Underlying impacts of invasive cats on islands: not only a question of predation

The domestic cat has been introduced on most islands worldwide, where it has established feral populations and is currently known to be one of the worst invasive mammalian predators. Predation is the strongest deleterious effect of cats on wildlife, inducing a direct negative impact on population size and dynamics, breeding success and changes in species assemblages. Direct predation is not the only damaging impact on native wildlife, since cats can be responsible for other poorly-documented underlying ecological impacts, like competition, hybridization, disease transmission, ecological process alteration, and behavioral change. Here, we pinpoint relevant examples of these ecological impacts, by searching for accurate data from published literature. We used electronic databases covering most of the world islands where the effects of cats were documented. Knowledge of these impacts can be of great importance to preserve insular ecosystem functions and persistence of endangered native species. We emphasize that direct predation processes should not be the only factor considered in the management of invasive cats on islands.     

Effect of alemtuzumab-based T-cell depletion on graft compositional change in vitro and immune reconstitution early after allogeneic stem cell transplantation

Background aimsTo reduce the risk of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloSCT), T-cell depletion (TCD) of grafts can be performed by the addition of alemtuzumab (ALT) “to the bag” (in vitro) before transplantation. In this prospective study, the authors analyzed the effect of in vitro incubation with 20 mg ALT on the composition of grafts prior to graft infusion. Furthermore, the authors assessed whether graft composition at the moment of infusion was predictive for T-cell reconstitution and development of GVHD early after TCD alloSCT.MethodsSixty granulocyte colony-stimulating factor-mobilized stem cell grafts were obtained from ≥9/10 HLA-matched related and unrelated donors. The composition of the grafts was analyzed by flow cytometry before and after in vitro incubation with ALT. T-cell reconstitution and incidence of severe GVHD were monitored until 12 weeks after transplantation.ResultsIn vitro incubation of grafts with 20 mg ALT resulted in an initial median depletion efficiency of T-cell receptor (TCR) α/β T cells of 96.7% (range, 63.5–99.8%), followed by subsequent depletion in vivo. Graft volumes and absolute leukocyte counts of grafts before the addition of ALT were not predictive for the efficiency of TCR α/β T-cell depletion. CD4^pos T cells were depleted more efficiently than CD8^pos T cells, and naive and regulatory T cells were depleted more efficiently than memory and effector T cells. This differential depletion of T-cell subsets was in line with their reported differential CD52 expression. In vitro depletion efficiencies and absolute numbers of (naive) TCR α/β T cells in the grafts after ALT incubation were not predictive for T-cell reconstitution or development of GVHD post- alloSCT.ConclusionsThe addition of ALT to the bag is an easy, fast and generally applicable strategy to prevent GVHD in patients receiving alloSCT after myeloablative or non-myeloablative conditioning because of the efficient differential depletion of donor-derived lymphocytes and T cells.     

Influencing Factors and Applicability of the Viability EMA-qPCR for a Detection and Quantification of Campylobacter Cells from Water Samples

In recent years, increasing numbers of human campylobacteriosis cases caused by contaminated water have been reported. As the culture-based detection of Campylobacter is time consuming and can yield false-negative results, the suitability of a quantitative real-time PCR method in combination with an ethidium monoazide pretreatment of samples (EMA-qPCR) for the rapid, quantitative detection of viable Campylobacter cells from water samples was investigated. EMA-qPCR has been shown to be a promising rapid method for the detection of viable Campylobacter spp. from food samples. Application of membrane filtration and centrifugation, two methods frequently used for the isolation of bacteria from water, revealed a mean loss of up to 1.08 log₁₀ cells/ml from spiked samples. Both methods used alone lead to a loss of dead bacteria and accumulation of viable bacteria in the sample as shown by fluorescence microscopy. After filtration of samples, no significant differences could be detected in subsequent qPCR experiments with and without EMA pretreatment compared to culture-based enumeration. High correlations (R² = 0.942 without EMA, R² = 0.893 with EMA) were obtained. After centrifugation of samples, qPCR results overestimated Campylobacter counts, whereas results from both EMA-qPCR and the reference method were comparable. As up to 81.59% of nonviable cells were detected in pond water, EMA-qPCR failed to detect correct quantities of viable cells. However, analyses of spiked tap water samples revealed a high correlation (R² = 0.863) between results from EMA-qPCR and the reference method. After membrane filtration, EMA-qPCR was successfully applied to Campylobacter field isolates, and results indicated an advantage over qPCR by analysing defined mixtures of viable and nonviable cells. In conclusion, EMA-qPCR is a suitable method to detect viable Campylobacter from water samples, but the isolation technique and the type/quality of the water sample impact the results.     

