bluuebunny/crossref_metadata_2025 huggingface dataset:
TheFusarium graminearumeffector protease FgTPP1 suppresses immune responses and facilitates Fusarium Head Blight Disease
Authors: Darino Martin , Jaiswal Namrata , Darma Reynaldi , Kroll Erika , Urban Martin , Xiang Youhuang , Srivastava Moumita , Kim Hye-Seon , Myers Ariana , Scofield Steven R. , Innes Roger W. , Hammond-Kosack Kim E. , Helm Matthew
Published: September 2024

Most plant pathogens secrete effector proteins to circumvent host immune responses, thereby promoting pathogen virulence. One such pathogen is the fungusFusarium graminearum, which causes Fusarium Head Blight (FHB) disease on wheat and barley. Transcriptomic analyses revealed thatF. graminearumexpresses many candidate effector proteins during early phases of the infection process, some of which are annotated as proteases. However, the contributions of these proteases to virulence remains poorly defined. Here, we characterize aF. graminearumendopeptidase, FgTPP1 (FGSG_11164), that is highly upregulated during wheat spikelet infection and is secreted from fungal cells. To elucidate the potential role of FgTPP1 inF. graminearumvirulence, we generatedFgTPP1deletion mutants (ΔFgtpp1) and performed FHB infection assays. While the number of completely bleached spikes infected byF.graminearumwild-type reached 50% of total infected spikes, the number of fully bleached spikes infected byΔFgtpp1mutants was 25%, suggesting FgTPP1 contributes to fungal virulence. Transient expression of green fluorescent protein (GFP)-tagged FgTPP1 revealed that FgTPP1 localizes, in part, to chloroplasts and attenuates chitin-mediated activation of mitogen-activated protein kinase (MAPK) signaling, reactive oxygen species production, and cell death induced by an autoactive disease resistance protein when expressedin planta. Notably, the FgTPP1 protein is conserved across theAscomycotaphylum, making it a core effector among ascomycete plant pathogens. These properties make FgTPP1 an ideal candidate for decoy substrate engineering, with the goal of engineering resistance to FHB, and likely other crop diseases caused by ascomycete fungi.
Physiological and transcriptional changes in soybean as adaptive responses to the combined effects of soil alkalinity and drought
Authors: Hasan Md Rokibul , Thapa Asha , Mostofa Mohammad Golam , Kabir Ahmad H.
Published: September 2024

Soil alkalinity and drought collectively cause severe growth retardation in crops. However, the adaptive responses and transcriptional changes under such conditions remain unclear in soybean. In this growth incubator study, soil alkalinity and drought stress led to significant reductions in plant biomass, chlorophyll, and nutrient uptake in soybean. However, the photochemical efficiency of photosystem II remained stable, suggesting the activation of protective mechanisms to maintain photosynthetic functions. RNA-seq analysis demonstrated 357 upregulated and 799 downregulated genes in roots due to combined soil alkalinity and drought. Analysis revealed a complex response, with upregulation of genes predominantly involved in mineral homeostasis (Iron dehydrogenase,Sulfurylase), reactive oxygen species scavenging (Glutamate synthase,L-Ascorbate peroxidase) and hormonal signaling. Particularly, several ethylene-responsive genes, including theTranscription factors TF5andTF018, were upregulated, indicating the activation of stress-related signaling pathways. In a targeted study, plants supplemented with an ethylene precursor showed significant improvements in morpho-physiological traits and Fe status under combined stress. However, ethylene precursor applied in non-stressed plants led to reduced growth, and Fe levels, suggesting an involvement of the context-dependent role of ethylene in promoting stress tolerance. Furthermore, ethylene precursors caused an increase in root flavonoid and rhizosphere siderophore while restoring bacterial and fungal microbial cells in roots under combined stress in soil. However, in healthy plants, flavonoid and siderophore levels decreased, accompanied by a reduction in microbial cells to control levels. This suggests that elevated ethylene may regulate root exudates to recruit microbes dominated by host response, aiding soybean plants cope with combined stresses, although this effect may not occur in non-stressed plants. This is the first report on the transcriptional response and physiological adjustments in soybean exposed to alkalinity and drought, potentially advancing knowledge for genetic and agronomic interventions to improve stress resilience in legume crops.
The ancestry of a genome or The amazing ubiquity of exponential distributions
Authors: Thompson Elizabeth
Published: September 2024

Motivated originally by the increasing number of examples where a lone member of a once thriving population or even species now survives, we investigate what genomes of that population the survivor may represent. More generally it is of interest to consider what genomes of our ancestry each of us may represent. We consider only diploid dioecious organisms, and consider primarily the ancestry of a haploid genome, for example the maternal autosomes of the focal individual. Our ancestors are many and, in an unbounded population, increase exponentially in number. Our genetic ancestors are few, bounded by the number of ancestral genome segments which increases linearly over past generations. First we show that the major loss of potential ancestral lineages is at 8-11 generations, and that thereafter the number of genetic ancestors increases approximately linearly, but does not approach the upper bound. Over many generations, there remain tightly linked but not contiguous segments that result from the same ancestral lineage. Second we analyze the process of these ”repeated” ancestral segments that continue to be formed in distant ancestry, even as others are lost by recombination. Thirdly, we consider the effect of a finite population, with one model of a geographically structured population. Ancestors are many, and soon fill the entire species range even with low migration rates. Genetic ancestors are not only few, but remain geographically local.
A scalable approach for genome-wide inference of ancestral recombination graphs
Authors: Gunnarsson Árni Freyr , Zhu Jiazheng , Zhang Brian C. , Tsangalidou Zoi , Allmont Alex , Palamara Pier Francesco
Published: September 2024

