bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-Related Social Cognitive Performance in Individuals With Psychotic Disorders and Their First-Degree Relatives
Authors: Velthorst Eva , Socrates Adam ,   GROUP Investigators, Alizadeh Behrooz Z , van Amelsvoort Therese , Bartels-Velthuis Agna A , Bruggeman Richard , Cahn Wiepke , de Haan Lieuwe , Schirmbeck Frederike , Simons Claudia J P , van Os Jim , Fett Anne-Kathrin
Published: May 2023

Background

Social cognitive impairment is a recognized feature of psychotic disorders. However, potential age-related differences in social cognitive impairment have rarely been studied.

Study Design

Data came from 905 individuals with a psychotic disorder, 966 unaffected siblings, and 544 never-psychotic controls aged 18–55 who participated in the Genetic Risk and Outcome of Psychosis (GROUP) study. Multilevel linear models were fitted to study group main effects and the interaction between group and age on emotion perception and processing (EPP; degraded facial affect recognition) and theory of mind (ToM; hinting task) performance. Age-related differences in the association between socio-demographic and clinical factors, and EPP and ToM were also explored.

Study Results

Across groups, EPP performance was associated with age (β = −0.02, z = −7.60, 95% CI: −0.02, −0.01, P < .001), with older participants performing worse than younger ones. A significant group-by-age interaction on ToM (X2(2) = 13.15, P = .001) indicated that older patients performed better than younger ones, while no age-related difference in performance was apparent among siblings and controls. In patients, the association between negative symptoms and ToM was stronger for younger than older patients (z = 2.16, P = .03).

Conclusions

The findings point to different age-related performance patterns on tests of 2 key social cognitive domains. ToM performance was better in older individuals, although this effect was only observed for patients. EPP was less accurate in older compared with younger individuals. These findings have implications with respect to when social cognitive training should be offered to patients.
Career Compromises and Dropout from Vocational Education and Training in Germany
Authors: Beckmann Janina , Wicht Alexandra , Siembab Matthias
Published: May 2023

This study investigates the relevance of career compromises (i.e., the discrepancy between the expected and the actually attained training position) to the decision to drop out of vocational education and training (VET), focusing on compromises in terms of social status and gender type. We pay particular attention to upward and downward compromises. Using longitudinal data on 7205 apprentices from the German National Educational Panel Study (Starting Cohort 4), the results of discrete event history models show that both dimensions of compromise are crucial to the decision to drop out of a first VET position. In particular, downward gender-type discrepancies increase the probability that female apprentices will drop out. These findings draw attention to the role of pre-entry VET policies, such as career counseling, in minimizing the incidence of career compromises.
Non-invasive detection of narcolepsy type I phenotypical features and disease progression by continuous home-cage monitoring of activity in two mouse models: the HCRT-KO and DTA model
Authors: Piilgaard Louise , Rose Laura , Justinussen Jessica L , Hviid Camille Gylling , Lemcke René , Wellendorph Petrine , Kornum Birgitte Rahbek
Published: May 2023

Narcolepsy type 1 (NT1) is a neurological disorder caused by disruption of hypocretin (HCRT; or orexin) neurotransmission leading to fragmented sleep/wake states, excessive daytime sleepiness, and cataplexy (abrupt muscle atonia during wakefulness). Electroencephalography and electromyography (EEG/EMG) monitoring is the gold standard to assess NT1 phenotypical features in both humans and mice. Here, we evaluated the digital ventilated home-cage (DVC®) activity system as an alternative to detect NT1 features in two NT1 mouse models: the genetic HCRT-knockout (-KO) model, and the inducible HCRT neuron-ablation hcrt-tTA;TetO-DTA (DTA) model, including both sexes. NT1 mice exhibited an altered dark phase activity profile and increased state transitions, compared to the wild-type (WT) phenotype. An inability to sustain activity periods >40 min represented a robust activity-based NT1 biomarker. These features were observable within the first weeks of HCRT neuron degeneration in DTA mice. We also created a nest-identification algorithm to differentiate between inactivity and activity, inside and outside the nest as a sleep and wake proxy, respectively, showing significant correlations with EEG/EMG-assessed sleep/wake behavior. Lastly, we tested the sensitivity of the activity system to detect behavioral changes in response to interventions such as repeated saline injection and chocolate. Surprisingly, daily consecutive saline injections significantly reduced activity and increased nest time of HCRT-WT mice. Chocolate increased total activity in all mice, and increased the frequency of short out-of-nest inactivity episodes in HCRT-KO mice. We conclude that the DVC® system provides a useful tool for non-invasive monitoring of NT1 phenotypical features, and has the potential to monitor drug effects in NT1 mice.
miR-486-5p Attenuates Steroid-Induced Adipogenesis and Osteonecrosis of the Femoral Head Via TBX2/P21 Axis
Authors: Chen Yu , Tang Boyu , Jiang Weiqian , Sun Mingjie , Zhang Hongrui , Tao Yuzhang , Wang Hongwei , Xiang Dulei , Bai Haobo , Guo Mingkang , Zhao Pei , Yan Wenlong , Huang Xiao , Chen Tingmei , Lian Chengjie , Zhang Jian
Published: May 2023

