Assessing risk factors for complications in computer tomography-guided lung biopsy: quantitative analysis for predicting pneumothorax.

BACKGROUND: Computer tomography (CT)-guided lung biopsy carries the risk of pneumothorax. A variety of other risk factors affect the occurrence of pneumothorax. OBJECTIVE: Assess the incidence and risk factors associated with pneumothorax complications in CT-guided lung biopsy, and to conduct a quantitative analysis of the variables among the significant risk factors to identify more effective indicators for predicting pneumothorax complications. DESIGN: Retrospective logistic. SETTING: Single center in China. PATIENTS AND METHODS: From June 2017 to May 2021, consecutive patients who underwent CT-guided lung biopsy were identified from the medical record system. Binary logistic regression analysis was used to identify potential risk factors for pneumothorax. Receiver operating characteristic (ROC) curves were constructed for continuous variables to determine cutoff values that optimized sensitivity and specificity. MAIN OUTCOME MEASURES: The incidence and risk factors of pneumothorax in CT-guided lung biopsy. SAMPLE SIZE: 132 patients. RESULTS: The incidence of pneumothorax was 28.9% (38/132), with 6.8% (9/132) of patients requiring chest tube insertion. Results indicated that smaller lesion size (OR 0.724; 95% CI 0.619-0.848; P=.0001), longer needle tract length (OR 1.320; 95% CI 1.145-1.521; P=.001), multiple passes through the pleura (OR 4.618; 95% CI 1.378-15.467; P=.013), and needle tract length/lesion diameter (L/D) ratio (OR 0.028; 95% CI 0.002-0.732; P=.007) were independent risk factors for pneumothorax. ROC curve analysis determined a cut-off value of 0.81 for the L/D ratio (sensitivity=89.5%, specificity=71.3%). The area under the ROC curve (AUC) values of maximum diameter, needle tract length, and L/D ratio for pneumothorax were 0.749, 0.812, and 0.850, respectively. CONCLUSIONS: The L/D ratio, multiple passes through the pleura, longer needle tract length, and smaller lesions were independent risk factors for pneumothorax. A L/D ratio of less than 0.81 may indicate a pneumothorax. It may be necessary to use the proper sealing procedure for this patient group. LIMITATIONS: Due to its retrospective nature, there may be inherent selection bias.

WASPSYN: A Challenge for Domain Adaptive Synapse Detection in Microwasp Brain Connectomes.

The size of image volumes in connectomics studies now reaches terabyte and often petabyte scales with a great diversity of appearance due to different sample preparation procedures. However, manual annotation of neuronal structures (e.g., synapses) in these huge image volumes is time-consuming, leading to limited labeled training data often smaller than 0.001% of the large-scale image volumes in application. Methods that can utilize in-domain labeled data and generalize to out-of-domain unlabeled data are in urgent need. Although many domain adaptation approaches are proposed to address such issues in the natural image domain, few of them have been evaluated on connectomics data due to a lack of domain adaptation benchmarks. Therefore, to enable developments of domain adaptive synapse detection methods for large-scale connectomics applications, we annotated 14 image volumes from a biologically diverse set of Megaphragma viggianii brain regions originating from three different whole-brain datasets and organized the WASPSYN challenge at ISBI 2023. The annotations include coordinates of pre-synapses and post-synapses in the 3D space, together with their one-to-many connectivity information. This paper describes the dataset, the tasks, the proposed baseline, the evaluation method, and the results of the challenge. Limitations of the challenge and the impact on neuroscience research are also discussed. The challenge is and will continue to be available at https://codalab.lisn.upsaclay.fr/competitions/9169. Successful algorithms that emerge from our challenge may potentially revolutionize real-world connectomics research and further the cause that aims to unravel the complexity of brain structure and function.

Cell-type-specific inhibitory circuitry from a connectomic census of mouse visual cortex.