The ancestral recombination graph (ARG) is a graph-like structure that encodes a detailed genealogical history of a set of individuals along the genome. ARGs that are accurately reconstructed from genomic data have several downstream applications, but inference from data sets comprising millions of samples and variants remains computationally challenging. We introduce Threads, a threading-based method that significantly reduces the computational costs of ARG inference while retaining high accuracy. We apply Threads to infer the ARG of 487,409 genomes from the UK Biobank using ∼10 million high-quality imputed variants, reconstructing a detailed genealogical history of the samples while compressing the input genotype data. Additionally, we develop ARG-based imputation strategies that increase genotype imputation accuracy for ultra-rare variants (MAC ≤10) from UK Biobank exome sequencing data by 5-10%. We leverage ARGs inferred by Threads to detect associations with 52 quantitative traits in non-European UK Biobank samples, identifying 22.5% more signals than ARG-Needle. These analyses underscore the value of using computationally efficient genealogical modeling to improve and complement genotype imputation in large-scale genomic studies.
Ethanol reduces grapevine water consumption by limiting transpiration
Authors: Kaci Neila Ait , Diot Alice , Quinquiry Beatrice , Yobregat Olivier , Pellegrino Anne , Maury Pierre , Chervin Christian
Published: September 2024

Studies suggest that ethanol (EtOH), triggers plant adaptation to various stresses at low concentrations (10 µM to 10 mM). This study investigates whether EtOH induces drought acclimation in grapevine, as demonstrated previously inArabidopsis, rice, and wheat. Preliminary results with bare root Gamay cuttings showed that those pre-treated with 10 µM EtOH aqueous solutions lost fewer leaves when deprived of water compared to controls. Subsequently, we ran a potted-cutting experiment with progressive soil water deficit. Plants pre-treated with 250 mM EtOH solutions exhibited slower depletion of the fraction of transpirable soil water (FTSW), compared to controls. While 250 mM EtOH decreased transpiration in early days, these EtOH pre-treated plants maintained higher leaf transpiration than controls after 10 days of soil water depletion. The transpiration response to FTSW was affected by EtOH application. EtOH pre-treatments limited plant leaf expansion without increasing leaf senescence. Interestingly, plants primed with EtOH followed typical hormesis curves. These results suggest that EtOH improves grapevine acclimation to drought, leading to potential water-savings in wine growing regions prone to high water shortages, linked to climate change. These should encourage further testing under various vineyard conditions.
Nitrogen nutrition impacts grapevine esca leaf symptom incidence, physiology and metabolism.
Authors: Dell'Acqua Ninon , Gambetta Gregory A , Comont Gwenaelle , Ferrer Nathalie , Rochepeau Adam , Petriacq Pierre , Delmas Chloe E. L.
Published: September 2024

Nitrogen plays a crucial role in plant growth and defence mechanisms, yet its role in plant-pathogen interactions is complex and remains largely unexplored, especially in perennial crops. This study aimed to investigate the effects of controlled nitrogen nutrition levels on disease incidence, fungal communities, and plant physiology and metabolism. Esca is a widespread grapevine vascular disease affecting physiology, xylem integrity and metabolism. Naturally infected Vitis vinifera L. cv. 'Sauvignon blanc' were subjected to three ammonium nitrate treatments across three seasons, resulting in reduced esca incidence under nitrogen deficiency compared with medium nutrition levels, while excess nitrogen had no significant impact. Nitrogen treatments significantly impacted vine physiology and leaf metabolites but did not affect fungal wood communities. Nitrogen deficiency significantly reduced stem diameter, photosynthesis, and leaf area, likely decreasing whole-plant transpiration, while excess nitrogen increased these factors suggesting a key role of plant transpiration in esca incidence. Additionally, nitrogen deficiency led to significantly higher production of phenylpropanoids, particularly antifungal flavonoids, in leaf metabolomes compared to the medium level. These findings highlight the pivotal role of nitrogen in the development of esca through alterations in vine morphology, physiology and metabolism. Fertilization practices may be crucial in the management of vascular diseases.
Anti-Candidaand antibiofilm activity of epinecidin-1 and its variants
Authors: Jeyarajan Sivakumar , Kumarasamy Anbarasu
Published: September 2024

To boost the stability and antimicrobial efficacy of the antimicrobial peptide (AMP) epinecidin-1, we previously engineered two variants — variant-1 and variant-2—by substituting alanine and histidine residues with lysine. This modification led to improved structural integrity and antibacterial function. Our current study builds on this foundation by assessing the anti-Candidacapabilities of epinecidin-1 and its variants against test organismsCandida albicans, Candida tropicalis, andCandida krusei. Both variants exhibited potent anti-Candidaactivity, particularly in disrupting biofilm formation. Minimum Inhibitory Concentrations (MICs) were found to be decreased for both variants compared to the original epinecidin-1 peptide, with variant-2 exhibiting the strongest activity. Electron microscopy confirmed that the mechanism of action involves pore formation and the induction of reactive oxygen species in theCandidacell membrane. Computational analysis showed the peptides have a high tendency to interact with theCandidacell membrane proteins like Exo-B-(1,3)-Glucanase, Secreted aspartic proteinase (Sap) 1, and N-terminal domain adhesin: Als 9-2, to prevent biofilm development.
Vascular network-inspired diffusible scaffolds for engineering functional neural organoids
Authors: Cai Hongwei , Tian Chunhui , Chen Lei , McCracken Kyle , Tchieu Jason , Gu Mingxia , Mackie Ken , Guo Feng
Published: September 2024

