Biology subjects

Ibanez, J.

Publications and source records attributed to Ibanez, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Lateralised Transmission of Beta Oscillations From Cortex to Muscle During Movement Cancellation Reflects Selective Motor Inhibition

Beta oscillations in the sensorimotor cortex are modulated across various stages of motor control, including movement preparation and cancellation, and are known to project to the motor neuron pool and muscles during Go/No-Go tasks. While these oscillations have been linked to motor inhibition, the specificity of their transmission to end-effector muscles during movement cancellation remains unclear. We investigated the selectivity of beta-band activity using a lateralised Go/No-Go paradigm. Participants maintained steady bimanual wrist extensor contractions and either executed a unilateral ballistic wrist extension (Go) or cancelled the planned movement (No-Go). Concurrent electroencephalographic and electromyographic recordings were measured throughout. Successful movement cancellation was characterised by contralateral cortical beta modulation accompanied by stronger and more clearly lateralised peripheral beta synchronisation in the muscle associated with the suppressed movement. Peripheral beta activity exhibited greater magnitude and clearer separability between left- and right-sided conditions than cortical signals. These findings demonstrate effector-specific brain-to-muscle beta transmission during movement cancellation and highlight the potential of peripheral measures to provide enhanced resolution of motor cortical dynamics.

bioengineering↗

bioRxiv2026

Neurofeedback Training on Motor Cancellation Enhances Peripheral but not Cortical Beta Band Oscillations

Beta oscillations (13-30 Hz) are a prominent sensorimotor neural rhythm and an important biomarker in neurorehabilitation. These oscillations propagate along the corticospinal pathway and are expressed in the discharge patterns of spinal motor neurons, enabling the assessment of corticomuscular coupling. Moreover, peripheral beta band oscillations have recently emerged as a potential control signal for motor augmentation interfaces. However, it remains unclear whether peripheral beta activity simply reflects cortical oscillations or is partly shaped by peripheral mechanisms, and to what extent it can be voluntarily controlled. To address these questions, we developed a 10-day neurofeedback protocol in which participants learned to up-regulate peripheral beta band activity. Subjects were trained to exploit movement cancellation, a behaviour naturally associated with increased cortical and muscle beta band activity, as a two-state strategy to voluntarily modulate peripheral beta band power. Each session included a guided familiarization phase based on a GO/NO-GO task, in which participants familiarized with movement cancellation through guided visual cues, followed by an asynchronous control phase in which they self-initiated the same strategy without external guidance to increase peripheral beta band activity in a target window. Participants progressively improved their ability to voluntarily modulate peripheral beta band activity. Peripheral beta band power during movement cancellation increased significantly across training days in both the familiarization and asynchronous control phases. Intramuscular coherence in the beta band also increased, indicating enhanced common synaptic input to the motor neuron pool in this band. In contrast, cortical beta power and corticomuscular coherence remained unchanged. Together, these findings demonstrate that peripheral beta band activity is a dynamic neural feature that can be voluntarily shaped through training, supporting its potential as a non-invasive control signal for future neurorehabilitation and motor augmentation technologies.

bioengineering↗

bioRxiv2026

A Reference Genome for the Critically Endangered Philippine Eagle (Pithecophaga jefferyi), the National Bird of the Philippines

