No net effect of host density on tick‐borne disease hazard due to opposing roles of vector amplification and pathogen dilution

To better understand vector‐borne disease dynamics, knowledge of the ecological interactions between animal hosts, vectors, and pathogens is needed. The effects of hosts on disease hazard depends on their role in driving vector abundance and their ability to transmit pathogens. Theoretically, a host that cannot transmit a pathogen could dilute pathogen prevalence but increase disease hazard if it increases vector population size. In the case of Lyme disease, caused by Borrelia burgdorferi s.l. and vectored by Ixodid ticks, deer may have dual opposing effects on vectors and pathogen: deer drive tick population densities but do not transmit B. burgdorferi s.l. and could thus decrease or increase disease hazard. We aimed to test for the role of deer in shaping Lyme disease hazard by using a wide range of deer densities while taking transmission host abundance into account. We predicted that deer increase nymphal tick abundance while reducing pathogen prevalence. The resulting impact of deer on disease hazard will depend on the relative strengths of these opposing effects. We conducted a cross‐sectional survey across 24 woodlands in Scotland between 2017 and 2019, estimating host (deer, rodents) abundance, questing Ixodes ricinus nymph density, and B. burgdorferi s.l. prevalence at each site. As predicted, deer density was positively associated with nymph density and negatively with nymphal infection prevalence. Overall, these two opposite effects canceled each other out: Lyme disease hazard did not vary with increasing deer density. This demonstrates that, across a wide range of deer and rodent densities, the role of deer in amplifying tick densities cancels their effect of reducing pathogen prevalence. We demonstrate how noncompetent host density has little effect on disease hazard even though they reduce pathogen prevalence, because of their role in increasing vector populations. These results have implications for informing disease mitigation strategies, especially through host management.     

Characterization of photodamage to escherichia coli in optical traps

Optical tweezers (infrared laser-based optical traps) have emerged as a powerful tool in molecular and cell biology. However, their usefulness has been limited, particularly in vivo, by the potential for damage to specimens resulting from the trapping laser. Relatively little is known about the origin of this phenomenon. Here we employed a wavelength-tunable optical trap in which the microscope objective transmission was fully characterized throughout the near infrared, in conjunction with a sensitive, rotating bacterial cell assay. Single cells of Escherichia coli were tethered to a glass coverslip by means of a single flagellum: such cells rotate at rates proportional to their transmembrane proton potential (. J. Mol. Biol. 138:541-561). Monitoring the rotation rates of cells subjected to laser illumination permits a rapid and quantitative measure of their metabolic state. Employing this assay, we characterized photodamage throughout the near-infrared region favored for optical trapping (790-1064 nm). The action spectrum for photodamage exhibits minima at 830 and 970 nm, and maxima at 870 and 930 nm. Damage was reduced to background levels under anaerobic conditions, implicating oxygen in the photodamage pathway. The intensity dependence for photodamage was linear, supporting a single-photon process. These findings may help guide the selection of lasers and experimental protocols best suited for optical trapping work.     

Striped catfish (Pangasianodon hypophthalmus) could be suitable for coastal aquaculture

Salinity intrusion in the coastal freshwater rivers due to climate change and construction of the dam in the upstream rivers are alarming in aquaculture. Hence, an experiment was conducted to know the effects of salinity on growth performance, hemato‐biochemical parameters and erythrocytes structure in a commercially cultivable catfish species, striped catfish (Pangasianodon hypophthalmus). Firstly, median lethal concentration (LC₅₀) of salinity for striped catfish was determined and then the fish were exposed to three salinity conditions (4, 8 and 12‰) and a control (0‰). Fish were sacrificed at day 7, 14, 28 and 56 after the start of salinity exposure. The 96 hr LC₅₀ value was found to be 14.87‰. Salinity levels from freshwater to 8‰ showed optimal conditions with high survival rate and good growth performances of fish in terms of weight gain and specific growth rate (SGR). Interestingly, the lowest food conversion ratio (FCR) was found in 4‰ group. The hemoglobin (Hb) level and number of red blood cells (RBCs) were found to be decreased significantly in 8 and 12‰ compared to 0 and 4‰ at the initial days of exposure, while number of white blood cells (WBCs) and glucose level showed opposite scenario. Frequencies of ENA (erythrocytic nuclear abnormalities) and ECA (erythrocytic cellular abnormalities) were significantly increased with increasing salinities in the initial days of exposure. Overall, findings of the present study revealed that striped catfish might be suitable fish species for culture in the brackish water containing salinity up to 10‰.     

