Complex Branching Patterns Research Articles

Specialized endothelial tip cells guide neuroretina vascularization and blood-retina-barrier formation.

Endothelial tip cells guiding tissue vascularization are primary targets for angiogenic therapies. Whether tip cells require differential signals to develop their complex branching patterns remained unknown. Here, we show that diving tip cells invading the mouse neuroretina (D-tip cells) are distinct from tip cells guiding the superficial retinal vascular plexus (S-tip cells). D-tip cells have a unique transcriptional signature, including high TGF-β signaling, and they begin to acquire blood-retina barrier properties. Endothelial deletion of TGF-β receptor I (Alk5) inhibits D-tip cell identity acquisition and deep vascular plexus formation. Loss of endothelial ALK5, but not of the canonical SMAD effectors, leads to aberrant contractile pericyte differentiation and hemorrhagic vascular malformations. Oxygen-induced retinopathy vasculature exhibits S-like tip cells, and Alk5 deletion impedes retina revascularization. Our data reveal stage-specific tip cell heterogeneity as a requirement for retinal vascular development and suggest that non-canonical-TGF-β signaling could improve retinal revascularization and neural function in ischemic retinopathy.

Optical Coherence Tomography Angiography Microvascular Variations in Pre- and Posttreatment of Retinoblastoma Tumors

Introduction: The purpose of this study is to describe variations in microvasculature before and after treatment of treatment-naive lesions and during consolidation therapy of retinoblastoma lesions using an investigational portable optical coherence tomography angiography (OCTA) system. Methods: This study is a single-center, prospective, observational case series. Recruited subjects were either undergoing surveillance for retinoblastoma or had newly detected retinoblastoma. Nine tumors from 7 eyes in 6 patients were included. During exams under anesthesia, the tumors were imaged with an investigational portable OCTA system. OCTA images were analyzed to assess vascular changes before and after treatment. Results: In all 6 presented cases, OCTA imaging revealed distinctive vascular patterns, such as dilated feeder arteries and draining veins, disorganized and complex branching patterns, irregular vessel calibers, and dilation and tortuosity of vessels. After treatment, OCTA imaging revealed decreased intrinsic tumor vascularity and reduced dilation of draining and feeder vessels. Tumor relapse demonstrated prominent vascularity (n = 1) that resolved on repeat OCTA after transpupillary thermotherapy treatment. Type 2 (n = 1), 3 (n = 6), and 4 (n = 1) tumor regression patterns were seen in our patients after treatment, and OCTA findings were consistent with a previously published report. Interestingly, in one of the presented cases, OCTA demonstrated clear feeder, draining, and intrinsic tumor vessels that were not as evident on fluorescein angiography. Conclusions: OCTA may offer a noninvasive and sensitive technique to evaluate the vasculature of both the tumor and the surrounding retina in retinoblastoma. With additional research and development into its use in patients with retinoblastoma, OCTA may one day be useful in assessing treatment response and residual tumor activity.

The Importance of Food Pulses in Benthic-Pelagic Coupling Processes of Passive Suspension Feeders

Benthic-pelagic coupling processes and the quantity of carbon transferred from the water column to the benthic suspension feeders need multiple intensive sampling approaches where several environmental variables and benthos performance are quantified. Here, activity, dietary composition, and capture rates of three Mediterranean gorgonians (Paramuricea clavata, Eunicella singularis, and Leptogorgia sarmentosa) were assessed in an intensive cycle considering different variables such as the seston concentration and quality (e.g., carbon, nitrogen, and zooplankton), the colony branch patterns, and the energetic input of the single species (i.e., mixotrophic and heterotrophic). The three species showed clear differences in their impact on the seston concentration. Paramuricea clavata, the most densely distributed, showed a greater impact on the near bottom water column seston. The lowest impact of E. singularis on the seston could be explained by its mixotrophy and colony branching pattern. Leptogorgia sarmentosa had a similar impact as E. singularis, having a much more complex branching pattern and more than an order of magnitude smaller number of colonies per meter square than the other two octocorals. The amount of carbon ingested in the peaks of the capture rates in the three species may cover a non-neglectable proportion of the potential carbon fluxes.