The worlds largest and rarest eagle, the Philippine Eagle (Pithecophaga jefferyi), also known as the monkey-eating eagle, is the national bird of the Philippines. This raptor species is endemic to the Philippine archipelago, with populations on the islands of Luzon, Leyte, Samar, and Mindanao. It is critically endangered, with an average estimated population of 392 potentially breeding pairs or 784 mature individuals. In this paper, we describe a reference genome of the Philippine Eagle (Pithecophaga jefferyi) from a female juvenile from the province of Nueva Ecija on the island of Luzon. We generated a de novo genome assembly with high contiguity and completeness, comprising 178 contigs totaling 1.345 Gbp. The genome was sequenced at a coverage of 75.2x, and Benchmarking Universal Single-Copy Orthologs (BUSCO)/Compleasm analysis yielded a BUSCO score of 99.92% (aves_odb12), corresponding to 99.7% single-copy, 0.21% duplicated, and 0.08% fragmented genes. A consensus mitogenome sequence of 19,377 bp was also generated. The genome assembly included 23,847 putative genes, and our annotation estimated that 15.78% of the genome consisted of repetitive elements. Genome heterozygosity (H) was estimated to be 0.020%, in comparison to other birds with genome heterozygosity values ranging from 0.0103% to 0.923%. Whole-genome comparisons with publicly available genomes suggest that the Philippine eagle belongs to the snake-eagle subfamily (Circaetinae) rather than the harpy-eagle subfamily (Harpiinae). Pairwise sequentially Markovian coalescent (PSMC) analysis suggests that the effective population size was around 4,000 individuals from about 100 KYA to about 1 KYA. Finally, we constructed a minimum spanning network, which revealed that our mitogenome from the northern island of Luzon occupies a peripheral position, separated from the dominant haplotype cluster found in the southern island of Mindanao by multiple mutational steps, indicating substantial mitochondrial divergence.

genomics↗

bioRxiv2026

Enhancing Transcriptional Data Reliability in Fish Oogenesis Using cDNA-Based Normalization

Transcriptomic analyses are widely used to elucidate the molecular mechanisms driving gametogenesis and reproduction in fish, yet their accuracy depends heavily on appropriate normalization of gene expression data. Conventional approaches that rely on single or multiple reference genes are problematic during teleost oogenesis, as profound structural and physiological remodeling of the ovary challenges the assumption that commonly used reference transcripts remain stable. In this study, we assessed by qPCR the transcriptional variability of four widely used reference genes (actb, ef-1, gapdh, and 18S rRNA) throughout the oogenic cycle of the thicklip grey mullet (Chelon labrosus), using geNorm and NormFinder analyses, and we additionally evaluated total cDNA concentration as an alternative normalization factor. To examine the performance and interpretive consequences of each normalization strategy, we compared expression patterns of key steroidogenic genes (star, cyp19a1a, and cyp11b) normalized by individual reference genes, combinations of reference genes, or total cDNA concentration. All evaluated reference genes displayed notable transcriptional variability across oogenesis, confirming their limited suitability as sole internal controls. In contrast, normalization approaches integrating multiple reference genes and/or total cDNA concentration consistently provided greater stability and more reliable biological interpretation. These results support a refined and more robust normalization framework for transcriptional analyses in fish ovaries, particularly during stages of extensive tissue remodeling. Our findings demonstrate cDNA-based normalization is straightforward, rapid, and easy to implement across laboratories, providing a practical alternative for achieving accurate, reproducible transcript quantification in fish ovary studies.

pharmacology and toxicology↗

bioRxiv2026

High-frequency common inputs entrain motoneuron subpopulations differently

Spinal motoneuron (MN) pools behave as linear systems that transmit common synaptic input to muscles. However, MNs are biophysically heterogeneous and intrinsically nonlinear. How different MN subpopulations integrate and transmit high-frequency inputs remains poorly understood, partly because conventional analyses treat the MN pool as a single functional system rather than examining subpools with different firing rates. Here, we addressed this gap using a combination of computational simulations and human MN recordings. Simulations of MNs receiving a common synaptic input at varying frequencies showed that MNs firings become phase-locked to input oscillations when the input frequency approximates the neurons firing rate or its harmonics. We refer to this frequency-dependent synchronization as entrainment. Importantly, this subpool-specific effect was masked when MN activity was analysed at the whole-pool level. Because entrained MNs effectively sample the input at their firing instants, we developed a MN-firing locked method that uses individual MN firings as endogenous triggering events for peristimulus frequencygrams across the pool. In simulations, this method revealed entrainment-driven firing rate modulations across MN subpools. We then applied this MN-firing locked method to MNs decomposed from high-density surface electromyography recordings obtained during isometric contractions in healthy individuals. We found that faster-firing MNs exhibited larger transient firing rate increases, time-locked to slower MN activity. Furthermore, these modulations correlated with common input in the alpha and beta bands implicating high frequency common input as the driving source. Together, these findings demonstrate that MN nonlinearities generate heterogeneous, frequency-dependent dynamics that remain hidden in conventional pool-level analyses.

