bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating descending activation patterns from EMG in fast and slow movements using a model of the stretch reflex
Authors: Zhang Lei , Schöner Gregor 
Published: October 2024

AbstractDue to spinal reflex loops, descending activation from the brain is not the only source of muscle activation that ultimately generates movement. This study directly estimates descending activation patterns from measured patterns of muscle activation (EMG) during human arm movements. A simple model of the spinal stretch reflex is calibrated in a postural unloading task and then used to estimate descending activation patterns from muscle EMG patterns and kinematics during voluntary arm motion performed at different speeds. We observed three key features of the estimated descending activation patterns: (1) Within about the first 15% of movement duration, descending and muscle activations are temporally aligned. Thereafter, they diverge and develop qualitatively different temporal profiles. (2) The time course of descending activation is monotonic for slow movements, non-monotonic for fast movements. (3) Varying model parameters like the spinal reflex gain or the level of co-contraction does not qualitatively change the temporal pattern of estimated descending activation. Our findings highlight the substantial contribution of spinal reflex loops to movement generation, while at the same time providing evidence that the brain must generate qualitatively different descending activation patterns for movements that vary in their mechanical dynamics.New & NoteworthyWe propose a new method that directly estimates descending activation from measured EMG signals and arm kinematics by inverting a model of the spinal stretch reflex, without the need for muscle models or for an arm dynamics model. This approach identifies key features of the time structure of descending activation as movement speed is varied, while also revealing the significant contribution of the spinal stretch reflex to movement generation.
Tumor Priming by Ultrasound Mechanogenetics for with SynNotch CAR T Therapy
Authors: Yoon Chi Woo , Song Chunyang , Minh Nguyen Dung Ngo , Zhu Linshan , Ho Phuong , Huang Ziliang , Lu Gengxi , Zamat Ali , Lewis Alexa , Chen Ruimin , Zeng Yushun , Lee Nan Sook , Jamieson Christina , Shung K. Kirk , Zhou Qifa , Wang Yingxiao 
Published: October 2024

AbstractCell-based cancer immunotherapy holds potential as a therapeutic approach, yet its application for solid tumor treatment remains challenging. We created a system where focused ultrasound (FUS) is able to remotely stimulate gene expressions in a specific tissue area through mechanical induction, gated by a chemical inducer to minimize the background noise. This system, known as CaDox, integrates FUS-triggered mechanical and calcium stimulation with doxycycline-responsive genetic circuits, which allows the localized expression of the clinically validated and specific antigen CD19 within a subpopulation of cancer cells upon FUS stimulation. These CD19-expressing cells can then function as “training centers” that activate synNotch chimeric antigen receptor (CAR) T cells to generate CARs that recognize a less specific but widespread antigen in cancer cells, thereby attacking and suppress the whole cancer cell population nearby at the tumor site. We validated the functionality of this CaDox systemin vitro, in organoids, andin vivo, demonstrating its potential for various cell types and as a versatile platform for precisely controllable immunotherapy. Our combinatorial approach thus offers a FUS-controlled remote and non-invasive priming of solid tumors for effective and safe CAR T immunotherapy via the induced production of clinically validated antigens.
Amelioration of Oxidative Stress in Sodium Fluoride-administered Wistar Rats byTamarindus indicaFruit Pulp Ethanolic Extract
Authors: Usman Lutfat A , Ajani Emmanuel O. , Ishiaku Muhammed A , Bankole Taofeeq A , Ibrahim Rasheed B. , Saka Dauda K. , Abdulameed Hassan T. , Aladodo Raliat A. 
Published: October 2024

