Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice

Gold nanoparticles (GNPs) offer a great promise in biomedicine. Currently, there is no data available regarding the accumulation of nanoparticles in vivo after repeated administration. The purpose of the present study was to evaluate the bioaccumulation and toxic effects of different doses (40, 200, and 400 μg/kg/day) of 12.5 nm GNPs upon intraperitoneal administration in mice every day for 8 days.The gold levels in blood did not increase with the dose administered, whereas in all the organs examined there was a proportional increase on gold, indicating efficient tissue uptake. Although brain was the organ containing the lowest quantity of injected GNPs, our data suggest that GNPs are able to cross the blood-brain barrier and accumulate in the neural tissue. Importantly, no evidence of toxicity was observed in any of the diverse studies performed, including survival, behavior, animal weight, organ morphology, blood biochemistry and tissue histology. The results indicate that tissue accumulation pattern of GNPs depend on the doses administered and the accumulation of the particles does not produce sub-acute physiological damage.     

Zinc limitation triggers anticipatory adaptations in Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) has complex and dynamic interactions with the human host, and subpopulations of Mtb that emerge during infection can influence disease outcomes. This study implicates zinc ion (Zn²⁺) availability as a likely driver of bacterial phenotypic heterogeneity in vivo. Zn²⁺ sequestration is part of “nutritional immunity”, where the immune system limits micronutrients to control pathogen growth, but this defense mechanism seems to be ineffective in controlling Mtb infection. Nonetheless, Zn²⁺-limitation is an environmental cue sensed by Mtb, as calprotectin triggers the zinc uptake regulator (Zur) regulon response in vitro and co-localizes with Zn²⁺-limited Mtb in vivo. Prolonged Zn²⁺ limitation leads to numerous physiological changes in vitro, including differential expression of certain antigens, alterations in lipid metabolism and distinct cell surface morphology. Furthermore, Mtb enduring limited Zn²⁺ employ defensive measures to fight oxidative stress, by increasing expression of proteins involved in DNA repair and antioxidant activity, including well described virulence factors KatG and AhpC, along with altered utilization of redox cofactors. Here, we propose a model in which prolonged Zn²⁺ limitation defines a population of Mtb with anticipatory adaptations against impending immune attack, based on the evidence that Zn²⁺-limited Mtb are more resistant to oxidative stress and exhibit increased survival and induce more severe pulmonary granulomas in mice. Considering that extracellular Mtb may transit through the Zn²⁺-limited caseum before infecting naïve immune cells or upon host-to-host transmission, the resulting phenotypic heterogeneity driven by varied Zn²⁺ availability likely plays a key role during early interactions with host cells.     

Contact call diversity in natural beluga entrapments in an Arctic estuary: Preliminary evidence of vocal signatures in wild belugas

Broadband, pulsed contact calls have been described for captive and temporarily restrained belugas, but little information exists on their usage in the wild. We examined vocal production during 14 natural beluga entrapments in a shallow channel in Cunningham Inlet, as isolation events offer ideal contexts to study contact calls. Drone footage, overhead photos, and shore‐based photos confirmed the number of individuals and age composition in each entrapment. Contact calls comprised the majority (61%) of vocalizations produced by entrapped whales compared to the free‐ranging herd (10%). We divided contact calls into complex (80%), those with a stereotyped, spectrographically prominent component overlapping the pulse train that characterizes all beluga contact calls, and simple (20%), those with no overlapping component. For each entrapment, we generated a catalogue of complex contact call types, totaling 87 types. Our classification was corroborated both quantitatively and by 55 naïve human judges. Occasional instances of overlapping contact calls of the same type indicated dyadic production. The number of contact call types per entrapment was strongly related to (never exceeding) the number of individuals, excluding neonates. Although this suggests a system of vocal signatures in belugas, consistent with their fission‐fusion society and earlier findings, whether signature identity is encoded individually or shared with related animals remains unknown.     

Single-molecule anisotropy imaging

A novel method, single-molecule anisotropy imaging, has been employed to simultaneously study lateral and rotational diffusion of fluorescence-labeled lipids on supported phospholipid membranes. In a fluid membrane composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, in which the rotational diffusion time is on the order of the excited-state lifetime of the fluorophore rhodamine, a rotational diffusion constant, D(rot) = 7 x 10(7) rad(2)/s, was determined. The lateral diffusion constant, measured by direct analysis of single-molecule trajectories, was D(lat) = 3.5 x 10(-8) cm(2)/s. As predicted from the free-volume model for diffusion, the results exhibit a significantly enhanced mobility on the nanosecond time scale. For membranes of DPPC lipids in the L(beta) gel phase, the slow rotational mobility permitted the direct observation of the rotation of individual molecules characterized by D(rot) = 1.2 rad(2)/s. The latter data were evaluated by a mean square angular displacement analysis. The technique developed here should prove itself profitable for imaging of conformational motions of individual proteins on the time scale of milliseconds to seconds.     

