elicit weak immune responses that permit multiple strains to co-exist and persist for years in a typical individual6. However, because they do not cause disease7 and due to the lack of an in vitro culture system, anelloviruses remain poorly understood8,9. Basic features of the virus, such as the identity of its structural protein, have been unclear until now. Here, we describe the first structure of an anellovirus particle, which includes a jelly roll domain that forms a 60-mer icosahedral particle core from which spike domains extend to form a salient part of the particle surface. The spike domains come together around the 5-fold symmetry axes to form crown-like features. Relatively conserved patches of amino acids are near the base of the spike domain while a hypervariable region is at the apex. We propose that this structure renders the particle less susceptible to antibody neutralization by hiding vulnerable conserved epitopes while exposing highly diverse epitopes as immunological decoys, thereby contributing to the immune evasion properties of anelloviruses. This would contrast with viruses such as beak and feather disease virus, canine parvovirus or adeno-associated virus which lack such pronounced surface features. These results shed light on the structure of anelloviruses and provide a framework to understand their interactions with the immune system.
Genome duplication and transposon mediated gene alteration shapes the pathogenicity of Rhizoctonia solani AG1-IA
Authors: Francis Aleena , Ghosh Srayan , Tyagi Kriti , Prakasam V. , Rani Mamta , Singh Nagendra Pratap , Pradhan Amrita , Sundaram R. M. , Priyanka C. , Laha G.S. , Kannan C. , Prasad M.S. , Chattopadhyay Debasis , Jha Gopaljee
Published: July 2022

Rhizoctonia solani AG1-IA is a polyphagous basidiomycete fungal pathogen that causes sheath blight disease in rice. In a high-quality genome assembly-based analysis, we report a recent whole genome duplication in R. solani AG1-IA. Duplicated syntenic gene blocks showed presence of district clusters of transposable elements (TEs), which introduced disruption in the continuity of synteny and caused alterations in gene structures. Genome duplication followed by TE-mediated gene structure alterations caused neofunctionalization of genes associated with pathogenicity, as experimentally shown by variation in expression patterns and their involvement during plant colonization. High throughput genome sequencing of forty-two rice field isolates of R. solani AG1-IA from different agro-climatic zones of India profiled the population genetic structure of the Indian isolates and classified those into three distinct groups and a subgroup of admixture, emphasizing exchange of genetic material under field conditions. Genetic diversity analysis of this population predicted the regions that are that are targets for diversifying and purifying selections. Experimental evidence showed that the genes undergoing diversifying and purifying selections were essential for pathogenicity. Together, our data and the analysis revealed profound impact of genome duplication and the transposable elements on genomic diversity and evolution that shaped the pathogenicity of R. solani AG1- IA.
APC couples neuronal mRNAs to multiple kinesins, EB1 and shrinking microtubule ends for bidirectional mRNA motility
Authors: Baumann Sebastian J. , Grawenhoff Julia , Rodrigues Elsa C. , Speroni Silvia , Gili Maria , Komissarov Artem , Maurer Sebastian P.
Published: July 2022

Understanding where in the cytoplasm mRNAs are translated is increasingly recognised as being as important as knowing the timing and level of protein expression. mRNAs are localised via active motor-driven transport along microtubules (MTs) but the underlying essential factors and dynamic interactions are largely unknown. Using biochemical in vitro reconstitutions with purified mammalian proteins, multi-colour TIRF-microscopy (TIRF-M), and interaction kinetics measurements, we show that adenomatous polyposis coli (APC) enables kinesin-1- and kinesin-2-based mRNA transport, and that APC is an ideal adaptor for long-range mRNA transport as it forms highly stable complexes with 3’UTR fragments of several neuronal mRNAs (APC-RNPs). The kinesin-1 KIF5A binds and transports several neuronal mRNP components such as FMRP, PURα, and mRNA fragments weakly, whereas the transport frequency of the mRNA fragments is significantly increased by APC. APC-RNP-motor complexes can assemble on MTs, generating highly processive mRNA transport events. We further find that EB1 recruits APC-RNPs to dynamically growing MT ends and APC-RNPs track shrinking MTs, producing MT minus-end-directed RNA motility due to the high dwell times of APC on MTs. Our findings establish APC as a versatile mRNA-kinesin adaptor and a key factor for the assembly and bidirectional movement of neuronal transport mRNPs.
Fishing Cat Cell Biobanking for Conservation
Authors: Sukparangsi Woranop , Thongphakdee Ampika , Karoon Santhita , Suban Na Ayuttaya Nattakorn , Hengkhunthod Intira , Parkongkeaw Rachapon , Bootsri Rungnapa , Sikaeo Wiewaree
Published: July 2022