Exclusion Performance in Dwarf Goats (Capra aegagrus hircus) and Sheep (Ovis orientalis aries)

Using a comparative approach, we investigated the ability of dwarf goats and sheep to use direct and indirect information about the location of a food reward in an object-choice task. Subjects had to choose between two cups with only one covering a reward. Before making a choice, subjects received information about the baited (direct information) or non-baited cup (indirect information). Both goats and sheep were able to use direct information (presence of food) in the object choice task. After controlling for local enhancement, we found that goats rather than sheep were able to use indirect information (i.e., the absence of food) to find a reward. The actual test setup could not clarify whether individual goats were able to inferentially reason about the content of the baited cup when only shown the content of the non-baited cup or if they simply avoided the empty cup in that situation. As browsing species, feral and wild goats exhibit highly selective feeding behaviour compared to the rather unselective grazing sheep. The potential influence of this species-specific foraging flexibility of goats and sheep for using direct and indirect information to find a food reward is discussed in relation to a higher aversion to losses in food acquisition in goats compared to sheep.     

Loss of Central Auditory Processing in a Mouse Model of Canavan Disease

Canavan Disease (CD) is a leukodystrophy caused by homozygous null mutations in the gene encoding aspartoacylase (ASPA). ASPA-deficiency is characterized by severe psychomotor retardation, and excessive levels of the ASPA substrate N-acetylaspartate (NAA). ASPA is an oligodendrocyte marker and it is believed that CD has a central etiology. However, ASPA is also expressed by Schwann cells and ASPA-deficiency in the periphery might therefore contribute to the complex CD pathology. In this study, we assessed peripheral and central auditory function in the Aspa^lacZ/lacZ rodent model of CD using auditory brainstem response (ABR). Increased ABR thresholds and the virtual loss of waveform peaks 4 and 5 from Aspa^lacZ/lacZ mice, indicated altered central auditory processing in mutant mice compared with Aspa^wt/wt controls and altered central auditory processing. Analysis of ABR latencies recorded from Aspa^lacZ/lacZ mice revealed that the speed of nerve conduction was unchanged in the peripheral part of the auditory pathway, and impaired in the CNS. Histological analyses confirmed that ASPA was expressed in oligodendrocytes and Schwann cells of the auditory system. In keeping with our physiological results, the cellular organization of the cochlea, including the organ of Corti, was preserved and the spiral ganglion nerve fibres were normal in ASPA-deficient mice. In contrast, we detected substantial hypomyelination in the central auditory system of Aspa^lacZ/lacZ mice. In summary, our data suggest that the lack of ASPA in the CNS is responsible for the observed hearing deficits, while ASPA-deficiency in the cochlear nerve fibres is tolerated both morphologically and functionally.     

