Biology subjects

Song, Y.

Publications and source records attributed to Song, Y..

At least 163 records · Page 9Linked to original sources

bioRxiv2024

TET2-mediated epigenetic modification promotes stress senescence of pancreatic β cells in type 2 diabetes mellitus

Epigenetic modification plays a key role in {beta} cell senescence. In the regulation of gene expression, there is a complex and close relationship between DNA methylation and histone modification. In order to explore its specific mechanism in T2DM {beta} cell senescence, we used postbisulfite aptamer labeling of genome-wide bisulfite-SEQ, chromatin immunocoprecipitation-SEQ, RNA-SEQ, CRISPR/Cas9 TETs knockout, RNA interference, TET2 inhibitors, lentiviral overexpression, and gene knockout mouse models. Our study found that demethylase TET2 was localized in the islets of mice, and the expression level increased with age. TET2 knockout in pancreatic {beta} cells can hypermethylate PTEN, up-regulate MOF and enrich H4K16ac, and reduce the level of aging markers. This study confirmed that TET2-mediated PTEN DNA methylation can promote a new mechanism of {beta} cell senescence by regulating H4K16ac, providing a new molecular mechanism and therapeutic target for T2DM {beta} cell senescence therapy.

cell biology↗

bioRxiv2024

The distribution of clade size in a coalescent diversification model

Characterizing the patterns and determinants of biological diversity is a central aim of evolutionary biology. Doing so requires developing expectations for clade size, the relationship between the number of species in a clade and its age, for standard diversification models, such as the coalescent or birth-death process. These expectations are necessary for identifying diversity outliers, specious or depauperate clades in the macroevolutionary context or transmission clusters of particular or little public health concern in the epidemiological context, and for testing alternative diversification hypotheses. Here, we derive a closed-form expression for the distribution of clade sizes under the widely used Kingman coalescent diversification model and extend the results to allow the number of niches (the effective population size) to vary through time. This result complements analogous results for the birth-death model in that it provides expectations for the joint distribution of clade sizes for a case where diversification is strongly density-dependent.

genetics↗

bioRxiv2024

Computer prediction and genetic analysis identifies retinoic acid modulation as a driver of conserved longevity pathways in genetically-diverse Caenorhabditis nematodes

Aging is a pan-metazoan process with significant consequences for human health and society--discovery of new compounds that ameliorate the negative health impacts of aging promise to be of tremendous benefit across a number of age-based comorbidities. One method to prioritize a testable subset of the nearly infinite universe of potential compounds is to use computational prediction of their likely anti-aging capacity. Here we present a survey of longevity effects for 16 compounds suggested by a previously published computational prediction set, capitalizing upon the comprehensive, multi-species approach utilized by the Caenorhabditis Intervention Testing Program (CITP). While eleven compounds (aldosterone, arecoline, bortezomib, dasatinib, decitabine, dexamethasone, erlotinib, everolimus, gefitinib, temsirolimus, and thalidomide) either had no effect on median lifespan or were toxic, five compounds (all-trans retinoic acid, berberine, fisetin, propranolol, and ritonavir) extended lifespan in Caenorhabditis elegans. These computer predictions yield a remarkable positive hit rate of 30%. Deeper genetic characterization of the longevity effects of one of the most efficacious compounds, the endogenous signaling ligand all-trans retinoic acid (atRA, designated tretinoin in medical products), which is widely prescribed for treatment of acne, skin photoaging and acute promyelocytic leukemia, demonstrated a requirement for the regulatory kinases AKT-1 and AKT-2. While the canonical Akt-target FOXO/DAF-16 was largely dispensable, other conserved Akt-targets (Nrf2/SKN-1 and HSF1/HSF-1), as well as the conserved catalytic subunit of AMPK AAK-2, were all necessary for longevity extension by atRA. Evolutionary conservation of retinoic acid as a signaling ligand and the structure of the downstream effector network of retinoic acid combine to suggest that the all-trans retinoic acid pathway is an ancient metabolic regulatory system that can modulate lifespan. Our results highlight the potential of combining computational prediction of longevity interventions with the power of nematode functional genetics and underscore that the manipulation of a conserved metabolic regulatory circuit by co-opting endogenous signaling molecules is a powerful approach for discovering aging interventions.

