bluuebunny/crossref_metadata_2025 huggingface dataset:
Charting the molecular landscape of neuronal organisation within the hippocampus using cryo electron tomography
Authors: Glynn Calina , Smith Jake L.R. , Case Matthew , Csöndör Rebecca , Katsini Ana , Sanita Maria E. , Glen Thomas S. , Pennington Avery , Grange Michael
Published: October 2024

Cellular cryo-electron tomography (cryoET) enables the capture of detailed structural information within a biologically relevant environment. However, information in more complex samples, such as tissues, is lacking. Importantly, these observations need to be set in context of populations; imaging on the molecular scale to-date is limited to few observationsin-situthat struggle to be generalised. This is due to limitations in throughput and versatility employed by current instrumentation. Here, we utilise plasma focused ion beam milling to examine the molecular landscape of mouse hippocampus by cryoET in targeted regions across multiple individuals revealing the complex organisation of macromolecules from the CA1 strata pyramidale (sp) to radiatum (sr). Our data represent a molecular atlas, producing snapshots of hippocampal architecture in adult mouse. The combination of instrumentation and application of technical advancements provides a framework to explore specific structural questions within native tissues in a targeted manner.
Deficient Memory, Long-Term Potentiation and Hippocampal Synaptic Plasticity in Galectin-4-KO Mice
Authors: Brocca María Elvira , Mora-Rubio Arancha , Alonso-Calviño Elena , Fernández-López Elena , Díez-Revuelta Natalia , Guirado Juan C. , Álvarez-Vélez Rebeca , Dopazo Ana , López-Merino Esperanza , Martos-Puñal David , Esteban José A. , Aguilar Juan , Higuero Alonso M. , Abad-Rodríguez José
Published: October 2024

Intestinal infections trigger inflammation and can contribute to degenerative and cognitive brain pathologies through the microbiota-gut-brain axis. Galectin-4 is an intestinal lectin key in the control of pathogenic bacterial infections. Here we report that galectin-4 deficient mice (Lgals4-KO) show an altered intestinal commensal microbiota in the absence of pathogens, defining a new role of galectin-4 in the modulation of commensal bacteria. Strikingly, Lgals4-KO mice present a deficient memory formation, and impaired hippocampal long-term potentiation (LTP)in vivoandex vivo. Furthermore, Lgals4-KO neurons show a reduced activation of the AMPA receptor and of the CaMKII upon chemically induced LTPin vitro. These mice also display significantly lower dendritic spine density and shorter spine length in hippocampal dendrites, as well as an increased area of the postsynaptic densities, all coherent with an alteration of the synaptic function. In all, our results demonstrate that the absence of galectin-4 induces synaptic dysfunctions and memory impairment, along with changes in gut microbial composition, suggesting that variations in endogenous intestinal microbiota may cause or contribute to such neurological pathologies.
Cardiolipin Inhibits the Noncanonical Inflammasome by Preventing LPS Binding to Caspase 4/11 to Mitigate Endotoxemia in Vivo
Authors: Pizzuto Malvina , Monteleone Mercedes , Burgener Sabrina Sofia , Began Jakub , Kurera Melan , Chia Jing Rong , Frampton Emmanuelle , Crawford Joanna , Oliveira Monalisa , Kenney Kirsten M. , Coombs Jared R. , Yamamoto Masahiro , Man Si Ming , Broz Petr , Pelegrin Pablo , Schroder Kate
Published: October 2024

In Gram-negative bacterial sepsis, excessive caspase 4/11 activation in response to circulating bacterial lipid LPS (endotoxemia) can cause organ damage and mortality. Current inhibitors of caspase 4/11 also block caspase 1 activity and are therefore not appealing clinical candidates for treating Gram-negative sepsis. Here, we identify double-unsaturated 18:2 cardiolipin as a selective inhibitor of caspase 4/11-dependent inflammatory cytokine secretion and pyroptosis, without affecting caspase-1 responses. Cardiolipin targets the CARD domain of caspase 4/11, impeding its interaction with LPS to restrain caspase 4/11 activation, thereby suppressing endotoxemia-induced systemic inflammationin vivo. Thus, we present cardiolipin as a promising candidate for preventing endotoxemia- induced sequelae in sepsis while preserving caspase-1-driven anti-microbial immune responses. By identifying cardiolipin as a specific caspase 4/11 inhibitor, we provide an urgently-needed tool for studying caspase 4/11 functions in inflammatory pathways, and open the way to studies of noncanonical inflammasome regulation by endogenous cardiolipin.
Diverse ancestries reveal complex symbiotic interactions during eukaryogenesis
Authors: Bernabeu Moisès , Manzano-Morales Saioa , Marcet-Houben Marina , Gabaldón Toni
Published: October 2024