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties. Synaptic connectivity powerfully shapes how each cell type participates in the cortical circuit, but mapping connectivity rules at the resolution of distinct cell types remains difficult. Here, we used millimeter-scale volumetric electron microscopy1 to investigate the connectivity of all inhibitory neurons across a densely-segmented neuronal population of 1352 cells spanning all layers of mouse visual cortex, producing a wiring diagram of inhibitory connections with more than 70,000 synapses. Taking a data-driven approach inspired by classical neuroanatomy, we classified inhibitory neurons based on the relative targeting of dendritic compartments and other inhibitory cells and developed a novel classification of excitatory neurons based on the morphological and synaptic input properties. The synaptic connectivity between inhibitory cells revealed a novel class of disinhibitory specialist targeting basket cells, in addition to familiar subclasses. Analysis of the inhibitory connectivity onto excitatory neurons found widespread specificity, with many interneurons exhibiting differential targeting of certain subpopulations spatially intermingled with other potential targets. Inhibitory targeting was organized into "motif groups," diverse sets of cells that collectively target both perisomatic and dendritic compartments of the same excitatory targets. Collectively, our analysis identified new organizing principles for cortical inhibition and will serve as a foundation for linking modern multimodal neuronal atlases with the cortical wiring diagram.

Pushing photon-pair generation rate in microresonators by Q factor manipulation.

Photon pairs generated by employing spontaneous nonlinear effects in microresonators are critically essential for integrated optical quantum information technologies, such as quantum computation and quantum cryptography. Microresonators featuring high-quality (Q) factors can offer simple yet power-efficient means to generate photon pairs, thanks to the intracavity field enhancement. In microresonators, it is known that the photon-pair generation rate (PGR) is roughly proportional to the cubic power of the Q factor. However, the upper limit on PGR is also set by the Q factor: a higher Q factor brings a longer photon lifetime, which in turn leads to a lower repetition rate allowing for photon flow emitted from the microresonator, constrained by the Fourier-transform limit. Exceeding this limit will result in the overlap of photon wave packets in the time domain, thus degrading the quantum character of single-photon light beams. To push the limit of PGR in a single resonator, we propose a method by harnessing the resonance linewidth-manipulated microresonators to improve the maximum achievable photon repetition rate while keeping the power efficiency. The maximum achievable PGR and power efficiency are thus balanced by leveraging the combination of low and high-Q resonances.

Outcomes of CT-Guided Deeper Localization Technique for Superficial Pulmonary Nodules.

BACKGROUND: The possibility of coil dislocation in computed tomography (CT)-guided microcoil localization of superficial pulmonary nodules is relatively high. The aim of the study is to investigate the outcomes of deeper localization technique during CT-guided microcoil localization of superficial pulmonary nodules before video-assisted thoracoscopic surgery (VATS). METHODS: Fifty-seven identified superficial pulmonary nodules (nodule-pleural distance ≤ 1 cm on CT image) from 51 consecutive patients underwent CT-guided microcoil localization, and subsequent VATSs were included. The rate of technical success, complications, and excised lung volume were compared between deeper localization technique group and conventional localization technique group. RESULTS: The technical success rate of the localization procedure was 100% (25/25) in the deeper localization group and 81.3% (26/32) in the conventional localization group (p = 0.030). Excluding one case of lobectomy, the excised lung volume in the deeper localization group and the conventional localization group was 39.3 ± 23.5 and 37.2 ± 16.2 cm3, respectively (p = 0.684). The incidence of pneumothorax was similar between the deeper localization group and the conventional localization group (24.0 vs. 21.9%, respectively, p = 0.850). The incidence of intrapulmonary hemorrhage in the deeper localization group was higher (16.0%) than that in the conventional localization group (6.3%), but the difference was not statistically significant (p = 0.388). CONCLUSION: CT-guided microcoil localization of superficial pulmonary nodules prior to VATS using a deeper localization technique is feasible. Deeper localization technique reduced the occurrence of dislocation but did not increase excised lung volume.