neuroscience↗

bioRxiv2026

TMS-Evoked Corticospinal Beta Oscillations in Humans Recorded from Muscles

BackgroundTranscranial magnetic stimulation (TMS) can entrain oscillatory brain activity, offering a promising approach to study motor-related neural oscillations such as beta rhythms. However, how TMS-induced corticospinal oscillations are generated, propagated, and related to endogenous activity remains unclear, partly due to limitations in brain recording techniques. Recording muscle activity provides an alternative and physiologically grounded window into corticospinal dynamics. MethodsWe investigated whether subthreshold TMS over the motor cortex induces corticospinal oscillatory activity detectable in muscles, and whether these responses share neural generators with endogenous beta rhythms. Single-pulse subthreshold TMS was applied over the motor cortex in healthy participants while electromyography (EMG) was recorded from tonically active muscles. Stimulation intensity, coil orientation, and stimulation site were systematically varied. Concurrent electroencephalography (EEG) was used to assess cortical responses and corticomuscular transmission. In additional experiments, advanced EMG techniques were employed to track motor neuron pools and characterize how TMS-evoked oscillations are transmitted at the motor unit level. ResultsTMS elicited a robust and short-latency increase in beta-band activity in the EMG. The analysis of the elicited muscle responses and the comparison of results across different TMS configurations indicate that the beta responses resulted from activation of inhibitory interneurons in the targeted primary motor cortex. Importantly, the characteristics of cortico-muscular coherence and beta projection to the muscles indicate that the elicited beta responses with TMS have same cortical sources as endogenously generated beta activity. ConclusionsThese findings demonstrate that muscle recordings provide a sensitive and physiologically meaningful readout of TMS-induced corticospinal beta oscillations.

neuroscience↗

bioRxiv2025

Task-Dependent Motor Unit Recruitment and Rate Coding Reveal Redistribution of Neural Drive in the Human Hand

Although Henneman's size principle dictates an orderly small-to-large activation for a given common input, evidence suggests a certain level of flexibility in the recruitment of spinal motoneurons depending on task demands. Here, we investigate motor unit (MU) recruitment flexibility in the human first dorsal interosseus (FDI) muscle while controlling for overall muscle activation across two functionally distinct tasks using High-Density intramuscular EMG (HD-iEMG) electrode arrays. Six participants performed isometric index finger abduction where the FDI serves as the prime mover, and flexion with the FDI functioning as a synergist. Recruitment thresholds (RT) and recruitment orders (RO) were highly consistent within the same task, but differed significantly between abduction and flexion. Across participants, 45.3% of MUs showed changes in recruitment above the coefficient of repeatability across tasks compared to only 5.0% within tasks. The spatial distribution of muscle activation did not shift between tasks, confirming that the same muscle region was engaged in both. Changes in RT were accompanied by corresponding adaptations in discharge rate (DR), preserving the inverse RT-DR relationship. Intramuscular coherence analysis revealed no differences in the delta (1-5 Hz) or alpha (5-13 Hz) band, but beta band (13-30 Hz) coherence was significantly lower during flexion than abduction, indicating reduced common input synchronization in this frequency range when FDI serves as a synergist muscle. Together, these results indicate different distributions of net excitatory input to FDI MUs across different functional tasks, potentially involving a stronger contribution of spinal circuits during flexion, as suggested by the reduced intramuscular beta coherence. Moreover, the present findings also demonstrate that common synaptic input and not intrinsic motoneuron properties determines the inverse relation between MU RT and DR.