The origin of eukaryotes remains a central enigma in biology. Ongoing debates agree on the pivotal role of a symbiosis between an alpha-proteobacterium and an Asgard archaeon. However, the involvement of other bacterial partners as significant donors of genetic material, or the role of interactions with viruses remain contentious. To address these questions, we employed advanced phylogenomic approaches and comprehensive datasets spanning the known diversity of cellular life and viruses. Our analysis provided an updated reconstruction of the last eukaryotic common ancestor (LECA) proteome, in which we traced the phylogenetic origin of each protein family. We found compelling evidence for multiple waves of horizontal gene transfer from diverse bacterial and viral donors, with some likely preceding the mitochondrial endosymbiosis. We inferred the proteomes of the potential major donors and their functional contributions to LECA. Our findings underscore the contribution of horizontal gene transfers in shaping the proteomes of pre-LECA ancestors and hint to a facilitating role of Nucleocytoviricota viruses. Altogether, our results suggest ancient eukaryotes originated within complex microbial ecosystems through a succession of symbiotic interactions that left a footprint of horizontally transferred genes.
Annual Variability in Diffuse Ratio and Spectral Characteristics of Solar Radiation: Cloud Effects in a Temperate Monsoon Region
Authors: Siriwardana Amila Nuwan , Kume Atsushi
Published: October 2024

Solar radiation (SR) dynamics have a profound effect on plant growth, development, and ecosystems, and they act as a primary energy source and important environmental signal that plants perceive through their photoreceptors, which primarily sense critical wavelength ratios (CWRs). The diffuse fraction of solar radiation (DF) is a key factor affecting the quality and distribution of light within the plant canopy. We analyzed one year of SR spectral observations measured by a ground-based rotating shadow-band spectroradiometer to evaluate the potential effects of DF and CWRs on plants in an outdoor environment in Fukuoka, Japan. The daily mean DF and all considered CWRs showed significant seasonal variations regardless of the solar meridian altitude. Cloudy or partly cloudy skies were prevalent throughout the year. The ratios of ultraviolet-A (UV-A)/UV-B, red (R)/blue (B), and R/green (G) increased during winter and decreased during summer. Conversely, the ratios of photosynthetically active radiation (PAR)/global solar radiation (GSI), UV/GSI, UV/PAR, B/G, R/far-red (FR), and UV-B/B increased during summer and decreased during winter. Specific CWRs correlated with air mass (AM) and vapor pressure (VP), and most of the CWR correlated with DF. AM, VP, and DF were also found to have a combined effect on specific CWRs that are important for plant light signals. This highlights the potential influence of AM, VP, and DF on plant light signals, thereby opening avenues for the development of innovative models of plant growth and ecological responses that incorporate plant photoreception.
Generalizability of Normative Models of Brain Morphometry Across Distinct Ethnoracial Groups
Authors: Ge Ruiyang , Yu Yuetong , New Faye , Haas Shalaila S , Sanford Nicole , Yu Kevin , Leon Julian Camillo Becerra , Yang Guoyuan , Gao Jia-Hong , Nemoto Kiyotaka , Fukunaga Masaki , Matsumoto Junya , Hashimoto Ryota , Jahanshad Neda , Thompson Paul M , Frangou Sophia
Published: October 2024

Normative modeling of brain morphometric data can inform about the clinical significance of deviations from typical patterns in brain structure. Their usefulness, however, is dependent on their applicability to diverse ethnoracial groups. With this in mind, we developed age- and sex-specific normative models for cortical thickness, surface area, and subcortical volumes using brain scans from 37,407 healthy individuals from a diverse international sample. Here we demonstrate the validity of these models in diverse and distinct populations. Specifically, we tested these pre-trained models on independent samples of healthy individuals that either self-identified as Black, South Asian, East Asian Chinese, East Asian Japanese, or we categorized as African, Admixed American, East Asian, and European based on their genetic ancestry. Regardless of ethnoracial definition, the performance of the pretrained models in these samples was exceptionally high; the relative mean absolute error for each regional brain morphometry measure was less than 10% across all the distinct ethnoracial groups. These findings affirm the broad applicability of our models, ensuring that brain morphometry assessments using these models are accurate and reliable for individuals regardless of background. This broad applicability has significant implications for advancing personalized medicine and improving health outcomes in diverse populations.
Effects of a transmissible cancer on life-history traits in Tasmanian devils
Authors: Strickland Kasha , Jones Menna , Lachish Shelly , Comte Sebastien , Hamede Rodrigo , Hohenlohe Paul , McCallum Hamish , Storfer Andrew , Kruuk Loeske
Published: October 2024

Shifts in life history traits, such as timing of reproduction, can help mediate population declines following perturbations, and early reproduction should be favoured when adult survival is impacted more than juvenile survival. In Tasmanian devils, following the emergence of a fatal transmissible cancer, females started to breed precocially (i.e., at age one instead of typically age two) and the same time as populations started to decline following disease emergence. Here, we focus on a diseased site (Freycinet Peninsula, Tasmania, Australia) with 18 years of continuous mark-recapture data to test: (1) whether rates of precocial breeding in females continued to increase after the initial rise after the emergence of the disease, (2) whether there was a relationship between body size and breeding success for either one-year-olds or adult females (i.e., at least two-years-old), and (3) whether there was inbreeding depression in breeding success for either age category. We show that rates of precocial breeding did not continue to rise, and that the proportion of precocially breeding females has plateaued at around 50%. We also show that there was no effect of body size on the probability of breeding for either one-year-old or for adult females. Finally, we show that there was no evidence for inbreeding depression in breeding success for either age class. We discuss possible constraints that may have inhibited further rise in rates of precocial breeding in the context of limitations to growth in the offspring of precocially breeding (and therefore smaller) females.
Origin of plant trait data matters: Shared species of Northwestern Europe and the Pannonian Ecoregion have different trait values in the two regions
Authors: Sonkoly Judit , Török Péter
Published: October 2024