Organoids, three-dimensional in vitro organ-like tissue cultures derived from stem cells, show promising potential for developmental biology, drug discovery, and regenerative medicine. However, the function and phenotype of current organoids, especially neural organoids, are still limited by insufficient diffusion of oxygen, nutrients, metabolites, signaling molecules, and drugs. Herein, we present Vascular network-Inspired Diffusible (VID) scaffolds to fully recapture the benefits of physiological diffusion physics for generating functional organoids and phenotyping their drug response. In a proof-of-concept application, the VID scaffolds, 3D-printed meshed tubular channel networks, support the successful generation of engineered human midbrain organoids almost without necrosis and hypoxia in commonly used well-plates. Compared to conventional organoids, these engineered organoids develop with more physiologically relevant features and functions including midbrain-specific identity, oxygen metabolism, neuronal maturation, and network activity. Moreover, these engineered organoids also better recapitulate pharmacological responses, such as neural activity changes to fentanyl exposure, compared to conventional organoids with significant diffusion limits. Combining these unique scaffolds and engineered organoids may provide insights for organoid development and therapeutic innovation.
Selective disruption of Traf1/cIAP2 interaction attenuates inflammatory responses and limits sepsis and rheumatoid arthritis
Authors: Tang Yitian , Aleithan Fatemah , Madahar Sahib Singh , Mirzaesmaeili Ali , Saran Sunpreet , Tang Jialing , Zangiabadi Safoura , Inman Robert , Sweeney Gary , Abdul-Sater Ali A.
Published: September 2024

Tumor necrosis factor receptor-associated factor 1 (TRAF1) is an immune signaling adapter protein linked to increased susceptibility to rheumatoid arthritis (RA). TRAF1 has dual roles in regulating NF-κB and MAPK signaling: it promotes signaling through its association with cellular inhibitor of apoptosis 2 (cIAP2) downstream of certain tumor necrosis factor receptor (TNFR) family members but inhibits Toll-like receptor (TLR) signaling by limiting linear ubiquitination of key signaling proteins. Here, we identify a critical mutation in TRAF1 (V203A in humans, V196A in mice) that disrupts its interaction with cIAP2, leading to a significant reduction in TLR signaling and downstream inflammation in human and murine macrophages. We demonstrate that TRAF1 is recruited to the TLR4 complex and is indispensable for the recruitment of cIAP2, facilitating TAK1 phosphorylation and the activation of NF-κB and MAPK signaling pathways. Remarkably, mice harboring the TRAF1 V196A mutation are protected from LPS-induced septic shock and exhibit markedly reduced joint inflammation and disease severity in a collagen antibody-induced arthritis (CAIA) model of RA. These findings reveal a previously unrecognized and crucial role for the TRAF1/cIAP2 axis in promoting inflammation and offer a promising foundation for the development of novel therapeutic strategies for inflammatory conditions, such as sepsis and RA.
Osteogenic CpG Oligodeoxynucleotide, iSN40, Inhibits Osteo-clastogenesis in a TLR9-Dependent Manner
Authors: Ikeda Rena , Kimura Chihaya , Nihashi Yuma , Umezawa Koji , Shimosato Takeshi , Takaya Tomohide
Published: September 2024

A CpG oligodeoxynucleotide (CpG-ODN), iSN40 (5’-GGA ACG ATC CTC AAG CTT-3’), was originally identified to promote osteoblast differentiation independent of Toll-like receptor 9 (TLR9). While CpG-ODNs are generally known to be recognized by TLR9 and inhibit osteoclasto-genesis. This study investigated the anti-osteoclastogenic effect of iSN40. The murine mono-cyte/macrophage cell line RAW264.7 was treated with receptor activator of nuclear factor-κB ligand (RANKL) to induce osteoclast differentiation, and the effects of iSN40 on osteoclast formation were quantified by tartrate-resistant acid phosphatase (TRAP) staining and real-time RT-PCR. iSN40 completely inhibited RANKL-induced differentiation into TRAP+multinucleated osteoclasts by suppressing osteoclastogenic genes (Nfatc1, Ctsk, andDcstamp) and inducing anti-/non-osteoclasto-genic genes (Irf8, Adgre1, andIl1b). Treatment with a TLR9 inhibitor, E6446, or mutation in the CpG motif of iSN40 abolished intracellular uptake and the anti-osteoclastogenic effect of iSN40. These results demonstrate that iSN40 is internalized subcellularly, recognized by TLR9 via its CpG motif, modulates RANKL-dependent osteoclastogenic gene expression, and ultimately inhibits osteoclast formation. Computational simulation of the iSN40 structure also suggested the importance of the superficial CpG motif for iSN40 function. Finally, iSN40 was confirmed to inhibit osteoclastogenesis of RAW264.7 cells cocultured with the murine osteoblast cell line MC3T3-E1, which is a model of bone remodeling. This study demonstrates that iSN40, which exerts both pro-osteogenic and anti-osteoclastogenic effects, may be a promising nucleic acid drug for osteoporosis.
STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer
Authors: Fang Huan , Liang Huichun , Yang Chuanyu , Jiang Dewei , Luo Qianmei , Cao Wenming , Zhang Huifeng , Chen Ceshi
Published: September 2024

