The actin-binding protein Shroom is essential for neural tube morphogenesis in multiple vertebrate organisms, indicating its function is evolutionarily conserved. Shroom facilitates neurulation by ...regulating the morphology of neurepithelial cells. Shroom localizes to the apical tip of adherens junctions of neural ectoderm cells in vivo and to the apical junctional complex (AJC) in MDCK cells. Induced expression of Shroom in polarized epithelia elicits apical constriction and dramatic reorganization of the apical arrangement and packing of cells without altering apical-basal polarity. These events likely mimic the cell shape changes and cellular movements required for neurulation in vivo. The observed phenotypes depend on the ability of Shroom to alter F-actin distribution and regulate the formation of a previously uncharacterized contractile actomyosin network associated with the AJC. Targeting the C-terminal domain of Shroom to the apical plasma membrane elicits constriction and reorganization of the actomyosin network, indicting that this domain mediates Shroom's activity. In vivo, Shroom-mutant neural epithelia show a marked reduction in apically positioned myosin. Thus, Shroom likely facilitates neural tube closure by regulating cell shape changes via the apical positioning of an actomyosin network in the neurepithelium.
Context.
The origin of the
γ
-ray emission of the blazar
Mrk 421
is still a matter of debate.
Aims.
We used 5.5 years of unbiased observing campaign data, obtained using the FACT telescope and the
...Fermi
-LAT detector at TeV and GeV energies, the longest and densest so far, together with contemporaneous multi-wavelength observations, to characterise the variability of
Mrk 421
and to constrain the underlying physical mechanisms.
Methods.
We studied and correlated light curves obtained by ten different instruments and found two significant results.
Results.
The TeV and X-ray light curves are very well correlated with a lag of < 0.6 days. The GeV and radio (15 Ghz band) light curves are widely and strongly correlated. Variations of the GeV light curve lead those in the radio.
Conclusions.
Lepto-hadronic and purely hadronic models in the frame of shock acceleration predict proton acceleration or cooling timescales that are ruled out by the short variability timescales and delays observed in Mrk 421. Instead the observations match the predictions of leptonic models.
Background: The morphogenetic events of early vertebrate development generally involve the combined actions of several populations of cells, each engaged in a distinct behavior. Neural tube closure, ...for instance, involves apicobasal cell heightening, apical constriction at hingepoints, convergent extension of the midline, and pushing by the epidermis. Although a large number of genes are known to be required for neural tube closure, in only a very few cases has the affected cell behavior been identified. For example, neural tube closure requires the actin binding protein Shroom, but the cellular basis of Shroom function and how it influences neural tube closure remain to be elucidated.
Results: We show here that expression of Shroom is sufficient to organize apical constriction in transcriptionally quiescent, naive epithelial cells but not in non-polarized cells. Shroom-induced apical constriction was associated with enrichment of apically localized actin filaments and required the small GTPase Rap1 but not Rho. Endogenous
Xenopus shroom was found to be expressed in cells engaged in apical constriction. Consistent with a role for Shroom in organizing apical constriction, disrupting Shroom function resulted in a specific failure of hingepoint formation, defective neuroepithelial sheet-bending, and failure of neural tube closure.
Conclusions: These data demonstrate that Shroom is an essential regulator of apical constriction during neurulation. The finding that a single protein can initiate this process in epithelial cells establishes that bending of epithelial sheets may be patterned during development by the regulation of expression of single genes.
Valdensia leaf spot, caused by
, is a serious disease of lowbush blueberry. The disease may develop rapidly, resulting in extensive defoliation of fields. The purpose of this study was to examine the ...effects of temperature and wetness duration on various components of the infection cycle to gain a better understanding of epidemic development that might lead to improved management practices. Lesions on leaves appeared 6 h after inoculation at 20°C and were larger on young 3-week-old leaves compared with 8-week-old leaves. Incidence of infection on 3-week-old leaves was lowest at 5°C, highest at 15 and 20°C, and failed to occur at 30°C. Defoliation began 48 h after inoculation at 20 and 25°C but was slower at higher and lower temperatures. Conidia production and release from colonized leaves began 48 h after inoculation at 15 and 19°C. Total conidia production was lowest at 7°C, highest at 15°C, and progressively declined at 19 and 23°C. Production of conidia lasted 2 to 3 days. Sclerotia formed mainly along the midveins and were similar in size at 5 to 15°C, largest at 20°C, and smallest at 25°C. Conidia formed directly on sclerotia that were overwintered outdoors and then incubated on moist filter paper. Conidia production began after 48 h at 10, 15, and 20°C. Total production was lowest at 5°C, highest at 20°C, failed to occur at 25°C, and ceased after 10 days at all temperatures. These data show that at optimal temperatures, relatively short wet periods are required for conidia production on overwintered sclerotia, infection of leaves, and subsequent conidia production on diseased leaves that may account for the sudden and rapid spread of disease in fields. The data will be useful for helping growers identify weather conditions favorable for disease development.
Congenital and childhood cataracts are uncommon but regularly seen in the clinics of most paediatric ophthalmology teams in the UK. They are often associated with profound visual loss and a large ...proportion have a genetic aetiology, some with significant extra-ocular comorbidities. Optimal diagnosis and treatment typically require close collaboration within multidisciplinary teams. Surgery remains the mainstay of treatment. A variety of surgical techniques, timings of intervention and options for optical correction have been advocated making management seem complex for those seeing affected children infrequently. This paper summarises the proceedings of two recent RCOphth paediatric cataract study days, provides a literature review and describes the current UK 'state of play' in the management of paediatric cataracts.
