Experimental evidence of size-selective harvest and environmental stochasticity effects on population demography,fluctuations and non-linearity

Theory and analyses of fisheries data sets indicate that harvesting can alter population structure and destabilise non-linear processes, which increases population fluctuations. We conducted a factorial experiment on the population dynamics of Daphnia magna in relation to size-selective harvesting and stochasticity of food supply. Harvesting and stochasticity treatments both increased population fluctuations. Timeseries analysis indicated that fluctuations in control populations were non-linear, and non-linearity increased substantially in response to harvesting. Both harvesting and stochasticity induced population juvenescence, but harvesting did so via the depletion of adults, whereas stochasticity increased the abundance of juveniles. A fitted fisheries model indicated that harvesting shifted populations towards higher reproductive rates and larger-magnitude damped oscillations that amplify demographic noise. These findings provide experimental evidence that harvesting increases the non-linearity of population fluctuations and that both harvesting and stochasticity increase population variability and juvenescence.     

Limited seed retention during winter inhibits vegetation establishment in spring,affecting lateral marsh expansion capacity

Coastal systems worldwide deliver vital ecosystem services, such as biodiversity, carbon sequestration, and coastal protection. Effectivity of these ecosystem services increases when vegetation is present. Understanding the mechanisms behind vegetation establishment in bio‐geomorphic systems is necessary to understand their ability to recover after erosive events and potential adaptations to climate change. In this study, we examined how seed availability affects vegetation establishment in the salt marsh–intertidal flat transition zone: the area with capacity for lateral marsh expansion. This requires vegetation establishment; therefore, seed availability is essential. In a 6‐month field experiment, we simulated a before and after winter seed dispersal at two locations, the salt‐marsh vegetation edge and the intertidal flat, and studied seed retention, the seed bank, and the seed viability of three pioneer marsh species: Salicornia procumbens, Aster tripolium, and Spartina anglica. During winter storm conditions, all supplied seeds eroded away with the sediment surface layer. After winter, supplied seeds from all three species were retained, mostly at the surface while 9% was bioturbated downwards. In the natural seed bank, A. tripolium and S. anglica were practically absent while S. procumbens occurred more frequently. The viability of S. procumbens seeds was highest at the surface, between 80% and 90%. The viability quickly decreased with depth, although viable S. procumbens seeds occurred up to 15 cm depth. Only when seeds were supplied after winter, many S. procumbens and some S. anglica individuals did establish successfully in the transition zone. Viable seed availability formed a vegetation establishment threshold, even with a local seed source. Our results suggest that, although boundary conditions such as elevation, inundation, and weather conditions were appropriate for vegetation establishment in spring, the soil surface in winter can be so dynamic that it limits lateral marsh expansion. These insights can be used for designing effective nature‐based coastal protection.     

Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons

Mesencephalic dopaminergic (MesDA) neurons play crucial roles in motor and behavioral processes; their loss in Parkinson's disease (PD) results in striatal dopamine (DA) deficiency and hypokinetic movement disorder. The Pitx3 homeobox gene is expressed in the MesDA system. We now show that only a subset of MesDA neurons express Pitx3 and that in Pitx3-deficient aphakia mice, this subset is progressively lost by apoptosis during fetal (substantia nigra, SN) and postnatal (ventral tegmental area) development, resulting in very low striatal DA and akinesia. Similar to human PD, dorsal SN neurons (which are Pitx3 negative) are spared in mutant mice. Thus, Pitx3 defines a pathway for survival of neurons that are implicated in PD and that are required for spontaneous locomotor activity.     

Functional Human Liver Preservation and Recovery by Means of Subnormothermic Machine Perfusion

There is currently a severe shortage of liver grafts available for transplantation. Novel organ preservation techniques are needed to expand the pool of donor livers. Machine perfusion of donor liver grafts is an alternative to traditional cold storage of livers and holds much promise as a modality to expand the donor organ pool. We have recently described the potential benefit of subnormothermic machine perfusion of human livers. Machine perfused livers showed improving function and restoration of tissue ATP levels. Additionally, machine perfusion of liver grafts at subnormothermic temperatures allows for objective assessment of the functionality and suitability of a liver for transplantation. In these ways a great many livers that were previously discarded due to their suboptimal quality can be rescued via the restorative effects of machine perfusion and utilized for transplantation. Here we describe this technique of subnormothermic machine perfusion in detail. Human liver grafts allocated for research are perfused via the hepatic artery and portal vein with an acellular oxygenated perfusate at 21 °C.     

