bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental pathways underlying sexual differentiation in a U/V sex chromosome system
Authors: Liesner Daniel , Cossard Guillaume , Zheng Min , Godfroy Olivier , Barrera-Redondo Josué , Haas Fabian B. , Coelho Susana M.
Published: February 2024

In many multicellular organisms, sexual development is not determined by XX/XY or ZW/ZZ systems but by U/V sex chromosomes. In U/V systems, sex determination occurs in the haploid phase, with U chromosomes in females and V chromosomes in males. Here, we explore several male, female and partially sex-reversed male lines of giant kelp to decipher how U/V sex chromosomes and autosomes initiate male versus female development. We identify a key set of genes on the sex chromosomes involved in triggering sexual development, and characterise autosomal effector genes underlying sexual differentiation. We show that male, but not female, development involves large-scale transcriptome reorganisation with pervasive enrichment in regulatory genes, faster evolutionary rates, and high species specificity of male-biased genes. Our observations imply that a female-like phenotype is the “ground state”, which is complemented by the presence of a U-chromosome, but overridden by a dominant male developmental program in the presence of a V-chromosome.
Serum proteomic profiling of physical activity reveals CD300LG as a novel exerkine with a potential causal link to glucose homeostasis
Authors: Lee-Ødegård Sindre , Hjorth Marit , Olsen Thomas , Moen Gunn-Helen , Daubney Emily , Evans David M , Hevener Andrea , Lusis Aldons Jake , Zhou Mingqi , Seldin Marcus Michael , Allayee Hooman , Hilser James R. , Viken Jonas Krag , Gulseth Hanne L. , Norheim Frode , Drevon Christian A. , Birkeland Kåre I.
Published: February 2024

Background

Physical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding of the precise molecular mechanisms underlying these effects remains incomplete and good biomarkers to objectively assess physical activity are lacking.

Methods

We analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks of a combined strength and endurance exercise intervention. We estimated insulin sensitivity with hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, and used MRI/MRS to evaluate body composition and organ fat depots. Muscle and subcutaneous adipose tissue biopsies were used for mRNA sequencing. Additional association analyses were performed in samples from up to 47,747 individuals in the UK Biobank, as well as using 2-sample Mendelian randomization and mice models.

Results

Following 12 weeks of exercise intervention, we observed significant changes in 283 serum proteins. Notably, 66 of these proteins were elevated in overweight men and positively associated with liver fat before the exercise regimen, but were normalized after exercise. Furthermore, for 19.7% and 12.1% of the exercise-responsive proteins, corresponding changes in mRNA expression levels in muscle and fat, respectively, were shown. The protein CD300LG displayed consistent alterations in blood, muscle, and fat. Serum CD300LG exhibited positive associations with insulin sensitivity, and to angiogenesis-related gene expression in both muscle and fat. Furthermore, serum CD300LG was positively associated with physical activity and negatively associated with glucose levels in the UK Biobank. In this sample, the association between serum CD300LG and physical activity was significantly stronger in men than in women. Mendelian randomization analysis suggested potential causal relationships between levels of serum CD300LG and fasting glucose, 2-hour glucose after an oral glucose tolerance test, and HbA1c. Additionally, Cd300lg responded to exercise in a mouse model, and we observed signs of impaired glucose tolerance in male, but not female,Cd300lgknockout mice.

Conclusion

Our study identified several novel proteins in serum whose levels change in response to prolonged exercise and were significantly associated with body composition, liver fat, and glucose homeostasis. Serum CD300LG increased with physical activity and is a potential causal link to improved glucose levels. CD300LG may be a promising exercise biomarker and a therapeutic target in type 2 diabetes.
Predator cues and environmental enrichment during development drive intraspecific variation in the behaviour and life history of juvenile lobsters
Authors: Polverino Giovanni , Latini Lorenzo , Nascetti Giuseppe , Grignani Giacomo , Bello Eleonora , Gili Claudia , Carere Claudio , Canestrelli Daniele
Published: February 2024

Intraspecific variation in ecologically relevant traits is critical for animal populations to survive in our rapidly changing world. This is especially true for species that suffer from intense harvesting regimes, whereby populations density is often low. Standard hatchery procedures can assist some management and conservation programs by producing large numbers of juveniles to be released into the wild. Yet we know surprisingly little on the impact that such standard, minimalistic settings have on the development of intraspecific variation in important phenotypes of the individuals, including among-individual variation in behavioural (individuality) and life-history traits, and in the plasticity of those traits in response to varying environmental conditions. Here, we fill this gap by testing whether early-life exposure to different environmental conditions alters the development of individuality and plasticity in ecologically relevant behaviours and life-history traits of the European lobster (Homarus gammarus)—one the most harvested species in the Mediterranean, which has been subjected to conservation programs for decades. By accessing one of the largest lobsters hatcheries in Italy, we used the progeny of wild-caught females and manipulated—in a full factorial design—the environmental complexity of the individual enclosures (i.e. presence/absence of substrate and/or shelter) and the level of exposure to cues from their natural predators. We repeatedly quantified behaviours (i.e. activity, refuge use, and aggressiveness) and life-history traits (i.e. carapace length and intermoult period) of the individuals throughout their early development, capturing both mean and individual-level variation across treatments. Our results offer solid evidence that effects of standard hatchery settings extend far beyond mean changes in the behaviour and life history of the animals, compromising the development of individual plasticity in those traits that are essentials for populations to survive in the wild—likely reducing the effectiveness of conservation programs.
Causal mediation analysis for time-varying heritable risk factors with Mendelian Randomization
Authors: Wu Zixuan , Lewis Ethan , Zhao Qingyuan , Wang Jingshu
Published: February 2024

