Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions

Visualizing sound emission of elephant vocalizations: evidence for two rumble production types

Recent comparative data reveal that formant frequencies are cues to body size in animals, due to a close relationship between formant frequency spacing, vocal tract length and overall body size. Accordingly, intriguing morphological adaptations to elongate the vocal tract in order to lower formants occur in several species, with the size exaggeration hypothesis being proposed to justify most of these observations. While the elephant trunk is strongly implicated to account for the low formants of elephant rumbles, it is unknown whether elephants emit these vocalizations exclusively through the trunk, or whether the mouth is also involved in rumble production. In this study we used a sound visualization method (an acoustic camera) to record rumbles of five captive African elephants during spatial separation and subsequent bonding situations. Our results showed that the female elephants in our analysis produced two distinct types of rumble vocalizations based on vocal path differences: a nasally- and an orally-emitted rumble. Interestingly, nasal rumbles predominated during contact calling, whereas oral rumbles were mainly produced in bonding situations. In addition, nasal and oral rumbles varied considerably in their acoustic structure. In particular, the values of the first two formants reflected the estimated lengths of the vocal paths, corresponding to a vocal tract length of around 2 meters for nasal, and around 0.7 meters for oral rumbles. These results suggest that African elephants may be switching vocal paths to actively vary vocal tract length (with considerable variation in formants) according to context, and call for further research investigating the function of formant modulation in elephant vocalizations. Furthermore, by confirming the use of the elephant trunk in long distance rumble production, our findings provide an explanation for the extremely low formants in these calls, and may also indicate that formant lowering functions to increase call propagation distances in this species'

From Food to Offspring Down: Tissue-Specific Discrimination and Turn-Over of Stable Isotopes in Herbivorous Waterbirds and Other Avian Foraging Guilds

Isotopic discrimination and turn-over are fundamental to the application of stable isotope ecology in animals. However, detailed information for specific tissues and species are widely lacking, notably for herbivorous species. We provide details on tissue-specific carbon and nitrogen discrimination and turn-over times from food to blood, feathers, claws, egg tissues and offspring down feathers in four species of herbivorous waterbirds. Source-to-tissue discrimination factors for carbon (δ13C) and nitrogen stable isotope ratios (δ15N) showed little variation across species but varied between tissues. Apparent discrimination factors ranged between −0.5 to 2.5‰ for δ13C and 2.8 to 5.2‰ for δ15N, and were more similar between blood components than between keratinous tissues or egg tissue. Comparing these results with published data from other species we found no effect of foraging guild on discrimination factors for carbon but a significant foraging-guild effect for nitrogen discrimination factors

Potential Geographic Distribution of Brown Marmorated Stink Bug Invasion (Halyomorpha halys)

BACKGROUND: The Brown Marmorated Stink Bug (BMSB), Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), native to Asia, is becoming an invasive species with a rapidly expanding range in North America and Europe. In the US, it is a household pest and also caused unprecedented damage to agriculture crops. Exploring its climatic limits and estimating its potential geographic distribution can provide critical information for management strategies. METHODOLOGY/PRINCIPALS: We used direct climate comparisons to explore the climatic niche occupied by native and invasive populations of BMSB. Ecological niche modelings based on the native range were used to anticipate the potential distribution of BMSB worldwide. Conversely, niche models based on the introduced range were used to locate the original invasive propagates in Asia. Areas with high invasion potential were identified by two niche modeling algorithms (i.e., Maxent and GARP). CONCLUSIONS/SIGNIFICANCE: Reduced dimensionality of environmental space improves native model transferability in the invade area. Projecting models from invasive population back to native distributional areas offers valuable information on the potential source regions of the invasive populations. Our models anticipated successfully the current disjunct distribution of BMSB in the US. The original propagates are hypothesized to have come from northern Japan or western Korea. High climate suitable areas at risk of invasion include latitudes between 30°-50° including northern Europe, northeastern North America, southern Australia and the North Island of New Zealand. Angola in Africa and Uruguay in South America also showed high climate suitability

Environmental drivers of distribution and reef development of the Mediterranean coral Cladocora caespitosa