Trait-based ecology considerably increased our comprehension of various fields related to ecology and evolution. As measuring traits can be time-consuming and costly, analyses regularly gather trait data from databases instead of carrying out new measurements. However, intraspecific trait variability can cause considerable differences between the trait values of different population and regions. Here we evaluated whether intraspecific trait variability causes considerable differences in trait values measured in two different regions of Europe. We tested whether regionally measured trait data from the Pannonian Ecoregion differ from trait data of the same species originating from Northwestern Europe, by comparing data from the Pannonian Database of Plant Traits (PADAPT) and the LEDA Traitbase. We evaluated six traits of the same set of species: thousand-seed mass (TSM), seed bank persistence index (SBPI), leaf area (LA), leaf dry matter content (LDMC), specific leaf area (SLA), and leaf dry mass. We found that trait data from the two databases significantly differed for TSM, SBPI, SLA, and LDMC. Our results indicate that the markedly different climate of the two regions can cause substantial intraspecific trait variation, therefore, the geographical origin of trait data matters in trait-based analyses. The findings corroborate the assumption that regionally measured trait data and building regional databases are essential for reliable regional-scale trait-based studies. We conclude that for studies analysing traits in the Pannonian Ecoregion (and possibly in Easter and Central Europe in general), it is advisable to use PADAPT instead of databases compiling data from regions with markedly different climatic conditions.
Mechanistic Insights into Alcohol-Induced DNA Crosslink Repair by the Fanconi Anemia Nuclease Slx4-Xpf-Ercc1
Authors: Havlikova Jana , Dejmek Milan , Huskova Andrea , Allan Anthony , Boura Evzen , Nencka Radim , Silhan Jan
Published: October 2024

During cell division, DNA replication stalls upon alcohol-derived interstrand crosslink, employing DNA repair pathways. Acetaldehyde, a toxic metabolite of alcohol, can induce DNA crosslinks between complementary DNA strands, causing significant genomic instability. The repair of acetaldehyde DNA crosslinks (AA-ICLs) is vital for maintaining genome integrity and preventing mutagenic events. The Fanconi anemia (FA) repair pathway’s involvement in fixing the AA-ICLs is crucial, ensuring cellular homeostasis and safeguarding genomic stability. Dysregulation of the FA pathway has been linked to Fanconi anemia, a rare genetic disorder characterized by hypersensitivity to DNA-damaging agents, including acetaldehyde. However, the precise mechanism of the repair and incision of AA-ICLs is unknown. Here, we demonstrate the role of the FA pathway nuclease SLX4-XPF-ERCC1 (SXE) in the repair of AA-ICL. We have generated site-specific AA-ICL within the replication fork, and we found SXE to excise the crosslink from the replication fork, bringing evidence of its role in the repair of alcohol-induced DNA lesions. This nuclease complex performs two precise incisions around the lesion. We also demonstrate that the SXE nuclease excises an abasic site interstrand crosslink in a similar manner. Given the evidence in conjunction with previous repair studies that have been conducted, our work suggests that SXE is a versatile nuclease complex.
Human Brain-Wide Activation of Sleep Rhythms
Authors: Wang Haiteng , Zou Qihong , Zhang Jinbo , Gao Jia-Hong , Liu Yunzhe
Published: October 2024

During sleep, our brain undergoes highly synchronized activity, orchestrated by distinct neural rhythms. Little is known about the associated brain activation during these sleep rhythms, and even less about their functional implications. In this study, we investigated the brain-wide activation underlying human sleep rhythms by employing simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) in 107 participants during nocturnal nap (first half of the night). We identified robust coupling between slow oscillations (SOs) and fast spindles during deep non-rapid eye movement (NREM) sleep (N2/3 stages), with spindle peaks consistently occurring just before the SO UP-state. This SO-spindle coupling was linked to elevated activation in both the thalamus and hippocampus, alongside increased functional connectivity from the hippocampus to the thalamus and from the thalamus to the medial prefrontal cortex (mPFC). An open-ended cognitive state decoding analysis suggested that these activations may relate to episodic memory processes, yet were distinct from task-related networks. Together, these findings highlight the thalamus as a key coordinator of hippocampal-cortical communication during sleep and provide new insights into the mechanisms by which synchronized sleep rhythms may support memory consolidation.
Synaptic targets and cellular sources of CB1 cannabinoid receptor and vesicular glutamate transporter-3 expressing nerve terminals in relation to GABAergic neurons in the human cerebral cortex
Authors: Somogyi Peter , Horie Sawa , Lukacs Istvan , Hunter Emily , Sarkany Barbara , Viney Tim James , Livermore James , Plaha Puneet , Stacey Richard , Ansorge Olaf , El Mestikawy Salah , Zhao Qianru
Published: October 2024

