scholarly journals Desmoglein 2 regulates cardiogenesis by restricting hematopoiesis in the developing murine heart

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hoda Moazzen ◽  
Kateryna Venger ◽  
Sebastian Kant ◽  
Rudolf E. Leube ◽  
Claudia A. Krusche

AbstractCardiac morphogenesis relies on intricate intercellular signaling. Altered signaling impacts cardiac function and is detrimental to embryonic survival. Here we report an unexpected regulatory role of the desmosomal cell adhesion molecule desmoglein 2 (Dsg2) on murine heart development. A large percentage of Dsg2-mutant embryos develop pericardial hemorrhage. Lethal myocardial rupture is occasionally observed, which is not associated with loss of cardiomyocyte contact but with expansion of abnormal, non-myocyte cell clusters within the myocardial wall. Two types of abnormal cell clusters can be distinguished: Type A clusters involve endocard-associated, round-shaped CD31+ cells, which proliferate and invade the myocardium. They acquire Runx1- and CD44-positivity indicating a shift towards a hematopoietic phenotype. Type B clusters expand subepicardially and next to type A clusters. They consist primarily of Ter119+ erythroid cells with interspersed Runx1+/CD44+ cells suggesting that they originate from type A cell clusters. The observed pericardial hemorrhage is caused by migration of erythrocytes from type B clusters through the epicardium and rupture of the altered cardiac wall. Finally, evidence is presented that structural defects of Dsg2-depleted cardiomyocytes are primary to the observed pathogenesis. We propose that cardiomyocyte-driven paracrine signaling, which likely involves Notch1, directs subsequent trans-differentiation of endo- and epicardial cells. Together, our observations uncover a hitherto unknown regulatory role of Dsg2 in cardiogenesis.

2013 ◽  
Vol 1 (1) ◽  
pp. 10
Author(s):  
Noar Muda Satyawan ◽  
Shelly Tutupoho ◽  
Yusli Wardiatno ◽  
Makoto Tsuchiya

Erosion rate on corals due to activities of other biota is called bioerosion. The rock-boring urchin, Echinometra mathaei, when it is abundant, plays a significant role in benthic ecosystems, including biological processes like coral erosion. During feeding, E. mathaei erodes calcium carbonate besides grazing on algae living on coral, so it plays an important role in both organic and inorganic carbons in coral reefs. The urchin E. mathaei actively feeds during the night time (nocturnal grazer). Although in Okinawa four types (A-D) of the urchin exist, the research only focused on the types A and B. Type A of E. mathaei produced 0.44951 g feces per day on average while type B produced 0.38030 g feces per day. CaCO3 analysis in feces and gut contents showed bioerosion rate of E. mathaei type A was 0.64492 g/individu/day, and 0.54436 g/individu/day in type B. There were no significant differences in bioerosion impact of E. mathaei type A and B© Laju erosi pada karang yang disebabkan oleh biota, dikenal dengan bioerosi. Bulu babi jenis Echinometra mathaei, ketika melimpah, menjadi sangat berpengaruh terhadap ekosistem bentik termasuk proses biologi seperti erosi karang. Selama aktivitas makan, E. mathaei menggerus kalsium karbonat dalam proporsi yang besar di samping alga yang tumbuh menempel pada karang sehingga memiliki peran penting dalam siklus karbon organik dan anorganik di ekosistem terumbu karang. Bulu babi E. mathaei aktif mencari makan pada malam hari (nocturnal grazer). Meskipun di Okinanawa ada 4 tipe (A-D), pada eksperimen kali ini memfokuskan pada tipe A dan B saja. Tipe A E. mathaei rata-rata memproduksi 0,44951 g feses/hari dan tipe B memproduksi 0,38030 g feses/hari. Berdasarkan analisis CaCO3 yang dilakukan pada feses dan isi lambung, laju bioerosi yang disebabkan oleh E. mathaei tipe A sebesar 0,64492 g/individu/hari sedangkan tipe B sebesar 0,54436 g/individu/hari. Tidak terdapat perbedaan dampak bioerosi yang signifikan antara E. mathaei tipe A dan B©


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Peiru Liu ◽  
Jing Zhang ◽  
Duo Du ◽  
Dandan Zhang ◽  
Zelin Jin ◽  
...  