Parastomal hernia after ileal conduit urinary diversion is an underestimated and undertreated clinical entity, which heavily impairs patients' quality of life due to symptoms of pain, leakage, ...application or skin problems. As for all gastrointestinal stomata the best surgical repair technique has yet to be determined. Thereby, surgery for ileal conduit parastomal hernias poses some specific perioperative challenges. This review aims to give an overview of current evidence on the surgical treatment of parastomal hernia after cystectomy and ileal conduit urinary diversion, and on the use of prophylactic mesh at index surgery in its prevention.
A systematic review was performed according to PRISMA-guidelines. The electronic databases Embase, PubMed, Cochrane Library, and Web of Science were searched. Studies were included if they presented postoperative outcomes of patients undergoing surgical treatment of parastomal hernia at the ileal conduit site, irrespective of the technique used. A search was performed to identify additional studies on prophylactic mesh in the prevention of ileal conduit parastomal hernia, that were not identified by the initial search.
Eight retrospective case-series were included for analysis, reporting different surgical techniques. If reported, highest complication rate was 45%. Recurrence rates varied highly, ranging from 0 to 80%. Notably, lower recurrence rates were reported in studies with shorter follow-up. Overall, available data suggest significant morbidity after the surgical treatment of ileal conduit parastomal hernias. Data from five conference abstracts on the matter were retrieved, and systematically reported. Regarding prophylactic mesh in the prevention of ileal conduit parastomal hernia, 5 communications were identified. All of them used keyhole mesh in a retromuscular position, and reported on favorable results in the mesh group without an increase in mesh-related complications.
Data on the surgical treatment of ileal conduit parastomal hernias and the use of prophylactic mesh in its prevention is scarce. Given the specific perioperative challenges and the paucity of reported results, more high-quality evidence is needed to determine the optimal treatment of this specific surgical problem. Initial results on the use of prophylactic mesh in the prevention of ileal conduit parastomal hernias seem promising.
Using gene trap mutagenesis, we have identified a mutation in mice that causes exencephaly, acrania, facial clefting, and spina bifida, all of which can be attributed to failed neural tube closure. ...This mutation is designated
shroom (
shrm) because the neural folds “mushroom” outward and do not converge at the dorsal midline.
shrm encodes a PDZ domain protein that is involved at several levels in regulating aspects of cytoarchitecture. First, endogenous Shrm localizes to adherens junctions and the cytoskeleton. Second, ectopically expressed Shrm alters the subcellular distribution of F-actin. Third, Shrm directly binds F-actin. Finally, cytoskeletal polarity within the neuroepithelium is perturbed in mutant embryos. In concert, these observations suggest that Shrm is a critical determinant of the cellular architecture required for proper neurulation.
The cellular mechanisms that drive growth and remodeling of the early intestinal epithelium are poorly understood. Current dogma suggests that the murine fetal intestinal epithelium is stratified, ...that villi are formed by an epithelial remodeling process involving the de novo formation of apical surface at secondary lumina, and that radial intercalation of the stratified cells constitutes a major intestinal lengthening mechanism. Here, we investigate cell polarity, cell cycle dynamics and cell shape in the fetal murine intestine between E12.5 and E14.5. We show that, contrary to previous assumptions, this epithelium is pseudostratified. Furthermore, epithelial nuclei exhibit interkinetic nuclear migration, a process wherein nuclei move in concert with the cell cycle, from the basal side (where DNA is synthesized) to the apical surface (where mitosis takes place); such nuclear movements were previously misinterpreted as the radial intercalation of cells. We further demonstrate that growth of epithelial girth between E12.5 and E14.5 is driven by microtubule- and actinomyosin-dependent apicobasal elongation, rather than by progressive epithelial stratification as was previously thought. Finally, we show that the actin-binding protein Shroom3 is crucial for the maintenance of the single-layered pseudostratified epithelium. In mice lacking Shroom3, the epithelium is disorganized and temporarily stratified during villus emergence. These results favor an alternative model of intestinal morphogenesis in which the epithelium remains single layered and apicobasally polarized throughout early intestinal development.
Epithelial invagination is a common feature of embryogenesis. An example of invagination morphogenesis occurs during development of the early eye when the lens placode forms the lens pit. This ...morphogenesis is accompanied by a columnar-to-conical cell shape change (apical constriction or AC) and is known to be dependent on the cytoskeletal protein Shroom3. Because Shroom3-induced AC can be Rock1/2 dependent, we hypothesized that during lens invagination, RhoA, Rock and a RhoA guanine nucleotide exchange factor (RhoA-GEF) would also be required. In this study, we show that Rock activity is required for lens pit invagination and that RhoA activity is required for Shroom3-induced AC. We demonstrate that RhoA, when activated and targeted apically, is sufficient to induce AC and that RhoA plays a key role in Shroom3 apical localization. Furthermore, we identify Trio as a RhoA-GEF required for Shroom3-dependent AC in MDCK cells and in the lens pit. Collectively, these data indicate that a Trio-RhoA-Shroom3 pathway is required for AC during lens pit invagination.
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