- Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function. [Journal Article]
- NINeurochem Int 2019 Jun 06; 129:104486
- Neuron function relies on and instructs the development and precise organization of neurovascular units that in turn support circuit activity. However, our understanding of the molecular cues that re…
Neuron function relies on and instructs the development and precise organization of neurovascular units that in turn support circuit activity. However, our understanding of the molecular cues that regulate this relationship remains sparse. Using a high-throughput screening pipeline, we recently identified several new regulators of vascular patterning. Among these was the potassium channel tetramerization domain-containing protein 7 (KCTD7). Mutations in KCTD7 are associated with progressive myoclonic epilepsy, but how KCTD7 regulates neural development and function remains poorly understood. To begin to identify such mechanisms, we focus on mouse retina, a tractable part of the central nervous system that contains precisely ordered neuron subtypes supported by a trilaminar vascular network. We find that deletion of Kctd7 induces defective patterning of the adult retina vascular network, resulting in increased branching, vessel length, and lacunarity. These alterations reflect early and specific defects in vessel development, as emergence of the superficial and deep vascular layers were delayed. These defects are likely due to a role for Kctd7 in inner retina neurons. Kctd7 is absent from vessels but present in neurons in the inner retina, and its deletion resulted in a corresponding increase in the number of bipolar cells in development and increased vessel branching in adults. These alterations were accompanied by retinal function deficits. Together, these data suggest that neuronal Kctd7 drives growth and patterning of the vasculature and that neurovascular interactions may participate in the pathogenesis of KCTD7-related human diseases.
- Role of gamma-giardin in ventral disc formation of Giardia lamblia. [Journal Article]
- PVParasit Vectors 2019 May 14; 12(1):227
- CONCLUSIONS: Knockdown experiments demonstrated that Glγ-giardin is a component of the trilaminar structure of the ventral disc. Expression of Glγ-giardin is induced in the G2-phase prior to active cell division, whereas its expression decreases during encystation, a dormant stage of G. lamblia.
- Role of Periostin in Cardiac Valve Development. [Journal Article]
- AEAdv Exp Med Biol 2019; 1132:177-191
- Although periostin plays a significant role in adult cardiac remodeling diseases, the focus of this review is on periostin as a valvulogenic gene. Periostin is expressed throughout valvular developme…
Although periostin plays a significant role in adult cardiac remodeling diseases, the focus of this review is on periostin as a valvulogenic gene. Periostin is expressed throughout valvular development, initially being expressed in endocardial endothelial cells that have been activated to transform into prevalvular mesenchyme termed "cushion tissues" that sustain expression of periostin throughout their morphogenesis into mature (compacted) valve leaflets. The phenotype of periostin null indicates that periostin is not required for endocardial transformation nor the proliferation of its mesenchymal progeny but rather promotes cellular behaviors that promote migration, survival (anti-apoptotic), differentiation into fibroblastic lineages, collagen secretion and postnatal remodeling/maturation. These morphogenetic activities are promoted or coordinated by periostin signaling through integrin receptors activating downstream kinases in cushion cells that activate hyaluronan synthetase II (Akt/PI3K), collagen synthesis (Erk/MapK) and changes in cytoskeletal organization (Pak1) which regulate postnatal remodeling of cells and associated collagenous matrix into a trilaminar (zonal) histoarchitecture. Pak1 binding to filamin A is proposed as one mechanism by which periostin supports remodeling. The failure to properly remodel cushions sets up a trajectory of degenerative (myxomatous-like) changes that over time reduce biomechanical properties and increase chances for prolapse, regurgitation or calcification of the leaflets. Included in the review are considerations of lineage diversity and the role of periostin as a determinant of mesenchymal cell fate.
- StatPearls: Anatomy, Abdomen and Pelvis, Deep Perineal Space [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- The perineum divides into an anterior urogenital triangle and a posterior anal triangle. The urogenital triangle of the perineum is divided into two pouches or spaces by a robust fibrous sheet known …
The perineum divides into an anterior urogenital triangle and a posterior anal triangle. The urogenital triangle of the perineum is divided into two pouches or spaces by a robust fibrous sheet known as the perineal membrane. This membrane is stretched across the urogenital triangle, attached laterally to the ischiopubic rami. The deep perineal pouch is superior to the perineal membrane, and the superficial perineal pouch is inferior. The deep perineal pouch is in the urogenital triangle of the perineum below the pelvic diaphragm. It presents as a triangular, trilaminar space with sphincter urethrae [external urethral sphincter], deep transverse perineal, and compressor urethrae [in females]. The fibromuscular structures of the pouch often go by the name of the urogenital diaphragm.
- Comparative Optical Coherence Tomography Angiography of Wild-Type and rd10 Mouse Retinas. [Journal Article]
- TVTransl Vis Sci Technol 2018; 7(6):42
- CONCLUSIONS: The most severe vascular impairment happened in the DCP, while the ICP showed the transient recovery of vascular density after the onset of retinal degeneration. The SVP was most resistant to the retinal degeneration, but the first-order blood vessel branches within the SVP showed progressive narrowing.