Understanding the causal pathogenic mechanisms of diseases is crucial in clinical research. When randomized controlled experiments are not available, Mendelian Randomization (MR) offers an alternative, leveraging genetic mutations as a natural “experiment” to mitigate environmental confoundings. However, most MR analyses treat the risk factors as static variables, potentially oversimplifying dynamic risk factor effects. The framework of life-course MR has been introduced to address this issue. However, current methods face challenges especially when the age-specific GWAS datasets have limited cohort sizes and there are substantial correlations between time points for a single trait. This study proposes a novel approach, estimating a unified system of structural equations for a sequence of temporally ordered heritable traits, requiring only GWAS summary statistics. The method facilitates statistical inference on direct, indirect, and path-wise causal effects and demonstrates superior efficiency and reliability, particularly with noisy GWAS data. By incorporating a spike-and-slab prior for genetic effects, the approach can address extreme polygenicity and weak instrument bias. Through this methodology, we uncovered a protective effect of BMI on breast cancer during a confined period of childhood development. We also analyzed how BMI, systolic blood pressure (SBP), and low-density cholesterol levels influence stroke risk across childhood and adulthood, and identified the intriguing relationships between these risk factors.
Impaired ovarian development in a zebrafishfmr1knockout model
Authors: Rani Rita , Sri N Sushma , Medishetti Raghavender , Chatti Kiranam , Sevilimedu Aarti
Published: February 2024

Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder and the leading genetic cause of autism spectrum disorders. FXS is caused by loss of function mutations in Fragile X mental retardation protein (FMRP), an RNA binding protein that is known to regulate translation of its target mRNAs, predominantly in the brain and gonads. The molecular mechanisms connecting FMRP function to neurodevelopmental phenotypes are well understood. However, neither the full extent of reproductive phenotypes, nor the underlying molecular mechanisms have been as yet determined. Here, we developed newfmr1knockout zebrafish lines and show that they mimic key aspects of FXS neuronal phenotypes across both larval and adult stages. Results from thefmr1knockout females also showed that altered gene expression in the brain, via the neuroendocrine pathway contribute to distinct abnormal phenotypes during ovarian development and oocyte maturation. We identified at least three mechanisms underpinning these defects, including altered neuroendocrine signaling in sexually mature females resulting in accelerated ovarian development, altered expression of germ cell and meiosis promoting genes at various stages during oocyte maturation, and finally a strong mitochondrial impairment in late stage oocytes from knockout females. Our findings have implications beyond FXS in the study of reproductive function and female infertility. Dissection of the translation control pathways during ovarian development using models like the knockout lines reported here may reveal novel approaches and targets for fertility treatments.

Abstract Figure

Graphical Abstract
Tropical and montaneA.ceranashow distinct dance-distance calibration curves
Authors: Bharath Kumar A. K , George Ebi Antony , Brockmann Axel
Published: February 2024

Social bees have evolved sophisticated communication systems to recruit nestmates to newly found food sources. As foraging ranges can vary from a few hundred meters to several kilometers depending on the environment or season, populations living in different climate zones likely show specific adaptations in their recruitment communication. Accordingly, studies in the western honey bee,Apis mellifera, demonstrated that temperate populations exhibit shallower dance-calibration curves compared to tropical populations. Here we report the first comparison of calibration curves for three IndianA. ceranalineages: the tropicalA. indica, and the two montane Himalayan populationsA. c. cerana(Himachal Pradesh) andA. c. kashmirensis(Jammu and Kashmir). We found that the colonies of the two montaneA. ceranapopulations show dance-distance calibration curves with significantly shallower slopes than the tropicalA. indica. Next, we transferredA. c. ceranacolonies to Bangalore (∼ 2600 km away) to obtain calibration curves in the same location asA. indica. The common garden experiment confirmed this difference in slopes, implying that the lineages exhibit genetically fixed differences in dance-distance coding. However, the slopes of the calibration curves of the transferredA. c. ceranacolonies were also significantly higher than those tested in Himachal Pradesh indicating an important effect of the environment. The differences in dance-distance coding between temperate and tropicalA. ceranalineages resemble those described forA. melliferasuggesting that populations of both species independently evolved similar adaptations.
Serotonin deficiency from constitutive SKN-1 activation drives pathogen apathy
Authors: Nair Tripti , Weathers Brandy A. , Stuhr Nicole L. , Nhan James D. , Curran Sean P.
Published: February 2024

