bluuebunny/crossref_metadata_2025 huggingface dataset:
Zymoseptoria triticieffectors structurally related to killer proteins UmV-KP4 and UmV-KP6 are toxic to fungi, and define extended protein families in fungi
Authors: de Guillen Karine , Mammri Léa , Gracy Jérôme , Padilla André , Barthe Philippe , Hoh François , Lahfa Mounia , Rouffet Justine , Petit-Houdenot Yohann , Kroj Thomas , Lebrun Marc-Henri
Published: October 2024

Fungal effectors play crucial roles in plant infection. Despite low sequence identity, effectors were recently classified into structural families. In this study, we have elucidated the structures of Zt-NIP1 and Mycgr3-91409 effectors of the wheat fungal pathogenZymoseptoria tritici,using X-ray crystallography and NMR. These effectors displayed a structural homology with, respectively, KP4 and KP6α killer toxins, from UmV dsRNA viruses infecting the corn fungal pathogenUstilago maydis. Consequently, Zt-NIP1 and Mycgr3-91409 were renamed Zt-KP4-1 and Zt-KP6-1. Orthologs and paralogs of Zt-KP4-1 and Zt-KP6-1 were identified inZymoseptoria, but not in other fungi, except Ecp2 effectors related to Zt-KP4-1. Assessment of the biological activities of Zt-KP6-1 and Zt-KP4-1 revealed their toxicity to fungi such asBotrytis cinereaandZ. tritici, but not to wheat. A novel pipeline relying on Foldseek and cysteine-pattern constrained HMM searches of AlphaFold2 predicted structures from Uniprot generated a comprehensive inventory of KP4 and KP6 proteins in fungi and plants. A structure-based classification of these proteins revealed four KP4 and three KP6 structural super families. This classification provided far-reaching hypotheses on their biological function and evolution. This unifying structural framework highlights the power of structure determination for the classification of effectors, and their functional investigation.
Data- and knowledge-derived functional landscape of human solute carriers
Authors: Goldmann Ulrich , Wiedmer Tabea , Garofoli Andrea , Sedlyarov Vitaly , Bichler Manuel , Wolf Gernot , Christodoulaki Eirini , Ingles-Prieto Alvaro , Ferrada Evandro , Frommelt Fabian , Teoh Shao Thing , Leippe Philipp , Haladik Ben , Onea Gabriel , Pfeifer Martin , Kohlbrenner Mariah , Chang Lena , Selzer Paul , Reinhardt Jürgen , Digles Daniela , Ecker Gerhard F. , Osthushenrich Tanja , MacNamara Aidan , Malarstig Anders , Hepworth David , Superti-Furga Giulio
Published: October 2024

Research on the understudied solute carrier (SLC) superfamily of membrane transporters would greatly profit from a comprehensive knowledgebase, synthesizing data and knowledge on different aspects of SLC function. We consolidated multi-omics data sets with selected curated information from the public domain, such as structure prediction, substrate annotation, disease association and subcellular localization. This SLC-centric knowledge is made accessible to the scientific community via a web portal, featuring interactive dashboards and a tool for family-wide, tree-based visualization of SLC properties. Making use of the systematically collected and curated data sets, we selected eight feature-dimensions to compute an integrated functional landscape of human SLCs. This landscape represents various functional aspects, harmonizing local and global features of the underlying data sets, as demonstrated by inspecting structural folds and subcellular locations of selected transporters. Based on all available data sets and their integration, we assigned a biochemical/biological function to each SLC, making it one of the largest systematic annotations of human gene function and likely acting as a blueprint for future endeavours.
Behavioral and neural alterations of the ventral tegmental area by Cafeteria diet exposure in rats
Authors: Lalanza Jaume F. , Oyem John C. , Huijgens Patty T. , McCutcheon James E. , Heijkoop Roy , Snoeren Eelke MS
Published: October 2024

The brain reward system is essential for regulating appetitive and consummatory behaviors in response to various incentive stimuli. Junk food, known for its high palatability, is particularly associated with the potential for excessive consumption. While previous studies have shown that excessive junk food intake can impact reward circuitry, the precise mechanisms remain unclear. Additionally, it is unknown whether the functionality of this brain system is similarly altered in response to other natural rewards. In this study, we used fiber photometry combined with a behavioral reward test to investigate how six weeks of excessive cafeteria (CAF) diet consumption affects VTA neural activity and behavioral responses to food and sexual rewards in sexually experienced female rats. For the first time, we demonstrate that prolonged exposure to a CAF diet decreases interest in a food reward, resulting in reduced consumption. These behavioral changes were accompanied by diminished neural activity in the VTA. Similarly, but to a lesser extent, reductions in VTA activity responses were observed in response to a sexual partner, although no significant behavioral differences were detected during sexual interactions. Furthermore, a two-week reversal diet of standard chow was insufficient to restore VTA neural activity in CAF-exposed animals, which continued to show decreased VTA responses to both food rewards and sexual partners. Our findings suggest that prolonged junk food exposure leads to desensitization of the VTA, a key node in the brain’s reward circuitry, resulting in reduced responsiveness to natural rewards.
Systems-level analysis provides insights on methanol-based production of L-glutamate and its decarboxylation product γ-aminobutyric acid byBacillus methanolicus
Authors: Irla Marta , Nærdal Ingemar , Virant David , Brautaset Trygve , Busche Tobias , Goranovič Dušan , Haupka Carsten , Heux Stéphanie , Kosec Gregor , Rückert-Reed Christian , Wendisch Volker F , Brito Luciana F , Vicente Cláudia M
Published: October 2024

Background

Bacillus methanolicusis the next workhorse in biotechnology using methanol, an alternative and economical one-carbon feedstock that can be obtained directly from carbon dioxide, as both carbon and energy source for the production of various value-added chemicals. The wild-type strainB. methanolicusMGA3 naturally overproducesl-glutamate in methanol-based fed-batch fermentations.