genetics↗

bioRxiv2024

Understanding the epidemiology and pathogenesis of Mycobacterium tuberculosis with non-redundant pangenome and population genetics

Tuberculosis is a major public health threat demanding more than one million lives every year. Many challenges exist to defeat this deadly infectious disease which address the importance of a thorough understanding of the biology of the causative agent Mycobacterium tuberculosis (MTB). We generated a non-redundant pangenome of 420 epidemic MTB strains from China. We estimate that MTB strains have a pangenome of 4,278 genes encoding 4,183 proteins, of which 3,438 of which are core genes. However, due to 99,694 interruptions in 2,447 coding genes, only 1,651 may be translated in all samples, which dramatically reduces the number of active core genes. Of these interruptions, 67,315 (67.52%) could be classified by various genetic variations detected by currently available tools, and more than half of them are due to structure variations, mostly small indels. We further describe differential evolutionary patterns of genes under the influences of selective pressure, population structure and background selection. While selective pressure is ubiquitous among these coding genes, evolutionary adaptations primarily occur in 1,313 genes. Genes located in the cell wall and membrane region are under the strongest selective pressure, while biological processes including regulation of transcription, translation and regulation of growth are under strongest background selection in MTB. The metabolism of fatty acids may be an outstanding example of evolutionary adaption for MTB under current selective pressure. This study provides a comprehensive view on the genetic diversity and evolution patterns of coding genes in MTB which may deepen our understanding of its epidemiology and pathogenicity.

microbiology↗

bioRxiv2024

Fungal spore seasons advanced across the US over two decades of climate change

Phenological shifts due to climate change have been extensively studied in plants and animals. Yet, the responses of fungal spores--crucial organisms that play important roles in ecosystems and act as airborne allergens--remain understudied. This knowledge gap in global change biology hinders our understanding of its ecological and public health implications. To bridge this gap, we acquired a long-term (2003 [~] 2022), large-scale (the continental US) dataset of airborne fungal spores collected by the US National Allergy Bureau. We first pre-processed the spore data by gap-filling and smoothing. Afterward, we extracted ten metrics describing the phenology (e.g., start and end of season) and intensity (e.g., peak concentration and integral) of fungal spore seasons. These metrics were derived using two complementary but not mutually exclusive approaches--ecological and public health approaches, defined as percentiles of total spore concentration and allergenic thresholds of spore concentration, respectively. Using linear mixed effects models, we quantified annual temporal shifts in these metrics across the continental US. We revealed a significant advancement in the onset of the spore seasons defined in both ecological (11 days, 95% confidence interval: 0.4 [~] 23 days) and public health (22 days, 6 [~] 38 days) approaches over two decades. Nevertheless, the total spore concentration in an annual cycle and in a spore allergy season tended to decrease over time. The earlier start of the spore season was significantly correlated with climatic variables, such as warmer temperatures and altered precipitations. Overall, our findings suggest possible climate-driven advanced fungal spore seasons, highlighting the importance of climate change mitigation and adaptation in public health decision-making.