When an organism encounters a pathogen, the host innate immune system activates to defend against pathogen colonization and toxic xenobiotics produced.C. elegansemploy multiple defense systems to ensure survival when exposed toPseudomonas aeruginosaincluding activation of the cytoprotective transcription factor SKN-1/NRF2. Although wildtypeC. elegansquickly learn to avoid pathogens, here we describe a peculiar apathy-like behavior towards PA14 in animals with constitutive activation of SKN-1, whereby animals choose not to leave and continue to feed on the pathogen even when a non-pathogenic and healthspan-promoting food option is available. Although lacking the urgency to escape the infectious environment, animals with constitutive SKN-1 activity are not oblivious to the presence of the pathogen and display the typical pathogen-induced intestinal distension and eventual demise. SKN-1 activation, specifically in neurons and intestinal tissues, orchestrates a unique transcriptional program which leads to defects in serotonin signaling that is required from both neurons and non-neuronal tissues. Serotonin depletion from SKN-1 activation limits pathogen defense capacity, drives the pathogen-associated apathy behaviors and induces a synthetic sensitivity to selective serotonin reuptake inhibitors. Taken together, our work reveals new insights into how animals perceive environmental pathogens and subsequently alter behavior and cellular programs to promote survival.

KEY POINTS

Identify an apathy-like behavioral response for pathogens resulting from the constitutive activation of the cytoprotective transcription factor SKN-1.

Uncover the obligate role for serotonin synthesis in both neuronal and non-neuronal cells for the apathy-like state and ability of serotonin treatment to restore normal behaviors.

Characterize the timing and tissue specificity of SKN-1 nuclear localization in neurons and intestinal cells in response to pathogen exposure.

Define the unique and context-specific transcriptional signatures of animals with constitutive SKN-1 activation when exposed to pathogenic environments.

Reveal necessity for both neuronal and non-neuronal serotonin signaling in host survival from pathogen infection.
Cellpose3: one-click image restoration for improved cellular segmentation
Authors: Stringer Carsen , Pachitariu Marius
Published: February 2024

Generalist methods for cellular segmentation have good out-of-the-box performance on a variety of image types. However, existing methods struggle for images that are degraded by noise, blurred or undersampled, all of which are common in microscopy. We focused the development of Cellpose3 on addressing these cases, and here we demonstrate substantial out-of-the-box gains in segmentation and image quality for noisy, blurry or undersampled images. Unlike previous approaches, which train models to restore pixel values, we trained Cellpose3 to output images that are well-segmented by a generalist segmentation model, while maintaining perceptual similarity to the target images. Furthermore, we trained the restoration models on a large, varied collection of datasets, thus ensuring good generalization to user images. We provide these tools as “one-click” buttons inside the graphical interface of Cellpose as well as in the Cellpose API.
Nuclear receptor interdomain communication is mediated by the hinge with ligand specificity
Authors: Hazarika Saurov , Yu Tracy , Biswas Arumay D , Dube Namita , Villalona Priscilla , Okafor C. Denise
Published: February 2024

Nuclear receptors are ligand-induced transcription factors that bind directly to target genes and regulate their expression. Ligand binding initiates conformational changes that propagate to other domains, allosterically regulating their activity. The nature of this interdomain communication in nuclear receptors is poorly understood, largely owing to the difficulty of experimentally characterizing full-length structures. We have applied computational modeling approaches to describe and study the structure of the full length farnesoid X receptor (FXR), approximated by the DNA binding domain (DBD) and ligand binding domain (LBD) connected by the flexible hinge region. Using extended molecular dynamics simulations (> 10 microseconds) and enhanced sampling simulations, we provide evidence that ligands selectively induce domain rearrangement, leading to interdomain contact. We use protein-protein interaction assays to provide experimental evidence of these interactions, identifying a critical role of the hinge in mediating interdomain contact. Our results illuminate previously unknown aspects of interdomain communication in FXR and provide a framework to enable characterization of other full length nuclear receptors.
Substrate recognition principles for the PP2A-B55 protein phosphatase
Authors: Kruse Thomas , Garvanska Dimitriya H. , Varga Julia , Garland William , McEwan Brennan , Hein Jamin B. , Weisser Melanie Bianca , Puy Iker Benavides , Chan Camilla Bachman , Parrila Paula Sotelo , Mendez Blanca Lopez , Arulanandam Jeyaprakash , Schueler-Furman Ora , Jensen Torben Heick , Kettenbach Arminja , Nilsson Jakob
Published: February 2024

The PP2A-B55 phosphatase regulates a plethora of signaling pathways throughout eukaryotes. How PP2A-B55 selects its substrates presents a severe knowledge gap. By integrating AlphaFold modelling with comprehensive high resolution mutational scanning, we show that α-helices in substrates bind B55 through an evolutionary conserved mechanism. Despite a large diversity in sequence and composition, these α-helices share key amino acid determinants that engage discrete hydrophobic and electrostatic patches. Using deep learning protein design, we generate a specific and potent competitive peptide inhibitor of PP2A-B55 substrate interactions. With this inhibitor, we uncover that PP2A-B55 regulates the nuclear exosome targeting complex by binding to an α-helical recruitment module in RBM7. Collectively, our findings provide a framework for the understanding and interrogation of PP2A-B55 in health and disease.