ABSTRACTInfertility is a significant global health issue often exacerbated by environmental toxins like sodium fluoride (NaF), which induces oxidative stress and reproductive dysfunction. Medicinal plants, such as Tamarindus indica, known for their antioxidant properties, offer potential natural remedies. This study evaluates the antioxidant potential of the ethanolic extract of Tamarindus indica fruit pulp in mitigating NaF-induced infertility in Wistar rats.Tamarindus indicafruits were authenticated and processed into a crude extract, with phytochemical screening revealing the presence of tannins and steroids. Seventy Wistar rats were divided into seven groups, receiving various treatments including T. indica extract, NaF, and Clomid. The acute toxicity test, conducted according to WHO and OECD guidelines, showed no lethal effects up to 5000 mg/kg of the extract. Phytochemical screening indicated that the antioxidant properties of the extract could be attributed to tannins and steroids.Experimental groups treated with T. indica extract exhibited significant improvements in oxidative stress markers such as malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) compared to control groups. The 200 mg/kg preventive group demonstrated the most notable antioxidant activity, comparable to the normal control group.The findings suggest that the ethanolic extract of Tamarindus indica fruit pulp at 200 mg/kg body weight has significant potential as a natural therapeutic agent against oxidative stress-induced infertility. This highlights its promise as an alternative to conventional treatments, offering a safe and effective option for managing reproductive health issues related to oxidative stress.
Single Cells Signal Non-self from Self via ‘XOR’ and ‘NOT EQUALS’ Logic in a Dimer of Dimers
Authors: An Rocky , Prakash Manu 
Published: October 2024

AbstractThe ciliateTetrahymena thermophila’s seven mating types are defined by unique receptor-ligand pairs (Mta/Mtb). While Mta and Mtb are known to participate in a mating signal complex, how they distinguish between oneself and six non-self cell types remains unknown. AlphaFold3 predictions reveal Mta/Mtb as large glycoproteins likely derived from ancient, unisexual, intercellular adhesion molecules. Since homologous binary-type systems perform XOR by switching mtA expression, we show spectrum (n) types naturally extend XOR to multi-bit NOT EQUALS operations via differential affinities of Mta/Mtb dimers. We model kinetics begetting the ‘n+ 1th’ type, demonstrating self-inhibition bytrans-homophilic Mtb-Mtb. A computational approach reconciles recent and classical evidence for mating exclusivity, including selfing failures (same type mating). Binding kinetics enables fast, robust intercellular computation across an intermembrane mating space. Thus, Mta/Mtb families are a model system allowing us to derive a ‘calculus’ of antigenic variation and inspire synthetic designs of XOR logic underlying self/non-self recognition.Graphical AbstractHighlightsWithin minutes, swimming cells signal compatible mating types via membrane proteinsAlphaFold insights reveal Mta/Mtb family as elongate adhesion receptors/ligandsRelative affinities of two dimers explain multi-bit intercellular signaling capacityDimer-of-dimers compute NOT EQUALS via homo-vs. hetero-philic interactionsIn BriefFree-living ciliatesT. thermophilabreed only when two cells are different in mating type, out of seven types total. Their mating-type-specific coexpression of a receptor-ligand glycoprotein pair reveals how competitive homophilic vs. heterophilic binding computes self vs. non-self recognition with single-layer intercellular logic. Proteins perform binary XOR gates (with two mating types) that extend to multi-bit ‘NOT EQUALS’ (with multiple mating types). The work illuminates principles of eXclusivity in molecular recognition and inspires the design of synthetic cellular recognition systems.
History bias and its perturbation of the stimulus representation in the macaque prefrontal cortex
Authors: Benozzo Danilo , Ferrucci Lorenzo , Ceccarelli Francesco , Genovesio Aldo 
Published: October 2024

AbstractMultiple history biases affect our representation of magnitudes, such as time, distance, and size. It is not clear whether the previous stimuli interfere with the discrimination process from the moment of stimulus presentation, during working memory retention, or even later during the decision-making phase. We used a spatial discrimination task involving two stimuli of different magnitudes, presented sequentially at various distances from the center. The monkey’s task was to select the farthest of them. We showed that the previous stimulus magnitude generated a contraction bias effect, but only when its stimulus features differed from those of the current stimulus. In this case, at the neural level we also observed that the decoding of the stimulus magnitude achieved the highest accuracy when it matched the magnitude of the preceding stimulus for which the decoder was trained. This indicates that past stimuli can affect magnitude processing already during the stimulus presentation, even before the decision process. Interestingly, this effect manifested when the trace of the previous stimulus magnitude reactivated in the second part of the stimulus presentation after an “activity-silent” period.
The MutRS quorum sensing system controls lantibiotic mutacin production in the human pathogenStreptococcus mutans
Authors: Wyllie Ryan M. , Jensen Paul A. 
Published: October 2024