Enhanced adipogenic differentiation of mesenchymal stem cells (MSCs) is considered as a major risk factor for steroid-induced osteonecrosis of the femoral head (SOFNH). The role of microRNAs during this process has sparked interest. miR-486-5p expression was down-regulated significantly in femoral head bone tissues of both SONFH patients and rat models. The purpose of this study was to reveal the role of miR-486-5p on MSCs adipogenesis and SONFH progression. The present study showed that miR-486-5p could significantly inhibit adipogenesis of 3T3-L1 cells by suppressing mitotic clonal expansion (MCE). And upregulated expression of P21, which was caused by miR-486-5p mediated TBX2 decrease, was responsible for inhibited MCE. Further, miR-486-5p was demonstrated to effectively inhibit steroid-induced fat formation in the femoral head and prevented SONFH progression in a rat model. Considering the potent effects of miR-486-5p on attenuating adipogenesis, it seems to be a promising target for the treatment of SONFH.
The Bite of HOPE Small Food Business Development Program: a clinic-based culinary medicine program targeting local business owners
Authors: Raber Margaret , Brozovich Joseph , Le Thuan , Brown Asyjia , Saenz Tabbie , Caracostis Andrea , Basen-Engquist Karen
Published: May 2023

Culinary medicine is a popular approach to health promotion, but most programs focus on patient or provider-facing education. While laudable, these efforts do not represent the full potential for culinary medicine to impact community health. We describe a novel approach to culinary medicine at a federally qualified health center (FQHC), the HOPE Clinic: Bite of HOPE Small Food Business Development (SFBD) program. Describe the design and implementation of the Bite of HOPE SFBD program and examine initial response to the program through interviews and focus groups with past participants. The SFBD program aims to create healthy food outlets by supporting local small businesses with education, resources, and mentorship support. Former participants in the SFBD program were invited to participate in focus groups and interviews exploring their experience and perceived program impact. Three focus groups (n = 10) and nine in-depth interviews were conducted. Most participants were Black or Hispanic and all operated their businesses in the community surrounding HOPE Clinic. Five themes emerged from the data including perceived program purpose, program discovery, motivating factors to participation, perceived program impact, and suggestions for improvement. Participants expressed high satisfaction with the program and positive changes in both business development and personal eating habits. There is an opportunity to leverage the culinary medicine model to support local small food business and improve community health. The Bite of HOPE SFBD program offers an example of how clinic-based resources can expand into the surrounding environment.
Recombination smooths the time signal disrupted by latency in within-host HIV phylogenies
Authors: Castro Lauren A , Leitner Thomas , Romero-Severson Ethan
Published: May 2023

Within-host Human immunodeficiency virus (HIV) evolution involves several features that may disrupt standard phylogenetic reconstruction. One important feature is reactivation of latently integrated provirus, which has the potential to disrupt the temporal signal, leading to variation in the branch lengths and apparent evolutionary rates in a tree. Yet, real within-host HIV phylogenies tend to show clear, ladder-like trees structured by the time of sampling. Another important feature is recombination, which violates the fundamental assumption that evolutionary history can be represented by a single bifurcating tree. Thus, recombination complicates the within-host HIV dynamic by mixing genomes and creating evolutionary loop structures that cannot be represented in a bifurcating tree. In this paper, we develop a coalescent-based simulator of within-host HIV evolution that includes latency, recombination, and effective population size dynamics that allows us to study the relationship between the true, complex genealogy of within-host HIV evolution, encoded as an ancestral recombination graph (ARG), and the observed phylogenetic tree. To compare our ARG results to the familiar phylogeny format, we calculate the expected bifurcating tree after decomposing the ARG into all unique site trees, their combined distance matrix, and the overall corresponding bifurcating tree. While latency and recombination separately disrupt the phylogenetic signal, remarkably, we find that recombination recovers the temporal signal of within-host HIV evolution caused by latency by mixing fragments of old, latent genomes into the contemporary population. In effect, recombination averages over extant heterogeneity, whether it stems from mixed time signals or population bottlenecks. Furthermore, we establish that the signals of latency and recombination can be observed in phylogenetic trees despite being an incorrect representation of the true evolutionary history. Using an approximate Bayesian computation method, we develop a set of statistical probes to tune our simulation model to nine longitudinally sampled within-host HIV phylogenies. Because ARGs are exceedingly difficult to infer from real HIV data, our simulation system allows investigating effects of latency, recombination, and population size bottlenecks by matching decomposed ARGs to real data as observed in standard phylogenies.
Mutation rate, selection, and epistasis inferred from RNA virus haplotypes via neural posterior estimation
Authors: Caspi Itamar , Meir Moran , Ben Nun Nadav , Abu Rass Reem , Yakhini Uri , Stern Adi , Ram Yoav
Published: May 2023