In the clinic, anti-tumor angiogenesis is commonly employed for treating recurrent, metastatic, drug-resistant triple-negative and advanced breast cancer. Our previous research revealed that the deubiquitinase STAMBPL1 enhances the stability of MKP-1, thereby promoting cisplatin resistance in breast cancer. In this study, we discovered that STAMBPL1 could upregulate the expression of the hypoxia-inducible factor HIF1α in breast cancer cells. Therefore, we investigated whether STAMBPL1 promotes tumor angiogenesis. We demonstrated that STAMBPL1 increasedHIF1Atranscription in a non-enzymatic manner, thereby activating the HIF1α/VEGFA signaling pathway to facilitate TNBC angiogenesis. Through RNA-seq analysis, we identified the transcription factor GRHL3 as a downstream target of STAMBPL1 that is responsible for mediatingHIF1Atranscription. Furthermore, we discovered that STAMBPL1 regulatesGRHL3transcription by interacting with the transcription factor FOXO1. These findings shed light on the role and mechanism of STAMBPL1 in the pathogenesis of breast cancer, offering novel targets and avenues for the treatment of triple-negative and advanced breast cancer.
Cluster randomized controlled trial to assess the effectiveness of a package of community-based intervention on continuum of maternal and newborn healthcare in Sidama, Ethiopia:The SiMaNeH trial protocol
Authors: Gebretsadik Achamyelesh , Shiferaw Yemisrach , Gemeda Hirut , Yaya Yaliso
Published: September 2024

Background

Maternal and newborn mortality and morbidity remain high in low-and middle-income countries such as Ethiopia. Limited access and dropouts from essential continuum of care interventions are critical factors. In Ethiopia about one in five complete the continuum of essential care through pregnancy, childbirth, and postnatal period Ethiopia. Evidence is limited on whether a package of interventions involving key community health actors increase the proportion completing essential maternal and newborn healthcare continuum in rural Sidama regional state, Ethiopia.

Objective

This study aims to implement and evaluate the effectiveness of community-based interventions designed to enhance involvement of key community health actors to improve completion rate of continuum of maternal care and utilization of newborn care.

Methods

Twenty rural kebeles (clusters) in Sidama Regional State, Ethiopia, are randomly allocated to intervention and control arms. A total of 2000 pregnant women, 1000 per arm, will be recruited between 20thand 26thweek of gestation after intervention. Then they will be followed until six weeks postpartum between June 2024 and February 2025. In the intervention arm, mothers and newborns will receive targeted interventions at home and in their community through a package of interventions designed to improve completion rate of recommended maternal and newborn care. Control clusters will receive normal care from the state public health system. Primary outcomes will be the difference in the completion of continuum of maternal care and essential and emergency newborn care between intervention and control clusters measured by composite indicator constructed from variables. Secondary outcomes include rates of antenatal care completion, facility deliveries with skilled care, completion of at least four postnatal care, essential newborn care, and emergency identification and referrals, mortality measures.

Conclusion

This trial will implement and evaluate community-based intervention package within existing community healthcare infrastructure to produce evidence for informed policy and practice to achieve improved community-based healthcare.
Identification of multimodal mental health signatures in the young population using deep phenotyping
Authors: Mørch Niels , Calderón Andrés B. , Kvamme Timo L. , Donskov Julie G. , Zana Blanka , Durand Simon , Bjekic Jovana , Machizawa Maro G. , Yamada Makiko , Ottosson Filip A. , Bybjerg-Grauholm Jonas , Ernst Madeleine , Børglum Anders D. , Sandberg Kristian , Qvist Per
Published: September 2024

Background

Mental health encompasses emotional, psychological, and social dimensions, extending beyond the mere absence of illness. Shaped by a complex interplay of hereditary factors and life experiences, mental health can deteriorate into clinical conditions necessitating intervention. However, the ambiguity between pathological and non-pathological states, along with overlapping clinical profiles, challenges traditional diagnostic procedures, highlighting the need for a dimensional approach in stratified psychiatry.

Methods

We analyzed comprehensive phenotypic data from ∼300 young Danish participants, including psychometric assessments, brain imaging, genetics, and circulatory OMICs markers. Using a novel psychometry-based archetyping approach, we employed soft-clustering analyses to stratify participants based on distinct cognitive, emotional, and behavioral patterns, while exploring their genetic and neurobiological underpinnings.

Results

Five psychometric archetypes were identified, representing a continuum of mental health traits. One archetype, characterized by high neuroticism, emotional dysregulation, and elevated stress and depression scores, was firmly associated with self-reported mental health diagnoses, psychiatric comorbidities, and family history of mental illness. Genetic predisposition to mental health conditions, reflected in polygenic scores (PGSs), accounted for up to 9% of the variance in archetypes, with significant contributions from neuroimaging-related PGSs. The overlaps between broader genetic profiles and archetypes further confirmed their biological foundations. Neuroimaging data linked the risk-associated archetype to both regional and global brain volumetric changes, while metabolomic analysis identified differentiating metabolites related to mood regulation and neuroinflammation.