ecology↗

bioRxiv2024

ENACT: End-to-End Analysis of Visium High Definition (HD) Data

MotivationSpatial transcriptomics (ST) enables the study of gene expression within its spatial context in histopathology samples. To date, a limiting factor has been the resolution of sequencing based ST products. The introduction of the Visium High Definition (HD) technology opens the door to cell resolution ST studies. However, challenges remain in the ability to accurately map transcripts to cells and in assigning cell types based on the transcript data. ResultsWe developed ENACT, the first tissue-agnostic pipeline that integrates advanced cell segmentation with Visium HD transcriptomics data to infer cell types across whole tissue sections. Our pipeline incorporates novel bin-to-cell assignment methods, enhancing the accuracy of single-cell transcript estimates. Validated on diverse synthetic and real datasets, our approach is both scalable and effective offering a robust solution for spatially resolved transcriptomics analysis. Availability and implementationENACT source code is available at https://github.com/Sanofi-Public/enact-pipeline. Experimental data is available at https://zenodo.org/records/13887921. Supplementary information: Supplementary data are available at BiorXiv online.

bioinformatics↗

bioRxiv2024

Bilateral Symmetry and Asymmetry in the C. elegans Connectome: A Graph-Theoretic Analysis based on Redundancy Measures

Understanding the balance between symmetry and asymmetry in animal nervous systems is crucial for unraveling the complexities of neural architectures and their functions. Previous studies have primarily focused on morphological symmetry, such as neuron placement, leaving the symmetry in the functional architecture largely unexplored. The current study investigates this aspect within the Caenorhabditis elegans connectomes by introducing a graph-theoretic approach. By defining a mirror-symmetry index, we quantitatively assess the symmetry in these connectomes, revealing a significant level of bilateral symmetry alongside notable asymmetry. Our approach also incorporates measures including connectivity similarity, motif-fingerprint differences, and path-compensation index to evaluate the networks functional redundancy and its capacity to compensate for unilateral disturbances. Here we show the C. elegans connectomes robust bilateral symmetry, which not only facilitates similar functions across neuron pairs but also ensures resilience against disruptions. This redundancy is not confined to symmetrical connections; it also includes asymmetric ones, adding to the neural networks complexity. An in-depth analysis into different neuron types shows varied redundancy levels: high in interneurons, moderate in motor neurons, and low in sensory neurons. This pattern suggests a strategic neural design where diverse inputs from sensory neurons, coupled with the stable integration by interneurons, lead to coordinated actions through motor neurons. This study advances our understanding of neural connectomes, offering insights into the intricate balance of symmetry and asymmetry in neural systems and their implications for complex, adaptive behaviors.

neuroscience↗

bioRxiv2024

Rapamycin Immunomodulation Utilizes Time-Dependent Alterations of Lymph Node Architecture, Leukocyte Trafficking, and Gut Microbiome

Transplant recipients require lifelong, multimodal immunosuppression to prevent rejection by reducing alloreactive immunity. Rapamycin, a mechanistic target of rapamycin (mTOR) inhibitor, is known to modulate adaptive and innate immunity, while the full spectrum of its immunosuppressive mechanisms remains incompletely understood. Given the broad expression of mTOR, we investigated the understudied effects of rapamycin on lymph node (LN) architecture, leukocyte trafficking, and the gut microbiome and metabolism after 3, 7, and 30 days of rapamycin treatment, to characterize the early, intermediate, and late changes. Rapamycin significantly reduced CD4+ T cells, CD8+ T cells, and regulatory T (Treg) cells in peripheral LNs, mesenteric LNs, and the spleen over time. Rapamycin induced early pro-inflammation transition to pro-tolerogenic status, by modulating the LN laminin 4:5 expression ratios through LN stromal cells laminin 5 expression and by adjusting Treg numbers and distribution. Additionally, rapamycin significantly altered gut microbiota composition and metabolic functions, shifting the Bacteroides to Firmicutes ratio and increasing amino acid bioavailability in the gut lumen. These effects were evident by 7 days and became most pronounced by 30 days in naive mice, with notable changes as early as 3 days in allogeneic splenocyte-stimulated mice. These findings reveal a novel mechanism of rapamycins action through time-dependent modulation of LN architecture and gut microbiome, which orchestrates changes in immune cell trafficking, providing a new framework for understanding and optimizing immunosuppressive therapies.