Results

Here we generated, by induced mutagenesis, an evolvedB. methanolicusstrain exhibiting enhancedl-glutamate production capability (>150%). To showcase the potential of this evolved strain, further metabolic engineering enabled the production of γ-aminobutyric acid (GABA) directly froml-glutamate, with a yield of 13.2 g/L from methanol during fed-batch fermentations. By using a systems-level analysis, encompassing whole-genome sequencing, RNA sequencing, fluxome analysis and genome-scale metabolic modelling, we were able to elucidate the metabolic and regulatory adaptations that sustain the biosynthesis of these products. The metabolism of the mutant strain evolved to prioritize energy conservation and efficient carbon utilization. Key metabolic shifts include the downregulation of energy-intensive processes such as flagellation and motility and the rerouting of carbon fluxes towards α-ketoglutarate and its derivative,l-glutamate. Moreover, we observed that transformation of the evolved strain with a GABA biosynthesis plasmid had a positive effect onl-glutamate production, likely due to an upregulation of various transaminases involved in thel-glutamate biosynthesis from α-ketoglutarate.

Conclusions

These results and insights provide a foundation for further rational metabolic engineering and bioprocess optimization, enhancing the industrial viability ofB. methanolicusfor sustainable production ofl-glutamate and its derivatives.
Dissociation of movement and outcome representations in metacognition of agency
Authors: Charalampaki Angeliki , Maurer Heiko , Maurer Lisa K. , Müller Hermann , Filevich Elisa
Published: October 2024

We studied the role of movement and outcome information in forming metacognitive representations of agency. Participants completed a goal-oriented task, a virtual version of a ball-throwing game. In two conditions, we manipulated either the visual representation of the throwing movement or its distal outcome (the resulting ball flight/trajectory). We measured participants’ accuracy in a discrimination agency task, as well as confidence in their responses and tested for differences in the electrophysiological (EEG) signal using linear mixed effect models. We found no mean differences between participants’ metacognitive efficiency between conditions, but we also found that metacognitive sensitivity did not correlate between the two conditions, suggesting a dissociation in their underlying mechanisms. Furthermore, exploratory analyses pointed toward a difference in the EEG signal between the two conditions. Taken together, our results suggest that while movement and outcome information contribute equally to participants’ sense of agency, they may do so through distinct underlying processes.
A novel downstream factor in willows replaces the ancestral sex determining gene
Authors: Wang Yuan , Xue Zhiqing , Zhang Ren-Gang , Horandl Elvira , Wang Xiao-Ru , Mank Judith E. , He Li
Published: October 2024

Sex chromosome turnover has occurred in many groups, and is mediated by the translocation or duplication of apical sex-determining genes, or the replacement of original sex determination genes by new ones. In dioecious plants, the former frequently occurs, while the latter is rarely reported. Here, we assembled four haplotype-resolved chromosome-level genomes from four lineages of the Salix polyclona complex, including three diploids (E, E-TS, and W1) and one autotetraploid (W2). Our analyses reveal that diploids have a ZW/ZZ system, while autotetraploid has a ZZZW/ZZZZ system on chromosome 15. The apical sex-determining genes of Salicaceae, ARR17-like duplicates on chromosomes 15 and 19, which can indirectly turn-on/off the expression of PISTILLATA (PI) gene and determine sex, appears to have lost the function of sex determination in the S. polyclona complex. We found a novel sex determining factor on the 15W of the complex, namely partial PI-like duplicates, which has taken over the function from the ARR17-like duplicates. In conclusion, a new dominant sex-determining gene was recruited in the S. polyclona complex, replacing the ancestral apical sex-determining ARR17-like duplicates. The newly identified partial PI-like duplicates exhibit a direct influence on the downstream intact PI-like duplications, providing valuable insights into the evolutionary trajectory of the top-down sex determination pathway.
Single-cell andin situspatial analyses reveal the diversity of newly born hematopoietic stem cells and of their niches
Authors: Torcq Léa , Vivier Catherine , Schmutz Sandrine , Loe-Mie Yann , Schmidt Anne A.
Published: October 2024

Hematopoietic stem cells (HSCs) and more committed progenitors (collectively referred to as HSPCs) emerge from vessels during development, via Endothelial-to-Hematopoietic Transition (EHT). Recently, using the zebrafish embryo, we showed that two EHT cell types emerge from the aorta, raising the question of their subsequent fate. To address this issue, we established a complex pipeline based on single-cell photoconversion and transgenic lines to characterize the transcriptomic profiles of single EHT cell type progenies. We obtained, at unprecedented resolution in the early larva, a cartography of HSPCs and highly diversified differentiated populations, notably NK-like cell types, innate lymphoid cells and early eosinophils. We show that the two EHT cell types previously characterized indeed lead to differentially fated cells, with significant differences in thymus colonization and T-lymphoid lineage commitment. Using HSPC signatures retrieved from our datasets – namelygata2bandcd34/podocalyxin -,and to address niches, we performedin situgene expression analyses via RNAscope. Unexpectedly, we unveil a niche contacting the supra-intestinal artery. Finally, integration with previous datasets reveal that our populations contain potential developmental HSCs bearing signatures highly similar with adult HSCs.