Establishment of biobank to keep wildlife cells secure long-term conservation. Fishing cat (Prionailurus viverrinus) is one of Vulnerable wild felids, currently under threaten by wetland destruction and other human activities. Here we aimed to generate cell biobanking of fishing cats by deriving various sources of primary cells from the living and postmortem animals and enhancing their expandable potency by virus-free cellular reprogramming. We show that cells can be propagated from several tissues harvested from both living and dead fishing cats with different derivation efficiency. Testes from the postmortem animals contain several tissues that can be derived primary cells as well as putative alkaline phosphatase positive and SOX2 positive adult spermatogonial stem cells. Primary cells from ear pinna and abdomen sources can only be obtained from the living fishing cats. These primary cells exhibited sign of cell senescence after a few sub-cultures, limited its usability for downstream applications. This obstacle can be overcome by reprogramming via either nucleofection or liposome-based DNA/RNA delivery. The putative iPSC colonies as well as expandable induced cells from episomal-based reprogramming appeared to be a suitable choice for expansion of cells for cryopreservation. Thus, here we provide current conservation plan using cell technology for fishing cats and also recommendation of tissue collection and culture procedures for zoo researches to facilitate the preservation of cells from postmortem animals and living animals.

Highlight

Biobanking of viable cells is essential to provide long-term security of wildlife existence. Current cell technology enables us to cultivate primary cells and adult germ cells from tissues of living and postmortem fishing cats for cryopreservation. The primary cells exhibited limited proliferation and cell senescence, which can be overcome by reprogramming the somatic cells toward pluripotent state. Here we explored the challenge of tissue collection from fishing cat and several virus-free approaches to induce cellular reprogramming in the fishing cat cells and provided insight into the techniques and conditions to enhance cell expansion, which support the success of generation of fishing cat cell biobank.
Discovering and targeting dynamic drugging pockets of the oncogene KRAS-G12D
Authors: Hu Zheyao , Martí Jordi
Published: July 2022

Activated KRAS-G12D mutations are the one of most frequent oncogenic drivers in human cancers. Unfortunately, no therapeutic agent directly targeting KRAS-G12D has been clinically approved yet, with such mutated species remaining undrugged. Notably, cofactor Mg2+ is closely related to the function of small GTPases, but no investigation has been done yet on Mg2+ when associated with KRAS. Herein, through microsecond scale molecular dynamics simulations we have found that Mg2+ plays a crucial role in the conformational changes of the KRAS-GDP complex. We have located two brand new druggable dynamic pockets exclusive to KRAS-G12D. Using the structural characteristics of these two dynamic pockets, we designed in silico the inhibitor DBD15-21-22, which can specifically and tightly target KRAS-G12D-GDP-Mg2+ ternary complex and we have verified that DBD15-21-22 is harmless for wild-type KRAS. Overall, we provide two brand new druggable pockets located on KRAS-G12D, as well as suitable strategies for KRAS-G12D inhibition.
Atypical intrinsic neural timescales in temporal lobe epilepsy
Authors: Xie Ke , Royer Jessica , Lariviere Sara , Rodriguez-Cruces Raul , Vos de Wael Reinder , Park Bo-yong , Auer Hans , Tavakol Shahin , DeKraker Jordan , Abdallah Chifaou , Caciagli Lorenzo , Bassett Dani S. , Bernasconi Andrea , Bernasconi Neda , Frauscher Birgit , Concha Luis , Bernhardt Boris C.
Published: July 2022

Objective

Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults. Here, we aimed to profile local neural function in TLE in vivo, building on prior evidence that has identified widespread structural alterations. Using multimodal MRI, we mapped intrinsic neural timescales (INT) at rest, examined associations to TLE-related structural compromise, and evaluated the clinical utility of INT.

Methods

We studied 46 TLE patients and 44 healthy controls from two independent sites, and mapped INT changes in patients relative to controls across hippocampal, subcortical, and neocortical regions. We examined region-specific associations to structural alterations and explored effects of age and epilepsy duration. A supervised machine learning paradigm assessed utility of INT for classifying patients-vs-controls and seizure focus lateralization.

Results

Relative to controls, TLE showed marked INT reductions across multiple regions bilaterally, indexing faster changing resting activity, with strongest effects in ipsilateral medial and lateral temporal regions, and sensorimotor cortices. Findings were consistent in each site and robust, albeit with reduced effect sizes, when correcting for structural alterations. TLE-related INT reductions increased with advancing disease duration, yet findings differed from aging effects seen in controls. Classifiers based on INT distinguished patients-vs-controls (balanced accuracy, 5-fold: 76±2.65%; cross-site, 72-83%) and lateralized the focus in TLE (balanced accuracy, 5-fold: 96±2.10%; cross-site, 95-97%) with high accuracies and generalization.