One sentence summary

α-helices in PP2A-B55 substrates bind a conserved pocket on B55 through a common mechanism that is conserved in eukaryotes.
Pushing the limits: expanding the temperature tolerance of a coral photosymbiont through differing selection regimes
Authors: Scharfenstein Hugo J. , Peplow Lesa M. , Alvarez-Roa Carlos , Nitschke Matthew R. , Chan Wing Yan , Buerger Patrick , van Oppen Madeleine JH
Published: February 2024

Coral thermal bleaching resilience can be improved by enhancing photosymbiont thermal tolerance via experimental evolution. While successful for some strains, selection under stable temperatures was ineffective at increasing the thermal threshold of an already thermo-tolerant photosymbiont (Durusdinium trenchii). Corals from environments with fluctuating temperatures tend to have comparatively high heat tolerance. Therefore, we investigated whether exposure to temperature oscillations can raise the upper thermal limit ofD. trenchii. We exposed aD. trenchiistrain to stable and fluctuating temperatures profiles, which varied in oscillation frequency. After 2.1 years (54-73 generations), we characterised the adaptive responses under the various experimental evolution treatments by constructing thermal performance curves of growth from 21 to 31°C for the heat-evolved and wild-types lineages. Additionally, oxidative stress, photophysiology, photosynthesis and respiration rates were assessed under increasing temperatures. Of the fluctuating temperature profiles investigated, selection under the most frequent oscillations (diurnal) induced the greatest widening ofD. trenchii’s thermal niche. Continuous selection under elevated temperatures induced the only increase in thermal optimum and a degree of generalism. Our findings demonstrate how differing levels of thermal homogeneity during selection drive unique adaptative responses to heat in a coral photosymbiont.
Sarbecovirus RBD indels and specific residues dictating ACE2 multi-species adaptiveness
Authors: Si Junyu , Chen Yuanmei , Gu Mengxue , Sun Yehui , Huang Meiling , Shi Lulu , Yu Xiao , Yang Xiao , Xiong Qing , Ma Chenbao , Liu Peng , Shi Zheng-Li , Yan Huan
Published: February 2024

Sarbecoviruses exhibit varying abilities in using angiotensin-converting enzyme 2 (ACE2) receptor1–3. However, a comprehensive understanding of their multi-species ACE2 adaptiveness and the underlying mechanism remains elusive, particularly for many sarbecoviruses with various receptor binding motif (RBM) insertions/deletions (indels)4–11. Here, we analyzed RBM sequences from 268 sarbecoviruses categorized into four RBM indel types. We extensively examined the capability of 14 representative sarbecoviruses and their derivatives in using ACE2 orthologues from 51 bats and five non-bat mammals. We revealed that most sarbecoviruses with longer RBMs (type-I), present broad ACE2 tropism, whereas viruses with single deletions in Region 1 (type-II) or Region 2 (type-III) generally exhibit narrow ACE2 tropism, typically favoring their hosts’ ACE2. Sarbecoviruses with double region deletions (type-IV) exhibit a complete loss of ACE2 usage. Subsequent investigations unveiled that both loop deletions and critical RBM residues significantly impact multi-species ACE2 tropism in different ways. Additionally, fine mapping based on type-IV sarbecoviruses elucidated the role of several clade-specific residues, both within and outside the RBM, in restricting ACE2 usage. Lastly, we hypothesized the evolution of sarbecovirus RBM indels and illustrated how loop length, disulfide, and adaptive mutations shape their multi-species ACE2 adaptiveness. This study provides profound insights into the mechanisms governing ACE2 usage and spillover risks of sarbecoviruses.
Acrylate reductase of an anaerobic electron transport chain of the marine bacteriumShewanella woodyi
Authors: Bertsova Yulia V. , Serebryakova Marina V. , Bogachev Vladimir A. , Baykov Alexander A. , Bogachev Alexander V.
Published: February 2024

Many microorganisms are capable of anaerobic respiration in the absence of oxygen, by using different organic compounds as terminal acceptors in electron transport chain. We identify here an anaerobic respiratory chain protein responsible for acrylate reduction in the marine bacteriumShewanella woodyi. When the periplasmic proteins ofS. woodyiwere separated by ion exchange chromatography, acrylate reductase activity copurified with an ArdA protein (Swoo_0275). Heterologous expression ofS. woodyi ardA gene (swoo_0275) inShewanella oneidensisMR-1 cells did not result in the appearance in them of periplasmic acrylate reductase activity, but such activity was detected when theardA gene was co-expressed with anardB gene (swoo_0276). Together, these genes encode flavocytochromecArdAB, which is thus responsible for acrylate reduction inS. woodyicells. ArdAB was highly specific for acrylate as substrate and reduced only methacrylate (at a 22-fold lower rate) among a series of other tested 2-enoates. In line with these findings, acrylate and methacrylate inducedardA gene expression inS. woodyiunder anaerobic conditions, which was accompanied by the appearance of periplasmic acrylate reductase activity. ArdAB-linked acrylate reduction supports dimethylsulfoniopropionate-dependent anaerobic respiration inS. woodyiand, possibly, other marine bacteria.
Electrophysiological Effects Of Kappa-Opioid Analgesic, RU-1205, Using Machine Learning Methods
Authors: Kalitin Konstantin Y. , Mukha Olga Y. , Spasov Alexander A.
Published: February 2024

This study focuses on RU-1205, a new kappa-opioid agonist exhibiting analgesic effect without causing dysphoric or aversive reactions. It is assumed that the absence of dysphoric or aversive effects can be attributed to functional selectivity or it might be due to an additional mechanism of action that involves blocking the p38 mitogen-activated protein kinase (MAPK).