RNA viruses are particularly notorious for their high levels of genetic diversity, which is generated through the forces of mutation and natural selection. However, disentangling these two forces is a considerable challenge, and this may lead to widely divergent estimates of viral mutation rates, as well as difficulties in inferring the fitness effects of mutations. Here, we develop, test, and apply an approach aimed at inferring the mutation rate and key parameters that govern natural selection, from haplotype sequences covering full-length genomes of an evolving virus population. Our approach employs neural posterior estimation, a computational technique that applies simulation-based inference with neural networks to jointly infer multiple model parameters. We first tested our approach on synthetic data simulated using different mutation rates and selection parameters while accounting for sequencing errors. Reassuringly, the inferred parameter estimates were accurate and unbiased. We then applied our approach to haplotype sequencing data from a serial passaging experiment with the MS2 bacteriophage, a virus that parasites Escherichia coli. We estimated that the mutation rate of this phage is around 0.2 mutations per genome per replication cycle (95% highest density interval: 0.051–0.56). We validated this finding with two different approaches based on single-locus models that gave similar estimates but with much broader posterior distributions. Furthermore, we found evidence for reciprocal sign epistasis between four strongly beneficial mutations that all reside in an RNA stem loop that controls the expression of the viral lysis protein, responsible for lysing host cells and viral egress. We surmise that there is a fine balance between over- and underexpression of lysis that leads to this pattern of epistasis. To recap, we have developed an approach for joint inference of the mutation rate and selection parameters from full haplotype data with sequencing errors and used it to reveal features governing MS2 evolution.
Computational infrared and Raman spectra by hybrid QM/MM techniques: a study on molecular and catalytic material systems
Authors: Guan Jingcheng , Lu You , Sen Kakali , Abdul Nasir Jamal , Desmoutier Alec W. , Hou Qing , Zhang Xingfan , Logsdail Andrew J. , Dutta Gargi , Beale Andrew M. , Strange Richard W. , Yong Chin , Sherwood Paul , Senn Hans M. , Catlow C. Richard A. , Keal Thomas W. , Sokol Alexey A.
Published: May 2023

Vibrational spectroscopy is one of the most well-established and important techniques for characterizing chemical systems. To aid the interpretation of experimental infrared and Raman spectra, we report on recent theoretical developments in the ChemShell computational chemistry environment for modelling vibrational signatures. The hybrid quantum mechanical and molecular mechanical approach is employed, using density functional theory for the electronic structure calculations and classical forcefields for the environment. Computational vibrational intensities at chemical active sites are reported using electrostatic and fully polarizable embedding environments to achieve more realistic vibrational signatures for materials and molecular systems, including solvated molecules, proteins, zeolites and metal oxide surfaces, providing useful insight into the effect of the chemical environment on the signatures obtained from experiment. This work has been enabled by the efficient task-farming parallelism implemented in ChemShell for high-performance computing platforms. 

This article is part of a discussion meeting issue ‘Supercomputing simulations of advanced materials’.
Exact distributed kinetic Monte Carlo simulations for on-lattice chemical kinetics: lessons learnt from medium- and large-scale benchmarks
Authors: Savva Giannis D. , Benson Raz L. , Christidi Ilektra-Athanasia , Stamatakis Michail
Published: May 2023

Kinetic Monte Carlo (KMC) simulations have been instrumental in multiscale catalysis studies, enabling the elucidation of the complex dynamics of heterogeneous catalysts and the prediction of macroscopic performance metrics, such as activity and selectivity. However, the accessible length- and time-scales have been a limiting factor in such simulations. For instance, handling lattices containing millions of sites with ‘traditional’ sequential KMC implementations is prohibitive owing to large memory requirements and long simulation times. We have recently established an approach for exact, distributed, lattice-based simulations of catalytic kinetics which couples the Time-Warp algorithm with the Graph-Theoretical KMC framework, enabling the handling of complex adsorbate lateral interactions and reaction events within large lattices. In this work, we develop a lattice-based variant of the Brusselator system, a prototype chemical oscillator pioneered by Prigogine and Lefever in the late 60s, to benchmark and demonstrate our approach. This system can form spiral wave patterns, which would be computationally intractable with sequential KMC, while our distributed KMC approach can simulate such patterns 15 and 36 times faster with 625 and 1600 processors, respectively. The medium- and large-scale benchmarks thus conducted, demonstrate the robustness of the approach, and reveal computational bottlenecks that could be targeted in further development efforts.

This article is part of a discussion meeting issue ‘Supercomputing simulations of advanced materials’.
Challenges in modelling dynamic processes in realistic nanostructured materials at operating conditions
Authors: Van Speybroeck Veronique
Published: May 2023

The question is addressed in how far current modelling strategies are capable of modelling dynamic phenomena in realistic nanostructured materials at operating conditions. Nanostructured materials used in applications are far from perfect; they possess a broad range of heterogeneities in space and time extending over several orders of magnitude. Spatial heterogeneities from the subnanometre to the micrometre scale in crystal particles with a finite size and specific morphology, impact the material's dynamics. Furthermore, the material's functional behaviour is largely determined by the operating conditions. Currently, there exists a huge length–time scale gap between attainable theoretical length–time scales and experimentally relevant scales. Within this perspective, three key challenges are highlighted within the molecular modelling chain to bridge this length–time scale gap. Methods are needed that enable (i) building structural models for realistic crystal particles having mesoscale dimensions with isolated defects, correlated nanoregions, mesoporosity, internal and external surfaces; (ii) the evaluation of interatomic forces with quantum mechanical accuracy albeit at much lower computational cost than the currently used density functional theory methods and (iii) derivation of the kinetics of phenomena taking place in a multi-length–time scale window to obtain an overall view of the dynamics of the process.