Cannabinoid receptor 1 (CB1) regulates synaptic transmission through presynaptic receptors in nerve terminals, and its physiological roles are of clinical relevance. The cellular sources and synaptic targets of CB1-expressing terminals in the human cerebral cortex are undefined. We demonstrate a variable laminar pattern of CB1-immunorective axons and electron microscopically show that CB1-positive GABAergic terminals make type-2 synapses innervating dendritic shafts (69%), dendritic spines (20%) and somata (11%) in neocortical layers 2-3. Of the CB1-immunopositive GABAergic terminals, 25% were vesicular-glutamate-transporter-3 (VGLUT3)-immunoreactive, suggesting GABAergic/glutamatergic co-transmission on dendritic shafts.In vitrorecorded and labelled VGLUT3 or CB1-positive GABAergic interneurons expressed cholecystokinin, vasoactive-intestinal-polypeptide and calretinin, had diverse firing, axons and dendrites, and included rosehip, neurogliaform and basket cells, but not double bouquet or axo-axonic cells. CB1-positive interneurons innervated pyramidal cells and GABAergic interneurons. Most glutamatergic synaptic terminals formed type-1 synapses and some were positive for CB1 receptor concentrated in the presynaptic active zone, unlike in GABAergic terminals. From the sampled VGLUT3-positive terminals, 60% formed type-1 synapses with dendritic spines (80%) or shafts (20%) and 52% were also positive for VGLUT1, suggesting intracortical origin. Some VGLUT3-positive terminals were immunopositive for vesicular-monoamine-transporter-2, suggesting 5-HT/glutamate co-transmission. Overall, the results show that CB1 regulates GABA release mainly to dendritic shafts of both pyramidal cells and interneurons, and predict CB1-regulated co-release of GABA and glutamate from single cortical interneurons. We also demonstrate the co-existence of multiple vesicular glutamate transporters in a select population of terminals probably originating from cortical neurons and innervating dendritic spines in the human cerebral cortex.
Biotic resistance predictably shifts microbial invasion regimes
Authors: Ye Xiaozhou , Shalev Or , Ratzke Christoph
Published: October 2024

Invading new territory is a central aspect of the microbial lifestyle, allowing microbes to expand to remote locations and pathogens to spread and infect their hosts. However, invading microbes rarely find novel territories uninhabited. In such a scenario, resident microbes can interact with the newcomers and, in many cases, impede their invasion, an effect known as biotic resistance. Accordingly, invasions are shaped by the interplay between dispersal and resistance. However, these two factors are difficult to disentangle or manipulate in natural systems, making their interplay difficult to understand. To address this challenge, we tracked microbial invasions in the lab over space and time, first in a model system of two interacting microbes, then in a multi-strain system involving a pathogen invading resident communities. In the presence of biotic resistance, we observed three qualitatively different invasion regimes: consistent, pulsed, and pinned, where, in the third regime, strong biotic resistance stalled the invasion entirely despite ongoing invader dispersal. Surprisingly, these rich invasion dynamics could be qualitatively predicted with a simple, parameter-free framework that ignores individual species interactions, even for rather complex communities. Moreover, we showed that this simple framework could accurately predict simulated invasions from different mechanistic models, indicating its broad applicability. Our work offers a thorough understanding of how biotic resistance impacts invasions and introduces a predictive tool to identify invasion-resistant communities.
Lowering the switching cost related to the activation of burdensome gene circuits promotes cell population homogeneity and productivity
Authors: Henrion Lucas , Vandenbroucke Vincent , Martinez Juan Andres , Kopp Julian , Telek Samuel , Zicler Andrew , Delvigne Frank
Published: October 2024

The activation of gene circuits can impose a significant burden on cells, leading to heterogeneous expression and reduced productivity. In this work, we focused on the T7 production system inE. coliBL21, a prime example of a burdensome gene circuit, to investigate the main cause for this gene expression heterogeneity and methods to mitigate it. Based on continuous cultivation analyzed and control by automated flow cytometry, we quantified the trade-off between cellular growth and gene expression and tracked the cell-to-cell heterogeneity in gene expression (measured as entropy). We concluded that the growth reduction associated to the activation of the burdensome gene circuit, i.e., the switching cost, is at the origin of the population heterogeneity. The loss of growth rate imposed by the burdensome activation of the gene is compensated at the population level by the overgrowth of less induced cells that safeguard the population by generating entropy. We tried to homogenize the population by pulsing the inducer with increasing frequency but found that the population escapes control through promoter mutation, leading to a genotype exhibiting reduced gene expression, but also, reduced entropy. To engineer a more homogeneous population without sacrificing gene expression, we decreased the switching cost associated to the induction by lowering the quality of the main carbon source. This strategy successfully led to a more homogeneous and productive population. Our approach allows for a precise quantification of the trade-off between growth and gene expression in cell population cultivated under dynamic conditions and highlights the importance of the switching cost for designing efficient approaches of cell population control.
Nonlinear Singular Value Decomposition Beamforming for Ultrasound Imaging of Gas Vesicles
Authors: Zhang Ge , Vert Mathis , Nouhoum Mohamed , Rivera Esteban , Haidour Nabil , Jimenez Anatole , Deffieux Thomas , Barral Simon , Hersen Pascal , Rabut Claire , Shapiro Mikhail , Tanter Mickael
Published: October 2024