Summary Statement

Single cell photoconversion of emerging hematopoietic precursor cells and transcriptomics unravel the diversity of hematopoietic stem and progenitor cell populations and homing in developmental nichesin toto, during zebrafish development.
Enhancing cortico-motoneuronal projections for vocalization in mice
Authors: Boyd J. Lomax , Kuper Louisa , Waidmann Elena , Yang Victor , Jarvis Erich D.
Published: October 2024

Several hypotheses have been proposed on the anatomical brain differences that endow some species with the rare ability of vocal learning, a critical component of spoken language. One long-standing thus far untested hypothesis is that a robust direct projection from motor cortex layer 5 neurons to brainstem vocal motor neurons enables fine motor control of laryngeal musculature in vocal learners. This connection has been proposed to form from specialized expression of axon guidance genes in human speech layer 5 neurons and the equivalent songbird neurons of the robust nucleus of the arcopallium. Here we generated mice with conditional knockdown of an axon-guidance receptor,PLXNA1,in motor cortex layer 5 neurons, to recapitulate the human and songbird brain expression patterns. These mice showed enhanced layer 5 cortical projections to brainstem vocal motor neurons, increased functional connectivity to phonatory muscles, and displayed a wider range of vocal abilities depending on developmental and social contexts. Our findings are consistent with the theory that direct vocal cortico-motoneuronal projections influence vocal behaviors.
Glymphatic system health in early Alzheimer’s disease and its relationship to sleep, cognition and CSF biomarkers
Authors: Ray Nicola Jane , Cullell Natalia , Clark Oliver , Delgado-Sanchez Ariane , Caruana Giovanni , Elias-Mas Andrea , Ferrer Julia , Buongiorno Mariateresa , Castejon Judith , Sánchez-Benavides Gonzalo , Granell Esther , Correa-Muller Sonia , Krupinski Jerzy
Published: October 2024

BACKGROUND

The glymphatic system is thought to facilitate waste clearance from the brain during sleep. Impairment in this system may underpin the elevated deposition of pathological proteins in neurodegenerative conditions like Alzheimer’s disease (AD). Putative glymphatic system activity has been measured with contrast-enhanced, serial MRI, revealing slower clearance in people who are sleep deprived. It is important that these methods are used to understand changes to glymphatic function in people with early-stage AD.

METHODS

Twenty-four individuals with mild cognitive impairment were recruited. N=20 had CSF biomarker data, with 16 meeting criteria for AD positivity (AD+). Participants underwent polysomnography, cognitive testing and serial T1 MRI with intravenous gadolinium-based contrast agent, diffusion tensor imaging along the perivascular space (DTI-ALPS index), and core AD CSF biomarkers collection. Rate (over 24hrs) and efficiency (the amount of tracer cleared after 28hrs relative to uptake after 4hrs) of GCBA clearance were measured.

RESULTS

Faster/more efficient GBCA clearance was associated with shorter sleep latency. In AD+ participants faster 24hr clearance of GBCA was associated with a lower ratio of Aβ1–42/Aβ1–40 in the CSF. In addition, better clearance efficiency was associated with greater levels of Aβ1-40, lower levels of Aβ-1-42, and a smaller ratio of Aβ1–42/Aβ1–40 in the CSF. Higher DTI-ALPS indicated better cognitive performance and, unexpectedly, higher tau levels. However, it was not associated with GCBA clearance.

CONCLUSIONS

We show, for the first time in humans, that glymphatic system function is associated with AD-related changes to sleep, cognition and core AD biomarker concentrations in CSF. However, for AD biomaker concentrations, these relationships are not in the expected direction: higher concentrations and lower Aβ1–42/Aβ1–40 ratio were associated with faster or more efficient clearance of GCBA. We suggest that increased neurodegeneration in those with elevated levels of tau and Aβ1–40 may paradoxically increase glymphatic activity locally to brain regions with more atrophy relative to less, but not in a way that improves sleep or cognition. In fact, larger extracellular spaces may exacerbate the spread of tau via the glymphatic system and therefore accelerate the progression of AD.
Improving Rectal Tumor Segmentation with Anomaly Fusion Derived from Anatomical Inpainting: A Multicenter Study
Authors: Cai Lishan , Abdelatty Mohamed A. , Han Luyi , Lambregts Doenja M. J. , van Griethuysen Joost , Pooch Eduardo , Beets-Tan Regina G.H. , Benson Sean , Brunekreef Joren , Teuwen Jonas
Published: October 2024

