Ensemble modelling of species distribution: the effects of geographical and environmental ranges

The aim of this study was to analyse the effects of species geographical and environmental ranges on the predictive performances of species distribution models (SDMs). We explored the usefulness of ensemble modelling approaches and tested whether species attributes influenced the outcomes of such approaches. Eight SDMs were used to model the current distribution of 35 fish species at 1110 stream sections in France. We first quantified the consensus among the resulting set of predictions for each fish species. Next, we created an average model by taking the average of the individual model predictions and tested whether the average model improved the predictive performances of single SDMs. Lastly, we described the ranges of fish species along four gradients: latitudinal, thermal, stream gradient (i.e. upstream‐downstream) and elevation. After accounting for the effects of phylogenetic relatedness and species prevalence, these four species attributes were related to the observed variations in both consensus among SDMs and predictive performances by using generalized estimation equations. Our results highlight the usefulness of ensemble approaches for identifying geographical areas of agreement among predictions. Although the geographical extent of species had no effect on the performances of SDMs, we demonstrated that more consensual and accurate predictions were obtained for species with low thermal and elevation ranges, validating the hypothesis that specialist species yield models with higher accuracy than generalist ones. We emphasized that significant improvements in the accuracy of SDMs can be achieved by using an average model. Furthermore, these improvements were higher for species with smaller ranges along the four gradients studied. The geographical extent and ranges of species along environmental gradients provide promising insights into our understanding of uncertainties in species distribution modelling.     

Fibrillin-3 expression in human development

Fibrillin proteins are the major components of extracellular microfibrils found in many connective tissues. Fibrillin-1 and fibrillin-2 are well studied and mutations in these proteins cause a number of fibrillinopathies including Marfan syndrome and congenital contractural arachnodactyly, respectively. Fibrillin-3 was more recently discovered and is much less well characterized. Fibrillin-1 is expressed throughout life, whereas fibrillins-2 and -3 are thought to be primarily present during development. Here, we report detailed fibrillin-3 expression patterns in early human development.A polyclonal antiserum against a C-terminal recombinant half of human fibrillin-3 was produced in rabbit. Anti-fibrillin-3 antibodies were affinity-purified and antibodies cross-reacting with the other fibrillins were removed by absorption resulting in specific anti-fibrillin-3 antibodies. Immunohistochemical analyses with these purified antibodies demonstrate that fibrillin-3 is temporally expressed in numerous tissues relatively evenly from the 6th to the 12th gestational week. Fibrillin-3 was found spatially expressed in perichondrium, perineurium, perimysium, skin, developing bronchi, glomeruli, pancreas, kidney, heart and testis and at the prospective basement membranes in developing epithelia and endothelia. Double immunohistochemical analyses showed that all fibrillins are globally expressed in the same organs, with a number of differences on the tissue level in cartilage, perichondrium and developing bronchi. These results suggest that fibrillin-3, compared to the other fibrillins, fulfills both overlapping and distinct functions in human development.     

Determination of uremic solutes in biological fluids of chronic kidney disease patients by HPLC assay

During chronic kidney disease (CKD), solutes called uremic solutes, accumulate in blood and tissues of patients. We developed an HPLC method for the simultaneous determination of several uremic solutes of clinical interest in biological fluids: phenol (Pol), indole-3-acetic acid (3-IAA), p-cresol (p-C), indoxyl sulfate (3-INDS) and p-cresol sulfate (p-CS). These solutes were separated by ion-pairing HPLC using an isocratic flow and quantified with a fluorescence detection. The mean serum concentrations of 3-IAA, 3-INDS and p-CS were 2.12, 1.03 and 13.03 μM respectively in healthy subjects, 3.21, 17.45 and 73.47 μM in non hemodialyzed stage 3-5 CKD patients and 5.9, 81.04 and 120.54 μM in hemodialyzed patients (stage 5D). We found no Pol and no p-C in any population. The limits of quantification for 3-IAA, 3-INDS, and p-CS were 0.83, 0.72, and 3.2 μM respectively. The within-day CVs were between 1.23 and 3.12% for 3-IAA, 0.98 and 2% for 3-INDS, and 1.25 and 3.01% for p-CS. The between-day CVs were between 1.78 and 5.48% for 3-IAA, 1.45 and 4.54% for 3-INDS, and 1.19 and 6.36% for p-CS. This HPLC method permits the simultaneous and quick quantification of several uremic solutes for daily analysis of large numbers of samples.     

EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy

Hepatitis C virus (HCV) is a major cause of liver disease, but therapeutic options are limited and there are no prevention strategies. Viral entry is the first step of infection and requires the cooperative interaction of several host cell factors. Using a functional RNAi kinase screen, we identified epidermal growth factor receptor and ephrin receptor A2 as host cofactors for HCV entry. Blocking receptor kinase activity by approved inhibitors broadly impaired infection by all major HCV genotypes and viral escape variants in cell culture and in a human liver chimeric mouse model in vivo. The identified receptor tyrosine kinases (RTKs) mediate HCV entry by regulating CD81-claudin-1 co-receptor associations and viral glycoprotein-dependent membrane fusion. These results identify RTKs as previously unknown HCV entry cofactors and show that tyrosine kinase inhibitors have substantial antiviral activity. Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection.     

Inner-membrane proteins PMI/TMEM11 regulate mitochondrial morphogenesis independently of the DRP1/MFN fission/fusion pathways

Mitochondria are highly dynamic organelles that can change in number and morphology during cell cycle, development or in response to extracellular stimuli. These morphological dynamics are controlled by a tight balance between two antagonistic pathways that promote fusion and fission. Genetic approaches have identified a cohort of conserved proteins that form the core of mitochondrial remodelling machineries. Mitofusins (MFNs) and OPA1 proteins are dynamin-related GTPases that are required for outer- and inner-mitochondrial membrane fusion respectively whereas dynamin-related protein 1 (DRP1) is the master regulator of mitochondrial fission. We demonstrate here that the Drosophila PMI gene and its human orthologue TMEM11 encode mitochondrial inner-membrane proteins that regulate mitochondrial morphogenesis. PMI-mutant cells contain a highly condensed mitochondrial network, suggesting that PMI has either a pro-fission or an anti-fusion function. Surprisingly, however, epistatic experiments indicate that PMI shapes the mitochondria through a mechanism that is independent of drp1 and mfn. This shows that mitochondrial networks can be shaped in higher eukaryotes by at least two separate pathways: one PMI-dependent and one DRP1/MFN-dependent.     

Pituitary stalk interruption syndrome: diagnostic delay and sensitivity of the auxological criteria of the growth hormone research society

Objectives

To study the diagnostic delay for pituitary stalk interruption syndrome (PSIS) with growth hormone deficiency (GHD) and the sensitivity of the auxological criteria of the Growth Hormone Research Society (GHRS) consensus guidelines.

Methods

A single-center retrospective case-cohort study covering records from January 2000 through December 2007 evaluated the performance of each GHRS auxological criterion for patients with GHD and PSIS. Diagnostic delay was calculated as the difference between the age at which the earliest GHRS criterion could have been observed and the age at diagnosis of PSIS with GHD. A diagnostic delay exceeding one year was defined as late diagnosis.

Results

The study included 21 patients, 16 (76%) of whom had isolated GHD and 5 (24%) multiple pituitary hormone deficiencies. The median age at diagnosis was 3.6 years (interquartile range, IQR, 2.6–5.5). The median diagnostic delay was 2.3 years (range 0–12.6; IQR 1.5–3.6), with late diagnosis for 17 patients (81%). Height more than 1.5 SDS below target height was the most effective criterion: 90% of the patients met the criterion before diagnosis at a median age of 1 year, and it was the first criterion to be fulfilled for 84%.

Conclusion

In our cohort, the delay for diagnosis of PSIS with GHD was long and could have been reduced by using the GHRS criteria, in particular, height more than 1.5 SDS below the target height. The specificity of such a strategy needs to be tested in healthy populations.     

Differences in the desire to eat in children and adults in the presence of an obese eater

Previous research has shown that the desire to eat foods decreases in adults in the presence of an obese eater compared to a normal-weight eater. This study investigated whether or not this decrease in eating desire was observed in younger children in the same way as in adults. Children aged 5 and 8 years old, as well as adults, were presented with photographs of liked and disliked foods presented either alone or with normal-weight and obese eaters expressing three different emotions--pleasure, disgust, and neutrality--toward these food products. The results showed that the eater's weight status had a greater effect on the adults' desire to eat than on that of the children. Adults were influenced by the eater's weight status, regardless of the facial expression or the food category. Compared to adults, the impact of the eater's weight status on the children's desire to eat depended on the emotional facial expression and the children's food preferences. Thus, when children did not like the foods, their eating desire was negatively influenced by the eater's obese status, as was that of adults. On the other hand, when children liked the food products, the eater's weight status had no effect on their eating desire. They were more influenced by the eater's facial expressions. Thus, an expression of pleasure increased the desire to eat the liked foods in the younger children, whereas an expression of disgust decreased it. These results are discussed in terms of the high sensitivity of young children to emotional facial expressions.     