Structural airway imaging metrics are differentially associated with persistent chronic bronchitis

BackgroundChronic bronchitis (CB) is strongly associated with cigarette smoking, but not all smokers develop CB. We aimed to evaluate whether measures of structural airway disease on CT are differentially associated...

Noncanonical TGFβ Signaling Promotes Specialized Neuroretina Tip-Cell Sprouting and Blood-Retina Barrier Formation

Endothelial tip cells guiding tissue vascularization are primary targets for angiogenic therapies. Whether tip cells require differential signals to develop their complex branching patterns remained unknown. Here we show that tip cells invading the neuroretina (D-tip cells) are distinct from tip cells guiding the superficial plexus (S-tip cells). D-tip cells have a unique transcriptional signature, display blood-retina barrier properties and TGFβ signaling requirements. Endothelial deletion of TGFβ receptor I (ALK5) inhibits D-tip cell differentiation and diving vessels. ALK5 endothelial deficiency results in a dysfunctional S-like tip cell molecular signature, aberrant contractile pericytes, and hemorrhagic vascular malformations, while SMAD mutants do not develop this phenotype. Oxygen-induced retinopathy retinas exhibit S-like tip cells with increased Alk5 signaling, and Alk5 deletion impedes retina revascularization. Our data reveal stage-specific tip cell heterogeneity as a requirement for retinal vascular development and suggest that noncanonical-TGFβ signaling could improve retinal revascularization and neural function in ischemic retinopathy.

Temporal Order of Neural Progenitor Division Controls Neural Connectivity

Spatiotemporal mechanisms generating neural diversity are fundamental for understanding neural processes. Here, we investigated how neural connection diversity arises from neurons coming from identical progenitors. In the dorsal thorax of Drosophila, rows of mechanosensory organs originate from the division of sensory organ progenitor (SOPs). We show that in each row of the notum, a central SOP divides first, then neighboring SOPs divide, and so on. This centrifugal wave of mitoses depends on cell-cell inhibitory interactions mediated by SOP cytoplasmic protrusions and Scabrous, a secreted protein interacting with the Delta/Notch complex. When scabrous was downregulated, the mitotic wave was abolished, axonal growth was more synchronous, axonal terminals had a complex branching pattern and fly behavior was impaired. We propose that the temporal order of progenitor divisions influences the birth order of sensory neurons which is critical for correct axon wiring and appropriate grooming behavior, supporting the idea that developmental timing controls neural connectivity.

Variability in the number of infraorbital foramina in rhesus macaques (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis).

This study aimed to determine the number of infraorbital foramina in monkeys of the Papionini tribe. The authors performed a μCT analysis of the morphology of the infraorbital foramina. A total number of 52 simian skulls belonged to two macaque species: Macaca mulatta and Macaca fascicularis were used in the study. The number of infraorbital foramina was counted macroscopically and with the use of a magnifying glass. Next, the skull representing the most common morphological type was selected and scanned by micro-computed tomography (μCT). The Shapiro-Wilk normality test was used in the study. To compare the differences in the number of infraorbital foramen between species, sex and sides, the Mann-Whitney U test was applied. Three infraorbital foramina were present in most individuals from the test group. The Mann-Whitney test revealed no statistically significant difference between the number of foramina on the right- and left-hand side. Likewise, no statistically significant differences between the numbers of infraorbital foramina across sexes were observed. Volumetric reconstructions revealed the presence of separate infraorbital canals for each infraorbital foramen. Craniofacial innervation in macaques is formed by complex branching patterns of cranial nerves. Variability in the number of infraorbital foramina suggests a variable maxillary innervation pattern in these animals. Based on the analysis of volumetric projections, the presence of two labial branches and a single nasal branch of the infraorbital nerve is suggested. Detailed descriptions are supported by quantitative data and μCT evidence.

Timing Is Everything: MND1 Regulates Meristem Phase Change in Barley.

