Biology subjects

Raz, A.

Publications and source records attributed to Raz, A..

16 recordsLinked to original sources

bioRxiv2026

Decoupling Transcription from Cell Fate Preserves Germ Cell Totipotency

Only germ cells can give rise to a totipotent embryo, yet a conserved transcriptional program for germ cell identity remains elusive. Profiling Drosophila primordial germ cells (PGCs) across embryogenesis, we find that nascent PGCs are not silent, as previously thought, but instead transcribe the same totipotency program as the early embryo, reflecting an open chromatin state. This chromatin state, established by the pioneer factor Zelda, persists in PGCs throughout development. The associated transcriptional program normally drives somatic differentiation, but in PGCs the conserved RNA-regulator Nanos represses its translation, leaving germline chromatin uncommitted. Cells that fail to establish the totipotent state die before reaching the gonad. Thus, germ cells preserve developmental potential not by restricting transcription, but by preventing transcripts from determining cell fate.

developmental biology↗

bioRxiv2026

An AI-assisted platform for quantitative histopathological analysis in interstitial lung disease

Interstitial lung diseases (ILDs) are heterogeneous pulmonary disorders characterized by chronic inflammation and/or fibrosis. 30-40% of ILD patients develop fibrotic disease that is associated with progressive respiratory decline and poor prognosis, particularly in idiopathic pulmonary fibrosis. Current antifibrotic therapies slow disease progression but do not reverse fibrosis, highlighting the need for improved therapeutic strategies. Robust histopathological evaluation in preclinical models is essential for drug development; however, conventional scoring systems are semi-quantitative, labor-intensive, subject to inter-observer variability, and rely on limited field sampling. Here, we introduce FibroSight, a standalone platform for compartment-resolved quantification of lung remodeling in Sirius Red-stained sections. By integrating deep learning- based structural segmentation with color-based feature extraction, FibroSight enables highly automated whole-lobe analysis without requiring complex computational setup. The platform quantifies complementary remodeling parameters, including parenchymal collagen fraction, parenchymal tissue density, nuclear area fraction, parenchymal airspace fraction, and airway- and vascular-associated remodeling. Validated in the bleomycin-induced fibrosis model, FibroSight-derived metrics strongly correlated with expert Ashcroft scoring and showed stronger associations with histological severity than corresponding outputs from a semi-automated ImageJ-based workflow. The platform further distinguished inflammatory from fibrotic remodeling in influenza-induced lung injury and demonstrated translational proof-of-concept applicability in human ILD biopsy specimens. By enabling scalable, reproducible, and multi-compartment histological quantification, FibroSight provides a practical framework for objective assessment of lung remodeling. This approach expands conventional fibrosis evaluation by integrating fibrotic, inflammatory, airway, and vascular-associated readouts, supporting more precise analysis of disease mechanisms and therapeutic responses in preclinical and translational ILD research.

pathology↗

bioRxiv2026

REM Sleep Disengagement of β Oscillations Permits Rapid Dream Movements in Parkinsonism

REM sleep behavior disorder is a hallmark of prodromal -synucleinopathies, yet why patients with Parkinsons disease can generate rapid, coordinated movements during REM sleep despite daytime bradykinesia remains unknown. Here we combined recordings of eye movements, cortical electroencephalography, and basal ganglia-thalamic neuronal activity across vigilance states in non-human primates before and after MPTP-induced parkinsonism. Parkinsonism enhanced {beta} oscillations and impaired movement-related neural dynamics during wakefulness and NREM sleep, whereas both pathological {beta} activity and motor impairments were attenuated during REM sleep. {beta} suppression preceded the onset of REM sleep, indicating that network reconfiguration begins before REM becomes behaviorally apparent. These findings demonstrate that Parkinsonian network dysfunction is dynamically gated by brain state rather than continuously imposed by dopamine depletion. REM sleep is a natural physiological condition in which {beta} oscillations are disengaged, uncovering a latent capacity, normally masked by REM atonia, for rapid movement even in the dopamine-depleted motor network.

neuroscience↗

bioRxiv2026

Fertility Gene Introns Harbor Transposable Elements that Shape Y-Loop Architecture