Accurate rectal tumor segmentation using magnetic resonance imaging (MRI) is paramount for effective treatment planning. It allows for volumetric and other quantitative tumor assessments, potentially aiding in prognostication and treatment response evaluation. Manual delineation of rectal tumors and surrounding structures is time-consuming and typically. Over the past few years, deep learning has shown strong results in automated tumor segmentation in MRI. Current studies on automated rectal tumor segmentation, however, focus solely on tumoral regions without considering the rectal anatomical entities and often lack a solid multicenter external validation. In this study, we improved rectal tumor segmentation by incorporating anomaly maps derived from anatomical inpainting. This inpainting was implemented using a U-Net-based model trained to reconstruct a healthy rectum and mesorectum from prostate T2-weighted images (T2WI). The rectal anomaly maps were generated from the difference between the original rectal and reconstructed pseudo-healthy slices during inference. The derived anomaly maps were used in the downstream tumor segmentation tasks by fusing them as an additional input channel (AAnnUNet). Alternative methods for integrating rectal anatomical knowledge were evaluated as baselines, including Multi-Target nnUNet (MTnnUNet), which added rectum and mesorectum segmentation as auxiliary tasks, and Multi-Channel nnUNet (MCnnUNet), which utilized rectum and mesorectum masks as an additional input channel. As part of this study, we benchmarked nine models for rectal tumor segmentation on a large multicenter dataset of preoperative T2WI as the baseline and nnUNet outperformed the other eight models on the external dataset. The MTnnUNet demonstrated improvements in both supervised and semi-supervised settings (AI-generated rectum and mesoretum were used) compared to nnUNet, while the MCnnUNet showed benefits only in the semi-supervised setting. Importantly, anomaly maps were strongly associated with tumoral regions, and their integration within AAnnUNet led to the best tumor segmentation results across both settings. The effectiveness of AAnnUNet demonstrated the value of the anomaly maps, indicating a promising direction for improving rectal tumor segmentation and model robustness for multicenter data.
Serum metabolomics identifies unique inflammatory signatures to distinguish rheumatoid arthritis responders and non-responders to TNF inhibitor therapy
Authors: Fresneda Alarcon Michele , Xu Yun , Lima Cassio , Ford Susanna , Goodacre Royston , Phelan Marie M , Wright Helen L
Published: October 2024

Introduction

Rheumatoid arthritis (RA) is an auto-immune disease which causes irreversible damage to tissue and cartilage within synovial joints. Rapid diagnosis and treatment with disease-modifying therapies is essential to reduce inflammation and prevent joint destruction. RA is a heterogeneous disease, and many patients do not respond to front-line therapies, requiring escalation of treatment onto biologics, of which TNF inhibitors (TNF-i) are the most common.

Objectives/Methods

In this study we determined whether serum metabolomics, using nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy, could discriminate RA blood sera from healthy human controls and whether serum metabolomics could be used to predict response or non-response to TNF inhibitor (TNF-i) therapy.

Results

NMR spectroscopy identified 35 metabolites in RA sera, with acetic acid being significantly lower in RA sera compared to healthy controls (HC, FDR<0.05). PLS-DA modelling identified 2-hydroxyisovalericacetic acid, acetoacetic acid, mobile lipids, alanine and leucine as important metabolites for discrimination of RA and HC sera by1H NMR spectroscopy (averaged 83.1% balanced accuracy, VIP score >1). FTIR spectroscopy identified a significant difference between RA and HC sera in the 1000-1200 cm-1spectral area, representing the mixed region of carbohydrates and nucleic acids (FDR<0.05). Sera from RA patients who responded to TNF-i were significantly different from TNF-i non-responder sera in the 1600-1700 cm-1region (FDR<0.05).

Conclusion

We propose that NMR and FTIR serum metabolomics could be used as a diagnostic tool alongside current clinical parameters to diagnose RA and to predict whether someone with severe RA will respond to TNF-i.
Outcome measures in implantable brain-computer interface research: a systematic review
Authors: Dohle Esmee , Swanson Eleanor , Yusuf Suraya , Jovanovic Luka , Thompson Lucy , Layard Horsfall Hugo , Muirhead William R , Bashford Luke , Brannigan Jamie
Published: October 2024

Implantable brain-computer interfaces (iBCIs) aim to restore function in patients with severe motor impairments by translating neural signals into motor outputs. As iBCI technology advances toward clinical application, assessing iBCI performance with robust and clinically relevant outcome measures becomes crucial. This systematic review analysed 77 studies, with 63.6% reporting outcome measures prospectively. Decoding outcomes were most frequently assessed (67.5%), followed by task performance (63.6%). Only 22.1% of studies reported a clinical outcome measure, often related to prosthetic limb function or activities of daily living. Successful iBCI translation and regulatory approval requires clinical outcomes developed collaboratively with individuals with motor impairments.