Conclusions

This study demonstrates the feasibility of data-driven stratification of the general population into distinct risk groups defined by multimodal mental health signatures. This stratification offers a robust framework for understanding mental health variation and holds significant potential for advancing early screening and targeted intervention strategies in the young population.
Negative feedback of cyclic di-GMP levels optimizes switching between sessile and motile lifestyles inVibrio cholerae
Authors: Rangarajan Aathmaja Anandhi , Schroeder Jeremy W. , Hurto Rebecca L. , Severin Geoffrey B. , Pell Macy E. , Hsieh Meng-Lun , Waters Christopher M. , Freddolino Lydia
Published: September 2024

The signaling molecule cyclic di-GMP (cdG) controls the switch between bacterial motility and biofilm production, and fluctuations in cellular levels of cdG have been implicated inVibrio choleraepathogenesis. Intracellular concentrations of cdG are controlled by the interplay of diguanylate cyclase (DGC) enzymes, which synthesize cdG to promote biofilms, and phosphodiesterase (PDE) enzymes, which hydrolyse cdG to drive motility. To track the complete regulatory logic of howV. choleraeresponds to changing cdG levels, we followed a timecourse of overexpression of either theV. harveyidiguanylate cyclase QrgB or a variant of QrgB lacking catalytic activity (QrgB*). We find that QrgB increases cdG levels relative to QrgB* for 30 minutes after overexpression, but the effect of QrgB on cdG levels plateaus at 30 minutes, indicating tight adaptive control of cdG levels. In contrast, loss of VpsR, a master regulator activating biofilm formation upon binding to cdG, leads to higher baseline levels of cdG and continuously increasing cdG through 60 minutes after QrgB induction, revealing the existence of a negative feedback loop on cdG levels operating through VpsR. Through a combination of RNA polymerase ChIP-seq, RNA-seq, and genetic approaches, we show that transcription of a gene encoding a PDE,cdgC, is activated by VpsR at high cdG concentrations, mediating this negative feedback on cdG levels. We further identify a transcript encoded within, and antisense to, thecdgCopen reading frame which we namesRNAnegativeregulator ofCdgC (SnrC). RNA polymerase ChIP-seq and RNA-seq demonstrate SnrC to be expressed specifically under conditions of high cdG in the absence of VpsR. Ectopic SnrC expression increases cdG levels in a manner dependent on CdgC, demonstrating that its effect on cdG levels is likely through interference with CdgC production. Further, although cells lackingcdgCexhibit enhanced biofilm formation, these mutants are outcompeted by wild typeV. choleraein colonization assays that reward a combination of attachment, dispersal, and motility behaviors. These results underscore the importance of negative feedback regulation of cdG to maintain appropriate homeostatic levels for efficient transitioning between biofilm formation and motility, both of which are necessary over the course of theV. choleraeinfection cycle.
Sense codon-misassociated eRF1 elicits widespread ribosome stalling and induction of quality control
Authors: Han Peixun , Mito Mari , Ito Takuhiro , Iwasaki Shintaro
Published: September 2024

Ribosome-associated quality control (RQC) is a surveillance system for aberrant translation that senses ribosome collisions. Although the molecular mechanism has been extensively studied, the endogenous targets of RQC in human cells are poorly understood. Here, beginning with a study of the codon specificity of the eukaryotic translation termination factor eRF1, we show that transient binding of eRF1 to the UUA sense codon leads to ribosome collision and provides a source of RQC substrates in humans. eRF1-selective Monosome-Seq and Disome-Seq revealed that eRF1 was recruited not only to stop codons but also to subcognate sense codons, including the UUA codon. The eRF1 on UUA codons delays translation elongation but does not trigger the termination reaction. Remarkably, Disome-Seq with the depletion of ASCC3 and 4EHP, key factors in RQC, showed that ribosomes stalled at UUA codons constitute a predominant subpopulation rescued by RQC. Failure to resolve ribosome collisions by RQC triggers p38 phosphorylation and expression of the stress-induced transcription factor ATF3. This study highlights the impact of sense codon misrecognition by the termination factor on translation homeostasis in human cells.
Enzyme activation by urea reveals the interplay between conformational dynamics and substrate binding: a single-molecule FRET study
Authors: Scheerer David , Levy Dorit , Casier Remi , Riven Inbal , Mazal Hisham , Haran Gilad
Published: September 2024

Proteins often harness extensive motions of domains and subunits to promote their function. Deciphering how these movements impact activity is key for understanding life’s molecular machinery. The enzyme adenylate kinase is an intriguing example for this relationship; it ensures efficient catalysis by large- scale domain motions that lead to the enclosure of the bound substrates ATP and AMP. At high concentrations, AMP also operates as an allosteric inhibitor of the protein. Surprisingly, the enzyme is activated by urea, a compound commonly acting as a denaturant. Combining single-molecule FRET spectroscopy and enzymatic activity studies, we find that urea interferes with two key mechanisms that contribute to enzyme efficacy. First, urea promotes the open conformation of the enzyme, aiding the proper positioning of the substrates. Second, urea decreases AMP affinity, paradoxically facilitating a more efficient progression towards the catalytically active complex. These results signify the important interplay between conformational dynamics and chemical steps, including binding, in the activity of enzymes. State-of-the-art tools, such as single-molecule fluorescence spectroscopy, offer new insights into how enzymes balance different conformations to regulate activity.
Two newly cultivated eukaryotrophic flagellates represent distinct anaerobic lineages within Rhizaria
Authors: Eglit Yana , Lawton Maggie , Simpson Alastair G.B. , Gawryluk Ryan M.R.
Published: September 2024