This article is part of a discussion meeting issue ‘Supercomputing simulations of advanced materials’.
Analysing ill-conditioned Markov chains
Authors: Woods Esmae J. , Kannan Deepti , Sharpe Daniel J. , Swinburne Thomas D. , Wales David J.
Published: May 2023

Discrete state Markov chains in discrete or continuous time are widely used to model phenomena in the social, physical and life sciences. In many cases, the model can feature a large state space, with extreme differences between the fastest and slowest transition timescales. Analysis of such ill-conditioned models is often intractable with finite precision linear algebra techniques. In this contribution, we propose a solution to this problem, namely partial graph transformation, to iteratively eliminate and renormalize states, producing a low-rank Markov chain from an ill-conditioned initial model. We show that the error induced by this procedure can be minimized by retaining both the renormalized nodes that represent metastable superbasins, and those through which reactive pathways concentrate, i.e. the dividing surface in the discrete state space. This procedure typically returns a much lower rank model, where trajectories can be efficiently generated with kinetic path sampling. We apply this approach to an ill-conditioned Markov chain for a model multi-community system, measuring the accuracy by direct comparison with trajectories and transition statistics.

This article is part of a discussion meeting issue ‘Supercomputing simulations of advanced materials’.
Structure prediction in low dimensions: concepts, issues and examples
Authors: Schön J. Christian
Published: May 2023

Structure prediction of stable and metastable polymorphs of chemical systems in low dimensions has become an important field, since materials that are patterned on the nano-scale are of increasing importance in modern technological applications. While many techniques for the prediction of crystalline structures in three dimensions or of small clusters of atoms have been developed over the past three decades, dealing with low-dimensional systems—ideal one-dimensional and two-dimensional systems, quasi-one-dimensional and quasi-two-dimensional systems, as well as low-dimensional composite systems—poses its own challenges that need to be addressed when developing a systematic methodology for the determination of low-dimensional polymorphs that are suitable for practical applications. Quite generally, the search algorithms that had been developed for three-dimensional systems need to be adjusted when being applied to low-dimensional systems with their own specific constraints; in particular, the embedding of the (quasi-)one-dimensional/two-dimensional system in three dimensions and the influence of stabilizing substrates need to be taken into account, both on a technical and a conceptual level.

This article is part of a discussion meeting issue ‘Supercomputing simulations of advanced materials’.
Buckletronics: how compression-induced buckling affects the mechanical and electronic properties of sp
2
-based two-dimensional materials
Authors: Lopez-Suarez Miquel , Lleopart Genis , Morales-Salvador Raul , Moreira Ibério de P. R. , Bromley Stefan T.
Published: May 2023

We explore the mechanical and electronic response of sp
2
-based two-dimensional materials under in-plane compression employing first principles density functional theory-based calculations. Taking two carbon-based graphynes (α-graphyne and γ-graphyne) as example systems, we show that the structures of both two-dimensional materials are susceptible to out-of-plane buckling, which emerges for modest in-plane biaxial compression (1.5–2%). Out-of-plane buckling is found to be more energetically stable than in-plane scaling/distortion and significantly lowers the in-plane stiffness of both graphenes. The buckling also gives rise to in-plane auxetic behaviour in both two-dimensional materials. Under compression, the induced in-plane distortions and out-of-plane buckling also lead to modulations of the electronic band gap. Our work highlights the possibility of using in-plane compression to induce out-of-plane buckling in, otherwise planar, sp
2
-based two-dimensional materials (e.g. graphynes, graphdiynes). We suggest that controllable compression-induced buckling in planar two-dimensional materials (as opposed to two-dimensional materials, which are buckled due to sp
3
hybridization) could provide a route to a new ‘buckletronics’ approach for tuning the mechanical and electronic properties of sp
2
-based systems.

This article is part of a discussion meeting issue ‘Supercomputing simulations of advanced materials’.
Solubility-consistent force field simulations for aqueous metal carbonate systems using graphical processing units
Authors: Armstrong Blake , Silvestri Alessandro , Demichelis Raffaella , Raiteri Paolo , Gale Julian D.
Published: May 2023

Crystallization of alkaline earth metal carbonates from water is important for biomineralization and environmental geochemistry. Here, large-scale computer simulations are a useful approach to complement experimental studies by providing atomistic insights and even by quantitatively determining the thermodynamics of individual steps. However, this is dependent on the existence of force field models that are sufficiently accurate while being computationally efficient enough to sample complex systems. Here, we introduce a revised force field for aqueous alkaline earth metal carbonates that reproduces both the solubilities of the crystalline anhydrous minerals, as well as the hydration free energies of the ions. The model is also designed to run efficiently on graphical processing units thereby reducing the cost of such simulations. The performance of the revised force field is compared against previous results for important properties relevant to crystallization, including ion-pairing and mineral–water interfacial structure and dynamics.

