Lack of prion transmission by sexual or parental routes in experimentally infected hamsters

Prion diseases are a group of neurodegenerative disorders affecting humans as well as captive and wild animals. The mechanisms and routes governing the natural spread of prions are not completely understood and several hypotheses have been proposed. In this study, we analyzed the effect of gender in prion incubation period, as well as the possibility of prion transmission by sexual and parental contact using 263K infected hamsters as a model. Our results show that males have significantly longer incubation periods compared with females when exposed to the same quantity of infectious material. Importantly, no evidence of sexual or parental prion transmission was found, even 500 d after sexual contact or birth, respectively. Western blotting and PMCA were unable to detect sub-clinical levels of PrP^Sc in experimental subjects, suggesting a complete absence of prion transmission by these routes. Our results show that sexual and parental transmission of prions does not occur in this model. It remains to be studied whether this conclusion is valid also for other prion strains and species.     

Integrated Application of Multiomics Strategies Provides Insights Into the Environmental Hypoxia Response in Pelteobagrus vachelli Muscle

Increasing pressures on aquatic ecosystems because of pollutants, nutrient enrichment, and global warming have severely depleted oxygen concentrations. This sudden and significant lack of oxygen has resulted in persistent increases in fish mortality rates. Revealing the molecular mechanism of fish hypoxia adaptation will help researchers to find markers for hypoxia induced by environmental stress. Here, we used a multiomics approach to identify several hypoxia-associated miRNAs, mRNAs, proteins, and metabolites involved in diverse biological pathways in the muscles of Pelteobagrus vachelli. Our findings revealed significant hypoxia-associated changes in muscles over 4 h of hypoxia exposure and discrete tissue-specific patterns. We have previously reported that P. vachelli livers exhibit increased anaerobic glycolysis, heme synthesis, erythropoiesis, and inhibit apoptosis when exposed to hypoxia for 4 h. However, the opposite was observed in muscles. According to our comprehensive analysis, fishes show an acute response to hypoxia, including activation of catabolic pathways to generate more energy, reduction of biosynthesis to decrease energy consumption, and shifting from aerobic to anaerobic metabolic contributions. Also, we found that hypoxia induced muscle dysfunction by impairing mitochondrial function, activating inflammasomes, and apoptosis. The hypoxia-induced mitochondrial dysfunction enhanced oxidative stress, apoptosis, and further triggered interleukin-1β production via inflammasome activation. In turn, interleukin-1β further impaired mitochondrial function or apoptosis by suppressing downstream mitochondrial biosynthesis–related proteins, thus resulting in a vicious cycle of inflammasome activation and mitochondrial dysfunction. Our findings contribute meaningful insights into the molecular mechanisms of hypoxia, and the methods and study design can be utilized across different fish species.     

Fatal attraction: vegetation responses to nutrient inputs attract herbivores to infectious anthrax carcass sites

Parasites can shape the foraging behaviour of their hosts through cues indicating risk of infection. When cues for risk co-occur with desired traits such as forage quality, individuals face a trade-off between nutrient acquisition and parasite exposure. We evaluated how this trade-off may influence disease transmission in a 3-year experimental study of anthrax in a guild of mammalian herbivores in Etosha National Park, Namibia. At plains zebra (Equus quagga) carcass sites we assessed (i) carcass nutrient effects on soils and grasses, (ii) concentrations of Bacillus anthracis (BA) on grasses and in soils, and (iii) herbivore grazing behaviour, compared with control sites, using motion-sensing camera traps. We found that carcass-mediated nutrient pulses improved soil and vegetation, and that BA is found on grasses up to 2 years after death. Host foraging responses to carcass sites shifted from avoidance to attraction, and ultimately to no preference, with the strength and duration of these behavioural responses varying among herbivore species. Our results demonstrate that animal carcasses alter the environment and attract grazing hosts to parasite aggregations. This attraction may enhance transmission rates, suggesting that hosts are limited in their ability to trade off nutrient intake with parasite avoidance when relying on indirect cues.     

