CX3CR1 Is a Modifying Gene of Survival and Progression in Amyotrophic Lateral Sclerosis

The objective of this study was to investigate the association of functional variants of the human CX3CR1 gene (Fractalkine receptor) with the risk of Amyotrophic Lateral Sclerosis (ALS), the survival and the progression rate of the disease symptoms in a Spanish ALS cohort. 187 ALS patients (142 sporadic [sALS] and 45 familial) and 378 controls were recruited. We investigated CX3CR1 V249I (rs3732379) and T280M (rs3732378) genotypes and their haplotypes as predictors of survival, the progression rate of the symptoms (as measured by ALSFRS-R and FVC decline) and the risk of suffering ALS disease. The results indicated that sALS patients with CX3CR1 249^I/I or 249^V/I genotypes presented a shorter survival time (42.27±4.90) than patients with 249^V/V genotype (67.65±7.42; diff −25.49 months 95%CI [−42.79,−8.18]; p = 0.004; adj-p = 0.018). The survival time was shorter in sALS patients with spinal topography and CX3CR1 249^I alleles (diff = −29.78 months; 95%CI [−49.42,−10.14]; p = 0.003). The same effects were also observed in the spinal sALS patients with 249^I–280^M haplotype (diff = −27.02 months; 95%CI [−49.57, −4.48]; p = 0.019). In the sALS group, the CX3CR1 249^I variant was associated with a faster progression of the disease symptoms (OR = 2.58; 95IC% [1.32, 5.07]; p = 0.006; adj-p = 0.027). There was no evidence for association of these two CX3CR1 variants with ALS disease risk. The association evidenced herein is clinically relevant and indicates that CX3CR1 could be a disease-modifying gene in sALS. The progression rate of the disease''s symptoms and the survival time is affected in patients with one or two copies of the CX3CR1 249I allele. The CX3CR1 is the most potent ALS survival genetic factor reported to date. These results reinforce the role of the immune system in ALS pathogenesis.     

Microbial nitrogen and phosphorus co-limitation across permafrost region

The status of plant and microbial nutrient limitation have profound impacts on ecosystem carbon cycle in permafrost areas, which store large amounts of carbon and experience pronounced climatic warming. Despite the long-term standing paradigm assumes that cold ecosystems primarily have nitrogen deficiency, large-scale empirical tests of microbial nutrient limitation are lacking. Here we assessed the potential microbial nutrient limitation across the Tibetan alpine permafrost region, using the combination of enzymatic and elemental stoichiometry, genes abundance and fertilization method. In contrast with the traditional view, the four independent approaches congruently detected widespread microbial nitrogen and phosphorus co-limitation in both the surface soil and deep permafrost deposits, with stronger limitation in the topsoil. Further analysis revealed that soil resources stoichiometry and microbial community composition were the two best predictors of the magnitude of microbial nutrient limitation. High ratio of available soil carbon to nutrient and low fungal/bacterial ratio corresponded to strong microbial nutrient limitation. These findings suggest that warming-induced enhancement in soil nutrient availability could stimulate microbial activity, and probably amplify soil carbon losses from permafrost areas.     

Seasonally different response of photosynthetic activity to daytime and night‐time warming in the Northern Hemisphere

Over the last century the Northern Hemisphere has experienced rapid climate warming, but this warming has not been evenly distributed seasonally, as well as diurnally. The implications of such seasonal and diurnal heterogeneous warming on regional and global vegetation photosynthetic activity, however, are still poorly understood. Here, we investigated for different seasons how photosynthetic activity of vegetation correlates with changes in seasonal daytime and night‐time temperature across the Northern Hemisphere (>30°N), using Normalized Difference Vegetation Index (NDVI) data from 1982 to 2011 obtained from the Advanced Very High Resolution Radiometer (AVHRR). Our analysis revealed some striking seasonal differences in the response of NDVI to changes in day‐ vs. night‐time temperatures. For instance, while higher daytime temperature (T_max) is generally associated with higher NDVI values across the boreal zone, the area exhibiting a statistically significant positive correlation between T_max and NDVI is much larger in spring (41% of area in boreal zone – total area 12.6 × 10⁶ km²) than in summer and autumn (14% and 9%, respectively). In contrast to the predominantly positive response of boreal ecosystems to changes in T_max, increases in T_max tended to negatively influence vegetation growth in temperate dry regions, particularly during summer. Changes in night‐time temperature (T_min) correlated negatively with autumnal NDVI in most of the Northern Hemisphere, but had a positive effect on spring and summer NDVI in most temperate regions (e.g., Central North America and Central Asia). Such divergent covariance between the photosynthetic activity of Northern Hemispheric vegetation and day‐ and night‐time temperature changes among different seasons and climate zones suggests a changing dominance of ecophysiological processes across time and space. Understanding the seasonally different responses of vegetation photosynthetic activity to diurnal temperature changes, which have not been captured by current land surface models, is important for improving the performance of next generation regional and global coupled vegetation‐climate models.     