The aim

of this study was the experimental identification of the mechanisms of action of RU-1205 associated with inhibition of MAPK p38 and functional selectivity at kappa-opioid receptors.

Materials and methods

Rats weighing 260-280 g were implanted with chronic cortical and deep electrodes. LFP activity was recorded after intracerebroventricular administration of well-studied reference substances: the selective kappa-opioid agonist U-50488 at a dose of 100 μg; the MAPK p38 blocker SB203580 at a dose of 1 μg; and the investigational compound RU-1205 at 350 μg. The weighted phase lag index (WPLI) was calculated. Subsequently, machine learning techniques were employed to reduce dimensionality and extract connectivity features using the principal component analysis method. Finally, signal classification was conducted using models based on Gaussian processes.

By applying the patch-clamp technique in the whole-cell configuration, the spike activity of pyramidal neurons in the basolateral amygdala was studied. The neurons were identified by their accommodation properties. After local perfusion of the test compounds, 3 dose-response curves were obtained for: (1) U-50488 at concentrations ranging from 0.001 to 10 μM; (2) combinations of U-50488 (0.001–10 μM) and RU-1205 (10 μM); and (3) combinations of U-50488 (0.01–10 μM) and RU-1205 (100 μM).

Results

The developed models were able to classify the compound RU-1205 as a «non-inhibitor» of MAPK p38 with a probability of 0.89. The results obtained were confirmed in patch clamp experiments on acute brain slices, where it was demonstrated that U-50488 statistically significantly increases the spike activity of pyramidal neurons in the basolateral amygdala (p <0.05) and RU-1205 interacts with U-50488, suppressing its effect on the spike activity of neurons.

Conclusions

The findings suggest that compound RU-1205 displays properties consistent with a functional kappa opioid receptor agonist and does not have a significant effect on MAPK p38. The study demonstrates the possibility of integrating electrophysiological measurements and advanced data analysis methods for a deep understanding of neuronal mechanisms of drug action and underscores the potential for further research in this area.
NRP1-expressing monocyte/macrophages promote arteriogenesis in the ischemic limb
Authors: Cho JS , Patel AS , Fantin A , Ludwinski FE , Pichette CJ , Rudnicki M. , Denti L , Mondragon A , Saha P , Smith A , Ruhrberg C , Modarai B
Published: February 2024

Peripheral arterial disease can cause limb threatening blood flow restriction, requiring amputation in up to a third of patients despite contemporary treatments. Stimulating new blood vessel growth in ischemic limbs using growth factors such as VEGF-A or supplying mixed cell populations via autologous transplantation has been investigated as a therapy for surgically intractable cases, but to date has proven ineffective in randomised controlled clinical studies. To identify more potent pro-arteriogenic cell populations, we have investigated VEGF-A responsive myeloid cell populations in a mouse model of severe hindlimb ischemia. We found that NRP1 ablation from monocytes and macrophages impaired arteriogenesis in the adductor muscle and flow recovery in the injured limb. Vice versa, the exogenous delivery of NRP1-expressing (but not NRP1-negative) macrophages enhanced arteriogenesis in the adductor and flow recovery in the ischemic limb in a VEGF signalling-dependent manner. Further, patient-derived NRP1-expressing monocytes promoted vascular morphogenesis ex vivo. As the levels of circulating NRP1-expressing monocytes were raised in patients with limb ischemia, the therapeutic delivery of autologous NRP1-expressing monocytes could be explored as a treatment for critical limb ischemia.
How to validate a Bayesian evolutionary model
Authors: Mendes Fábio K. , Bouckaert Remco , Carvalho Luiz M. , Drummond Alexei J.
Published: February 2024

Biology has become a highly mathematical discipline in which probabilistic models play a central role. As a result, research in the biological sciences is now dependent on computational tools capable of carrying out complex analyses. These tools must be validated before they can be used, but what is understood as validation varies widely among methodological contributions. This may be a consequence of the still embryonic stage of the literature on statistical software validation for computational biology. Our manuscript aims to advance this literature. Here, we describe and illustrate good practices for assessing the correctness of a model implementation, with an emphasis on Bayesian methods. We also introduce a suite of functionalities for automating validation protocols. It is our hope that the guidelines presented here help sharpen the focus of discussions on (as well as elevate) expected standards of statistical software for biology.
A latent pool of neurons silenced by sensory-evoked inhibition can be recruited to enhance perception
Authors: Gauld Oliver M. , Packer Adam M. , Russell Lloyd E. , Dalgleish Henry W.P. , Iuga Maya , Sacadura Francisco , Roth Arnd , Clark Beverley A. , Häusser Michael
Published: February 2024

