An efficient and low-cost method of examining larval movement in Drosophila melanogaster is needed to study how mutations and/or alterations in the muscular, neural, and olfactory systems affect locomotor behavior. Here, we describe the implementation of wrMTrck, a freely available ImageJ plugin originally developed for examining multiple behavioral parameters in the nematode C. elegans. Our optimized method is rapid, reproducible and does not require automated microscope setups or the purchase of proprietary software. To demonstrate the utility of this method, we analyzed the velocity and crawling paths of two Drosophila mutants that affect muscle structure and/or function. Additionally, we show that this approach is useful for tracking the behavior of adult insects, including Tribolium castaneum and Drosophila melanogaster.

Objectives: The current demographic information from China reports that 10%-19% of patients hospitalized with coronavirus disease (COVID-19) were diabetic. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are considered firstline agents in patients with diabetes because of their nephroprotective effects, but administration of these drugs leads to upregulation of angiotensin-converting enzyme 2 (ACE2), which is responsible for the viral entry of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). Data are lacking to determine what pulmonary effects ACEIs or ARBs may have in patients with diabetes, which could be relevant in the management of patients infected with SARS-CoV-2. This study aims to assess the prevalence of pulmonary adverse drug effects (ADEs) in patients with diabetes who were taking ACEI or ARBs to provide guidance as to how these medications could affect outcomes in acute respiratory illnesses such as SARS-CoV-2 infection. Methods: 1DATA, a unique data platform resulting from collaboration across veterinary and human health care, used an intelligent medicine recommender system (1DrugAssist) developed using several national and international databases to evaluate all ADEs reported to the Food and Drug Administration for patients with diabetes taking ACEIs or ARBs. Results: Mining of this data elucidated the proportion of a cluster of pulmonary ADEs associated with specific medications in these classes, which may aid health care professionals in understanding how these medications could worsen or predispose patients with diabetes to infections affecting the respiratory system, specifically COVID-19. Based on this data mining process, captopril was found to have a statistically significantly higher incidence of pulmonary ADEs compared with other ACEIs (P ¼ 0.005) as well as ARBs (P ¼ 0.012), though other specific drugs also had important pulmonary ADEs associated with their use. Conclusion: These analyses suggest that pharmacists and clinicians will need to consider the specific medication's adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19.

Expression of human disease-causing LGMD2H alleles in Drosophila causes muscle degeneration and elevated levels of integrin and sarcoglycan costamere proteins, likely exacerbating disease progression.

The highly chromophoric drugs, ethidium bromide (EtBr), 9-aminoacridine (9AA) and proflavine (PF) (3,6diaminoacridine) bind to DNA by insertion of a polycyclic aromatic ring between adjacent base pairs of the double helix. Despite similar intercalative mechanisms, these drugs exhibit distinct DNA affinities and produce characteristic mutagenic effects. Complexes of the intercalants with small nucleotide fragments have been investigated by various methods, including X-ray crystallography. However, the structural impact of drug intercalation on a DNA molecule of genetic consequence has not yet been reported. Here, we employ near-infrared laser excitation (752 nm) and a DNA target of genomic size to obtain and compare Raman spectra of complexes of EtBr, 9AA and PF with DNA. Raman signatures of solution complexes have been analyzed by difference methods to reveal the specific structural changes induced at the drug/DNA intercalation sites. Perturbation of the DNA backbone geometry, as reflected in the Raman marker diagnostic of the phosphodiester group (800-880 cm −1 ), ranges from disruption of the B-form duplex in favor of either the A-form duplex, or separated strands, or a combination of altered DNA backbone geometries. The acridine intercalants, PF and 9AA, also perturb hydrogen-bonding interactions between the paired bases of duplex DNA, although in distinct ways. Conversely, base pairing is relatively unperturbed by ethidium intercalation. The results are discussed in relation to frameshift mutagenic activities of the intercalating drugs.

IHF and HU are small basic proteins of eubacteria that bind as homodimers to double-stranded DNA and bend the duplex to promote architectures required for gene regulation. These architectural proteins share a common alpha/beta fold but exhibit different nucleic acid binding surfaces and distinct functional roles. With respect to DNA-binding specificity, for example, IHF is sequence specific, while HU is not. We have employed Raman difference spectroscopy and gel mobility assays to characterize the molecular mechanisms underlying such differences in DNA recognition. Parallel studies of solution complexes of IHF and HU with the same DNA nonadecamer (5' --> 3' sequence: TC TAAGTAGTTGATTCATA, where the phage lambda H1 consensus sequence of IHF is underlined) show the following. (i) The structure of the targeted DNA site is altered much more dramatically by IHF than by HU binding. (ii) In the IHF complex, the structural perturbations encompass both the sugar-phosphate backbone and the bases of the consensus sequence, whereas only the DNA backbone is altered by HU binding. (iii) In the presence of excess protein, complexes of order higher than 1 dimer per duplex are detected for HU:DNA, though not for IHF:DNA. The results differentiate structural motifs of IHF:DNA and HU:DNA solution complexes, provide Raman signatures of prokaryotic sequence-specific and nonspecific recognition, and suggest that the architectural role of HU may involve the capability to recruit additional binding partners to even relatively short DNA sequences.