immunology↗

bioRxiv2024

Age dependency of neurometabolite T1 relaxation times

PurposeTo measure T1 relaxation times of metabolites at 3T in a healthy aging population and investigate age dependence. MethodsA cohort of 101 healthy adults were recruited with approximately 10 male and 10 female participants in each decade band: 18-29, 30-39, 40-49, 50-59, and 60+ years old. Inversion-recovery PRESS data (TE/TR: 30/2000 ms) were acquired at 8 inversion times (TIs) (300, 400, 511, 637, 780, 947, 1148 and 1400 ms) from voxels in white-matter-rich centrum semiovale (CSO) and gray-matter-rich posterior cingulate cortex (PCC). Modeling of TI-series spectra was performed in Osprey 2.5.0. Quantified metabolite amplitudes for total N-acetylaspartate (tNAA2.0), total creatine at 3.0 ppm (tCr3.0) and 3.9 ppm (tCr3.9), total choline (tCho), myo-inositol (mI), and the sum of glutamine and glutamate (Glx) were modeled to calculate T1 relaxation times of metabolites. ResultsT1 relaxation times of tNAA2.0 in CSO and tNAA2.0, tCr3.0, mI and Glx in PCC decreased with age. These correlations remained significant when controlling for cortical atrophy. T1 relaxation times were significantly different between PCC and CSO for all metabolites except tCr3.0. We also propose linear models for predicting metabolite T1s at 3T to be used in future aging studies. ConclusionMetabolite T1 relaxation times change significantly with age, an effect that will be important to consider for accurate quantitative MRS, particularly in studies of aging.

neuroscience↗

bioRxiv2024

Conformational flexibility is a critical factor in designing broad-spectrum human norovirus protease inhibitors

Human norovirus (HuNoV) infection is a global health and economic burden. Currently, there are no licensed HuNoV vaccines or antiviral drugs available. The protease encoded by the HuNoV genome plays a critical role in virus replication by cleaving the polyprotein and is, therefore, an excellent target for developing small molecule inhibitors. While rupintrivir, a potent small-molecule inhibitor of several picornavirus proteases, effectively inhibits GI.1 protease, it is an order of magnitude less effective against GII protease. Other GI.1 protease inhibitors also tend to be less effective against GII proteases. To understand the structural basis for the potency difference, we determined the crystal structures of proteases of GI.1, pandemic GII.4 (Houston and Sydney), and GII.3 in complex with rupintrivir. These structures show that the open substrate pocket in GI protease binds rupintrivir without requiring significant conformational changes, whereas, in GII proteases, the closed pocket flexibly extends, reorienting arginine-112 in the BII-CII loop to accommodate rupintrivir. Structures of R112A protease mutants with rupintrivir, coupled with enzymatic and inhibition studies, suggest R112 is involved in displacing both substrate and ligands from the active site, implying a role in the release of cleaved products during polyprotein processing. Thus, the primary determinant for differential inhibitor potency between the GI and GII proteases is the increased flexibility in the BII-CII loop of the GII proteases caused by H-G mutation in this loop. Therefore, the inherent flexibility of the BII-CII loop in GII proteases is a critical factor to consider when developing broad-spectrum inhibitors for HuNoV proteases. IMPORTANCEHuman noroviruses are a significant cause of sporadic and epidemic gastroenteritis worldwide. There are no vaccines or antiviral drugs currently available to treat infections. Our work elucidates the structural differences between GI.1 and GII proteases in response to inhibitor binding and will inform the future development of broad-spectrum norovirus protease inhibitors.

biochemistry↗

bioRxiv2024

Comparison of test-retest reproducibility of DESPOT and 3D-QALAS for water T1 and T2 mapping

