Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A

Variants in the high confident autism spectrum disorder (ASD) gene ANK2 target both ubiquitously expressed 220 kDa ankyrin-B and neurospecific 440 kDa ankyrin-B (AnkB440) isoforms. Previous work showed that knock-in mice expressing an ASD-linked Ank2 variant yielding a truncated AnkB440 product exhibit ectopic brain connectivity and behavioral abnormalities. Expression of this variant or loss of AnkB440 caused axonal hyperbranching in vitro, which implicated AnkB440 microtubule bundling activity in suppressing collateral branch formation. Leveraging multiple mouse models, cellular assays, and live microscopy, we show that AnkB440 also modulates axon collateral branching stochastically by reducing the number of F-actin-rich branch initiation points. Additionally, we show that AnkB440 enables growth cone (GC) collapse in response to chemorepellent factor semaphorin 3 A (Sema 3 A) by stabilizing its receptor complex L1 cell adhesion molecule/neuropilin-1. ASD-linked ANK2 variants failed to rescue Sema 3A-induced GC collapse. We propose that impaired response to repellent cues due to AnkB440 deficits leads to axonal targeting and branch pruning defects and may contribute to the pathogenicity of ANK2 variants.

Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor Sema 3A

Variants in the high confident autism spectrum disorder gene ANK2 target both ubiquitously expressed 220-kDa ankyrin- B and neurospecific 440-kDa ankyrin-B (AnkB440) isoforms. Previous work showed that knock-in mice expressing an ASD linked Ank2 variant yielding a truncated AnkB440 product exhibit ectopic brain connectivity and behavioral abnormalities. Expression of this variant or loss of AnkB440 caused axonal hyperbranching in vitro, which implicated AnkB440 microtubule bundling activity in suppressing collateral branch formation. Leveraging multiple mouse models, cellular assays, and live microscopy, we show that AnkB440 also modulates axon collateral branching stochastically by reducing the number of F-actin-rich branch initiation points. Additionally, we show that AnkB440 enables growth cone (GC) collapse in response to chemorepellent factor semaphorin 3A (Sema 3A) by stabilizing its receptor complex L1 cell adhesion molecule/neuropilin-1. ASD-linked ANK2 variants failed to rescue Sema 3A-induced GC collapse. We propose that impaired response to repellent cues due to AnkB440 deficits leads to axonal guidance and branch pruning defects and may contribute to the pathogenicity of ANK2 variants.

Antagonistic activities of Fmn2 and ADF regulate axonal F-actin patch dynamics and the initiation of collateral branching

ABSTRACTInterstitial collateral branching of axons is a critical component in the development of functional neural circuits. Axon collateral branches are established through a series of cellular processes initiated by the development of a specialized, focal F-actin network in axons. The formation, maintenance and remodelling of this F-actin patch is critical for the initiation of axonal protrusions that are subsequently consolidated to form a collateral branch. However, the mechanisms regulating F-actin patch dynamics are poorly understood.Fmn2 is a formin family member implicated in multiple neurodevelopmental disorders. We find that Fmn2 regulates the initiation of axon collateral protrusions. Fmn2 localises to the protrusion-initiating axonal F-actin patches and regulates the lifetime and size of these F-actin networks. The F-actin nucleation activity of Fmn2 is necessary for F-actin patch stability but not for initiating patch formation. We show that Fmn2 insulates the F-actin patches from disassembly by the actin-depolymerizing factor, ADF, and promotes long-lived, larger patches that are competent to initiate axonal protrusions.The regulation of axonal branching can contribute to the neurodevelopmental pathologies associated with Fmn2 and the dynamic antagonism between Fmn2 and ADF may represent a general mechanism of formin-dependent protection of Arp2/3-initiated F-actin networks from disassembly.

The Suffix -ic-ĭ in the Slavonic Languages

The section in some way continues the previous work on the name of the Great Moravia’s prince Ðàñò¸öü, in which suffix -ic-ь stands out. The section discusses controversial issues related to the suffix -ic-ь. The analysis reveals that at the level of the Proto-Slavonic language the suffix -ic-ь can be distinguished with meanings of diminution and agent nouns as non productive palatalized correlate of suffix -ik-ъ. This derivational formant was typical for South Slavonic languages, its presence in East Slavonic languages is discussional, and it is unknown to West Slavonic languages. Regarding the name Ðàñò¸öü an assumption was made that it means ‘short man, shorty’ or ‘sprout’ if we assume that the prince might be an indirect descendant (a collateral branch) of his family.

