Atrioventricular valve development during late embryonic and postnatal stages involves condensation and extracellular matrix remodeling

Although the signaling molecules regulating the early stages of valvular development have been well described, little is known on the late steps leading to mature fibrous leaflets. We hypothesized that atrioventricular (AV) valve development continues after birth to adjust to the postnatal maturation of the heart. By doing a systematic analysis of the AV valves of mice from embryonic day (E) 15.5 to 8 weeks old, we identified key developmental steps that map the maturation process of embryonic cushion-like leaflets into adult stress-resistant valves. Condensation of the mesenchymal cells occurred between E15.5 and E18.5 and was accompanied by increased cellular proliferation and adhesion. Cellular proliferation also contributed transiently to the concomitant elongation of the leaflets. Patterning of the extracellular matrix (ECM) proteins along the AV axis was achieved 1 week after birth, with the differentiation of two reciprocal structural regions, glycosaminoglycans and versican at the atrial side, and densely packed collagen fibers at the ventricular side. Formation and remodeling of the nodular thickenings at the closure points of the leaflets occurred between N4.5 and N11.5. In conclusion, AV valve development during late embryonic and postnatal stages includes condensation, elongation, formation of nodular thickenings, and remodeling of tension-resistant ECM proteins.     

T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?

Introduction

A hallmark of systemic autoimmune diseases like systemic lupus erythematosus (SLE) is the increased expression of interferon (IFN) type I inducible genes, so-called IFN type I signature. Recently, T-helper 17 subset (Th17 cells), which produces IL-17A, IL-17F, IL-21, and IL-22, has been implicated in SLE. As CCR6 enriches for Th17 cells, we used this approach to investigate whether CCR6⁺ memory T-helper cells producing IL-17A, IL-17F, IL-21, and/or IL-22 are increased in SLE patients and whether this increase is related to the presence of IFN type I signature.

Methods

In total, 25 SLE patients and 15 healthy controls (HCs) were included. SLE patients were divided into IFN type I signature-positive (IFN⁺) (n = 16) and negative (IFN^-) (n = 9) patients, as assessed by mRNA expression of IFN-inducible genes (IFIGs) in monocytes. Expression of IL-17A, IL-17F, IL-21, and IL-22 by CD4⁺CD45RO⁺CCR6⁺ T cells (CCR6⁺ cells) was measured with flow cytometry and compared between IFN⁺, IFN^- patients and HCs.

Results

Increased percentages of IL-17A and IL-17A/IL-17F double-producing CCR6⁺ cells were observed in IFN⁺ patients compared with IFN^- patients and HCs. IL-17A and IL-17F expression within CCR6⁺ cells correlated significantly with IFIG expression. In addition, we found significant correlation between B-cell activating factor of the tumor necrosis family (BAFF)–a factor strongly correlating with IFN type I - and IL-21 producing CCR6⁺ cells.

Conclusions

We show for the first time higher percentages of IL-17A and IL-17A/IL-17F double-producing CCR6⁺ memory T-helper cells in IFN⁺ SLE patients, supporting the hypothesis that IFN type I co-acts with Th17 cytokines in SLE pathogenesis.     

The relationship between lateral meniscus shape and joint contact parameters in the knee: a study using data from the Osteoarthritis Initiative

Introduction

The meniscus has an important role in force transmission across the knee, but a detailed three-dimensional (3D) morphometric shape analysis of the lateral meniscus to elucidate subject-specific function has not been conducted. The aim of this study was to perform 3D morphometric analyses of the lateral meniscus in order to correlate shape variables with anthropometric parameters, thereby gaining a better understanding of the relationship between lateral meniscus shape and its load-bearing function.

Methods

The lateral meniscus (LM) was manually segmented from magnetic resonance images randomly selected from the Osteoarthritis Initiative (OAI) non-exposed control subcohort. A 3D statistical shape model (SSM) was constructed to extract the principal morphological variations (PMV) of the lateral meniscus for 50 subjects (25 male and 25 female). Correlations between the principal morphological variations and anthropometric parameters were tested. Anthropometric parameters that were selected included height, weight, body mass index (BMI), femoral condyle width and axial rotation.

Results

The first principal morphological variation (PMV) was found to correlate with height (r = 0.569), weight (r = 0.647), BMI (r = 0.376), and femoral condyle width (r = 0.622). The third PMV was found to correlate with height (r = 0.406), weight (r = 0.312), and femoral condyle width (r = 0.331). The percentage of the tibial plateau covered by the lateral meniscus decreases as anthropometric parameters relating to size of the subject increase. Furthermore, when the size of the subject increases, the posterior and anterior horns become proportionally longer and wider.

