bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue Context Drives Regional Differences in Trophoblast Differentiation in Fetal Membranes and Chorionic Villi
Authors: Yang Liheng (Henry) , Caldwell Allyson , Coyne Carolyn B.
Published: November 2024

Trophoblasts within the fetal membrane primarily serve as protective barriers, shielding the developing fetus from the external environment, while those in chorionic villi facilitate interactions between the maternal and fetal compartments. Although these distinct trophoblast populations perform specialized roles based on their placental location, the mechanisms governing their development and differentiation remain largely unknown. In this study, we derived trophoblast organoids from both the smooth chorion of fetal membranes and chorionic villi from matched human placentas to create parallelin vitromodels of these distinct trophoblast populations. Using comparative transcriptional profiling with both bulk and single-cell RNA sequencing, we identified subtle transcriptional variations, while overall gene expression patterns and cellular composition remained highly conserved. Comparative single-cell RNA sequencing and differentiation trajectory analysis of organoids derived from chorion and villous tissues, along with their respective tissue counterparts, revealed region-specific gene expression patterns that were only partially conserved in organoids. The similarity between thesein vitromodels suggests that regional differences in trophoblast expression observedin vivoare driven by environmental and regional cues. These findings highlight the critical role of local environmental factors in shaping trophoblast function and offer insights into the conserved mechanisms that support placental integrity and fetal development, while emphasizing the influence of region-specific cuesin vivo.
Nerpa 2: linking biosynthetic gene clusters to nonribosomal peptide structures
Authors: Olkhovskii Ilia , Kushnareva Aleksandra , Tagirdzhanov Azat , Gurevich Alexey
Published: November 2024

Here, we introduce Nerpa 2, a tool for linking computationally-predicted biosynthetic gene clusters of nonribosomal peptides (NRPs) to their putative products. Nerpa 2 is based on our previous tool, Nerpa, but outperforms it in accuracy and sensitivity thanks to the software and algorithmic updates, including a wholly revised scoring function and extension of the training dataset. Nerpa 2 handles a variety of NRP biosynthesis use cases not supported by the original tool, is purely cross-platform, and provides output results in convenient HTML reports.

Availability and implementation

Nerpa 2 is available athttps://github.com/gurevichlab/nerpa.
Phytoplankton Photophysiology Reveals Depth Specific Zooplankton Grazing
Authors: Graff Jason R. , Maas Amy E.
Published: November 2024

Marine particle forensics frequently uncover information on composition, age, size, and ecological history. Zooplankton fecal pellets are also studied for process-related data, such as grazing rates and carbon sequestration potential. Here, flow cytometric analyses of fecal pellet contents revealed intact phytoplankton with photophysiological characteristics mirroring those of free-living cells. Mapping the cytometrically derived properties of cells inside fecal pellets onto vertical profiles from free-living cells revealed the potential to estimate depth specific grazing by individual zooplankton. An experiment conducted at sea confirmed that the photophysiological characteristics of free-living phytoplankton from multiple depths, consumed by zooplankton, and excreted within fecal pellets are retained for at least 24 hours after grazing is initiated. These results have implications for high resolution modeling of individual or group specific zooplankton grazing dynamics that are critical for accurately linking zooplankton grazing in the surface ocean with the mesopelagic and deep ocean food webs and carbon export.

Scientific Significance Statement

Fecal pellet forensics have provided significant contributions to the study of zooplankton grazing and the marine carbon cycle. Gaps in knowledge about these processes remain, and continued investigations into fecal pellet contents and their fate are important for assessing connections between the surface and deeper ocean ecosystems. We describe a study conducted in the North Atlantic in the Spring of 2021 using flow cytometry to investigate fecal pellets contents. Observations that intact phytoplankton within the pellets had similar photophysiological properties to the free-living community led to a series of sample collections and experiments which provided a path forward for determining depth specific grazing by zooplankton community members. Phytoplankton survival after passing through zooplankton guts and being packaged into fecal pellets, with their potential for release far below the surface mixed layer, support prior observations of healthy phytoplankton communities at depth and validate this mechanism for the rapid transport of freshly fixed carbon to deep ocean systems. The results should be of interest to plankton ecologists and carbon cycle scientists connecting surface and deep ocean ecosystems as application of this approach at a broader scale will provide opportunities for high resolution modeling of individual and group specific zooplankton behaviors.
Gaia: A Context-Aware Sequence Search and Discovery Tool for Microbial Proteins
Authors: Jha Nishant , Kravitz Joshua , West-Roberts Jacob , Camargo Antonio , Roux Simon , Cornman Andre , Hwang Yunha
Published: November 2024

Protein sequence similarity search is fundamental to genomics research, but current methods are typically not able to consider crucial genomic context information that can be indicative of protein function, especially in microbial systems. Here we present Gaia (Genomic AI Annotator), a sequence annotation platform that enables rapid, context-aware protein sequence search across genomic datasets. Gaia leverages gLM2, a mixed-modality genomic language model trained on both amino acid sequences and their genomic neighborhoods to generate embeddings that integrate sequence-structure-context information. This approach allows for the identification of functionally related genes that are found in conserved genomic contexts, which may be missed by traditional sequence- or structure-based search alone. Gaia enables real-time search of a curated database comprising over 85M protein clusters (defined at 90% sequence identity) from 131,744 microbial genomes. We compare the sequence, structure and context sensitivity of gLM2 embedding-based search against existing tools like MMseqs2 and Foldseek. We showcase Gaia-enabled discoveries of phage tail proteins and siderophore synthesis loci that were previously difficult to annotate with traditional tools. Gaia search is freely available athttps://gaia.tatta.bio.
Controlling human stem cell-derived islet composition using magnetic sorting
Authors: Kelley Allison B. , Shunkarova Mira , Maestas Marlie M. , Gale Sarah E. , Hogrebe Nathaniel J. , Millman Jeffrey R.
Published: November 2024