The shoot and inflorescence architecture of grasses are characterized by complex branching patterns, which contribute to the great diversity of this plant clade ([Whipple 2017][1]). During crop domestication, plants were selected for a variety of body plans ([Pautler et al., 2013][2]). For example,

The Purinergic Receptor P2rx3 is Required for Spiral Ganglion Neuron Branch Refinement during Development.

The mammalian cochlea undergoes a highly dynamic process of growth and innervation during development. This process includes spiral ganglion neuron (SGN) branch refinement, a process whereby Type I SGNs undergo a phase of “debranching” before forming unramified synaptic contacts with inner hair cells. Using Sox2CreERT2 and R26RtdTomato as a strategy to genetically label individual SGNs in mice of both sexes, we report on both a time course of SGN branch refinement and a role for P2rx3 in this process. P2rx3 is an ionotropic ATP receptor that was recently implicated in outer hair cell spontaneous activity and Type II SGN synapse development (Ceriani et al., 2019), but its function in Type I SGN development is unknown. Here, we demonstrate that P2rx3 is expressed by Type I SGNs and hair cells during developmental periods that coincide with SGN branching refinement. P2rx3 null mice show SGNs with more complex branching patterns on their peripheral synaptic terminals and near their cell bodies around the time of birth. Loss of P2rx3 does not appear to confer general changes in axon outgrowth or hair cell formation, and alterations in branching complexity appear to mostly recover by postnatal day (P)6. However, when we examined the distribution of Type I SGN subtypes using antibodies that bind Calb2, Calb1, and Pou4f1, we found that P2rx3 null mice showed an increased proportion of SGNs that express Calb2. These data suggest P2rx3 may be necessary for normal Type I SGN differentiation in addition to serving a role in branch refinement.

The brain structure of selected trypanorhynch tapeworms.

The brain architecture in four species of tapeworms from the order Trypanorhyncha has been studied. In all species, the brain consists of paired anterior and lateral lobes, and an unpaired central lobe. The anterior lobes connect by dorsal and ventral semicircular commissures; the central and lateral lobes connect by a median and an X-shaped crisscross commissure. In the center of the brain, five well-developed compact neuropils are present. The brain occupies a medial position in the scolex pars bothrialis. The ventral excretory vessels are situated outside the lateral lobes of the brain; the dorsal excretory vessels are located inside the brain and dorsal to the median commissure. The brain gives rize four anterior proboscis nerves and four posterior bulbar nerves with myelinated giant axons (GAs). The cell bodies of the GAs are located within the X-commissure and in the bulbar nerves. Highly developed serotonergic neuropils are present in the anterior and lateral lobes; numerous 5-HT neurons are found in the brain lobes including the central unpaired lobe. The X-cross commissure consists of the α-tub-immunoreactive and 5-HT-IR neurites. Eight ultrastructural types of neurons were found in the brain of the three species investigated. In addition, different types of synapses were present in the neuropils. Glial cells ensheath the brain lobes, the neuropils, the GAs, and the bulbar nerves. Glia cell processes form complex branching patterns of thin cytoplasmic sheets sandwiched between adjacent neural processes and filling the space between neurons. Multilayer myelin-like envelopes and a mesaxon-like structure have been found in Trypanorhyncha nervous system. We compared the brain architecture of Trypanorhyncha with that of an early basal cestode taxon, that is, Diphyllobothriidea, and present a hypothesis about the homology of the anterior brain lobes in order Trypanorhyncha; and the lateral lobes and median commissure are homologous brain structures within Eucestoda.