Huntingtin-associated Protein 1 (HAP1) Is a cGMP-dependent Kinase Anchoring Protein (GKAP) Specific for the cGMP-dependent Protein Kinase Iβ Isoform

Protein-protein interactions are important in providing compartmentalization and specificity in cellular signal transduction. Many studies have hallmarked the well designed compartmentalization of the cAMP-dependent protein kinase (PKA) through its anchoring proteins. Much less data are available on the compartmentalization of its closest homolog, cGMP-dependent protein kinase (PKG), via its own PKG anchoring proteins (GKAPs). For the enrichment, screening, and discovery of (novel) PKA anchoring proteins, a plethora of methodologies is available, including our previously described chemical proteomics approach based on immobilized cAMP or cGMP. Although this method was demonstrated to be effective, each immobilized cyclic nucleotide did not discriminate in the enrichment for either PKA or PKG and their secondary interactors. Hence, with PKG signaling components being less abundant in most tissues, it turned out to be challenging to enrich and identify GKAPs. Here we extend this cAMP-based chemical proteomics approach using competitive concentrations of free cyclic nucleotides to isolate each kinase and its secondary interactors. Using this approach, we identified Huntingtin-associated protein 1 (HAP1) as a putative novel GKAP. Through sequence alignment with known GKAPs and secondary structure prediction analysis, we defined a small sequence domain mediating the interaction with PKG Iβ but not PKG Iα. In vitro binding studies and site-directed mutagenesis further confirmed the specificity and affinity of HAP1 binding to the PKG Iβ N terminus. These data fully support that HAP1 is a GKAP, anchoring specifically to the cGMP-dependent protein kinase isoform Iβ, and provide further evidence that also PKG spatiotemporal signaling is largely controlled by anchoring proteins.     

Acquisition of macrophage tropism during the pathogenesis of feline infectious peritonitis is determined by mutations in the feline coronavirus spike protein

In feline coronavirus (FCoV) pathogenesis, the ability to infect macrophages is an essential virulence factor. Whereas the low-virulence feline enteric coronavirus (FECV) isolates primarily replicate in the epithelial cells of the enteric tract, highly virulent feline infectious peritonitis virus (FIPV) isolates have acquired the ability to replicate efficiently in macrophages, which allows rapid dissemination of the virulent virus throughout the body. FIPV 79-1146 and FECV 79-1683 are two genetically closely related representatives of the two pathotypes. Whereas FECV 79-1683 causes at the most a mild enteritis in young kittens, FIPV 79-1146 almost invariably induces a lethal peritonitis. The virulence phenotypes correlate with the abilities of these viruses to infect and replicate in macrophages, a feature of FIPV 79-1146 but not of FECV 79-1683. To identify the genetic determinants of the FIPV 79-1146 macrophage tropism, we exchanged regions of its genome with the corresponding parts of FECV 79-1683, after which the ability of the FIPV/FECV hybrid viruses to infect macrophages was tested. Thus, we established that the FIPV spike protein is the determinant for efficient macrophage infection. Interestingly, this property mapped to the C-terminal domain of the protein, implying that the difference in infection efficiency between the two viruses is not determined at the level of receptor usage, which we confirmed by showing that infection by both viruses was equally blocked by antibodies directed against the feline aminopeptidase N receptor. The implications of these findings are discussed.     

Is There a Role for Combined EMG-fMRI in Exploring the Pathophysiology of Essential Tremor and Improving Functional Neurosurgery?

Background

Functional MRI combined with electromyography (EMG-fMRI) is a new technique to investigate the functional association of movement to brain activations. Thalamic stereotactic surgery is effective in reducing tremor. However, while some patients have satisfying benefit, others have only partial or temporary relief. This could be due to suboptimal targeting in some cases. By identifying tremor-related areas, EMG-fMRI could provide more insight into the pathophysiology of tremor and be potentially useful in refining surgical targeting.

Objective

Aim of the study was to evaluate whether EMG-fMRI could detect blood oxygen level dependent brain activations associated with tremor in patients with Essential Tremor. Second, we explored whether EMG-fMRI could improve the delineation of targets for stereotactic surgery.

Methods

Simultaneous EMG-fMRI was performed in six Essential Tremor patients with unilateral thalamotomy. EMG was recorded from the trembling arm (non-operated side) and from the contralateral arm (operated side). Protocols were designed to study brain activations related to voluntary muscle contractions and postural tremor.

Results

Analysis with the EMG regressor was able to show the association of voluntary movements with activity in the contralateral motor cortex and supplementary motor area, and ipsilateral cerebellum. The EMG tremor frequency regressor showed an association between tremor and activity in the ipsilateral cerebellum and contralateral thalamus. The activation spot in the thalamus varied across patients and did not correspond to the thalamic nucleus ventralis intermedius.

Conclusion

EMG-fMRI is potentially useful in detecting brain activations associated with tremor in patients with Essential Tremor. The technique must be further developed before being useful in supporting targeting for stereotactic surgery.     

Gain, preservation, and loss of a group 1a coronavirus accessory glycoprotein

Coronaviruses are positive-strand RNA viruses of extraordinary genetic complexity and diversity. In addition to a common set of genes for replicase and structural proteins, each coronavirus may carry multiple group-specific genes apparently acquired through relatively recent heterologous recombination events. Here we describe an accessory gene, ORF3, unique to canine coronavirus type I (CCoV-I) and characterize its product, glycoprotein gp3. Whereas ORF3 is conserved in CCoV-I, only remnants remain in CCoV-II and CCoV-II-derived porcine and feline coronaviruses. Our findings provide insight into the evolutionary history of coronavirus group 1a and into the dynamics of gain and loss of accessory genes.