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2021 ◽  
Author(s):  
Allen W. Lynch ◽  
Christina V. Theodoris ◽  
Henry Long ◽  
Myles Brown ◽  
X. Shirley Liu ◽  
...  

Rigorously comparing gene expression and chromatin accessibility in the same single cells could illuminate the logic of how coupling or decoupling of these mechanisms regulates fate commitment. Here, we present MIRA: Probabilistic Multimodal Models for Integrated Regulatory Analysis, a comprehensive methodology that systematically contrasts transcription and accessibility to infer the regulatory circuitry driving cells along developmental trajectories. MIRA leverages joint topic modeling of cell states and regulatory potential modeling of individual gene loci. MIRA thereby represents cell states in an efficient and interpretable latent space, infers high fidelity lineage trees, determines key regulators of fate decisions at branch points, and exposes the variable influence of local accessibility on transcription at distinct loci. Applied to epidermal maintenance differentiation and embryonic brain development from two different multimodal platforms, MIRA revealed that early developmental genes were tightly regulated by local chromatin landscape whereas terminal fate genes were titrated without requiring extensive chromatin remodeling.


2021 ◽  
pp. 193864002110027
Author(s):  
Shannon I. Kuruvilla ◽  
Christine V. Schaeffer ◽  
Minton T. Cooper ◽  
Brent R. DeGeorge

Background Despite multiple surgical modalities available for the management of Morton’s neuroma, complications remain common. Targeted muscle reinnervation (TMR) has yet to be explored as an option for the prevention of recurrence of Morton’s neuroma. The purpose of the present investigation was to determine the consistency of the relevant foot neurovascular and muscle anatomy and to demonstrate the feasibility of TMR as an option for Morton’s neuroma. Methods The anatomy of 5 fresh-tissue donor cadaver feet was studied, including the course and location of the medial and lateral plantar nerves (MPNs and LPNs), motor branches to abductor hallucis (AH) and flexor digitorum brevis (FDB), as well as the course of sensory plantar digital nerves. Measurements for the locations of the muscular and sensory branches were taken relative to landmarks including the navicular tuberosity (NT), AH, FDB, and the third metatarsophalangeal joint (third MTPJ). Results The mean number of nerve branches to FDB identified was 2. These branch points occurred at an average of 8.6 cm down the MPN or LPN, 9.0 cm from the third MTPJ, 3.0 cm distal to AH distal edge, and 4.8 cm from the NT. The mean number of nerves to AH was 2.2. These branch points occurred at an average of 6.3 cm down the MPN, 11.9 cm from the third MTPJ, 0.8 cm from the AH distal edge, and 3.8 cm from the NT. Conclusions Recurrent interdigital neuroma, painful scar, and neuropathic pain are common complications of operative management for Morton’s neuroma. Targeted muscle reinnervation is a technique that has demonstrated efficacy for the prevention and treatment of neuroma, neuropathic pain, and phantom limb pain in amputees. Herein, we have described the neuromuscular anatomy for the application of TMR for the management of Morton’s neuroma. Target muscles, including the AH and FDB, have consistent innervation patterns in the foot, and consequently, TMR represents a viable option to consider for the management of recalcitrant Morton’s neuroma. Levels of Evidence: V


2021 ◽  
Vol 2021 (11) ◽  
Author(s):  
Wei Fan ◽  
Angelos Fotopoulos ◽  
Stephan Stieberger ◽  
Tomasz R. Taylor ◽  
Bin Zhu

Abstract In a recent paper, here referred to as part I, we considered the celestial four-gluon amplitude with one gluon represented by the shadow transform of the corresponding primary field operator. This correlator is ill-defined because it contains branch points related to the presence of conformal blocks with complex spin. In this work, we adopt a procedure similar to minimal models and construct a single-valued completion of the shadow correlator, in the limit when the shadow is “soft.” By following the approach of Dotsenko and Fateev, we obtain an integral representation of such a single-valued correlator. This allows inverting the shadow transform and constructing a single-valued celestial four-gluon amplitude. This amplitude is drastically different from the original Mellin amplitude. It is defined over the entire complex plane and has correct crossing symmetry, OPE and bootstrap properties. It agrees with all known OPEs of celestial gluon operators. The conformal block spectrum consists of primary fields with dimensions ∆ = m + iλ, with integer m ≥ 1 and various, but always integer spin, in all group representations contained in the product of two adjoint representations.