One Sentence Summary

Implantable brain-computer interface studies primarily evaluate engineering-related outcome measures over clinical outcome measures.
Differential contribution of P73+Cajal-Retzius cells and Reelin to cortical morphogenesis
Authors: Elorriaga Vicente , Bouloudi Benoît , Saillour Yoann , Morel Juliette S , Delberghe Elodie , Azzam Patrick , Moreau Matthieu X , Stottmann Rolf , Bahi-Buisson Nadia , Pierani Alessandra , Spassky Nathalie , Causeret Frédéric
Published: October 2024

Cajal-Retzius cells (CRs) are a peculiar neuronal type within the developing mammalian cerebral cortex. One of their best documented feature is the robust secretion of Reln, a glycoprotein essential for the establishment of cortical layers through the control of radial migration of glutamatergic neurons. We previously identifiedGmncas a critical fate determinant for P73+CRs subtypes from the hem, septum and thalamic eminence. InGmnc-/-mutants, P73+CRs are initially produced, cover the telencephalic vesicle but undergo massive apoptosis resulting in their complete depletion at mid-corticogenesis. Here we investigated the consequence of such a CRs depletion on dorsal cortex lamination and hippocampal morphogenesis. We found preplate splitting occurs normally inGmnc-/-mutants but is followed by defective radial migration arrest in the dorsal cortex, altered cellular organization in the lateral cortex, aberrant hippocampal progenitor proliferation resulting in abnormal CA1 folding and lack of vasculature development in the hippocampal fissure. We then performed conditionalRelndeletion in P73+CRs to evaluate its relative contribution and found that only radial migration defects were recapitulated. We concluded that at mid-corticogenesis, CRs-derived Reln is required for radial migration arrest and additionally identified Reln-independent functions for CRs in the control of hippocampal progenitor proliferation and vessel remodelling.
Cell-extrinsic controls over neocortical neuron fate and diversity
Authors: Baumann Natalia , Morassut Ilaria , Roig-Puiggros Sergi , Klingler Esther , Bartolini Giorgia , Fièvre Sabine , Jabaudon Denis
Published: October 2024

Cellular diversity in the neocortex emerges gradually during prenatal and postnatal development. While environmental interactions occur during this extended maturation period, the impact of extrinsic cues on determining the fate of distinct neuron types remains unknown. To address this question, we exposed developing neocortical cells to various environmental conditions and examined how this affects cell fate and diversity. Our developmental analyses reveal a hierarchical molecular program in which cell class-distinguishing features emerge first, followed by subclass- and type-related characteristics, with distinct developmental paces among cell populations. Environmental contribution was assessed in vivo, using genetically modified mice models in which position or innervation are altered, and in vitro using two-dimensional cultures. Acquisition of cellular identity and diversity remained stable across in vivo models. In contrast, in vitro glutamatergic neurons showed decreased expression of identity-defining genes, reduced diversity and alterations in canonical cortical connectivity. Cellular identity and diversity were restored towards in vivo values in organotypic slice cultures. These findings reveal cell population-specific responses to environmental conditions and highlight the role of extracellular context in shaping cell diversity in the maturing neocortex.
ZMYND11 Functions in Bimodal Regulation of Latent Genes and Brain-like Splicing to Safeguard Corticogenesis
Authors: Chang Xuyao , Li Wenqi , Matsui Satoshi , Huynh Cindy , Cederquist Gustav Y. , Studer Lorenz , Iwafuchi Makiko , Shillington Amelle , Chronis Constantinos , Tchieu Jason
Published: October 2024

Despite the litany of pathogenic variants linked to neurodevelopmental disorders (NDD) including autism (ASD) and intellectual disability1,2, our understanding of the underlying mechanisms caused by risk genes remain unclear. Here, we leveraged a human pluripotent stem cell model to uncover the neurodevelopmental consequences of mutations inZMYND11, a newly implicated risk gene3,4. ZMYND11, known for its tumor suppressor function, encodes a histone-reader that recognizes sites of transcriptional elongation and acts as a co-repressor5,6. Our findings reveal that ZMYND11-deficient cortical neural stem cells showed upregulation of latent developmental pathways, impairing progenitor and neuron production. In addition to its role on histones, ZMYND11 controls a brain-specific isoform switch involving the splicing regulator RBFOX2. Extending our findings to other chromatin-related ASD risk factors revealed similar developmental pathway activation and splicing dysregulation, partially rescuable through ZMYND11’s regulatory functions.
De novo genome assemblies of two cryptodiran turtles with ZZ/ZW and XX/XY sex chromosomes provide insights into patterns of genome reshuffling and uncover novel 3D genome folding in amniotes
Authors: Bista Basanta , González-Rodelas Laura , Álvarez-González Lucía , Wu Zhi-qiang , Montiel Eugenia E. , Lee Ling Sze , Badenhorst Daleen B. , Radhakrishnan Srihari , Literman Robert , Navarro-Dominguez Beatriz , Iverson John B. , Orozco-Arias Simon , González Josefa , Ruiz-Herrera Aurora , Valenzuela Nicole
Published: October 2024