Stem cell-derived islets (SC-islets) consists of multiple hormone-producing cell types and offer a promising therapeutic avenue for treating type 1 diabetes (T1D). Currently, the composition of cell types generated within these SC-islets currently cannot be controlled via soluble factors during this differentiation process and consist of off-target cell types. In this study, we devised a magnetic-activated cell sorting (MACS) protocol to enrich SC-islets for CD49a, a marker associated with functional insulin-producing β cells. SC-islets were generated from human pluripotent stem cells (hPSCs) using an adherent differentiation protocol and then sorted and aggregated into islet-like clusters to produce CD49a-enriched, CD49a-depleted, and unsorted SC-islets. Single-cell RNA sequencing (scRNA-seq) and immunostaining revealed that CD49a-enriched SC-islets had higher proportions of β cells and improved transcriptional identity compared to other cell types. Functional assays demonstrated that CD49a-enriched SC-islets exhibited enhanced glucose-stimulated insulin secretion bothin vitroandin vivofollowing transplantation into diabetic mice. These findings suggest that CD49a-based sorting significantly improves β cell identity and the overall function of SC-islets, improving their effectiveness for T1D cell replacement therapies.
Mechanism of Nucleotide-Dependent Allosteric Regulation inEscherichia coliAspartate Transcarbamoylase
Authors: Miller Robert C. , Patterson Michael G. , Bhatt Neti , Pei Xiaokun , Ando Nozomi
Published: November 2024

Discovered nearly 70 years ago, the allosteric regulation ofEscherichia coliaspartate transcarbamoylase (ATCase) is discussed in every biochemistry textbook. ATCase catalyzes the first step in pyrimidine bio-synthesis. Despite extensive research, the mechanism by which this enzyme is regulated by pyrimidine and purine nucleotides has remained elusive. Here, we present a detailed analysis ofE. coliATCase using a combination of biochemical assays, small-angle X-ray scattering (SAXS), cryo-electron microscopy (cryo-EM), and X-ray crystallography, revealing the mechanism of allosteric communication between nucleotide-binding sites and active sites. We show how the pyrimidine pair, CTP and UTP, synergistically inhibit the enzyme by inducing a quaternary structure that enforces active-site cooperativity. Additionally, we provide the first evidence of how the purine pair, ATP and GTP, drive the enzyme into its most active state by promoting an expanded conformation that allows independent function of the active sites. Our findings resolve longstanding questions in the literature and uncover a novel mechanism by whichE. coliATCase regulates the balance of pyrimidines and purines.
Metabolic Divergence Between Healthy and Conditional Presenilin-1/2 knockout Dementia Model Mice under Chronic Nicotine exposure
Authors: Si Youwen , Qiu Shuai , Wang Lina , Meng Bo , Qi Feiyan
Published: November 2024

Nicotine, a primary bioactive compound in tobacco, influences a wide range of metabolic pathways, with potential implications for neurodegenerative diseases such as Alzheimer’s disease (AD). This study investigates the metabolic effects of chronic nicotine administration in presenilin-1/2 double knockout (DKO) mice and wild-type (WT) control mice. Eight-month-old DKO and WT mice underwent a three-month oral nicotine administration which did not significantly affect body weight or spontaneous locomotor activity in either DKO or WT mice, as measured by weekly body weight measurement and open field test.

The metabolomic analyses were performed using untargeted LC-MS and GC-MS techniques. The results revealed distinct metabolic profiles between DKO and WT mice under nicotine exposure. In DKO mice, nicotine exacerbated deficits in purine and nicotinamide metabolism, further highlighting dysregulation in energy homeostasis. Key findings include reduced adenosine and elevated dopamine levels in DKO serum, alongside increased cotinine concentrations, suggesting altered nicotine metabolism. WT mice showed significant changes in energy and lipid metabolism pathways, though with less pronounced alterations compared to DKO mice. Enrichment analyses identified significant pathway disruptions, particularly in choline metabolism, amino acid metabolism, and central carbon metabolism, with genotype-dependent responses to nicotine.