AbstractMicrobes use quorum sensing systems to respond to ecological and environmental changes. In the oral microbiome, the pathogenic bacteriumStreptococcus mutansuses quorum sensing to control the production of bacteriocins. These antimicrobial peptides kill off ecological competetors and allowS. mutansto dominate the microenviornment of dental plaques and form dental caries. One class of bacteriocins produced byS. mutans, the lantibiotic mutacins, are particularly effective at killing due to their broad spectrum of activity. Despite years of study, the regulatory mechanisms governing production of lantibiotic mutacins I, II, and III inS. mutanshave never been elucidated. We discovered a distinct class of quorum sensing system, MutRS, that regulates mutacins and is widespread among the streptococci. We demonstrate that MutRS systems are activated by a short peptide pheromone (Mutacin Stimulating Peptide, or MSP) and show that MutRS controls production of three separate lantibiotic mutacins in three different strains ofS. mutans. Finally, we show that paralogous MutRS systems participate in inter- and intrastrain crosstalk, providing further evidence of the interplay between quorum sensing systems in the oral streptococci.
An integrative proteotranscriptomics approach reveals new ADAM9 substrates and downstream pathways
Authors: Lu Congyu , Xu Xiaolu , Sindhu Neha , Rainey Jessica , Polson Shawn W. , Qiu Jing , Wei Shuo 
Published: October 2024

AbstractMembrane protein shedding is a key regulatory mechanism for cell signaling and adhesion, and dysregulated shedding is associated with diseases. Many membrane proteases can catalyze shedding, but the substrate spectra and downstream targets of these “sheddases” remain largely elusive. While secretomics-based methods have been applied to the systematic identification of sheddase substrates, these methods are not always effective and do not provide much information on downstream targets. Here we developed an integrative proteotranscriptomics approach to uncover the transcriptional and post-transcriptional targets of the disintegrin metalloproteinase ADAM9, a sheddase that has been implicated in solid tumors, autoimmunity, inflammatory diseases and COVID-19. This systematic approach revealed signaling pathways downstream of ADAM9, including the oncogenic mTOR and tumor suppressor FOXO pathways. We further identified several direct and indirect substrates for ADAM9, which may mediate the pathophysiological roles of ADAM9 in various diseases. Of note, some of these substrates are difficult to detect by secretomics. This new approach can be applied to other sheddases to systematically identify their substrates and targets.
Two-dimensional condensates of HRS drive the assembly of flat clathrin lattices on endosomes
Authors: Hakala Markku , Moparthi Satish Babu , Ganeva Iva , Bernat-Silvestre César , Espadas Javier , Kukulski Wanda , Vassilopoulos Stéphane , Kaksonen Marko , Roux Aurélien 
Published: October 2024

AbstractAmongst the different clathrin structures in mammalian cells, bi-layered clathrin coat colocalizing with endosomal sorting complex required for transport (ESCRT)-0 remains one of the most ambiguous. Despite being observed for the first time twenty years ago, their structure and how they are assembled remains unknown. Here, we reconstitutedin vitrothe ESCRT-0 clathrin assembly onto various types of membranes. The ESCRT-0 protein HRS, a known clathrin adaptor on endosomes, was found to form protein condensates. These condensates spread into a thin layer on PI(3)P-rich membranes. Platinum replica electron microscopy revealed that, surprisingly, the assembly of clathrin was different depending on the HRS phase. Protein droplets recruited clathrin as a dense, curved lattice, with many cage-like structures. On two-dimensional condensates, HRS recruited clathrin as a dense flat assembly. Two-dimensional HRS-clathrin condensates promoted the clustering of cholesterol in the underlying membrane, while cholesterol enhanced PI(3)P- dependent HRS recruitment on the membrane. On free-standing membranes, two-dimensional HRS-clathrin condensates promoted membrane flattening. Overall, these results show that a two- dimensional HRS condensate creates a unique membrane structure for sorting cargo molecules, defining a new mechanism in membrane trafficking processes.
Conservation of an immune homeostasis module in land plants
Authors: Dou Ruoqi , Mahboubi Karima El , Tanney Cailun A.S. , Chu Jiashu , Bredow Melissa , Rodriguez Gallo Maria Camila , Lauressergues Dominique , Keller Jean , Miguel Virginia Natali , DeFalco Thomas A. , Glen Uhrig R. , Zipfel Cyril , Delaux Pierre-Marc , Monaghan Jacqueline 
Published: October 2024