A complete reconstruction of the early visual system of an adult insect.

For most model organisms in neuroscience, research into visual processing in the brain is difficult because of a lack of high-resolution maps that capture complex neuronal circuitry. The microinsect Megaphragma viggianii, because of its small size and non-trivial behavior, provides a unique opportunity for tractable whole-organism connectomics. We image its whole head using serial electron microscopy. We reconstruct its compound eye and analyze the optical properties of the ommatidia as well as the connectome of the first visual neuropil-the lamina. Compared with the fruit fly and the honeybee, Megaphragma visual system is highly simplified: it has 29 ommatidia per eye and 6 lamina neuron types. We report features that are both stereotypical among most ommatidia and specialized to some. By identifying the "barebones" circuits critical for flying insects, our results will facilitate constructing computational models of visual processing in insects.

CAVE: Connectome Annotation Versioning Engine.

Advances in Electron Microscopy, image segmentation and computational infrastructure have given rise to large-scale and richly annotated connectomic datasets which are increasingly shared across communities. To enable collaboration, users need to be able to concurrently create new annotations and correct errors in the automated segmentation by proofreading. In large datasets, every proofreading edit relabels cell identities of millions of voxels and thousands of annotations like synapses. For analysis, users require immediate and reproducible access to this constantly changing and expanding data landscape. Here, we present the Connectome Annotation Versioning Engine (CAVE), a computational infrastructure for immediate and reproducible connectome analysis in up-to petascale datasets (~1mm3) while proofreading and annotating is ongoing. For segmentation, CAVE provides a distributed proofreading infrastructure for continuous versioning of large reconstructions. Annotations in CAVE are defined by locations such that they can be quickly assigned to the underlying segment which enables fast analysis queries of CAVE's data for arbitrary time points. CAVE supports schematized, extensible annotations, so that researchers can readily design novel annotation types. CAVE is already used for many connectomics datasets, including the largest datasets available to date.

Neuronal wiring diagram of an adult brain.

Connections between neurons can be mapped by acquiring and analyzing electron microscopic (EM) brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative, yet inadequate for understanding brain function more globally. Here, we present the first neuronal wiring diagram of a whole adult brain, containing 5×107 chemical synapses between ~130,000 neurons reconstructed from a female Drosophila melanogaster. The resource also incorporates annotations of cell classes and types, nerves, hemilineages, and predictions of neurotransmitter identities. Data products are available by download, programmatic access, and interactive browsing and made interoperable with other fly data resources. We show how to derive a projectome, a map of projections between regions, from the connectome. We demonstrate the tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine, and descending neurons), across both hemispheres, and between the central brain and the optic lobes. Tracing from a subset of photoreceptors all the way to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviors. The technologies and open ecosystem of the FlyWire Consortium set the stage for future large-scale connectome projects in other species.

Cyclic structure with cellular precision in a vertebrate sensorimotor neural circuit.

Neuronal wiring diagrams reconstructed by electron microscopy1,2,3,4,5 pose new questions about the organization of nervous systems following the time-honored tradition of cross-species comparisons.6,7 The C. elegans connectome has been conceptualized as a sensorimotor circuit that is approximately feedforward,8,9,10,11 starting from sensory neurons proceeding to interneurons and ending with motor neurons. Overrepresentation of a 3-cell motif often known as the "feedforward loop" has provided further evidence for feedforwardness.10,12 Here, we contrast with another sensorimotor wiring diagram that was recently reconstructed from a larval zebrafish brainstem.13 We show that the 3-cycle, another 3-cell motif, is highly overrepresented in the oculomotor module of this wiring diagram. This is a first for any neuronal wiring diagram reconstructed by electron microscopy, whether invertebrate12,14 or mammalian.15,16,17 The 3-cycle of cells is "aligned" with a 3-cycle of neuronal groups in a stochastic block model (SBM)18 of the oculomotor module. However, the cellular cycles exhibit more specificity than can be explained by the group cycles-recurrence to the same neuron is surprisingly common. Cyclic structure could be relevant for theories of oculomotor function that depend on recurrent connectivity. The cyclic structure coexists with the classic vestibulo-ocular reflex arc for horizontal eye movements,19 and could be relevant for recurrent network models of temporal integration by the oculomotor system.20,21.

