IHG-1 increases mitochondrial fusion and bioenergetic function

Induced in high glucose-1 (IHG-1) is a conserved mitochondrial protein associated with diabetic nephropathy (DN) that amplifies profibrotic transforming growth factor (TGF)-β1 signaling and increases mitochondrial biogenesis. Here we report that inhibition of endogenous IHG-1 expression results in reduced mitochondrial respiratory capacity, ATP production, and mitochondrial fusion. Conversely, overexpression of IHG-1 leads to increased mitochondrial fusion and also protects cells from reactive oxygen species-induced apoptosis. IHG-1 forms complexes with known mediators of mitochondrial fusion-mitofusins (Mfns) 1 and 2-and enhances the GTP-binding capacity of Mfn2, suggesting that IHG-1 acts as a guanine nucleotide exchange factor. IHG-1 must be localized to mitochondria to interact with Mfn1 and Mfn2, and this interaction is necessary for increased IHG-1-mediated mitochondrial fusion. Together, these findings indicate that IHG-1 is a novel regulator of both mitochondrial dynamics and bioenergetic function and contributes to cell survival following oxidant stress. We propose that in diabetic kidney disease increased IHG-1 expression protects cell viability and enhances the actions of TGF-β, leading to renal proximal tubule dedifferentiation, an important event in the pathogenesis of this devastating condition.

Expertly validated models and phylogenetically-controlled analysis suggests responses to climate change are related to species traits in the Order Lagomorpha

Climate change during the last five decades has impacted significantly on natural ecosystems and the rate of current climate change is of great concern among conservation biologists. Species Distribution Models (SDMs) have been used widely to project changes in species’ bioclimatic envelopes under future climate scenarios. Here, we aimed to advance this technique by assessing future changes in the bioclimatic envelopes of an entire mammalian order, the Lagomorpha, using a novel framework for model validation based jointly on subjective expert evaluation and objective model evaluation statistics. SDMs were built using climatic, topographical and habitat variables for all 87 lagomorph species under past and current climate scenarios. Expert evaluation and Kappa values were used to validate past and current models and only those deemed ‘modellable’ within our framework were projected under future climate scenarios (58 species). Phylogenetically-controlled regressions were used to test whether species traits correlated with predicted responses to climate change. Climate change is likely to impact more than two-thirds of lagomorph species, with leporids (rabbits, hares and jackrabbits) likely to undertake poleward shifts with little overall change in range extent, whilst pikas are likely to show extreme shifts to higher altitudes associated with marked range declines, including the likely extinction of Kozlov’s Pika (Ochotona koslowi). Smaller-bodied species were more likely to exhibit range contractions and elevational increases, but showing little poleward movement, and fecund species were more likely to shift latitudinally and elevationally. Our results suggest that species traits may be important indicators of future climate change and we believe multi-species approaches, as demonstrated here, are likely to lead to more effective mitigation measures and conservation management. We strongly advocate studies minimising data gaps in our knowledge of the Order, specifically collecting more specimens for biodiversity archives and targeting data deficient geographic regions.

Biogeography, macroecology and species’ traits mediate competitive interactions in the order Lagomorpha

1. In addition to abiotic determinants, biotic factors, including competitive, interspecific interactions, limit species’ distributions. Environmental changes in human disturbance, land use and climate are predicted to have widespread impacts on interactions between species, especially in the order Lagomorpha due to the higher latitudes and more extreme environmental conditions they occupy.
2. We reviewed the published literature on interspecific interactions in the order Lagomorpha, and compared the biogeography, macroecology, phylogeny and traits of species known to interact with those of species with no reported interactions, to investigate how projected future environmental change may affect interactions and potentially alter species’ distributions.
3. Thirty-three lagomorph species have competitive interactions reported in the literature; the majority involve hares (Lepus sp.) or the eastern cottontail rabbit (Sylvilagus floridanus). Key regions for interactions are located between 30-50°N of the Equator, and include eastern Asia (southern Russia on the border of Mongolia) and North America (north western USA).
4. Closely related, large-bodied, similarly sized species occurring in regions of human-modified, typically agricultural landscapes, or at high elevations are significantly more likely to have reported competitive interactions than other lagomorph species.
5. We identify species’ traits associated with competitive interactions, and highlight some potential impacts that future environmental change may have on interspecific interactions. Our approach using bibliometric and biological data is widely applicable, and with relatively straightforward methodologies, can provide insights into interactions between species.
6. Our results have implications for predicting species’ responses to global change, and we advise that capturing, parameterizing and incorporating interspecific interactions into analyses (for example, species distribution modelling) may be more important than suggested by the literature.