Flow and Sediment Flux Asymmetry in a Branching Channel Delta

AbstractRiver deltas form complex branching patterns that distribute sediment to the coastal sea. The routing and storage of this sediment in deltas are poorly understood. We present results of a 1‐month study of the sediment and water transport through two branches of the Wax Lake Delta on the coast of Louisiana. The two channels maintained near‐equal total partitioning of flow and sediment discharge. East Pass was narrower and had higher tidally averaged velocities, lower tidal velocity fluctuations, more sediment flux, and less alluvial bed cover than Main Pass. We connected these differences to small differences in the geometry of the channels and feedbacks between these differences. East Pass was slightly shorter than Main Pass, leading to a steeper mean free surface profile, yielding higher subtidal currents and advective sediment fluxes. Main Pass received the tides from Atchafalaya Bay earlier than East Pass, allowing tides to reach their junction earlier from Main Pass. This led to Main Pass capturing tidal prism from East Pass and higher tidal velocity fluctuations in Main Pass. These fluctuations caused larger flow convergences in Main Pass, pumping sediment out of East Pass on tidal timescales. Since East Pass had higher mean velocities and lower tidal fluctuations, it spent less time in flow regimes that would allow the formation of alluvial bed cover. By explaining these asymmetries with physical arguments, we showed how geometric differences drive asymmetries in branching systems. Barrier island inlets, coastal lagoons, and other systems may display similar behavior.

Topical shading substantially inhibits vegetative branching by altering leaf photosynthesis and hormone contents of cotton plants

Cotton plants have complex branching patterns formed by distal fruiting branches (FB) and basal vegetative branches (VB). Our prior study showed that cotton’s vegetative branching was considerably inhibited under high plant density via altered hormone contents in VB tips and photosynthetic production in VB leaves. Here, our current objective was to determine whether or not shading of VB reduced vegetative branching, and whether this effect was elicited via a similar mechanism(s) as that under high plant density. To this end, cotton was planted on 76-cm row widths at a moderate density (5 plants m−2). Vegetative branches of cotton plants were shaded to approximate 60% of full solar exposure by using polyethylene nets during squaring; those without shading served as the control. The growth and development of VB, as well as underlying agronomic, physiological and molecular events of both shaded and control plants were examined. Shading VB reduced its numbers by 56.2%; its length by 88.8% and the ratio of VB biomass to total biomass by 91.3%, but it increased FB biomass by 30.8%, compared with the control at 69 days after seeding. Compared with control, shading did not reduce seedcotton yield, suggesting a yield stability similar to that found previously under high plant density. The net photosynthetic rate, chlorophyll content and ribulose-1,5-bisphosphate carboxylase activity in VB leaves were considerably decreased by shading. The sucrose biosynthesis gene GhCYFBP in leaves and GhphyB gene in tips of VB were down-regulated under its shading, followed by lower soluble sugar and starch contents. Suppressed photosynthetic production in leaves of VB was a key reason for poor vegetative branching under shaded conditions. Shading diminished both the auxin (IAA) content and auxin transport from VB tips by decreasing the expression of corresponding genes for auxin biosynthesis (GhYUC5) and transport (GhPIN1and GhPIN5). This treatment also reduced the content of cytokinins (CTKs) in the VB tips by decreasing the expression of the CTKs biosynthesis gene, GhIPT3. By contrast, the SL receptor gene, GhD14 was upregulated in the VB tips, followed by a greater content of strigolactones (SLs). We proposed that lower IAA, CTKs and brassinosteroid contents plus higher SLs content due to differential expression of hormone-related genes in the VB tips suppressed vegetative branching when shaded. Our results suggest this mechanism is not unlike how high plant density inhibits vegetative branching in cotton.

Angiolymphoid hyperplasia with eosinophilia treated with Mohs micrographic surgery

A 60-year-old healthy man presented with several enlarging, tender, spontaneously bleeding, and episodically pruritic nodules on his ear. Five agminated pink-red papulonodules of the superior postauricular sulcus were noted on examination. Pathological examination revealed a lobular dermal vascular proliferation with plump endothelial cells protruding into the lumen in a hobnail pattern, along with a dense perivascular inflammatory infiltrate composed of plasma cells, lymphocytes, and numerous eosinophils. The diagnosis of angiolymphoid hyperplasia with eosinophilia was confirmed. After discussing treatment modalities, the patient opted for Mohs micrographic surgery (MMS). Three stages of MMS were able to remove all large vessel involvement and clear the peripheral margins, but the tumor had a complex branching pattern of growth in the deep bed of the wound with numerous tiny foci remaining. Owing to risk of disfigurement, no further excision was undertaken. The area was reconstructed with a temporalis fascia flap and a full-thickness skin graft. Despite remaining microscopic disease, the patient remained without recurrence or symptoms at one year of follow up.