This article is part of a discussion meeting issue ‘Supercomputing simulations of advanced materials’.
Review: understanding the properties of amorphous materials with high-performance computing methods
Authors: Christie J. K.
Published: May 2023

Amorphous materials have no long-range order in their atomic structure. This makes much of the formalism for the study of crystalline materials irrelevant, and so elucidating their structure and properties is challenging. The use of computational methods is a powerful complement to experimental studies, and in this paper we review the use of high-performance computing methods in the simulation of amorphous materials. Five case studies are presented to showcase the wide range of materials and computational methods available to practitioners in this field.

This article is part of a discussion meeting issue ‘Supercomputing simulations of advanced materials’.
The structural and functional modularity of ovarian follicle epithelium in the pill-millipedeHyleoglomeris japonica(Myriapoda: Diplopoda: Pentazonia: Glomerida) and the morphological reconsideration of somatic tissues around oocytes in Myriapoda
Authors: Chikami Yasuhiko , Yahata Kensuke
Published: May 2023

Ovarian somatic tissues around oocytes are essential for oogenesis in many metazoans. The functional ovarian somatic tissues sometimes have structural properties specific to their roles. In contrast, there is no evidence of such structural modularity of the follicle epithelium in Myriapoda, suggesting that myriapod ovarian soma may not participate in oogenesis. The ultrastructural nature of follicle cells also supports solitary oogenesis in most myriapods investigated. In contrast, here, we report two structurally and developmentally distinct domains of the follicle epithelium in the Japanese pill millipede,Hyleoglomeris japonica. The follicle epithelium ofH. japonicahas a thick cell mass on the apex of the follicle. These thick cells contain the rich rough endoplasmic reticulum, mitochondria, and Goldi bodies and possess many microvilli, indicating synthetic/secretory activities, and become thicker along with the oogenetic progress. Another region of epithelium does not exhibit these features. These results show the structural and functional modularity specific to some functions of the follicle epithelium ofH. japonica. Therefore, the follicle epithelium of Myriapoda is divided into 3 types: physiologically functional uniformly, nonfunctional only, and those with both. We suggest the need to reconsider the nature and roles of ovarian somatic tissues of Myriapoda and Arthropoda.
Establishment of hairy root culture and its genetic transformation ofStephania tetrandraS. Moore for production of BIAs
Authors: Zhang Xiuhua , Bu Junling , Zhao Yujun , Li Qishuang , Li Xinyi , Ma Ying , Tang Jinfu , Wang Jian , Lai Changjiangsheng , Cui Guanghong , Guo Juan , Huang Luqi
Published: May 2023

Metabolic engineering improvement of plants will play an essential role in future agriculture, but this largely depends on the establishment of genetic transformation.Stephania tetrandraS. Moore is a traditional Chinese medicine used for rheumatalgia that accumulates benzylisoquinoline alkaloids as its main active ingredients. Wild or farmed plants have remained the main source of these essential medicines, resulting in supply pressure due to the scarcity of wild plant resources and the slow growth rate in cultivation. Here, we constructedAgrobacterium rhizogenes(C58C1)-mediated hairy root culture and a co-transformation system inS. tetrandrato obtain a new source of bisbenzylisoquinoline alkaloids production. We show that the biomass of the hairy roots increased by 10-fold, and the content of tetrandrine reached 8.382 ± 0.160 mg/g DW after 50 days of cultivation. In addition, overexpression of (R, S)-norcoclaurine 6-O-methyltransferase (6OMT) gene or treatment of hairy roots with methyl jasmonate (MJ) increased protoberberine alkaloid content. This work provides a method of obtaining hairy roots and a genetic transformation system forS. tetrandra, not only broadening the access toS. tetrandraresources, but also laying a foundation for further elucidation of the biosynthesis of tetrandrine and related alkaloids.
On-farm hatching and contact with adult hen post hatch induce sex-dependent effects on performance, health and robustness in broiler chickens
Authors: Guilloteau L. A. , Bertin A. , Crochet S. , Bagnard C. , Hondelatte A. , Ravon L. , Schouler C. , Germain K. , Collin A.
Published: May 2023

To improve the early perinatal conditions of broiler chicks, alternative hatching systems have been developed. On-farm hatching (OFH) with an enriched microbial and stimulating environment by the presence of an adult hen is a promising solution. Day-old chicks were allotted within five hatching and rearing conditions: OFH, conventional hatchery (CH), CH and post-hatching treatment with antibiotics (CH + AB), as well as both hatching systems with an adult hen at hatching (OFH + H, CH + H). To challenge the robustness of chickens, they were exposed on D27 to suboptimal rearing conditions by combining for 4 h transport in boxes in a new room at a lower temperature and fasting. On their return to the original room, the chicken density was increased, and birds were orally vaccinated with the Gumboro vaccine. The impacts of these conditions on hatchability, chick quality score, performance, health and robustness were determined. The OFH chick body weights (BWs) were significantly greater than those of CH chicks at hatching. Whereas there was no effect of hatching conditions, the presence of hens decreased the hatchability rate, the quality score of OFH chicks and increased mortality at hatching. Treatment of CH chicks with antibiotics (CH + AB) temporarily decreased chicken BW at D19, but the feed conversion ratio (FCR) was not modified. At D19, OFH chicks had the highest BW compared to the other groups, and the presence of hens at hatching harmed chicken BW regardless of the hatching condition and FCR. An interaction between the effect of experimental rearing conditions and chicken sex was observed later for BW. In males, the OFH chickens were the heaviest compared to the other groups at D34 but not at D56. The presence of hens negatively impacted CH chicken BW at D56. In females, there was no effect of hatching condition on the BWs at D34 and D56, and the presence of hens had a positive impact on OFH chicken BW. There was no effect of hatching conditions on health parameters. In conclusion, the OFH system was a hatching system at least equivalent to the CH system. The presence of the hen at hatching and during the chick start-up phase on performance interacted with the hatching condition and the sex of the chickens.
Enhancing anti-gastrointestinal cancer activities of CLDN18.2 CAR-T armored with novel synthetic NKG2D receptors Containing DAP10 and DAP12 signaling domains
Authors: Sun Minmin , Wang Hongye , Hao Ruidong , Wang Youtao , Li Yantao , Zhong Yunpeng , Zhang Shuangshuang , Zhai Bo , Cheng Yuanguo
Published: May 2023

