Membrane currents and pacemaking in corticotrophs and hiPSC-derived dopaminergic neurons

Many neural networks are required to function at particular frequencies. These processes are often driven by rhythmic, intrinsically generated electrical activity that is produced by cells described as pacemaker neurons. Two disease-relevant in-vitro models were investigated that display poorly understood pacemaker activity; AtT20 anterior pituitary corticotrophs and human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons. Using electrophysiology and Ca2+ imaging, gaps in our understanding of pacemaking in these cell types were investigated. For AtT20s, it was revealed that hormone secretion in this cell type is uncoupled from its electrical activity. Novel roles were found for T-type voltage-gated calcium channels (VGCCs) in pacemaking and for L-type VGCCs in maintaining intracellular Ca2+ concentrations. hiPSC-derived DA neurons were found to produce apparently spontaneous electrical activity in culture that was dependent upon L-type VGCCs. This pacemaking was not found to be intrinsic, instead being driven by and developing in parallel with synaptic input in culture. These DA neurons immunostained for the L-type VGCC subtype CaV1.3, which is involved in the death of DA neurons in Parkinson's disease. Using a novel cell death assay these neurons were found to be selectively susceptible to the DA toxin 6-hydroxydopamine but displayed a resistance to glutamate-induced excitotoxicity. Data here provides valuable information on the similarities and differences between these in-vitro models and their in-vivo counterparts. This allowed for an in-depth assessment of their suitability as models for their respective diseases, hopefully leading to the targeted, efficient design of studies that use these cell types

Auditory Spatial Acuity Approximates the Resolving Power of Space-Specific Neurons

The relationship between neuronal acuity and behavioral performance was assessed in the barn owl (Tyto alba), a nocturnal raptor renowned for its ability to localize sounds and for the topographic representation of auditory space found in the midbrain. We measured discrimination of sound-source separation using a newly developed procedure involving the habituation and recovery of the pupillary dilation response. The smallest discriminable change of source location was found to be about two times finer in azimuth than in elevation. Recordings from neurons in its midbrain space map revealed that their spatial tuning, like the spatial discrimination behavior, was also better in azimuth than in elevation by a factor of about two. Because the PDR behavioral assay is mediated by the same circuitry whether discrimination is assessed in azimuth or in elevation, this difference in vertical and horizontal acuity is likely to reflect a true difference in sensory resolution, without additional confounding effects of differences in motor performance in the two dimensions. Our results, therefore, are consistent with the hypothesis that the acuity of the midbrain space map determines auditory spatial discrimination

Data from: Processes of community assembly in an environmentally heterogeneous, high biodiversity region

Despite decades of study, the relative importance of niche-based versus neutral processes in community assembly remains largely ambiguous. Recent work suggests niche-based processes are more easily detectable at coarser spatial scales, while neutrality dominates at finer scales. Analyses of functional traits with multi-year multi-site biodiversity inventories may provide deeper insights into assembly processes and the effects of spatial scale. We examined associations between community composition, species functional traits, and environmental conditions for plant communities in the Kouga-Baviaanskloof region, an area within South Africa's Cape Floristic Region (CFR) containing high α and β diversity. This region contains strong climatic gradients and topographic heterogeneity, and is comprised of distinct vegetation classes with varying fire histories, making it an ideal location to assess the role of niche-based environmental filtering on community composition by examining how traits vary with environment. We combined functional trait measurements for over 300 species with observations from vegetation surveys carried out in 1991/1992 and repeated in 2011/2012. We applied redundancy analysis, quantile regression, and null model tests to examine trends in species turnover and functional traits along environmental gradients in space and through time. Functional trait values were weakly associated with most spatial environmental gradients and only showed trends with respect to vegetation class and time since fire. However, survey plots showed greater compositional and functional stability through time than expected based on null models. Taken together, we found clear evidence for functional distinctions between vegetation classes, suggesting strong environmental filtering at this scale, most likely driven by fire dynamics. In contrast, there was little evidence of filtering effects along environmental gradients within vegetation classes, suggesting that assembly processes are largely neutral at this scale, likely the result of very high functional redundancy among species in the regional species pool