Understanding the evolution of chromatin conformation among species is fundamental to elucidate the architecture and plasticity of genomes. Nonrandom interactions of linearly distant loci regulate gene function in species-specific patterns, affecting genome function, evolution, and, ultimately, speciation. Yet, data from nonmodel organisms are scarce. To capture the macroevolutionary diversity of vertebrate chromatin conformation, here we generate de novo genome assemblies for two cryptodiran (hidden-neck) turtles via Illumina sequencing, chromosome conformation capture, and RNA-seq:Apalone spinifera(ZZ/ZW, 2n= 66) andStaurotypus triporcatus(XX/XY, 2n= 54). We detected differences in the three-dimensional (3D) chromatin structure in turtles compared to other amniotes beyond the fusion/fission events detected in the linear genomes. Namely, whole-genome comparisons revealed distinct trends of chromosome rearrangements in turtles: (1) a low rate of genome reshuffling inApalone(Trionychidae) whose karyotype is highly conserved when compared to chicken (likely ancestral for turtles), and (2) a moderate rate of fusions/fissions inStaurotypus(Kinosternidae) andTrachemys scripta(Emydidae). Furthermore, we identified a chromosome folding pattern that enables “centromere–telomere interactions” previously undetected in turtles. The combined turtle pattern of “centromere–telomere interactions” (discovered here) plus “centromere clustering” (previously reported in sauropsids) is novel for amniotes and it counters previous hypotheses about amniote 3D chromatin structure. We hypothesize that the divergent pattern found in turtles originated from an amniote ancestral state defined by a nuclear configuration with extensive associations among microchromosomes that were preserved upon the reshuffling of the linear genome.
Doubled Haploid Technology: Generation of Doubled Haploid Maize Lines Using Haploid Inducers
Authors: Grüning Vencke K. , Lübberstedt Thomas , Frei Ursula K.
Published: October 2024

Doubled haploid (DH) technology allows for the development of completely homozygous lines from heterozygous plants in only two generations. This approach has been widely adopted in maize breeding programs, as it expedites the generation of inbred lines compared to traditional methods. The DH approach is based on the use of maize genotypes that have the ability to induce haploid seeds when used as the pollen parent. The most common method for producing maize haploid plants for the generation of DH lines is in vivo maternal haploid induction. The process involves pollination with a haploid inducer maize line to generate haploid seeds. Then, haploids are screened for and identified (typically via the expression of a particular marker gene), germinated, treated with an exogenous doubling agent to induce genome duplication, and transplanted to the field. Following successful self-pollination, seeds harvested from the ear represent fully homozygous lines. The seed set at this stage, however, is often low, necessitating one or two additional rounds of self-pollination to increase the number of fully homozygous inbred lines. Here, we describe a protocol for the generation of maize DH lines using maternal haploid-inducing maize lines. We outline the steps for setting up the donor material, performing induction crosses, selecting haploids based on two different marker alleles, treating seedlings with colchicine to double the genome, transplanting the treated seedlings to the field, and self-pollinating the treated plants.
Considerations for Using Phage Display Technology in Therapeutic Antibody Drug Discovery
Authors: Pohl Mary Ann , Almagro Juan C.
Published: October 2024

Phage display is a versatile and effective platform for the identification and engineering of biologic-based therapeutics. Using standard molecular biology laboratory techniques, one can create a highly diverse and functional antibody phage-displayed library, and rapidly identify antibody fragments that bind to a target of interest with exquisite specificity and high affinity. Here, we discuss key aspects for the development of an antibody discovery strategy to harness the power of phage display technology to obtain molecules that can successfully be developed into therapeutics, including target validation, antibody design goals, and considerations for preparing and executing phage panning campaigns. Careful design and implementation of discovery campaigns—regardless of the target—provides the best chance of identifying desirable antibody fragments for further therapeutic development, so these principles can be applied to any new discovery project.
Hard jet substructure in a multistage approach
Authors: Tachibana Y. , Kumar A. , Majumder A. , Angerami A. , Arora R. , Bass S. A. , Cao S. , Chen Y. , Dai T. , Du L. , Ehlers R. , Elfner H. , Fan W. , Fries R. J. , Gale C. , He Y. , Heffernan M. , Heinz U. , Jacak B. V. , Jacobs P. M. , Jeon S. , Ji Y. , Kauder K. , Kasper L. , Ke W. , Kelsey M. , Kordell M. , Latessa J. , Lee Y.-J. , Liyanage D. , Lopez A. , Luzum M. , Mak S. , Mankolli A. , Martin C. , Mehryar H. , Mengel T. , Mulligan J. , Nattrass C. , Oliinychenko D. , Paquet J.-F. , Putschke J. H. , Roland G. , Schenke B. , Schwiebert L. , Sengupta A. , Shen C. , Silva A. , Sirimanna C. , Soeder D. , Soltz R. A. , Soudi I. , Staudenmaier J. , Strickland M. , Velkovska J. , Vujanovic G. , Wang X.-N. , Wolpert R. L. , Zhao W. ,   JETSCAPE Collaboration
Published: October 2024

We present predictions and postdictions for a wide variety of hard jet-substructure observables using a multistage model within the framework. The details of the multistage model and the various parameter choices are described in []. A novel feature of this model is the presence of two stages of jet modification: a high-virtuality phase [modeled using the modular all twist transverse-scattering elastic-drag and radiation model ()], where modified coherence effects diminish medium-induced radiation, and a lower virtuality phase [modeled using the linear Boltzmann transport model ()], where parton splits are fully resolved by the medium as they endure multiple scattering induced energy loss. Energy-loss calculations are carried out on event-by-event viscous fluid dynamic backgrounds constrained by experimental data. The uniform and consistent descriptions of multiple experimental observables demonstrate the essential role of modified coherence effects and the multistage modeling of jet evolution. Using the best choice of parameters from [], and with no further tuning, we present calculations for the medium modified jet fragmentation function, the groomed jet momentum fraction zg and angular separation rg distributions, as well as the nuclear modification factor of groomed jets. These calculations provide accurate descriptions of published data from experiments at the Large Hadron Collider. Furthermore, we provide predictions from the multistage model for future measurements at the BNL Relativistic Heavy Ion Collider.