This study highlights the intrinsic metabolic alterations in DKO mice, such as disruptions in purine and nicotinamide metabolism, which contribute to their neurodegenerative pathology and unique responses to nicotine. By revealing the differential metabolic impacts of nicotine on healthy and neurodegenerative states, the findings provide valuable insights into its dual therapeutic and pathological roles. These results may guide future research into the metabolic underpinnings of neurodegeneration and the potential for nicotine as a targeted therapeutic intervention.
Diversity of Aβ aggregates produced in a gut-basedDrosophilamodel of Alzheimer’s disease
Authors: Elovsson Greta , Klingstedt Therése , Nilsson K Peter R , Brorsson Ann-Christin
Published: November 2024

Alzheimer’s disease (AD) is a neurodegenerative disease manifested by memory loss and premature death. One major histopathological hallmark of AD is the amyloid plaques formed by aggregates of the amyloid-beta (Abeta) peptide and the Abeta aggregation process results in amyloid fibrils with different structures. Herein, we investigate the heterogeneity of Abeta aggregates produced by Drosophila melanogaster expressing the Abeta1-42 peptide with the Arctic mutation E22G (Arctic flies) or a dimeric construct of Abeta1-42 (T22Abeta1-42 flies) in the digestive tract. Staining of the gut of the flies using luminescent conjugated oligothiophenes (LCOs) revealed that the amount of Abeta aggregates increased in both genotypes with age. The LCOs also exhibited distinct staining patterns in the flies. The expression of T22Abeta1-42 resulted in a heavier Abeta load compared to Abeta1-42 with the Arctic mutation. Since the genotypes have similar median survival times, the result indicates that the toxicity of the combined number of aggregates in the Arctic flies is higher compared to the T22Abeta1-42 flies. Stability measurements showed that the most accumulated Abeta species in the Arctic and the T22Abeta1-42 flies were found in the 4 M and 5 M Gua-HCl-fraction, respectively. This indicates that prefibrillar Abeta aggregates constitute the toxic species in Arctic flies while the cause of death in T22Abeta1-42 flies might be the massive load of insoluble aggregates. The study shows that even though the different Abeta peptides resulted in an equal reduction of the lifespan, they formed an array of different aggregates confirming the heterogeneity of this process. Overall, our findings support that distinct Abeta aggregates can exhibit different pathological effects, and we foresee that our Drosophila models can potentially aid in identifying anti-Abeta agents targeting different types of aggregated Abeta species.
A divide-and-conquer approach based on deep learning for long RNA secondary structure prediction: focus on pseudoknots identification
Authors: Loïc Omnes , Eric Angel , Pierre Bartet , François Radvanyi , Fariza Tahi
Published: November 2024

The accurate prediction of RNA secondary structure, and pseudoknots in particular, is of great importance in understanding the functions of RNAs since they give insights into their folding in three-dimensional space. However, existing approaches often face computational challenges or lack precision when dealing with long RNA sequences and/or pseudoknots. To address this, we propose a divide-and-conquer method based on deep learning, called DivideFold, for predicting the secondary structures including pseudoknots of long RNAs. Our approach is able to scale to long RNAs by recursively partitioning sequences into smaller fragments until they can be managed by an existing model able to predict RNA secondary structure including pseudoknots. We show that our approach exhibits superior performance compared to state-of-the-art methods for pseudoknots prediction and secondary structure prediction including pseudoknots for long RNAs. The source code of DivideFold, along with all the datasets used in this study, is accessible athttps://evryrna.ibisc.univ-evry.fr/evryrna/dividefold/home.
Complex regulation of Cav2.2 N-type Ca2+channels by Ca2+and G-proteins Short title: Cav2.2 modulation by Ca2+and G-proteins
Authors: Thomas Jessica R. , Sun Jinglang , De la Rosa Vazquez Juan , Lee Amy
Published: November 2024

G-protein coupled receptors inhibit Cav2.2 N-type Ca2+channels by a fast, voltage-dependent pathway mediated by Gαi/ Gβγ and a slow, voltage-independent pathway mediated by Gαq−dependent reductions in phosphatidylinositol 4,5-bisphosphate (PIP2) or increases in arachidonic acid. Studies of these forms of regulation generally employ Ba2+as the permeant ion, despite that Ca2+-dependent pathways may impinge upon G-protein modulation. To address this possibility, we compared tonic G-protein inhibition of currents carried by Ba2+(IBa) and Ca2+(ICa) in HEK293T cells transfected with Cav2.2. BothIBaandICaexhibited voltage-dependent facilitation (VDF), consistent with Gβγ unbinding from the channel. Compared to that forIBa, VDF ofICawas less sensitive to an inhibitor of Gα proteins (GDP-β-S) and an inhibitor of Gβγ (C-terminal construct of G-protein coupled receptor kinase 2). While insensitive to high intracellular Ca2+buffering, VDF ofICathat remained in GDP-β-S was blunted by reductions in PIP2. We propose that when G-proteins are inhibited, Ca2+influx through Cav2.2 promotes a form of VDF that involves PIP2. Our results highlight the complexity whereby Cav2.2 channels integrate G-protein signaling pathways, which may enrich the information encoding potential of chemical synapses in the nervous system.
Modelling the influence of changes in vaccination timing, timeliness and coverage on the example of measles outbreaks in the UK between 2010-19
Authors: Suffel Anne M , Warren-Gash Charlotte , McDonald Helen I , Kucharski Adam , Robert Alexis
Published: November 2024

Background

The Measles-Mumps-Rubella vaccine is given as a two-dose course in childhood, but the schedule of the second dose varies between countries. England recommended bringing forward the second dose from three years and four months to 18 months by 2025. We aim to quantify how changing the vaccine schedule could impact measles transmission dynamics.

