bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene-by-environment interactions involving maternal exposures with orofacial cleft risk in Filipinos
Authors: Erdogan-Yildirim Zeynep , Carlson Jenna C. , Mukhopadhyay Nandita , Leslie Elizabeth J. , Padilla Carmencita , Murray Jeffrey C. , Beaty Terri H. , Weinberg Seth M. , Marazita Mary L. , Shaffer John R.
Published: December 2024

Maternal exposures are known to influence the risk of isolated cleft lip with or without cleft palate (CL/P) – a common and highly heritable birth defect with a multifactorial etiology. To identify new CL/P risk loci, we conducted a genome-wide gene-environment interaction (GEI) analysis of CL/P on a sample of 540 cases and 260 controls recruited from the Philippines, incorporating the interaction effects of genetic variants with maternal smoking and vitamin use. As GEI analyses are typically low in power and the results can be difficult to interpret, we used multiple testing frameworks to evaluate potential GEI effects: 1 degree-of-freedom (1df) GxE test, the 3df joint test, and the two-step EDGE approach. While we did not detect any genome-wide significant interactions, we detected 12 suggestive GEI with smoking and 25 suggestive GEI with vitamin use between all testing frameworks. Several of these loci showed biological plausibility. Notable interactions with smoking include loci nearFEZF1,TWIST2,andNET1.WhileFEZF1is involved in early neuronal development,TWIST2andNET1regulate epithelial-mesenchymal transition which is required for proper lip and palate fusion. Interactions with vitamins encompassCECR2— a chromatin remodeling protein required for neural tube closure—andFURIN,a critical protease during early embryogenesis that activates various growth factor and extracellular-matrix protein. The activity of both proteins is influenced by folic acid. Our findings highlight the critical role of maternal exposures in identifying genes associated with structural birth defects such as CL/P and provide new paths to explore for CL/P genetics.
Sensor Fusion Algorithm to Improve Accuracy of Robotic Superposition Testing using 6-DOF Position Sensors
Authors: Gillespie Callan M. , Arant Lesley R. , Roth Joshua D. , Colbrunn Robb W.
Published: December 2024

To quantify the contributions of specific ligaments to overall joint biomechanics, the principle of superposition has been used for nearly 30 years. This principle relies on a robotic test system to move a biological joint to the same pose before and after transecting a ligament. The magnitude of the vector difference in joint forces before and after transecting the ligament is assumed to be the transected ligament’s tension. However, the robotic test system’s ability to accurately return the joint to the commanded pose is dependent on the compliance of the system’s various components, which is often neglected. An alternative approach to superposition testing is to use additional sensors attached directly to the joint to inform robot motion. Accordingly, there are two objectives in this manuscript: (1)Describea testing methodology with 6-DOF position sensors to correct for system compliance, and (2)Demonstratethe effectiveness of this methodology to reduce uncertainty of in-situ forces determined using superposition. A Sensor Fusion algorithm fuses 6-DOF position sensors with robot pose measurements to compensate for system compliance. Using a surrogate knee joint with the Traditional testing method, errors in pose of approximately 100 microns resulted in a 23% underestimation of computed ligament tension. With the Sensor Fusion algorithm, errors in pose fell below the noise floor of the 6-DOF position sensors, and errors in computed ligament tension were reduced to 3%. Thus, this Sensor Fusion algorithm is a promising approach to minimize errors in superposition testing caused by compliance in a robotic test system.
Responses to temperature shocks inZymoseptoria triticireveal specific transcriptional reprogramming and novel candidate genes for thermal adaptation
Authors: Minana-Posada Silvia , Feurtey Alice , Alassimone Julien , McDonald Bruce A. , Lorrain Cécile
Published: December 2024

Pathogens’ responses to sudden temperature fluctuations, spanning various temporal scales, are critical determinants of their survival, growth, reproduction, and homeostasis. Here, we combined phenotyping, transcriptomics, and genome-wide association approaches to investigate how the wheat pathogenZymoseptoria triticiresponds to and recovers from temperature shocks. Survival emerged as the most significantly affected trait immediately following temperature shocks across 122 geographically diverse strains. In contrast, post-recovery phenotypic traits, including growth rate and melanization, showed no significant deviations from control conditions. Transcriptomic analyses of a reference strain revealed temperature stress-specific gene expression patterns, with genes involved in protein folding, redox homeostasis, membrane stabilization, and cell-wall remodeling playing central roles in the response. A multi-reference k-mer genome-wide association study (GWAS) identified six loci significantly associated with cold shock responses. Among these, two loci emerged as strong candidates for near-freezing temperature adaptation, including a 60S ribosomal protein gene involved in protein synthesis and stress recovery, and an NADH oxidoreductase gene implicated in redox homeostasis and oxidative stress tolerance. These findings shed light on the distinct molecular strategiesZ. triticiemploys to adapt to temperature stress and provide novel insights into fungal resilience under dynamic environmental conditions.