Chimeric antigen receptor (CAR) T therapies have shown remarkable efficacy in hematopoietic malignancies, but their therapeutic benefits in solid tumors have been limited due to heterogeneities in both antigen types and their expression levels on tumor cells. NK group 2 member D ligands (NKG2DLs) are extensively expressed on various tumors and absent on normal tissues, making them a promising target for cellular immunotherapy. DAP10 and DAP12 function as adaptor proteins in NK cells to transduce activating signals, and recent studies have revealed DAP10 and DAP12’s additional role as a co-stimulatory signal in T cells. Our pre-clinical data showed that CAR-T targeting CLDN18.2 is highly effective in gastrointestinal (GI) cancers, but the heterogeneous expression of CLDN18.2 poses a treatment challenge. To complement this antigen deficiency, we demonstrated that NKG2DLs were extensively expressed in GI tumor tissues and formed an ideal dual target. Here, we reported a CLDN18.2 CAR design armored with synthetic NKG2D receptors (SNR) containing DAP10 and DAP12 signaling domains. This novel CAR-T showed improved cytotoxicity against tumor cells with heterogeneous expression of CLDN18.2. The possible underlined mechanism is that SNR promotes CAR-T memory formation and reduces their exhaustion, while also enhancing their expansion and ability to infiltrate immune-excluded tumors in vivo. Taken together, SNR with DAP10/12 signaling and their synergistic involvement, increased CAR-T function and overcame the antigen deficiency, providing a novel treatment modality for solid GI tumor.
Pig herd management and infection transmission dynamics: a challenge for modellers
Authors: Sicard Vianney , Picault Sébastien , Andraud Mathieu
Published: May 2023

The control of epidemics requires a thorough understanding of the complex interactions between pathogen transmission, disease impact, and population dynamics and management. Mechanistic epidemiological modelling is an effective way to address this issue, but handling highly structured and dynamic systems, remains challenging. We therefore developed a novel approach that combines Multi-Level Agent-Based Systems (MLABS) with spatial and temporal organization, allowing for a tuned representation of the transmission processes amongst the host population. We applied this method to model the spread of a PRRSv-like virus in pig farms, integrating the clinical consequences (conception and reproduction failures), in terms of animal husbandry practices. Results highlighted the importance to account for spatial and temporal structuring and herd management policies in epidemiological models. Indeed, disease-related abortions, inducing reassignments of sows in different batches, was shown to enhance the transmission process, favouring the persistence of the virus at the herd level. Supported by a declarative Domain-Specific Language (DSL), our approach provides flexible and powerful solutions to address the issues of on-farm epidemics and broader public health concerns. The present application, based on a simple Susceptible-Exposed-Infected-Recovered (SEIR) model, opens the way to the representation of more complex epidemiological systems, including more specific features such as maternally derived antibodies, vaccination, or dual infections, along with their respective clinical consequences on the management practices.
Ecological factors shaping the ectoparasite community assembly of the Azara’s Grass Mouse,Akodon azarae(Rodentia: Cricetidae)
Authors: Carolina Colombo Valeria , Marcela Lareschi , Daniel Monje Lucas , Raúl Antoniazzi Leandro , Serge Morand , Martín Beldomenico Pablo
Published: May 2023

Parasites are integral members of the global biodiversity. They are useful indicators of environmental stress, food web structure and diversity. Ectoparasites have the potential to transmit vector-borne diseases of public health and veterinary importance and to play an important role in the regulation and evolution of host populations. The interlinkages between hosts, parasites and the environment are complex and challenging to study, leading to controversial results. Most previous studies have been focused on one or two parasite groups, while host are often co-infected by different taxa. The present study aims to assess the influence of environmental and host traits on the entire ectoparasite community composition of the rodent Akodon azarae. A total of 278 rodents were examined and mites (Mesostigmata), lice (Phthiraptera), ticks (Ixodida) and fleas (Siphonaptera) were determined. A Multi Correspondence Analyses was performed in order to analyse interactions within the ectoparasite community and the influence of environmental and host variables on this assembly. We found that environmental variables have a stronger influence on the composition of the ectoparasite community of A. azarae than the host variables analysed. Minimum temperature was the most influential variable among the studied. In addition, we found evidence of agonistic and antagonistic interactions between ticks and mites, lice and fleas. The present study supports the hypothesis that minimum temperature play a major role in the dynamics that shape the ectoparasite community of A. azarae, probably through both direct and indirect processes. This finding becomes particularly relevant in a climate change scenario.
iDeLUCS: A deep learning interactive tool for alignment-free clustering of DNA sequences
Authors: Arias Pablo Millán , Hill Kathleen A. , Kari Lila
Published: May 2023