SummaryCalcium-dependent protein kinases (CDPKs or CPKs) are a unique family of Ca2+-regulated kinases with diverse functions in plants1. CPK28 regulates immune homeostasis, stress responses, and growth in multiple angiosperms including tomato2,3, rice4–7, cotton8–10, andArabidopsis thaliana(hereafter, Arabidopsis)11–17. In Arabidopsis, CPK28 phosphorylates and activates the E3 ubiquitin ligases PLANT U-BOX 25 (PUB25) and PUB26 that target the major immune signaling protein BOTRYTIS-INDUCED KINASE 1 (BIK1), resulting in its turnover12,18. The CPK28-PUB25/26-BIK1 regulatory module maintains precise levels of BIK1 in the cell and is thought to optimize immune responses19. Separated from angiosperms by 450M years of evolution, the liverwortMarchantia polymorpha(hereafter, Marchantia) has emerged as a model system to study the evolution of signaling modules across land plants20. Here, we demonstrate that the function of CPK28 is conserved in Marchantia. MpCPK28 displays Ca2+-dependent protein kinase activity and is inhibited by calmodulinin vitro. Over-expression ofMpCPK28results in pronounced developmental phenotypes and decreased chitin-induced oxidative burst, andMpCPK28can functionally complement the mutant phenotypes of the Arabidopsiscpk28-1mutant. MpCPK28 associates with and phosphorylates multiple residues on Marchantia AVRPPHB SUSCEPTIBLE 1 (PBS1)-like (PBL)-a (MpPBLa), a functional ortholog of AtBIK1, as well as MpPUB20e (a putative ortholog of AtPUB25/26). MpPBLa undergoes proteasomal degradation in Marchantia and can be polyubiquitinated by MpPUB20e. The occurrence of the CPK28-PUB25/26-BIK1 module across land plants reveals that the regulation of immune amplitude has been conserved throughout plant evolution.HighlightsMpCPK28 is a Ca2+-dependent protein kinase that regulates immune homeostasis and development in Marchantia and is functionally orthologous to AtCPK28.MpCPK28 phosphorylates the E3 ubiquitin ligase MpPUB20e and the receptor-like cytoplasmic kinase MpPBLa.MpPBLa is subject to proteasomal degradation and is ubiquitinated by MpPUB20e.In BriefDeploying robust immune responses to deter pathogens while minimizing host damage is critical to plant survival. Here, Douet al. show that optimizing the protein accumulation of receptor-like cytoplasmic kinase MpPBLa is an ancient property of the plant immune system, controlled by the MpCPK28-MpPUB20e regulatory module.
A molecular basis for plant SCAR/WAVE functional divergence
Authors: Brumm Sabine , Gavrin Aleksandr , Macleod Matthew , Chesneau Guillaume , Usländer Annika , Schornack Sebastian 
Published: October 2024