Author summary

Temperature fluctuations, an inherent aspect of natural environments, are increasingly exacerbated by climate change, intensifying challenges for organisms to maintain homeostasis amid more frequent and severe extreme weather events. This study reveals distinct phenotypic, transcriptomic, and genetic mechanisms underlyingZ. tritici’s responses to short-term temperature shocks. Survival-related phenotypic traits were significantly reduced by heat and cold shocks, while other traits measured after a recovery period demonstrated the resilience ofZ. triticistrains to temperature stress, reflecting efficient recovery mechanisms. Transcriptomic analyses uncovered temperature-specific gene expression patterns, emphasizing unique regulatory strategies, which mostly return to baseline levels after a recovery period. The discovery of novel loci associated with cold shock responses provides valuable insights into the genetic basis of resilience to short-term temperature stress, offering a foundation for future research on pathogen adaptation to fluctuating environments.
Spread of a single superclone drives insecticide resistance inAcyrthosiphon kondoiacross an invasive range
Authors: Thia Joshua A. , Hunt Benjamin J. , Wang Shuchao , Troczka Bartlomiej J , Brown Courtney J. , Arinanto Leonhard S. , Chirgwin Evatt , Stelmach Monica , Richardson Kelly , Joglekar Chinmayee , Dorai Ashritha P. S. , Yang Qiong , Babineau Marielle , Bass Chris , Hoffmann Ary A. , Umina Paul A.
Published: December 2024

Populations under similar selection pressures may adapt via parallel evolution or dispersal of advantageous alleles. Here, we investigated insecticide resistance in the invasive blue-green aphid,Acyrthosiphon kondoi, which reproduces clonally in Australia and has rapidly developed resistance across geographic locations. Using genomic, transcriptomic, and experimental approaches, we explored the evolutionary origins and molecular mechanisms of resistance. We developed the first reference genome forA. kondoi(443.8 Mb, 28,405 annotated genes, BUSCO score 97.5%) and established isofemale strains from southern Australia with varying resistance statuses. All resistant strains shared a common ancestor, supporting the spread of a resistant ‘superclone’ distinct from susceptible strains. Resistance was associated with overexpression of an esterase gene homologous to the E4/FE4 esterases linked to multi-chemical resistance in other aphid pests. Functional experiments inDrosophila melanogasterconfirmed the causal role of this E4-like esterase in resistance to organophosphates, carbamates, and pyrethroids. These findings highlight how clonal dispersal and insecticide overuse can transform local adaptation into a widespread pest management issue. Our results suggest a parallel macroevolutionary response to insecticide selection inA. kondoiand other aphid species at the gene family level, but with a distinct regulatory mechanism inA. kondoi. Given the rapid spread of the resistant superclone, alternative management strategies, including expanded chemical control options and enhanced biological control, are urgently needed to mitigate this growing pest problem.
LPS stimulates dynamic changes in B cell metabolism to promote proliferation
Authors: Cheung Dana M.S. , Razsolkov Momchil , Bonacina Fabrizia , Andrews Stephen , Sumoreeah Megan , Sinclair Linda V. , Howden Andrew J.M. , Arthur J. Simon C.
Published: December 2024

Following activation, naïve B cells exit quiescence and enter a proliferative phase before becoming mature antibody-producing or memory B cells. One method of activation is to use Lipopolysaccharide (LPS), a well-established B cell mitogen that can drive proliferationex vivo.Using quantitative proteomics, we identify an upregulation of proteins following LPS stimulation involved in metabolic pathways including amino acid uptake and cholesterol biosynthesis. We highlight the large, neutral amino acid transporter SLC7A5 as a target of LPS-induced activation, and by utilising SLC7A5 conditional knockout mice, we demonstrate the requirement of this transporter for B cell proliferationex vivo. LPS stimulation increased cellular cholesterol levels and inhibition of the rate-limiting enzymes HMG-CoA-reductase (HMGCR) and Squalene monooxygenase in the cholesterol biosynthesis pathway significantly reduced proliferation. The critical role of the cholesterol biosynthetic pathway was not limited to LPS. Stimulation via TLR7, TLR9, CD40 and the B Cell Receptor also increased cholesterol levels and inhibition of HMGCR reduced proliferation. Together these results suggest a common requirement for metabolic rewiring in B cells to allow proliferation in response to activation.
Modelling co-development between the somites and neural tube in human Trunk-like Structures (hTLS)
Authors: Makwana Komal , Tilley Louise , Chakravarty Probir , Thompson Jamie , Baillie-Benson Peter , Rodriguez-Polo Ignacio , Moris Naomi
Published: December 2024

Human stem cell-based embryo models have opened new avenues of research in development by providing experimentally amenablein vitrosystems. One of the features of embryo models is their multilineage differentiation, which allows the co-development of, and interactions between, tissues. Here, we utilise a human Trunk-like Structure (hTLS) model to explore trunk development. We show that hTLS have morphologically organised somites and a neural tube that form through self-organised, endogenous signalling including anteroposterior FGF, Wnt and Retinoic Acid (RA) gradients that modulate the fate of neuromesodermal progenitors. Comparison to an existing dataset from organogenesis-stage human embryos shows that hTLS cells approximate Carnegie Stage 13-14 (28-35 days post-fertilisation). The absence of a notochord leads to a dorsal identity, but exogenous exposure to smoothened agonist (promoting Sonic Hedgehog signalling) progressively ventralises both somites and neural tube in a dose-dependent manner. Furthermore, we identify endogenous signalling from the neural tube to the somites, which leads to medially localisedALDH1A2,and subsequent RA signalling from the somites to the neural tube, which leads to spontaneous neural progenitor patterning andPAX6expression. Together, our data highlight the value of modularity in embryo models which we leverage to explore human trunk co-development.