Ultrasound imaging holds significant promise for the observation of molecular and cellular phenomena through the utilization of acoustic contrast agents and acoustic reporter genes. Optimizing imaging methodologies for enhanced detection represents an imperative advancement in this field. Most advanced techniques relying on amplitude modulation scheme such as cross amplitude modulation (xAM) and ultrafast amplitude modulation (uAM) combined with Hadamard encoded multiplane wave transmissions have shown efficacy in capturing acoustic signals of gas vesicles (GVs). Nonetheless, uAM sequence requires odd- or even-element transmissions leading to imprecise amplitude modulation emitting scheme, and the complex multiplane wave transmission scheme inherently yields overlong pulse durations. xAM sequence is limited in terms of field of view and imaging depth. To overcome these limitations, we introduce an innovative ultrafast imaging sequence called nonlinear singular value decomposition (SVD) beamforming. Our method demonstrated a contrast imaging sensitivity comparable to the current gold-standard xAM and uAM, while requiring 4.8 times less pulse transmissions. With similar number of transmit pulses, nonlinear SVD beamforming outperforms xAM and uAM in terms of an improvement in signal-to-background ratio of + 4.78 ± 0.35 dB and + 8.29 ± 3.52 dB respectively. Additionally, our method provides a higher flexibility in terms of the selection of acoustic pressure amplitude compared to the other methods. Furthermore, it shows a significant potential for application in the realm of ultrasound localization microscopy (ULM), where it stands poised to facilitate the more precise extraction of nonlinear signatures originating from contrast agents.
TRENDY: Gene Regulatory Network Inference Enhanced by Transformer
Authors: Tian Xueying , Patel Yash , Wang Yue
Published: October 2024

Gene regulatory networks (GRNs) play a crucial role in the control of cellular functions. Numerous methods have been developed to infer GRNs from gene expression data, including mechanism-based approaches, information-based approaches, and more recent deep learning techniques, the last of which often overlooks the underlying gene expression mechanisms. In this work, we introduce TRENDY, a novel GRN inference method that integrates transformer models to enhance the mechanism-based WENDY approach. Through testing on both simulated and experimental datasets, TRENDY demonstrates superior performance compared to existing methods. Furthermore, we apply this transformer-based approach to three additional inference methods, showcasing its broad potential to enhance GRN inference.
Chronic obesity does not alter cancer survival inTp53R270H/+mice
Authors: Panzeri Ilaria , Madaj Zachary , Fagnocchi Luca , Apostle Stefanos , Tompkins Megan , Hostetter Galen , Andrew Pospisilik J.
Published: October 2024

Obesity is a complex chronic disease characterized by excessive adiposity and associations with numerous co-morbidities, including cancer. Despite extensive research, we have limited understanding of the mechanisms coupling obesity to cancer risk, and, of the contexts in which obesity does or does not exacerbate disease. Here, we show that chronic high-fat diet (HFD)-induced obesity has no significant effect on theTp53R270H/+mouse, a model of human Li-Fraumeni multi-cancer syndrome. Surprisingly, despite inducing rapid and highly penetrant obesity and long-term differences in metabolic and adiposity, greater than one year of HFD had no significant effect on survival or tumor burden. These findings were replicated in two separate cohorts and thus provide important negative data for the field. Given strong publication bias against negative data in the literature, this large cohort study represents a clear case where chronic diet-induced obesity does not accelerate or aggravate cancer outcomes. The data thus carry high impact for researchers, funders, and policymakers alike.
Pan-cistrome analysis of the leaf accessible chromatin regions of 214 maize inbred lines
Authors: Zhu Yongli , Ngan Heiyuen , Zhu Tao , Nan Lili , Li Wenqiang , Xiao Yingjie , Zhuo Lin , Chen Dijun , Tu Xiaoyu , Gao Kang , Yan Jianbing , Zhong Silin , Yang Ning
Published: October 2024

Characterizing the noncoding regions of the genome, particularly the cis-regulatory elements (CREs) located in accessible chromatin regions (ACRs) in gene promoters, is crucial for understanding how gene expression is regulated and how genotype contributes to phenotypic diversity in plants.In this study, we used ATAC-seq to resequence and map the ACRs of 214 maize inbred lines. We identified 82,174 ACRs and reported that 39.55% of them exhibited significant variation across the population. Next, we used the accessibility of ACRs as a quantitative feature and performed a chromatin associability GWAS (caGWAS), resulting in 27,004 caQTLs. Among them, 2,463 were predicted to disrupt the cis-regulatory elements that TF binds in these ACRs, suggesting that TF binding affects chromatin accessibility. Specifically, we identified two caACRs that regulate the expression offad7, which encodes a fatty acid desaturase and affects the linolenic acid content.Our findings highlight the dynamic nature of maize ACRs and demonstrate that chromatin accessibility information could be used for GWASs, offering key insights into the genetic and regulatory mechanisms of chromatin accessibility and its impact on complex traits in plants.
Genomic Discovery of EF-24 Targets Unveils Antitumorigenic Mechanisms in Leukemia Cells
Authors: Singh Ajeet P. , Wax Noah , Duncan James , Fernandes Ana , Jacobs Jonathan L.
Published: October 2024