Transposable elements (TEs) are powerful drivers of genome evolution, yet how they persist under selection and become incorporated into host regulatory networks remains poorly understood. In the Drosophila male germline, TEs are highly expressed during the spermatocyte stage, coinciding with activation of giant fertility genes on the Y chromosome. These genes contain megabase-scale introns enriched for repetitive DNA, and three of these genes form prominent nuclear structures known as Y-loops, providing a unique system to investigate gene regulation. Here, we show that multiple TEs expressed in spermatocytes are transcribed from the introns of Y-linked fertility genes. RNA fluorescence in situ hybridization (FISH) targeting several TEs, including accord2, Juan, and HMS Beagle, illuminates distinct nuclear regions corresponding to kl-2, kl-3, and kl-5, respectively. Genetic perturbation of these fertility gene loci or disruption of RNA-processing factors eliminates these TE transcripts, demonstrating that these TE sequences are embedded within Y chromosome-associated nascent transcripts rather than being independently transcribed. The identity and expression patterns of Y-loop-associated TEs vary extensively among closely related Drosophila species, consistent with the previously documented rapid evolution of Y-linked loci and suggesting that TEs may contribute to the genetic diversification of these giant fertility genes. We propose that continual turnover of repetitive elements within Y-linked introns provides a mechanism by which rapidly evolving repetitive DNA influences germline gene regulation, male fertility, and speciation.

genomics↗

bioRxiv2026

Isoflurane preferentially modulates synaptic responses to corticocortical stimulation over thalamocortical stimulation

ObjectiveTo test the effect of Isoflurane on synaptic transmission of cortico-cortical and thalamocortical projections to the auditory cortex, and investigate how it modulates cortical sensory information processing to produce unconsciousness. MethodsUsing murine auditory thalamocortical brain slices, afferent pathways from the medial geniculate body (MGB) and layer 1 of the proximal cortex were stimulated to evoke excitatory postsynaptic potentials (eEPSPs) in cortical neurons. Whole-cell recordings were made from pyramidal and fast-spiking neurons in layer 2/3 and layer 5. eEPSPs were evaluated along with intrinsic membrane properties in response to stimulation of both pathways with and without isoflurane. ResultsIsoflurane administration resulted in significant eEPSP amplitude reduction following stimulation of both thalamic and cortical pathways, in layer 2/3 (p=0.015, p<0.001) and layer 5 (p<0.001, p<0.001) pyramidal neurons; while it only significantly reduced eEPSP amplitude in fast-spiking interneurons with cortical stimulation (p<0.001). Overall, isoflurane preferentially suppressed synaptic responses to cortico-cortical stimulation compared to thalamocortical (p=0.0002). Under isoflurane, cortico-cortical compared to thalamocortical stimulation evoked eEPSPs with reduced 10-90% rise time in both layer 2/3 and 5 pyramidal neurons, and shorter latency layer 5 neurons. Paired pulse ratio was not changed by isoflurane application, although an interesting loss of depression trend appear in layer 5 pyramidal neurons stimulated by cortical activation. Additional intrinsic neuronal measurements revealed that isoflurane reduced spike threshold significantly in both layer 2/3 and layer 5 neurons, reduced spike latency in layer 2/3 neurons, and input resistance in layer 5 neurons. However, these intrinsic neuronal changes were not seen in fast-spiking interneurons. All isoflurane induced changes were reversible during wash out. ConclusionsApplication of 1% isoflurane to brain slices significantly reduced the amplitudes of eEPSPs and modulated intrinsic neuronal properties. The effects on eEPSP amplitude were greater for cortical stimulation compared to thalamic stimulation. Isoflurane modulated intrinsic neuronal firing properties in pyramidal neurons, but not in fast-spiking interneurons.