AbstractDynamic actin cytoskeleton reorganisation enables plant developmental processes requiring polarised transport such as root hair and leaf trichome formation. The SCAR/WAVE complex plays a crucial role in regulating these dynamics through ARP2/3-mediated actin branching.SCAR/WAVEgenes occur as small families across a wide range of plant species but whether and how they fulfil different functions remains unclear. We utilise a systematic chimaera approach to define the differential functionality of two closely relatedMedicago truncatulaSCAR proteins in plant development. We show that SCAR/WAVE contribution toMedicago truncatularoot hair orArabidopsis thalianatrichome formation is dependent on two central intrinsically disordered regions (IDRs). Differential functionalities ofMedicago truncatulaSCAR proteins were furthermore associated with the presence/absence of a 42-amino acid sequence within the IDR that impacted protein stability. Through uncovering a molecular basis for functional differences, we advance our understanding of plant SCAR/WAVE complexes.One Sentence SummaryIntrinsically disordered regions in SCAR/WAVE proteins drive diverse functions in root hair and leaf trichome development.
Anisotropic stretch biases the self-organization of actin fibers in multicellular Hydra aggregates
Authors: Bailles Anaïs , Serafini Giulia , Andreas Heino , Zechner Christoph , Modes Carl , Tomancak Pavel 
Published: October 2024

AbstractDuring development, groups of cells generate shape by coordinating their mechanical properties through an interplay of self-organization and pre-patterning. Hydra displays a striking planar pattern of actin fibers at the organism scale, and mechanics influence the morphogenesis of biological structures during its pre-patterned regeneration. However, how mechanics participate in the formation of an ordered pattern from a totally disordered state remains unknown. To study this, we used cellular aggregates formed from dissociated Hydra cells, which initially lose all actin polarity yet regenerate a long-range actin pattern. We showed quantitatively that the actin meshwork evolves from a disordered symmetric state to an ordered state in which rotational symmetry is broken, and translation symmetry is partially broken, with the nematic and smectic order parameters increasing over days. During the first hours, the actin meshwork displayed spatial heterogeneity in the nematic order parameter, and ordered domains separated by lines of defects progressively grew and fused. This suggests that local cell-cell interactions drive the transition from disorder to order. To understand the mechanism of ordering, we perturbed the tissue’s physical constraints. We showed that while topology and geometry do not have a direct effect, anisotropic stretch biases the emerging orientation of the actin meshwork within hours. Surprisingly, although a Wnt protein gradient is expected to play a role in the actin ordering, the stretch-associated alignment happened without a Wnt enrichment. This demonstrates the role of tissue mechanics in the alignment of the actin fibers during the disorder-to-order transition.
Intraspecific body size variation across distributional moments reveals trait filtering processes
Authors: Fitzgerald Jacquelyn L. , Ogilvie Jane E. , CaraDonna Paul J. 
Published: October 2024

Abstract

Natural populations are composed of individuals that vary in their morphological traits, timing and interactions. The distribution of a trait can be described by several dimensions, or mathematical moments—mean, variance, skew and kurtosis. Shifts in the distribution of a trait across these moments in response to environmental variation can help to reveal which trait values are gained or lost, and consequently how trait filtering processes are altering populations.

To examine the role and drivers of intraspecific variation within a trait filtering framework, we investigate variation in body size among five wild bumblebee species in the Colorado Rocky Mountains. First, we examine the relationships between environmental factors (climate and floral food resources) and body size distributions across bumblebee social castes to identify demographic responses to environmental variation. Next, we examine changes in the moments of trait distributions to reveal potential mechanisms behind intraspecific shifts in body size. Finally, we examine how intraspecific body size variation is related to diet breadth and phenology.

We found that climate conditions have a strong effect on observed body size variation across all distributional moments, but the filtering mechanism varies by social caste. For example, with earlier spring snowmelt queens declined in mean size and became negatively skewed and more kurtotic. This suggests a skewed filter admitting a greater frequency of small individuals. With greater availability of floral food resources, queens increased in mean size, but workers and males decreased in size. Observed shifts in body size variation also correspond with variation in diet breadth and phenology. Populations with larger average body size were associated with more generalized foraging in workers of short‐tongued species and increased specialization in longer‐tongued workers. Altered phenological timing was associated with species‐ and caste‐specific shifts in skew.

Across an assemblage of wild bumblebees, we find complex patterns of trait variation that may not have been captured if we had simply considered mean and variance. The four‐moment approach we employ here provides holistic insight into intraspecific trait variation, which may otherwise be overlooked and reveals potential underlying filtering processes driving such variation within populations.