The Mouse Hindbrain As a Model for Studying Embryonic Neurogenesis

The mouse embryo forebrain is the most commonly employed system for studying mammalian neurogenesis during development. However, the highly folded forebrain neuroepithelium is not amenable to wholemount analysis to examine organ-wide neurogenesis patterns. Moreover, defining the mechanisms of forebrain neurogenesis is not necessarily predictive of neurogenesis in other parts of the brain; for example, due to the presence of forebrain-specific progenitor subtypes. The mouse hindbrain provides an alternative model for studying embryonic neurogenesis that is amenable to wholemount analysis, as well as tissue sections to observe the spatiotemporal distribution and behavior of neural progenitors. Moreover, it is easily dissected for other downstream applications, such as cell isolation or molecular biology analysis. As the mouse hindbrain can be readily analyzed in the vast number of cell lineage reporter and mutant mouse strains that have become available, it offers a powerful model for studying the cellular and molecular mechanisms of developmental neurogenesis in a mammalian organism. Here, we present a simple and quick method to use the mouse embryo hindbrain for analyzing mammalian neural progenitor cell (NPC) behavior in wholemount preparations and tissue sections

Cross-talk between blood vessels and neural progenitors in the developing brain

The formation of the central nervous system (CNS) involves multiple cellular and molecular interactions between neural progenitor cells (NPCs) and blood vessels to establish extensive and complex neural networks and attract a vascular supply that support their function. In this review, we discuss studies that have performed genetic manipulations of chick, fish and mouse embryos to define the spatiotemporal roles of molecules that mediate the reciprocal regulation of NPCs and blood vessels. These experiments have highlighted core functions of NPC-expressed ligands in initiating vascular growth into and within the neural tube as well as establishing the blood-brain barrier. More recent findings have also revealed indispensable roles of blood vessels in regulating NPC expansion and eventual differentiation, and specific regional differences in the effect of angiocrine signals. Accordingly, NPCs initially stimulate blood vessel growth and maturation to nourish the brain, but blood vessels subsequently also regulate NPC behaviour to promote the formation of a sufficient number and diversity of neural cells. A greater understanding of the molecular cross-talk between NPCs and blood vessels will improve our knowledge of how the vertebrate nervous system forms and likely help in the design of novel therapies aimed at regenerating neurons and neural vasculature following CNS disease or injury

Process Capability Database Usage In Industry: Myth vs. Reality

Process capability data (PCD) is needed for robust design, optimal tolerance allocation, and variation simulation analysis. Process capability databases (PCDBs) have been developed in many industries and are being used by the manufacturing community to monitor quality; however, they are not being effectively utilized by design. When the PCDBs1 were developed, the intent was for design to use PCD for optimization and product cost minimization, but this ideal situation has not been realized. A survey of a variety of design and manufacturing companies was circulated to determine both the state-ofthe- art in PCDBs and the barriers preventing design from fully utilizing PCD. Two key barriers were identified for internal PCDBs: lack of a company-wide vision for PCD usage and poor communication between manufacturing and design. Supplier PCDBs have the additional barriers of lack of trust between suppliers and customers and time lag for data entry. Management support, training, database population, and common systems were identified as potential solutions to the identified barriers

Current nanocarrier strategies improve vitamin B12 pharmacokinetics, ameliorate patients’ lives, and reduce costs

Vitamin B12 (VitB12) is a naturally occurring compound produced by microorganisms and an essential nutrient for humans. Several papers highlight the role of VitB12 deficiency in bone and heart health, depression, memory performance, fertility, embryo development, and cancer, while VitB12 treatment is crucial for survival in inborn errors of VitB12 metabolism. VitB12 is administrated through intramuscular injection, thus impacting the patients’ lifestyle, although it is known that oral administration may meet the specific requirement even in the case of malabsorption. Furthermore, the high-dose injection of VitB12 does not ensure a constant dosage, while the oral route allows only 1.2% of the vitamin to be absorbed in human beings. Nanocarriers are promising nanotechnology that can enable therapies to be improved, reducing side effects. Today, nanocarrier strategies applied at VitB12 delivery are at the initial phase and aim to simplify administration, reduce costs, improve pharmacokinetics, and ameliorate the quality of patients’ lives. The safety of nanotechnologies is still under investigation and few treatments involving nanocarriers have been approved, so far. Here, we highlight the role of VitB12 in human metabolism and diseases, and the issues linked to its molecule properties, and discuss how nanocarriers can improve the therapy and supplementation of the vitamin and reduce possible side effects and limits

Effect of Grid Topology on Numerical Simulations of Flow Fields around Wind Turbine Nacelle Anemometer

In this paper, the effect of mesh topology on the numerical predictions of the immediate near wake region of a horizontal axis wind turbine is investigated. The present work focuses on the nacelle anemometry measurements. Steady Reynolds Averaged Navier-Stokes (RANS) equations are applied to describe the airflow around the wind turbine nacelle. The k-ε turbulence model is used. To model the turbine rotor, the approach based on the actuator disc concept is considered. The computational domain has been meshed with five different configurations of grid; namely, quasi-structured, unstructured and three different hybrid grids constituted of blending of quasi-structured and unstructured grids. The obtained results are compared to the available experimental data. The hybrid mesh with quasi-structured grid in the boundary layer region and unstructured grid in the vicinity of the nacelle is found to be more promising to simulate the near wake generated downstream of the wind turbine nacelle and to predict accurately the nacelle anemometry measurements