Diversity, extinction, and threat status in Lagomorphs

A quarter of all lagomorphs (pikas, rabbits, hares and jackrabbits) are threatened with extinction, including several genera that contain only one species. The number of species in a genus correlates with extinction risk in lagomorphs, but not in other mammal groups, and this is concerning because the non-random extinction of small clades disproportionately threatens genetic diversity and phylogenetic history. Here, we use phylogenetic analyses to explore the properties of the lagomorph phylogeny and test if variation in evolution, biogeography and ecology between taxa explains current patterns of diversity and extinction risk. Threat status was not related to body size (and, by inference, its biological correlates), and there was no phylogenetic signal in extinction risk. We show that the lagomorph phylogeny has a similar clade-size distribution to other mammals, and found that genus size was unrelated to present climate, topography, or geographic range size. Extinction risk was greater in areas of higher human population density and negatively correlated with anthropogenically modified habitat. Consistent with this, habitat generalists were less likely to be threatened. Our models did not predict threat status accurately for taxa that experience region-specific threats. We suggest that pressure from human populations is so severe and widespread that it overrides ecological, biological, and geographic variation in extant lagomorphs.

Effects of Elodea nuttallii on temperate freshwater plants, microalgae and invertebrates: small differences between invaded and uninvaded areas

The invasive aquatic plant species Elodea nuttallii could pose a considerable risk to European freshwater ecosystems based on its current distribution, rate of spread and potential for high biomass. However, little research has been conducted on the impacts of this species on native biota. This study takes an ecosystem-wide approach and examines the impact of E. nuttallii on selected physicochemical parameters (dissolved oxygen and pH), algae, invertebrate and macrophyte communities. Elodea nuttallii had small but significant impacts on plant, invertebrate and algal species. The richness of algal periphyton was lower on E. nuttallii than on native macrophytes. The taxonomic composition of invertebrate communities associated with E. nuttallii differed from that associated with similar native plant species, but did not differ in terms of total biomass or species richness. Macrophyte species richness and total cover were positively correlated with percentage cover of E. nuttallii. Not all macrophyte species responded in the same way to E. nuttallii invasion; cover of the low-growing species, Elodea canadensis and charophytes were negatively correlated with E. nuttallii cover, whilst floating-rooted plants were positively correlated with E. nuttallii cover. All observed differences in the macrophyte community were small relative to other factors such as nutrient levels, inter-annual variation and differences between sites. Despite this, the observed negative association between E. nuttallii and charophytes is a key concern due to the rarity and endangered status of many charophyte species.

Evaluation of the diagnostic potential of a novel field immunomagnetic separation-immunochromatographic lateral flow assay to detect Mycobacterium bovis cells in European badger (Meles meles) faeces

The European badger (Meles meles) is a natural reservoir for Mycobacterium bovis, the causative agent of Bovine Tuberculosis, and has consequently been implicated in transmission of the disease to cattle. This study describes application of a novel M. bovis-specific immunochromatographic (lateral flow) assay in combination with immunomagnetic separation (IMS-LFD), to test badger faeces samples. In total, 441 faeces samples from badgers of unknown disease status collected from latrines at 110 badger setts throughout Northern Ireland (NI) and 100 faeces samples from badgers of known infection status from Great Britain (GB) were tested. Faeces (approx. 1g) was homogenised in 9 ml phosphate buffered saline, filtered (70 µm), and then 6-8 ml subjected to the IMS-LFD test. Residual clarified faecal homogenates were subjected to automated IMS followed by MGIT™ liquid culture (AIMS-MGIT™ culture) and qPCR (AIMS-qPCR). Evidence for the presence of M. bovis was obtained for 78 (18%), 61 (14%) and 140 (32%) of 441 NI badger faeces samples, and 10 (10%), 41 (41%) and 56 (56%) of 100 GB badger faeces samples, by IMS-LFD, AIMS-MGIT culture and AIMS-qPCR tests, respectively. The IMS-LFD test was less sensitive than AIMS-qPCR for detection of M. bovis and was, therefore, detecting badgers shedding high numbers of M. bovis in their faeces only. However, these ‘super shedders’ may be primarily responsible for the spread of Bovine Tuberculosis so are, therefore, an important target. This non-invasive test could form the basis of a field surveillance tool to indicate infected badger groups which are actively spreading M. bovis.

Ellerman Bombs with Jets: Cause and Effect

Ellerman Bombs (EBs) are thought to arise as a result of photospheric magnetic reconnection. We use data from the Swedish 1-m Solar Telescope(SST), to study EB events on the solar disk and at the limb. Both datasets show that EBs are connected to the foot-points of forming chromospheric jets. The limb observations show that a bright structure in the H$\alpha$ blue wing connects to the EB initially fuelling it,leading to the ejection of material upwards. The material moves along a loop structure where a newly formed jet is subsequently observed in the red wing of H$\alpha$. In the disk dataset, an EB initiates a jet which propagates away from the apparent reconnection site within the EB flame.The EB then splits into two, with associated brightenings in the inter-granular lanes (IGLs). Micro-jets are then observed, extending to500 km with a lifetime of a few minutes. Observed velocities of themicro-jets are approximately 5-10 km s$^{-1}$, while their chromospheric counterparts range from 50-80 km s$^{-1}$. MURaM simulations of quiet Sun reconnection show that micro-jets with similar properties to that of the observations follow the line of reconnection in the photosphere,with associated H$\alpha$ brightening at the location of increased temperature.

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.

METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.

RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)).

CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.