The Diversity of Coral Reefs: What Are We Missing?

Tropical reefs shelter one quarter to one third of all marine species but one third of the coral species that construct reefs are now at risk of extinction. Because traditional methods for assessing reef diversity are extremely time consuming, taxonomic expertise for many groups is lacking, and marine organisms are thought to be less vulnerable to extinction, most discussions of reef conservation focus on maintenance of ecosystem services rather than biodiversity loss. In this study involving the three major oceans with reef growth, we provide new biodiversity estimates based on quantitative sampling and DNA barcoding. We focus on crustaceans, which are the second most diverse group of marine metazoans. We show exceptionally high numbers of crustacean species associated with coral reefs relative to sampling effort (525 species from a combined, globally distributed sample area of 6.3 m(2)). The high prevalence of rare species (38% encountered only once), the low level of spatial overlap (81% found in only one locality) and the biogeographic patterns of diversity detected (Indo-West Pacific>Central Pacific>Caribbean) are consistent with results from traditional survey methods, making this approach a reliable and efficient method for assessing and monitoring biodiversity. The finding of such large numbers of species in a small total area suggests that coral reef diversity is seriously under-detected using traditional survey methods, and by implication, underestimated.     

ERK is involved in the reorganization of somatosensory cortical maps in adult rats submitted to hindlimb unloading

Sensorimotor restriction by a 14-day period of hindlimb unloading (HU) in the adult rat induces a reorganization of topographic maps and receptive fields. However, the underlying mechanisms are still unclear. Interest was turned towards a possible implication of intracellular MAPK signaling pathway since Extracellular-signal-Regulated Kinase 1/2 (ERK1/2) is known to play a significant role in the control of synaptic plasticity. In order to better understand the mechanisms underlying cortical plasticity in adult rats submitted to a sensorimotor restriction, we analyzed the time-course of ERK1/2 activation by immunoblot and of cortical reorganization by electrophysiological recordings, on rats submitted to hindlimb unloading over four weeks. Immunohistochemistry analysis provided evidence that ERK1/2 phosphorylation was increased in layer III neurons of the somatosensory cortex. This increase was transient, and parallel to the changes in hindpaw cortical map area (layer IV). By contrast, receptive fields were progressively enlarged from 7 to 28 days of hindlimb unloading. To determine whether ERK1/2 was involved in cortical remapping, we administered a specific ERK1/2 inhibitor (PD-98059) through osmotic mini-pump in rats hindlimb unloaded for 14 days. Results demonstrate that focal inhibition of ERK1/2 pathway prevents cortical reorganization, but had no effect on receptive fields. These results suggest that ERK1/2 plays a role in the induction of cortical plasticity during hindlimb unloading.     

T cells contribute to tumor progression by favoring pro-tumoral properties of intra-tumoral myeloid cells in a mouse model for spontaneous melanoma

Tumors affect myelopoeisis and induce the expansion of myeloid cells with immunosuppressive activity. In the MT/ret model of spontaneous metastatic melanoma, myeloid cells are the most abundant tumor infiltrating hematopoietic population and their proportion is highest in the most aggressive cutaneous metastasis. Our data suggest that the tumor microenvironment favors polarization of myeloid cells into type 2 cells characterized by F4/80 expression, a weak capacity to secrete IL-12 and a high production of arginase. Myeloid cells from tumor and spleen of MT/ret mice inhibit T cell proliferation and IFNγ secretion. Interestingly, T cells play a role in type 2 polarization of myeloid cells. Indeed, intra-tumoral myeloid cells from MT/ret mice lacking T cells are not only less suppressive towards T cells than corresponding cells from wild-type MT/ret mice, but they also inhibit more efficiently melanoma cell proliferation. Thus, our data support the existence of a vicious circle, in which T cells may favor cancer development by establishing an environment that is likely to skew myeloid cell immunity toward a tumor promoting response that, in turn, suppresses immune effector cell functions.