PurposeRelaxometry, specifically T1 and T2 mapping, has become an essential technique for assessing the properties of biological tissues related to various physiological and pathological conditions. Many techniques are being used to estimate T1 and T2 relaxation times, ranging from the traditional inversion or saturation recovery and spin-echo sequences to more advanced methods. Choosing the appropriate method for a specific application is critical since the precision and accuracy of T1 and T2 measurements are influenced by a variety of factors including the pulse sequence and its parameters, the inherent properties of the tissue being examined, the MRI hardware, and the image reconstruction. The aim of this study is to evaluate and compare the test-retest reproducibility of two advanced MRI relaxometry techniques (Driven Equilibrium Single Pulse Observation of T1 and T2, DESPOT, and 3D Quantification using an interleaved Look-Locker acquisition Sequence with a T2 preparation pulse, QALAS), for T1 and T2 mapping in a healthy volunteer cohort. Methods10 healthy volunteers underwent brain MRI at 1.3 mm3 isotropic resolution, acquiring DESPOT and QALAS data ([~]11.8 and [~]5 minutes duration, including field maps, respectively), test-retest with subject repositioning, on a 3.0 Tesla Philips Ingenia Elition scanner. To reconstruct the T1 and T2 maps, we used an equation-based algorithm for DESPOT and a dictionary-based algorithm that incorporates inversion efficiency and B1-field inhomogeneity for QALAS. The test-retest reproducibility was assessed using the coefficient of variation (CoV), intraclass correlation coefficient (ICC) and Bland-Altman plots. ResultsOur results indicate that both the DESPOT and QALAS techniques demonstrate good levels of test-retest reproducibility for T1 and T2 mapping across the brain. Higher whole-brain voxel-to-voxel ICCs are observed in QALAS for T1 (0.84 {+/-} 0.039) and in DESPOT for T2 (0.897 {+/-} 0.029). The Bland-Altman plots show smaller bias and variability of T1 estimates for QALAS (mean of -0.02 s, and upper and lower limits of -0.14 and 0.11 s, 95% CI) than for DESPOT (mean of -0.02 s, and limits of -0.31 and 0.27 s). QALAS also showed less variability (mean 1.08 ms, limits -1.88 to 4.04 ms) for T2 compared to DESPOT (mean of 2.56 ms, and limits -17.29 to 22.41 ms). The within-subject CoVs for QALAS range from 0.6% (T2 in CSF) to 5.8% (T2 in GM), while for DESPOT they range from 2.1% (T2 in CSF) to 6.7% (T2 in GM). The between-subject CoVs for QALAS range from 2.5% (T2 in GM) to 12% (T2 in CSF), and for DESPOT they range from 3.7% (T2 in WM) to 9.3% (T2 in CSF). ConclusionOverall, QALAS demonstrated better reproducibility for T1 and T2 measurements than DESPOT, in addition to reduced acquisition time.

neuroscience↗

bioRxiv2024

Episodic Transport of Protein Aggregates Achieves a Positive Size Selectivity in Aggresome Formation

Eukaryotic cells direct toxic misfolded proteins to various protein quality control pathways based on their chemical features and aggregation status. Aggregated proteins are targeted to selective autophagy or specifically sequestered into the "aggresome," a perinuclear inclusion at the microtubule-organizing center (MTOC). However, the mechanism for selectively sequestering protein aggregates into the aggresome remains unclear. To investigate aggresome formation, we reconstituted MTOC-directed aggregate transport in Xenopus laevis egg extract using AgDD, a chemically inducible aggregation system. High-resolution single-particle tracking revealed that dynein-mediated transport of aggregates was highly episodic, with average velocity positively correlated with aggregate size. Our mechanistic model suggests that the recurrent formation of the dynein transport complex biases larger aggregates towards the active transport state, compensating for the slowdown due to viscosity. Both episodic transport and positive size selectivity are specifically associated with aggresome-dynein adaptors. Coupling conventional dynein-activating adaptors to the aggregates perturbs aggresome formation and reverses size selectivity.

cell biology↗

bioRxiv2024

Predicting reproductive phenology of wind-pollinated trees via PlanetScope time series