The failed invasion of Harmonia axyridis in the Azores,Portugal: Climatic restriction or wrong population origin?

We tested two questions:(i)whether the climatic conditions of the Azorean Islands in Portugal may have restricted the invasion of Harmonia axyridis across this archipelago and(ii)determine what population of this species could have a higher probability of invading the islands.We used MaxEnt to project the climate requirements of different H.axyridis populations from three regions of the world,and the potential global niche of the species in the Azorean islands.Then we assessed the suitability of the islands for each of the three H.axyridis populations and global potential niche through histograms analysis,Principal Component Analysis(PCA)of climate variables,and a variable-by-variable assessment of the suitability response curves compared with the climatic conditions of the Azores.Climatic conditions of the Azores are less suitable for the U.S.and native Asian populations of H.axyridis,and more suitable for European populations and the global potential niche.The PCA showed that the climatic conditions of the islands differed from the climatic requirements of H.axyridis.This difference is mainly explained by precipitation of the wettest month,isothermality,and the minimum temperature of the coldest month.We concluded that the climatic conditions of the Azores could have influenced the establishment and spread of H.axyridis on these islands from Europe.Our results showed that abiotic resistance represented by the climate of the potentially colonizable zones could hinder the establishment of invasive insects,but it could vary depending of the origin of the colonizing population.     

A spin label study of the urinary bladder luminal membrane

Spin label experiments have been carried out on the urinary bladder luminal membrane of the bovine transitional epithelium employing the 5-, 7-, 12-, and 16-doxyl substituted stearic acid methyl esters, and compared for reference to similarly labeled bovine erythrocytes. The bladder membranes are significantly different from the bovine red blood cell membranes and show a lower order and polarity near the membrane surface. This fact and the general similarity of results for the bladder and isolated plaque membranes suggests that the highly organized proteins of the bladder membrane may act as a coat on the lipid bilayer and, while intrinsic in nature, do not significantly perturb the hydrophobic core of the lipid bilayer.     

Interferon therapy in acute lymphatic leukemia and hepatitis B in childhood

1. The use of interferon in hepatitis B will bring about a favourable course of the disease, which is reflected in a normalisation of liver function tests. 2. The concentration of surface antigens is distinctly reduced, with a lower titre remaining for a longer period of time. 3. The level of the dosage chosen seems to be optimal. However, treatment has to be continued for a period of several months, probably for about 1 year. 4. In childhood the side-effects of interferon are minimal, they are restricted to febrile reactions. 5. In our investigations no sure hematological deviations could be identified in the treatment with interferon. 6. The study must be complemented by analysing further antigens, such as E antigen, allowing the course of disease to be characterised more distinctly. 7. In order to give a final assessment of the therapy the observation of patients must be continued after terminating the treatment, the histological improvement in the further course having to be confirmed by liver biopsies.     

Neurotoxicity of Prion Peptides Mimicking the Central Domain of the Cellular Prion Protein

The physiological functions of PrP^C remain enigmatic, but the central domain, comprising highly conserved regions of the protein may play an important role. Indeed, a large number of studies indicate that synthetic peptides containing residues 106–126 (CR) located in the central domain (CD, 95–133) of PrP^C are neurotoxic. The central domain comprises two chemically distinct subdomains, the charge cluster (CC, 95–110) and a hydrophobic region (HR, 112–133). The aim of the present study was to establish the individual cytotoxicity of CC, HR and CD. Our results show that only the CD peptide is neurotoxic. Biochemical, Transmission Electron Microscopy and Atomic Force Microscopy experiments demonstrated that the CD peptide is able to activate caspase-3 and disrupt the cell membrane, leading to cell death.     

Is metapopulation patch occupancy in nature well predicted by the Levins model?

Although the Levins model has made important theoretical contributions to ecology, its empirical support has not been conclusively established yet. We used published colonization and extinction data from 55 metapopulations to calculate their Levins equilibrium patch occupancy. Over all species, there were not significant differences between the observed patch occupancies and the Levins model's estimates. However, invertebrates and vertebrate species with some degree of threat had patch occupancies larger than the model's expectancies. A temporal sampling effect was found for invertebrate species, with departure from the Levins model decreasing as the length of the study period increased. There was a negative relationship between patch occupancy and extinction probability, as expected under the “rescue effect”. The high rates at which invertebrates produce propagules could lead the Levins model to underestimate patch occupancy, whereas the observed patch occupancy of threatened species may be a transient phenomenon that results from extinction probabilities that increase over time. Therefore, the Levins model captures the metapopulation dynamics of a wide range of species in a simple formula whereas its equilibrium point can be used as evidence of metapopulation stability. Although mechanistic models provide more precise and accurate metapopulation predictions, they also can sacrifice the generality and simplicity of the Levins model.