We present aninteractiveDeep Learning-based software tool for Unsupervised Clustering of DNA Sequences (iDeLUCS), that detects genomic signatures and uses them to cluster DNA sequences, without the need for sequence alignment or taxonomic identifiers.iDeLUCS is scalable and user-friendly: Its graphical user interface, with support for hardware acceleration, allows the practitioner to fine-tune the different hyper-parameters involved in the training process without requiring extensive knowledge of deep learning. The performance ofiDeLUCS was evaluated on a diverse set of datasets: several real genomic datasets from organisms in kingdoms Animalia, Protista, Fungi, Bacteria, and Archaea, three datasets of viral genomes, a dataset of simulated metagenomic reads from microbial genomes, and multiple datasets of synthetic DNA sequences. The performance ofiDeLUCS was compared to that of two classical clustering algorithms (k-means++ and GMM) and two clustering algorithms specialized in DNA sequences (MeShClust v3.0 and DeLUCS), using both intrinsic cluster evaluation metrics and external evaluation metrics. In terms of unsupervised clustering accuracy,iDeLUCS outperforms the two classical algorithms by an average of ∼ 20%, and the two specialized algorithms by an average of ∼ 12%, on the datasets of real DNA sequences analyzed. Overall, our results indicate thatiDeLUCS is a robust clustering method suitable for the clustering of large and diverse datasets of unlabelled DNA sequences.

Availability and implementation

iDeLUCS is available at our github repository under the terms of the MIT licence.

Contact

pmillana@uwaterloo.ca

Supplementary information

Supplementary data are available atBioinformaticsonline.
Adversarial training improves model interpretability in single-cell RNA-seq analysis
Authors: Sadria Mehrshad , Layton Anita , Bader Gary D.
Published: May 2023

For predictive computational models to be considered reliable in crucial areas such as biology and medicine, it is essential for them to be accurate, robust, and interpretable. A sufficiently robust model should not have its output affected significantly by a slight change in the input. Also, these models should be able to explain how a decision is made. Efforts have been made to improve the robustness and interpretability of these models as independent challenges, however, the effect of robustness and interpretability on each other is poorly understood. Here, we show that predicting cell type based on single-cell RNA-seq data is more robust by adversarially training a deep learning model. Surprisingly, we find this also leads to improved model interpretability, as measured by identifying genes important for classification. We believe that adversarial training will be generally useful to improve deep learning robustness and interpretability, thereby facilitating biological discovery.
Model Agnostic Semi-Supervised Meta-Learning Elucidates Understudied Out-of-distribution Molecular Interactions
Authors: Wu You , Xie Li , Liu Yang , Xie Lei
Published: May 2023

Many biological problems are understudied due to experimental limitations and human biases. Although deep learning is promising in accelerating scientific discovery, its power compromises when applied to problems with scarcely labeled data and data distribution shifts. We developed a semi-supervised meta learning framework Meta Model Agnostic Pseudo Label Learning (MMAPLE) to address these challenges by effectively exploring out-of-distribution (OOD) unlabeled data when transfer learning fails. The power of MMAPLE is demonstrated in multiple applications: predicting OOD drug-target interactions, hidden human metabolite-enzyme interactions, and understudied interspecies microbiome metabolite-human receptor interactions, where chemicals or proteins in unseen data are dramatically different from those in training data. MMAPLE achieves 11% to 242% improvement in the prediction-recall on multiple OOD benchmarks over baseline models. Using MMAPLE, we reveal novel interspecies metaboliteprotein interactions that are validated by bioactivity assays and fill in missing links in microbiome-human interactions. MMAPLE is a general framework to explore previously unrecognized biological domains beyond the reach of present experimental and computational techniques.
Noisy delay denoises biochemical oscillators
Authors: Song Yun Min , Campbell Sean , Shiau LieJune , Kim Jae Kyoung , Ott William
Published: May 2023

Genetic oscillations are generated by delayed transcriptional negative feedback loops, wherein repressor proteins inhibit their own synthesis after a temporal production delay. This delay is distributed because it arises from a sequence of noisy processes, including transcription, translation, folding, and translocation. Because the delay determines repression timing and therefore oscillation period, it has been commonly believed that delay noise weakens oscillatory dynamics. Here, we demonstrate that noisy delay can surprisingly denoise genetic oscillators. Moderate delay noise unexpectedly sharpens oscillation peaks and improves temporal peak reliability without impacting period. We show that this denoising phenomenon occurs in a variety of well-studied genetic oscillators and we use queueing theory to uncover the universal mechanisms that produce it.
Polyene-based colouration preserved in 12 million-year-old gastropod shells
Authors: Wolkenstein Klaus , Schmidt Burkhard C. , Harzhauser Mathias
Published: May 2023