2021 ◽  
Vol 13 (19) ◽  
pp. 3802
Author(s):  
Illia Ziamtsov ◽  
Kian Faizi ◽  
Saket Navlakha

Modern plant phenotyping requires tools that are robust to noise and missing data, while being able to efficiently process large numbers of plants. Here, we studied the skeletonization of plant architectures from 3D point clouds, which is critical for many downstream tasks, including analyses of plant shape, morphology, and branching angles. Specifically, we developed an algorithm to improve skeletonization at branch points (forks) by leveraging the geometric properties of cylinders around branch points. We tested this algorithm on a diverse set of high-resolution 3D point clouds of tomato and tobacco plants, grown in five environments and across multiple developmental timepoints. Compared to existing methods for 3D skeletonization, our method efficiently and more accurately estimated branching angles even in areas with noisy, missing, or non-uniformly sampled data. Our method is also applicable to inorganic datasets, such as scans of industrial pipes or urban scenes containing networks of complex cylindrical shapes.


2021 ◽  
Author(s):  
Lianne H. Scholtens ◽  
Rory Pijnenburg ◽  
Siemon C. de Lange ◽  
Inge Huitinga ◽  
Martijn P. van den Heuvel ◽  
...  

AbstractThe brain requires efficient information transfer between neurons and between large-scale brain regions. Brain connectivity follows predictable organizational principles: at the cellular level, larger supragranular pyramidal neurons have larger dendritic trees, more synapses, more complex branching and perform more complex neuronal computations; at the macro-scale, region-to-region connections are suggested to display a diverse architecture with highly connected hub-areas facilitating complex information integration and computation. Here, we explore the hypothesis that the branching structure of large-scale region-to-region connectivity follows similar organizational principles as known for the neuronal scale. We examine microscale connectivity of basal dendritic trees of supragranular pyramidal neurons (300+) across ten cortical areas in five human donor brains (1M/4F). Dendritic complexity was quantified as the number of branch points, tree length, spine count, spine density and overall branching complexity. High-resolution diffusion-weighted MRI was used to construct ‘white matter trees’ of cortico-cortical wiring. Examining the complexity of the resulting white matter trees using the same measures as for dendritic trees shows multimodal association areas to have larger, more complexly branched white matter trees than primary areas (all p<0.0001) and regional macroscale complexity to run in parallel with microscale measures, in terms of number of inputs (r=0.677, p=0.032), branch points (r=0.790, p=0.006), total tree length (r=0.664, p=0.036) and branching complexity (r=0.724, p=0.018). Our findings support the integrative theory that brain connectivity is structured following similar ‘principles of connectivity’ at the neuronal and macroscale level, and provide a framework to study connectivity changes in brain conditions at multiple levels of brain organization.


Development ◽  
2021 ◽  
Vol 148 (18) ◽  
Author(s):  
Adam J. Isabella ◽  
Jason A. Stonick ◽  
Julien Dubrulle ◽  
Cecilia B. Moens

ABSTRACT Regeneration after peripheral nerve damage requires that axons re-grow to the correct target tissues in a process called target-specific regeneration. Although much is known about the mechanisms that promote axon re-growth, re-growing axons often fail to reach the correct targets, resulting in impaired nerve function. We know very little about how axons achieve target-specific regeneration, particularly in branched nerves that require distinct targeting decisions at branch points. The zebrafish vagus motor nerve is a branched nerve with a well-defined topographic organization. Here, we track regeneration of individual vagus axons after whole-nerve laser severing and find a robust capacity for target-specific, functional re-growth. We then develop a new single-cell chimera injury model for precise manipulation of axon-environment interactions and find that (1) the guidance mechanism used during regeneration is distinct from the nerve's developmental guidance mechanism, (2) target selection is specified by neurons' intrinsic memory of their position within the brain, and (3) targeting to a branch requires its pre-existing innervation. This work establishes the zebrafish vagus nerve as a tractable regeneration model and reveals the mechanistic basis of target-specific regeneration.


