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Abstract Terbinafine, fluconazole, and amorolfine inhibit fungal ergosterol synthesis by acting on their target enzymes at different steps in the synthetic pathway, causing the accumulation of various intermediates. We found that the effects of these three in- hibitors on yeast morphology were different. The number of morphological parameters commonly altered by these drugs was only approximately 6% of the total. Using a rational strategy to find commonly changed parameters,we focused on hidden essential similarities in the phenotypes possibly due to decreased ergosterol levels. This resulted in higher apparent morphological similarity. Improvements in morphological similarity were observed even when canonical correlation analysis was used to select biologically meaningful morphological parameters related to gene function. In addition to changes in cell morphology, we also observed differences in the synergistic effects among the three inhibitors and in their fungicidal effects against pathogenic fungi possibly due to the accumulation of different intermediates. This study provided a comprehensive understanding of the properties of inhibitors acting in the same biosynthetic pathway.

Summary: During a molt or eclosion, insects shed their cuticle, an extracellular matrix made by underlying epidermal cells, by cleavage along a defined line. This means that the “cut here line” is pre-formed on the cuticle, and its formation is indispensable for insect life. Here, we show that the proper formation of the operculum ridge (OR), which is the “cut here line” on the puparium (pupal case) of Drosophila melanogaster, involves Notch signaling activation in the epidermal cells just beneath the future OR region (OR-forming cells). The inhibition of Notch signaling causes defects in eclosion due to failure in OR cleavage, the chitin organization and several cuticular proteins localization, glucose dehydrogenase (Gld) activity, and OR-forming cell shape. Our findings provide the first insight into the molecular basis of the structure and formation of the “cut here line” on the cuticle.

The main goal of group testing is to identify a small number of specific items among a large population of items. In this paper, we consider specific items as positives and inhibitors and non-specific items as negatives. In particular, we consider a novel model called group testing with blocks of positives and inhibitors. A test on a subset of items is positive if the subset contains at least one positive and does not contain any inhibitors, and it is negative otherwise. In this model, the input items are linearly ordered, and the positives and inhibitors are subsets of small blocks (at unknown locations) of consecutive items over that order. We also consider two specific instantiations of this model. The first instantiation is that model that contains a single block of consecutive items consisting of exactly known numbers of positives and inhibitors. The second instantiation is the model that contains a single block of consecutive items containing known numbers of positives and inhibitors. Our contribution is to propose efficient encoding and decoding schemes such that the numbers of tests used to identify only positives or both positives and inhibitors are less than the ones in the state-of-the-art schemes. Moreover, the decoding times mostly scale to the numbers of tests that are significantly smaller than the state-of-the-art ones, which scale to both the number of tests and the number of items.