Polyene pigments represent a major class of pigments in present-day organisms. Their occurrence in fossils has been frequently discussed, but to date no spectroscopic evidence was found. Here, we usein situRaman microspectroscopy to examine the chemistry of exceptionally well-preserved gastropod shells with colour preservation from the Middle Miocene of the Vienna Basin (Austria, Hungary). Raman signals indicative for the presence of intact, i.e. non-hydrogenated polyene pigments were obtained from the fossil gastropods, thus revealing the first record of intact polyenes in fossils. The observed Raman values are in good agreement with those of unmethylated (non-carotenoid) polyenes. Fossil polyene pigments were detected in representatives of the superfamily Cerithioidea, but not in representatives of other gastropod families with colour preservation found at the same localities. Our results show that Raman spectroscopy represents a valuable tool for the non-destructive screening of rare fossils with colour preservation for the occurrence of polyene pigments.
Electrical stimulation of the dorsal motor nucleus of the vagus regulates inflammation without affecting the heart rate
Authors: Falvey Aidan , Palandira Santhoshi P. , Chavan Sangeeta S. , Brines Michael , Tracey Kevin J. , Pavlov Valentin A.
Published: May 2023

Background

The vagus nerve plays an important role in neuroimmune interactions and in the regulation of inflammation. A major source of efferent vagus nerve fibers that contribute to the regulation of inflammation is the brainstem dorsal motor nucleus of the vagus (DMN) as recently shown using optogenetics. In contrast to optogenetics, electrical neuromodulation has broad therapeutic implications, but the anti-inflammatory efficacy of electrical DMN stimulation (eDMNS) was not previously investigated. Here, we examined the effects of eDMNS on heart rate (HR) and cytokine levels in murine endotoxemia as well as the cecal ligation and puncture (CLP) model of sepsis.

Methods

Anesthetized male 8–10-week-old C57BL/6 mice on a stereotaxic frame were subjected to eDMNS using a concentric bipolar electrode inserted into the left or right DMN or sham stimulation. eDMNS (50, 250 or 500 μA and 30 Hz, for 1 min) was performed and HR recorded. In endotoxemia experiments, sham or eDMNS utilizing 250 μA or 50 μA was performed for 5 mins and was followed by LPS (0.5 mg/kg) i.p. administration. eDMNS was also applied in mice with cervical unilateral vagotomy or sham operation. In CLP experiments sham or left eDMNS was performed immediately post CLP. Cytokines and corticosterone were analyzed 90 mins after LPS administration or 24h after CLP. CLP survival was monitored for 14 days.

Results

Either left or right eDMNS at 250 μA and 500 μA decreased HR, compared with pre- and post-stimulation. This effect was not observed at 50 μA. Left side eDMNS at 50 μA, compared with sham stimulation, significantly decreased serum and splenic levels of the pro-inflammatory cytokine TNF and increased serum levels of the anti-inflammatory cytokine IL-10 during endotoxemia. The anti-inflammatory effect of eDMNS was abrogated in mice with unilateral vagotomy and were not associated with serum corticosterone alterations. Right side eDMNS suppressed serum TNF levels but had no effects on serum IL-10 and on splenic cytokines. In mice with CLP, left side eDMNS suppressed serum TNF and IL-6, as well as splenic IL-6 and increased splenic IL-10 and significantly improved the survival rate of CLP mice.

Conclusions

For the first time we show that a regimen of eDMNS which does not cause bradycardia alleviates LPS-induced inflammation and these effects require an intact vagus nerve and are not associated with corticosteroid alterations. eDMNS also decreases inflammation and improves survival in a model of polymicrobial sepsis. These findings are of interest for further studies exploring bioelectronic anti-inflammatory approaches targeting the brainstem DMN.
In silicoidentification of switching nodes in metabolic networks
Authors: Mairet Francis
Published: May 2023

Abstract

Cells modulate their metabolism according to environmental conditions. A major challenge to better understand metabolic regulation is to identify, from the hundreds or thousands of molecules, the key metabolites where the re-orientation of fluxes occurs. Here, a method called ISIS (forIn SilicoIdentification of Switches) is proposed to locate these nodes in a metabolic network, based on the analysis of a set of flux vectors (obtained e.g. by parsimonious flux balance analysis with different inputs). A metabolite is considered as a switch if the fluxes at this point are redirected in a different way when conditions change. The soundness of ISIS is shown with four case studies, using both core and genome-scale metabolic networks ofEscherichia coli, Saccharomyces cerevisiaeand the diatomPhaeodactylum tricornutum. Through these examples, we show that ISIS can identify hot-spots where fluxes are reoriented. Additionally, switch metabolites are deeply involved in post-translational modification of proteins, showing their importance in cellular regulation. InP. tricornutum, we show that Erythrose 4-phosphate is an important switch metabolite for mixotrophy suggesting the importance of this metabolite in the non-oxidative pentose phosphate pathway to orchestrate the flux variations between glycolysis, the Calvin cycle and the oxidative pentose phosphate pathway when the trophic mode changes. Finally, a comparison between ISIS and reporter metabolites identified with transcriptomic data confirms the key role of metabolites such as L-glutamate or L-aspartate in the yeast response to nitrogen input variation. Overall, ISIS opens up new possibilities for studying cellular metabolism and regulation, as well as potentially for developing metabolic engineering.