neuroscience↗

bioRxiv2025

Genomic Analysis Reveals Recent Population Decline and Exceptionally Low Genome-Wide Heterozygosity of the Critically Endangered Philippine Eagle, Pithecophaga jefferyi (Aves: Accipitridae)

The Philippine Eagle (Pithecophaga jefferyi), is one of the rarest eagles in the world and is the national bird of the Philippines. It is listed by the International Union for Conservation of Nature (IUCN) as a critically endangered raptor and has been the subject of an intensive captive breeding program which started more than 30 years ago to ensure the survival and conservation of the species. To infer the genetic diversity and demographic history of the Philippine Eagle, we sequenced and analyzed the genomes of 35 individuals under the captive breeding program of the Philippine Eagle Foundation. Phylogenetic analysis of the draft reference sequence generated in this study placed P. jefferyi within the subfamily Circaetinae of Accipitridae. Demographic history reconstruction from genome-wide variants revealed two historical bottlenecks, as well as an ongoing population decline which was found to predate documented deforestation in the Philippines. This observation suggests that unobserved natural or anthropogenic factors might have severely affected the Philippine Eagle population long before habitat fragmentation. Genome-wide heterozygosity estimates placed the Philippine Eagle as having one of the lowest genome-wide heterozygosity levels measured among raptors. This highlights the precarious genetic state of the Philippine Eagle, as critically low heterozygosity raises risks of inbreeding depression, reduced reproductive success, and increased vulnerability to diseases, climate change, and habitat loss. The genomic resources generated in this study can therefore guide conservation strategies such as breeding program design, genetic monitoring, and other efforts to diversify existing populations to ensure both demographic stability and genetic resilience of the Philippine Eagle. Subject AreasPhilippine Eagle, Genomics, Genome-wide heterozygosity, Demographic History, Conservation, Biodiversity, Bioinformatics

genomics↗

bioRxiv2025

Spinal Motor Neuron Pools May be Partly Driven by Impulsive Common Inputs

Spinal motor neurons serve as the link between the nervous system and muscles. As the final common pathway of the neuromuscular system, they receive inputs from both higher-level controllers and afferent pathways. It is often assumed that spinal motor neurons are primarily driven by continuous common inputs (cCI) within different frequency bands. Within this framework, the motor neuron pool behaves as a linear amplifier of the cCI. However, this framework overlooks the possibility that motor neurons could also be driven by impulsive common inputs (iCI), which can induce synchronization among them and disrupt the linear transmission of other synaptic inputs at the pool level. To test this hypothesis, computational simulations and experimental data from human subjects were used to characterize different aspects related to motor neuron spiking synchronization at the pool level. Our findings suggest that, indeed, iCI can account for relevant features observed in experimental data such as the presence of synchronization events at the pool level. We also observed that such impulsive inputs can affect the linearity in the transmission of cCI by the motor neuron pool. This study represents pioneering indirect evidence of the existence of iCI as inputs to motor neurons. Significant StatementMotor unit pool behavior in terms of spiking synchronization and spectral content typically observed in experimental recordings cannot be reproduced in simulations that only use continuous common inputs (cCI) to motor neurons. This study shows, for the first time, evidence supporting that spinal motor neurons receive a portion of their synaptic input in the form of impulsive common inputs (iCI) that synchronize their activity. The study also shows how such iCI can affect the linear transmission of other cCI by the motor neuron pool.

neuroscience↗

bioRxiv2025

Classification of motor-related brain states using high frequency information from muscle recordings

Motor neural interfaces use recordings from the nervous system to extract control signals used to interact with the environment. Muscle signals are becoming an increasingly popular choice for motor interfaces, especially when used to estimate the neural motor commands driving muscle contractions and eventually movement. Here we study the possibility of using electromyography (EMG) to classify motor-related cortical states associated with the cancellation of movement in a GO/NO-GO task, which has been previously linked to changes in cortical beta oscillations. We show that beta (13-30Hz) and low gamma (30-45Hz) frequency bands have the most predictive power in electroencephalography (EEG) and EMG recordings. Moreover, we found comparable accuracy in cancellation state decoding from EEG (average of 74%) and EMG (average of 77%) recordings, which supports the concept of using peripheral signals to predict cortical activity associated to specific motor-related brain states.