Using a 3D, stem cell-based model of human embryonic trunk development, we examine the interactions across somitic and neural tissues to better understand the dynamics of human trunk co-development.
Sotalol dose optimization for fetal tachycardia: a pregnancy physiologically based pharmacokinetic model study
Authors: van Hove Hedwig , van der Heijden Joyce E.M. , van Uden Anne , Gijsen Violette M.G.J. , Greupink Rick , de Wildt Saskia N. , van Drongelen Joris
Published: December 2024

Objective

To establish an optimized sotalol dosing strategy for fetal tachycardia by using a pregnancy computational model for dose simulations.

Methods

A physiologically-based computational model, including pregnancy-related changes and placental transfer values, was established and verified. Simulations of the current dosing advises and prospective dosing scenarios were performed. To avoid maternal dose-related toxicity (QT-prolongation) we aimed for maternal concentrations <2.5 mg/L. Based on neonatal concentration-effect data, we aimed for a fetal Ctroughconcentrations of 0.4 – 1.0 mg/L.

Results

The pregnancy physiologically-based pharmacokinetic model accurately predicted maternal and fetal exposures. Predictions indicate that almost 16% of maternal plasma concentrations exceed the toxic level of 2.5 mg/L at the maximum oral daily dose of 480 milligram, while 90% of fetuses have a Ctroughconcentration within the therapeutic window. When lowering the maximum daily dose to 400 mg, 0.1% of maternal plasma concentrations exceed 2.5 mg/L, while 87% of the fetal plasma concentrations remain in the therapeutic window. Additionally dosing 480 mg in three times daily reduces the risk of high maternal plasma exposure to 0.3%, while maintaining effective fetal Ctroughconcentrations in 95% of fetuses.

Conclusion

Pregnancy computational modeling can be used to adequately predict maternal and fetal sotalol exposures. Our simulations suggest that daily doses should not exceed 400 milligram and that dividing the oral daily dose over three doses improves the balance between high maternal plasma exposure and effective fetal concentrations.

Funding

This publication is based on research funded by the Bill & Melinda Gates Foundation (INV-023795).
Diminished functional gradient of the precuneus during altered states of consciousness
Authors: Lyu Dian , Adapa Ram , Carhart-Harris Robin L. , Roseman Leor , Owen Adrian M. , Naci Lorina , Menon David K. , Stamatakis Emmanuel A.
Published: December 2024

The relationship between the default mode network (DMN) and task-positive networks, such as the frontoparietal control network (FPCN), is a prominent feature of functional connectivity (FC) in the human brain. This relationship is primarily anticorrelated at rest in healthy brains and is disrupted in altered states of consciousness. Although the DMN and FPCN seem to perform distinct and even opposing roles, they are anatomically adjacent and exhibit ambiguous boundaries. To test the hypothesis that the DMN-FPCN distinction manifests probabilistically rather than having absolute anatomical boundaries, we examined the differences in FC along the dorsal-ventral (d-v) axis in the posterior precuneus (PCu), which serves a convergence zone between the DMN and FPCN. Our findings indicate that the connectivity differences along this axis are continuous as characterized by linear slopes. Notably, these linear relationships (i.e., functional gradients of the precuneus/FGp) are present only within the territories of the DMN and FPCN, respectively associating with positive and negative slopes. Furthermore, the gradient is functionally relevant, as its spatial configurations change in specific ways in altered states of consciousness (ASC): the magnitude of FGp is similarly impaired across different types of ASC, while the spatial entropy of FGp differs between psychedelic and sedative states. These results suggest that the DMN and FPCN, while appearing distinct, may originate from a single, integrated mechanism.

Significance Statement

This research provides new insights into the brain’s functional organization underlying human conscious states by examining the relationship between two large-scale networks: the default mode network (DMN) and the frontoparietal control network (FPCN). These networks, which are attuned to handle internal and external information respectively, are often viewed as oppositional. However, our findings indicate they form an integrated system with continuous connectivity. We identified the posterior precuneus as a key convergence point, revealing a gradient of connectivity between the two networks. This gradient flattens during altered states of consciousness induced by psychedelics or sedatives, showing a loss of functional differentiation between the DMN and FPCN.
Keeping Your Eye, Head, and Hand on the Ball: Rapidly Orchestrated Visuomotor Behavior in a Continuous Action Task
Authors: Schroeger Anna , Goettker Alexander , Braun Doris I. , Gegenfurtner Karl R.
Published: December 2024

