Mosquitoes are vectors for some of the most devastating diseases on the planet. Given the centrality of acoustic sensing in the precopulatory behavior of these vectors, the use of an exogenous acoustic stimulus offers the potential of interfering with the courtship behavior of these insects. Previous research on the acoustotactic response of mosquitoes has been conducted on tethered preparations using low-intensity sound stimuli. To quantify differences in acoustotactic responses between mosquitos of distinct sex and species, we examined the effects of incidental sound stimuli on the flight behavior of free-flying male vs. female Aedes aegypti and Anopheles gambiae mosquitoes. The key variables were sound frequency (100–1000 Hz) and intensity (67–103 dB, measured at 12.5 cm from the source), and the acoustotactic response was measured in terms of the relative increase in flight speed in response to the stimulus. The data show, for the first time, significant sex- and species-specific differences in acoustotactic responses. A. aegypti exhibited a greater response to sound stimulus compared to An. gambiae, and the response also extended over a larger range of frequencies. Furthermore, the males of both species displayed a greater acoustotactic response than females, with An. gambiae females exhibiting minimal response to sound.
Myopathies are among the major causes of mortality in the world. There is no complete cure for this heterogeneous group of diseases, but a sensitive, specific, and fast diagnostic tool may improve therapy effectiveness. In this study, Raman spectroscopy is applied to discriminate between muscle mutants in Drosophila on the basis of associated changes at the molecular level. Raman spectra were collected from indirect flight muscles of mutants, upheld(1) (up(1)), heldup(2) (hdp(2)), myosin heavy chain(7) (Mhc(7)), actin88F(KM88) (Act88F(KM88)), upheld(101) (up(101)), and Canton-S (CS) control group, for both 2 and 12 days old flies. Difference spectra (mutant minus control) of all the mutants showed an increase in nucleic acid and β-sheet and/or random coil protein content along with a decrease in α-helix protein. Interestingly, the 12th day samples of up(1) and Act88F(KM88) showed significantly higher levels of glycogen and carotenoids than CS. A principal components based linear discriminant analysis classification model was developed based on multidimensional Raman spectra, which classified the mutants according to their pathophysiology and yielded an overall accuracy of 97% and 93% for 2 and 12 days old flies, respectively. The up(1) and Act88F(KM88) (nemaline-myopathy) mutants form a group that is clearly separated in a linear discriminant plane from up(101) and hdp(2) (cardiomyopathy) mutants. Notably, Raman spectra from a human sample with nemaline-myopathy formed a cluster with the corresponding Drosophila mutant (up(1)). In conclusion, this is the first demonstration in which myopathies, despite their heterogeneity, were screened on the basis of biochemical differences using Raman spectroscopy.
Striated muscle contraction is regulated by the translocation of troponin-tropomyosin strands over the thin filament surface. Relaxation relies partly on highly-favorable, conformationdependent electrostatic contacts between actin and tropomyosin, which position tropomyosin such that it impedes actomyosin associations. Impaired relaxation and hypercontractile properties are hallmarks of various muscle disorders. The α-cardiac actin M305L hypertrophic cardiomyopathy-causing mutation lies near residues that help confine tropomyosin to an inhibitory position along thin filaments. Here, we investigate M305L actin in vivo, in vitro, and in silico to resolve emergent pathological properties and disease mechanisms. Our data suggest the mutation reduces actin flexibility and distorts the actin-tropomyosin electrostatic energy landscape that, in muscle, result in aberrant contractile inhibition and excessive force. Thus, actin flexibility may be required to establish and maintain interfacial contacts with tropomyosin as well as facilitate its movement over distinct actin surface features and is, therefore, likely necessary for proper regulation of contraction.
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