Methods

We used a mathematical model stratified by age group and region to generate stochastic outbreaks with different vaccine schedules. We used detailed information on vaccine uptake for different age groups by region and year from electronic health records and modelled alternative scenarios changing the timing of the second MMR dose or changing uptake of either dose. We simulated measles incidence between 2010 and 2019 and compared the number of cases in each scenario.

Results and discussion

Delivering the second MMR vaccine at younger age resulted in a lower number of cases than in the reference set of simulations with 16% (IQR: 1.93– 28.48%) cases averted when the second dose was given at 18 months. The number of cases decreased even if the coverage of the second dose decreased by up to 3% (median reduction 15.94%; IQR: 0.41 −28.21%). The impact on case numbers was equivalent to increasing first dose coverage by 0.5% every year between 2010 and 2019 (16.38 % reduction, IQR:1.90 - 28.45), more cases could be avoided (28.60%, IQR: 17.08 - 38.05) if the first dose coverage was increased by 1% every year.

Our data highlighted how patterns of vaccination uptake translate into outbreak risk. Although increasing coverage of the first MMR dose led to the best results, this may be challenging to achieve requiring substantial resources with already high coverage of the first dose. Hence, an earlier second MMR dose presents a good alternative for mitigating the risk of measles outbreaks.
Optimisation of DNA extraction from nasal lining fluid to assess the nasal microbiome using third-generation sequencing
Authors: Montgomery Samuel T. , Carr Phoebe G. , Caparrós-Martín Jose A.
Published: November 2024

Background

Sampling nasal lining fluid (NLF) via nasosorption is minimally invasive and well tolerated, but the feasibility of assessing the nasal microbiome using this technique is unknown. However, low biomass makes airway samples particularly susceptible to issues related to contaminant DNA. In this study, we evaluated the suitability of DNA isolated using methodologies for low-biomass respiratory samples and assessed how well lining fluid collected via nasosorption captures the nasal microbial diversity and composition compared to the traditional swab sampling approach.

Methods

Nasal swabs and NLF were collected from adult volunteers. DNA was extracted from a mock microbial community and NLF using a column-based kit (ZymoBIOMICS), a precipitation-based kit (Qiagen), or a previously published precipitation-based method. Quality and quantity of DNA was assessed and short-read16S rRNAsequencing performed to assess feasibility and extraction bias. An optimised extraction methodology was then used to extract DNA from NLF and nasal swabs, and full-length16S rRNAsequencing performed to compare microbial profiles between NLF and nasal swabs. Taxonomy was assigned using the nf-core/ampliseq pipeline, the PacificBiosciences/pb-16S-nf pipeline, or the software Emu, and downstream analyses were performed using R packages phyloseq and mixOmics.

Results

All extraction methods recovered DNA from the mock community, but only precipitation-based methods yielded sufficient DNA from NLF. Extraction methodologies significantly affected microbial profiles, with mechanical lysis needed to minimize bias against specific genera. Profiles obtained from NLF and swabs were comparable with long-read sequencing.

Conclusions

Our findings demonstrate the feasibility of profiling the nasal microbiome using NLF collected via nasosorption and validated two extraction methodologies as suitable for full-length16S rRNAsequencing of low-biomass respiratory samples. Our data demonstrate the importance of unbiased DNA extraction methodologies in low-biomass respiratory samples, and the subsequent impact of DNA extraction on observed microbial profiles. Additionally, we demonstrated NLF may be an appropriate surrogate samples for nasal swabs to assess the nasal microbiome using16S rRNAsequencing.
Optimizing PSC culture for generating neural organoids
Authors: Sutcliffe Magdalena A. , Jensen Pia , Tan Joycelyn , Morris Charles A.J. , Fazakerley Daniel , Larsen Martin R. , Lancaster Madeline A.
Published: November 2024

Cerebral organoids generated according to unguided protocols produce neural tissue with exceptional cell diversity and fidelity to in vivo. However, with only minimal extrinsic intervention, the importance of high quality starting material becomes paramount. Better understanding of what constitutes a high quality stem cell line and how to maintain those properties throughout prolonged culture is therefore a crucial foundation for successful organoid differentiation. In this study, we investigate the proteome and phospho-proteome of human pluripotent stem cells to uncover the mechanisms that drive neural organoid competence. We identify aberrant cell-extracellular matrix interaction and increased oxidative metabolism as hallmarks of poor neural differentiators. Drawing on the proteomic data and published literature, we optimise culturing conditions by using improved coating matrix, sustained supply of the key growth factor FGF2 and reducing oxidative stress. These adjustments improve brain organoid generation across all tested cell lines, though with varying degrees of efficiency. This work highlights the importance of optimal culture conditions to best support stem cells, ultimately enhancing the quality of brain organoids produced.
Inhibition of Cardiac p38 Highlights the Role of the Phosphoproteome in Heart Failure Progression
Authors: Sedighi Sogol , Liu Ting , O’Meally Robert , Cole Robert N. , O’Rourke Brian , Foster D. Brian
Published: November 2024