The Role of Temperature in Determining Species' Vulnerability to Ocean Acidification: A Case Study Using Mytilus galloprovincialis

Ocean acidification (OA) is occurring across a backdrop of concurrent environmental changes that may in turn influence species'' responses to OA. Temperature affects many fundamental biological processes and governs key reactions in the seawater carbonate system. It therefore has the potential to offset or exacerbate the effects of OA. While initial studies have examined the combined impacts of warming and OA for a narrow range of climate change scenarios, our mechanistic understanding of the interactive effects of temperature and OA remains limited. Here, we use the blue mussel, Mytilus galloprovincialis, as a model species to test how OA affects the growth of a calcifying invertebrate across a wide range of temperatures encompassing their thermal optimum. Mussels were exposed in the laboratory to a factorial combination of low and high pCO₂ (400 and 1200 µatm CO₂) and temperatures (12, 14, 16, 18, 20, and 24°C) for one month. Results indicate that the effects of OA on shell growth are highly dependent on temperature. Although high CO₂ significantly reduced mussel growth at 14°C, this effect gradually lessened with successive warming to 20°C, illustrating how moderate warming can mediate the effects of OA through temperature''s effects on both physiology and seawater geochemistry. Furthermore, the mussels grew thicker shells in warmer conditions independent of CO₂ treatment. Together, these results highlight the importance of considering the physiological and geochemical interactions between temperature and carbonate chemistry when interpreting species'' vulnerability to OA.     

Novel High Efficient Coatings for Anti-Microbial Surgical Sutures Using Chlorhexidine in Fatty Acid Slow-Release Carrier Systems

Sutures can cause challenging surgical site infections, due to capillary effects resulting in bacteria permeating wounds. Anti-microbial sutures may avoid these complications by inhibiting bacterial pathogens. Recently, first triclosan-resistances were reported and therefore alternative substances are becoming clinically relevant. As triclosan alternative chlorhexidine, the “gold standard” in oral antiseptics was used. The aim of the study was to optimize novel slow release chlorhexidine coatings based on fatty acids in surgical sutures, to reach a high anti-microbial efficacy and simultaneously high biocompatibility. Sutures were coated with chlorhexidine laurate and chlorhexidine palmitate solutions leading to 11, 22 or 33 µg/cm drug concentration per length. Drug release profiles were determined in aqueous elutions. Antibacterial efficacy against Staphylococcus aureus was assessed in agar diffusion tests. Biocompatibility was evaluated via established cytotoxicity assay (WST-1). A commercially triclosan-containing suture (Vicryl Plus), was used as anti-microbial reference. All coated sutures fulfilled European Pharmacopoeia required tensile strength and proved continuous slow drug release over 96 hours without complete wash out of the coated drug. High anti-microbial efficacy for up to 5 days was observed. Regarding biocompatibility, sutures using 11 µg/cm drug content displayed acceptable cytotoxic levels according to ISO 10993-5. The highest potential for human application were shown by the 11 µg/cm chlorhexidine coated sutures with palmitic acid. These novel coated sutures might be alternatives to already established anti-microbial sutures such as Vicryl Plus in case of triclosan-resistance. Chlorhexidine is already an established oral antiseptic, safety and efficacy should be proven for clinical applications in anti-microbial sutures.     

Differential Modulation by IL-17A of Cholangitis versus Colitis in IL-2Rα Deleted Mice

IFN-γ is a signature Th1 cell associated cytokine critical for the inflammatory response in autoimmunity with both pro-inflammatory and potentially protective functions. IL-17A is the hallmark of T helper 17 (Th17) cell subsets, produced by γδT, CD8+ T, NK and NKT cells. We have taken advantage of our colony of IL-2Rα^−/− mice that spontaneously develop both autoimmune cholangitis and inflammatory bowel disease. In this model CD8+ T cells mediate biliary ductular damage, whereas CD4+ T cells mediate induction of colon-specific autoimmunity. Importantly, IL-2Rα^−/− mice have high levels of interferon γ (IFN-γ), and interleukin-17A (IL-17A). We produced unique double deletions of mice that were either IL-17A^−/−IL-2Rα^−/− or IFN-γ^−/−IL-2Rα^−/− to specifically address the precise role of these two cytokines in the natural history of autoimmune cholangitis and colitis. Of note, deletion of IL-17A in IL-2Rα^−/− mice led to more severe liver inflammation, but ameliorated colitis. In contrast, there were no significant changes in the immunopathology of double knock-out IFN-γ^−/− IL-2Rα^−/− mice, compared to single knock-out IL-2Rα^−/− mice with respect to cholangitis or colitis. Furthermore, there was a significant increase in pathogenetic CD8+ T cells in the liver of IL-17A^−/−IL-2Rα^−/− mice. Our data suggest that while IL-17A plays a protective role in autoimmune cholangitis, it has a pro-inflammatory role in inflammatory bowel disease. These data take on particular significance in the potential use of anti-IL-17A therapy in humans with primary biliary cirrhosis.     

