Convolutional neural networks improve species distribution modelling by capturing the spatial structure of the environment

Convolutional Neural Networks (CNNs) are statistical models suited for learning complex visual patterns. In the context of Species Distribution Models (SDM) and in line with predictions of landscape ecology and island biogeography, CNN could grasp how local landscape structure affects prediction of species occurrence in SDMs. The prediction can thus reflect the signatures of entangled ecological processes. Although previous machine-learning based SDMs can learn complex influences of environmental predictors, they cannot acknowledge the influence of environmental structure in local landscapes (hence denoted “punctual models”). In this study, we applied CNNs to a large dataset of plant occurrences in France (GBIF), on a large taxonomical scale, to predict ranked relative probability of species (by joint learning) to any geographical position. We examined the way local environmental landscapes improve prediction by performing alternative CNN models deprived of information on landscape heterogeneity and structure (“ablation experiments”). We found that the landscape structure around location crucially contributed to improve predictive performance of CNN-SDMs. CNN models can classify the predicted distributions of many species, as other joint modelling approaches, but they further prove efficient in identifying the influence of local environmental landscapes. CNN can then represent signatures of spatially structured environmental drivers. The prediction gain is noticeable for rare species, which open promising perspectives for biodiversity monitoring and conservation strategies. Therefore, the approach is of both theoretical and practical interest. We discuss the way to test hypotheses on the patterns learnt by CNN, which should be essential for further interpretation of the ecological processes at play.     

An apicoplast‐resident folate transporter is essential for sporogony of malaria parasites

Malaria parasites are fast replicating unicellular organisms and require substantial amounts of folate for DNA synthesis. Despite the central role of this critical co‐factor for parasite survival, only little is known about intraparasitic folate trafficking in Plasmodium. Here, we report on the expression, subcellular localisation and function of the parasite's folate transporter 2 (FT2) during life cycle progression in the murine malaria parasite Plasmodium berghei. Using live fluorescence microscopy of genetically engineered parasites, we demonstrate that FT2 localises to the apicoplast. In invasive P. berghei stages, a fraction of FT2 is also observed at the apical end. Upon genetic disruption of FT2, blood and liver infection, gametocyte production and mosquito colonisation remain unaltered. But in the Anopheles vector, FT2‐deficient parasites develop inflated oocysts with unusual pulp formation consisting of numerous single‐membrane vesicles, which ultimately fuse to form large cavities. Ultrastructural analysis suggests that this defect reflects aberrant sporoblast formation caused by abnormal vesicular traffic. Complete sporogony in FT2‐deficient oocysts is very rare, and mutant sporozoites fail to establish hepatocyte infection, resulting in a complete block of parasite transmission. Our findings reveal a previously unrecognised organellar folate transporter that exerts critical roles for pathogen maturation in the arthropod vector.     

Calcium/Calmodulin-Dependent Protein Kinase Is Negatively and Positively Regulated by Calcium,Providing a Mechanism for Decoding Calcium Responses during Symbiosis Signaling

The establishment of symbiotic associations in plants requires calcium oscillations that must be decoded to invoke downstream developmental programs. In animal systems, comparable calcium oscillations are decoded by calmodulin (CaM)–dependent protein kinases, but symbiotic signaling involves a calcium/CaM–dependent protein kinase (CCaMK) that is unique to plants. CCaMK differs from the animal CaM kinases by its dual ability to bind free calcium, via calcium binding EF-hand domains on the protein, or to bind calcium complexed with CaM, via a CaM binding domain. In this study, we dissect this dual regulation of CCaMK by calcium. We find that calcium binding to the EF-hand domains promotes autophosphorylation, which negatively regulates CCaMK by stabilizing the inactive state of the protein. By contrast, calcium-dependent CaM binding overrides the effects of autophosphorylation and activates the protein. The differential calcium binding affinities of the EF-hand domains compared with those of CaM suggest that CCaMK is maintained in the inactive state at basal calcium concentrations and is activated via CaM binding during calcium oscillations. This work provides a model for decoding calcium oscillations that uses differential calcium binding affinities to create a robust molecular switch that is responsive to calcium concentrations associated with both the basal state and with oscillations.     

Anti-hypertensive effects of Rosuvastatin are associated with decreased inflammation and oxidative stress markers in hypertensive rats

Among their pleiotropic effects, statins exert antioxidant and anti-inflammatory properties. The aim of this study was to evaluate in normotensive (WKY) and in spontaneously hypertensive rats (SHR) the effect of rosuvastatin (ROSU) treatment on (1) plasma inflammation markers and endogenous NO synthase inhibitor (ADMA) levels, (2) reactive oxygen species (ROS) generated by circulating leukocytes and (3) vascular oxidative stress and tissue inflammation markers. Plasma cytokines were higher in SHR than in WKY, except for IL-4, which was lower in SHR than in WKY. SHR monocytes exhibited higher production of ROS than did WKY monocytes. In the experimental conditions, ROSU did not modify plasma cholesterol levels in SHR but attenuated the increase in systolic blood pressure. In SHR only, ROSU lessened pro-inflammatory cytokines and ADMA levels, increased IL-4 and reduced ROS production in circulating monocytes. These results demonstrate the beneficial effects of ROSU in SHR, independently of any lowering of cholesterol levels.     