Conclusions

Our findings robustly demonstrate atypical macroscale function in TLE in a topography that extends beyond mesiotemporal epicenters. INT measurements can assist in TLE diagnosis, seizure focus lateralization, and monitoring of disease progression, which suggests clinical utility.
Brachiopod and mollusc biomineralisation is a conserved process that was lost in the phoronid-bryozoan stem lineage
Authors: Wernström Joel Vikberg , Gąsiorowski Ludwik , Hejnol Andreas
Published: July 2022

Background

Brachiopods and molluscs are lophotrochozoans with hard external shells which are often believed to have evolved convergently. While palaeontological data indicates that both groups are descended from biomineralising Cambrian ancestors, the closest relatives of brachiopods – phoronids and bryozoans – are mineralised to a much lower extent and are comparatively poorly represented in the Palaeozoic fossil record. Although brachiopod and mollusc shells are structurally analogous, genomic and proteomic evidence indicates that their formation involves a complement of conserved, orthologous genes. Here, we study a set of genes comprised of three homeodomain transcription factors, one signalling molecule and 6 structural proteins which are implicated in mollusc and brachiopod shell formation, search for their orthologs in transcriptomes or genomes of brachiopods, phoronids and bryozoans, and present expression patterns of 8 of the genes in postmetamorphic juveniles of the rhynchonelliform brachiopodTerebratalia transversa.

Results

Transcriptome and genome searches for the 10 target genes in the brachiopodsT. transversa, Lingula anatina, Novocrania anomala, the bryozoansBugula neritinaandMembranipora membranacea, and the phoronidsPhoronis australisandPhoronopsis harmeriresulted in the recovery of orthologs of the majority of the genes in all taxa. While the full complement of genes was present in all brachiopods with a single exception inL. anatina, a bloc of four genes could consistently not be retrieved from bryozoans and phoronids. The genesengrailed, distal-less, ferritin, perlucin, sp1andsp2were shown to be expressed in the biomineralising mantle margin ofT. transversajuveniles.

Conclusions

The gene expression patterns we recovered indicate that while mineralised shells in brachiopods and molluscs are structurally analogous, their formation builds on a homologous process that involves a conserved complement of orthologous genes. Losses of some of the genes related to biomineralisation in bryozoans and phoronids indicate that loss of the capacity to form mineralised structures occurred already in the phoronid-bryozoan stem group and supports the idea that mineralised skeletons evolved secondarily in some of the bryozoan subclades.
SiPLATZ12 transcript factor regulates multiple yield traits and salt tolerance in foxtail millet (Setaria italica)
Authors: Xiao Shenghui , Wan Yiman , Zhang Linlin , Tang Sha , Sui Yi , Bai Yichao , Wang Yan , Liu Miao , Fan Jiayin , Zhang Shizhong , Huang Jinguang , Yang Guodong , Yan Kang , Diao Xianmin , Zheng Chengchao , Wu Changai
Published: July 2022

Grain yield and salt tolerance are critical for crop production. However, the genetic and biochemical basis underlying the trade-off of these characters remain poorly described in crops. We show here that SiPLATZ12 transcription factor positively regulates multiple elite yield traits at the expense of salt tolerance in foxtail millet. SiPLATZ12 overexpression increases seed size, panicle length, and stem diameter, while reduces plant height and salt tolerance of foxtail millet. A 9-bp insertion in the SiPLATZ12 promoter has significant effects on the different expression of SiPLATZ12, multiple yield traits, and salt tolerance between foxtail millet and its wild ancestor, green foxtail. Moreover, SiPLATZ12 upregulates the expression of genes involved in seed development, but repressing the transcription of most NHX, SOS, and CBL genes to regulate Na+, K+ and pH homeostasis. Therefore, our results uncover a domesticated site that could be used to improve grain yield and salt tolerance in foxtail millet.
Impacts and mechanisms of CO2 narcosis in bumble bees: Narcosis depends on dose, caste and mating status and is not induced by anoxia
Authors: Cressman Anna , Amsalem Etya
Published: July 2022

Carbon dioxide (CO2) is commonly used to immobilize insects and to induce reproduction in bees. However, despite its wide use and potential off-target impacts, its underlying mechanisms are not fully understood. Here we used Bombus impatiens to examine whether CO2 impacts are mediated by anoxia and whether these mechanisms differ between female castes or following mating.

