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Obesity incidence is increasing worldwide with the urgent need to identify new therapeutics. Sex differences in immune cell activation drive obesity-mediated pathologies where males are more susceptible to obesity comorbidities and exacerbated inflammation. Here, we demonstrate that the macrophage-secreted protein RELMα critically protects females against high-fat diet (HFD)-induced obesity. Compared to male mice, serum RELMα levels were higher in both control and HFD-fed females and correlated with frequency of adipose macrophages and eosinophils. RELMα-deficient females gained more weight and had proinflammatory macrophage accumulation and eosinophil loss in the adipose stromal vascular fraction (SVF), while RELMα treatment or eosinophil transfer rescued this phenotype. Single-cell RNA-sequencing of the adipose SVF was performed and identified sex and RELMα-dependent changes. Genes involved in oxygen sensing and iron homeostasis, including hemoglobin and lncRNA Gm47283/Gm21887, correlated with increased obesity, while eosinophil chemotaxis and response to amyloid-beta were protective. Monocyte-to-macrophage transition was also dysregulated in RELMα-deficient animals. Collectively, these studies implicate a RELMα–macrophage–eosinophil axis in sex-specific protection against obesity and uncover new therapeutic targets for obesity.

K&S developed and tested the Advanced Process Diagnostics (APD) algorithm to classify bonding outliers in ultrasonic wire bond production. APD is a software feature, part of Kulicke & Soffa wedge bonders to measure and analyze process signals and detect and classify bond outliers. APD helps bonder operators, production supervisors and process engineers to detect process deviations and fix the underlying root causes. APD measures bond signals, such as deformation, ultrasonic current and ultrasonic frequency. Bonds are automatically divided into subgroups based on bond order and process parameters and the signals within a subgroup are then normalized. For outlier classification, the features are extracted from the normalized signals and combined into failure class values. The failure classes, such as contamination, misaligned wire and unstable substrate, are calculated independently. Within the APD feature, a user can define limits for the failure class values and define bonder actions based on the severity of the detected outlier. We measured the detection rates for large wire Al bond failure classes and demonstrate how APD calculates failure class values from the signals. Additionally, we show how new signal features and failure classes can be defined to detect production specific or rare failure classes. Finally, we present outlier classification performance metrics against large production data sets.

Understanding how environmental drivers induce changes in plant composition and diversity across evolutionary time can provide important insights into the mechanisms of community assembly. We evaluated how taxonomic and phylogenetic diversity and structure of plant communities change along a local-scale edaphic and topographic gradient in the Tepequém table mountain, Brazilian Amazon. We selected three phytophysiognomies along the altitudinal gradient: Open Rupestrian Grassland, Shrubby Rupestrian Grassland, and Forest. We compared community composition and taxonomic and phylogenetic diversity between phytophysiognomies, and we tested regression linear effect models to investigate the effect of altitude and soil properties on taxonomic and phylogenetic diversity. The highest species richness and phylogenetic diversity were found at lower elevation for Forest. Mean pairwise phylogenetic distance, mean nearest taxon phylogenetic distance, and all standardised phylogenetic metrics were significantly lower in Shrubby Rupestrian Grassland. This phytophysiognomy showed phylogenetic clustering. Forest showed a cluster pattern when only terminal nodes are considered and random dispersion to deep phylogenetic nodes. Open Rupestrian Grassland also showed random phylogenetic structure. The regression analyses showed that species richness and different phylogenetic diversity metrics were explained by altitude and soil properties. However, standardised metrics were not explained by these environmental variables. Comprehensive studies including the role of environmental drivers in plant evolutionary history along the altitudinal gradient are necessary for explaining community assembly patterns and provide additional information for conservation planning.

Fungal infections caused by Candida and Cryptococcus are particularly dangerous for immunocompromised individuals. In this study, we identified that benzimidazole fused pyrrolo[3,4-b]quinoline compounds have potent antifungal activity against several clinical isolates of pathogenic fungal strains. Specifically, the compound 6a did not show cytotoxicity against mammalian cells at a concentration that inhibits the growth of fungal strains. In addition, the compound 6a also significantly reduced the metabolic activity of fungal cells in the Candida albicans biofilms. Collectively, our results indicate that benzimidazole fused quinoline compounds have a potential to develop as an antifungal agents.

Candida albicans is one of the most common causes of fungal infections in humans with a significant mortality rate. However, the factors involved in C. albicans gastrointestinal (GI) colonization remain unclear. We hypothesize that secondary bile acids have direct antifungal activity against C. albicans and may play a critical role in maintaining GI colonization resistance against C. albicans. In this study, we investigated the effect of secondary bile acids including lithocholic acid (LCA) and deoxycholic acid (DCA) on C. albicans growth and morphogenesis. Results indicate that LCA and DCA at in vivo cecal micelle concentrations inhibit C. albicans growth in vitro. Interestingly, LCA and DCA also significantly inhibited the germ tube, hyphae and biofilm formation in C. albicans. In addition, pre-treatment of C. albicans with LCA and DCA significantly reduced the percentage of C. albicans cells attached to a colon cancer cell line. Collectively, our results demonstrate that secondary bile acids play an important role in controlling the growth and morphological switching of C. albicans. Results from this study demonstrate that secondary bile acid possess direct antifungal activity against C. albicans, explaining a potential mechanism for gastrointestinal colonization resistance against C. albicans.