Anatomical and Imagistic Aspects of the Aortic Arch in Chinchilla lanigera

Background: The investigation on the cardiocirculatory system in chinchilla has become increasingly important due to the use of the species in experimental medicine (toxicology, pathology, parasitology etc.). Even though initially this species was regarded with a strict economic interest, in the last period, chinchillas have become an increasingly-encountered patient in veterinary clinics and hospitals. Another aspect is the use of the species in medical research, as experimental model or in parasitology. The present study tackles a combined anatomical and radiological (angiographical) study to accurately describe the vascular anatomy of the initial part of the aortic arch (Arcus aortae).Materials, Methods & Results: The anatomical distribution of collaterals detached from arcus aorticus (brachiocephalic trunk and subclavian arteries) are highlighted in this paper. To do that, the classical stratigraphic anatomical investigation, followed by the radiological study with the help of the contrast substance injected into the vascular bed were used in combination. Several Chinchilla lanigera female carcasses, obtained from a private commercial farming unit in Cluj county, Romania were used for this study. Ten carcasses were used for the anatomical study, being injected into the vascular bed with a mixture of latex and acrylic dye, fixated into formaldehyde 5% and later dissected, while the other ten carcasses were injected at the level of the aortic arch with Visipaque 320 contrast substance and subjected to the angiographical procedure.The anatomical investigation was carried after an initial 5 day-fixation period, while the angiographic procedure was initiated using the TEMCO Grx-01 device and the Veterinary Digital Imaging System® as digital imaging processing software. This combined study shows the differential mode of emergence of the subclavian and carotid arteries in this species. The brachiocephalic trunk is the first large collateral branch arising from the initial part of the aortic cross while the left subclavian artery, in all studied cases, stems from this initial part of the aortic arch. The right subclavian artery arises from the terminal part of the brachiocephalic trunk, at the cranial border of the first rib. The continuation of the trunk is represented by right common carotid artery that follows the right jugular groove. The left common carotid artery emerges at the medial aspect of the first intercostal space as a collateral branch detached from the brachiocephalic trunk, in its initial sector. In respect to the collaterals emerging from the subclavian arteries, our study showed that in all studied cases, four branches arise in sequence- the internal thoracic, dorsal scapular, vertebral and superficial cervical arteries. The existence of the common trunks (internal thoracic, dorsal scapular arteries and superficial and deep cervical arteries (as described by other authors) was not confirmed on the investigated specimens.Discussion: The paper highlights some interesting facts referring to the specific morphology of the aortic arch in chinchilla, as literature data provides some divergent data. Some of the aspects noted are confirmed (the emergence of subclavian arteries) while some others are still subjects to discussion and further investigation (collateral branches of subclavian arteries). Our approach focuses also on the comparative aspects of the morphology of the branches emerging from the aortic arch. According to the available literature, the following species were used as comparison: leporids, Guinea pig, squirrel, yellow-necked mouse, Egyptian mouse, rat, armadillo, nutria, capybara, paca, fox and leopard.

In vitro Remote Aspiration Embolectomy for the Treatment of Acute Ischemic Stroke

Background: “Remote aspiration,” using suction from the proximal internal carotid artery (ICA) to open terminus occlusions, has been reported in small case series. However, it remains unclear whether remote aspiration is feasible for middle cerebral artery occlusions in the setting of potential inflow from communicating arteries. We performed an in vitro study to assess whether suction applied at various locations proximal to an occlusion could successfully aspirate the clot. Methods: A glass model of 4 mm inner diameter (ID) with 1 mm distal narrowing and 2 mm side branch to simulate a communicating artery was constructed. A proximal side branch was placed to simulate inflow from the proximal ICA. The impact of three different-sized catheters (ID 0.088, 0.070, and 0.056 in) on histologically different (red blood cell-cell rich, fibrin-rich, and mixed) clot analogues was tested with the catheter tip placed remotely either distal or proximal to the collateral branch. Aspiration was attempted with (1) open system (flow in both the ICA and the collateral branch, (2) flow arrest with open collateral (no flow in the ICA, but flow in the collateral branch), and (3) closed system (no flow in either the ICA or the collateral branch). The outcome was success or failure of remote aspiration. Results: For the 0.088-in catheter, remote aspiration was successful in all conditions. For the 0.070-in catheter, remote aspiration was unsuccessful without proximal flow arrest, but was successful in all other scenarios. For the 0.056-in catheter, remote aspiration was successful only with complete flow arrest. Conclusions: In a noncollapsible system, remote aspiration can be successfully achieved even in the setting of prominent branch arteries by using relatively large aspiration catheters. Proximal flow arrest may facilitate successful remote aspiration for some catheter sizes.