neuroscience↗

bioRxiv2025

Basal ganglia-independent thalamic bursts do not wake cortex during sleep

The thalamus is a key forebrain structure that gates peripheral, subcortical, and cortico-cortical communication1,2. Awake thalamic bursts provide the cortex with a "wake-up" signal2-4. Paradoxically, thalamic neurons discharge tonically during cellular depolarization and activated brain states (wakefulness, REM sleep) but burst during hyperpolarization and NREM sleep5-9. It has been proposed that NREM thalamic bursts do not awaken the cortex because of their periodic and synchronized nature2-4; however, this has never been tested in vivo during natural sleep. We simultaneously recorded polysomnographic signals, local field potentials, and spiking activity from multiple thalamic neurons in the ventral anterior and centromedian nuclei of two female non-human primates during naturally occurring vigilance states. These nuclei receive GABAergic output from the basal ganglia10,11, with discharge rate and GABA outflow decreasing during NREM sleep12. We found that despite the expected thalamic depolarization, bursting increased significantly. NREM bursts were neither periodic nor highly synchronized. However, EEG activity time-locked to burst onset during NREM sleep differed markedly from that observed during wakefulness and REM sleep. These results support a modulatory, rather than a driving, relationship between the basal ganglia and thalamus. NREM thalamic bursts do not awaken the cortex, probably due to unique state-dependent thalamocortical dynamics.

neuroscience↗

bioRxiv2023

Unravelling the neural dynamics of hypnotic susceptibility: Aperiodic neural activity as a central feature of hypnosis

How well a person responds to hypnosis is a stable trait, which exhibits considerable inter-individual diversity across the general population. Yet, its neural underpinning remains elusive. Here, we address this gap by combining EEG data, multivariate statistics, and machine learning in order to identify brain patterns that differentiate between individuals high and low in susceptibility to hypnosis. In particular, we computed the periodic and aperiodic components of the EEG power spectrum, as well as graph theoretical measures derived from functional connectivity, from data acquired at rest (pre-induction) and under hypnosis (post-induction). We found that the 1/f slope of the EEG spectrum at rest was the best predictor of hypnotic susceptibility. Our findings support the idea that hypnotic susceptibility is a trait linked to the balance of cortical excitation and inhibition at baseline and offers novel perspectives on the neural foundations of hypnotic susceptibility. Future work can explore the contribution of background 1/f activity as a novel target to distinguish the responsiveness of individuals to hypnosis at baseline in the clinic. Significance StatementHypnotic phenomena reflect the ability to alter ones subjective experiences based on targeted verbal suggestions. This ability varies greatly in the population. The brain correlates to explain this variability remain elusive. Addressing this gap, our study employs machine learning to predict hypnotic susceptibility. By recording electroencephalography (EEG) before and after a hypnotic induction and analyzing diverse neurophysiological features, we were able to determine that several features differentiate between high and low hypnotic susceptible individuals both at baseline and during hypnosis. Our analysis revealed that the paramount discriminative feature is non-oscillatory EEG activity before the induction--a new finding in the field. This outcome aligns with the idea that hypnotic susceptibility represents a latent trait observable through a plain five-minutes resting-state EEG.

neuroscience↗

bioRxiv2022

Exogenous attention interferes with endogenous attention processing via lateralized alpha power

Current theories of attention differentiate exogenous (bottom-up) from endogenous (top-down) orienting of visuospatial attention. While both forms of attentional processing engage different processes, endogenous and exogenous attention are thought to share processing resources, as shown by recent empirical evidence of their functional interactions. Here, we aim to uncover the neurobiological basis of how salient events that drive exogenous attention disrupts endogenous attention processes. We hypothesize that interference from exogenous attention over endogenous attention involves alpha-band activity, a neural marker of visuospatial attention. To test this hypothesis, we contrast the effects of endogenous attention across two experimental conditions: a single cueing condition where endogenous attention is engaged in isolation, and a double cueing condition where endogenous attention is concurrently engaged with exogenous attention. Our results are consistent with previous work and show that the concurrent engagement of exogenous attention interferes with endogenous attention processes. Importantly, we evaluate our main hypothesis using a moderated mediation model. We found that changes in alpha-band activity mediate the relationship between endogenous attention and its benefits on task performance, and that the interference of exogenous attention on endogenous attention occurs via the moderation of this indirect effect. Altogether, our results substantiate a model of attention, whereby top-down and bottom-up attentional processes compete for shared neurophysiological resources. This model accounts for the observed patterns of interference between exogenous and endogenous attention. Significance StatementScientists differentiate top-down and bottom-up visuospatial attention processes. While bottom-up attention is rapidly engaged by emerging demands from the environment, top-down attention reflects slow voluntary shifts of attention. Several lines of research substantiate the idea that top-down and bottom-up attentional processes involve distinct brain systems. An increasing number of studies, however, argue that both attention systems share brain processing resources. The current study examines how salient visual events that engage bottom-up processes interfere with top-down processes. Using neurophysiological recordings and multivariate pattern classification techniques, the researchers show that both top-down and bottom-up attention processes do share brain resources expressed via alpha-band neurophysiological activity (8-12 Hz). The results further demonstrate that the interference patterns observed over brain activity in the alpha-band between both attention systems explains, in part, the interference between top-down and bottom-up attention at the behavioural level. The authors conclude by proposing a model of visuospatial attention whereby the dynamics between both attention systems are determined by their competition for limited brain processing resources.