Published by the American Physical Society
2024
Quasinormal modes of slowly-spinning horizonless compact objects
Authors: Saketh M. V. S. , Maggio Elisa
Published: October 2024

One of the main predictions of general relativity is the existence of black holes featuring a horizon beyond which nothing can escape. Gravitational waves from the remnants of compact binary coalescences have the potential to probe new physics close to the black hole horizons. This prospect is of particular interest given several quantum-gravity models that predict the presence of horizonless and singularity-free compact objects. The membrane paradigm is a generic framework that allows one to parametrize the interior of compact objects in terms of the properties of a fictitious fluid located at the object’s radius. It has been used to derive the quasinormal mode spectrum of static horizonless compact objects. Extending the membrane paradigm to rotating objects is crucial to constrain the properties of the spinning merger remnants. In this work, we extend the membrane paradigm to linear order in spin and use it to analyze the relationships between the quasinormal modes, the object’s reflectivity, and the membrane parameters. We find a breaking of isospectrality between axial and polar modes when the object is partially reflecting or the compactness differs from the black hole case. We also find that in reflective ultracompact objects some of the modes tend toward instability as the spin increases. Finally, we show that the spin enhances the deviations from the black-hole quasinormal mode spectrum as the compactness decreases. This implies that spinning horizonless compact objects may be more easily differentiated than nonspinning ones in the prompt ringdown.

Published by the American Physical Society
2024
de Sitter geometric inflation from dynamical singularities
Authors: Cisterna Adolfo , Grandi Nicolás , Oliva Julio
Published: October 2024

Within the framework of geometric inflation, where the Friedmann equation is modified to incorporate an infinite series of higher curvature corrections, we describe the emergence of a de Sitter inflationary phase near the poles of an arbitrary dynamical function. Our analysis is quite general and does not depend on any specific choice of cosmological dynamics.

Published by the American Physical Society
2024
Understanding secondary order parameters in perovskites with tilted octahedra
Authors: Trotsenko Ekaterina G. , Talanov Mikhail V.
Published: October 2024

In the family of perovskite materials, the tilts of BX
6 octahedra are the most common type of structural distortion. Conventionally, the formation of low-symmetry perovskite phases with tilted octahedra is analyzed by considering only primary order parameters. However, octahedral tilting also gives rise to secondary order parameters which contribute to additional atomic displacements, ordering and lattice distortions. Our study highlights the significant impact of secondary order parameters on the structural formation and emergent physical properties of perovskites. Through group-theoretical and crystallographic analyses, we have identified all secondary order parameters within Glazer-type tilt systems and clarified their physical manifestations. We explore the fundamental symmetry relationships among various structural degrees of freedom in perovskites, including tilt-induced ferroelasticity, correlations between displacements and ordering of atoms occupying different positions, and the potential for rigid unit rotations and unconventional octahedral tilts. Particular emphasis is placed on the emergence of secondary order parameters and their coupling with primary order parameters, as well as their symmetry-based hierarchy, illustrated through a modified Bärnighausen tree. We applied our theoretical insights to elucidate phase transitions in well known perovskites such as CaTiO3 and RMnO3 (where R = La and lanthanide ions), thereby demonstrating the significant influence of secondary order parameters on crystal structure formation. Our results serve as a symmetry-based guide for the design, identification and structural characterization of perovskites with tilted octahedra, and for understanding tilt-induced physical properties.
Examinations of search interactions, experiences and communication in collaborative search
Authors: Zhang Lu , Liu Chang , Zhang Pengyi
Published: October 2024

Purpose

This study aims to explore the characteristics of collaborative information searching by comparing the differences in search experience and interaction between collaborative search mode and individual search mode and by analyzing the communication content and patterns during collaborative searches.

Design/methodology/approach

A user experiment was conducted using the Conference and Labs of the Evaluation Forum (CLEF)-Social Book Search platform, recruiting 16 individual and 18 collaborative participants. Each of the participants was required to complete two types of book search tasks in a lab setting. Interactions with the system were logged, and participants' experiences were captured through pre/post-search questionnaires. Additionally, the communication among collaborative participants was recorded and coded.

Findings

This study identified characteristics of collaborative information searching in three aspects. (1) Search experience: collaborative searchers showed a higher appreciation for the system’s functionality and aesthetics and were more engaged than individual searchers, despite experiencing slightly more mental strain. (2) Search strategies: in focus tasks, collaborative searchers made more decisions than individual searchers, indicating a need for book sorting. In open tasks, collaborative searchers take longer before making decisions, likely due to a higher level of interest and participation. (3) Communication content and pattern: collaborative searchers mainly discussed understanding and judgment of books and task plan. Searchers with same cognitive style talked more about search operations than those with different cognitive styles, while less about book judgment. Three communication patterns were identified: understanding-judgment, judgment-dominant and balanced. Judgment-dominant participants generally reported higher satisfaction with their search results than those in the other two patterns.

