Biology subjects

Blaum, N.

Publications and source records attributed to Blaum, N..

3 recordsLinked to original sources

bioRxiv2022

Release site plasticity via Unc13A regulatory domains mediates synaptic short-term facilitation and homeostatic potentiation

Chemical synaptic transmission relies on neurotransmitter release from presynaptic release sites and on transmitter-sensing by the postsynaptic cell. Presynaptic plasticity increasing neurotransmitter release achieves two fundamental nervous system functions: It tunes some synapses to be more responsive to millisecond repetitive activation and it maintains signals when postsynaptic transmitter sensitivity is reduced. How enhanced neurotransmitter release is achieved in these phenomena, termed short-term facilitation and homeostatic potentiation, remains unknown. We combine mathematical modeling and experimental analysis of Drosophila neuromuscular junction model synapses to elucidate the molecular mechanisms underlying these forms of plasticity. Our results indicate that both phenomena depend on a rapid increase in the participation of neurotransmitter release sites which is controlled by the regulatory domains of the evolutionarily conserved (M)Unc13A protein that bind Ca2+/Calmodulin and diacylglycerol. Mutation of the Calmodulin binding (CaM) domain increased baseline transmission and impaired both short-term facilitation and acute homeostatic potentiation. Mathematical modeling indicated that these defects result from too many release sites participating at rest combined with the inability to plastically further increase their number. Super-resolution microscopy revealed that this coincided with a redistribution of Unc13As functionally essential MUN domain closer to the synaptic plasma membrane, which may constitute the molecular switch to increase release site participation. Similar consequences (enhanced baseline transmission, block of both short-term facilitation and homeostatic potentiation) were caused by the acute pharmacological activation of the C1 domain of wildtype Unc13A using phorbol esters. This treatment had no effect on Unc13A CaM domain mutants, indicating that both the CaM and C1 domains activate a binary release site switch. Thus, our findings indicate that Unc13A regulatory domains are tuned to integrate a multitude of signals on various timescales to switch release site participation for synaptic plasticity.

neuroscience↗

bioRxiv2022

Clarifying space use concepts in ecology: range vs. occurrence distributions

Quantifying animal movements is necessary for answering a wide array of research questions in ecology and conservation biology. Consequently, ecologists have made considerable efforts to identify the best way to estimate an animals home range, and many methods of estimating home ranges have arisen over the past half century. Most of these methods fall into two distinct categories of estimators that have only recently been described in statistical detail: those that measure range distributions (methods such as Kernel Density Estimation that quantify the long-run behavior of a movement process that features restricted space use) and those that measure occurrence distributions (methods such as Brownian Bridge Movement Models and the Correlated Random Walk Library that quantify uncertainty in an animal movement path during a specific period of observation). In this paper, we use theory, simulations, and empirical analysis to demonstrate the importance of applying these two classes of space use estimators appropriately and distinctly. Conflating range and occurrence distributions can have serious consequences for ecological inference and conservation practice. For example, in most situations, home-range estimates quantified using occurrence estimators are too small, and this problem is exacerbated by ongoing improvements in tracking technology that enable more frequent and more accurate data on animal movements. We encourage researchers to use range estimators to estimate the area of home ranges and occurrence estimators to answer other questions in movement ecology, such as when and where an animal crosses a linear feature, visits a location of interest, or interacts with other animals. Open Research StatementTracking data on Aepyceros melampus, Beatragus hunteri, Bycanistes bucinator, Cerdocyon thous, Eulemur rufifrons, Glyptemys insculpta, Gyps coprotheres, Madoqua guentheri, Ovis canadensis, Propithecus verreauxi, Sus scrofa, and Ursus arctos are publicly archived in the Dryad repository (Noonan et al. 2018; https://doi.org/10.5061/dryad.v5051j2), as are data from Procapra gutturosa (Fleming et al. 2014a; https://doi.org/10.5061/dryad.45157). Data on Panthera onca were taken from (Morato et al. 2018). Additional data are publicly archived in the Movebank repository under the following identifiers: Canis latrans, 8159699; Canis lupus, 8159399; Chrysocyon brachyurus, 18156143; Felis silvestris, 40386102; Gyps africanus, 2919708; Lepus europaeus, 25727477; Martes pennanti, 2964494; Panthera leo, 220229; Papio cynocephalus, 222027; Syncerus caffer, 1764627; Tapirus terrestris, 443607536; Torgos tracheliotus, 2919708; and Ursus americanus, 8170674.

ecology↗

bioRxiv2022

Resource asynchrony and landscape homogenization as drivers of virulence evolution

In the last years, the emergence of zoonotic diseases and the frequency of disease outbreaks have increased substantially, fuelled by habitat encroachment and asynchrony of biological cycles due to global change. The virulence of these diseases is a key aspect for their success. In order to understand the complex processes of pathogen virulence evolution in the global change context, we adapted an established individual-based model of host-pathogen dynamics. Our model simulates a population of social hosts affected by an evolving pathogen in a dynamic landscape. Pathogen virulence evolution is explored by the inclusion of multiple strains in the model that differ in their transmission capability and lethality. Simultaneously, the hosts resource landscape is subjected to spatial and temporal dynamics, emulating effects of global change. We found an increase in pathogenic virulence and a shift in strain dominance with increasing landscape homogenisation. Our model further shows a trend to lower virulence pathogens being dominant in fragmented landscapes, although pulses of highly virulent strains are expected under resource asynchrony. While all landscape scenarios favour coexistence of low and high virulent strains, when host density increases, the high virulence strains capitalize on the high possibility for transmission and are likely to become dominant. Author SummaryDisease outbreaks primarily caused by contact with animals are increasing in recent years, related to habitat destruction and altered biological cycles due to climate change. Pathogens associated with such outbreaks will be more successful the more effectively they can spread in a population. Thus, understanding the conditions over which those pathogens evolve will help us to limit the impact of disease outbreaks in the future. To this end, we used an individual based model that allowed us to study different scenarios. Our model had three main components: a host-pathogen system, a dynamic resource landscape with different degrees of fragmentation and temporal resource mismatches. We used dynamic landscapes with varying resource amounts over the years and consisting of multiple large or smaller habitat clusters. Our simulations showed that homogenous landscapes resulted in higher virulent pathogens and fragmented landscapes in lesser virulent pathogens. However, across all scenarios, high and low virulent pathogen strains were able to coexist.

ecology↗