CT-guided microcoil localization for scapula-blocked pulmonary nodules using penetrating lung puncture before video-assisted thoracic surgery.

PURPOSE: To retrospectively analyze the effectiveness and safety of computed tomography (CT)-guided microcoil localization for scapula-blocked pulmonary nodules using penetrating lung puncture prior to video-assisted thoracic surgery (VATS). METHODS: One hundred thirty-eight patients with 138 pulmonary nodules were included in this single-center retrospective study. Among them, 110 patients who underwent CT-guided microcoil localization using the routine puncture technique formed the routine group; the other 28 patients who underwent the CT-guided microcoil localization using the penetrating lung puncture technique formed the penetrating lung group. The main outcomes were the success rate and complication rate of the two groups. RESULTS: The localization success rate was 95.5% (105/110) in the routine group and 89.3% (25/28) in the penetrating lung group (P = 0.205). There was no statistical difference in any of the complications (pneumothorax, intrapulmonary hemorrhage, or moderate and severe chest pain) in both groups (P = 0.178, P = 0.204, P = 0.709, respectively). Localization procedure time was significantly increased in the penetrating lung group compared with the routine group (31.0 ± 3.0 min vs. 21.2 ± 2.8 min, P < 0.001). CONCLUSION: CT-guided microcoil localization for scapula-blocked pulmonary nodules using penetrating lung puncture prior to VATS resection is effective and safe. However, the deployment of the microcoil using penetrating lung puncture required more time than the routine puncture method.

NEURD: automated proofreading and feature extraction for connectomics.

We are now in the era of millimeter-scale electron microscopy (EM) volumes collected at nanometer resolution (Shapson-Coe et al., 2021; Consortium et al., 2021). Dense reconstruction of cellular compartments in these EM volumes has been enabled by recent advances in Machine Learning (ML) (Lee et al., 2017; Wu et al., 2021; Lu et al., 2021; Macrina et al., 2021). Automated segmentation methods can now yield exceptionally accurate reconstructions of cells, but despite this accuracy, laborious post-hoc proofreading is still required to generate large connectomes free of merge and split errors. The elaborate 3-D meshes of neurons produced by these segmentations contain detailed morphological information, from the diameter, shape, and branching patterns of axons and dendrites, down to the fine-scale structure of dendritic spines. However, extracting information about these features can require substantial effort to piece together existing tools into custom workflows. Building on existing open-source software for mesh manipulation, here we present "NEURD", a software package that decomposes each meshed neuron into a compact and extensively-annotated graph representation. With these feature-rich graphs, we implement workflows for state of the art automated post-hoc proofreading of merge errors, cell classification, spine detection, axon-dendritic proximities, and other features that can enable many downstream analyses of neural morphology and connectivity. NEURD can make these new massive and complex datasets more accessible to neuroscience researchers focused on a variety of scientific questions.

Functional connectomics reveals general wiring rule in mouse visual cortex.