Which patterns of neural activity in sensory cortex are relevant for perceptual decision-making? To address this question, we used simultaneous two-photon calcium imaging and targeted two-photon optogenetics to probe barrel cortex activity during a perceptual discrimination task. Head-fixed mice discriminated bilateral whisker deflections and reported decisions by licking left or right. Two-photon calcium imaging revealed sparse coding of contralateral and ipsilateral whisker input in layer 2/3 while most neurons did not show task-related activity. Activating small groups of pyramidal neurons using two-photon holographic photostimulation evoked a perceptual bias that scaled with the number of neurons photostimulated. This effect was dominated by the optogenetic activation of a small number of non-coding neurons, which did not show sensory or motor-related activity during task performance. Patterned photostimulation also revealed potent recruitment of cortical inhibition during sensory processing, which strongly and preferentially suppressed non-coding neurons. Our results provide a novel perspective on the circuit basis for the sparse coding model of somatosensory processing in which a pool of non-coding neurons, selectively suppressed by strong network inhibition during whisker stimulation, can be recruited to enhance perception.

Highlights

All-optical interrogation of barrel cortex during bilateral whisker discrimination

Sparse coding of contralateral and ipsilateral whisker information

Selective sensory-evoked inhibition helps ensure sparse coding

Optogenetic recruitment of stimulus non-coding neurons can aid perception
Zapit: Open Source Random-Access Photostimulation For Neuroscience
Authors: Lohse Michael , Gauld Oliver M , Skrętowska Maja T , Vincent Peter , Pajot-Moric Quentin , Townsend Simon , Duan Chunyu A , Akrami Athena , Mrsic-Flogel Thomas D , Campbell Robert AA
Published: February 2024

Optogenetic tools are indispensable for understanding the causal neural mechanisms underlying animal behaviour. While optogenetic actuators provide millisecond-precision control over genetically defined neural populations, successful optogenetic experiments also critically depend on associated hardware for targeted light delivery. Optic-fibres are suitable for certain experiments, however fibre implantation can be invasive and limits flexibility of spatial targeting. In contrast, random-access laser-scanning optogenetic systems provide far greater flexibility for targeting distributed cortical areas. However, these systems can be technically challenging to build, and at present no open source solution is available.

Here we present ‘Zapit’, a complete open source platform for spatio-temporally precise random-access laser-scanning optogenetic experiments in head-fixed mice. We describe the system, quantify its performance, and show results from proof of principle cortical photoinhibition experiments in behaving mice.
Amelioration of signalling deficits underlying metabolic shortfall in TREM2R47Hhuman iPSC-derived microglia
Authors: Vasilopoulou Foteini , Piers Thomas M. , Jingzhang Wei , Hardy John , Pocock Jennifer M.
Published: February 2024

Classic immunometabolic switching from oxidative phosphorylation (OXPHOS) to glycolysis occurs in myeloid cells such as microglia when encountering pathogenic insults. We previously showed that patient iPSC-derived microglia (iPS-Mg) harbouring the Alzheimer’s disease (AD) TREM2R47Hhypomorph display deficits in the ability to metabolically switch from OXPHOS to glycolysis, with both reduced mitochondrial maximal respiration and glycolytic capacity. To resolve this, we generated common variant, TREM2R47Hand TREM2−/−variant human iPS-Mg and we assessed the ability of supplementation with citrate or succinate, key metabolites and cell cycle breaking points upon microglia activation, to overcome deficits in a number of functions we identified previously as affected by TREM2 loss of function phenotypes. Succinate supplementation was more effective than citrate at overcoming mitochondrial deficits in OXPHOS and did not promote a switch to glycolysis. Citrate enhanced the lipid content of TREM2R47HiPS-Mg and was more effective at overcoming phagocytic deficits whereas succinate increased lipid content and phagocytic capacity in TREM2−/−iPS-Mg. Microglia cytokine release upon activation was differentially affected by citrate or succinate and neither metabolite altered soluble TREM2 shedding. Neither citrate nor succinate enhanced glycolysis but drove their effects through oxidative phosphorylation. Our data point to discrete pathway linkage between microglial metabolism and functional outcomes with implications for AD pathogenesis and treatments.
Polarization-modulation-based orientation metrology of optically levitated rotating birefringent particles
Authors: Zeng Kai , Wu Yulie , Wu Xuezhong , Xiao Dingbang
Published: February 2024

The ultrafast rotation of optically levitated particles has propelled advancements in sensing and precision measurement, while its orientation remains largely unexplored for the spherical shape. Here, we proposed an orientation measurement method for the birefringent rotating particles, which extracts both the azimuthal and polar angles of the optical axis from the polarization of the transmitted laser. A bulk birefringent crystal with a known orientation is measured by this method to verify its effectiveness, and then the orientation of vaterite particles is extracted from the rotational signal. This method paves the way to investigate the orientational dynamics and gyroscope application.