Baviaanskloof percent cover, trait, and environment dataset

A dataset combining trait measurements for species observed in releve plots in the Baviaankloof region of South Africa. Environmental conditions at those plots also included

Processes of plant community assembly in the environmentally heterogeneous, high biodiversity Baviaanskloof Mega-reserve

<p>A talk about community assembly in the Baviaanskloof region of South Africa given at the symposium Plant Diversity in the GCFR: From Genomes to Biomes</p

Insights into Supramolecular Sites Responsible for Complete Separation of Biomass-Derived Phenolics and Glucose in Metal–Organic Framework NU-1000

The molecular origins of adsorption of lignin-derived phenolics to metal–organic framework NU-1000 are investigated from aqueous solution as well as in competitive mode with glucose present in the same aqueous mixture. A comparison of adsorption equilibrium constants (<i>K</i>_ads) for phenolics functionalized with either carboxylic acid or aldehyde substituents demonstrated only a slight increase (less than a factor of 6) for the former according to both experiments and calculations. This small difference in <i>K</i>_ads between aldehyde and carboxylic-acid substituted adsorbates is consistent with the pyrene unit of NU-1000 as the adsorption site, rather than the zirconia nodes, while at saturation coverage, the adsorption capacity suggests multiple guests per pyrene. Experimental standard free energies of adsorption directly correlated with the molecular size and electronic structure calculations confirmed this direct relationship, with the pyrene units as adsorption site. The underlying origins of this relationship are grounded in noncovalent π–π interactions as being responsible for adsorption, the same interactions present in the condensed phase of the phenolics, which to a large extent govern their heat of vaporization. Thus, NU-1000 acts as a preformed aromatic cavity for driving aromatic guest adsorption from aqueous solution and does so specifically without causing detectable glucose adsorption from aqueous solution, thereby achieving complete glucose–phenolics separations. The reusability of NU-1000 during an adsorption/desorption cycle was good, even with some of the phenolic compounds with greatest affinity not easiliy removed with water and ethanol washes at room temperature. A competitive adsorption experiment gave an upper bound for <i>K</i>_ads for glucose of at most 0.18 M^–1, which can be compared with <i>K</i>_ads for the phenolics investigated here, which fell in the range of 443–42 639 M^–1. The actual value of <i>K</i>_ads for glucose may be much closer to zero given the lack of observed glucose uptake with NU-1000 as adsorbent

The contribution of the nonhomologous region of Prs1 to the maintenance of cell wall integrity and cell viability

Item does not contain fulltextThe gene products of the five-membered PRS gene family in Saccharomyces cerevisiae have been shown to exist as three minimal functional entities, Prs1/Prs3, Prs2/Prs5, and Prs4/Prs5, each capable of supporting cell viability. The Prs1/Prs3 heterodimer can be regarded as the most important because its loss causes temperature sensitivity. It has been shown that the GFP signal generated by an integrated GFP-Prs1 construct is lost in the absence of Prs3. In addition to interacting with Prs3, Prs1 also interacts with Slt2, the MAPK of the cell wall integrity (CWI) pathway. Lack of the nonhomologous region (NHR1-1) located centrally in Prs1 abolished the temperature-induced increase in Rlm1 expression. Furthermore, in vitro point mutations generated in PRS1 corresponding to missense mutations associated with human neuropathies or in the divalent cation and/or 5-phosphoribosyl-1(alpha)-pyrophosphate binding sites also display increased Rlm1 expression at 30 degrees C and 37 degrees C and most give rise to caffeine sensitivity. Human PRPS1 cDNA cannot rescue the synthetic lethality of a prs1Delta prs5Delta strain because it lacks sequences corresponding to NHR1-1 of yeast Prs1. The correlation between caffeine sensitivity and increased basal expression of Rlm1 in the altered versions of PRS1 can be extended to their inability to rescue the synthetic lethality of a prs1Delta prs5Delta strain implying that impaired CWI may contribute to the observed loss of viability