Abstract Background Thoracic aortic dissection (TAD) is a severe disease with limited understandings in its pathogenesis. Altered DNA methylation has been revealed to be involved in many diseases etiology. Few studies have examined the role of DNA methylation in the development of TAD. This study explored alterations of the DNA methylation landscape in TAD and examined the potential role of cell-free DNA (cfDNA) methylation as a biomarker in TAD diagnosis. Results Ascending aortic tissues from TAD patients (Stanford type A; n = 6) and healthy controls (n = 6) were first examined via whole-genome bisulfite sequencing (WGBS). While no obvious global methylation shift was observed, numerous differentially methylated regions (DMRs) were identified, with associated genes enriched in the areas of vasculature and heart development. We further confirmed the methylation and expression changes in homeobox (Hox) clusters with 10 independent samples using bisulfite pyrosequencing and quantitative real-time PCR (qPCR). Among these, HOXA5, HOXB6 and HOXC6 were significantly down-regulated in TAD samples relative to controls. To evaluate cfDNA methylation pattern as a biomarker in TAD diagnosis, cfDNA from TAD patients (Stanford type A; n = 7) and healthy controls (n = 4) were examined by WGBS. A prediction model was built using DMRs identified previously from aortic tissues on methylation data from cfDNA. Both high sensitivity (86%) and specificity (75%) were achieved in patient classification (AUC = 0.96). Conclusions These findings showed an altered epigenetic regulation in TAD patients. This altered epigenetic regulation and subsequent altered expression of genes associated with vasculature and heart development, such as Hox family genes, may contribute to the loss of aortic integrity and TAD pathogenesis. Additionally, the cfDNA methylation in TAD was highly disease specific, which can be used as a non-invasive biomarker for disease prediction.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Fred I Chasalow ◽  
Ron Bochner

Abstract Background: In 1987, Graves observed that during the 3rd trimester, some patients with pre-eclampsia had high levels of unknown materials that could be detected with assays for digoxin (DLM). In 2018, we characterized a new candidate for the DLM, Ionotropin. It is a phosphocholine (PC) ester of a novel steroid with 23 carbon atoms. As Ionotropin shares structural features (a) with spironolactone (both have spiral lactones in the E-ring) and (b) with digoxin (E-ring lactone and 3α-5β configuration), we have proposed that Ionotropin may function as a potassium (K+) sparing diuretic. This suggestion is supported by the observations that [1] patients who cannot make Ionotropin (7-dehydrosterol reductase deficiency) are K+ wasting and [2] breast cyst fluids with high K+ levels also have high Ionotropin levels. Hypothesis: During the 3rd trimester, fetal requirements for K+ reach a maximum, fetal blood pressure increases and aldosterone signaling is blocked. This blockage leads to fetal sodium (Na+) wasting and is essential for formation of amniotic fluid. These events are consistent with a normal role for an unknown endogenous K+ sparing hormone and would be the basis for a modest elevation of maternal DLM during the 3rd trimester. Our hypothesis is that if any of the functions were inadequate, then the fetal-placental unit would synthesize excess PC-spiral steroids; the woman would exhibit symptoms of K+ sparing hormone excess (hypertension and proteinuria) and would be diagnosed with pre-eclampsia. Experimental Results: We have just reported a pilot study associating elevated PC esters of spiral steroids in women with pre-eclampsia. In brief, 12 of 19 women had elevated levels of at least one of the PC steroids (Z-score > 2) when compared to the levels in 20 pregnant women matched for gestational age and fetal sex. There are two basic mechanisms for this dichotomy: (a) there may be episodic secretion with of a DLM with a short half-life or (b) there may be two different underlying biochemical causes. In prior studies, there has been no indication of episodic secretion of DLM similar to that observed with glucocorticoids, Ionotropin or other PC spiral steroids. Discussion: There are two basic types of K+ sparing diuretics. Type A: Spironolactone functions by regulating the NaK-ATPase. Type B: Triamterene functions by blocking synthesis of epithelial Na+ channels. Thus, Type A would have high levels of spiral steroids and Type B would have low levels of spiral steroids. Type A patients would be expected to have higher risk of long-term consequences when compared to the Type B patients. Conclusion: The recognition of the division of pre-eclampsia into two separate diseases might be the key observation for developing Type-specific diagnosis and therapy. For example, a Type A patient might benefit from a low salt diet but that diet would not be expected to benefit a patient with Type B disease.