Published by the American Physical Society
2024
Laser-Induced Electron Diffraction in Chiral Molecules
Authors: Rajak Debobrata , Beauvarlet Sandra , Kneller Omer , Comby Antoine , Cireasa Raluca , Descamps Dominique , Fabre Baptiste , Gorfinkiel Jimena D. , Higuet Julien , Petit Stéphane , Rozen Shaked , Ruf Hartmut , Thiré Nicolas , Blanchet Valérie , Dudovich Nirit , Pons Bernard , Mairesse Yann
Published: February 2024

Strong laser pulses enable probing molecules with their own electrons. The oscillating electric field tears electrons off a molecule, accelerates them, and drives them back toward their parent ion within a few femtoseconds. The electrons are then diffracted by the molecular potential, encoding its structure and dynamics with angstrom and attosecond resolutions. Using elliptically polarized laser pulses, we show that laser-induced electron diffraction is sensitive to the chirality of the target. The field selectively ionizes molecules of a given orientation and drives the electrons along different sets of trajectories, leading them to recollide from different directions. Depending on the handedness of the molecule, the electrons are preferentially diffracted forward or backward along the light propagation axis. This asymmetry, reaching several percent, can be reversed for electrons recolliding from two ends of the molecule. The chiral sensitivity of laser-induced electron diffraction opens a new path to resolve ultrafast chiral dynamics.

Published by the American Physical Society
2024
Integrated Photonics for Quantum Communications and Metrology
Authors: Labonté Laurent , Alibart Olivier , D’Auria Virginia , Doutre Florent , Etesse Jean , Sauder Gregory , Martin Anthony , Picholle Éric , Tanzilli Sébastien
Published: February 2024

Over the last two decades, integrated photonics has profoundly revolutionized the domain of quantum technologies. The ongoing second quantum revolution stands as a timely opportunity for a state-of-the-art review and, most important, an exploration of the directions undertaken by integrated quantum photonics. Within this perspective, based on the recent advances, we discuss the current challenges and future trends related to different technological platforms. Key examples will be considered across various subfields, including quantum communication, quantum metrology, and quantum memories. Our discussion encompasses disruptive concepts, progress, and potential limitations. The main objective of this Perspective is to provide the reader with a forward-looking discussion ranging from state-of-the-art developments to open challenges of the field.

Published by the American Physical Society
2024
Leave or stay? Factors influencing consumers’ purchase intention during the transformation of a content anchor to a live stream anchor
Authors: Cao Cong , Chu Chengxiang , Ding Xinyi , Shi Yangyan
Published: February 2024

Purpose

As live streaming becomes a widely used online sales mode, previously content-centred anchors are attempting to switch to e-commerce live streaming. The purpose of this research was to explore the mechanisms that prompt consumers to stay or leave after content anchors transfer to live e-commerce broadcasts. In addition, we explored the factors affecting consumption from the perspectives of anchors, consumers and the external environment.

Design/methodology/approach

We distributed questionnaires to a group of fans who had experienced the transition of content anchors to live streaming and received back 375 valid questionnaires. Using psychological contract theory, we constructed a theoretical model for the scenario in which content anchors transition to live e-commerce broadcasting and analysed the data using partial least squares structural equation modelling (PLS-SEM).

Findings

The results show that circle culture, mainstream culture, initial trust and live streaming content all positively influenced consumers’ attitudes, whilst consumers’ past shopping experiences negatively influenced consumers’ attitudes. The personal charm of the content anchors did not have a significant effect on consumers’ attitudes. Additionally, we found that only anchors with a significant circle culture and good trust levels amongst fans were able to transition to live e-commerce streaming successfully.

Originality/value

This study extends the application of psychological contract theory to the field of e-commerce and describes the transformation of different types of psychological contracts. The paper’s conclusions provide a reference for decision-making and the implementation of transformation by content-based anchors to live streaming, helping them to coordinate their relationships with fans more effectively.
An optimization model for just-in-time (JIT) delivery of precast components considering 3D loading constraints, real-time road conditions and assembly time
Authors: Mao Wenqi , Ran Kexin , Wang Ting-Kwei , Yu Anyuan , Lv Hongyue , Chen Jieh-Haur
Published: February 2024

Purpose

Although extensive research has been conducted on precast production, irregular component loading constraints have received little attention, resulting in limitations for transportation cost optimization. Traditional irregular component loading methods are based on past performance, which frequently wastes vehicle space. Additionally, real-time road conditions, precast component assembly times, and delivery vehicle waiting times due to equipment constraints at the construction site affect transportation time and overall transportation costs. Therefore, this paper aims to provide an optimization model for Just-In-Time (JIT) delivery of precast components considering 3D loading constraints, real-time road conditions and assembly time.

Design/methodology/approach

In order to propose a JIT (just-in-time) delivery optimization model, the effects of the sizes of irregular precast components, the assembly time, and the loading methods are considered in the 3D loading constraint model. In addition, for JIT delivery, incorporating real-time road conditions in the transportation process is essential to mitigate delays in the delivery of precast components. The 3D precast component loading problem is solved by using a hybrid genetic algorithm which mixes the genetic algorithm and the simulated annealing algorithm.

Findings

A real case study was used to validate the JIT delivery optimization model. The results indicated this study contributes to the optimization of strategies for loading irregular precast components and the reduction of transportation costs by 5.38%.