Vascularisation of the central nervous system

The developing central nervous system (CNS) is vascularised through the angiogenic invasion of blood vessels from a perineural vascular plexus, followed by continued sprouting and remodelling until a hierarchical vascular network is formed. Remarkably, vascularisation occurs without perturbing the intricate architecture of the neurogenic niches or the emerging neural networks. We discuss the mouse hind brain, forebrain and retina as widely used models to study developmental angiogenesis in the mammalian CNS and provide an overview of key cellular and molecular mechanisms regulating the vascularisation of these organs

Effects mediated by the α7 nicotinic acetylcholine receptor on cell proliferation and migration in rat adipose-derived stem cells

Adipose-derived stem cells (ASCs) are an attractive source for regenerative medicine as they can be easily iso-lated, rapidly expandable in culture and show excellent in vitro differentiation potential. Acetylcholine (ACh), one of the main neurotransmitters in central and peripheral nervous systems, plays key roles in the control of several physiological processes also in non-neural tissues. As demonstrated in our previous studies, ACh can contribute to the rat ASCs physiology, negatively modulating ASCs proliferation and migration via M2 mus-carinic receptor (mAChR) activation. In the present work we show that rat ASCs also express α7 nicotinic receptors (nAChRs). In particular, we have investigated the effects mediated by the selective activation of α7 nAChRs, which causes a reduction of ASC proliferation without affecting cell survival and morphology, and significantly promotes cell migration via upregulation of the CXCR4 expression. Interestingly, the activation of the α7 nAChR also upregulates the expression of M2 mAChR protein, indicating a cooperation between muscarinic and nicotinic receptors in the inhibition of ASC proliferation

Attempts to identify Cassava Brown Streak Virus in western Democratic Republic of Congo

Open Access ArticleRoot necrosis similar to those of the cassava brown streak disease (CBSD) were observed on cassava in western provinces of the Democratic Republic of Congo (DR.Congo) in the early 2000’s. However molecular laboratory diagnosis were not able to detect any causative agent responsible for the attacks, hence, the disease related to these symptoms was named CBSD-like disease. In order to assess the distribution and the incidence of the CBSD-like disease, surveys were carried out in four western provinces, comprising, Kwango and Kwilu, Sud Ubangi, Kinshasa and Kongo Central. CBSD-like disease was observed in all surveyed provinces on the basis of root symptoms because foliar symptoms were different to those of the documented cases of CBSD in other parts of east Africa. CBSD-like disease incidence was high in Kongo Central and Sud Ubangi, exceeding an average of 50 %, but low in Kwango and Kwilu (32.8%) and in Kinshasa (19.1%). During the surveys, cassava leaf samples were collected for lab identification of the causal agent. PCR diagnosis was done on these samples using primers specific for the two known CBSVs. All samples tested negative with no amplification of DNA fragments of the correct size. Thus, further analysis on the causative organism is needed using Next Generation Sequencing (NGS) approaches. NGS approaches will help also to identify the causative organism in other Central Africa countries (Angola, Congo-Brazzaville and Gabon) where such cassava root necrosis have been reported or are suspected

In the Interests of clients or commerce? Legal aid, supply, demand, and 'ethical indeterminacy' in criminal defence work

As a professional, a lawyer's first duty is to serve the client's best interests, before simple monetary gain. In criminal defence work, this duty has been questioned in the debate about the causes of growth in legal aid spending: is it driven by lawyers (suppliers) inducing unnecessary demand for their services or are they merely responding to increased demand? Research reported here found clear evidence of a change in the handling of cases in response to new payment structures, though in ways unexpected by the policy's proponents. The paper develops the concept of 'ethical indeterminacy' as a way of understanding how defence lawyers seek to reconcile the interests of commerce and clients. Ethical indeterminacy suggests that where different courses of action could each be said to benefit the client, the lawyer will tend to advise the client to decide in the lawyer's own interests. Ethical indeterminacy is mediated by a range of competing conceptions of 'quality' and 'need'. The paper goes on to question the very distinction between 'supply' and 'demand' in the provision of legal services

Cell death and impairment of glucose-stimulated insulin secretion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the beta-cell line INS-1E.

The aim of this research was to characterize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity on the insulin-secreting beta-cell line INS-1E. A sharp decline of cell survival (below 20%) was observed after 1 h exposure to TCDD concentrations between 12.5 and 25 nM. Ultrastructurally, beta-cell death was characterized by extensive degranulation, appearance of autophagic vacuoles, and peripheral nuclear condensation. Cytotoxic concentrations of TCDD rapidly induced a dose-dependent increase in intracellular calcium concentration. Blocking calcium entry by EGTA significantly decreased TCDD cytotoxicity. TCDD was also able to rapidly induce mitochondrial depolarization. Interestingly, 1 h exposition of INS-1E cells to very low TCDD concentrations (0.05-1 nM) dramatically impaired glucose-stimulated but not KCl-stimulated insulin secretion. In conclusion, our results clearly show that TCDD exerts a direct beta-cell cytotoxic effect at concentrations of 15-25 nM, but also markedly impairs glucose-stimulated insulin secretion at concentrations 20 times lower than these. On the basis of this latter observation we suggest that pancreatic beta-cells could be considered a specific and sensitive target for dioxin toxicity