pH-dependent amyloid and protofibril formation by the ABri peptide of familial British dementia

The ABri is a 34 residue peptide that is the major component of amyloid deposits in familial British dementia. In the amyloid deposits, the ABri peptide adopts aggregated beta-pleated sheet structures, similar to those formed by the Abeta peptide of Alzheimer's disease and other amyloid forming proteins. As a first step toward elucidating the molecular mechanisms of the beta-amyloidosis, we explored the ability of the environmental variables (pH and peptide concentration) to promote beta-sheet fibril structures for synthetic ABri peptides. The secondary structures and fibril morphology were characterized in parallel using circular dichroism, atomic force microscopy, negative stain electron microscopy, Congo red, and thioflavin-T fluorescence spectroscopic techniques. As seen with other amyloid proteins, the ABri fibrils had characteristic binding with Congo red and thioflavin-T, and the relative amounts of beta-sheet and amyloid fibril-like structures are influenced strongly by pH. In the acidic pH range 3.1-4.3, the ABri peptide adopts almost exclusively random structure and a predominantly monomeric aggregation state, on the basis of analytical ultracentrifugation measurements. At neutral pH, 7.1-7.3, the ABri peptide had limited solubility and produced spherical and amorphous aggregates with predominantly beta-sheet secondary structure, whereas at slightly acidic pH, 4.9, spherical aggregates, intermediate-sized protofibrils, and larger-sized mature amyloid fibrils were detected by atomic force microscopy. With aging at pH 4.9, the protofibrils underwent further association and eventually formed mature fibrils. The presence of small amounts of aggregated peptide material or seeds encourage fibril formation at neutral pH, suggesting that generation of such seeds in vivo could promote amyloid formation. At slightly basic pH, 9.0, scrambling of the Cys5-Cys22 disulfide bond occurred, which could lead to the formation of covalently linked aggregates. The presence of the protofibrils and the enhanced aggregation at slightly acidic pH is consistent with the behavior of other amyloid-forming proteins, which supports the premise that a common mechanism may be involved in protein misfolding and beta-amyloidosis.     

Atmospheric Production of Glycolaldehyde Under Hazy Prebiotic Conditions

The early Earth’s atmosphere, with extremely low levels of molecular oxygen and an appreciable abiotic flux of methane, could have been a source of organic compounds necessary for prebiotic chemistry. Here, we investigate the formation of a key RNA precursor, glycolaldehyde (2-hydroxyacetaldehyde, or GA) using a 1-dimensional photochemical model. Maximum atmospheric production of GA occurs when the CH₄:CO₂ ratio is close to 0.02. The total atmospheric production rate of GA remains small, only 1×10⁷ mol yr^???1. Somewhat greater amounts of GA production, up to 2 × 10⁸ mol yr^???1, could have been provided by the formose reaction or by direct delivery from space. Even with these additional production mechanisms, open ocean GA concentrations would have remained at or below ~1 μM, much smaller than the 1–2 M concentrations required for prebiotic synthesis routes like those proposed by Powner et al. (Nature 459:239–242, 2009). Additional production or concentration mechanisms for GA, or alternative formation mechanisms for RNA, are needed, if this was indeed how life originated on the early Earth.