neuroscience↗

bioRxiv2022

Evidence for shared resources in visuospatial attention: Endogenous attention misleads the decoding of exogenous attention in alpha rhythms

Prevailing accounts of visuospatial attention differentiate exogenous (involuntary shifts) from endogenous (voluntary control) orienting of attention. While these two forms of attentional processes are functionally separable, their interactions have been at the center of ongoing debates for more than two decades. One hypothesis is that exogenous and endogenous attention interfere because they share processing resources. Here, we confirm that endogenous attention alters exogenous attention processing, and examine the role of alpha-band neurophysiological activity in such interference events. We contrast the effects of exogenous attention across two experimental conditions: a single-cueing condition where exogenous attention is engaged alone, and a double-cueing condition where exogenous attention is concurrently engaged with endogenous attention. Our results show that the engagement of endogenous attention alters the emergence of exogenous attention across cue-related and target-related brain processes. Importantly, we also report that classifiers trained to decode exogenous attention from the power and phase of alpha-band brain activity in the single-cueing condition fail to do so in the doublecueing condition, where endogenous attention is also engaged. Taken together, our observations challenge the idea that exogenous attention operates independently from top-down processes and demonstrate that both forms of attention orienting engage shared brain processes, which constrain their interactions. Significance StatementVisuospatial attention is often dichotomized into top-down and bottom-up components: Top-down attention reflects slow voluntary shifts of attention orienting, while bottom-up attention is recruited by emerging demands from the environment. A large body of previous findings support the view that these two forms of attention orienting are functionally separable, with some interactions. The current study examines such interactions between top-down and bottom-up attention. Using electroencephalography (EEG) and multivariate pattern classification techniques, the researchers show that top-down attention interferes with the brain activity patterns of bottom-up attention. Moreover, machine learning classifiers trained to detect bottom-up attention based on brain activity in the alpha band (8-12 Hz), a marker of visuospatial attention, fail systematically when top-down attention is also engaged. The authors therefore conclude that both forms of visuospatial orienting are supported by overlapping processes that share brain resources.

neuroscience↗

bioRxiv2022

The genetic structure of a wild wheat population has remained associated with microhabitats over 36 years

Long-term genetic studies of wild populations are very scarce, but are essential for connecting ecological and population genetics models, and for understanding the dynamics of biodiversity. We present a study of a wild wheat population sampled over a 36-year period at high spatial resolution. We genotyped 832 individuals from regular sampling along transects during the course of the experiment. Genotypes were clustered into ecological microhabitats over scales of tens of metres, and this clustering was remarkably stable over the 36 generations of the study. Simulations show that it is difficult to explain this spatial and temporal stability using only limited dispersal, suggesting a role for fine-scale local adaptation to ecological parameters. Using a common-garden experiment, we showed that the genotypes found in distinct microhabitats differ phenotypically, further supporting the hypothesis of local adaptation. Our results provide a rare insight into the population genetics of a natural population over a long monitoring period.

evolutionary biology↗

bioRxiv2020

Spatio-temporal patterns of population responses in the visual cortex under Isoflurane: from wakefulness to loss of consciousness