While many studies on eye movements focus on highly controlled, repetitive conditions, we expanded this approach by measuring eye, head, and hand movements of participants playing an iPad-based version of the classic computer game Pong. This allowed us to capture more natural sequential behavior while maintaining the benefits of experimental control. Participants intercepted a moving ball by sliding a paddle at the bottom of the screen so that the ball bounced back and moved toward the computerized opponent. We tested i) how participants adapted their eye, hand, and head movements to this dynamic, continuous task, ii) whether these adaptations are related to interception performance, and iii) how their behavior changed under different conditions and over time. We found that eye, hand, and head movements are largely shaped towards participant’s action (and lesser so towards the opponent’s action). Movements that reduce or destabilize visual input, like saccades, blinks and head movements, are reduced during critical periods of interception. Instead, participants increase the frequency of pursuit eye movements, ensuring that they closely track the ball when their action comes closer. This pursuit strategy is associated with better game performance. Our results demonstrate an orchestration of eye, head, and hand movement patterns, which is rapidly established and finely adjusted to meet the evolving demands of impending actions and task demands.
Comparative transcriptomics reveal contrasting fungal strategies in a plant pathogen versus an endophyte during initial host colonization
Authors: Moonjely Soumya , Trail Frances
Published: December 2024

Conidial germination marks the beginning of the fungal life cycle on the host plant, leading to disease or mutually beneficial relationships. Here, we use comparative transcriptomics to unravel the transcriptional similarities and differences during conidial germination and initial colony establishment of the plant pathogenFusarium graminearum,and the endophyteMetarhizium anisopliae. Our comparison crosses four stages from fresh conidia to polar growth, hyphal extension, ending in either first hyphal branching (on medium) or appressorium formation (on barley).F. graminearumexhibited a higher number of upregulated genes for CAZymes, specialized metabolites and effectors compared toM. anisopliaeduring the interaction with the host, particularly during the appressorium stage, reflecting its pathogenic nature. The formation of appressoria byM. anisopliaeconidia during germination on barley roots has not been documented previously and includes both morphological characteristics and gene expression patterns that regulate appressorium development. Our analysis reveals reduced transcript levels of CAZyme and specialized metabolite genes inM. anisopliaecompared toF. graminearum, reflecting a less aggressive host penetration approach. The candidate genes associated with indole-3-acetic acid synthesis were upregulated inM. anisopliaeduring the appressorium stage, supporting its endophytic lifestyle, and suggesting that the fungus uses a phytohormone based strategy to interact with plant hosts. Collectively, our findings expand the transcriptome resources and provide valuable insights into the gene networks involved in conidial germination and initiation of infection in pathogenic versus endophytic fungi, as well as documenting appressorium formation for the first time, in the endophytic life cycle ofM. anisopliae.

IMPORTANCE

Conidial germination is the initial step for fungal colonization in diverse environments. Here we examine the transcriptional similarities and differences in conidial germination and colony establishment ofFusarium graminearumandMetarhizium anisopliae, two fungal species belongs to the Order Hypocreales with distinct lifestyles.F. graminearumis a plant pathogen and the causal agent of Fusarium head blight on cereal crops, whereasM. anisopliaeis an insect pathogen and root endophyte which forms beneficial associations with plants. We compared the transcriptome profiles of these species under two nutrient conditions across four stages of conidial germination. Our study shows that the expression profile of the genes encoding carbohydrate-active enzymes, specialized metabolites, and putative effectors varies betweenF. graminearumandM. anisopliae. The results of this study provide insights into gene networks associated with spore germination stages on the host in a pathogenic versus an endophytic fungus.
Priestia megateriumILBB592 based biofertilizer increases the efficiency of phosphorus fertilization, positively affects soybean nutrition and yield and modifies the rhizospheric bacterial community
Authors: Torres Pablo , Fresia Pablo , Beyhaut Elena , Cuitiño María José , Altier Nora , Abreo Eduardo
Published: December 2024

Phosphorus (P) is needed by soybean plants to form vital molecules like ATP and nucleotides and perform plant functions like photosynthesis and Nitrogen biological fixation at nodules. Because P concentration in the soil solution is naturally low, P fertilization is applied to satisfy soybean requirements in high yielding crops. However, a small portion of added P is readily available to the plants, while most is retained by the soil matrix and eventually made available or lost through erosion and run-off to water bodies, where it promotes eutrophication. Therefore, technologies that enhance P uptake by crops could lead to lower P inputs and outputs from soybean cropping systems, improving sustainability. Priestia megaterium ILBB592 and Bacillus pumilus ILBB44 are two PGPR with P mobilization features that were single formulated as biofertilizers and co-inoculated with Bradyrhizobium elkanii on seeds of soybean Genesis 5602 in two consecutive years in the field, with and without P fertilization. Co-inoculation with ILBB592 improved plant P uptake, along with N and K, with and without P fertilization. Diversity was increased by co-inoculation with ILBB44 and ILBB592, and predicted genes related with P cycling in the rhizospheric soils were also augmented after co-inoculation with ILBB592, mostly with P fertilization. Shoot dry weight and yield were also improved although effect on yield was not statistically significant. P fertilization alone had no effect in the first year but showed some effect on nodules dry weight, P uptake and yield on the second year, suggesting a sufficient P level was obtained after repeated fertilizations. ILBB592 biofertilizer showed a positive effect on most plant parameters, including nodulation and P uptake in both years and both P fertilization regimes and is therefore considered as a useful technology to reduce P fertilization without jeopardizing plant performance.
Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control
Authors: Grabarczyk Daniel B , Ehrmann Julian F , Murphy Paul , Kurzbauer Robert , Bell Lillie E , Deszcz Luiza , Neuhold Jana , Schleiffer Alexander , Shulkina Alexandra , Versteeg Gijs A , Meinhart Anton , Zavodszky Eszter , Hegde Ramanujan S , Clausen Tim
Published: December 2024