We examined the behavior, physiology, and gene expression of workers, mated and virgin queens following exposure to anoxia, hypoxia, full and partial hypercapnia, and control. Hypercapnia and anoxia caused immobilization, but only hypercapnia resulted in behavioral, physiological, and molecular impacts in bees. Recovery from hypercapnia resulted in increased abdominal contractions and took longer in queens. Additionally, hypercapnia activated queens’-but inhibited workers’ ovaries in a dose-dependent manner and caused a depletion of fat-body lipids in both. All responses of hypercapnia were weaker following mating in queens. Analysis of gene expression related to hypoxia and hypercapnia supported the physiological findings in queens, demonstrating that the overall impacts of CO2, excluding virgin queen ovaries, were unique and were not induced by anoxia. This study contributes to our understanding of the impacts and the mechanistic basis of CO2 narcosis in insects and its impacts on bees’ physiology.
Aligning Model and Macaque Inferior Temporal Cortex Representations Improves Model-to-Human Behavioral Alignment and Adversarial Robustness
Authors: Dapello Joel , Kar Kohitij , Schrimpf Martin , Geary Robert , Ferguson Michael , Cox David D. , DiCarlo James J.
Published: July 2022

While some state-of-the-art artificial neural network systems in computer vision are strikingly accurate models of the corresponding primate visual processing, there are still many discrepancies between these models and the behavior of primates on object recognition tasks. Many current models suffer from extreme sensitivity to adversarial attacks and often do not align well with the image-by-image behavioral error patterns observed in humans. Previous research has provided strong evidence that primate object recognition behavior can be very accurately predicted by neural population activity in the inferior temporal (IT) cortex, a brain area in the late stages of the visual processing hierarchy. Therefore, here we directly test whether making the late stage representations of models more similar to that of macaque IT produces new models that exhibit more robust, primate-like behavior. We conducted chronic, large-scale multi-electrode recordings across the IT cortex in six non-human primates (rhesus macaques). We then use these data to fine-tune (end-to-end) the model “IT” representations such that they are more aligned with the biological IT representations, while preserving accuracy on object recognition tasks. We generate a cohort of models with a range of IT similarity scores validated on held-out animals across two image sets with distinct statistics. Across a battery of optimization conditions, we observed a strong correlation between the models’ IT-likeness and alignment with human behavior, as well as an increase in its adversarial robustness. We further assessed the limitations of this approach and find that the improvements in behavioral alignment and adversarial robustness generalize across different image statistics, but not to object categories outside of those covered in our IT training set. Taken together, our results demonstrate that building models that are more aligned with the primate brain leads to more robust and human-like behavior, and call for larger neural data-sets to further augment these gains.
SARS-CoV-2 3CLpro mutations confer resistance to Paxlovid (nirmatrelvir/ritonavir) in a VSV-based, non-gain-of-function system
Authors: Heilmann Emmanuel , Costacurta Francesco , Volland Andre , von Laer Dorothee
Published: July 2022

Protease inhibitors are among the most powerful antiviral drugs. A first protease inhibitor against the SARS-CoV-2 protease 3CLpro, Paxlovid (nirmatrelvir / ritonavir), has recently been authorized by the U.S. FDA for emergency use (EUA 105 Pfizer Paxlovid). To find resistant mutants against the protease-inhibitor-component of Paxlovid, nirmatrelvir, we engineered a chimeric Vesicular Stomatitis Virus (VSV). By replacing an intergenic region, which is essential for separate gene transcription, with 3CLpro, this chimeric VSV became dependent on the protease to process two of its genes. We then applied selective pressure with nirmatrelvir to induce mutations. The effect of those mutants was confirmed by re-introduction in the 3CLpro and testing with a recently developed cellular assay. Furthermore, we found that mutations predicted by our method already exist in SARS-CoV-2 sequence depositions in NCBI and GISAID data bases. These may represent emerging resistant virus variants or a natural heterogeneity in the susceptibility to nirmatrelvir.

One-Sentence Summary

Mutations of the main protease of SARS-CoV-2 result in resistance against licensed drugs such as Paxlovid (nirmatrelvir / ritonavir).

Graphical abstract
Dissociable neuronal modules in the orbitofrontal cortex representing single and multi-attribute choice tasks
Authors: Xu Chengze , Ni Kuntan , Cai Xinying
Published: July 2022