Originality/value

This study establishes a JIT delivery optimization model with the aim of reducing transportation costs by considering 3D loading constraints, real-time road conditions and assembly time. The irregular precast component is simplified into 3D bounding box and loaded with three-space division heuristic packing algorithm. In addition, the hybrid algorithm mixing the genetic algorithm and the simulated annealing algorithm is to solve the 3D container loading problem, which provides both global search capability and the ability to perform local searching. The JIT delivery optimization model can provide decision-makers with a more comprehensive and economical strategy for loading and transporting irregular precast components.
Developing a sense of belonging among ethnic minority youth in Hong Kong: challenges and opportunities
Authors: Hue Ming Tak , Karim Shahid
Published: February 2024

Purpose

Developing a sense of belonging among immigrant youth in multicultural contexts has attracted significant attention from scholars during the last few decades. Studies have already underscored how various educational factors hinder or facilitate students’ sense of belonging to the school or the larger society. Although most students in Hong Kong schools are ethnic Chinese, a significant number of non-Chinese children make students diversity an essential aspect of schooling. The study investigated how schools can develop a sense of belonging among ethnic minority youth in Hong Kong.

Design/methodology/approach

As the education system in Hong Kong lacks a multicultural education policy, how can schools help develop a sense of belonging to the school and the larger society among young ethnic minority people? To answer this question, this paper consolidates the two sets of data originally gathered for two research projects. The data was collected through semi-structured in-depth interviews with nine secondary school teachers (Chinese and non-Chinese) and 15 students (non-Chinese) and analysed thematically.

Findings

The thematic analysis of the qualitative data identified several challenges and opportunities for developing ethnic minority students’ sense of belonging in Hong Kong.

Research limitations/implications

Researchers in comparative education can further explore how multicultural education and inclusive education approach together can help ensure inclusive and equitable quality education for all and cater to students' diverse learning needs across the education systems.

Practical implications

Given that the aims of multicultural education and inclusive education resonate with each other, schools can focus on the Whole School Approach to developing a sense of belonging among ethnic minority youth in Hong Kong. However, policymakers and practitioners may need to adopt a multifaceted perspective on inclusive education that strives to ensure equitable quality education for all.

Originality/value

The study contributes to the existing body of scholarship on multicultural education and inclusive education. The study findings underscore the importance of an interdisciplinary research framework in education and advocate an integrative approach to supporting students with diverse learning needs in multicultural contexts.
Unleashing the power of organizational social capital: exploring the mediating role of social entrepreneurship orientation in social enterprises' performances
Authors: Loukopoulos Argyrios , Papadimitriou Dimitra , Glaveli Niki
Published: February 2024

Purpose

This study investigates the influence of organizational social capital (OSC) on the social and economic performance of social enterprises (SEs) in Greece and the mediating role of social entrepreneurship orientation (SEO) in these relationships.

Design/methodology/approach

A theoretical framework was developed integrating resource-based theory, OSC theory and behavioral entrepreneurship theory. The data were collected from 345 Greek SEs and structural equation modeling (SEM) with bootstrap analysis was employed to estimate path coefficients.

Findings

This study shows that OSC positively impacts SEs’ social and economic performance, while SEO mediates only the relationship between OSC and SEs’ social performance. This research offers insights for scholars, practitioners and policymakers in social entrepreneurship by highlighting the significance of OSC and SEO.

Originality/value

This study contributes to the literature on SEs by integrating resource-based theory, OSC theory and behavioral entrepreneurship theory, presenting a novel comprehensive theoretical framework for understanding SEs’ performances. Additionally, the study advances the understanding of SEO as a mediator in the relationship between OSC and SEs’ social and economic performance. The unique focus on the Greek context provides a valuable setting for examining the relationships among OSC, SEO and SEs’ performances.
Research on tourists' travel intention and usage of VR technologies based on SOR model: mediating role of personal values
Authors: Jiang Chunyu , Phoong Seuk Wai
Published: February 2024

Purpose

This study investigated the travel intentions (TIs) of Chinese travelers and their utilization of virtual tourism technology during the Zero COVID-19 policy period by using a stimulus-organism-response (SOR) model. The study specifically examines the interplay between knowledge of policy, perception of risk, TI, usage of virtual tourism technology (UVTT) and the mediating role of personal values.

Design/methodology/approach

The data were collected from 333 Chinese travelers through an online questionnaire, and structural equation modeling (SEM) was employed to test the proposed hypotheses.

Findings

The study suggests that knowledge of policy and risk perception increase changes in personal values (PVs), which, in turn, affect Chinese travelers' TIs and the UVTT, with PVs playing a mediating role. Risk perception has a positive effect on the UVTT.

Practical implications

This study highlights the positive impact of tourism policy knowledge and risk awareness on individual values as a stimulus. Stakeholders need to implement industry-specific policies that are in line with scientific developments. Tourism managers should prioritize understanding the psychological reactions of tourists in crises and provide support to mitigate negative emotions. Anticipating changes in PVs is crucial, as instability affects tourists' behavior. The findings of the study also provide valuable insights for technology designers and underscore the substitutability of virtual technologies in improving the tourism experience.

Originality/value

This study is the first to examine the mediating role of PVs in the relationship between knowledge of policy, tourism risk perception (TRP), TI and the UVTT based on the SOR model. The insights gained from this analysis can assist policymakers and tourism managers in understanding the psychological changes of tourists, thereby facilitating the development of appropriate tourism planning.