Eukaryotic cells have evolved sophisticated quality control mechanisms to eliminate aggregation-prone proteins that compromise cellular health. Central to this defense is the ubiquitin-proteasome system, where UBR4 acts as essential E4 ubiquitin ligase, amplifying degradation marks on defective proteins. Our cryo-EM analysis of UBR4 in complex with its cofactors KCMF1 and CALM1 reveals a massive 1.3 MDa ring structure, featuring a central substrate-binding arena and flexibly attached catalytic units. Structural data illustrate how UBR4 binds substrate and extends K48-specific ubiquitin chains. Importantly, efficient substrate targeting depends on both pre-ubiquitination and specific N-degrons, with KCMF1 acting as key substrate filter. Furthermore, we show that the architecture of the E4 megacomplex is conserved across eukaryotes but with species specific adaptations, allowing UBR4 to perform its precisely tuned quality-control function in diverse cellular environments.
Mother-to-infant plasmid transmission in early postpartum and its association with dominant gut bacteria
Authors: Kuriyama Yuki , Suganuma Natsuki , Ito Kohei
Published: December 2024

Background

The gut microbiome plays a crucial role in human health, and it is known that the microbiome is transmitted from mother to infant at birth and has profound effects on an individual’s health. Although extensive research has been conducted on mother-to-infant microbiome transmission, little is known about plasmid transmission and its effects on the infant microbiome. Plasmids are considered important contributors to early development of the gut microbiome due to their functions, such as antibiotic resistance, and their ability to be transferred between a wide range of host bacteria.

Methods

In this study, we assembled plasmid sequences from longitudinal fecal data of 65 mother-infant pairs and analyzed plasmid sharing between mothers and infants during the first year of life. After identifying shared plasmids, we investigated the relationship between plasmid sharing and delivery mode. We also characterized the functions and host range of shared plasmids.

Results

We found that the number of plasmids was lower in infants than in mothers, probably reflecting the lower overall diversity of the infant microbiome. Additionally, we detected shared plasmids between mothers and infants, marking the first discovery of mother-to-infant plasmid transmission. Our findings revealed that plasmids are more likely to be transmitted from mother to infant immediately after birth, with the likelihood of transmission decreasing as infants age. This underscores the critical role of the maternal microbiome in shaping early development of the gut microbiome. Moreover, plasmids from dominant bacteria in mother-to-infant microbiome transmission, such asBacteroides, were frequently transmitted to infants and carried specific functional traits. In particular, plasmid genes such asmbpA, mbpB, and mbpCwere frequently shared between mothers and infants. Each of these genes encodes a protein of a specific size and plays an important role in plasmid mobilization, or the transfer of plasmids to other bacteria. Plasmids improve the fitness and environmental adaptability of host bacteria, which may contribute to the development of a healthy gut microbiome in infants.

Conclusions

This study revealed that mother-to-infant plasmid transmission likely occurs during the early postpartum period and is influenced by dominant gut bacteria. These findings provide new insights into the mother’s role in shaping the infant’s gut microbiome development.
C. elegansnucleolar RG repeats are sufficient for nucleolar accumulation but insufficient for sub-nucleolar compartmentalization
Authors: Spaulding Emily L. , Updike Dustin L.
Published: December 2024

Intrinsically disordered arginine-glycine (RG) repeat domains are enriched in multilayered biomolecular condensates such as the nucleolus.C. elegansnucleolar RG repeats are dispensable for nucleolar accumulation and instead contribute to the organization of sub-nucleolar compartments. The sufficiency of RG repeats to facilitate sub-nucleolar compartmentalization is unclear. In this study, we drive expression of full-length RG repeats in theC. elegansgermline to test their ability to localize to nucleoli and organize into nucleolar sub-compartmentsin vivo. We find that repeats accumulate within germ cell nucleoli but do not enrich in the correct sub-compartment. Our results suggest RG repeats may indirectly influence nucleolar organization by creating an environment favorable for sub-nucleolar compartmentalization of proteins primarily based on their function within the nucleolus.
DNAJC13 localization to endosomes is opposed by its J domain and its disordered C- terminal tail
Authors: Adoff Hayden , Novy Brandon , Holland Emily , Lobingier Braden T
Published: December 2024