Curcumin, a polyphenolic compound derived from the plantCurcuma longaL., has demonstrated a wide range of therapeutic properties, including potential anticancer effects. However, its clinical efficacy is limited due to poor bioavailability and stability. To overcome these challenges, curcumin analogs like EF-24 have been developed with improved pharmacological properties. In this study, we used whole-transcriptome profiling to identify the genome-wide functional impacts of EF-24 treatment in leukemia cells to improve our understanding of its potential mechanisms of action. This approach allowed us to establish a model system for associating druggable genes with clinical disease targets. We used the chronic myeloid leukemia (CML) cell line K-562 and acute myeloid leukemia (AML) cell lines HL-60, Kasumi-1, and THP-1 to conduct EF-24 treatment studies. Cell viability was significantly decreased in the EF-24–treated cells as compared to the untreated controls. We discovered that the genes ATF3, CLU, HSPA6, OSGIN1, ZFAND2A, and CXCL8, which are associated with reduced cell viability and proliferation, were consistently upregulated in all EF-24–treated cell lines. Further analysis of the tested cell lines revealed the activation of various signaling pathways, including the STAT1 regulated S100 family signaling pathway, that controlled downstream gene expression in response to EF-24 treatment. Our results elucidate the molecular mechanisms underlying EF-24’s antitumor efficacy against leukemia, highlighting its multifaceted impact on signaling pathways and gene networks that regulate cell survival, proliferation, and immune responses in myeloid leukemia cells.

Significance

This study reveals how EF-24, a curcumin analog, disrupts key signaling pathways in chronic and acute myeloid leukemia cell lines, offering insights to enhance targeted therapies and provide new targets for investigation.

Conflict of Interest Statement

The authors declare no potential conflicts of interest.
Information transfer from spatial to social distance in rats: implications for the role of the posterior parietal cortex in spatial-social integration
Authors: Wise Taylor B. , Templer Victoria , Burwell Rebecca D.
Published: October 2024

Humans and other social animals can represent and navigate complex networks of social relationships in ways that are suggestive of representation and navigation in space. There is some evidence that cortical regions initially required for processing space have been adapted to include processing of social information. One candidate region for supporting both spatial and social information processing is the posterior parietal cortex (PPC). We examined the hypothesis that rats can transfer or generalize distance information across spatial and social domains and that this phenomenon requires the PPC. In a novel apparatus, rats learned to discriminate two conspecifics positioned at different spatial distances (near vs. far) in a goal-driven paradigm.

Following spatial learning, subjects were tested on probe trials in which spatial distance was replaced with social distance (cagemate vs. less familiar conspecific). The PPC was chemogenetically inactivated during a subset of probe sessions. We predicted that, in control probe trials, subjects would select conspecifics whose social distance matched the previously learned spatial distance. That is, if trained on the near distance, the rat would choose the highly familiar cagemate, and if trained on the far distance, the rat would choose the less familiar conspecific. Subjects learned to discriminate conspecifics based on spatial distance in our goal-driven paradigm. Moreover, choice for the appropriate social distance in the first probe session was significantly higher than chance. This result suggests that rats transferred learned spatial information to social contexts. Contrary to our predictions, PPC inactivation did not impair spatial to social information transfer. Possible reasons are discussed. To our knowledge, this is the first study to provide evidence that spatial and social distance are processed by shared cognitive mechanisms in the rat model.
A top-down insular cortex circuit crucial for non-nociceptive fear learning
Authors: Han Junho , Suh Boin , Han Jin-Hee
Published: October 2024

Understanding how threats in environments drive fear memory formation is crucial to understanding how organisms adapt to changing environments and treat threat-related disorders such as PTSD. Despite decades of pioneering work using the Pavlovian conditioning model, our understanding has been limited because only one type (an electric shock) among diverse threats has been exclusively used. We developed a threat conditioning paradigm by utilizing a looming visual threat as an unconditioned stimulus (US) in mice and identified a distinct threat conditioning circuit. Parabrachial CGRP neurons were required for conditioning and memory retrieval. Their upstream neurons in the posterior insular cortex (pIC) responded to looming stimuli and projections of these neurons to the parabrachial nucleus induced aversive affective states and drove conditioning. But the pIC to PBN pathway was dispensable for foot-shock conditioning. Our findings provide insights into how a simple pattern of non-nociceptive visual stimuli can induce aversive states and drive fear memory formation.
PUBLIC ATTITUDES TOWARDS FOOD TAXES FOR HEALTHY EATING IN THE UNITED KINGDOM
Authors: Martínez-Jiménez Mario , Brinsden Hannah , Sassi Franco
Published: October 2024

Introduction

Appropriately designed food taxes can improve diet quality and health. Fiscal levers are used in several countries to combat the rise in obesity and diet-related diseases. This study aims to investigate public attitudes, knowledge, and policy preferences regarding food taxes for promoting healthy eating in the UK.

Methods

A survey was administered through YouGov Plc to a nationally representative sample of 2,125 adults, gathering information on: acceptability and support for different types of food taxes, awareness and knowledge of existing taxes, and preferences for the characteristics of possible new taxes.