Systematization of the Brain Base Arteries in Nutria (Myocastor coypus)

Background: The nutria (Myocastor coypus) is a medium-size, semi-aquatic rodent, valued in skin and meat industry. The brain circulation has been well studied in rodents but not in nutria. To understand and compare the phylogenetic development of the arteries of the base of the brain in rodents, this paper aims to describe and systematize these arteries, establishing a standard model and its main variations in nutria.Materials, Methods & Results: Following approval by the Ethics Committee of Federal University of Rio Grande do Sul, thirty nutrias from a commercial establishment authorized by Brazilian Institute of Environment and Natural Resources (IBAMA) were studied. For euthanasia, was applied heparin (10000 U.I for animal), intraperitoneally, and after thirty minutes the animals ware sedated with acepromazine (0.5 mg/kg) and meperidine (20 mg/kg), intramuscularly. After sedation, they were euthanized with thiopental sodium (120 mg/kg) and lidocaine (10 mg/mL), intraperitoneally. The heart was accessed, the cardiac apex was sectioned, the aorta was cannulated via the left ventricle and clamped close to the diaphragm, and the arterial system was washed with saline solution and filled with latex. The animals were submerged in water for latex polymerization, the trunk was sectioned, the skin removed and a bony window was opened in the skull vault. The pieces were fixed in formaldehyde. The brains were removed, and schematic drawings of the arteries from the base of the brain were made for elaboration of the results. The nutria’s brain was vascularized by the vertebro-basilar system. The terminal branches of the right and left vertebral artery were anastomosed on the ventral surface of the medulla oblongata, forming the basilar artery, and caudally the ventral spinal artery. The basilar artery formed collateral branches, the caudal and middle cerebellar and trigeminal arteries, and at the height of the rostral pons groove, divided into its two terminal branches, the rostral cerebellar and cerebral caudal arteries. The terminal branches of the basilar artery projected rostrally, forming the hypophyseal and rostral choroid arteries. The basilar artery passed the optic tract and bifurcated in the middle cerebral artery, its last collateral branch, and in the rostral cerebral artery, its terminal branch. The rostral cerebral artery formed the medial branch, closing the cerebral arterial circle caudally in 40% of the cases.Discussion: In rodents, variability of the cerebral arterial circle was observed due to the degree of atrophy of the internal carotid artery. The basilar artery was a rectilinear vessel of great caliber in all described rodents, and in rodents with a vertebro-basilar system, it was divided into its terminal branches after crossing the pons, forming the rostral cerebellar, hypophyseal, rostral choroid, caudal, middle and rostral cerebral arteries. The caudal cerebellar artery had variation of origin and sometimes duplication. The median cerebellar artery, a collateral branch of the caudal cerebellar artery, was a branch of the basilar artery in capybara. The caudal cerebral artery had variations between rodents. In capybara, chinchilla and nutria the middle cerebral artery was the collateral branch of the terminal branches of the basilar artery, and distributed on the convex surface of the cerebral hemisphere. The rostral cerebral artery, a branch of the terminal branch of the basilar artery, was a branch of the internal carotid artery in other rodents, forming the medial branch, which was anastomosed with that of the opposite antimer, when present, forming the rostral communicating artery. In nutria, the cerebral arterial circle was closed caudally in all cases, as in other rodents, however, it was opened rostrally in 60% of cases, compared to 70% in chinchilla and 10% in capybara.

Macroscopic Aspects of the Cranial Mesenteric Artery (Arteria Mesenterica Cranialis) in Chinchilla Lanigera Species

In this study we have used 10 carcasses of chinchilla females slaughtered by the owner for commercial purposes. The studied animals have been subjected to an antemortem exam in which the semiological constants like: temperature; breats per minute and pulse were recorded. After the examination the subjects were declared clinically healthy. After skinning 30 ml coloring agent was injected intraluminally and dissection of the cranial mesenteric artery was performed. The first collateral branch of this vessel was the caudal pancreatico-duodenal artery (Arteria pancreaticoduodenalis caudalis), followed by 4-5 jejunal arteries (Arteriae jejunales). The cranial mesenteric artery gives off the dorsal cecal artery (Arteria cecalis dorsalis) as one of terminal branches to supply the haustrated part of cecum, the medial cecal artery (Arteria cecalis media) distributed to the tubular part of cecum (second terminal) and ileocolic artery (Arteria ileocolica)(the third terminal). To the best of our knowledge, our results brings significant information about the blood supply of intestines in chinchilla, that could be a real help for clinicians and researchers studying this topic.

Differential roles of α-, β-, and γ-actin in axon growth and collateral branch formation in motoneurons

Axonal branching and terminal arborization are fundamental events during the establishment of synaptic connectivity. They are triggered by assembly of actin filaments along axon shafts giving rise to filopodia. The specific contribution of the three actin isoforms, Actα, Actβ, and Actγ, to filopodia stability and dynamics during this process is not well understood. Here, we report that Actα, Actβ, and Actγ isoforms are expressed in primary mouse motoneurons and their transcripts are translocated into axons. shRNA-mediated depletion of Actα reduces axonal filopodia dynamics and disturbs collateral branch formation. Knockdown of Actβ reduces dynamic movements of growth cone filopodia and impairs presynaptic differentiation. Ablation of Actβ or Actγ leads to compensatory up-regulation of the two other isoforms, which allows maintenance of total actin levels and preserves F-actin polymerization. Collectively, our data provide evidence for specific roles of different actin isoforms in spatial regulation of actin dynamics and stability in axons of developing motoneurons.