A striking example of the relationship between regulation of transcription and phenotype is the central role of the Y-chromosomal gene Sry in mammalian sex determination. Sry is the founding member of a large family of so-called Sox genes. During murine embryogenesis, the transcriptional activator Sox-4 is expressed at several sites, but in adult mice expression is restricted to immature B and T lymphocytes. Using targeted gene distruption, we have found that SOX-4(-/-) embryos succumb to circulatory failure at day E14. This was a result of impaired development of the endocardial ridges (a specific site of Sox-4 expression) into the semilunar valves and the outlet portion of the muscular ventricular septum. The observed range of septation defects is known as 'common arterial trunk' in man. We studied haemopoiesis in lethally irradiated mice reconstituted with SOX-4(-/-) fetal liver cells and found that a specific block occurred in B-cell development at the pro-B cell stage. In line with this, the frequency and proliferative capacity of IL-7-responsive B cell progenitors in fetal liver were severely decreased in vitro.

Skeleton-based action recognition has made great progress recently, but many problems still remain unsolved. For example, the representations of skeleton sequences captured by most of the previous methods lack spatial structure information and detailed temporal dynamics features. In this paper, we propose a novel model with spatial reasoning and temporal stack learning (SR-TSL) for skeleton-based action recognition, which consists of a spatial reasoning network (SRN) and a temporal stack learning network (TSLN). The SRN can capture the high-level spatial structural information within each frame by a residual graph neural network, while the TSLN can model the detailed temporal dynamics of skeleton sequences by a composition of multiple skip-clip LSTMs. During training, we propose a clip-based incremental loss to optimize the model. We perform extensive experiments on the SYSU 3D Human-Object Interaction dataset and NTU RGB+D dataset and verify the effectiveness of each network of our model. The comparison results illustrate that our approach achieves much better results than the state-of-the-art methods.

The outflow tract (OFT) provides the structural components forming the ventriculoarterial connection. The prevailing concept that this junction "rotates" to acquire its definitive topography also requires a concept of "counterrotation" and is difficult to reconcile with cell-marking studies. Rats between 10 embryonic days (EDs) and 2 postnatal days were stained immunohistochemically and by in situ hybridization. DNA replication was determined by incorporation of bromodeoxyuridine and apoptosis by the annexin V binding and terminal deoxynucleotidyl transferase-mediated dUTP-X nick end labeling (TUNEL) assays. Starting at ED12, cardiomyocytes in the distal (truncal) part of the OFT begin to shed their myocardial phenotype without proceeding into apoptosis, suggesting transdifferentiation. Myocardial regression is most pronounced on the dextroposterior side and continues until after birth, as revealed by the disappearance of the myocardial cuff surrounding the coronary roots and semilunar sinuses and by the establishment of fibrous continuity between mitral and aortic semilunar valves. Fusion of the endocardial ridges of the truncus on late ED13 is accompanied by the organization of alpha-smooth muscle actin-and nonmuscle myosin heavy chain-positive myofibroblasts into a central whorl and the appearance of the semilunar valve anlagen at their definitive topographical position within the proximal portion of the truncus. After fusion of the proximal (conal) portion of the endocardial ridges, many of the resident myofibroblasts undergo apoptosis and are replaced by cardiomyocytes. The distal myocardial boundary of the OFT is not a stable landmark but moves proximally over the spiraling course of the aortic and pulmonary routes, so that the semilunar valves develop at their definitive topographic position. After septation, the distal boundary of the OFT continues to regress, particularly in its subaortic portion. The myocardializing conus septum, on the other hand, becomes largely incorporated into the right ventricle. These opposite developments account for the pronounced asymmetry of the subaortic and subpulmonary outlets in the formed heart.

Cardiac malformation in connexin43 (CX43)-disrupted mice is restricted to the junction between right ventricle and outflow tract, even though CX43 is also expressed abundantly elsewhere. We analyzed cardiac morphogenesis in immunohistochemically and hybridohistochemically stained and three-dimensionally reconstructed serial sections of CX43-deficient embryos between embryonic day (ED) 10 and birth. The establishment of the D configuration in the ascending loop of CX43-deficient hearts is markedly retarded, so that the right ventricle retains a craniomedial position and is connected with the outflow tract by a more acute bend in ED10 and ED11 embryos. Because of the subsequent growth of the right ventricle, this condition usually evolves into a D loop, but when it persists, a "crisscross" configuration develops, with the atrioventricular cushions rotated 90 degrees, a horizontal muscular ventricular septum, and a parallel course of the endocardial ridges of the outflow tract. After ED12, large intertrabecular pouches develop at the ventricular side of both shelflike myocardial structures that support the endocardial ridges of the outflow tract, ie, at the location that was earlier characterized by the acute bend between the right ventricle and the outflow tract and that subsequently develops into the anterosuperior leaflet of the tricuspid valve. Retarded development of the D configuration in the ascending loop of the embryonic heart predisposes the myocardium at the junction of the right ventricle and outflow tract to excessive development of intertrabecular pouches during subsequent development.

