Summary 1.Elevational tree line change in the southern Swedish Scandes was quantified for the period 1915-2007 and for two sub-periods 1915-1975 and 1975-2007. The study focused on Betula pubescens ssp. czerepanovii , Picea abies and Pinus sylvestris at a large number of sites distributed over an 8000-km 2 area. The basic approach included revisitations of fixed sites (elevational belt transects) and measurements of tree line positions (m a.s.l.) during these three periods. 2. Over the past century, tree lines of all species rose at 95% of the studied localities, with means of 70-90 m. All three species displayed maximum upshifts by about 200 m, which manifests a near-perfect equilibrium with instrumentally recorded air temperature change. This magnitude of response was realized only in particular topographic situations, foremost wind-sheltered and steep concave slopes. Other sites, with more wind-exposed topoclimatic conditions, experienced lesser magnitudes of upshifts. Thus, spatial elevational tree line responses to climate change are markedly heterogeneous and site-dependent. Modelling of the future evolution of the forest-alpine tundra transition has to consider this fact. Even in a hypothetical case of substantial climate warming, tree lines are unlikely to advance on a broad front and a large proportion of the alpine tundra will remain treeless. 3. During the period 1975-2007, the tree lines of Picea and Pinus (in particular) advanced more rapidly than that of Betula towards the alpine region. These species-specific responses could signal a potential trajectory for the evolution of the ecotone in a warmer future. Thereby a situation with some resemblance with the relatively warm and dry early Holocene would emerge. 4. Substantial tree line upshifts over the past two to three decades coincide with air and soil warming during all seasons. This implies that both summer and winter temperatures have to be included in models of climate-driven tree line performance. 5. Synthesis . Maximum tree line rise by 200 m represents a unique trend break in the long-term Holocene tree line regression, which has been driven by average climate cooling for nearly 10 000 years. Tree line positions are well-restored to their pre-Little Ice Age positions. Recent tree line ascent is a truly anomalous event in Holocene vegetation history and possibly unprecedented for seven millennia.

Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin signal transduction in adipose tissue and the liver. Skeletal muscle is an important tissue for controlling energy expenditure and whole-body insulin sensitivity; however, the physiological importance of SOCS3 in this tissue has not been examined. Therefore, we generated mice that had SOCS3 specifically deleted in skeletal muscle (SOCS MKO). The SOCS3 MKO mice had normal muscle development, body mass, adiposity, appetite, and energy expenditure compared with wild-type (WT) littermates. Despite similar degrees of obesity when fed a high-fat diet, SOCS3 MKO mice were protected against the development of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance.

Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.

Asthma exacerbations are triggered by rhinovirus infections. We employed a systems biology approach to delineate upper-airway gene network patterns underlying asthma exacerbation phenotypes in children. Cluster analysis unveiled distinct IRF7 hi versus IRF7 lo molecular phenotypes, the former exhibiting robust upregulation of Th1/type I IFN responses and the latter an alternative signature marked by upregulation of cytokine and growth factor signaling and downregulation of IFN-g. The two phenotypes also produced distinct clinical phenotypes. For IRF7 lo children, symptom duration prior to hospital presentation was more than twice as long from initial symptoms (p = 0.011) and nearly three times as long for cough (p < 0.001), the odds ratio of admission to hospital was increased more than 4-fold (p = 0.018), and time to recurrence was shorter (p = 0.015). In summary, our findings demonstrate that asthma exacerbations in children can be divided into IRF7 hi versus IRF7 lo phenotypes with associated differences in clinical phenotypes.

Plant mitogenomes can be difficult to assemble because they are structurally dynamic and prone to intergenomic DNA transfers, leading to the unusual situation where an organelle genome is far outnumbered by its nuclear counterparts. As a result, comparative mitogenome studies are in their infancy and some key aspects of genome evolution are still known mainly from pregenomic, qualitative methods. To help address these limitations, we combined machine learning and in silico enrichment of mitochondrial-like long reads to assemble the bacterial-sized mitogenome of Norway spruce (Pinaceae: Picea abies). We conducted comparative analyses of repeat abundance, intergenomic transfers, substitution and rearrangement rates, and estimated repeat-by-repeat homologous recombination rates. Prompted by our discovery of highly recombinogenic small repeats in P. abies, we assessed the genomic support for the prevailing hypothesis that intramolecular recombination is predominantly driven by repeat length, with larger repeats facilitating DNA exchange more readily. Overall, we found mixed support for this view: Recombination dynamics were heterogeneous across vascular plants and highly active small repeats (ca. 200 bp) were present in about one-third of studied mitogenomes. As in previous studies, we did not observe any robust relationships among commonly studied genome attributes, but we identify variation in recombination rates as a underinvestigated source of plant mitogenome diversity.