Endosomes are a central sorting hub for membrane cargos. DNAJC13/RME-8 plays a critical role in endosomal trafficking by regulating the endosomal recycling or degradative pathways. DNAJC13 localizes to endosomes through its N-terminal Plekstrin Homology (PH)-like domain, which directly binds endosomal phosphoinositol-3-phosphate (PI(3)P). However, little is known about how DNAJC13 localization is regulated. Here, we show that two regions within DNAJC13, its J domain and disordered C-terminal tail, act as negative regulators of its PH-like domain. Using a structure-function approach combined with quantitative proteomics, we mapped these control points to a conserved YLT motif in the C-terminal tail as well as the catalytic HPD triad in its J domain. Mutation of either motif enhanced DNAJC13 endosomal localization in cells and increased binding to PI(3)Pin vitro. Further, these effects required the N-terminal PH-like domain. We show that, similar to other PI(3)P binding domains, the N-terminal PH-like domain binds PI(3)P weakly in isolation and requires oligomerization for efficient PI(3)P binding and endosomal localization. Together, these results demonstrate that interaction between DNAJC13 and PI(3)P serves as a molecular control point for regulating DNAJC13 localization to endosomes.

Significance Statement

DNAJC13 controls endosomal sorting by regulating proteins which mediate the endosomal recycling and degradative subdomains.

Here we show that subcellular localization of DNAJC13 is regulated through the coordinated action of three of its domains: the PH-like domain which has low affinity for PI(3)P, the J domain, and a YLT motif in its disordered C-terminus.

This study defines a novel mechanism by which DNAJC13 function is regulated.
Autologous host-pathogen pairing enhances early immune responses and bacterial growth control in tuberculosisin vitrogranuloma model
Authors: Genestet Charlotte , Bourg Chloé , Hodille Elisabeth , Bahuaud Olivier , Ader Florence , Dumitrescu Oana
Published: December 2024

Tuberculosis (TB), caused byMycobacterium tuberculosis(Mtb), remains a global health challenge, characterized by significant heterogeneity in its clinical presentation and physiopathology, underscoring the need for optimized models to better understand host-pathogen interactions. This study evaluated the impact of both host and Mtb clinical isolate variability on bacterial growth and dormancy and immune responses using anin vitrogranuloma model. Peripheral blood mononuclear cells from active TB patients were infected with autologous and heterologous Mtb clinical isolates, as well as the H37Rv Mtb reference strain. Bacterial growth and dormancy dynamics and cytokines release were assessed at 0-, 7-, 14- and 21-days post-infection. Results revealed that bacterial growth and dormancy dynamics were mostly isolate-dependent, with almost no impact of PBMC donor. However, at 7-days post-infection, autologous infections exhibited lower bacterial loads and elevated Th1-type cytokines, such as TNF-α and IFN-γ. Yet, this early advantage in bacterial control did not persist at later time points. These findings highlight the importance of host-pathogen pairing in shaping immune responses and validate thein vitrogranuloma model as a relevant tool for studying TB pathogenesis and evaluating therapeutic interventions. Furthermore, further research is needed to decipher the specificities of autologous immune response.
Magnetic field tuned superconducting and normal-phase magnetism in
CeCo0.5Rh0.5In5
Authors: Howell A. , Songvilay M. , Rodriguez-Rivera J. A. , Niedermayer Ch. , Husges Z. , Manuel P. , Saha S. , Eckberg C. , Paglione J. , Stock C.
Published: December 2024

By tuning the superconducting order parameter with an applied magnetic field, we use neutron diffraction to compare the magnetically ordered phases in superconducting and normal states of CeCo0.5Rh0.5In5. At zero applied field, CeCo0.5Rh0.5In5 displays both superconductivity (Tc=1.3K) and spatially long-ranged commensurate ↑↓↑↓ antiferromagnetism [TN=2.5K, propagation vector Q⃗=(12,12,12)]. Neutron spectroscopy fails to measure propagating magnetic excitations from this ground state with only temporally overdamped fluctuations observable. On applying a magnetic field which suppresses superconductivity, we find anisotropic behavior in the static magnetism. When the applied magnetic field is along the crystallographic c axis, no change in the static magnetic response is observable. However, when the field is oriented within the a−b plane, an increase in TN and change in the critical response are measured. At low temperatures in the superconducting phase, the elastic magnetic intensity increases linearly (∝|H|) with small

a

−

b

oriented fields. However, this trend is interrupted at intermediate fields where commensurate block ↑↑↓↓ magnetism with propagation vector Q⃗=(12,12,14) forms. For large applied fields in the [11¯0] direction which completely suppresses superconductivity, weakly incommensurate magnetic order along L is observed to replace the commensurate response present in the superconducting and vortex phases. We discuss experimental considerations related to this shift in momentum and suggest field-induced incommensurate static magnetism, present in the normal state of superconducting and antiferromagnetic CeCo0.5Rh0.5In5 for a−b plane oriented magnetic fields. We speculate that these field-dependent properties are tied to the field-induced anisotropy associated with the local Ce3+ crystal field environment of the tetragonal “115” structure.