A Dynamic Co-expression Map of Early Inflorescence Development in Setaria viridis Provides a Resource for Gene Discovery and Comparative Genomics.

The morphological and functional diversity of plant form is governed by dynamic gene regulatory networks. In cereal crops, grain and/or pollen-bearing inflorescences exhibit vast architectural diversity and developmental complexity, yet the underlying genetic framework is only partly known. Setaria viridis is a small, rapidly growing grass species in the subfamily Panicoideae, a group that includes economically important cereal crops such as maize and sorghum. The S. viridis inflorescence displays complex branching patterns, but its early development is similar to that of other panicoid grasses, and thus is an ideal model for studying inflorescence architecture. Here we report a detailed transcriptional resource that captures dynamic transitions across six sequential stages of S. viridis inflorescence development, from reproductive onset to floral organ differentiation. Co-expression analyses identified stage-specific signatures of development, which include homologs of previously known developmental genes from maize and rice, suites of transcription factors and gene family members, and genes of unknown function. This spatiotemporal co-expression map and associated analyses provide a foundation for gene discovery in S. viridis inflorescence development, and a comparative model for exploring related architectural features in agronomically important cereals.

Neuropeptide Mapping of Dimmed Cells of Adult Drosophila Brain.

Neuropeptides are structurally highly diverse messenger molecules that act as regulators of many physiological processes such as development, metabolism, reproduction or behavior in general. Differentiation of neuropeptidergic cells often corresponds with the presence of the transcription factor DIMMED. In the central nervous system of the fruit fly Drosophila melanogaster, DIMMED commonly occurs in neuroendocrine neurons that release peptides as neurohormones but also in interneurons with complex branching patterns. Fly strains with green fluorescence protein (GFP)-expressing dimmed cells make it possible to systematically analyze the processed neuropeptides in these cells. In this study, we mapped individual GFP-expressing neurons of adult D. melanogaster from the dimmed (c929)>GFP line. Using single cell mass spectrometry, we analyzed 10 types of dimmed neurons from the brain/gnathal ganglion. These cells included neuroendocrine cells with projection into the retrocerebral complex but also a number of large interneurons. Resulting mass spectra not only provided comprehensive data regarding mature products from 13 neuropeptide precursors but also evidence for the cellular co-localization of neuropeptides from different neuropeptide genes. The results can be implemented in a neuroanatomical map of the D. melanogaster brain. Graphical Abstract ᅟ.

Endovascular treatment of middle cerebral artery aneurysms: A single center experience with a focus on thromboembolic complications.

Background Endovascular treatment of middle cerebral artery (MCA) aneurysms has traditionally been considered difficult due to complex branching patterns, frequent involvement of parent vessels within the aneurysm neck, and a high incidence of thromboembolic complications. Methods The cases of 93 MCA aneurysms treated with endovascular intervention at our institution between 2003 and 2015 were retrospectively reviewed. Demographic, clinical, and radiographic variables were recorded and analyzed. Results Immediate complete or near-complete occlusion was achieved in 81 (90%) cases. At the longest follow up of 6 months or greater, 83.3% of the aneurysms were stable-to-improved in the Raymond occlusion classification, 8.3% were found to have minor recanalization not requiring retreatment, and 8.3% required retreatment due to significant recanalization. Thromboembolic events occurred in 18 (19.3%) of cases, but only 1 resulted in permanent vessel occlusion and only 1 resulted in permanent neurologic impairment. Thrombus was resolved with intra-arterial thrombolysis or mechanical thrombectomy in 17 of the 18 cases. There were only two cases resulting in morbidity (2.15%). There was no statistically significant correlation between aneurysm location, size, morphology, or use of adjuvant device with radiographic outcome or thromboembolic event. Conclusions While the rate of thromboembolic events in our series was 19%, the overall morbidity was only 2%. This highlights the fact that even complex MCA aneurysms can safely and effectively be treated by endovascular means with or without the use of balloon or stent assistance, as long as the interventionalist is astutely aware of the possibility of thrombus formation and acts accordingly with thrombolytic therapy when necessary.