Endomyxans are a poorly sampled and incompletely resolved aggregate of Rhizarian lineages that fall outside Filosa and Retaria. Among them, “Novel Clade 12” (NC12; Bass et al. 2009) is an environmental clade comprised primarily of sequences derived from anoxic sediments, hitherto lacking a morphologically-characterised representative. We have cultivated a marine anaerobic eukaryotroph, SSF, that we identify as the first representative of NC12. SSF is a teardrop-shaped cell with two unequal flagella emerging a third of the way down the cell behind a distinctive row of refractile globules. The posterior end of the cell is filled with food vacuoles. There is a surface thickening discernible in light microscopy. We also describe another distinct anaerobe eukaryotrophic lineage, also cultivated from marine sediment: PG. It consists of large pyriform cells with a substantial trailing “tail” and two unequal flagella, the posterior exceptionally long. In small subunit ribosomal RNA gene phylogenies, it falls outside the characterised clades and forms a distinct novel rhizarian lineage in its own right. Together, SSF and PG represent two additional independent adaptations to anoxic conditions within Rhizaria.
Viral adaptations to alternative hosts in the honey bee pathogenPaenibacillus larvae
Authors: Paull Keera , Spencer Emma , Miller Craig R. , Van Leuven James T.
Published: September 2024

Bacteriophages (phages) that are intended to be used to treat bacterial infections are often improved using genetic engineering or experimental evolution. A protocol called “Appelmans” utilizes evolution in microtiter plates to promote the evolution of phages that can infect nonpermissive hosts. We tested a modification of the Appelmans protocol using the honey bee pathogen,Paenibacillus larvae. Three phages evolved together on fourP. larvaestrains following the standard Appelmans protocol and a modified version to ensure high phage diversity throughout ten rounds of passaging. The host range of 360 plaques were characterized and six new phage lysis patterns were identified. These new phage lysis patterns included plaque formation on previously nonpermissive, phage-resistant isolates that were used to identify phage types. The modified protocol did not drastically change the rate or number of new phage types observed but did prevent the phage population from being dominated by one phage that tended to rapidly raise in frequency. These findings showed how a minor modification of the Appelmans protocol influenced the development of phages for phage therapy. The method also provided improved phages for the treatment of bacterial infections in honey bees.
Soil nutrition-dependent dynamics of the root-associated microbiome in paddy rice
Authors: Adachi Asahi , Utami Yuniar Devi , Dominguez John Jewish , Fuji Masako , Kirita Sumire , Imai Shunsuke , Murakami Takumi , Hongoh Yuichi , Shinjo Rina , Kamiya Takehiro , Fujiwara Toru , Minamisawa Kiwamu , Ono Naoaki , Kanaya Shigehiko , Saijo Yusuke
Published: September 2024

Plants accommodate diverse microbial communities (microbiomes), which can change dynamically during plant adaptation to varying environmental conditions. However, the direction of these changes and the underlying mechanisms driving them, particularly in crops adapting to the field conditions, remain poorly understood.

We investigate the root-associated microbiome of rice (Oryza sativaL.) using 16S rRNA gene amplicon and metagenome sequencing, across four consecutive cultivation seasons in a high-yield, non-fertilized, and pesticide-free paddy field, compared to a neighboring fertilized and pesticide-treated field.

Our findings reveal that root microbial community shifts and diverges based on soil fertilization status and plant developmental stages. Notably, nitrogen-fixing bacteria such asTelmatospirillum, BradyrhizobiumandRhizomicrobiumwere over-represented in rice grown in the non-fertilized field, implying that the assembly of these microbes supports rice adaptation to nutrient-deficient environments.

A machine learning model trained on the microbiome data successfully predicted soil fertilization status, highlighting the potential of root microbiome analysis in forecasting soil nutrition levels. Additionally, we observed significant changes in the root microbiome ofccamkmutants, which lack a master regulator of mycorrhizal symbiosis, under laboratory conditions but not in the field, suggesting a condition-dependent role for CCaMK in establishing microbiomes in paddy rice.
KAI2-dependent signaling controls vegetative reproduction inMarchantia polymorphathrough activation of LOG-mediated cytokinin synthesis
Authors: Komatsu Aino , Fujibayashi Mizuki , Kumagai Kazato , Suzuki Hidemasa , Hata Yuki , Takebayashi Yumiko , Kojima Mikiko , Sakakibara Hitoshi , Kyozuka Junko
Published: September 2024

