Mesodermal expression of integrin α5β1 regulates neural crest development and cardiovascular morphogenesis

Integrin α5-null embryos die in mid-gestation from severe defects in cardiovascular morphogenesis, which stem from defective development of the neural crest, heart and vasculature. To investigate the role of integrin α5β1 in cardiovascular development, we used the Mesp1^Cre knock-in strain of mice to ablate integrin α5 in the anterior mesoderm, which gives rise to all of the cardiac and many of the vascular and muscle lineages in the anterior portion of the embryo. Surprisingly, we found that mutant embryos displayed numerous defects related to the abnormal development of the neural crest such as cleft palate, ventricular septal defect, abnormal development of hypoglossal nerves, and defective remodeling of the aortic arch arteries. We found that defects in arch artery remodeling stem from the role of mesodermal integrin α5β1 in neural crest proliferation and differentiation into vascular smooth muscle cells, while proliferation of pharyngeal mesoderm and differentiation of mesodermal derivatives into vascular smooth muscle cells was not defective. Taken together our studies demonstrate a requisite role for mesodermal integrin α5β1 in signaling between the mesoderm and the neural crest, thereby regulating neural crest-dependent morphogenesis of essential embryonic structures.     

Multi-segment foot kinematics and ground reaction forces during gait of individuals with plantar fasciitis

Background

Clinically, plantar fasciitis (PF) is believed to be a result and/or prolonged by overpronation and excessive loading, but there is little biomechanical data to support this assertion. The purpose of this study was to determine the differences between healthy individuals and those with PF in (1) rearfoot motion, (2) medial forefoot motion, (3) first metatarsal phalangeal joint (FMPJ) motion, and (4) ground reaction forces (GRF).

Methods

We recruited healthy (n=22) and chronic PF individuals (n=22, symptomatic over three months) of similar age, height, weight, and foot shape (p>0.05). Retro-reflective skin markers were fixed according to a multi-segment foot and shank model. Ground reaction forces and three dimensional kinematics of the shank, rearfoot, medial forefoot, and hallux segment were captured as individuals walked at 1.35 ms⁻¹.

Results

Despite similarities in foot anthropometrics, when compared to healthy individuals, individuals with PF exhibited significantly (p<0.05) (1) greater total rearfoot eversion, (2) greater forefoot plantar flexion at initial contact, (3) greater total sagittal plane forefoot motion, (4) greater maximum FMPJ dorsiflexion, and (5) decreased vertical GRF during propulsion.

Conclusion

These data suggest that compared to healthy individuals, individuals with PF exhibit significant differences in foot kinematics and kinetics. Consistent with the theoretical injury mechanisms of PF, we found these individuals to have greater total rearfoot eversion and peak FMPJ dorsiflexion, which may put undue loads on the plantar fascia. Meanwhile, increased medial forefoot plantar flexion at initial contact and decreased propulsive GRF are suggestive of compensatory responses, perhaps to manage pain.     