Airborne pollen triggers allergic reactions which result in public health consequences. A better understanding of flowering and pollen phenology could improve airborne pollen predictions and reduce pollen exposure. Data on the timing of flowering and pollen release are needed to improve models of airborne pollen concentrations, but existing in-situ data collection efforts are expensive and spatially sparse. Satellite-based estimates of plant phenology could potentially enable large-scale data collection, but it is difficult to detect the reproductive phenology of wind-pollinated flowers from space. Here, we infer the reproductive phenology of wind-pollinated plants using PlanetScope time series with a spatial resolution of 3 m and a daily revisit cycle, complemented by in-situ flower and pollen observations, leveraging the correlation between vegetative and reproductive phenology. On the individual tree level, we extracted PlanetScope-derived green-up time and validated its correlation to flowering time using flower observations in a national-scale observatory network. Scaling up to the city level, we developed a novel approach to characterize pollen phenology from PlanetScope-derived vegetative phenology, by optimizing two tuning parameters: the threshold of green-up or green-down and the time lag between green-up/down and flowering. We applied this method to seven cities in the US and seven key wind-pollinated tree genera, calibrated by measurements of airborne pollen concentrations. Our method characterized pollen phenology accurately, not only in-sample (Spearman correlation: 0.751, nRMSE: 13.5%) but also out-of-sample (Spearman correlation: 0.691, nRMSE: 14.5%). Using the calibrated model, we further mapped the pollen phenology landscape within cities, showing intra-urban heterogeneity. Using high spatiotemporal resolution remote sensing, our novel approach enables us to infer the flowering and pollen phenology of wind-pollinated plant taxa on a large scale and a fine resolution, including areas with limited prior in-situ flower and pollen observations. The use of PlanetScope time series therefore holds promise for developing process-based pollen models and targeted public health strategies to mitigate the impact of allergenic pollen exposure.

ecology↗

bioRxiv2024

Astrocyte extracellular matrix modulate neuronal dendritic development

Major developmental events occurring in the hippocampus during the third trimester of human gestation and neonatally in altricial rodents include rapid and synchronized dendritic arborization and astrocyte proliferation and maturation. We tested the hypothesis that signals sent by developing astrocytes to developing neurons modulate dendritic development in vivo. We altered neuronal development by neonatal (third trimester-equivalent) ethanol exposure in mice; this treatment increased dendritic arborization in hippocampal pyramidal neurons. We next assessed concurrent changes in the mouse astrocyte translatome by translating ribosomal affinity purification (TRAP)-seq. We followed up on ethanol-inhibition of astrocyte Chpf2 and Chsy1 gene translation because these genes encode for biosynthetic enzymes of chondroitin sulfate glycosaminoglycan (CS-GAG) chains (extracellular matrix components that inhibit neuronal development and plasticity) and have not been explored before for their roles in dendritic arborization. We report that Chpf2 and Chsy1 are enriched in astrocytes and their translation is inhibited by ethanol, which also reduces the levels of CS-GAGs measured by Liquid Chromatography/Mass Spectrometry. Finally, astrocyte-conditioned medium derived from Chfp2-silenced astrocytes increased neurite branching of hippocampal neurons in vitro. These results demonstrate that CS-GAG biosynthetic enzymes in astrocytes regulates dendritic arborization in developing neurons.

neuroscience↗

bioRxiv2024

A biodegradable and restorative peripheral neural interface for the interrogation of neuropathic injuries

Monitoring the early-stage healing of severe traumatic nerve injuries is essential to gather physiological and pathological information for timely interventions and optimal clinical outcomes. While implantable peripheral nerve interfaces provide direct access to nerve fibers for precise interrogation and modulation, conventional non-degradable designs pose limited utilization in nerve injury rehabilitation. Here, we introduce a biodegradable and restorative neural interface for wireless real-time tracking and recovery of long-gap nerve injuries. Leveraging machine learning techniques, this electronic platform deciphers nerve recovery status and identifies traumatic neuroma formation at the early phase, enabling timely intervention and significantly improved therapeutic outcomes. The biodegradable nature of the device eliminates the need for retrieval procedures, reducing infection risks and secondary tissue damage. This research sheds light on bioresorbable multifunctional peripheral nerve interfaces for probing neuropathic injuries, offering vital information for early diagnosis and therapeutic intervention.

