LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the Primitive Erythroid Lineage.

The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YS HSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages. Fetal liver (FL) and adult HSPCs showed 35%-40% Lyve1-Cre marking. Analysis of circulation-deficient Ncx1-/- concepti identified the YS as a major source of Lyve1-Cre labeled HSPCs. FL proerythroblast marking was extensive at embryonic day (E) 11.5-13.5, but decreased to hematopoietic stem cell (HSC) levels by E16.5, suggesting that HSCs from multiple sources became responsible for erythropoiesis. Lyve1-Cre thus marks the divergence between YS primitive and definitive hematopoiesis and provides a tool for targeting YS definitive hematopoiesis and FL colonization

Excess caffeine exposure impairs eye development during chick embryogenesis

Caffeine has been an integral component of our diet and medicines for centuries. It is now known that over consumption of caffeine has detrimental effects on our health, and also disrupts normal foetal development in pregnant mothers. In this study, we investigated the potential teratogenic effect of caffeine over-exposure on eye development in the early chick embryo. Firstly, we demonstrated that caffeine exposure caused chick embryos to develop asymmetrical microphthalmia and induced the orbital bone to develop abnormally. Secondly, caffeine exposure perturbed Pax6 expression in the retina of the developing eye. In addition, it perturbed the migration of HNK-1(+) cranial neural crest cells. Pax6 is an important gene that regulates eye development, so altering the expression of this gene might be the cause for the abnormal eye development. Thirdly, we found that reactive oxygen species (ROS) production was significantly increased in eye tissues following caffeine treatment, and that the addition of anti-oxidant vitamin C could rescue the eyes from developing abnormally in the presence of caffeine. This suggests that excess ROS induced by caffeine is one of the mechanisms involved in the teratogenic alterations observed in the eye during embryogenesis. In sum, our experiments in the chick embryo demonstrated that caffeine is a potential teratogen. It causes asymmetrical microphthalmia to develop by increasing ROS production and perturbs Pax6 expression

reslife: Residual Lifetime Analysis Tool in R

Mean residual lifetime is an important measure utilized in various fields, including pharmaceutical companies, manufacturing companies, and insurance companies for survival analysis. However, the computation of mean residual lifetime can be laborious and challenging. To address this issue, the R package reslife has been developed, which enables efficient calculation of mean residual lifetime based on closed-form solution in a user-friendly manner. reslife offers the capability to utilize either the results of a flexsurv regression or user-provided parameters to compute mean residual lifetime. Furthermore, there are options to return median and percentile residual lifetime. If the user chooses to use the outputs of a flexsurv regression, there is an option to input a data frame with unobserved data. In this article, we present reslife, explain its underlying mathematical principles, illustrate its functioning, and provide examples on how to utilize the package. The aim is to facilitate the use of mean residual lifetime, making it more accessible and efficient for practitioners in various disciplines, particularly those involved in survival analysis within the pharmaceutical industry

PTEN is involved in modulation of vasculogenesis in early chick embryos

Summary PTEN is a tumor suppressor gene that is mutated and/or deleted in many types of tumor. This gene also plays a very distinct role in the early stages of embryonic development such as cell migration, proliferation and migration. Nevertheless, little is known of the function of PTEN in vasculogenesis during chick embryonic development. In this study, we used in situ hybridization to first demonstrate the expression pattern of PTEN during gastrulation. PTEN was found mainly expressed in the blood islands of area opaca, the neural tube and mesodermal structures. Overexpression of PTEN obstructed the epithelial–mesenchymal transition (EMT) process in the primitive streak. EMT is the first prerequisite required for the emigration of hemangioblasts during vasculogenesis. When PTEN expression was silenced, we observed that it produced an adverse effect on mesodermal cell emigration to the extra-embryonic blood islands. In addition, we also demonstrated that even if the perturbed-PTEN cells did not affect the formation of blood islands, migrant mesodermal cells overexpressing wt PTEN-GFP had difficulties integrating into the blood islands. Instead, these cells were either localized on the periphery of the blood islands or induced to differentiate into endothelial cells if they managed to integrate into blood islands. Development of the intra-embryonic primary vascular plexus was also affected by overexpression of PTEN. We proposed that it was elevated PTEN lipid phosphatase activity that was responsible for the morphogenetic defects induced by PTEN overexpression. In this context, we did not find PTEN affecting VEGF signaling. In sum, our study has provided evidence that PTEN is involved in vasculogenesis during the early stages of chick embryo development