neuroscience↗

bioRxiv2025

Rigid Control of Motor Unit Firing Rates in the Human Tibialis Anterior Muscle Persists during Neurofeedback

The conventional framework of motor-unit (MU) control assumes that MUs in a MU pool are constrained by a fixed recruitment order and a common input. This rigid-control framework has been challenged by recent findings suggesting that MU activity could be flexibly modulated, potentially mediated by descending cortical inputs. In this study, rather than evaluating flexibility from the perspective of recruitment thresholds, we investigated control flexibility by assessing if human participants can voluntarily modulate MU firing rates beyond rigid-control constraints. Specifically, we examined whether participants could voluntarily modulate the firing rates of a pair of MUs from the tibialis anterior muscle during real-time feedback. Two tasks involving target-reach with different visual feedback derived from the MUs firing rates were conducted. In both tasks, there was no evidence that participants were able to change MU firing rates in a way that would violate rigid control robustly. Our findings demonstrate limited flexibility in MU control in human tibialis anterior muscle within single-session training, even when real-time MU activity feedback was provided. The results suggest that MU flexibility is not inherently present in the human lower limb.

neuroscience↗

bioRxiv2023

Diploid genome assembly of the Malbec grapevine cultivar enables haplotype-aware analysis of transcriptomic differences underlying clonal phenotypic variation

1.To preserve their varietal attributes, established grapevine cultivars (Vitis vinifera L. ssp. vinifera) must be clonally propagated, due to their highly heterozygous genomes. Malbec is a France-originated cultivar appreciated for producing high-quality wines, and is the offspring of cultivars Prunelard and Magdeleine Noire des Charentes. Here, we have built a diploid genome assembly of Malbec, after trio binning of PacBio long reads into the two haploid complements inherited from either parent. After haplotype-aware deduplication and corrections, complete assemblies for the two haplophases were obtained with very low haplotype switch-error rate (<0.025). The haplophases alignment identified >25% of polymorphic regions. Gene annotation including RNA-seq transcriptome assembly and ab initio prediction evidence resulted in similar gene model numbers for both haplophases. The annotated diploid assembly was exploited in the transcriptomic comparison of four clonal accessions of Malbec that exhibited variation in berry composition traits. Analysis of the ripening pericarp transcriptome using either haplophases as reference yielded similar results, although some differences were observed. Particularly, among the differentially expressed genes identified only with the Magdeleine-inherited haplotype as reference, we observed an over-representation of hypothetically hemizygous genes. The higher berry anthocyanin content of clonal accession 595 was associated with increased abscisic acid responses, possibly leading to the observed overexpression of phenylpropanoid metabolism genes and deregulation of genes associated to abiotic stress response. Overall, the results highlight the importance of producing diploid assemblies to fully represent the genomic diversity of highly heterozygous woody crop cultivars and to unveil the molecular bases of clonal phenotypic variation.

genomics↗

bioRxiv2023

Accurate Identification of Motoneuron Discharges from Ultrasound Images Across the Full Muscle Cross-Section