Mathematical modelling of the mitochondrial apoptosis pathway

Mitochondria are pivotal for cellular bioenergetics, but are also a core component of the cell death machinery. Hypothesis-driven research approaches have greatly advanced our understanding of the role of mitochondria in cell death and cell survival, but traditionally focus on a single gene or specific signalling pathway at a time. Predictions originating from these approaches become limited when signalling pathways show increased complexity and invariably include redundancies, feedback loops, anisotropies or compartmentalisation. By introducing methods from theoretical chemistry, control theory, and biophysics, computational models have provided new quantitative insights into cell decision processes and have led to an increased understanding of the key regulatory principles of apoptosis. In this review, we describe the currently applied modelling approaches, discuss the suitability of different modelling techniques, and evaluate their contribution to the understanding of the mitochondrial apoptosis pathway. This article is part of a Special Issue entitled Mitochondria: the deadly organelle.     

High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal

Background

The activities of mitochondrial complex III (ubiquinol-cytochrome c reductase, EC 1.10.2.2) and complex IV (cytochrome c oxidase EC 1.9.3.1) are reduced by 30-70% in Huntington's disease and Alzheimer's disease, respectively, and are associated with excitotoxic cell death in these disorders. In this study, we investigated the control that complexes III and complex IV exert on glutamate release from the isolated nerve terminal.

Results

Inhibition of complex III activity by 60-90% was necessary for a major increase in the rate of Ca²⁺-independent glutamate release to occur from isolated nerve terminals (synaptosomes) depolarized with 4-aminopyridine or KCl. Similarly, an 85-90% inhibition of complex IV activity was required before a major increase in the rate of Ca²⁺-independent glutamate release from depolarized synaptosomes was observed. Inhibition of complex III and IV activities by ~ 60% and above was required before rates of glutamate efflux from polarized synaptosomes were increased.

Conclusions

These results suggest that nerve terminal mitochondria possess high reserves of complex III and IV activity and that high inhibition thresholds must be reached before excess glutamate is released from the nerve terminal. The implications of the results in the context of the relationship between electron transport chain enzyme deficiencies and excitotoxicity in neurodegenerative disorders are discussed.     

Effects of age,replicative lifespan and growth rate of human nucleus pulposus cells on selecting age range for cell-based biological therapies for degenerative disc diseases

Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases.     

Characterization of AmphiF-spondin reveals the modular evolution of chordate F-spondin genes

The F-spondin genes are a family of extracellular matrix molecules united by two conserved domains, FS1 and FS2, at the amino terminus plus a variable number of thrombospondin repeats at the carboxy terminus. Currently, characterized members include a single gene in Drosophila and multiple genes in vertebrates. The vertebrate genes are expressed in the midline of the developing embryo, primarily in the floor plate of the neural tube. To investigate the evolution of chordate F-spondin genes, I have used the basal position in chordate phylogeny of the acraniate amphioxus. A single F-spondin-related gene, named AmphiF-spondin, was isolated from amphioxus. Based on molecular phylogenetics, AmphiF-spondin is closely related to a particular subgroup of vertebrate F-spondin genes that encode six thrombospondin repeats. However, unlike these genes, expression of AmphiF-spondin is not confined to the midline but is found through most of the central nervous system. Additionally, AmphiF-spondin has lost three thrombospondin repeats and gained two fibronectin type III repeats, one of which has strong identity to a fibronectin type III repeat from Deleted in Colorectal Cancer (DCC). Taken together, these results suggest a complex evolutionary history for chordate F-spondin genes that includes (1) domain loss, (2) domain gain by tandem duplication and divergence of existing domains, and (3) gain of heterologous domains by exon shuffling.