A p75NTR Pivoting Paradigm Propels Perspicacity

The p75 neurotrophin receptor (p75NTR) is involved in numerous neuronal signaling paths but its fundamental signaling mechanisms are unknown. In this issue of Neuron, Vilar et al. show that p75NTR functions as a covalently crosslinked dimer to transduce NGF-induced signaling events

High Affinity Not in the Vicinity?

Functional interactions between the p75 neurotrophin receptor (p75NTR) and the Trk receptors were demonstrated several years ago, but their mechanistic basis remains uncertain. In this issue of Neuron, Wehrman et al. provide a three-dimensional structure of the full TrkA ectodomain complexed to NGF and examine the possibility of a ternary p75NTR-NGF-TrkA complex

p75NTR Is Positively Promiscuous Novel Partners and New Insights

AbstractAlthough identified almost 20 years ago, the precise physiological role of the p75 neurotrophin receptor (p75NTR) has remained elusive. Recent studies have revealed that p75NTR is a component of three distinct receptor platforms that bind different ligands and that, under differing circumstances, facilitate cell survival, cell death, or growth inhibition. These recent developments provide new insights into the functions of this enigmatic receptor

Diatoms as paleolimnological indicators: a reconstruction of Late Quaternary environments in two East African salt lakes

Lakes Magadi (Kenya) and Manyara (Tanzania) occupy closed basins in the southern Gregory Rift valley. Water in these lakes is presently shallow and saline, testifying to the dominance of evaporation (E) over precipitation (P). Past changes in the P: E ratio, and hence in palaeoclimate, can be reconstructed from evidence of the former extent of these lakes. Lake-level fluctuations engender marked variation in water chemistry, and consequently on the composition of the limnological biota. One approach is to examine the sedimentary record of diatoms (unicellular algae), which are excellent indicators of water chemistry and relative water depth, and whose modem distribution is sufficiently well known to allow the quantitative reconstruction of chemical parameters. Diatom analysis of 116 samples from a series of radiometrically dated (14C and U/Ib) sediment cores has revealed significant changes amongst the diatom assemblages during the Late Quaternary. Conductivity and pH have been estimated from the fossil samples by transfer functions (Gasse unpublished, Gasse 1986b). However, the interpretation of fossil diatom assemblages is often problematical in hypersaline environments. Difficulties arise as a result of the operation of taphonomic and diagenetic processes which can severely alter the composition of the diatom assemblagesfr om the ambient population at the time of deposition. Probably the most important factor responsible for assemblage diagenesis in saline lakes is silica dissolution, and this is explored further by a series of laboratory experiments. Results indicate that silica dissolution acts differentially between species, by removing the smaller, more delicate taxa first, and causing the relative enrichment of large robust forms in the fossil samples. A similar dissolution gradient may be reflected in modem samples studied near hot springs at Magadi. Differential dissolution is potentially an important source of error in palaeoenvironmental reconstructions, but, with the outcome of these experiments, it has been possible to assess the extent to which the dissolution process may have shaped the diatom records from Magadi and Manyara. The bulk of the palaeolimnological evidence is focussed upon two periods, 30,000-20,000 BP and 12,700-9,500 BP. The earlier period is most clearly dated in the core from Manyara, where the diatom record suggests the development of an intermediate level lake between c. 27,500 BP and c. 26,000 BP. This is a more complete representation of the same lake phase found in earlier studies from Manyara by Holdship (1976) based on diatoms, and by Casanova (1986a) on stromatolites 20M above the present lake. This time interval may also be represented by the central portion of the Magadi cores NF1 and NF2 but here dating is more problematical. The period 12,700-9,500 BP was one of major lacustrine transgression across Africa although the fine-structure of this event is less well known. Cores NF1 and NF2 from Magadi provide a detailed register of this phase indicating a major highstand from c. 12,700-11,000 BP when the lake became deep enough to stratify and deposit laminated couplets. At c. 11,000 BP the diatoms show that salinity increased greatly from fresh-oligosaline to meso-hypersaline which was probably a consequence of lake level falling

Wettest December in the Lake District for over 200 years

Wettest December in the Lake District for over 200 year

Drip water electrical conductivity as an indicator of cave ventilation at the event scale