An important component of biological intelligence lies in the capacity to learn and execute various cognitive tasks. This ability may be facilitated by a neural system comprising functionally dissociable neuronal modules. Within the orbitofrontal cortex (OFC) lies a neural circuit that supports economic decision-making across diverse contexts. To investigate the functional specialization of this circuit, we compared the neural activity of OFC neurons in rhesus monkeys during multi-attribute choice (MC) and single-attribute choice (SC) tasks. In MC, the monkeys made subjective tradeoffs between competing attributes, whereas in SC, choices were deterministic based on a single attribute’s value. Neuronally, in MC, OFC neurons primarily encoded offer value, chosen value, and choice in goods space. Upon transitioning from MC to SC, a significant portion of MC-modulated neurons disengaged, while a separate set of neurons emerged to encode SC-related variables in a spatial reference frame. Notably, we observed the clustering of value-encoding neurons in MC but not SC. In essence, our findings suggest that choice tasks involving different mental processes are represented by dissociable neuronal modules within the OFC.
Altered virome structrue and function characterization in Helicobacter pylori-driven colorectal carcinogenesis and H. pylori eradication
Authors: Luo Shiqi , Xue Jinling , Ru Jinlong , Mirzaei Mohammadali Khan , Ralser Anna , Mejías-Luque Raquel , Gerhard Markus , Deng Li
Published: July 2022

The understanding of gut virome and its role in Helicobacter pylori-driven colorectal cancer (CRC), as well as the long-term impact of H. pylori eradication via antibiotic treatment on it could contribute to better understanding the mechanisms of the disruption of gut bacteriome homeostasis involved in H. pylori-driven colorectal carcinogenesis and antibiotic therapy for H. pylori eradication. In the dynamic analysis of viral genome shotgun metagenomic of samples from lower gastrointestinal tract of the Apc+/1638N and C57BL/6 mice with H. pylori infection and eradication, stable viral abundance and replacement of bursted unique viral contigs in infected and uninfected Apc+/1638N mice were observed. Temperate phages, which encoding comprehensive microbial functional genes and targeting various susceptible hosts, were expanded extremely prior to cancer exacerbation. In addition, short-term antibiotic exposure for H. pylori eradication was able to alter the gut virome and thrive the antibiotic resistance genes (ARGs) in the viral genome for at least 6 months. Collectively, these results point toward a potential role of the altered, but dynamically balanced gut virome, characterized by the expanded temperate phages, in contributing to the H. pylori-driven CRC, and indicate that viral genome may act as ARG reservoir for the antibiotic resistance of bacteria after the antibiotics therapy to H. pylori eradication.
A novel hyper-parameter can increase the prediction accuracy in a single-step genetic evaluation
Authors: Neshat Mehdi , Lee Soohyun , Momin Md. Moksedul , Truong Buu , van der Werf Julius H. J. , Lee S. Hong
Published: July 2022

The H-matrix best linear unbiased prediction (HBLUP) method has been widely used in livestock breeding programs. It can integrate all information, including pedigree, genotypes, and phenotypes on both genotyped and non-genotyped individuals into one single evaluation that can provide reliable predictions of breeding values. The existing HBLUP method (e.g., that implemented in BLUPf90 software) requires hyper-parameters that should be adequately optimised as otherwise the genomic prediction accuracy may decrease. In this study, we assess the performance of HBLUP using various hyper-parameters such as blending, tuning and scale factor in simulated as well as real data on Hanwoo cattle. In both simulated and cattle data, we show that blending is not necessary, indicating that the prediction accuracy decreases when using a blending hyper-parameter < 1. The tuning process (adjusting genomic relationships accounting for base allele frequencies) improves prediction accuracy in the simulated data, confirming previous studies, although the improvement is not statistically significant in the Hanwoo cattle data. We also demonstrate that a scale factor, α, which determines the relationship between allele frequency and per-allele effect size, can improve the HBLUP accuracy in both simulated and real data. Our findings suggest that an optimal scale factor should be considered to increase the prediction accuracy, in addition to blending and tuning processes, when using HBLUP.

Author Summary

Despite significant advancements in genotyping technologies, the capability to predict the phenotypes of complex traits is still limited. H-matrix best linear unbiased prediction (HBLUP) method has been used to tackle this limitation to demonstrate a promising prediction accuracy. However, the performance of HBLUP depends heavily on the optimisation of hyper-parameters (e.g. blending and tuning). In this study, we introduce a scale factor (α), as a new hyper-parameter in HBLUP, which accounts for the relationship between allele frequency and per-allele effect size. Using simulation and real data analysis, we investigate the impact of the hyper-parameters (blending, tuning, and scale factor) on the performance of HBLUP. In general, the blending process may not improve the prediction accuracy for simulation and cattle data although a marginally improved prediction accuracy is observed with a blending hyper-parameter = 0.86 for one of carcass traits in the cattle data. In contrast, the tuning process can increase the HBLUP accuracy particularly in simulated data. Furthermore, we observe that an optimal scale factor plays a significant role in improving the prediction accuracy in both simulated and real data, and the improvement is relatively large compared with blending and tuning processes. In this context, we propose considering the scale factor as a hyper-parameter to increase the predictive performance of HBLUP.
Tissue-specific regulation of gene expression via unproductive splicing
Authors: Mironov Alexey , Petrova Marina , Margasyuk Sergei , Vlasenok Maria , Mironov Andrei A. , Skvortsov Dmitry , Pervouchine Dmitri D.
Published: July 2022