Heart failure (HF) is a complex condition characterized by the inability of the heart to pump sufficient oxygen to the organs to meet their metabolic needs. Among the altered signal transduction pathways associated with HF pathogenesis, the p38 mitogen-activated protein kinase (p38 MAPK) pathway—activated in response to stress— has attracted considerable attention for its potential role in HF progression and cardiac hypertrophy. However, the exact mechanisms by which p38 MAPK influences HF remain unclear. Addressing knowledge gaps may provide insight on why p38 inhibition has yielded inconsistent outcomes in clinical trials. Here we investigate the effects of p38 MAPK inhibition via SB203580 on cardiac remodeling in a guinea pig model of HF and sudden cardiac death. Using a well-established HF model with ascending aortic constriction and daily isoproterenol (ACi) administration, we assessed proteomic changes across three groups: sham-operated controls, untreated ACi, and ACi treated with SB203580 (ACiSB). Cardiac function was evaluated by M-mode echocardiography, while proteome and phosphoproteome profiles were analyzed using multiplexed tandem mass tag labeling and LC-MS/MS. Our findings demonstrate that chronic SB203580 treatment offers protection against progressive decline in cardiac function in HF. The proteomic data indicate that SB203580-treatment exerts broad protection of the cardiac phosphoproteome, beyond inhibiting maladaptive p38-dependent phosphorylation, extending to PKA and AMPK networks among others, ultimately protecting the phosphorylation status of critical myofibrillar and Ca2+-handling proteins. Though SB203580 had a more restricted impact on widespread protein changes in HF, its biosignature was consistent with preserved mitochondrial energetics as well as reduced oxidative and inflammatory stress.
What’s in Cow Dung Manure? Insights into Its Potential for Supporting Plant Defense System
Authors: Wilson Karun , Arunachalam Sathiavelu
Published: November 2024

Solanum lycopersicum, a prominent vegetable crop, suffers major yield losses from early blight disease driven byAlternaria solani.Sustainable alternatives to conventional chemical fungicides are urgently needed to mitigate these losses while minimizing environmental impact. This study investigates the application of the microbial consortium derived from Gir cow dung for enhancing tomato resistance against early blight. Metagenomic analysis of Gir cow dung revealed a rich diversity of beneficial microbes, withBacillusspecies being one of the prominent. Three key strainsBacillus subtilis,Bacillus tequilensis, andBacillus licheniformiswere isolated, characterized, and tested for their antagonistic activity againstA. solani. The microbial consortium exhibited significant antifungal properties, and the application of the consortium on tomato plants led to a marked reduction in disease progression. Histochemical analyses of treated plants revealed a pronounced increase of hydrogen peroxide, phenolic compounds, and superoxide dismutase, suggesting enhanced activation of plant defense pathways. Comparative gene expression profiling showed the upregulation of key defense-related genes, including PR2b, Chi3, and Pto kinase, in Bo-treated plants, indicating a systemic activation of host defense mechanisms.

Untargeted metabolomic analysis using LC-MS/MS further demonstrated significant metabolic reprogramming in microbial consortium-treated plants. Pathway enrichment analysis revealed enhanced accumulation of secondary metabolites, including phenolics and terpenoids, which are known to play vital roles in pathogen defense. Additionally, hierarchical clustering of metabolite profiles highlighted distinct metabolic signatures between Bo-treated and control plants, underscoring the broad biochemical impact of the microbial treatment. Collectively, our findings demonstrate that the microbial consortium derived from Gir cow dung significantly enhances tomato plant resistance toA. solanithrough multifaceted biochemical, molecular, and metabolic mechanisms. This study provides a sustainable biocontrol strategy that could effectively replace chemical fungicides, contributing to resilient tomato production and advancing the field of agroecological plant disease management.
Multi-year drought strengthens positive and negative functional diversity effects on tree growth response
Authors: Serrano-León Hernán , Blondeel Haben , Glenz Paula , Steurer Johannes , Schnabel Florian , Baeten Lander , Guillemot Joannès , Martin-StPaul Nicolas , Skiadaresis Georgios , Scherer-Lorenzen Michael , Bonal Damien , Boone Matthieu , Decarsin Renaud , Druel Arsène , Godbold Douglas L. , Gong Jialiang , Hajek Peter , Jactel Hervé , Koricheva Julia , Mereu Simone , Ponette Quentin , Rewald Boris , Sandén Hans , Van den Bulcke Jan , Verheyen Kris , Werner Ramona , Bauhus Jürgen
Published: November 2024

Mixed-species forests are proposed as strategy to increase the resistance and resilience of forests to drought stress. However, evidence suggest that increasing tree species richness does not consistently enhance tree growth responses to drought. Moreover, tree diversity effects under unprecedented multiyear droughts remain uncertain, calling for a better understanding of the underlying processes.

Here, we used a network of planted tree diversity experiments to investigate how drought-induced growth responses of individual trees are influenced by neighborhood tree diversity and the functional traits of the focal tree species. We analyzed tree cores (948 trees across 16 species) from nine experiments across Europe featuring gradients of tree species richness (1–6 species), which experienced severe droughts in recent years. Radial growth response to drought was quantified as tree-ring biomass increment using X-ray computed tomography. We applied hydraulic trait-based growth models to analyze single-year drought responses across all sites and site-specific responses during consecutive drought years for six sites as a function of neighborhood tree diversity.

The large variability in tree growth responses to a single-year drought was partially explained by the focal species’ hydraulic safety margin (representing species’ drought tolerance) and drought intensity, but independent of neighborhood species richness or functional trait diversity. However, tree diversity effects on growth responses strengthened during consecutive drought years and were site-specific, with contrasting direction (both positive and negative). This indicated opposing pathways of diversity effects under consecutive drought events, possibly resulting from competitive release or greater water consumption in diverse mixtures.