Published by the American Physical Society
2024
Magnetic effects in the hadron resonance gas
Authors: Marczenko Michał , Szymański Michał , Lo Pok Man , Karmakar Bithika , Huovinen Pasi , Sasaki Chihiro , Redlich Krzysztof
Published: December 2024

We discuss the modeling of the hadronic phase of QCD at finite magnetic field in the framework of hadron resonance gas (HRG). We focus on the statistical description of particle yields that include contribution from resonance decays. We demonstrate that the swift increase in the number of protons with magnetic field predicted in the HRG is due to the assumption of structureless resonances. We discuss fluctuations of conserved charges and show that at present the qualitative comparison of the model predictions with the lattice QCD data should be treated with care. We also discuss the principle of detailed balance which allows us to study the magnetic field dependence of neutral resonances.

Published by the American Physical Society
2024
General mass variable flavor number scheme for
Z
boson production in association with a heavy quark at hadron colliders
Authors: Guzzi Marco , Nadolsky Pavel , Reina Laura , Wackeroth Doreen , Xie Keping
Published: December 2024

We present a methodology to streamline implementation of massive-quark radiative contributions in calculations with a variable number of active partons in proton-proton collisions. The methodology introduces and heavy-quark parton distribution functions (PDFs) to implement calculations in the Aivazis–Collins–Olness–Tung (ACOT) factorization scheme and its simplified realization in various processes up to the next-to-the-next-to-leading order in the QCD coupling strength. Interpolation tables for bottom-quark subtraction and residual distributions for CT18 NLO and NNLO PDF ensembles are provided in the common LHAPDF6 format. A numerical calculation of Z-boson production with at least one b jet at the Large Hadron Collider beyond the lowest order in QCD is considered for illustration purposes.

Published by the American Physical Society
2024
Single isolated photon production in the
NLO*
approximation of the parton Reggeization approach
Authors: Chernyshev A. A. , Saleev V. A.
Published: December 2024

The hadroproduction of single isolated photon at high energies is studied within the framework of the next-to-leading order (NLO⋆) approximation of the parton Reggeization approach based on the modified multi-Regge limit of the hard scattering quantum chromodynamics (QCD) amplitudes. The contribution from the LO subprocess QQ¯→γ and the NLO tree-level corrections QR→γq and QQ¯→γg are considered. To avoid specific double counting in rapidity between tree-level corrections to the hard scattering coefficient and unintegrated PDFs, a corresponding subtraction scheme is proposed. We demonstrated self-consistency of the parton Reggeization approach using the subtraction scheme. The results of calculations are compared with data from various collaborations in the wide energy range

S

=

24

 

 

GeV

–

13

 

 

TeV

. We obtained a quite satisfactory agreement with data up to pTγ/S≃0.2–0.3. Predictions for the future SPD NICA experiment were discussed.

Published by the American Physical Society
2024
Neutrino many-body flavor evolution: The full Hamiltonian
Authors: Cirigliano Vincenzo , Sen Srimoyee , Yamauchi Yukari
Published: December 2024

We study neutrino flavor evolution in the quantum many-body approach using the full neutrino-neutrino Hamiltonian, including the usually neglected terms that mediate nonforward scattering processes. Working in the occupation number representation with plane waves as single-particle states, we explore the time evolution of simple initial states with up to N=10 neutrinos. We discuss the time evolution of the Loschmidt echo, one body flavor and kinetic observables, and the one-body entanglement entropy. For the small systems considered, we observe “thermalization” of both flavor and momentum degrees of freedom on comparable time scales, with results converging towards expectation values computed within a microcanonical ensemble. We also observe that the inclusion of nonforward processes generates a faster flavor evolution compared to the one induced by the truncated (forward) Hamiltonian.

Published by the American Physical Society
2024
New nonrenormalization theorem from UV/IR mixing
Authors: Abel Steven , Dienes Keith R. , Nutricati Luca A.
Published: December 2024

In this paper, we prove a new nonrenormalization theorem which arises from UV/IR mixing. This theorem and its corollaries are relevant for all four-dimensional perturbative tachyon-free closed string theories which can be realized from higher-dimensional theories via geometric compactifications. As such, our theorem therefore holds regardless of the presence or absence of spacetime supersymmetry and regardless of the gauge symmetries or matter content involved. This theorem resolves a hidden clash between modular invariance and the process of decompactification, and enables us to uncover a number of surprising phenomenological properties of these theories. Chief among these is the fact that certain physical quantities within such theories cannot exhibit logarithmic or power-law running and instead enter an effective fixed-point regime above the compactification scale. This cessation of running occurs as the result of the UV/IR mixing inherent in the theory. These effects apply not only for gauge couplings but also for the Higgs mass and other quantities of phenomenological interest, thereby eliminating the logarithmic and/or power-law running that might have otherwise appeared for such quantities. These results illustrate the power of UV/IR mixing to tame divergences—even without supersymmetry—and reinforce the notion that UV/IR mixing may play a vital role in resolving hierarchy problems without supersymmetry.