- Sublaminar organization of the human subplate: developmental changes in the distribution of neurons, glia, growing axons and extracellular matrix. [Journal Article]
- JAJ Anat 2018 Dec 13
- The objective of this paper was to collect normative data essential for analyzing the subplate (SP) role in pathogenesis of developmental disorders, characterized by abnormal circuitry, such as hypox…
The objective of this paper was to collect normative data essential for analyzing the subplate (SP) role in pathogenesis of developmental disorders, characterized by abnormal circuitry, such as hypoxic-ischemic lesions, autism and schizophrenia. The main cytological features of the SP, such as low cell density, early differentiation of neurons and glia, plexiform arrangement of axons and dendrites, presence of synapses and a large amount of extracellular matrix (ECM) distinguish this compartment from the cell-dense cortical plate (CP; towards pia) and large fiber bundles of external axonal strata of fetal white matter (towards ventricle). For SP delineation from these adjacent layers based on combined cytological criteria, we analyzed the sublaminar distribution of different microstructural elements and the associated maturational gradients throughout development, using immunocytochemical and histological techniques on postmortem brain material (Zagreb Neuroembryological Collection). The analysis revealed that the SP compartment of the lateral neocortex shows changes in laminar organization throughout fetal development: the monolayer in the early fetal period (presubplate) undergoes dramatic bilaminar transformation between 13 and 15 postconceptional weeks (PCW), followed by subtle sublamination in three 'floors' (deep, intermediate, superficial) of midgestation (15-21 PCW). During the stationary phase (22-28 PCW), SP persists as a trilaminar compartment, gradually losing its sublaminar organization towards the end of gestation and remains as a single layer of SP remnant in the newborn brain. Based on these sublaminar transformations, we have documented developmental changes in the distribution, maturational gradients and expression of molecular markers in SP synapses, transitional forms of astroglia, neurons and ECM, which occur concomitantly with the ingrowth of thalamo-cortical, basal forebrain and cortico-cortical axons in a deep to superficial fashion. The deep SP is the zone of ingrowing axons - 'entrance (ingrowth) zone'. The process of axonal ingrowth begins with thalamo-cortical fibers and basal forebrain afferents, indicating an oblique geometry. During the later fetal period, deep SP receives long cortico-cortical axons exhibiting a tangential geometry. Intermediate SP ('proper') is the navigation and 'nexus' sublamina consisting of a plexiform arrangement of cellular elements providing guidance and substrate for axonal growth, and also containing transient connectivity of dendrites and axons in a tangential plane without radial boundaries immersed in an ECM-rich continuum. Superficial SP is the axonal accumulation ('waiting compartment') and target selection zone, indicating a dense distribution of synaptic markers, accumulation of thalamo-cortical axons (around 20 PCW), overlapping with dendrites from layer VI neurons. In the late preterm brain period, superficial SP contains a chondroitin sulfate non-immunoreactive band. The developmental dynamics for the distribution of neuronal, glial and ECM markers comply with sequential ingrowth of afferents in three levels of SP: ECM and synaptic markers shift from deep to superficial SP, with transient forms of glia following this arrangement, and calretinin neurons are concentrated in the SP during the formation phase. These results indicate developmental and morphogenetic roles in the SP cellular (transient glia, neurons and synapses) and ECM framework, enabling the spatial accommodation, navigation and establishment of numerous connections of cortical pathways in the expanded human brain. The original findings of early developmental dynamics of transitional subtypes of astroglia, calretinin neurons, ECM and synaptic markers presented in the SP are interesting in the light of recent concepts concerning its functional and morphogenetic role and an increasing interest in SP as a prospective substrate of abnormalities in cortical circuitry, leading to a cognitive deficit in different neurodevelopmental disorders.
- Encapsulating Peritoneal Sclerosis: The Abdominal Cocoon. [Journal Article]
- RRadiographics 2019 Jan-Feb; 39(1):62-77
- Encapsulating peritoneal sclerosis (EPS) is a rare but serious condition that results in (a) encapsulation of bowel within a thickened fibrocollagenous peritoneal membrane and (b) recurrent episodes …
Encapsulating peritoneal sclerosis (EPS) is a rare but serious condition that results in (a) encapsulation of bowel within a thickened fibrocollagenous peritoneal membrane and (b) recurrent episodes of bowel obstruction. Although described by various names in the literature, the preferred term is encapsulating peritoneal sclerosis because it best describes the morphologic and histologic changes in this disorder. The etiology of EPS is multifactorial, with a wide variety of implicated predisposing factors that disrupt the normal physiologic function of the peritoneal membrane-prime among these factors being long-term peritoneal dialysis and bacterial peritoneal infections, especially tuberculosis. The clinical features of EPS are usually nonspecific, and knowledge of the radiologic features is necessary to make a specific diagnosis. The findings on radiographs are usually normal. Images from small-bowel follow-through studies show the bowel loops conglomerated in a concertina-like fashion with a serpentine arrangement in a fixed U-shaped configuration. US demonstrates a "cauliflower" appearance of bowel with a narrow base, as well as a "trilaminar" appearance depicted especially with use of high-resolution US probes. CT is the imaging modality of choice and allows identification of the thickened contrast material-enhanced abnormal peritoneal membrane and the encapsulated clumped bowel loops. In addition, CT can potentially help identify the cause of EPS (omental granuloma in tuberculosis), as well as the complications of EPS (bowel obstruction). Conservative medical treatment and surgical therapy early in the course of EPS have been used for management of the condition. The purpose of this article is to review the nomenclature and etiopathogenesis of EPS, describe the multimodality imaging appearances of EPS, including differentiating its features from those of other conditions mimicking EPS, and give an overview of management options. Online DICOM image stacks are available for this article. ©RSNA, 2018.