Anesthetic drugs are widely used in medicine and research to mediate loss of consciousness (LOC). Despite the vast use of anesthesia, how LOC affects cortical sensory processing and the underlying neural circuitry, is not well understood. We measured neuronal population activity in the visual cortices of awake and isoflurane anesthetized mice and compared the visually evoked responses under different levels of consciousness. We used voltage-sensitive dye imaging (VSDI) to characterize the temporal and spatial properties of cortical responses to visual stimuli over a range of states from wakefulness to deep anesthesia. VSDI enabled measuring the neuronal population responses at high spatial (meso-scale) and temporal resolution from several visual regions (V1, extrastiate-lateral (ESL) and extrastiate-medial (ESM)) simultaneously. We found that isoflurane has multiple effects on the population evoked response that augmented with anesthetic depth, where the largest changes occurred at LOC. Isoflurane reduced the response amplitude and prolonged the latency of response in all areas. In addition, the intra-areal spatial spread of the visually evoked activity decreased. During visual stimulation, intra-areal and inter-areal correlation between neuronal populations decreased with increasing doses of isoflurane. Finally, while in V1 the majority of changes occurred at higher doses of isoflurane, higher visual areas showed marked changes at lower doses of isoflurane. In conclusion, our results demonstrate a reverse hierarchy shutdown of the visual cortices regions: low-dose isoflurane diminishes the visually evoked activity in higher visual areas before lower order areas and cause a reduction in inter-areal connectivity leading to a disconnected network.

neuroscience↗

bioRxiv2020

More than just front or back: Parietal-striatal-thalamic circuits predict consciousness level

Major theories of consciousness disagree on the key neural substrates. In Global Neuronal Workspace Theory and Higher-order Theories, consciousness depends on frontal cortex, whereas Integrated Information Theory and Recurrent Processing Theory highlight posterior contributions. Most theories omit subcortical influences. To test these theories, we performed simultaneous frontal, parietal, striatal and thalamic recordings from awake, sleeping and anesthetized macaques, further manipulating consciousness with deep-brain thalamic stimulation. Information theoretic measures and machine learning approaches suggested parietal cortex, striatum and thalamus contribute more to consciousness level than frontal cortex. While these findings provide greater support for Integrated Information Theory than the others, the theory does not incorporate subcortical structures such as the striatum. We therefore propose that thalamo-striatal circuits have a cause-effect structure to generate integrated information. One Sentence SummaryParietal, but not frontal, circuits incorporating striatum and thalamus predict consciousness.

neuroscience↗

bioRxiv2020

Optogenetic activation of afferent pathways in brain slices and modulation of responses by volatile anesthetics

Anesthetics influence consciousness in part via their actions on thalamocortical circuits. However, the extent to which volatile anesthetics affect distinct cellular and network components of these circuits remains unclear. Ex vivo brain slices provide a means by which investigators may probe discrete components of complex networks and disentangle potential mechanisms underlying the effects of volatile anesthetics on evoked responses. To isolate potential cell type- and pathway-specific drug effects in brain slices, investigators must be able to independently activate afferent fiber pathways, identify non-overlapping populations of cells, and apply volatile anesthetics to tissue in aqueous solution. In this protocol, we describe methods to measure optogenetically-evoked responses to two independent afferent pathways to neocortex in ex vivo brain slices. We record extracellular responses to assay network activity and conduct targeted whole-cell patch clamp recordings in somatostatin- and parvalbumin-positive interneurons. We also describe a means by which to deliver physiologically relevant concentrations of isoflurane via artificial cerebral spinal fluid to modulate cellular and network responses. SUMMARYEx vivo brain slices can be used to study the effects of volatile anesthetics on evoked responses to afferent inputs. We employ optogenetics to independently activate thalamocortical and corticocortical afferents to non-primary neocortex, and we modulate synaptic and network responses with isoflurane.

neuroscience↗

bioRxiv2019

Central thalamus modulates consciousness by controlling layer-specific cortical interactions

Consciousness is the capacity to experience ones environment and internal states. The minimal mechanisms sufficient to produce this experience, the neural correlates of consciousness (NCC), are thought to involve thalamocortical and intracortical interactions, but the key operations and circuit paths are unclear. We simultaneously recorded neural activity in central thalamus and across layers of fronto-parietal cortex in awake, sleeping and anesthetized macaques. Spiking activity was selectively reduced in deep cortical layers and thalamus during unconsciousness, as were intracolumnar and interareal interactions at alpha and gamma frequencies. Gamma-frequency stimulation, when focused on the central lateral thalamus of anesthetized macaques, counteracted these neural changes and restored consciousness. These findings suggest that the NCC involve both corticocortical feedforward and feedback pathways coordinated with intracolumnar and thalamocortical loops.\n\nSummaryStimulation of central lateral thalamus counters anesthesia to restore wake cortical dynamics and consciousness.