2019 ◽  
Vol 34 (2) ◽  
pp. 2541-2553 ◽  
Author(s):  
Wei‐Yun Shen ◽  
Cong Luo ◽  
Plinio Reinaldo Hurtado ◽  
Ernesto Hurtado‐Perez ◽  
Ru‐Yi Luo ◽  
...  

1988 ◽  
Vol 5 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Joel J. Hillhouse ◽  
Edward B. Blanchard ◽  
Kenneth A. Appelbaum ◽  
Cynthia Kirsch

Chronic headache sufferers (N = 133) were assessed for Type A behaviour pattern using the Jenkins Activity Survey (JAS). The Type A score frequency distribution for all headache subjects combined, and each headache type separately were examined. Median scores of the all subjects combined group fell into the indeterminate range of Type A scores, that is, neither Type A or Type B. This was also the case for migraine and tension sufferers. Mixed subject's scores fell into the range of scores usually classified as Type A. Forty-five percent of the mixed subjects fit the criteria for Type A behaviour pattern. Follow-up bivariate and multivariate analysis using J AS subscale scores as independent predictors and headache activity scores, from daily diaries, as dependent variables revealed only three correlations which approached significance. These results argue against a clear linear relationship between chronic headache and Type A behaviour pattern. There may be some utility in this construct when differentiated by headache type.


Physiology ◽  
1997 ◽  
Vol 12 (6) ◽  
pp. 263-268 ◽  
Author(s):  
F Benedetti

Several lines of evidence indicate that cholecystokinin (CCK) antagonists potentiate analgesia induced by exogenous opioids. Similarly, CCK antagonists enhance analgesia induced by procedures that activate endogenous opioid systems. However, because there are substantial species differences in receptor specificity and distribution, the role of CCK type A and type B receptors has yet to be clearly established.


Diachronica ◽  
1992 ◽  
Vol 9 (2) ◽  
pp. 239-257
Author(s):  
Martha Ratliff

SUMMARY Tone languages can be characterized by the degree to which they realize one of two tone language prototypes defined in terms of tone function. Type A tone languages (usually Asian) employ tone lexically and in minor morphological patterns. Type B tone languages (usually African and Mesoamerican) employ tone to make major morphological distinctions in addition to performing type A functions. For communicative reasons, these functions are necessarily linked to other structural properties of the languages of each type. This paper discusses three tone languages which have undergone different degrees of tone language type change and, as a result, are genetically or areally atypical: !Xũ (Khoisan), Gokana (Niger-Congo), and Mpi (Tibeto-Burman). It is the claim of the author that the driving force behind tone language type change, as exemplified by these three languages, is a change in the role of segmental morphology. RÉSUMÉ On peut caractériser les langues tonales par le degré par lequel elles réalisent un des deux prototypes de langues tonales définis en terme de fonction tonale. Les langues tonales de type A (généralement asiatiques) emploient le ton pour des fonctions lexicales et des fonctions morphologiques mineures. Outre les fonctions de type A, les langues tonales de type B (généralement africaines et mésoaméricaines) emploient le ton pour des fonctions morphologiques majeures. La communication ayant ses exigences, ces fonctions sont inévitablement liées aux autres propriétés structurales de chaque type. Dans cette étude il s'agit de trois langues tonales qui ont subi différents degrés de changement de type tonal et qui sont, par conséquent, atypiques du point de vue génétique et régional: !Xũ (Khoisan), Gokana (Niger-Congo), et Mpi (Tibeto-Birman). Se fondant sur ces trois langues, l'auteur émet l'hypothèse que la causalité de l'évolution du ton se trouve dans un changement du rôle de la morphologie segmentate. ZUSAMMENFASSUNG Tonsprachen kônnen nach dem Grade, nach dem sie einem der beiden Pro-totypen folgen, charakterisiert werden, und zwar im Sinne ihrer Funktion: Typ A Tonsprachen (meistens asiatische) verwenden Ton lexikalisch und in we-niger wichtigen morphologischen Strukturen; Typ B Tonsprachen (zumeist afrikanische und mittelamerikanische) hingegen verwenden Ton, um wichtige morphologische Unterscheidungen zu treffen, wâhrend sie gleichzeitig auch Funktionen des Typ A wahrnehmen. Aus kommunikativen Griinden sind die Funktionen notwendigerweise mit anderen Struktureigenschaften der Sprachen des jeweiligen Typs verbunden. Der Aufsatz analysiert drei Tonsprachen, die zu verschiedenen Graden Ànderungen in ihrem Tonsystemtyp erfahren haben und daher als entweder genetisch oder areal gesehen atypisch sind: !Xu (Khoi-san), Gokana (Niger-Kongo) und Mpi (Tibeto-Burmesisch). Die Autorin ist der Auffassung, daB die treibende Kraft hinter diesem Tonsprachentypwandel, wie er in diesen drei Sprachen aufgezeigt wird, in der Verânderung in der Rolle der segmentalen Morphologie in diesen Sprachen zu suchen sei.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nanako Okawa ◽  
Kotaro Shimai ◽  
Kohei Ohnishi ◽  
Masamichi Ohkura ◽  
Junichi Nakai ◽  
...  

