β-Amyloid 1-42 Oligomers Impair Function of Human Embryonic Stem Cell-Derived Forebrain Cholinergic Neurons

Cognitive impairment in Alzheimer's disease (AD) patients is associated with a decline in the levels of growth factors, impairment of axonal transport and marked degeneration of basal forebrain cholinergic neurons (BFCNs). Neurogenesis persists in the adult human brain, and the stimulation of regenerative processes in the CNS is an attractive prospect for neuroreplacement therapy in neurodegenerative diseases such as AD. Currently, it is still not clear how the pathophysiological environment in the AD brain affects stem cell biology. Previous studies investigating the effects of the β-amyloid (Aβ) peptide on neurogenesis have been inconclusive, since both neurogenic and neurotoxic effects on progenitor cell populations have been reported. In this study, we treated pluripotent human embryonic stem (hES) cells with nerve growth factor (NGF) as well as with fibrillar and oligomeric Aβ1-40 and Aβ1-42 (nM-µM concentrations) and thereafter studied the differentiation in vitro during 28-35 days. The process applied real time quantitative PCR, immunocytochemistry as well as functional studies of intracellular calcium signaling. Treatment with NGF promoted the differentiation into functionally mature BFCNs. In comparison to untreated cells, oligomeric Aβ1–40 increased the number of functional neurons, whereas oligomeric Aβ1–42 suppressed the number of functional neurons. Interestingly, oligomeric Aβ exposure did not influence the number of hES cell-derived neurons compared with untreated cells, while in contrast fibrillar Aβ1–40 and Aβ1–42 induced gliogenesis. These findings indicate that Aβ1–42 oligomers may impair the function of stem cell-derived neurons. We propose that it may be possible for future AD therapies to promote the maturation of functional stem cell-derived neurons by altering the brain microenvironment with trophic support and by targeting different aggregation forms of Aβ

The Palaeontology of Browsing and Grazing

Peer reviewe

The influence of passenger load, driving cycle, fuel price and different types of buses on the cost of transport service in the BRT system in Curitiba, Brazil

This study analyses the influence of passenger load, driving cycle, fuel price and four different types of buses on the cost of transport service for one bus rapid transit (BRT) route in Curitiba, Brazil. First, the energy use is estimated for different passenger loads and driving cycles for a conventional bi-articulated bus (ConvBi), a hybrid-electric two-axle bus (HybTw), a hybrid-electric articulated bus (HybAr) and a plug-in hybrid-electric two-axle bus (PlugTw). Then, the fuel cost and uncertainty are estimated considering the fuel price trends in the past. Based on this and additional cost data, replacement scenarios for the currently operated ConvBi fleet are determined using a techno-economic optimisation model. The lowest fuel cost ranges for the passenger load are estimated for PlugTw amounting to (0.198–0.289) USD/km, followed by (0.255–0.315) USD/km for HybTw, (0.298–0.375) USD/km for HybAr and (0.552–0.809) USD/km for ConvBi. In contrast, the coefficient of variation (Cv role= presentation style= box-sizing: inherit; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; \u3eCvCv) of the combined standard uncertainty is the highest for PlugTw (Cv role= presentation style= box-sizing: inherit; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; \u3eCvCv: 15–17%) due to stronger sensitivity to varying bus driver behaviour, whereas it is the least for ConvBi (Cv role= presentation style= box-sizing: inherit; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; \u3eCvCv: 8%). The scenario analysis shows that a complete replacement of the ConvBi fleet leads to considerable higher cost of transport service on the BRT route, amounting to an increase by 64% to 139%, depending on the bus fleet composition. Meanwhile, the service quality is improved resulting in 42% up to 64% less waiting time for passengers at a bus stop

Cold-Water Coral in Aquaria: Advances and Challenges. A Focus on the Mediterranean

Knowledge on basic biological functions of organisms is essential to understand not only the role they play in the ecosystems but also to manage and protect their populations. The study of biological processes, such as growth, reproduction and physiology, which can be approached in situ or by collecting specimens and rearing them in aquaria, is particularly challenging for deep-sea organisms like cold-water corals. Field experimental work and monitoring of deep-sea populations is still a chimera. Only a handful of research institutes or companies has been able to install in situ marine observatories in the Mediterranean Sea or elsewhere, which facilitate a continuous monitoring of deep-sea ecosystems. Hence, today’s best way to obtain basic biological information on these organisms is (1) working with collected samples and analysing them post-mortem and / or (2) cultivating corals in aquaria in order to monitor biological processes and investigate coral behaviour and physiological responses under different experimental treatments. The first challenging aspect is the collection process, which implies the use of oceanographic research vessels in most occasions since these organisms inhabit areas between ca. 150 m to more than 1000 m depth, and specific sampling gears. The next challenge is the maintenance of the animals on board (in situations where cruises may take weeks) and their transport to home laboratories. Maintenance in the home laboratories is also extremely challenging since special conditions and set-ups are needed to conduct experimental studies to obtain information on the biological processes of these animals. The complexity of the natural environment from which the corals were collected cannot be exactly replicated within the laboratory setting; a fact which has led some researchers to question the validity of work and conclusions drawn from such undertakings. It is evident that aquaria experiments cannot perfectly reflect the real environmental and trophic conditions where these organisms occur, but: (1) in most cases we do not have the possibility to obtain equivalent in situ information and (2) even with limitations, they produce relevant information about the biological limits of the species, which is especially valuable when considering potential future climate change scenarios. This chapter includes many contributions from different authors and is envisioned as both to be a practical “handbook” for conducting cold-water coral aquaria work, whilst at the same time offering an overview on the cold-water coral research conducted in Mediterranean laboratories equipped with aquaria infrastructure. Experiences from Atlantic and Pacific laboratories with extensive experience with cold-water coral work have also contributed to this chapter, as their procedures are valuable to any researcher interested in conducting experimental work with cold-water corals in aquaria. It was impossible to include contributions from all laboratories in the world currently working experimentally with cold-water corals in the laboratory, but at the conclusion of the chapter we attempt, to our best of our knowledge, to supply a list of several laboratories with operational cold-water coral aquaria facilities