To understand how the brain computes, it is important to unravel the relationship between circuit connectivity and function. Previous research has shown that excitatory neurons in layer 2/3 of the primary visual cortex of mice with similar response properties are more likely to form connections. However, technical challenges of combining synaptic connectivity and functional measurements have limited these studies to few, highly local connections. Utilizing the millimeter scale and nanometer resolution of the MICrONS dataset, we studied the connectivity-function relationship in excitatory neurons of the mouse visual cortex across interlaminar and interarea projections, assessing connection selectivity at the coarse axon trajectory and fine synaptic formation levels. A digital twin model of this mouse, that accurately predicted responses to arbitrary video stimuli, enabled a comprehensive characterization of the function of neurons. We found that neurons with highly correlated responses to natural videos tended to be connected with each other, not only within the same cortical area but also across multiple layers and visual areas, including feedforward and feedback connections, whereas we did not find that orientation preference predicted connectivity. The digital twin model separated each neuron's tuning into a feature component (what the neuron responds to) and a spatial component (where the neuron's receptive field is located). We show that the feature, but not the spatial component, predicted which neurons were connected at the fine synaptic scale. Together, our results demonstrate the "like-to-like" connectivity rule generalizes to multiple connection types, and the rich MICrONS dataset is suitable to further refine a mechanistic understanding of circuit structure and function.

Computed Tomography-Guided Microcoil Localization of Pulmonary Nodules: Effects of Multiple Punctures.

BACKGROUND: The aim of the study is to analyze the effect of multiple punctures in computed tomography (CT)-guided microcoil localization of pulmonary nodules with other risk factors for common complications. METHODS: Consecutive patients who underwent CT-guided microcoil localization and subsequent video-assisted thoracoscopic surgery (VATS) between January 2020 and February 2021 were enrolled. Nodules successfully located after only one puncture were defined as the single puncture group, and nodules requiring two or more punctures were defined as the multiple puncture group. Binary logistic regression analysis was performed to assess the relationship between the number of punctures and pneumothorax and intrapulmonary hemorrhage. RESULTS: A total of 121 patients were included. There were 98 (68.1%) pulmonary nodules in the single puncture group compared with 46 (31.9%) nodules in the multiple puncture group. The frequencies of pneumothorax and intrapulmonary hemorrhage were higher in the multiple puncture group than in the single puncture group (p = 0.019 and <0.001, respectively). Binary logistic regression demonstrated that independent risk factors for developing pneumothorax included lateral positioning of the patient (p < .001) and prone positioning (p = 0.014), as well as multiple punctures (p = 0.013). Independent risk factors for intrapulmonary hemorrhage included the distance between the distal end of the coil and the surface of the pleura (p = 0.033), multiple punctures (p = 0.003), and passage through the pulmonary vasculature (p < 0.001). CONCLUSION: Multiple punctures resulted in an increased incidence of pneumothorax and intrapulmonary hemorrhage compared with single puncture during CT-guided microcoil localization of pulmonary nodules and were independently associated with both pneumothorax and intrapulmonary hemorrhage.

Investigation of the Flame Retardant Properties of High-Strength Microcellular Flame Retardant/Polyurethane Composite Elastomers.

Flame retardants (FRs) often reduce the mechanical properties of polymer materials, and FR/microcellular polyurethane elastomer (MPUE) composite materials have not been systemically studied. Hence, we conducted this study on FR/MPUE composites by using multiple liquid FRs and/or expandable graphite (EG). Compared with liquid flame retardants, the LOI of an expandable graphite/dimethyl methylphosphonate (EG/DMMP) (3:1) combination was significantly increased (~36.1%), and the vertical combustion grade reached V-0 without a dripping phenomenon. However, the corresponding tensile strength was decreased by 17.5%. With the incorporation of EG alone, although the corresponding LOI was not a match with that of DMMP/EG, there was no droplet phenomenon. In addition, even with 15 wt% of EG, there was no significant decline in the tensile strength. Cone calorimeter test results showed that PHRR, THR, PSPR, and TSR were significantly reduced, compared to the neat MPUE, when the EG content surpassed 10 wt%. The combustion process became more stable and thus the fire risk was highly reduced. It was found that flame retardancy and mechanical properties could be well balanced by adding EG alone. Our proposed strategy for synthesizing FR/MPUE composites with excellent flame retardancy and mechanical properties was easy, effective, low-cost and universal, which could have great practical significance in expanding the potential application fields of MPUEs.