Eukaryotic gene expression is regulated post-transcriptionally by a mechanism called unproductive splicing, in which mRNA is triggered to degradation by the nonsense-mediated decay (NMD) pathway as a result of regulated alternative splicing (AS). Only a few dozen unproductive splicing events (USEs) are currently documented, and many more remain to be identified. Here, we analyzed RNA-seq experiments from the Genotype-Tissue Expression (GTEx) Consortium to identify USEs, in which an increase in the NMD isoform splicing rate is accompanied by tissue-specific downregulation of the host gene. Further, to characterize RBPs that regulate USEs, we superimposed these results with RNA-binding protein (RBP) footprinting data and experiments on the response of the transcriptome to the perturbation of expression of a large panel of RBPs. Concordant tissue-specific changes between the expression of RBP and USE splicing rate revealed a high-confidence regulatory network including 27 tissue-specific USEs with strong evidence of RBP binding. Among them, we found previously unknown PTBP1-controlled events in the DCLK2 and IQGAP1 genes, for which we confirmed the regulatory effect using siRNA-knockdown experiments in the A549 cell line. In sum, we present a transcriptomic pipeline that allows the identification of tissue-specific USEs, potentially many more than we have reported here using stringent filters.
Contrasting patterns of single nucleotide polymorphisms and structural variations across multiple invasions
Authors: Stuart Katarina C. , Edwards Richard J. , Sherwin William B. , Rollins Lee A.
Published: July 2022

Adaptive divergence is a fundamental process that shapes genetic diversity within and across species. Structural variants (SVs) are large-scale genetic differences (insertion, deletions, and rearrangements) within a species or population. SVs can cause important functional differences in the individual’s phenotype. Characterising SVs across invasive species will help fill knowledge gaps regarding how patterns of genetic diversity and genetic architecture shape rapid adaptation in response to new selection regimes. In this project we seek to understand patterns in genetic diversity within the globally invasive European starling,Sturnus vulgaris. We use whole genome sequencing of eight native United Kingdom (UK), eight invasive North America (NA), and 33 invasive Australian (AU) starlings to examine patterns in genome-wide SNPs and SVs between populations and within Australia. The findings of our research demonstrate that even within recently diverged lineages or populations, there may be high amounts of structural variation. Further, patterns of genetic diversity estimated from SVs do not necessarily reflect relative patterns from SNP data, either when considering patterns of diversity along the length of the organism’s chromosomes (owing to enrichment of SVs in sub telomeric repeat regions), or interpopulation diversity patterns (possibly a result of altered selection regimes or introduction history). Finally, we find that levels of balancing selection within the native range differ across SNP and SV of different classes and outlier classifications. Overall, our results demonstrate that the processes that shape allelic diversity within populations is complex and supports the need for further investigation of SVs across a range of taxa to better understand correlations between oft well studied SNP diversity and that of SVs.
Fifty years of reduction in sulphur deposition drives recovery in soil pH and plant communities
Authors: Seaton Fiona M. , Robinson David A. , Monteith Don , Lebron Inma , Bürkner Paul , Tomlinson Sam , Emmett Bridget A. , Smart Simon M.
Published: July 2022

Sulphur deposition through rainfall has led to species loss and ecosystem degradation globally, and across Europe huge reductions in sulphur emissions since the 1970s were expected to promote the recovery of acidified ecosystem. However, the rate and ecological impact of recovery from acidification in terrestrial ecosystems is still unclear as is the influence of management and climate, as to date there has been no long-term spatially extensive evaluation of these changes.

Here we present data from thousands of sites across Great Britain surveyed repeatedly from 1978-2019 and assess change in soil pH and plant acidity preference (Ellenberg R) in response to atmospheric deposition of sulphur and nitrogen. We analyse change in grasslands managed for pasture, referred to as high-intensity habitats, and compare to semi-natural habitats comprising rough grassland, broadleaved woodland, bog and heathland, referred to as low-intensity habitats.

Soil pH increased from 1978 to 2007 but then decreased between 2007 and 2019, resulting in a net increase of ~0.2 pH units in low-intensity habitats but no change in high-intensity habitats. The community average Ellenberg R increased in semi-natural habitats by ~0.2 units but remained stable in intensive grasslands.

In semi-natural habitats, but not intensive grasslands, these changes in plant community composition were associated with the soil pH changes which were in turn linked to decreasing sulphur deposition and differences in rainfall.