Marchantia polymorphareproduces vegetatively (asexually) by producing propagules known as gemmae within gemma cups and sexually through spores. We previously reported that KARRIKIN INSENSITIVE 2 (KAI2)-dependent signaling promotes gemma cup and gemma formation. KAI2A perceives unidentified endogenous ligand(s), tentatively referred to as KAI2 ligands (KL). Perception of KL by KAI2 triggers MAX2-dependent proteolysis of MpSMXL. In this study, we identified genes working downstream of KAI2-dependent signaling inM. polymorpha. We found that KAI2-dependent signaling positively controls the expression of MpLONLEY GUY(MpLOG), encoding a cytokinin biosynthesis enzyme. Disruption of the MpLOGfunction decreased endogenous cytokinin levels and caused defects similar to KAI2-dependent signaling mutants. Moreover, supplying exogenous cytokinins rescued the defects of Mplogand KAI2-dependent signaling mutants, implying that cytokinins work downstream of KAI2-dependent signaling. Activation of MpLOGby KAI2-dependent signaling occurs in a highly cell-type-specific manner, leading to cell-specific induction ofGEMMA CUP-ASSOCIATED MYB1(GCAM1), the master regulator of vegetative reproduction ofM. polymorpha. We propose a genetic cascade, starting from KAI2-dependent signaling, that promotes vegetative reproduction through the induction of MpLOGandGCAM1. The interaction between KAI2-dependent signaling and cytokinin inM. polymorphaprovides a novel insight into the function and evolution of KAI2-dependent signaling.
Pangenomic context reveals the extent of intraspecific plant NLR evolution
Authors: Teasdale Luisa C , Murray Kevin D , Collenberg Max , Contreras-Garrido Adrián , Schlegel Theresa , van Ess Leon , Jüttner Justina , Lanz Christa , Deusch Oliver , Fitz Joffrey , Mencia Regina , Velthoven Rosanne van D , Drost Hajk-Georg , Weigel Detlef , Shirsekar Gautam
Published: September 2024

Nucleotide-binding leucine-rich repeat (NLR) proteins are a major component of the plant immune system, which directly or indirectly detect molecular signals of pathogen invasion. Despite their critical role, the processes by which NLR genes diversify remain poorly characterised due to the extraordinary sequence, structural, and regulatory variability of NLRs, even among closely related individuals. To understand the evolution of NLR diversity in Arabidopsis thaliana, we leverage graph-based methods to define pangenomic NLR neighbourhoods in 17 genetically diverse genomes. We integrate full-length transcript and transposable element information to exhaustively annotate all intact and degraded NLRs, enabling exploration of the processes that underpin the birth, death and maintenance of NLR diversity within a species. Our main finding is that many uncorrelated mutational processes create NLR diversity, and that there is no single metric that captures on its own the true extent of NLR structural and sequence variation. This immense diversity in plant immune system diversification allows populations to survive the constant onslaught of pathogens, not unlike vertebrate adaptive immunity, where variation is also generated by a variety of complementary mechanisms, albeit at the level of individuals.
K0.72Na1.71Ca5.79Si6O19 – the first oligosilicate based on [Si6O19]-hexamers and its stability compared to cyclosilicates
Authors: Kahlenberg Volker , Krüger Hannes , Garber Sonja , Krüger Biljana , Libowitzky Eugen , Kröll Stefanie , Hofer Thomas S. , Gallmetzer Josef M. , Purtscher Felix R. S.
Published: September 2024

Synthesis experiments were conducted in the quaternary system K2O–Na2O–CaO–SiO2, resulting in the formation of a previously unknown compound with the composition K0.72Na1.71Ca5.79Si6O19. Single crystals of sufficient size and quality were recovered from a starting mixture with a K2O:Na2O:CaO:SiO2 molar ratio of 1.5:0.5:2:3. The mixture was confined in a closed platinum tube and slowly cooled from 1150°C at a rate of 0.1°C min−1 to 700°C before being finally quenched in air. The structure has tetragonal symmetry and belongs to space group P4122 (No. 91), with a = 7.3659 (2), c = 32.2318 (18) Å, V = 1748.78 (12) Å3, and Z = 4. The silicate anion consists of highly puckered, unbranched six-membered oligomers with the composition [Si6O19] and point group symmetry 2 (C
2). Although several thousands of natural and synthetic oxosilicates have been structurally characterized, this compound is the first representative of a catena-hexasilicate anion, to the best of our knowledge. Structural investigations were completed using Raman spectroscopy. The spectroscopic data was interpreted and the bands were assigned to certain vibrational species with the support of density functional theory at the HSEsol level of theory. To determine the stability properties of the novel oligosilicate compared to those of the chemically and structurally similar cyclosilicate combeite, we calculated the electronegativity of the respective structures using the electronegativity equalization method. The results showed that the molecular electronegativity of the cyclosilicate was significantly higher than that of the oligostructure due to the different connectivities of the oxygen atoms within the molecular units.
Comparison of two crystal polymorphs of NowGFP reveals a new conformational state trapped by crystal packing
Authors: Kim Jin Kyun , Jeong Hannah , Seo Jeongwoo , Kim Seoyoon , Kim Kyung Hyun , Min Duyoung , Kim Chae Un
Published: September 2024

Crystal polymorphism serves as a strategy to study the conformational flexibility of proteins. However, the relationship between protein crystal packing and protein conformation often remains elusive. In this study, two distinct crystal forms of a green fluorescent protein variant, NowGFP, are compared: a previously identified monoclinic form (space group C2) and a newly discovered orthorhombic form (space group P212121). Comparative analysis reveals that both crystal forms exhibit nearly identical linear assemblies of NowGFP molecules interconnected through similar crystal contacts. However, a notable difference lies in the stacking of these assemblies: parallel in the monoclinic form and perpendicular in the orthorhombic form. This distinct mode of stacking leads to different crystal contacts and induces structural alteration in one of the two molecules within the asymmetric unit of the orthorhombic crystal form. This new conformational state captured by orthorhombic crystal packing exhibits two unique features: a conformational shift of the β-barrel scaffold and a restriction of pH-dependent shifts of the key residue Lys61, which is crucial for the pH-dependent spectral shift of this protein. These findings demonstrate a clear connection between crystal packing and alternative conformational states of proteins, providing insights into how structural variations influence the function of fluorescent proteins.
Digital transformation in human resources management and work-at-home
Authors: Pham Nhat Tan , Ngoc Thuy Vo Thi , Hai Quang Nguyen , Tuan Tran Hoang , Uyen Nguyen Hong
Published: September 2024

Purpose

Based on the ability, motivation and opportunity (AMO) theory, this study aims to investigate the role of digital human resources management (digital-HRM) practices in influencing hotel employee behaviors, especially their adoption of work-at-home (WAH).