Comparative Study on Nosocomial Biliary Tract Infection Rate Between Biliary Stent Loaded with Radioactive 125 I Seeds and Conventional Biliary Stent in the Treatment of Distal Malignant Biliary Obstruction.

BACKGROUND: The purpose of this prospective randomized study was to compare the nosocomial biliary tract infection rate of biliary stent implantation with a biliary stent loaded with radioactive 125 I seeds (radioactive biliary stent, RBS) and conventional biliary stent (CBS); additionally, to preliminary discuss the causes of postoperative cholangitis. Moreover, the results will provide clinical evidence for the prevention of postoperative biliary tract infection. MATERIALS AND METHODS: We prospectively analyzed the nosocomial infection rate of the distal malignant biliary obstruction (MBO) treatment by stent implantation with RBS and CBS. All MBO patients who initially visited our tertiary hospital between July 2015 and December 2019 (n= 196) were evaluated, enrolled, and randomly divided into 2 groups, RBS (n=97) and CBS (n=99) group. χ 2 test was used to evaluate the categorical data, and t test was used to evaluate the numerical data. RESULTS: Our analysis of the study showed the incidence of postoperative infections of a biliary tract of the RBS group (23.7%) was significantly higher than the CBS group (11.1%). The difference was statistically significant (χ 2 =5.425, P =0.020). Our study also showed the most common pathogenic bacteria after surgery was Escherichia coli (26.5%). CONCLUSION: Treatment for distal MBO with biliary stent loaded with radioactive 125 I seeds had a higher nosocomial infection rate, and the most common pathogenic bacteria was E coli. , Supplemental Digital Content 1, http://links.lww.com/sle/A350.

Igneous: Distributed dense 3D segmentation meshing, neuron skeletonization, and hierarchical downsampling.

Three-dimensional electron microscopy images of brain tissue and their dense segmentations are now petascale and growing. These volumes require the mass production of dense segmentation-derived neuron skeletons, multi-resolution meshes, image hierarchies (for both modalities) for visualization and analysis, and tools to manage the large amount of data. However, open tools for large-scale meshing, skeletonization, and data management have been missing. Igneous is a Python-based distributed computing framework that enables economical meshing, skeletonization, image hierarchy creation, and data management using cloud or cluster computing that has been proven to scale horizontally. We sketch Igneous's computing framework, show how to use it, and characterize its performance and data storage.

CT-guided placement of microcoil end in the pleural cavity for video-assisted thoracic surgical resection of ground-glass opacity: a retrospective study.

BACKGROUND: The aim of the study was to investigate and summarize the effectiveness and safety of CT-guided microcoil localization before video-assisted thoracic surgery (VATS) for the removal of ground-glass opacity (GGO). METHODS: A total of 147 patients with GGO who were treated at our hospital between January 2019 and February 2021 were retrospectively analyzed. They were divided into two groups according to the final position at the end of the microcoil: intracavity (n = 78) and extracavity (n = 69), which were compared based on puncture complications and influence of the coil end position on VATS. RESULTS: The proportions of supine and prone positions in the intracavity group were significantly higher than those in the extracavity group (82.1% vs. 66.7%, P < 0.05). The incidence of intrapulmonary hemorrhage, chest pain, and coil displacement in the intracavity group was significantly lower than that in the extracavity group (28.2% vs. 46.4%, 19.2% vs. 39.1%, 1.3% vs. 11.6%, P < 0.05, respectively); however, the incidence of pneumothorax was not significantly different (P > 0.05). The time of VATS and the rate of conversion to thoracotomy in the intracavity group were significantly lower than those in the extracavity group (103.4 ± 21.0 min vs. 112.2 ± 17.3 min, 0% vs. 5.8%, P < 0.05, respectively). CONCLUSION: CT-guided placement of the microcoil is a practical, simple, and convenient localization method before VATS, with a high success rate and few complications. Furthermore, it is a better alternative method to place the end of the coil in the pleural cavity because of the lower complication rate, shorter VATS time, and lower rate of thoracotomy conversion.