ObjectiveNon-invasive identification of motoneuron (MN) activity is commonly done using (EMG). However, surface EMG (sEMG) signals detect only superficial sources, at less than approximately 10-mm depth. Intramuscular EMG can detect deep sources, but it is limited to sources within a few mm of the detection site. Conversely, ultrasound (US) images have high spatial resolution across the whole muscle cross-section. The activity of MNs can be extracted from US images due to the movements that MN activation generates in the innervated muscle fibers. Current US-based decomposition methods can accurately identify the location and average twitch induced by MN activity. However, they cannot accurately detect MN discharge times. MethodsHere, we present a method based on the convolutive blind source separation of US images to estimate MN discharge times with high accuracy. The method was validated across 10 participants using concomitant sEMG decomposition as the ground truth. Results140 unique MN spike trains were identified from US images, with a rate of agreement (RoA) with sEMG decomposition of 87.4 {+/-} 10.3 %. Over 50% of these MN spike trains had a RoA greater than 90%. Furthermore, with US, we identified additional MUs well beyond the sEMG detection volume, at up to >30 mm below the skin. ConclusionThe proposed method can identify discharges of MNs innervating muscle fibers in a large range of depths within the muscle from US images. SignificanceThe proposed methodology can non-invasively interface with the outer layers of the central nervous system innervating muscles across the full cross-section.

bioengineering↗

bioRxiv2023

High-frequency cortical neural inputs to muscles during movement cancellation

Cortical beta (13-30 Hz) and gamma (30-60 Hz) oscillations have been investigated during motor processing. Although they are at frequencies greater than the dynamic bandwidth of muscle contraction, these oscillations are partly transmitted from the cortex to motoneurons and muscles. Little is known about when and why this transmission occurs. We developed an experimental approach to examine these high frequency inputs to motoneurons under different motor states while maintaining a stable force, thus constraining behaviour. We acquired brain and muscle activity during a GO/NO-GO task. In this experiment, the effector muscle for the task (tibialis anterior) was kept tonically active during the trials, while participants (N=9) reacted to sequences of auditory stimuli by either keeping the contraction unaltered ( NO-GO trials), or by quickly performing a ballistic contraction ( GO trials). Motor unit (MU) firing activity was extracted from high-density surface and intramuscular electromyographic signals, and the changes in its spectral contents in the NO-GO trials were analysed. We observed an increase in beta and low-gamma (30-45 Hz) activity post NO-GO cue at the brain and muscle levels. There was also an increase in the activity within 8-12 Hz, which was only observed at the muscle level. Overall, our results suggest that the cortical processing of movement cancellation occurs at least in part via increased power of high-frequency oscillations transmitted downstream to the muscles. These changes occur without alterations in behaviour, suggesting that the downstream transmission of these high-frequency oscillations does not have a direct functional impact.

neuroscience↗

bioRxiv2023

Non-linearity in motor unit velocity twitch dynamics: Implications for ultrafast ultrasound source separation

Ultrasound (US) muscle image series can be used for peripheral human-machine interfacing based on global features, or even on the decomposition of US images into the contributions of individual motor units (MUs). With respect to state-of-the-art surface electromyography (sEMG), US provides higher spatial resolution and deeper penetration depth. However, the accuracy of current methods for direct US decomposition, even at low forces, is relatively poor. These methods are based on linear mathematical models of the contributions of MUs to US images. Here, we test the hypothesis of linearity by comparing the average velocity twitch profiles of MUs when varying the number of other concomitantly active units. We observe that the velocity twitch profile has a decreasing peak-to-peak amplitude when tracking the same target motor unit at progressively increasing contraction force levels, thus with an increasing number of concomitantly active units. This observation indicates non-linear factors in the generation model. Furthermore, we directly studied the impact of one MU on a neighboring MU, finding that the effect of one source on the other is not symmetrical and may be related to unit size. We conclude that a linear approximation is limiting the decomposition methods to decompose full velocity twitch trains from velocity images, highlighting the need for more advanced models and methods for US decomposition than those currently employed.

bioengineering↗

bioRxiv2022

Low-frequency motor cortex EEG predicts four levels of rate of change of force during ankle dorsiflexion