A Topological Representation of Branching Neuronal Morphologies

Many biological systems consist of branching structures that exhibit a wide variety of shapes. Our understanding of their systematic roles is hampered from the start by the lack of a fundamental means of standardizing the description of complex branching patterns, such as those of neuronal trees. To solve this problem, we have invented the Topological Morphology Descriptor (TMD), a method for encoding the spatial structure of any tree as a “barcode”, a unique topological signature. As opposed to traditional morphometrics, the TMD couples the topology of the branches with their spatial extents by tracking their topological evolution in 3-dimensional space. We prove that neuronal trees, as well as stochastically generated trees, can be accurately categorized based on their TMD profiles. The TMD retains sufficient global and local information to create an unbiased benchmark test for their categorization and is able to quantify and characterize the structural differences between distinct morphological groups. The use of this mathematically rigorous method will advance our understanding of the anatomy and diversity of branching morphologies.

Identifying early pathogenic events during vascular calcification in uremic rats

Vascular calcification in chronic kidney disease is a very complex process traditionally explained in multifactorial terms. Here we sought to clarify relevance of the diverse agents acting on vascular calcification in uremic rats and distinguish between initiating and complicating factors. After 5/6 nephrectomy, rats were fed a 1.2% phosphorus diet and analyzed at different time points. The earliest changes observed in the aortic wall were noticed 11 weeks after nephrectomy: increased Wnt inhibitor Dkk1 mRNA expression and tissue non-specific alkaline phosphatase (TNAP) expression and activity. First deposits of aortic calcium were observed after 12 weeks in areas of TNAP expression. Increased mRNA expressions of Runx2, BMP2, Pit1, Pit2, HOXA10, PHOSPHO1, Fetuin-A, ANKH, OPN, Klotho, cathepsin S, MMP2, and ENPP1 were also found after TNAP changes. Increased plasma concentrations of activin A and FGF23 were observed already at 11 weeks post-nephrectomy, while plasma PTH and phosphorus only increased after 20 weeks. Plasma pyrophosphate decreased after 20 weeks, but aortic pyrophosphate was not modified, nor was the aortic expression of MGP, Msx2, several carbonic anhydrases, osteoprotegerin, parathyroid hormone receptor-1, annexins II and V, and CD39. Thus, increased TNAP and Dkk1 expression in the aorta precedes initial calcium deposition, and this increase is only preceded by elevations in circulating FGF23 and activin A. The expression of other agents involved in vascular calcification only changes at later stages of chronic kidney disease, in a complex branching pattern that requires further clarification.

Magnetic Resonance Neurography of the Pelvic Nerves

Chronic pelvic pain syndrome is commonly caused by nerve injury, inflammation, or entrapment. Owing to the complex anatomy and branching patterns of pelvic nerves, pelvic neuropathies are often difficult to illustrate and diagnose. High-resolution 3-T magnetic resonance neurography is a promising technique for the evaluation of peripheral neuropathy. In this article, the authors discuss the normal anatomy of major pelvic nerves, technical considerations of high-resolution imaging, and normal and abnormal imaging appearances with relevant case examples.

Pudendal nerve and branch neuropathy: magnetic resonance neurography evaluation

Pudendal neuralgia is being increasingly recognized as a cause of chronic pelvic pain, which may be related to nerve injury or entrapment. Due to its complex anatomy and branching patterns, the pudendal nerve abnormalities are challenging to illustrate. High resolution 3 T magnetic resonance neurography is a promising technique for the evaluation of peripheral neuropathies. In this article, the authors discuss the normal pudendal nerve anatomy and its variations, technical considerations of pudendal nerve imaging, and highlight the normal and abnormal appearances of the pudendal nerve and its branches with illustrative case examples.