Conclusion

The correlations discovered suggest that variations in meniscal shape can be at least partially explained by the levels of loads transmitted across the knee on a regular basis. Additionally, as the size of the subject increases and body weight rises, the coverage percentage of the meniscus is reduced, suggesting that there would be an increase in the load-bearing by the cartilage. However, this reduced coverage percentage is compensated by the proportionally wider and longer meniscal horn.     

Evolution and Development of Ventricular Septation in the Amniote Heart

During cardiogenesis the epicardium, covering the surface of the myocardial tube, has been ascribed several functions essential for normal heart development of vertebrates from lampreys to mammals. We investigated a novel function of the epicardium in ventricular development in species with partial and complete septation. These species include reptiles, birds and mammals. Adult turtles, lizards and snakes have a complex ventricle with three cava, partially separated by the horizontal and vertical septa. The crocodilians, birds and mammals with origins some 100 million years apart, however, have a left and right ventricle that are completely separated, being a clear example of convergent evolution. In specific embryonic stages these species show similarities in development, prompting us to investigate the mechanisms underlying epicardial involvement. The primitive ventricle of early embryos becomes septated by folding and fusion of the anterior ventricular wall, trapping epicardium in its core. This folding septum develops as the horizontal septum in reptiles and the anterior part of the interventricular septum in the other taxa. The mechanism of folding is confirmed using DiI tattoos of the ventricular surface. Trapping of epicardium-derived cells is studied by transplanting embryonic quail pro-epicardial organ into chicken hosts. The effect of decreased epicardium involvement is studied in knock-out mice, and pro-epicardium ablated chicken, resulting in diminished and even absent septum formation. Proper folding followed by diminished ventricular fusion may explain the deep interventricular cleft observed in elephants. The vertical septum, although indistinct in most reptiles except in crocodilians and pythonidsis apparently homologous to the inlet septum. Eventually the various septal components merge to form the completely septated heart. In our attempt to discover homologies between the various septum components we aim to elucidate the evolution and development of this part of the vertebrate heart as well as understand the etiology of septal defects in human congenital heart malformations.     

Courtship Behavior of Zaprionus indianus (Gupta) (Diptera: Drosophilidae) from Populations Colonizing South America

We describe for the first time the sexual behavior and the courtship song of males of the African fly Zaprionus indianus (Gupta), a recent invader of South America. The male courtship song is formed by monocyclic pulses and the courtship behavior is simple when compared to that of species of Drosophila. Two interpulse interval (IPI) distributions were observed: pre-mounting and mounting. No significant difference was observed between the pre-mounting IPIs of males that descended from three geographical populations from South America. We also observed the songs produced by females and the homosexual behavior exhibited by males. A sequence of bursts is produced by females as a refusal signal against males, while males emit a characteristic song that identifies sex genus, which differs from the courtship song. The short courtship and mating latencies recorded reveal vigorous males and receptive females, respectively.     

Removing celiac disease-related gluten proteins from bread wheat while retaining technological properties: a study with Chinese Spring deletion lines

Background  

Gluten proteins can induce celiac disease (CD) in genetically susceptible individuals. In CD patients gluten-derived peptides are presented to the immune system, which leads to a CD4⁺ T-cell mediated immune response and inflammation of the small intestine. However, not all gluten proteins contain T-cell stimulatory epitopes. Gluten proteins are encoded by multigene loci present on chromosomes 1 and 6 of the three different genomes of hexaploid bread wheat (Triticum aestivum) (AABBDD).     

Development of Lactococcus lactis encoding fluorescent proteins,GFP, mCherry and iRFP regulated by the nisin-controlled gene expression system

Fluorescent proteins are useful reporter molecules for a variety of biological systems. We present an alternative strategy for cloning reporter genes that are regulated by the nisin-controlled gene expression (NICE) system. Lactoccocus lactis was genetically engineered to express green fluorescent protein (GFP), mCherry or near-infrared fluorescent protein (iRFP). The reporter gene sequences were optimized to be expressed by L. lactis using inducible promoter pNis within the pNZ8048 vector. Expression of constructions that carry mCherry or GFP was observed by fluorescence microscopy 2 h after induction with nisin. Expression of iRFP was evaluated at 700 nm using an infrared scanner; cultures induced for 6 h showed greater iRFP expression than non-induced cultures or those expressing GFP. We demonstrated that L. lactis can express efficiently GFP, mCherry and iRFP fluorescent proteins using an inducible expression system. These strains will be useful for live cell imaging studies in vitro or for imaging studies in vivo in the case of iRFP.     

The realigment of the orchid flora in the mountain range of Guamuahaya,Cienfuegos, Cuba

The present study of the Orchidaceae family was carried out in Guamuahaya’s mountain range, from 2000 to March 2013. Fifteen districts were explored after 33 expeditions in the Province of Cienfuegos. Ninety two plant species were identified in the studied area, taking into account the ecological parameters of the mountainous areas of Cienfuegos and Cumanayagua municipalities.