Results

Overall, 48% of respondents support higher taxes on unhealthy foods, rising to 72% if taxes made healthy foods more affordable. Respondents with high socio-economic status and those living in London showed the highest support. Respondents had limited awareness of existing food and beverage taxes, and prioritised discretionary items such as cakes and crisps for possible increased taxation.

Conclusions

The survey shows a high level of support for taxing unhealthy foods, as well as concern for the affordability of healthy foods. A carefully designed holistic approach to food taxation can be part of a wider public health strategy and can be favourably met by the general population in the UK.
Perceptual Expertise and Attention: An Exploration using Deep Neural Networks
Authors: Das Soukhin , Mangun G.R. , Ding Mingzhou
Published: October 2024

Perceptual expertise and attention are two important factors that enable superior object recognition and task performance. While expertise enhances knowledge and provides a holistic understanding of the environment, attention allows us to selectively focus on task-related information and suppress distraction. It has been suggested that attention operates differently in experts and in novices, but much remains unknown. This study investigates the relationship between perceptual expertise and attention using convolutional neural networks (CNNs), which are shown to be good models of primate visual pathways. Two CNN models were trained to become experts in either face or scene recognition, and the effect of attention on performance was evaluated in tasks involving complex stimuli, such as superimposed images containing superimposed faces and scenes. The goal was to explore how feature-based attention (FBA) influences recognition within and outside the domain of expertise of the models. We found that each model performed better in its area of expertise—and that FBA further enhanced task performance, but only within the domain of expertise, increasing performance by up to 35% in scene recognition, and 15% in face recognition. However, attention had reduced or negative effects when applied outside the models’ expertise domain. Neural unit-level analysis revealed that expertise led to stronger tuning towards category-specific features and sharper tuning curves, as reflected in greater representational dissimilarity between targets and distractors, which, in line with the biased competition model of attention, leads to enhanced performance by reducing competition. These findings highlight the critical role of neural tuning at single as well as network level neural in distinguishing the effects of attention in experts and in novices and demonstrate that CNNs can be used fruitfully as computational models for addressing neuroscience questions not practical with the empirical methods.
Disrupted Hippocampal-Prefrontal Networks in a Rat Model of Fragile X Syndrome: A Study Linking Neural Dynamics to Autism-Like Behavioral Impairments
Authors: Ouardouz Mohamed , Jasinski Patrick , Khalife Mohamed , Mahoney J Matthew , Hernan Amanda E , Scott Rod C
Published: October 2024

Fragile X Syndrome (FXS) is associated with autism spectrum disorder (ASD) symptoms that are associated with cognitive, learning, and behavioral challenges. We investigated how known molecular disruptions in the Fmr1 knockout (FMR-KO) rat model of FXS negatively impact hippocampal-prefrontal cortex (H-PFC) neural network activity and consequent behavior.

Methods

FMR-KO and control rats underwent a battery of behavioral tests assessing sociability, memory, and anxiety. Single-unit electrophysiology recordings were then conducted to measure patterns of neural activity in H-PFC circuit. Advanced mathematical models were used to characterize the patterns that were then compared between groups using generalized linear mixed models.

Results

FMR-KO rats demonstrated significant behavioral deficits in sociability, spatial learning, and anxiety, aligning with symptoms of ASD. At the neural level, these rats exhibited abnormal firing patterns in the H-PFC circuit that is critical for learning, memory, and social behavior. The neural networks in FMR-KO rats were also less densely connected and more fragmented, particularly in hippocampal-PFC correlated firing. These findings suggest that disruptions in neural network dynamics underlie the observed behavioral impairments in FMR-KO rats.

Conclusion

FMR-KO significantly disrupts several characteristics of action potential firing in the H-PFC network, leading to deficits in social behavior, memory, and anxiety, as seen in FXS. This disruption is characterized by less organized and less resilient hippocampal-PFC networks. These findings suggest that therapeutic strategies aimed at normalizing neural dynamics, such as with brain stimulation, could potentially improve behavior and cognitive functions in autistic individuals.

HIGHLIGHTS

Fragile X Syndrome is associated with autism, cognitive challenges and anxiety

The loss of Fmr1 protein disrupts processes involved in building neural networks

The consequence is abnormal neural dynamics in hippocampal-prefrontal cortex networks

Normalization of dynamics could improve outcomes in FXS and ASD
Implied motion guides neither gaze following nor intention attribution
Authors: Görner Marius , Shafiei Masih , Thier Peter
Published: October 2024