Author(s):  
Katsuhiro Moriya

AbstractFor a given minimal surface in the n-sphere, two ways to construct a minimal surface in the m-sphere are given. One way constructs a minimal immersion. The other way constructs a minimal immersion which may have branch points. The branch points occur exactly at each point where the original minimal surface is geodesic. If a minimal surface in the 3-sphere is given, then these ways construct Lawson’s polar variety and bipolar surface.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Dong Cao

Abstract Background Circular RNAs (circRNAs) play diverse roles in different biological and physiological environments and are always expressed in a tissue-specific manner. Especially, circRNAs are enriched in the brain tissues of almost all investigated species, including humans, mice, Drosophila, etc. Although circRNAs were found in C. elegans, the neuron-specific circRNA data is not available yet. Exon-skipping is found to be correlated to circRNA formation, but the mechanisms that link them together are not clear. Results Here, through large-scale neuron isolation from the first larval (L1) stage of C. elegans followed by RNA sequencing with ribosomal RNA depletion, the neuronal circRNA data in C. elegans were obtained. Hundreds of novel circRNAs were annotated with high accuracy. circRNAs were highly expressed in the neurons of C. elegans and were positively correlated to the levels of their cognate linear mRNAs. Disruption of reverse complementary match (RCM) sequences in circRNA flanking introns effectively abolished circRNA formation. In the zip-2 gene, deletion of either upstream or downstream RCMs almost eliminated the production of both the circular and the skipped transcript. Interestingly, the 13-nt RCM in zip-2 is highly conserved across five nematode ortholog genes, which show conserved exon-skipping patterns. Finally, through in vivo one-by-one mutagenesis of all the splicing sites and branch points required for exon-skipping and back-splicing in the zip-2 gene, I showed that back-splicing still happened without exon-skipping, and vice versa. Conclusions Through protocol optimization, total RNA obtained from sorted neurons is increased to hundreds of nanograms. circRNAs highly expressed in the neurons of C. elegans are more likely to be derived from genes also highly expressed in the neurons. RCMs are abundant in circRNA flanking introns, and RCM-deletion is an efficient way to knockout circRNAs. More importantly, these RCMs are not only required for back-splicing but also promote the skipping of exon(s) to be circularized. Finally, RCMs in circRNA flanking introns can directly promote both exon-skipping and back-splicing, providing a new explanation for the correlation between them.


Author(s):  
Hamza Ghilas ◽  
Meriem Gagaoua ◽  
Abdelkamel Tari ◽  
Mohamed Cheriet

This paper addresses the challenging task of word spotting in Arabic handwritten documents. We proposed a novel feature that we called Spatial Distribution of Ink at Keypoints (SDIK). The proposed feature captures the characteristics of Arabic handwriting concentrated at endpoints and branch points. SDIK feature quantizes the spatial repartition of ink pixels in the neighborhoods of keypoints. The resulting SDIK features are very fast to match, we take this advantage to match a query word with lines images rather than words images. By this matching mechanism, we overcome the hard task of segmenting an Arabic document into words. The method proposed in this study is tested on historical Arabic document with IBN SINA dataset and on modern handwriting with IFN/ENIT database. The obtained results are great of interest for retrieving query words in an Arabic document.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ahsan Irshad ◽  
Huijun Guo ◽  
Shoaib Ur Rehman ◽  
Xueqing Wang ◽  
Jiayu Gu ◽  
...  

Manipulation of genes involved in starch synthesis could significantly affect wheat grain weight and yield. The starch-branching enzyme (SBE) catalyzes the formation of branch points by cleaving the α-1,4 linkage in polyglucans and reattaching the chain via an α-1,6 linkage. Three types of SBE isoforms (SBEI, SBEII, and SBEIII) exist in higher plants, with the number of SBE isoforms being species-specific. In this study, the coding sequence of the wheat TaSBEIII gene was amplified. After the multiple sequence alignment of TaSBEIII genome from 20 accessions in a wheat diversity panel, one SNP was observed in TaSBEIII-A, which formed the allelic marker allele-T. Based on this SNP at 294 bp (C/T), a KASP molecular marker was developed to distinguish allelic variation among the wheat genotypes for thousand grain weight (TGW). The results were validated using 262 accessions of mini core collection (MCC) from China, 153 from Pakistan, 53 from CIMMYT, and 17 diploid and 18 tetraploid genotypes. Association analysis between TaSBEIII-A allelic variation and agronomic traits found that TaSBEIII-A was associated with TGW in mini core collection of China (MCC). The accessions possessing Allele-T had higher TGW than those possessing Allele-C; thus, Allele-T was a favorable allelic variation. By analyzing the frequency of the favorable allelic variation Allele-T in MCC, it increased from pre-1950 (25%) to the 1960s (45%) and increased continuously from 1960 to 1990 (80%). The results suggested that the KASP markers can be utilized in grain weight improvement, which ultimately improves wheat yield by marker-assisted selection in wheat breeding. The favorable allelic variation allele-T should be valuable in enhancing grain yield by improving the source and sink simultaneously. Furthermore, the newly developed KASP marker validated in different genetic backgrounds could be integrated into a breeding kit for screening high TGW wheat.


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