In-situ neutron diffraction study of micromechanical shear failure in an aerospace composite

Glass fibre reinforced polypropylene (GF/PP) composite is a well-established material system for fabricating bistable composite tape-spring (CTS) structure. It is light-weight and multifunctional, and has attracted growing interest in shape-adaptive and energy harvesting systems in defence, civil and especially aerospace engineering. The factors governing its bistability have been well-understood; whist there is limited research concerning the micromechanics and microstructural failure. In this research, we investigate the failure mechanisms of the GF/PP composite. This is achieved by performing in-situ neutron diffraction on composite specimens using the ENGIN-X neutron diffractometer at Rutherford Appleton Laboratory. Shear failures are characterised at both macroscopic and microscopic scales. Elastic and viscoelastic strain evolutions at different levels reveal the micromechanical shear failure. The failure mechanisms are then proposed, which will benefit optimisation of structural design and structural integrity of the CTS in aerospace applications

In-situ multiscale shear failure of a bistable composite tape-spring

A bistable composite tape-spring (CTS) is stable in both the extended and coiled configurations, with fibres oriented at ±45°. It is light weight and multifunctional, and has attracted growing interest in shape-adaptive and energy harvesting systems in defence-, civil- and, especially aerospace engineering. The factors governing its bistability have been well-understood, but there is limited research concerning the mechanics of structural failure: here, we investigate the shear failure mechanisms in particular. We perform in-situ neutron diffraction on composite specimens using the ENGIN-X neutron diffractometer at Rutherford Appleton Laboratory (STFC, UK), and shear failure is characterised at both macroscopic and microscopic scales. Elastic and viscoelastic strain evolutions at different strain levels reveal the fundamentals of micromechanical shear failure, and their temperature dependency. Multiscale shear failure mechanisms are then proposed, which will benefit the optimisation of structural design to maintain structural integrity of CTS in aerospace applications.ISIS Neutron and Muon Source, Rutherford Appleton Laboratory, Science and Technology Facilities Council (STFC), Grant no. RB1910213 Innovate UK, ‘‘Large Landing Gear of the Future: Bistable Composite Technologies’’, Grant no. 113077 EPSRC, "NRFIS", Grant no. EP/P013848/

Hearing Loss in Patients with Nasopharyngeal Carcinoma after Chemotherapy and Radiation

In light of the possible adverse effects of radiation on hearing, we conducted a study to evaluate the long-term sensorineural hearing status following radiotherapy (RT) in patients suffering from nasopharyngeal carcinoma. Audiologic examinations were performed at regular intervals before and after RT. We also analyzed the effects of age, chemotherapy, pre-RT hearing status, and post-RT otitis media with effusion (OME) on post-RT hearing change. A total of 150 patients (261 ears) were enrolled in this study and followed up for a mean of 43.8 months. After RT, 8.9-28.8% of ears had at least a 10 dB loss in bone conduction threshold at speech frequency, which was defined as an average of hearing threshold at 0.5 kHz, 1 kHz, and 2 kHz, while the percentage was 18-34.2% at 4 kHz. Patient age was related to these changes at speech frequency, and the presence of post-RT OME was related to significant loss at both speech frequency and 4 kHz. Pre-RT hearing status and chemotherapy did not influence hearing change. To sum up, sensorineural hearing loss began as early as after completion of RT. Early changes may be transient, but the effect of radiation on hearing tended to be chronic and progressive