- A novel gel patch for minimally invasive repair of tympanic membrane perforations. [Journal Article]
- IJInt J Pediatr Otorhinolaryngol 2018; 115:27-32
- CONCLUSIONS: The gel is promising regarding thickness and trilaminar regenerated tissue, perhaps due to the biomechanical properties of the gel, and further refinements in the material and technique are anticipated to increase ease and efficacy of treatment while minimizing complications.
- Structural and molecular tear film changes in glaucoma. [Journal Article]
- CMCurr Med Chem 2018 Oct 09
- The tear film (TF) is a trilaminar and dynamic fluid covering the entire ocular surface (OS), consisting of a mucus, aqueous, and lipid layer deeply interacting between them. Because of its structure…
The tear film (TF) is a trilaminar and dynamic fluid covering the entire ocular surface (OS), consisting of a mucus, aqueous, and lipid layer deeply interacting between them. Because of its structure and functions, TF plays a pivotal role in the preservation of the OS integrity and the quality of vision. Medical therapy for glaucoma is recognized to profoundly disturb the OS homeostasis by altering all components of the ocular surface unit, including TF. The presence of preservatives, the number of daily eye drops instillations, and the duration of therapy are the main contributors to TF changes. From the physio-pathological side, TF alterations are induced by toxic and allergic mechanisms, and result from goblet cell and Meibomian gland loss, dysfunction of accessory lacrimal glands, and epithelial disruption. In detail, TF changes are represented by mucus layer thinning, reduced mucin concentration, aqueous layer volume reduction, and lipid layer thinning with increased tear evaporation. Hyper-osmolarity and instability represent the main hallmarks of these changes and are expression of a iatrogenic form of dry eye. TF undergoes also molecular modifications that primarily reflect a therapy- or disease-induced inflammatory status of the OS. Over the last years, this field of research gained a progressively growing interest since molecular variations may be considered as potential candidate biomarkers of glaucoma. The aim of this review is to report the main TF changes occurring during glaucoma, exploring the relationship they may have with the glaucoma-related ocular surface disease and the patient quality of life, and their utility as potential biomarkers of disease.
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- Influence of hyperthermal regimes on experimental teratoma development in vitro. [Journal Article]
- IJInt J Exp Pathol 2018; 99(3):131-144
- We screened for the impact of hyperthermal regimes varying in the cumulative equivalent minutes at 43°C (CEM43°C) and media composition on tumour development using an original teratoma in vitro model…
We screened for the impact of hyperthermal regimes varying in the cumulative equivalent minutes at 43°C (CEM43°C) and media composition on tumour development using an original teratoma in vitro model. Rat embryos (three germ layers) were microsurgically isolated and cultivated at the air-liquid interface. During a two week period, ectodermal, mesodermal and endodermal derivatives developed within trilaminar teratomas. Controls were grown at 37°C. Overall growth was measured, and teratoma survival and differentiation were histologically assessed. Cell proliferation was stereologically quantified by the volume density of Proliferating Cell Nuclear Antigen. Hyperthermia of 42°C, applied for 15 minutes after plating (CEM43°C 3.75 minutes), diminished cell proliferation (P ˂ .0001) and enhanced differentiation of both myotubes (P ˂ .01) and cylindrical epithelium (P ˂ .05). Hyperthermia of 43°C applied each day for 30 minutes during the first week (CEM43°C 210 minutes) impaired overall growth (P ˂ .01) and diminished cell proliferation (P ˂ .0001). Long-term hyperthermia of 40.5°C applied for two weeks (CEM43°C 630 minutes) significantly impaired survival (P ˂ .005). Long-term hyperthermia of 40.5°C applied from the second day when differentiation of tissues begins (CEM43°C 585 minutes) impaired survival (P ˂ .0001), overall growth (P ˂ .01) and cartilage differentiation (P ˂ .05). No teratomas survived extreme regimes: 43°C for 24 hours (CEM43°C 1440 minutes), hyperthermia in the scant serum-free medium (CEM43°C 630 minutes) or treatment with an anti-HSP70 antibody before long-term hyperthermia 40.5°C from the second day (CEM43°C 585 minutes). This in vitro research provided novel insights into the impact of hyperthermia on the development of experimental teratomas from their undifferentiated sources and are thus of potential interest for future therapeutic strategies in corresponding in vivo models.