Published by the American Physical Society
2024
The Heisenberg-RIXS instrument at the European XFEL
Authors: Schlappa Justine , Ghiringhelli Giacomo , Van Kuiken Benjamin E. , Teichmann Martin , Miedema Piter S. , Delitz Jan Torben , Gerasimova Natalia , Molodtsov Serguei , Adriano Luigi , Baranasic Bernard , Broers Carsten , Carley Robert , Gessler Patrick , Ghodrati Nahid , Hickin David , Hoang Le Phuong , Izquierdo Manuel , Mercadier Laurent , Mercurio Giuseppe , Parchenko Sergii , Stupar Marijan , Yin Zhong , Martinelli Leonardo , Merzoni Giacomo , Peng Ying Ying , Reuss Torben , Sreekantan Nair Lalithambika Sreeju , Techert Simone , Laarmann Tim , Huotari Simo , Schroeter Christian , Langer Burkhard , Giessel Tatjana , Buchheim Jana , Gwalt Grzegorz , Sokolov Andrey , Siewert Frank , Buechner Robby , Vaz da Cruz Vinicius , Eckert Sebastian , Liu Chun-Yu , Sohrt Christian , Weniger Christian , Pietzsch Annette , Neppl Stefan , Senf Friedmar , Scherz Andreas , Föhlisch Alexander
Published: December 2024

Resonant inelastic X-ray scattering (RIXS) is an ideal X-ray spectroscopy method to push the combination of energy and time resolutions to the Fourier transform ultimate limit, because it is unaffected by the core-hole lifetime energy broadening. Also, in pump–probe experiments the interaction time is made very short by the same core-hole lifetime. RIXS is very photon hungry so it takes great advantage from high-repetition-rate pulsed X-ray sources like the European XFEL. The Heisenberg RIXS instrument is designed for RIXS experiments in the soft X-ray range with energy resolution approaching the Fourier and the Heisenberg limits. It is based on a spherical grating with variable line spacing and a position-sensitive 2D detector. Initially, two gratings were installed to adequately cover the whole photon energy range. With optimized spot size on the sample and small pixel detector the energy resolution can be better than 40 meV (90 meV) at any photon energy below 1000 eV with the high-resolution (high-transmission) grating. At the SCS instrument of the European XFEL the spectrometer can be easily positioned thanks to air pads on a high-quality floor, allowing the scattering angle to be continuously adjusted over the 65–145° range. It can be coupled to two different sample interaction chambers, one for liquid jets and one for solids, each state-of-the-art equipped and compatible for optical laser pumping in collinear geometry. The measured performances, in terms of energy resolution and count rate on the detector, closely match design expectations. The Heisenberg RIXS instrument has been open to public users since the summer of 2022.
Visualization of four-dimensional X-ray absorption fine structure data using a virtual reality system
Authors: Igarashi Haruo , Kido Daiki , Ishii Yutaka , Niwa Yasuhiro , Okamoto Atsushi , Kimura Masao
Published: December 2024

X-ray spectromicroscopy is extensively utilized for nondestructive mapping of chemical states in materials. However, understanding and analyzing the geometric and topological aspects of such data pose challenges due to their representation in 4D space, encompassing (x, y, z) coordinates along with the energy (E) axis and often extending to 5D space with the inclusion of time (t) or reaction degree. In this study, we addressed this challenge by developing a new approach and introducing a device named `4D-XASView', specifically designed for visualizing X-ray absorption fine structures (XAFS) data in 4D (comprising 3D space and energy), through a multi-projection system, within the virtual reality (VR) environment. As a test case for the new system, X-ray spectromicroscopy measurements were conducted on a specimen prepared from serpentinized harzburgite sourced from the upper mantle section of the Oman ophiolite. Our 4D-XASView facilitates the visualization and analysis of the geometric and topological aspects of the data using VR goggles, enabling detailed exploration of microstructures via rotation and zooming functionalities. This capability allows us to extract XAFS spectral data by selecting specific positions and regions, thereby aiding in the identification of `trigger sites' (magnetite in serpentine), which are characteristic locations within materials that substantially influence the macroscopic propagation of reactions. Our methodology establishes a new platform for analyzing 4D or 5D XAFS data that has applicability potential in various other multidimensional datasets, including microstructures coupled with spectroscopy and diffraction data.
The venture capital lifecycle: the role of foreign venture capital in a developing startup scene in China
Authors: Jansen Hendrik J.
Published: December 2024

Purpose

This study aims to examine the venture capital (VC) industry, which is critical for supporting startups and typically dominated by individuals with startup experience. Recognizing the challenges faced by catching-up economies, this research seeks to understand the successful development of the VC industry in China, thereby addressing the classic “chicken or the egg” problem.

Design/methodology/approach

Using a comprehensive data set from the TechCrunch database, this paper conducts both descriptive and empirical analyses. Based on theoretically grounded observations, seven hypotheses are formulated and tested using multiple linear regression.

Findings

The findings indicate that foreign VC has played a significant role in establishing the VC industry in China. These foreign investors tend to lead the market and co-invest with local partners, facilitating knowledge transfer. In addition, the investment preferences of foreign VCs differ markedly from those of their local counterparts.

Research limitations/implications

This study offers valuable insights for policymakers and enhances strategy development for VC firms. It also highlights potential areas for future research, further exploring the intricacies of VC in emerging markets.

Originality/value

While considerable literature exists on the rise of startup funding in the USA and Europe, studies focusing on emerging economies are scarce. By using a comprehensive, yet underused data set, this research illuminates fundamental dynamics within the VC industry in these regions.