Many insects use patterns of polarized light in the sky to orient and navigate. Here we functionally characterize neural circuitry in the fruit fly, Drosophila melanogaster, that conveys polarized light signals from the eye to the central complex, a brain region essential for the fly's sense of direction. Neurons tuned to the angle of polarization of ultraviolet light are found throughout the anterior visual pathway, connecting the optic lobes with the central complex via the anterior optic tubercle and bulb, in a homologous organization to the 'sky compass' pathways described in other insects. We detail how a consistent, map-like organization of neural tunings in the peripheral visual system is transformed into a reduced representation suited to flexible processing in the central brain. This study identifies computational motifs of the transformation, enabling mechanistic comparisons of multisensory integration and central processing for navigation in the brains of insects.
Drug repurposing, or identifying new uses for existing drugs, has emerged as an alternative to traditional drug discovery processes involving de novo synthesis. Drugs that are currently approved or under development for non-antibiotic indications may possess antibiotic properties, and therefore may have repurposing potential, either alone or in combination with an antibiotic. They might also serve as “antibiotic adjuvants” to enhance the activity of certain antibiotics.
The widespread emergence of antibiotic-resistant gram-negative organisms has compromised the utility of current treatment options for severe infections caused by these pathogens. The rate of gram-negative multidrug resistance is worsening, threatening the effectiveness of newer broad-spectrum antibiotic agents. Infections associated with multidrug-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae are having a substantial impact on hospital costs and mortality rates. The potential for these resistant gram-negative nosocomial pathogens must always be a primary consideration when selecting antibiotic therapy for critically ill patients. Empiric combination therapy directed at gram-negative pathogens is a logical approach for patients with suspected health care-associated infections, particularly those with risk factors for infections caused by multidrug-resistant pathogens. Although in vitro synergy tests have shown potential benefits of continued combination therapy, convincing clinical data that demonstrate a need for combination therapy once susceptibilities are known are lacking. Thus, deescalation to a single agent once susceptibilities are known is recommended for most patients and pathogens. Use of polymyxins, often in combination with other antimicrobials, may be necessary for salvage therapy.
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