The “gaze beam hypothesis (GBH)” of gaze following posits that the other’s eyes emit imaginary beams of moving energy travelling to the other’s object of attention (1), drawing the observer’s attention to the same object. This idea was initially supported by behavioral experiments showing a motion aftereffect (MAE), indicated by longer reaction times in detecting motion direction after viewing a cartoon face looking at an object in the same direction (2). However, this effect could also be expected if the observer used gaze direction to assume an intentional link between the looker and the object, envisioning directed actions toward the latter (3). To critically compare the two hypotheses, we tested whether an MAE could be induced by having human subjects detect motion direction after viewing various cue images, designed to differentiate the explanatory power of the two. Cues either suggested a connection between an agent and an object through the agent’s gaze or an object-oriented intention by the presence of equipment in the agent’s hand, without the agent directly looking at the object. Using Bayesian statistics, our findings provided strong evidence against both hypotheses at the population level, as reaction time modulations did not align with the MAE, leading us to reject motion adaptation as the underlying mechanism for gaze following but also intention attribution. As on an individual level we observed highly diverse effects, with some compatible with one or the other hypothesis, we assume that individual subjects may resort to different perceptual strategies based on different scene interpretations.
A Cortical Site that Encodes Vocal Expression and Reception
Authors: Pomberger Thomas , Kaplan Katherine S , Carter Rene , Harmon Thomas C , Mooney Richard
Published: October 2024

Socially effective vocal communication requires brain regions that encode expressive and receptive aspects of vocal communication in a social context-dependent manner. Here, we combined a novel behavioral assay with microendoscopy to interrogate neuronal activity in the posterior insula (pIns) in socially interacting mice as they switched rapidly between states of vocal expression and reception. We found that distinct but spatially intermingled subsets of pIns neurons were active during vocal expression and reception. Notably, pIns activity during vocal expression increased prior to vocal onset and was also detected in congenitally deaf mice, pointing to a motor signal. Furthermore, receptive pIns activity depended strongly on social cues, including female odorants. Lastly, tracing experiments reveal that deep layer neurons in the pIns directly bridge the auditory thalamus to a midbrain vocal gating region. Therefore, the pIns is a site that encodes vocal expression and reception in a manner that depends on social context.
Whistle variability and social acoustic interactions in bottlenose dolphins
Authors: Mustun Faadil , Semenzin Chiara , Rance Dean , Marachlian Emiliano , Guillerm Zohria-Lys , Mancini Agathe , Bouaziz Inès , Fleck Elisabeth , Shashar Nadav , de Polavieja Gonzalo G. , Sumbre Germán
Published: October 2024

Bottlenose dolphins exhibit a sophisticated social structure, known as a fission-fusion society. To sustain this complex system, dolphins rely on a rich vocal repertoire: clicks exclusively used for echolocation, burst-pulse sounds associated with emotions during social interactions, and whistles, including signature whistles that serve as individual-specific identifiers (‘names’).

How dolphins maintain their complex social structure based only on a limited repertoire of sounds remains elusive. Previous studies suggest that contextual information can be transferred by the modulation of the whistles.

Here, we investigated the whistle variability using a comprehensive computational approach, and studied the structure of the interactions between the whistle variants. Using a unique large dataset, acquired in a natural environment, we observed that signature whistles exhibit variations in their frequency contours. Unsupervised clustering revealed that signature whistles could be classified into sub-categories (signature whistle variants). The existence of these categories, and their independence on the emitter dolphin, indicate that these variations are not random. Analysis of pairwise interactions between sub-categories revealed a clustered structure similar to that of their social hierarchy. Network analysis of this structure showed that whistle sub-categories had different functional roles: some acted as hubs, others as bridges, and certain were used for turn-taking between the main whistle categories. We also found that the dolphins emit signature whistles of their deceased mothers, a phenomenon only observed in human language.

Overall, these findings suggest that dolphins modulate signature whistles to transmit additional information beyond individual identity, and that they engage in "dialogue-like" acoustic interactions.
Study of Plasma Adiponectin Levels in Patients with Metabolic Syndrome and Therapeutic Indication in Bangladesh
Authors: Parul Salina Shaheen , Ahmmed Reaz , Hasan Md. Taohid , Islam Ariful , Rahman Md. Motiar , Manirujjaman M. , Bari Md. Wasim , Ahmed Md. Sakil , Hasan Md. Sohel , Islam Mohammad Amirul
Published: October 2024

Background

The metabolic syndrome (Met-S) is a cluster of some interrelated common clinical disorders, including central obesity, dyslipidemia, hypertension, and glucose intolerance. Central obesity, accompanied by insulin resistance, is a key factor for the development of metabolic syndrome. Adiponectin is an adipose-specific plasma protein, secreted from adipocyte with anti-atherogenic and insulin-sensitizing activities.

Purpose

This study aimed to investigate the relationship of plasma adiponectin levels with metabolic syndrome, related disorders and its drug repurposing through in silico approach.

Materials and Methods

For this study, 269 individuals were recruited with written consent. The participants were selected based on their full medical history, clinical examination, and laboratory reports. Anthropometric measurements as well as blood pressure was measured before sample collection. Fasting blood samples were collected for the estimation of lipid profile, blood glucose, and serum adiponectin levels.

Results

Our results show that the adiponectin levels in the subjects with Met-S were significantly lower than those of without Met-S (p <0.0001). Among the metabolic syndrome risk factors, adiponectin levels were associated with hypertriglyceridemia and reduced HDL-cholesterol (p<0.0001). Three drugs (Saquinavir, Candesartan and Glimepiride) were suggested to control the plasma adiponectin level in the subjects with Met-S.

Conclusions

Since the plasma adiponectin levels are significantly lower in patients with Met-S, it might be used as diagnostic & prognostic marker for Met-S disorder and adiponectin targeted drugs might be minimize the Met-S of the subjects.