Crocodile swim tracks from the latest Cretaceous of Europe

Recently discovered evidence of tracks in the continental beds of the Late Cretaceous Tremp Formation in the southern Pyrenees (NE Iberian Peninsula) has been identified as scratch marks made by buoyant crocodiles. The tracks are preserved in two distinct environments and substrates (marly limestones originating in a littoral mud flat and fine‐grained sandstones deposited in fluvial settings). Most of the crocodylian traces are ascribed to ichnogenus Characichnos, whereas a single plantigrade pes track is assigned to ichnogenus cf. Crocodylopodus. The crocodylian swim traces (Characichnos ichnofacies) found in the early and late Maastrichtian co‐occur with Brontopodus ichnofacies attributable to terrestrial tetrapods (titanosaur sauropods, cf. Brontopodus ichnogenus; and hadrosaurid ornithopods, Hadrosauropodus ichnogenus). Analysis of the tracks allows the interpretation of palaeoenvironmental settings and track production. Thus, in lagoonal environments, swim tracks of crocodylians were produced during the rise of the water level in successive tide cycles; in fluvial settings, the swim traces of crocodylians were produced within the channel at the low‐water stage. To date, there are no reports of Late Cretaceous crocodylian tracks in Europe, and the studied evidence represents the first and youngest track record of the group in the latest part of the Cretaceous (C29r) in this continent and probably in the world.     

Fibronectin immobilization on to robotic-dispensed nanobioactive glass/polycaprolactone scaffolds for bone tissue engineering

Biotechnology Letters - Bioactive nanocomposite scaffolds with cell-adhesive surface have excellent bone regeneration capacities. Fibronectin (FN)-immobilized nanobioactive glass...     

Association between Ω3 and Ω6 fatty acid intakes and serum inflammatory markers in COPD

Dietary intake of polyunsaturated fatty acids, including omega-3 and omega-6, could modulate chronic obstructive pulmonary disease (COPD) persistent inflammation. We aimed to assess the relationship between dietary intake of omega-3 and omega-6 fatty acids and serum inflammatory markers in COPD. A total of 250 clinically stable COPD patients were included. Dietary data of the last 2 years were assessed using a validated food frequency questionnaire (122 items), which provided levels of three omega-3 fatty acids: docosahexaenoic acid, eicosapentaenoic acid and α-linolenic acid (ALA); and two omega-6 fatty acids: linoleic acid and arachidonic acid (AA). Inflammatory markers [C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor alpha (TNFα)] were measured in serum. Fatty acids and inflammatory markers were dichotomised according to their median values, and their association was assessed using multivariate logistic regression. Higher intake of ALA (an anti-inflammatory omega-3 fatty acid) was associated with lower TNFα concentrations [adjusted odds ratio (OR)=0.46; P=.049]. Higher AA intake (a proinflammatory omega-6 fatty acid) was related to higher IL-6 (OR=1.96; P=.034) and CRP (OR=1.95; P=.039) concentrations. Therefore, this study provides the first evidence of an association between dietary intake of omega-3 and omega-6 fatty acids and serum inflammatory markers in COPD patients.     

The Melibiose Transporter of Escherichia coli: CRITICAL CONTRIBUTION OF LYS-377 TO THE STRUCTURAL ORGANIZATION OF THE INTERACTING SUBSTRATE BINDING SITES*

We examine the role of Lys-377, the only charged residue in helix XI, on the functional mechanism of the Na⁺-sugar melibiose symporter from Escherichia coli. Intrinsic fluorescence, FRET, and Fourier transform infrared difference spectroscopy reveal that replacement of Lys-377 with either Cys, Val, Arg, or Asp disables both Na⁺ and melibiose binding. On the other hand, molecular dynamics simulations extending up to 200–330 ns reveal that Lys-377 (helix XI) interacts with the anionic side chains of two of the three putative ligands for cation binding (Asp-55 and Asp-59 in helix II). When Asp-59 is protonated during the simulations, Lys-377 preferentially interacts with Asp-55. Interestingly, when a Na⁺ ion is positioned in the Asp-55-Asp-59 environment, Asp-124 in helix IV (a residue essential for melibiose binding) reorients and approximates the Asp-55-Asp-59 pair, and all three acidic side chains act as Na⁺ ligands. Under these conditions, the side chain of Lys-377 interacts with the carboxylic moiety of these three Asp residues. These data highlight the crucial role of the Lys-377 residue in the spatial organization of the Na⁺ binding site. Finally, the analysis of the second-site revertants of K377C reveals that mutation of Ile-22 (in helix I) preserves Na⁺ binding, whereas that of melibiose is largely abolished according to spectroscopic measurements. This amino acid is located in the border of the sugar-binding site and might participate in sugar binding through apolar interactions.     