We conclude that tree diversity effects on growth responses to single-year droughts may differ considerably from responses to consecutive drought years. Our study highlights the need to consider trait-based approaches (specifically, hydraulic traits) and tree neighborhood scale processes to understand the multifaceted growth responses of tree mixtures under prolonged drought stress.
Lactate potentiates NMDA receptor currents via an intracellular redox mechanism targeting cysteines in the C-terminal domain of GluN2B subunits: implications for synaptic plasticity
Authors: Fiumelli Hubert , Herrera-López Gabriel , Lemtiri-Chlieh Fouad , Mottier Lorène , Girgis John , Ben-Adiba Carine , Jourdain Pascal , Carrano Nicolò , Mahmood Hanan , Ooi Amanda , Arold Stefan T. , Luca Monica Di , Gardoni Fabrizio , Magistretti Pierre J.
Published: November 2024

Summary

Through the Astrocyte Neuron Lactate Shuttle, astrocyte-derived lactate fuels the high-energy demands of neurons and acts as a signaling molecule, promoting synaptic plasticity and memory consolidation. Lactate regulates neuronal excitability and modulates the expression of genes related to synaptic plasticity and neuroprotection, but the molecular mode for these signaling actions is uncertain. Using patch-clamp recordings in cultured cortical neurons, we found that lactate enhances both the amplitude and the inactivation time constant of NMDA receptor currents (INMDAR) evoked by brief applications of glutamate and glycine. Not reproduced by HCAR1 agonists, this modulation depends on monocarboxylate transporters and lactate dehydrogenase, indicating the requirement for lactate entry and metabolic conversion into pyruvate and NADH formation within neurons. Disruption of intracellular calcium dynamics or inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII), a NMDAR-associated kinase linking Ca2+signal to long-term potentiation (LTP), significantly diminishes the effects of lactate on INMDAR. We identified two redox-sensitive cysteine- containing sequences in the intrinsically disordered intracellular C-terminal domain of the GluN2B subunit that play a role in the potentiation of NMDAR by lactate. In a compelling set of experiments using HEK cells, we observed that the presence of functional CaMKII and GluN2B-containing NMDARs is necessary for the lactate-enhancing effects. Mutations in GluN2B that prevent CaMKII binding or redox regulation via cysteines abrogate the modulatory action of lactate. Immunoprecipitation experiments in neurons attest that lactate increases the association between CaMKII and GluN2B. This interaction is crucial for the potentiation of INMDARamplitude by lactate. Proximity ligation assays between GluN2B and the postsynaptic density marker PSD-95 revealed that lactate induced an accumulation of GluN2B in dendritic spines, an effect that was prevented by a CaMKII peptide inhibitor. These results highlight a mechanistic pathway whereby lactate boosts NMDAR function through intracellular metabolic conversion and redox-sensitive interactions requiring CaMKII, establishing a link between astrocyte metabolism and synaptic modulation in neurons.
Loss of PI3Kδ activity drives autoimmune colitis by impairing extrathymic Treg differentiation
Authors: Lim Ee Lyn , Qian Yamin , Sugihara Fuminori , Tanaka Atsushi , Sakaguchi Shimon
Published: November 2024

Peripherally-derived regulatory T cells (pTregs) have a prominent role in maintaining intestinal immune homeostasis. In cases of phosphoinositide-3-kinase δ (PI3Kδ) inactivation, such as in patients receiving PI3Kδ inhibitor idelalisib as a cancer treatment, breakdown of intestinal immune tolerance occurs frequently in the form of diarrhoea and colon inflammation. In a mouse model of systemic PI3Kδ inactivation, both enhancement of anti-tumor immunity and colitis have been described, as a result of Treg impairment. However, in view of the critical role for Tregs in the prevention of systemic autoimmunity, the basis for such tissue-restricted breach of immune tolerance upon loss of PI3Kδ function is not yet understood. We report here that mice lacking PI3Kδ activity do not suffer a general defect in Treg immunosuppression, but specifically fail to develop Helios-pTregs in the colon. We demonstrate reduced extrathymic Treg induction, in vitro and in vivo, from naïve CD4+T cells with inactive PI3Kδ, along with dysregulation of a tissue-resident phenotype. These results suggest a non-redundant role for PI3Kδ-dependent pTreg differentiation in maintaining tolerance to commensal microbial antigens in the gut.
Genotype-by-environment interactions shape ubiquitin-proteasome system activity
Authors: Avery Randi R. , Collins Mahlon A. , Albert Frank W.
Published: November 2024