bioengineering↗

bioRxiv2024

Biological changes, political ideology, and scientific communication shape human perceptions of pollen seasons

Climate change is changing the timing and intensity of pollen seasons, thereby increasing human exposure to allergenic pollen. Climate-driven changes in pollen seasons present a unique opportunity to craft messaging aimed at communicating climate change impacts on public health through changes in the biological systems. However, it is unclear how pollen seasons are experienced and understood by the public, including how well we detect pollen seasons or what factors we view as responsible for changes in pollen seasons. Here, we use social media data in the United States from 2012 to 2022 to assess public perceptions of pollen seasons at large spatiotemporal scales. We show that pollen seasons detected by social media (Twitter) users align well with natural pollen seasons. Attribution of changing pollen seasons, however, varies based on political ideology: liberal users, compared to conservative users, are more likely to attribute changing pollen seasons to climate change. Mass media and scientific experts play a key role in communicating how climate change drives changing pollen seasons. Our findings reveal how changes in biological systems, political ideology, and scientific communications collectively shape public perceptions of pollen seasons under climate change. Our findings constitute a step towards more effective climate change impact communication and public health intervention design.

scientific communication and education↗

bioRxiv2024

Cell Storage Conditions Impact Single-Cell Proteomic Landscapes

Single-cell transcriptomics (SCT) has revolutionized our understanding of cellular heterogeneity, yet the emergence of single-cell proteomics (SCP) promises a more functional view of cellular dynamics. A challenge is that not all mass spectrometry facilities can perform SCP, and not all labs have access to cell sorting equipment required for SCP, which together motivate an interest in sending bulk cell samples through the mail for sorting and SCP analysis. Shipping requires cell storage, which has an unknown impact on SCP results. This study investigates the impact of cell storage conditions on the proteomic landscape at the single-cell level utilizing a Data-Independent Acquisition (DIA) coupled with Parallel Accumulation Serial Fragmentation (diaPASEF). Three storage conditions were compared in 293T cells: (1) 37{degrees}C (control), (2) 4{degrees}C overnight, and (3) - 80{degrees}C storage followed by liquid nitrogen preservation. Either cold or frozen storage induced significant alterations in cell diameter, elongation, and proteome composition. By elucidating how cell storage conditions alter cellular morphology and proteome profiles, this study contributes foundational technical information about SCP sample preparation and data quality.

cell biology↗

bioRxiv2024

Parallel Synapses with Transmission Nonlinearities Enhance Neuronal Classification Capacity

Cortical neurons often establish multiple synaptic contacts with the same postsynaptic neuron. To avoid functional redundancy of these parallel synapses, it is crucial that each synapse exhibits distinct computational properties. Here we model the current to the soma contributed by each synapse as a sigmoidal transmission function of its presynaptic input, with learnable parameters such as amplitude, slope, and threshold. We evaluate the classification capacity of a neuron equipped with such nonlinear parallel synapses, and show that with a small number of parallel synapses per axon, it substantially exceeds that of the Perceptron. Furthermore, the number of correctly classified data points can increase superlinearly as the number of presynaptic axons grows. When training with an unrestricted number of parallel synapses, our model neuron can effectively implement an arbitrary aggregate transmission function for each axon, constrained only by monotonicity. Nevertheless, successful learning in the model neuron often requires only a small number of parallel synapses. We also apply these parallel synapses in a feedforward neural network trained to classify MNIST images, and show that they can increase the test accuracy. This demonstrates that multiple nonlinear synapses per input axon can substantially enhance a neurons computational power.

neuroscience↗