Nitrogen deposition, which was relatively stable over the survey period, showed no additional effect upon soil acidity once sulphur deposition was accounted for.

Synthesis:Our results provide conclusive evidence that reductions in acid emissions are stimulating the gradual recovery of chronically acidified terrestrial ecosystems at a whole-country scale, while also suggesting this recovery is being compromised by changing climate and land management.
LUZP1 regulates the constriction velocity of the contractile ring during cytokinesis
Authors: Hyodo Toshinori , Asano-Inami Eri , Ito Satoko , Sugiyama Mai , Nawa Akihiro , Rahman Md. Lutfur , Hasan Muhammad Nazmul , Mihara Yuko , Lam Vu Quang , Karnan Sivasundaram , Ota Akinobu , Tsuzuki Shinobu , Hamaguchi Michinari , Hosokawa Yoshitaka , Konishi Hiroyuki
Published: July 2022

There has been a great deal of research on cell division and its mechanisms; however, its processes have not yet been entirely elucidated. To find novel proteins that regulate cell division, we performed the screening using siRNAs and/or the expression plasmid of the target genes and identified leucine zipper protein 1 (LUZP1). Recent studies have shown that LUZP1 interacts with various proteins and stabilizes the actin cytoskeleton; however, the function of LUZP1 in mitosis is not known. In this study, we found that LUZP1 colocalized with the chromosomal passenger complex (CPC) at the centromere in metaphase and at the central spindle in anaphase and that these LUZP1 localizations were regulated by CPC activity and kinesin family member 20A (KIF20A). Mass spectrometry analysis identified that LUZP1 interacted with death-associated protein kinase 3 (DAPK3), one regulator of the cleavage furrow ingression in cytokinesis. In addition, we found that LUZP1 also interacted with myosin light chain 9 (MYL9), a substrate of DAPK3, and comprehensively inhibited MYL9 phosphorylation by DAPK3. In line with a known role for MYL9 in the actin-myosin contraction, LUZP1 suppression accelerated the constriction velocity at the division plane in our timelapse analysis. Our study indicates that LUZP1 is a novel regulator for cytokinesis that regulates the constriction velocity of the contractile ring.
Architecture of the MKK6-p38α complex defines the basis of MAPK specificity and activation
Authors: Juyoux Pauline , Galdadas Ioannis , Gobbo Dorothea , Velsen Jill von , Pelosse Martin , Tully Mark , Vadas Oscar , Gervasio Francesco Luigi , Pellegrini Erika , Bowler Matthew W.
Published: July 2022

The MAP kinase p38α is a central component of signalling in inflammation and the immune response and is, therefore, an important drug target. Little is known about the molecular mechanism of its activation by double-phosphorylation from MAP2Ks, due to the challenge of trapping a transient and dynamic hetero-kinase complex. Here, we applied a multidisciplinary approach to generate the first structure of p38α in complex with its MAP2K MKK6 and understand the activation mechanism. Integrating cryo-EM with MD simulations, HDX-MS andin celluloexperiments, we demonstrate a dynamic, multi-step, phosphorylation mechanism, reveal new catalytically relevant interactions, and show that MAP2K disordered N-termini determine pathway specificity. Our work captures, for the first time, a fundamental step of cell signalling: a kinase phosphorylating its downstream target kinase.

One-Sentence Summary

Integrative Cryo-EM and MD analysis of an active hetero-kinase complex reveals details of cellular signal transmission
Crystal structure determination of the halogenase CtcP from Streptomyces aureofaciens
Authors: Yin Lijuan
Published: July 2022

Chlortetracycline (CTC), a derivative of tetracycline (TC), is a broadly used antibiotic that inhibits the synthesis of bacterial proteins by competing with the A-site tRNA on ribosomes. A recent study showed that during the biosynthesis of CTC in Streptomyces aureofaciens, the halogenase CtcP catalyzes the final chlorination reaction and transforms TC into CTC. However, the structure of this fundamental enzyme is still lacking. Here, selenomethionine-derivatized CtcP from S. aureofaciens was overexpressed and purified and its structure was determined at 2.7 Å resolution. The structure of CtcP reveals the conserved monooxygenase domain shared by all flavin-dependent halogenases and a unique C-terminal domain. Although FAD was not observed in the structure, the monooxygenase domain has a conserved FAD-binding pocket and active center. The C-terminal domain displays an α-helical bundle fold, which could contribute to substrate specificity. This work provides a molecular basis for enzyme engineering to improve the industrial production of CTC.
Conceptualizing and theorizing green human resource management: a narrative review
Authors: Mukherji Anuradha , Bhatnagar Jyotsna
Published: July 2022

Purpose

The study reviews the recent conceptualizations and theorizing of green human resource management (GHRM) and explores GHRM's interconnections with the sustainability literature. The research findings have implications affecting GHRM measurement and design of future studies in the sparsely investigated human resource management (HRM)-environment-sustainability-responsibility spectrum.