The use of speleothems to reconstruct past climatic and environmental change through chemical proxies is becoming increasingly common. Speleothem chemistry is controlled by hydrological and atmospheric processes which vary over seasonal time scales. However, as many reconstructions using speleothem carbonate are now endeavouring to acquire information about precipitation and temperature dynamics at a scale that can capture short term hydrological events, our understanding of within cave processes must match this resolution. Monitoring within Cueva de Asiul (N. Spain) has identified rapid (hourly resolution) changes in drip water electrical conductivity (EC), which is regulated by the pCO2 in the cave air. Drip water EC is therefore controlled by different modes of cave ventilation. In Cueva de Asiul a combination of density differences, and external pressure changes control ventilation patterns. Density driven changes in cave ventilation occur on a diurnal scale at this site irrespective of season, driven by fluctuations in external temperature across the cave internal temperature threshold. As external temperatures drop below those within the cave low pCO2 external air enters the void, facilitating the deposition of speleothem carbonate and causing a reduction in measured drip water EC. Additionally, decreases in external pressure related to storm activity act as a secondary ventilation mechanism. Reductions in external air pressure cause a drop in cave air pressure, enhancing karst air draw down, increasing the pCO2 of the cave and therefore the EC measured within drip waters. EC thereby serves as a first order indicator of cave ventilation, regardless of changes in speleothem drip rates and karst hydrological conditions. High resolution monitoring of cave drip water electrical conductivity reveals the highly sensitive nature of ventilation dynamics within cave environments, and highlights the importance of this for understanding trace element incorporation into speleothem carbonate at the event scale

Gene and Cell-Based Therapies for Parkinson’s Disease: Where Are We?

Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder that carries large health and socioeconomic burdens. Current therapies for PD are ultimately inadequate, both in terms of symptom control and in modification of disease progression. Deep brain stimulation and infusion therapies are the current mainstay for treatment of motor complications of advanced disease, but these have very significant drawbacks and offer no element of disease modification. In fact, there are currently no agents that are established to modify the course of the disease in clinical use for PD. Gene and cell therapies for PD are now being trialled in the clinic. These treatments are diverse and may have a range of niches in the management of PD. They hold great promise for improved treatment of symptoms as well as possibly slowing progression of the disease in the right patient group. Here, we review the current state of the art for these therapies and look to future strategies in this fast-moving field

Gene and Cell-Based Therapies for Parkinson’s Disease: Where Are We?

Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder that carries large health and socioeconomic burdens. Current therapies for PD are ultimately inadequate, both in terms of symptom control and in modification of disease progression. Deep brain stimulation and infusion therapies are the current mainstay for treatment of motor complications of advanced disease, but these have very significant drawbacks and offer no element of disease modification. In fact, there are currently no agents that are established to modify the course of the disease in clinical use for PD. Gene and cell therapies for PD are now being trialled in the clinic. These treatments are diverse and may have a range of niches in the management of PD. They hold great promise for improved treatment of symptoms as well as possibly slowing progression of the disease in the right patient group. Here, we review the current state of the art for these therapies and look to future strategies in this fast-moving field

Developmental axon degeneration requires trpv1-dependent Ca 2+ influx

Development of the nervous system relies on a balance between axon and dendrite growth and subsequent pruning and degeneration. The developmental degeneration of dorsal root ganglion (DRG) sensory axons has been well studied in part because it can be readily modeled by removing the trophic support by nerve growth factor (NGF) in vitro. We have recently reported that axonal fragmentation induced by NGF withdrawal is dependent on Ca2+, and here, we address the mechanism of Ca2+ entry required for developmental axon degeneration of mouse embryonic DRG neurons. Our results show that the transient receptor potential vanilloid family member 1 (TRPV1) cation channel plays a critical role mediating Ca2+ influx in DRG axons withdrawn from NGF. We further demonstrate that TRPV1 activation is dependent on reactive oxygen species (ROS) generation that is driven through protein kinase C (PKC) and NADPH oxidase (NOX)-dependent pathways that become active upon NGF withdrawal. These findings demonstrate novel mechanistic links between NGF deprivation, PKC activation, ROS generation, and TRPV1-dependent Ca2+ influx in sensory axon degeneration.Fil: Johnstone, Aaron D.. University of British Columbia; Canadá. McGill University; CanadáFil: de Léon, Andrés. University of British Columbia; Canadá. McGill University; CanadáFil: Unsain, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Gibon, Julien. University of British Columbia; CanadáFil: Barker, Philip A.. University of British Columbia; Canad