Design/methodology/approach

The study was conducted in two stages in hotels in Vietnam. Stage 1 used a mixed method to develop an instrument to measure digital-HRM practices. In Stage 2, through a survey of 303 respondents, the research investigated digital-HRM practices’ additive and interactive effects on WAH.

Findings

The study shows that digital-HRM comprised five factors. Except for digital recruitment, the other digital-HRM practices significantly affected WAH. In addition, the research suggests that digital training and employee involvement should be combined to enhance employee willingness for WAH.

Research limitations/implications

Drawing on the AMO theory, this study constructs a digital-HRM measurement scale to study the antecedents and consequences of these practices to improve employees’ digital work efficiency. In addition, through both additive and combinative (a two-way interaction) models, the study enhances the HRM and hotel management theory by understanding why digital-HRM practices are essential to boost employees’ digital competencies to adopt remote working.

Practical implications

By investigating the role of digital-HRM practices in improving employees’ adoption of WAH, this study provides empirical implications for hotels to manage digital-HRM practices better and thus makes remote working effective.

Originality/value

The existing literature reveals the lack of a deep understanding of how HRM practices can promote digital devices and services and their influence on employee behaviors, especially in the hotel sector. To the best of the authors’ knowledge, this study is unique in extending the AMO theory into the digital context to illuminate components of digital-HRM practices and clarify how digitalizing HRM practices can motivate hotel employees to accept WAH.
A systematic review of the use of FHIR to support clinical research, public health and medical education
Authors: Pavão João , Bastardo Rute , Rocha Nelson Pacheco
Published: September 2024

Purpose

This systematic review aimed to identify and categorize applications using Fast Healthcare Interoperability Resources (FHIR) to support activities outside of direct healthcare provision.

Design/methodology/approach

A systematic electronic search was performed, and 53 studies were included after the selection process.

Findings

The results show that FHIR is being used to support (1) clinical research (i.e. clinical research based on interventional trials, data interoperability to support clinical research and advanced communication services to support clinical research), (2) public health and (3) medical education. Despite the FHIR potential to support activities outside of direct healthcare provision, some barriers were identified, namely difficulties translating the proposed applications to clinical environments or FHIR technical issues that require further developments.

Originality/value

This study provided a broad review of how FHIR is being applied in clinical activities outside of direct clinical care and identified three major domains, that is, clinical research, public health and medical education, being the first and most representative in terms of number of publications.
Practicing variation theory beyond learning study
Authors: Mårtensson Pernilla , Runesson Kempe Ulla , Hansson Henrik
Published: September 2024

Purpose

The purpose of this paper is to explore whether and how principles from variation theory can contribute to the planning of teaching and learning beyond learning study.

Design/methodology/approach

We study whether and how principles from variation theory contributed to a group of teachers’ planning of teaching and learning about decimal numbers in Grades 4 to 7 working in Subject Didactic Groups – a collaborative arrangement suited to daily teaching. A theoretical thematic analysis approach was used when analyzing eight audio-recorded meetings and written documents.

Findings

The study shows that variation theory principles contributed to the teachers’ planning of teaching and learning. Two themes were identified: the theory contributed to the teachers being able to (1) specify what their students needed to learn and (2) design tasks that they anticipated would afford the opportunity to learn what was identified as being necessary to learn.

Originality/value

The paper demonstrates how variation theory can contribute to teachers’ planning of teaching and learning when used in a collaborative arrangement other than learning study. This leads into a discussion about variation theory being used separately from learning study and the benefits and limitations this other collaborative arrangement can have for gaining knowledge of what is to be learned and taught.
Innovative collaboration among developing countries: the role of national innovation systems in Latin America
Authors: Velez-Calle Andres , Sanchez-Henriquez Fernando , Moore Elizabeth M. , Pacheco Larissa Marchiori
Published: September 2024

Purpose

Building on current debates on innovation, knowledge diffusion, and institutional dynamics, we explore the influence of national innovation systems (NISs) on international innovation collaborations in Latin America, focusing on intellectual property rights (IPR), access to scientific knowledge and regulatory quality.

Design/methodology/approach

We analyze data from 17 Latin American countries from 2002–2015 using time-series panel analysis to evaluate how different NIS elements affect regional cooperation for innovation.

Findings

Regulatory quality can improve international collaboration by compensating for weaker IPR and scientific knowledge bases. Interestingly, while both IPR and scientific knowledge inherently promote cooperation, stronger regulatory environments may diminish the effectiveness of IPR protections, suggesting a potential substitution effect.

Practical implications

The study offers actionable insights for policymakers in developing regions to help them craft more effective policies for collaboration in innovation that consider the balancing act between regulatory quality and other NIS elements.

Originality/value

This research shifts focus from the conventional analysis of how developing countries attract collaboration from developed nations to how they can foster innovation among themselves, providing a unique perspective on the interaction between institutional factors and innovation capabilities within the Latin American context.