Design/methodology/approach

The study uses a narrative style based on a review of quantitative field evidence from 38 recent empirical papers to provide an analytical framework on how the GHRM research agenda has broadened to include aspects of corporate sustainability (CS) and corporate social responsibility (CSR).

Findings

The study finds support from the literature on the impact of environment-related HR initiatives on building long-term capabilities and enhancing firm-specific social outcomes. Further, the study finds that different perspectives used in the conceptualization of GHRM reveal GHRM's differential impact on organization and environmental sustainability underlying GHRM's growing recognition as an important tool for organizations to demonstrate their commitment to being a responsible stakeholder of the socio-economic system.

Originality/value

GHRM scholars would find the review useful as the review provides a detailed explanation of how GHRM problems are defined and measured. The understanding of the process of conceptualization has been identified as a research gap in previous reviews; thus, one of the aims of this paper is to aid further knowledge development by understanding how research has progressed previously. The other benefit of the review is that management practitioners would find the insights useful to align HRM initiatives with organization CS/CSR objectives.
Building corporate reputation through corporate social responsibility: the mediation role of employer branding
Authors: Binu Raj Asha , N. Akbar Jan , A.K. Subramani
Published: July 2022

Purpose

The paper analyses the link between corporate social responsibility (CSR), employer branding (EB), and corporate reputation (CR). Considering the signaling theory and social commitment of organisations, the paper investigates the role of EB as a mediator.

Design/methodology/approach

Data were collected through structured questionnaires from 684 employees from the Indian information technology (IT) sector. The conceptual model and hypotheses were tested using the structural equation modelling (SEM) approach.

Findings

As a part of employer attractiveness, the social value/social commitment of companies perceived as a result of CSR strengthens the CR. The results also suggest that EB mediates the relation between CSR and CR.

Research limitations/implications

The paper contributes by integrating the CSR of organisations with their EB process for creating CR. Based on signaling theory, it further demonstrates scholarly value addition by providing a deeper understanding of the mediation effect of EB from a social commitment perspective. Scholars may further consider other stakeholders’ perspectives to test the role of CSR based on ethical/legal/environmental dimensions in building CR.

Practical implications

The paper would help managers/employers invest in CSR activities, creating strong employer brands to attract various stakeholders. It will also help companies to focus on an attractive value proposition to attract various stakeholders, mainly job seekers.

Originality/value

This study extends the literature on CSR and EB by suggesting a statistically tested model of mediation of EB for creating CR. Furthermore, considering the signaling theory, the paper views CSR, CR, and EB from the employee’s perspective and explores their linkages.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-09-2021-0541.
Analysis of rice production and the impacts of the usage of certified seeds on yield and income in Côte d'Ivoire
Authors: Akanbi Sheu-Usman Oladipo , Mukaila Ridwan , Adebisi Abdourasaque
Published: July 2022

Purpose

After a long observation of the high rate of rice importation and low productivity in Côte d’Ivoire, the certified rice seed was introduced and encouraged to be used by the local farmers. This study evaluates the profitability of rice production and the impact of certified seed usage on the yield and income of farmers in Côte d’Ivoire.

Design/methodology/approach

Data were collected from 265 rice farmers. Descriptive statistics were used to identify the challenges faced in using certified seeds. Profitability analysis was used to examine the profitability of rice production. To eliminate bias due to the counterfactuals, the endogenous switching regression was employed to investigate the impact of the certified seeds on income and yield.

Findings

The difficulties faced by the rice farmers in the procurement of certified seeds were the unavailability of seeds, the high cost of seeds and poor credit access. Furthermore, rice farmers using certified seeds get a higher net income (USD 263.74/ha) than those using farmers' seeds (USD 212.31/ha). The average treatment on the treated was 1.61 for the yield and 574.75 for the income. The average treatment on the untreated was 1.20 for the yield and 422.59 for the income. These indicate a higher yield and income among adopters of certified rice seed.

Research limitations/implications

Certified rice seed usage is profitable and enhances the output and income of rice farmers. The study advocates the creation of a stronger relationship between the farmers and the extension agents to encourage the use of certified seeds and increase the profit of the farmers.

Originality/value

There is scant information on the profitability of certified rice seed usage and how it affect yield and income. Therefore, this study serves as empirical evidence for policymakers to develop strategies that are required to enhance certified seed usage, boost rice productivity and achieve food security.