Two-phase importance sampling for inference about transmission trees

There has been growing interest in the statistics community to develop methods for inferring transmission pathways of infectious pathogens from molecular sequence data. For many datasets, the computational challenge lies in the huge dimension of the missing data. Here, we introduce an importance sampling scheme in which the transmission trees and phylogenies of pathogens are both sampled from reasonable importance distributions, alleviating the inference. Using this approach, arbitrary models of transmission could be considered, contrary to many earlier proposed methods. We illustrate the scheme by analysing transmissions of Streptococcus pneumoniae from household to household within a refugee camp, using data in which only a fraction of hosts is observed, but which is still rich enough to unravel the within-household transmission dynamics and pairs of households between whom transmission is plausible. We observe that while probability of direct transmission is low even for the most prominent cases of transmission, still those pairs of households are geographically much closer to each other than expected under random proximity.     

Concurrent biotic interactions influence plant performance at their altitudinal distribution margins

Recent studies have shown that biotic interactions can shape species' distributions, but empirical data on multiple biotic interactions are scarce. Therefore, we examined effects of plant–plant and plant–herbivore interactions on plant survival, growth and reproduction at different altitudes. For these purposes we conducted a factorial neighbor removal and large herbivore exclusion experiment with six transplant species (three tall forbs with their main distribution at low altitudes and three small forbs with their main distribution at high altitudes) on Låkta?ohkka Mountain, northern Sweden, replicated at two altitudes (ca 600 and 900 m a.s.l.) and consequently a 2.1°C difference in summer air temperatures. Overall transplant survival was 93%. Two out of three tall forbs grew better at low than at high altitudes, while no significant differences in growth between altitudes were found for any of the three small forbs. Since the main difference in abiotic conditions between the altitudes was most likely in temperature (as the sites were topographically and edaphically matched as closely as possible), this result indicates that climatic warming could induce upward migration of tall low‐altitude forbs. Negative plant–plant interactions prevailed at both altitudes, and we found indications that competition may set the lower altitudinal limits of some small tundra forbs. Thus, increased competition in response to climate warming may potentially shift the lower margins of high‐altitude forbs' distributions upward. Large mammalian grazers reduced the growth of tall forbs and enhanced the flowering of small forbs, and grazers could thus at least partly counteract the anticipated warming‐induced distribution shifts.     

Expression of photosynthesis- and senescence-related genes during leaf development and senescence in silver birch (Betula pendula) seedlings

Leaf development and senescence were studied in greenhouse-grown silver birch ( Betula pendula Roth) seedlings over a period of 7 weeks. Prior to the experiment, leaves from 100 seedlings were marked for five sampling dates. Timing of the developmental phases was studied with biochemical analyses of total soluble protein, Rubisco protein, chlorophyll concentration and at the level of gene expression related to photosynthesis, energy metabolism, ethylene synthesis and protein degradation. During the sampling period, an initial increase in photosynthetic capacity could be seen, when expression of the Rubisco small subunit gene ( RbcS ) and Rubisco protein (EC 4.1.1.39) were examined. Down-regulation of photosynthesis, visible as a decrease in Rubisco protein and RbcS mRNA, started soon after full expansion of the leaves and processes related to senescence followed. mRNA accumulation for the ethylene-forming enzyme 1-aminocyclopropane-1-carboxylic acid oxidase increased first during the onset of senescence. Protein degradation was observed as a loss of soluble proteins, with a simultaneous increase in the leucine aminopeptidase (EC 3.4.11.1) mRNA levels. The mRNA levels of ribonuclease-like pathogenesis-related protein 10 also increased clearly during senescence, but the mitochondrial phosphate translocator mRNA showed only a slight increase. Chlorophyll concentration of the leaves decreased after the mRNA levels of these senescence-related genes had become more abundant.     

Blue LED causes autophagic cell death in human osteosarcoma by increasing ROS generation and dephosphorylating EGFR

Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light-emitting diodes (LED)-based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation-induced autophagy characterized by alterations in autophagy protein markers including Beclin-1, LC3-II/LC3-I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti-tumour activities of blue LED irradiation. Next, ROS scavenger N-acetyl-L-cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED-induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin-1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin-1 and EGFR-immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin-1 upon blue LED irradiation in OS cells. In addition, Beclin-1 down-regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti-tumour effects on OS by triggering ROS and EGFR/Beclin-1-mediated autophagy signalling pathway, representing a potential approach for human OS treatment.