Fibroblast growth factor (FGF) signaling plays critical roles in key biological processes ranging from embryogenesis to wound healing and has strong links to several hallmarks of cancer. Genetic alterations in FGF receptor (FGFR) family members are associated with increased tumor growth, metastasis, angiogenesis, and decreased survival. JNJ-42756493, erdafitinib, is an orally active small molecule with potent tyrosine kinase inhibitory activity against all four FGFR family members and selectivity versus other highly related kinases. JNJ-42756493 shows rapid uptake into the lysosomal compartment of cells in culture, which is associated with prolonged inhibition of FGFR signaling, possibly due to sustained release of the inhibitor. In xenografts from human tumor cell lines or patient-derived tumor tissue with activating FGFR alterations, JNJ-42756493 administration results in potent and dose-dependent antitumor activity accompanied by pharmacodynamic modulation of phospho-FGFR and phospho-ERK in tumors. The results of the current study provide a strong rationale for the clinical investigation of JNJ-42756493 in patients with tumors harboring FGFR pathway alterations.

SummaryFungi of the genus Aspergillus are widespread in the environment. Some Aspergillus species, most commonly Aspergillus fumigatus, may lead to a variety of allergic reactions and life‐threatening systemic infections in humans. Invasive aspergillosis occurs primarily in patients with severe immunodeficiency, and has dramatically increased in recent years. There are several factors at play that contribute to aspergillosis, including both fungus and host‐related factors such as strain virulence and host pulmonary structure/immune status, respectively. The environmental tenacity of Aspergilllus, its dominance in diverse microbial communities/habitats, and its ability to navigate the ecophysiological and biophysical challenges of host infection are attributable, in large part, to a robust stress‐tolerance biology and exceptional capacity to generate cell‐available energy. Aspects of its stress metabolism, ecology, interactions with diverse animal hosts, clinical presentations and treatment regimens have been well‐studied over the past years. Here, we synthesize these findings in relation to the way in which some Aspergillus species have become successful opportunistic pathogens of human‐ and other animal hosts. We focus on the biophysical capabilities of Aspergillus pathogens, key aspects of their ecophysiology and the flexibility to undergo a sexual cycle or form cryptic species. Additionally, recent advances in diagnosis of the disease are discussed as well as implications in relation to questions that have yet to be resolved.

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Brettanomyces (Dekkera) bruxellensis is an ascomycetous yeast of major importance in the food, beverage and biofuel industry. It has been isolated from various man-made ecological niches that are typically characterized by harsh environmental conditions such as wine, beer, soft drink, etc. Recent comparative genomics studies revealed an immense intraspecific diversity, but it is still unclear whether this genetic diversity also leads to systematic differences in fermentation performance and (off-)flavor production, and to what extent strains have evolved to match their ecological niche. Here, we present an evaluation of the fermentation properties of eight genetically diverse B. bruxellensis strains originating from beer, wine and soft drinks. We show that sugar consumption and aroma production during fermentation are determined by both the yeast strain and composition of the medium. Furthermore, our results indicate a strong niche adaptation of B. bruxellensis, most clearly for wine strains. For example, only strains originally isolated from wine were able to thrive well and produce the typical Brettanomyces-related phenolic off-flavors 4-ethylguaiacol and 4-ethylphenol when inoculated in red wine. Sulfite tolerance was found as a key factor explaining the observed differences in fermentation performance and off-flavor production. Sequence analysis of genes related to phenolic off-flavor production, however, revealed only marginal differences between the isolates tested, especially at the amino acid level. Altogether, our study provides novel insights in the Brettanomyces metabolism of flavor production, and is highly relevant for both the wine and beer industry.

Nectar is a crucial energy resource that strongly mediates the interactions between plants and animal pollinators or plant defenders. Previous research has shown that nectar is frequently colonized by microorganisms, most commonly bacteria and yeasts, which can have a strong impact on nectar chemistry. However, at present little is known about the effects of microorganisms on the fitness of animals feeding on nectar. We used three nectar bacteria representing different metabolic groups (Asaia sp., Lactococcus sp. and Rosenbergiella sp.) and the common generalist aphid parasitoid Aphidius ervi (Haliday; Hymenoptera: Braconidae) to test the hypothesis that different nectar‐dwelling bacteria affect nectar consumption and insect longevity differently by altering the chemistry of nectar. Bacteria significantly affected nectar chemistry by altering its acidity, sugar and amino acids composition/concentration and by adding compounds synthesized by the microbes. Although inoculation with bacteria did not affect nectar consumption, a significant difference in insect longevity was observed. The impact on longevity was species specific, with Lactococcus being beneficial and Asaia having a detrimental effect. Bacteria have a strong impact on nectar chemistry and changes in nectar chemistry may not only influence the foraging behaviour of flower‐visiting animals and impact on plant fitness, but also influence the fitness of nectar‐consuming organisms. As effects were species dependent, changes in nectar chemistry induced by different bacteria may have contrasting effects on the interactions between plants and insects. It is therefore essential to know how different microbes alter nectar chemistry to understand the relationships between plants, nectar‐inhabiting microbes and nectar‐consuming animals. A http://onlinelibrary.wiley.com/doi/10.1111/1365-2435.12933/suppinfo is available for this article.