Cladocora caespitosa is the only Mediterranean scleractinian similar to tropical reef-building corals. While this species is part of the recent fossil history of the Mediterranean Sea, it is currently considered endangered due to its decline during the last decades. Environmental factors affecting the distribution and persistence of extensive bank reefs of this endemic species across its whole geographic range are poorly understood. In this study, we examined the environmental response of C. caespitosa and its main types of assemblages using ecological niche modeling and ordination analysis. We also predicted other suitable areas for the occurrence of the species and assessed the conservation effectiveness of Mediterranean marine protected areas (MPAs) for this coral. We found that phosphate concentration and wave height were factors affecting both the occurrence of this versatile species and the distribution of its extensive bioconstructions in the Mediterranean Sea. A set of factors (diffuse attenuation coefficient, calcite and nitrate concentrations, mean wave height, sea surface temperature, and shape of the coast) likely act as environmental barriers preventing the species from expansion to the Atlantic Ocean and the Black Sea. Uncertainties in our large-scale statistical results and departures from previous physiological and ecological studies are also discussed under an integrative perspective. This study reveals that Mediterranean MPAs encompass eight of the ten banks and 16 of the 21 beds of C. caespitosa. Preservation of water clarity by avoiding phosphate discharges may improve the protection of this emblematic species.Spanish Ministry of Economy and Competitiveness [CTM2014-57949-R]info:eu-repo/semantics/publishedVersio

Poly-Thymidine Oligonucleotides Mediate Activation of Murine Glial Cells Primarily Through TLR7, Not TLR8

The functional role of murine TLR8 in the inflammatory response of the central nervous system (CNS) remains unclear. Murine TLR8 does not appear to respond to human TLR7/8 agonists, due to a five amino acid deletion in the ectodomain. However, recent studies have suggested that murine TLR8 may be stimulated by alternate ligands, which include vaccinia virus DNA, phosphothioate oligodeoxynucleotides (ODNs) or the combination of phosphothioate poly-thymidine oligonucleotides (pT-ODNs) with TLR7/8 agonists. In the current study, we analyzed the ability of pT-ODNs to induce activation of murine glial cells in the presence or absence of TLR7/8 agonists. We found that TLR7/8 agonists induced the expression of glial cell activation markers and induced the production of multiple proinflammatory cytokines and chemokines in mixed glial cultures. In contrast, pT-ODNs alone induced only low level expression of two cytokines, CCL2 and CXCL10. The combination of pT-ODNs along with TLR7/8 agonists induced a synergistic response with substantially higher levels of proinflammatory cytokines and chemokines compared to CL075. This enhancement was not due to cellular uptake of the agonist, indicating that the pT-ODN enhancement of cytokine responses was due to effects on an intracellular process. Interestingly, this response was also not due to synergistic stimulation of both TLR7 and TLR8, as the loss of TLR7 abolished the activation of glial cells and cytokine production. Thus, pT-ODNs act in synergy with TLR7/8 agonists to induce strong TLR7-dependent cytokine production in glial cells, suggesting that the combination of pT-ODNs with TLR7 agonists may be a useful mechanism to induce pronounced glial activation in the CNS

Tertiary hypothyroidism in a dog

<p/> <p>A nine-year-old male entire Labrador was diagnosed with pituitary dependent hyperadrenocorticism. Following seven months of successful mitotane therapy, the dog presented with marked weight gain, seborrhoea and alopecia. Routine clinicopathological analyses revealed marked hypercholesterolaemia. Serum total and free thyroxine (T4) concentrations were below their respective reference ranges. Serum thyroid stimulating hormone (cTSH) concentration was within reference range. TSH and thyrotropin releasing hormone (TRH) response tests revealed adequate stimulation of total T4 in both, and cTSH in the latter test. Magnetic resonance imaging revealed a mass arising from the pituitary fossa, with suprasellar extension. A diagnosis of tertiary hypothyroidism was made. Following four weeks of levothyroxine therapy, circulating cholesterol concentration had declined, weight loss had ensued and dermatological abnormalities had improved. Euthanasia was performed four months later due to the development of neurological signs. A highly infiltrative pituitary adenoma, with effacement of the overlying hypothalamus was identified on post mortem examination. Tertiary hypothyroidism has not been previously reported in dogs.</p