Habitat loss-induced tipping points in metapopulations with facilitation

Habitat loss is known to pervade extinction thresholds in metapopulations. Such thresholds result from a loss of stability that can eventually lead to collapse. Several models have been developed to understand the nature of these transitions and how they are affected by the locality of interactions, fluctuations or external drivers. Most models consider the impact of grazing or aridity as a control parameter that can trigger sudden shifts, once critical values are reached. Others explore instead the role played by habitat loss and fragmentation. Here we consider a minimal model incorporating facilitation between the individuals of the same species along with habitat destruction, with the aim of understanding how local cooperation and habitat loss interact with each other. A mathematical model incorporating facilitation and habitat destruction is derived, along with a spatially explicit simulation model. It is found that a catastrophic shift is expected for increasing levels of habitat loss, but the bifurcation becomes continuous when dispersal is local. Under these conditions, spatial patchiness is found and the qualitative change from discontinuous to continuous results are in agreement with previous studies on ecological systems. Our results suggest that species exhibiting facilitation and displaying short-range dispersal will be markedly more capable of avoiding catastrophic tipping points.     

Patterns and controls of the variability of radiation use efficiency and primary productivity across terrestrial ecosystems

Aim The controls of gross radiation use efficiency (RUE), the ratio between gross primary productivity (GPP) and the radiation intercepted by terrestrial vegetation, and its spatial and temporal variation are not yet fully understood. Our objectives were to analyse and synthesize the spatial variability of GPP and the spatial and temporal variability of RUE and its climatic controls for a wide range of vegetation types. Location A global range of sites from tundra to rain forest. Methods We analysed a global dataset on photosynthetic uptake and climatic variables from 35 eddy covariance (EC) flux sites spanning between 100 and 2200 mm mean annual rainfall and between ?13 and 26°C mean annual temperature. RUE was calculated from the data provided by EC flux sites and remote sensing (MODIS). Results Rainfall and actual evapotranspiration (AET) positively influenced the spatial variation of annual GPP, whereas temperature only influenced the GPP of forests. Annual and maximum RUE were also positively controlled primarily by annual rainfall. The main control parameters of the growth season variation of gross RUE varied for each ecosystem type. Overall, the ratio between actual and potential evapotranspiration and a surrogate for the energy balance explained a greater proportion of the seasonal variation of RUE than the vapour pressure deficit (VPD), AET and precipitation. Temperature was important for determining the intra‐annual variability of the RUE at the coldest energy‐limited sites. Main conclusions Our analysis supports the idea that the annual functioning of vegetation that is adapted to its local environment is more constrained by water availability than by temperature. The spatial variability of annual and maximum RUE can be largely explained by annual precipitation, more than by vegetation type. The intra‐annual variation of RUE was mainly linked to the energy balance and water availability along the climatic gradient. Furthermore, we showed that intra‐annual variation of gross RUE is only weakly influenced by VPD and temperature, contrary to what is frequently assumed. Our results provide a better understanding of the spatial and temporal controls of the RUE and thus could lead to a better estimation of ecosystem carbon fixation and better modelling.     

Radiation and phylogeography in the Japanese macaque, Macaca fuscata

The Japanese macaque (Macaca fuscata) presumably differentiated from eastern rhesus macaque (Macaca mulatta) populations during the Pleistocene and the two species are closely related. In order to analyse speciation and subspeciation events in the Japanese macaque and to describe historical and current relationships among their populations, we sequenced and analysed a fragment of 392bp of mitochondrial DNA (mtDNA) control region in 50 individuals belonging to six populations of Japanese macaque and compared these sequences with 89 eastern rhesus macaque control region sequences from GenBank/EMBL database. There were high genetic similarities between both species and only two positions were fixed within each species, which supports the inclusion of the Japanese macaque in a single species with eastern populations of rhesus macaques. Japanese macaque ancestors colonised Japan after the separation of the two species, estimated at between 0.31 and 0.88 million years ago (Mya). The star-like phylogeny, multimodal mismatch distribution, and lack of correlation between geographic and genetic distances are in accordance with a rapid dispersion of macaques throughout the archipelago after the arrival into Japan. The species shows low genetic variation within populations and high levels of genetic differentiation among populations with no mtDNA haplotype shared across populations. Genetic distances between Yakushima macaques (Macaca fuscata yakui) and any other population of Macaca fuscata fuscata subspecies are comparable to the distances between populations of Honshu, Awajishima, and Kyushu, not supporting the classification of Yakushima macaques as a different subspecies.