Oligodendrocyte precursor cells ingest axons in the mouse neocortex.

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form. This physical transformation of neurons is facilitated by the engulfment and degradation of axonal branches and synapses by surrounding glial cells, including microglia and astrocytes. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia have made it difficult to define the contribution of these and other glial cell types to this crucial process. Here, we used large-scale, serial section transmission electron microscopy (TEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex, providing unprecedented resolution of their morphology and composition. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors, frequently surrounded small branches of axons. Numerous phagosomes and phagolysosomes (PLs) containing fragments of axons and vesicular structures were present inside their processes, suggesting that OPCs engage in axon pruning. Single-nucleus RNA sequencing from the developing mouse cortex revealed that OPCs express key phagocytic genes at this stage, as well as neuronal transcripts, consistent with active axon engulfment. Although microglia are thought to be responsible for the majority of synaptic pruning and structural refinement, PLs were ten times more abundant in OPCs than in microglia at this stage, and these structures were markedly less abundant in newly generated oligodendrocytes, suggesting that OPCs contribute substantially to the refinement of neuronal circuits during cortical development.

Binary and analog variation of synapses between cortical pyramidal neurons.

Learning from experience depends at least in part on changes in neuronal connections. We present the largest map of connectivity to date between cortical neurons of a defined type (layer 2/3 [L2/3] pyramidal cells in mouse primary visual cortex), which was enabled by automated analysis of serial section electron microscopy images with improved handling of image defects (250 × 140 × 90 µm3 volume). We used the map to identify constraints on the learning algorithms employed by the cortex. Previous cortical studies modeled a continuum of synapse sizes by a log-normal distribution. A continuum is consistent with most neural network models of learning, in which synaptic strength is a continuously graded analog variable. Here, we show that synapse size, when restricted to synapses between L2/3 pyramidal cells, is well modeled by the sum of a binary variable and an analog variable drawn from a log-normal distribution. Two synapses sharing the same presynaptic and postsynaptic cells are known to be correlated in size. We show that the binary variables of the two synapses are highly correlated, while the analog variables are not. Binary variation could be the outcome of a Hebbian or other synaptic plasticity rule depending on activity signals that are relatively uniform across neuronal arbors, while analog variation may be dominated by other influences such as spontaneous dynamical fluctuations. We discuss the implications for the longstanding hypothesis that activity-dependent plasticity switches synapses between bistable states.

MORC3 restricts human cytomegalovirus infection by suppressing the major immediate-early promoter activity.

During the long coevolution of human cytomegalovirus (HCMV) and humans, the host has formed a defense system of multiple layers to eradicate the invader, and the virus has developed various strategies to evade host surveillance programs. The intrinsic immunity primarily orchestrated by promyelocytic leukemia (PML) nuclear bodies (PML-NBs) represents the first line of defense against HCMV infection. Here, we demonstrate that microrchidia family CW-type zinc finger 3 (MORC3), a PML-NBs component, is a restriction factor targeting HCMV infection. We show that depletion of MORC3 through knockdown by RNA interference or knockout by CRISPR-Cas9 augmented immediate-early protein 1 (IE1) gene expression and subsequent viral replication, and overexpressing MORC3 inhibited HCMV replication by suppressing IE1 gene expression. To relief the restriction, HCMV induces transient reduction of MORC3 protein level via the ubiquitin-proteasome pathway during the immediate-early to early stage. However, MORC3 transcription is upregulated, and the protein level recovers in the late stages. Further analyses with temporal-controlled MORC3 expression and the major immediate-early promoter (MIEP)-based reporters show that MORC3 suppresses MIEP activity and consequent IE1 expression with the assistance of PML. Taken together, our data reveal that HCMV enforces temporary loss of MORC3 to evade its repression against the initiation of immediate-early gene expression.