The movement-related cortical potential (MRCP) is a low-frequency component of the electroencephalography (EEG) signal recorded from the motor cortex and its neighboring cortical areas. Since the MRCP encodes motor intention and execution, it may be utilized as an interface between patients and neurorehabilitation technologies. This study investigates the EEG signal recorded from the Cz electrode to discriminate between four levels of rate of force development (RFD) of the tibialis anterior muscle. For classification, three feature sets were evaluated to describe the EEG traces. These were (i) MRCP morphological characteristics in the{delta} -band such as amplitude and timing, (ii) MRCP statistical characteristics in the{delta} -band such as mean, standard deviation, and kurtosis, and (iii) wideband time-frequency features in the 0.5-90 Hz range. Using a support vector machine for classification, the four levels of RFD were classified with a mean (SD) accuracy of 82% (7%) accuracy when using the time-frequency feature space, and with an accuracy of 75% (12%) when using the MRCP statistical characteristics. It was also observed that some of the key features from the statistical and morphological sets responded monotonically to the intensity of the RFD. Examples are slope and standard deviation in the (0, 1)s window for the statistical, and min1 and minn for the morphological sets. This monotonical response of features explains the observed performance of the{delta} -band MRCP and corresponding high discriminative power. Results from temporal analysis considering the pre-movement phase ((-3, 0)s) and three windows of the post-movement phase ((0, 1)s, (1, 2)s, and (2, 3)s)) suggest that the complete MRCP waveform represents high information content regarding the planning, execution, duration, and ending of the isometric dorsiflexion task using the tibialis anterior muscle. Results shed light on the role of{delta} -band in translating to motor command, with potential applications in neural engineering systems.

bioengineering↗

bioRxiv2022

Augmenting CAR NK cell Anti-tumor Activity by Synapse Tuning

Introductory ParagraphChimeric antigen receptor (CAR) technologies have been clinically implemented for the treatment of hematological malignancies; however, solid tumors remain resilient to CAR therapeutics1-3. Natural Killer (NK) cells may provide an optimal class of immune cells for CAR-based approaches due to their inherent anti-tumor functionality. We sought to tune CAR synapses in NK cells by adding an intracellular scaffolding protein binding site to the CAR. We employed a PDZ binding motif (PDZbm) that specifically binds Scribble4 resulting in additional scaffolding crosslinking to enhance synapse formation and cell polarization5,6. Combined effects of this novel CAR design resulted in increased effector cell functionality in vitro and in vivo. Synapse-tuned CAR-NK cells exhibited amplified synaptic strength, number and abundance of secreted cytokines, enhanced killing of tumor cells, and prolonged survival with tumor clearance in two solid tumor models. Thus, synapse tuning has the potential to improve the efficacy of CAR-based cell therapeutics.

immunology↗

bioRxiv2022

Peritubular macrophages phagocyte remains of undifferentiated spermatogonia in mouse testis

The cells involved in spermatogenesis are germ-cells, called spermatogonia, classified as: type A-undifferentiated, type A-intermediate and type B. During the spermatogenesis, more than 75% of the germ-cells undergo apoptosis and most of them are phagocyted by Sertoli cells. Peritubular macrophages in adult mouse testis are macrophages that both stimulate the proliferation and differentiation of undifferentiated spermatogonia in the wall of the seminiferous tubule. They have long processes and ramified appearance that squished between the lateral sides of neighbor myoid cells. We show, that a population of peritubular macrophages, grouped in pairs and activated, phagocyted undifferentiated spermatogonia in apoptosis. In adult mouse testis, 3.3x 105 undifferentiated spermatogonia are in the germinal epithelium and 8,250 of them are in apoptosis. We counted in the testis 2,634.2 {+/-}160 peritubular macrophages with phagocytic activity. If each one phagocyted one undifferentiated spermatogonia in apoptosis, it may indicated that peritubular macrophages phagocyted 31.9 % of the total undifferentiated spermatogonia in apoptosis. According to our knowledges, this is the first time that it is shown that undifferentiated spermatogonia in apoptosis are cleaned by peritubular macrophages. Summary SentenceWe report that peritubular macrophages of adult mouse testis, phagocytic remains of apoptotic undifferentiated spermatogonia. These results show that peritubular macrophages, like Sertoli cells, participate in the remotion of germinal cells in the testis.

cell biology↗