In genotype-by-environment interactions (GxE), the effect of a genetic variant on a trait depends on the environment. GxE influences numerous organismal traits across eukaryotic life. However, we have a limited understanding of how GxE shapes the molecular processes that give rise to organismal traits. Here, we characterized how GxE shapes protein degradation, an essential molecular process that influences numerous aspects of cellular and organismal physiology. Using the yeastSaccharomyces cerevisiae, we characterized GxE in the activity of the ubiquitin-proteasome system (UPS), the primary protein degradation system in eukaryotes. By mapping genetic influences on the degradation of six substrates that engage multiple distinct UPS pathways across eight diverse environments, we discovered extensive GxE in the genetics of UPS activity. Hundreds of locus effects on UPS activity varied depending on the substrate, the environment, or both. Most of these cases corresponded to loci that were present in one environment but not another (“presence / absence” GxE), while a smaller number of loci had opposing effects in different environments (“sign change” GxE). The number of loci exhibiting GxE, their genomic location, and the type of GxE (presence / absence or sign change) varied across UPS substrates. Loci exhibiting GxE were clustered at genomic regions that contain core UPS genes and especially at regions containing variation that affects the expression of thousands of genes, suggesting indirect contributions to UPS activity. Our results reveal highly complex interactions at the level of substrates and environments in the genetics of protein degradation.
Characterization and engineering of a blue-sensitive, Gi/o-biased, and bistable ciliary opsin from a fan worm
Authors: Fukuzawa Sachiko , Kawaguchi Tomoki , Shimomura Takushi , Kubo Yoshihiro , Tsukamoto Hisao
Published: November 2024

Ciliary opsins have been identified not only in vertebrates but also in invertebrates. An invertebrate ciliary opsin was recently identified in the fan wormAcromegalomma interruptum(formerly namedMegalomma interrupta); however, its spectral and signaling characteristics are unknown. In the present study, we characterized the spectral properties and light-induced cellular signaling properties of the opsin (AcrInvC-opsin).AcrInvC-opsin showed an absorption maximum at 464 nm and upon blue-light absorption, the spectrum was red-shifted by approximately 50 nm. The two states are inter-convertible by illumination with blue and orange light. Blue light illumination ofAcrInvC-opsin caused specific coupling with Gi, sustained Gi dissociation, decreased intracellular cAMP levels, and activation of GIRK channels. The cellular responses by the activated opsin were partially terminated by orange light illumination. These light-dependent responses indicate that the InvC-opsin is a typical bistable pigment wherein the resting and activated states can be inter-converted by visible light illumination. We also attempted to modulate the spectral and functional properties ofAcrInvC-opsin using site-directed mutagenesis. Substitution of Ser-94 with Ala caused little spectral shift in the resting state but a further red-shift of ∼10 nm in the activated state, indicating that the absorption spectra of the two states were tuned differently. In contrast, the S94A substitution did not significantly affect the light-dependent signaling properties ofAcrInvC-opsin. BecauseAcrInvC-opsin is a blue-sensitive, Gi/o-biased, and bistable pigment, it has the potential to serve as an optical control tool to specifically and reversibly regulate Gi/o-dependent signaling pathways by visible light.
Phenomenological model for the
γ*γ→ηπ+π−
reaction in the
f1(1285)
energy region
Authors: Ren Xiu-Lei , Danilkin Igor , Vanderhaeghen Marc
Published: November 2024

Motivated by the ongoing analysis by the BESIII Collaboration on the single-tagged e+e−→e+e−ηπ+π− reaction, we present a phenomenological study of the diphoton fusion to ηπ+π−, focusing on the production mechanism of the f1(1285) resonance. Contributions from the f1(1285)→a0(980)±π∓ and f1(1285)→σ/f0(500)η channels are included without introducing free parameters within an effective Lagrangian approach. Assuming the destructive interference between the amplitudes, we predict the invariant mass distributions, angular distributions, and total cross sections of the γ*γ→ηπ+π− process, which will be tested by the forthcoming BESIII measurements.

Published by the American Physical Society
2024
Exploring flavor space of an economical SU(5) GUT in future proton decay measurements
Authors: Fang Gao-Xiang , Zhou Ye-Ling
Published: November 2024

We discuss the potential of future proton decay experiments on the exploration of the flavor space of grand unification. We focus on an eaconomical SU(5) grand unified model (GUT) with the fermion sector extended by including only one copy of 24-plet. Neutrino masses are generated via type-(I+III) seesaw mechanism with the lightest neutrino massless. Gauge unification requires masses of fermions in the 24-plet to be hierarchical, in particular, the electroweak singlet and triplet heavy leptons to be around the canonical seesaw scale and TeV scale, respectively. We address how extra parameters in the flavor space which cannot be touched in flavor measurements can be tested by a multichannel analysis in future proton decay measurements.

Published by the American Physical Society
2024
Emergence of self-organized criticality and phase transition in the Olami-Feder-Christensen model with a single defect
Authors: Otani Tetsuto , Kame Nobuki
Published: November 2024

We examine the conditions for the emergence of self-organized criticality in the Olami-Feder-Christensen model by introducing a single defect under periodic boundary conditions. Our findings reveal that strong localized energy dissipation is crucial for self-organized criticality emergence, while weak localized or global energy dissipation leads to its disappearance in this model. Furthermore, slight dissipation perturbations to a system in a self-organized criticality reveal a novel state characterized by a limit cycle of distinct configurations. This newly discovered state offers significant insights into the fundamental mechanisms governing the emergence of self-organized criticality.