Embryonic mice lacking functional Sox4 transcription factor die from cardiac failure at embryonic day (ED) 14. Heart morphogenesis in these embryos was analyzed in hematoxylin-azophlochsin or immunohistochemically stained, 3-dimensionally reconstructed serial sections between ED12 and ED14. Although Sox4 is expressed in the endocardially derived tissue of both the outflow tract and atrioventricular canal, Sox4-deficient hearts only suffer from defective transformation of the endocardial ridges into semilunar valves and from lack of fusion of these ridges, usually resulting in common trunk, although the least affected hearts should be classified as having a large infundibular septal defect. The more serious cases are, in addition, characterized by an abnormal number and position of the semilunar valve-leaflet anlagen, a configuration of the ridges typical for transposition of the great arteries (with linear rather than spiral course of both ridges and posterior position of the pulmonary trunk at the level of the valve), and variable size of the aorta relative to the pulmonary trunk. The coronary arteries always originated from the aorta, irrespective of its position relative to the pulmonary trunk. The restriction of the malformations to the arterial pole implies that the interaction between the endocardially derived tissue of the outflow tract and the neural crest-derived myofibroblasts determines proper development of the arterial pole.

Text-based person search aims to retrieve the corresponding person images in an image database by virtue of a describing sentence about the person, which poses great potential for various applications such as video surveillance. Extracting visual contents corresponding to the human description is the key to this cross-modal matching problem. Moreover, correlated images and descriptions involve different granularities of semantic relevance, which is usually ignored in previous methods. To exploit the multilevel corresponding visual contents, we propose a pose-guided multi-granularity attention network (PMA). Firstly, we propose a coarse alignment network (CA) to select the related image regions to the global description by a similarity-based attention. To further capture the phrase-related visual body part, a fine-grained alignment network (FA) is proposed, which employs pose information to learn latent semantic alignment between visual body part and textual noun phrase. To verify the effectiveness of our model, we perform extensive experiments on the CUHK Person Description Dataset (CUHK-PEDES) which is currently the only available dataset for text-based person search. Experimental results show that our approach outperforms the state-of-the-art methods by 15 % in terms of the top-1 metric.

T he intricate process of formation of the heart relies on the spatiotemporal regulation of differentiation and growth of its different parts. Errors in these processes can result in hypoplasia of the chambers and incorrect alignment of the atria and great arteries with the ventricles, with such abnormalities producing the worst forms of congenital heart disease. 1 Although recent advances in molecular embryology have greatly improved our understanding of normal cardiac development, our insights into the pathogenesis of human cardiac malformations remain limited. 2 With the current lack of data on gene expression in humans, inferences concerning morphogenesis rely on classic studies of human cardiac development or on extrapolation of experimental data from animal studies. Most textbooks on human embryology describe the embryonic heart tube as already possessing a linear array of the definitive components, despite this so-called segmental concept being disproved some time ago by fatemapping experiments in chickens, 3,4 which are now endorsed by recent molecular lineage analyses in mice. 5 Proliferation studies in chickens revealed that the primary heart tube proliferates minimally and that its growth occurs through addition of differentiating cells from visceral mesoderm at the venous and arterial poles. 6 These findings underscore previous lineage studies performed in mice, which have shown that transcription factors Islet1 and Tbx1 play a crucial role in the intricate balance between the cardiac precursor state and differentiation. 7,8 Subsequent to its formation, the heart tube elongates and loops, producing its inner and outer curvatures and providing the general building plan for formation of the chambers and conduction system. 9 The chambers themselves form by local proliferation and differentiation at the outer curvature. 10,11 At the same time, the differentiating chamber myocardium remains flanked by primary myocardium, which is prevented from further differentiation by the transcriptional repressors T-box factors 2 and 3 (TBX2 and TBX3), thus providing the precursors of the cardiac conduction system. 9 Because it is impossible to perform experiments in the developing human heart and because of the scarcity of gene expression data, the descriptions of its development remained controversial. In this study, we report patterns of proliferation and gene expression in tubular and chamber-forming stages of the human heart, supplementing our account with 3-dimensional (3D) analyses presented in interactive fashion. Our findings show the comparability of the mechanisms governing cardiac development in humans, mice, and chickens. Methods Human EmbryosWe used human embryos ranging from Carnegie stages 9 to 16 derived from 2 different collections. Acquisition and preparation of the first group of embryos were performed at the Gynecology Department of Tartu University Hospital, Tartu, Estonia. To extend the number of embryos in this study, we have included a series of previously performed stainings of ser...

No abstract