Abstract Tunicate larvae have a non-reproductive gonadotropin-releasing hormone (GnRH) system with multiple ligands and receptor heterodimerization enabling complex regulation. In Ciona intestinalis type A larvae, one of the gnrh genes, gnrh2, is conspicuously expressed in the motor ganglion and nerve cord, which are homologous structures to the hindbrain and spinal cord, respectively, of vertebrates. The gnrh2 gene is also expressed in the proto-placodal sensory neurons, which are the proposed homologue of vertebrate olfactory neurons. Tunicate larvae occupy a non-reproductive dispersal stage, yet the role of their GnRH system remains elusive. In this study, we investigated neuronal types of gnrh2-expressing cells in Ciona larvae and visualized the activity of these cells by fluorescence imaging using a calcium sensor protein. Some cholinergic neurons and dopaminergic cells express gnrh2, suggesting that GnRH plays a role in controlling swimming behavior. However, none of the gnrh2-expressing cells overlap with glycinergic or GABAergic neurons. A role in motor control is also suggested by a relationship between the activity of gnrh2-expressing cells and tail movements. Interestingly, gnrh2-positive ependymal cells in the nerve cord, known as a kind of glia cells, actively produced Ca2+ transients, suggesting that active intercellular signaling occurs in the glia cells of the nerve cord.


2000 ◽  
Vol 47 (4) ◽  
pp. 1045-1060 ◽  
Author(s):  
J Hutny ◽  
J E Wilson

Previous work has indicated that two types (A and B) of binding sites for hexokinase exist, but in different proportions, on brain mitochondria from various species. Hexokinase is readily solubilized from Type A sites by glucose 6-phosphate (Glc-6-P), while hexokinase bound to Type B sites remains bound even in the presence of Glc-6-P. Type A:Type B ratios are approximately 90:10, 60:40, 40:60, and 20:80 for brain mitochondria from rat, rabbit, bovine and human brain, respectively. The present study has indicated that MgCl2-dependent partitioning of mitochondrially bound hexokinase into a hydrophobic (Triton X-114) phase is generally correlated with the proportion of Type B sites. This partitioning behavior is sensitive to phospholipase C, implying that the factor(s) responsible for conferring hydrophobic character is(are) phospholipid(s). Substantial differences were also seen in the resistance of hexokinase, bound to brain mitochondria from various species, to solubilization by Triton X-100, Triton X-114, or digitonin. This resistance increased with proportion of Type B sites. Enrichment of bovine brain mitochondria in acidic phospholipids (phosphatidylserine or phosphatidylinositol), but not phosphatidylcholine or phosphatidylethanolamine, substantially increased solubilization of the enzyme after incubation at 37 degrees C. Collectively, the results imply that the Type A and Type B sites are located in membrane domains of different lipid composition, the Type A sites being in domains enriched in acidic phospholipids which lead to greater susceptibility to solubilisation by Glc-6-P.


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