An S-glutathiomimetic Provides Structural Insights into Stromal Interaction Molecule-1 Regulation

Stromal interaction molecule 1 (STIM1) is an endo/sarcoplasmic reticulum (ER/SR) calcium (Ca²⁺) sensing protein that regulates store-operated calcium entry (SOCE). In SOCE, STIM1 activates Orai1-composed Ca²⁺ channels in the plasma membrane (PM) after ER stored Ca²⁺ depletion. S-Glutathionylation of STIM1 at Cys56 evokes constitutive SOCE in DT40 cells; however, the structural and biophysical mechanisms underlying the regulation of STIM1 by this modification are poorly defined. By establishing a protocol for site-specific STIM1 S-glutathionylation using reduced glutathione and diamide, we have revealed that modification of STIM1 at either Cys49 or Cys56 induces thermodynamic destabilization and conformational changes that result in increased solvent-exposed hydrophobicity. Further, S-glutathionylation or point-mutation of Cys56 reduces Ca²⁺ binding affinity, as measured by intrinsic fluorescence and far-UV circular dichroism spectroscopies. Solution NMR showed S-glutathionylated-induced perturbations in STIM1 are localized to the α1 helix of the canonical EF-hand, the α3 and α4 helices of the non-canonical EF-hand and α6 and α8 helices of the SAM domain. Finally, we designed an S-glutathiomimetic mutation that strongly recapitulates the structural, biophysical and functional effects within the STIM1 luminal domain and we envision to be another tool for understanding the effects of protein S-glutathionylation in vitro, in cellulo and in vivo.     

A simple mathematical model for Ebola in Africa

We deal with the following question: Can the consumption of contaminated bush meat, the funeral practices and the environmental contamination explain the recurrence and persistence of Ebola virus disease outbreaks in Africa? We develop an SIR-type model which, incorporates both the direct and indirect transmissions in such a manner that there is a provision of Ebola viruses. We prove that the full model has one (endemic) equilibrium which is locally asymptotically stable whereas, it is globally asymptotically stable in the absence of the Ebola virus shedding in the environment. For the sub-model without the provision of Ebola viruses, the disease dies out or stabilizes globally at an endemic equilibrium. At the endemic level, the number of infectious is larger for the full model than for the sub-model without provision of Ebola viruses. We design a nonstandard finite difference scheme, which preserves the dynamics of the model. Numerical simulations are provided.     

Single vesicle tracking for studying synaptic vesicle dynamics in small central synapses

Sustained neurotransmission is driven by a continuous supply of synaptic vesicles to the release sites and modulated by synaptic vesicle dynamics. However, synaptic vesicle dynamics in synapses remain elusive because of technical limitations. Recent advances in fluorescence imaging techniques have enabled the tracking of single synaptic vesicles in small central synapses in living neurons. Single vesicle tracking has uncovered a wealth of new information about synaptic vesicle dynamics both within and outside presynaptic terminals, showing that single vesicle tracking is an effective tool for studying synaptic vesicle dynamics. Particularly, single vesicle tracking with high spatiotemporal resolution has revealed the dependence of synaptic vesicle dynamics on the location, stages of recycling, and neuronal activity. This review summarizes the recent findings from single synaptic vesicle tracking in small central synapses and their implications in synaptic transmission and pathogenic mechanisms of neurodegenerative diseases.     

Albedo and transmittance of short-wave radiation for bat wings

1. 1.|Independent of their diverse feeding habits almost all bats are nocturnal. One hypothesis for chiropteran nocturnality is that bats flying in the day experience fatal hyperthermia because their wings take up significant amounts of short-wave radiation which they are unable to dissipate convectively. Factors that will critically affect a bat's susceptibility to overheating are the albedo and transmittance of wing membranes to short-wave radiation.

2. 2.|Albedo of taut segments of bat wings from four species of insectivorous bats and one Pteropid varied between 0.026 (for Rhinolophus hipposideros) and 0.069 (Plecotus auritus).

3. 3.|Transmittance exceeded albedo in all species studied and varied from 0.077 (Pipistrellus pipistrellus) to 0.194 (P. auritus). In this small sample there was no relationship between albedo and transmittance.

4. 4.|Total absorbed short-wave radiation amounted to between 70 and 92% of the incident radiation, and averaged 81.9% (SE = 2.4%, n = 9). Given a clear sky short-wave flux density of about 971 W · m⁻² a typical small insectivorous bat (5g, wing AREA = 0.013 m², ABSORPTIVITY = 81.9%) with fully outstretched wings and the sun directly overhead would absorb about 10.65 W, compared with the maximum endogenous heat production from flight of 0.83 W.

5. 5.|Predicted maximum exogenous heat load relative to maximum endogenous heat load declined as a function of body mass, however, even in the largest known bats (1.4 kg) the exogenous burden exceeded by a factor of 3 the endogenous heat load.