neuroscience↗

bioRxiv2019

The APL1 immune factor is encoded by a single ancestral gene in most Anopheles species and expanded to three paralogs with distinct function in the Anopheles gambiae complex

BackgroundThe recent reference genome assembly and annotation of the Asian malaria vector Anopheles stephensi revealed only one gene encoding the leucine-rich repeat immune factor APL1, while in Anopheles gambiae and sibling Anopheles coluzzii, APL1 factors are encoded by a family of three paralogs. The phylogeny and biological function of the unique APL1 gene in A. stephensi have not yet been specifically examined.\n\nMethodsThe APL1 locus was manually sequenced to confirm the computationally predicted single APL1 gene in A. stephensi, and APL1 evolution within Anopheles was explored by phylogenomic analysis. The single or paralogous APL1 genes were silenced in A. stephensi and A. coluzzii, respectively, followed by mosquito survival analysis, experimental infection with Plasmodium, and expression analysis.\n\nResultsAPL1 is present as a single ancestral gene in most Anopheles including A. stephensi, but has expanded to three paralogs in an African lineage that includes only the Gambiae species complex and Anopheles christyi. Silencing of the unique APL1 copy in A. stephensi results in significant mosquito mortality. Elevated mortality of APL1-depleted A. stephensi is rescued by antibiotic treatment, suggesting that bacteria are the cause of mortality, and that the unique APL1 gene is essential for host survival. Successful Plasmodium development in A. stephensi depends upon APL1 activity for protection from high host mortality, probably caused by exposure to enteric bacteria when parasites cross the midgut epithelial barrier. In contrast, silencing of all three APL1 paralogs in A. coluzzii does not result in elevated mortality, either with or without Plasmodium infection. Expression of the single APL1 gene is regulated by both the Imd and Toll immune pathways, while control by the two pathways is subdivided to different paralogs in the expanded APL1 locus.\n\nConclusionsAPL1 underwent neofunctionalization with both loss and gain of functions concomitant with expansion from a single ancestral gene to three paralogs in one lineage of African Anopheles. The evolution of an expanded APL1 gene family could be a factor contributing to the exceptional levels of malaria transmission mediated by human-feeding members of the Gambiae complex in Africa.

genetics↗

bioRxiv2017

Propofol-Induced Unresponsiveness is Associated with Impaired Feedforward Connectivity in the Cortical Hierarchy

BackgroundImpaired consciousness has been associated with impaired cortical signal propagation following transcranial magnetic stimulation (TMS). Herein we hypothesized that the reduced current propagation under propofol-induced unresponsiveness is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy.\n\nMethodsEight subjects underwent left occipital TMS coupled with high-density electroencephalograph (EEG) recordings during wakefulness and propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical cortical sources involved in visual processing. Dynamic causal modelling (DCM) of evoked and induced source-space responses was used to investigate propofols effects on connectivity between regions.\n\nResultsPropofol produced a wideband reduction in evoked power following TMS in five out of six electrodes. Bayesian Model Selection supported a DCM with hierarchical feedforward and feedback connections to best fit the data. DCM of induced responses revealed that the primary effect of propofol was impaired feedforward responses in cross frequency theta/alpha-gamma coupling and within frequency theta coupling (F contrast, Family Wise Error corrected p<0.05). An exploratory analysis (thresholded at uncorrected p<0.001) also suggested that propofol impaired feedforward and feedback beta band coupling. Posthoc analyses showed impairments in all feedforward connections and one feedback connection from parietal to occipital cortex. DCM of the evoked response potential showed impaired feedforward connectivity between left sided occipital and parietal cortex (T contrast p=0.004, Bonferroni corrected).\n\nConclusionsOur data suggest that propofol-induced loss of consciousness is associated with reduced evoked power and impaired hierarchical feedforward connectivity following occipital TMS.

neuroscience↗