孕中晚期胎儿主动脉弓狭窄的超声诊断参数分析及其影响因素分析

摘要 目的：探究孕中晚期胎儿主动脉弓狭窄的超声诊断参数分析,并就超声诊断参数对孕中晚期胎儿主动脉弓狭窄的影响因素开展分析。方法：选择2020年7月至2021年7月于我院就诊后被确诊为孕中晚期主动脉弓狭窄的40例胎儿为狭窄组,另取同期体格检查正常的40例胎儿为对照组,以胎儿出生后超声心动图检测或尸检结果为金标准,比较两组胎儿超声指标Z-分数（AI Z-score）、升主动脉Z-分数（AO Z-score）、主动脉峡部/升主动脉（AI/AO）差异,分别绘制AI Z-score、AO Z-score以及AI/AO对孕中晚期胎儿主动脉弓狭窄的诊断ROC曲线,并计算其曲线下面积（AUC）,最后采用Logistic回归分析的方式计算孕中晚期胎儿主动脉弓狭窄影响因素。结果：（1）窄缩组胎儿的超声参数AI Z-score、AO Z-score以及AI/AO均明显低于对照组（P<0.05）;（2）AI/AO为孕中晚期胎儿主动脉弓狭窄的危险因素（P<0.05）;（3）AI Z-score、AO Z-score、AI/AO以及联合检测对胎儿主动脉弓狭窄的诊断AUC分别为0.801（95% CI=0.691-0.910,P<0.001）、0.835（95% CI=0.739-0.932,P<0.001）、0.843（95% CI=0.757-0.929,P<0.001）、0.920（95% CI=0.865-0.975,P<0.001）,截断值分别为-1.64、-1.47和0.535,诊断灵敏度和特异度分别为72.50%和72.50%、77.50%和77.50%、75.00%和80.00%、85.00%和82.50%。结论：超声诊断对孕中晚期胎儿主动脉弓狭窄具有较好的诊断价值,其指标AI Z-score、AO Z-score、AI/AO能够量化分析孕中晚期胎儿主动脉弓狭窄风险,可以考虑将其应用于临床中。     

Delta‐like ligand‐4 regulates Notch‐mediated maturation of second heart field progenitor‐derived pharyngeal arterial endothelial cells

Mesodermal progenitors in the second heart field (SHF) express Delta‐like‐ligand 4 (Dll4) that regulates Notch‐mediated proliferation. As cells of SHF lineage mature to assume endocardial and myocardial cell fates, we have shown that Dll4 expression is lost, and the subsequent expression of another Notch ligand Jagged1 regulates Notch‐mediated maturation events in the developing heart. A subset of SHF progenitors also matures to form the pharyngeal arch artery (PAA) endothelium. Dll4 was originally identified as an arterial endothelial‐specific Notch ligand that plays an important role in blood vessel maturation, but its role in aortic arch maturation has not been studied to date secondary to the early lethality observed in Dll4 knockout mice. We show that, unlike in SHF‐derived endocardium and myocardium, Dll4 expression persists in SHF‐derived arterial endothelial cells. Using SHF‐specific conditional deletion of Dll4, we demonstrate that as SHF cells transition from their progenitor state to an endothelial fate, Dll4‐mediated Notch signalling switches from providing proliferative to maturation cues. Dll4 expression maintains arterial identity in the PAAs and plays a critical role in the maturation and re‐organization of the 4th pharyngeal arch artery, in particular. Haploinsufficiency of Dll4 in SHF leads to highly penetrant aortic arch artery abnormalities, similar to those observed in the clinic, primarily resulting from aberrant reorganization of bilateral 4th pharyngeal arch arteries. Hence, we show that cells of SHF lineage that assume an arterial endothelial fate continue to express Dll4 and the resulting Dll4‐mediated Notch signalling transitions from an early proliferative to a later maturation role during aortic arch development.     

Accuracy in Dental Medicine,A New Way to Measure Trueness and Precision

Reference scanners are used in dental medicine to verify a lot of procedures. The main interest is to verify impression methods as they serve as a base for dental restorations. The current limitation of many reference scanners is the lack of accuracy scanning large objects like full dental arches, or the limited possibility to assess detailed tooth surfaces. A new reference scanner, based on focus variation scanning technique, was evaluated with regards to highest local and general accuracy. A specific scanning protocol was tested to scan original tooth surface from dental impressions. Also, different model materials were verified. The results showed a high scanning accuracy of the reference scanner with a mean deviation of 5.3 ± 1.1 µm for trueness and 1.6 ± 0.6 µm for precision in case of full arch scans. Current dental impression methods showed much higher deviations (trueness: 20.4 ± 2.2 µm, precision: 12.5 ± 2.5 µm) than the internal scanning accuracy of the reference scanner. Smaller objects like single tooth surface can be scanned with an even higher accuracy, enabling the system to assess erosive and abrasive tooth surface loss. The reference scanner can be used to measure differences for a lot of dental research fields. The different magnification levels combined with a high local and general accuracy can be used to assess changes of single teeth or restorations up to full arch changes.     