Originality/value

This study enhances understanding of collaborative search by comparing it with individual search and analyzing communication content, potentially inspiring collaborative search system and experiment design. Additionally, the coding table for communication between collaborative searchers offers valuable insights for future research.
Investigating the impact of multiple governance mechanisms on new infrastructure projects performance: evidence from China
Authors: Xie Lin-Lin , Lin Guixin , Luo Yifei
Published: October 2024

Purpose

This study aims to construct a “contractual–relational–governmental” 3D governance framework for new infrastructure projects (NIPs) within China’s distinct institutional context. The primary objective is to explore the impact of multiple governance mechanisms on the NIP performance, thus identifying the key governance mechanisms and proposing targeted performance improvement strategies.

Design/methodology/approach

The research design follows a sequential mixed methodology of integrating qualitative and quantitative data collection and analysis. Firstly, project governance and performance indicators were collected from relevant literature and expert interviews. Secondly, a questionnaire was developed, and data were collected through on-site and online means. Finally, the partial least square structural equation model (PLS-SEM) was utilized to examine and analyze the relationships between governance mechanisms and NIP performance.

Findings

Contractual, relational and governmental governance all have a certain role in promoting the NIP performance. Specifically, contract stringency, trust and governmental decision are the core elements of contractual, relational and governmental governance, respectively, while commitment does not significantly affect NIP performance. Generally, relational and governmental governance exert a more substantial influence compared to contractual governance, with governmental decision and trust being the most effective.

Originality/value

This paper contributes to the field by introducing PLS-SEM as a measurement tool for exploring the impact of multiple governance mechanisms on governance performance in NIPs. The results offer valuable insights for project managers, enabling them to concentrate on core factors while refining and optimizing governance mechanisms and strategies.
Developing employee proactivity in entrepreneurial ventures through training: an organisational identity approach
Authors: Sim Siew Chen , Huang Sheng , Mustafa Michael James , Chan Wen Li
Published: October 2024

Purpose

This study aims to explore how training influences employee proactive behaviours in entrepreneurial ventures. Specifically, the study develops and tests a model in which organisational identification (OID) mediates the relationship between perceptions of training and two employee proactive behaviours: taking charge and creative behaviour.

Design/methodology/approach

Data was collected from 136 employee-supervisor dyads from 24 entrepreneurial ventures in Malaysia’s high technology industry. Smart–partial least square structural equations modelling was used to test our proposed hypothesis.

Findings

The findings suggest that entrepreneurial ventures can use training to strengthen employees’ identification with the ventures, which in turn encourages proactive behaviours.

Originality/value

This study shows how HRD practices found in larger firms can work in different ways to influence desirable behaviours among employees of entrepreneurial firms. Specifically, by demonstrating how the relationship between training and employee proactive behaviours occurs through OID in the context of entrepreneurial ventures, the authors provide a complementary explanation of how HRD practices in entrepreneurial ventures can influence employee positive behaviours.
How do employees feel their health is valued? a descriptive case study
Authors: McCart Andrew , Alagaraja Meera
Published: October 2024

Purpose

A descriptive case study approach was adopted to examine employees' perceptions of the prevalence and usefulness of wellness programs. Relying on Centers for Disease Control and Prevention Health ScoreCard (CDC HSC), this study aims to assess the prevalence of worksite wellness programs, policies and benefits in general and incorporated employee perspectives to contextualize the CDC HSC wellness assessments.

Design/methodology/approach

The authors first compared the CDC HSC assessments to evaluate the effectiveness of wellness programs in 20 select organizations. Follow-up employee interviews (n = 25) were conducted to contextualize the CDC HSC assessments.

Findings

A variety of wellness programs are likely to increase employee engagement and participation when organizations adopt a bundling approach to combine wellness policies, incentives and an array of wellness programming opportunities that encourage and incentivize employees’ health promotion behaviors.

Research limitations/implications

Future researchers might examine health metrics, in terms of dollars, doctor visits or biometrics before and after the implementation of a wellness program or paid wellness coordinator. Because this study interviewed employees and not members of executive leadership or finance and accounting, financial metrics were not available or the focus of this study. The inclusion of leaders and directors of wellness initiatives would offer additional ways for examining the impact of wellness initiatives on employee behaviors on organizational outcomes.

Practical implications

Nutrition, weight management and chronic disease management were identified as major challenges impacting the health of employees. Even when organizations reported robust scores in their CDC HSC assessments, employers identified these three areas as critical for sustaining the health and well-being of their employees. Finally, the issue of employee safety was a top priority for all organizations regardless of how they scored on their CDC HSC assessments.

Social implications

The authors suggest that when high-impact wellness practices are linked to organizational supports in the workplace, these efforts are likely to have more positive effects on both employee outcomes and organizational outcomes. A regular routine of checking on wellness issues can help keep potential problems from going unnoticed. An example of this is a reminder to stretch at a morning meeting or during work hours as a reminder to stay focused on health and well-being.

Originality/value

The authors aggregated the organizational assessments for different wellness interventions and compared the scores (falling above or below) with standardized CDC wellness scores. The incorporation of the CDC scorecard ensured a standardized and evidence-based evaluation of workplace wellness programs. This additional step informed the interview guide and follow-up with employees who offered recommendations for how organizations could enhance their wellness programs and policies.