Comprehensive Ubiquitin E2 Profiling of Ten Ubiquitin E3 Ligases

The ubiquitin pathway regulates diverse functions including protein localization and stability. The complexity of the pathway involving nearly 40 identified E2 conjugating enzymes and over 600 E3 ligases raises the issue of specificity. With the E2s and E3s fitting into a limited number of classes based on bioinformatics, structures, and proven activities, there is not a clear picture as to what would determine which E2/E3 enzyme pair would be functional. There have been many reports of limited E2/E3 activity profiling with a small number of E2s and E3s. We have expanded on this to investigate the activity of ubiquitin E2s covering the majority of the reported classes/families in concert with a number of E3s implicated in a variety of diseases. Using an ELISA-based assay we screened 10 E3 ligases against a panel of 11 E2s to determine which E2/E3 pairs exhibited E3 autoubiquitylation activity. In addition, the ubiquitin chain linkage preference by certain E2/E3 pairs was investigated. Finally, substrate ubiquitylation was assayed for the E3 ligase MuRF1 using various E2/MuRF1 pairs. These studies demonstrate the utility of identifying the correct E2/E3 pair to monitor specific substrate ubiquitylation.     

The cephalic morphology of the Gondwanan key taxon Hackeriella (Coleorrhyncha,Hemiptera)

External and internal head structures of Coleorrhyncha, a key-taxon within the Hemiptera, are described in detail and documented using modern techniques. The main focus is on Hackeriella veitchi, but two additional representatives of the Gondwanan relict group were also examined, and also head structures of Enicocephalidae, a member of a potentially basal heteropteran lineage. Features were compared to those documented in literature for the Sternorrhyncha, Auchenorrhyncha, and Heteroptera. Coleorrhyncha are characterized by highly modified head structures and correspondingly an entire series of autapomorphies, such as for instance a strongly flattened head capsule with fenestrations. However, they also display features that are likely plesiomorphic compared to members of other hemipteran groups. These include the almost complete tentorium and the lack of the gula. The sistergroup relationship between Coleorrhyncha and Heteroptera is well supported by cephalic features. Potential synapomorphies are the presence of a distinct mandibular sulcus, the reduced number of antennomeres, the absence of clasping organs in the labial groove, coiled accessory salivary ducts, the presence of a small cervical muscle M1a (M. pronotopostoccipitalis medialis), the presence of a second mandibular promotor M14 (M. zygomaticus mandibulae), the presence of M28 (M. verticopharyngalis), and M30 (M. frontobuccalis posterior).     

Monitoring Blending of Pharmaceutical Powders with Multipoint NIR Spectroscopy

Blending of powders is a crucial step in the production of pharmaceutical solid dosage forms. The active pharmaceutical ingredient (API) is often a powder that is blended with other powders (excipients) in order to produce tablets. The blending efficiency is influenced by several external factors, such as the desired degree of homogeneity and the required blending time, which mainly depend on the properties of the blended materials and on the geometry of the blender. This experimental study investigates the mixing behavior of acetyl salicylic acid as an API and α-lactose monohydrate as an excipient for different filling orders and filling levels in a blender. A multiple near-infrared probe setup on a laboratory-scale blender is used to observe the powder composition quasi-simultaneously and in-line in up to six different positions of the blender. Partial least squares regression modeling was used for a quantitative analysis of the powder compositions in the different measurement positions. The end point for the investigated mixtures and measurement positions was determined via moving block standard deviation. Observing blending in different positions helped to detect good and poor mixing positions inside the blender that are affected by convective and diffusive mixing.     

Hsps are up-regulated in melanoma tissue and correlate with patient clinical parameters

Heat shock proteins (hsps) have been studied in numerous cancer types, but a clear view of their clinical relevance in melanoma remains elusive. Therefore, the aim of this study was to investigate the expression of hsps in melanoma with respect to patient clinical parameters. Using Western immunoblotting, hsps 90, 70, 60, 40 and 32 were observed to be widely expressed in metastatic melanomas (n = 31), while immunofluorescence demonstrated that in the majority of samples these hsps, apart from hsp32, were increased in expression in melanoma cells compared with surrounding non-melanoma cells in situ (n = 8). Correlating hsp expression with patient clinical parameters indicated that greater hsp90 (P < 0.02) and hsp40 (P < 0.03) expression correlated with advanced stage (stage III Vs stage IV), while in the case of hsp40, this was additionally associated with reduced patient survival (P < 0.05). In contrast, higher hsp32 expression was associated with improved patient survival (P < 0.007). On the other hand, the expression of the other hsps did not correlate with any obtainable patient clinical parameters. This study provides further evidence for the importance of hsps in melanoma and for their use as therapeutic targets and biomarkers, but larger-scale follow-up studies are required to confirm these results.

Electronic supplementary material

The online version of this article (doi:10.1007/s12192-012-0363-1) contains supplementary material, which is available to authorized users.     

Apodemia mormo in Canada: population genetic data support prior conservation ranking

Like many species, the Mormon Metalmark butterfly (Apodemia mormo) has been given conservation ranking in Canada based on limited data. This species is widespread across western North America, but has only two populations in Canada: an “endangered” population in the Similkameen valley of British Columbia, and a “threatened” population in Grasslands National Park (GNP) in Saskatchewan. Here we present genetic data from 1498 base pairs of the cytochrome oxidase I gene sequence and six novel microsatellite loci in order to assess (1) whether the two populations are related, (2) the degree to which they are genetically diverse and demographically stable, and (3) what their relationships are to the nearest unranked populations of A. mormo across the Canada-United States border. Our principal conclusion is that the two populations are not closely related genetically. We also found that the British Columbia population is genetically depauperate and, with the exception of the nearest neighboring populations across the border, not recently genetically connected to other populations in the Pacific Northwest. In comparison, the Saskatchewan population is genetically diverse, and gene flow occurs with several other eastern populations. Population structure was not detected within either the British Columbia or the Saskatchewan populations. This research supports the prior conservation rankings of both populations and provides new insight that will help to inform future management decisions for the Canadian populations of this charismatic butterfly.