Ultrastructure of the branchial epithelium of an amphibious brackish-water crab

The ultrastructure of the branchial epithelium of the amphibious brackish-water crab Uca mordax (Smith) was investigated in relation to adaptation to the salinity of the medium. No distinct differences were observed in the epithelial structure of animals adapted to either 100% sea water or to 1% sea water. Thus any interpretation of the significance of particular structures in relation to specific transport processes should be regarded with caution. Apart from strict epithelial cells, pillar cells and glycogen (presumed) storage cells were found. The epithelial cells showed very well-developed apical microvilli or lamellae and basal interdigitations with adjacent cells. Well-developed junctional complexes were seen (band desmosomes, septate desmosomes, gap junctions). The cells are extremely rich in mitochondria. Microtubules, peroxisome-like bodies, multivesicular bodies and near-nuclear Golgi complexes were present.     

Behavior of symbionts during oogenesis and early stages of development in the German cockroach, Blattella germanica (Blattodea)

In this paper, adaptations and microanatomic changes in the branchial chamber, as well as influence of parasitosis on the reproductive function of shrimp, are analyzed. Probopyrus cf. oviformis was observed in the branchial chamber of shrimps of both sexes, with an infestation rate of 29%. The infestation frequency in relation to sex and size was not uniform, and two trends were observed: a higher frequency in bigger males in contrast to females, with less infestation frequency in older individuals. This aspect was related to changes in the sex ratio of shrimps, infested and noninfested, with the following conclusions: (1) Sexual inversions were not observed in females of P. argentinus; (2) male infestation with P. cf. oviformis showed tertiary sexual rate bias. It occurred because the metabolic parasite-host relationship led to an increase in size. These infested males were incorporated into a normal population characterized by females being bigger than males. The morphological and functional changes observed were (1) branchial chamber reduction, slendering of the cephalothorax lateral wall, together with local injury (oxygen consumption was below the normal values; and (2) the ovaries of infested females of P. argentinus remained stationary in incipient maturity (secondary vitellogenesis was not observed).     

A new origin for the maxillary jaw

One conserved feature of craniofacial development is that the first pharyngeal arch has two components, the maxillary and mandibular, which then form the upper and lower jaws, respectively. However, until now, there have been no tests of whether the maxillary cells originate entirely within the first pharyngeal arch or whether they originate in a separate condensation, cranial to the first arch. We therefore constructed a fate map of the pharyngeal arches and environs with a series of dye injections into stage 13-17 chicken embryos. We found that from the earliest stage examined, the major contribution to the maxillary bud is from post-optic mesenchyme with a relatively minor contribution from the maxillo-mandibular cleft. Cells labeled within the first pharyngeal arch contributed exclusively to the mandibular prominence. Gene expression data showed that there were different molecular codes for the cranial and caudal maxillary prominence. Two of the genes examined, Rarbeta (retinoic acid receptor beta) and Bmp4 (bone morphogenetic protein) were expressed in the post-optic mesenchyme and epithelium prior to formation of the maxillary prominence and then were restricted to the cranial half of the maxillary prominence. In order to determine the derivatives of the maxillary prominence, we performed focal injections of CM-DiI into the stage 24 maxillary prominence. Labeled cells contributed to the maxillary, palatine, and jugal bones, but not the other elements of the upper beak, the premaxilla and prenasal cartilage. We also determined that the cranial cells give rise to more distal parts of the upper beak, whereas caudal cells form proximal structures. Grafts of stage 24 maxillary prominences were also analyzed to determine skeletal derivatives and these results concurred with the DiI maps. These early and later fate maps indicate that the maxillary prominence and its skeletal derivatives are not derived from the first pharyngeal arch but rather from a separate maxillary condensation that occurs between the eye and the maxillo-mandibular cleft. These data also suggest that during evolution, recession of the first pharyngeal arch-derived palatoquadrate cartilage to a more proximal position gave way to the bony upper jaw of amniotes.