Published by the American Physical Society
2024
Next-to-Next-to-Leading Order QCD Corrections to Polarized Semi-Inclusive Deep-Inelastic Scattering
Authors: Goyal Saurav , Lee Roman N. , Moch Sven-Olaf , Pathak Vaibhav , Rana Narayan , Ravindran V.
Published: November 2024

Polarized semi-inclusive deep-inelastic scattering (SIDIS) is a key process in the quest for a resolution of the proton spin puzzle. We present the complete results for the polarized SIDIS process at next-to-next-to-leading order (NNLO) in perturbative quantum chromodynamics. Our analytical results include all partonic channels for the scattering of polarized leptons off hadrons and a spin-averaged hadron identified in the final state. A numerical analysis of the NNLO corrections illustrates their significance and the reduced residual scale dependence in the kinematic range probed by the future electron-ion collider.

Published by the American Physical Society
2024
Research on the spillover effects of promotion preannouncements on other selling products within and across brands
Authors: Gu Chenyan , Jia Shuyue , Chang Xinsiyu
Published: November 2024

Purpose

As e-commerce platforms and merchants increasingly adopt promotion preannouncements, understanding their spillover effects on other products within and across brands is crucial. This study aims to comprehensively investigate these spillover effects to optimize the use of promotion preannouncements.

Design/methodology/approach

The study uses quantitative analysis of real-world e-commerce data and four between-subjects experiments to examine the spillover effects of promotion preannouncements.

Findings

Promotion preannouncements negatively impact products within the same brand and category, while positively influencing products in different categories. Additionally, preannouncements create negative spillover effects on products within the same brand echelon. Moreover, powerful brands are more likely to harm different-echelon products compared to weak brands.

Research limitations/implications

The experiment has its own limitations because there will be differences between the simulated scenario and the real shopping scenario. Considering the practical factors, randomized field experiments cannot be conducted at the e-commerce platform level.

Practical implications

The findings provide managerial insights on brands and merchants to arrange the preannounced products and products being sold.

Originality/value

This study contributes to the field of preannouncements by developing new knowledge through a combination of quantitative analysis using e-commerce data and experiments, capturing the novel phenomenon of promotion preannouncement and its spillover effects. We study the preannouncement phase of promotions, thus enriching the multistage research on promotions. In addition, this paper innovatively divides the spillover effects of promotion preannouncement into four components and uses brand echelon as a categorization factor.
Organizational justice and proactive customer service performance mediate the role of work engagement in the hospitality industry
Authors: Sharma Praveen Kumar , Kumra Rajeev
Published: November 2024

Purpose

This study aims to evaluate the mediating role of work engagement (WE) in the relationship between four independent variables, such as procedural justice (PJ), distributive justice (DJ), interactional justice (INTJ) and informational justice (INFJ), along with an outcome variable, i.e. proactive customer service performance (PCSP) within the hospitality industry.

Design/methodology/approach

We used 432 frontline supervisor–subordinate dyads. Using partial least squares structural equation modeling, we obtained data for 47 supervisors and 432 subordinates from the hotel industry. Notably, we used two distinct questionnaires to capture data from each pair in order to avoid common method bias.

Findings

Broadly, the findings show that there is a significant and positive relationship between DJ, PJ, INTJ and INFJ vis-à-vis WE. Besides, WE is also significantly and positively associated with PCSP. Additionally, the results indicate that WE acts as a mediator between the four independent variables (DJ, PJ, INTJ and INFJ) and one outcome variable, PCSP.

Practical implications

Based on our findings, whereby different forms of justice (DJ, PJ, INTJ and INFJ) have a positive impact on WE, and PCSP has practical ramifications, organizations would need to set priorities and implement OJ strategies within the work environment. In turn, this would enable the employees to be more engaged in their work, resulting in improved performance and greater job satisfaction.

Originality/value

This study offers unique theoretical and practical learnings for the hospitality industry with the usage of supervisor–subordinate dyads.
Effectiveness of value co-creation in healthcare system from patients' perspectives
Authors: Sandhu Maqsood Ahmad , AlMeraikhi Mariam Hamad , Saleem Asima , Farooq Mariam
Published: November 2024

Purpose

This study explores the determinants of value co-creation in the semi-government hospitals managed by Abu Dhabi Health Services Company (SEHA) and Mubadala in the United Arab Emirates (UAE).

Design/methodology/approach

The data were collected through a structured survey questionnaire from 1,000 patients attending different healthcare facilities in the UAE. To minimize errors, a pilot study was performed on 50 respondents. The study took the structural equation modelling (SEM) approach, adopting confirmatory factor analysis (CFA), reliability analysis and regression analysis to test the hypothesis.

Findings

This study confirms the substantial influence of communication, relationships, technological enhancement and customized service delivery on the co-creation of value. The findings also confirm in all respects the mediating role of trust in building value co-creation. This sheds light on the ways that healthcare facilities can enhance value co-creation and elevate healthcare services. Notably, the direct and indirect influence of knowing on trust is deemed insignificant in the context of value creation.

Research limitations/implications

The main limitation of this research derives from its coverage of a subject that few empirical studies have targeted before; there were few models to draw on to demonstrate validity.

Practical implications

The research aids healthcare administrators in uncovering the dynamics of interactions between practitioners and patients, facilitating advances in the commitment to co-create value. The comprehensive insights into value co-creation contribute to the development of a versatile knowledge foundation, empowering proactive initiatives in the design of healthcare delivery models.

Originality/value

The uniqueness of this study lies in its expansion of previous research, making clear the effectiveness of various engagements that contribute to value co-creation in healthcare settings. It specifically focuses on semi-government hospitals managed by SEHA and Mubadala in the UAE.