Browsing by Author "Echodu, Dorothy C."
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Item Hydration dependent dynamics in RNA(Journal of biomolecular NMR, 2009) Olsen, Greg L.; Bardaro Jr., Michael F.; Echodu, Dorothy C.; Drobny, Gary P.; Varani, GabrieleThe essential role played by local and collective motions in RNA function has led to a growing interest in the characterization of RNA dynamics. Recent investigations have revealed that even relatively simple RNAs experience complex motions over multiple time scales covering the entire ms–ps motional range. In this work, we use deuterium solid-state NMR to systematically investigate motions in HIV-1 TAR RNA as a function of hydration. We probe dynamics at three uridine residues in different structural environments ranging from helical to completely unrestrained. We observe distinct and substantial changes in 2H solid-state relaxation times and lineshapes at each site as hydration levels increase. By comparing solid-state and solution state 13C relaxation measurements, we establish that ns–ls motions that may be indicative of collective dynamics suddenly arise in the RNA as hydration reaches a critical point coincident with the onset of bulk hydration. Beyond that point, we observe smaller changes in relaxation rates and lineshapes in these highly hydrated solid samples, compared to the dramatic activation of motion occurring at moderate hydration.Item Hyperfine Coupling in Colloidal n-Type ZnO Quantum Dots: Effects on Electron Spin Relaxation(The Journal of Physical Chemistry, 2010) Whitaker, Kelly M.; Ochsenbein, Stefan T.; Smith, Alyssa L.; Echodu, Dorothy C.; Robinson, Bruce H.; Gamelin, Daniel R.Colloidal semiconductor nanocrystals are excellent systems for exploring the fundamental properties of quantum-confined charge carriers. Tremendous progress has already been made in understanding the properties of electron-hole pairs (excitons) confined in colloidal quantum dots (QDs) using optical spectroscopic techniques.1-6 In contrast with charge carriers in QD electronic excited states, the properties of QDs containing excess carriers in their ground states have received substantially less attention.7-19 To date, the primary experimental probe of such charged QDs has been electronic absorption spectroscopy, in which low-energy intraband excitations can be used to define the carrier wave function.Item Impact of population based indoor residual spraying with and without mass drug administration with dihydroartemisinin-piperaquine on malaria prevalence in a high transmission setting: a controlled trial in northeastern Uganda(Research Square, 2022) Echodu, Dorothy C.; Yeka, Adoke; Eganyu, Thomas; Odude, Wycliff; Bukenya, Fred; Nankabirwa, JoaniterDeclines in malaria burden in Uganda have slowed. Modelling predicts that indoor residual spraying (IRS) and mass drug administration (MDA), when co-timed, have synergistic impact. This study investigated additional protective impact of population-based MDA on malaria prevalence, if any, when added to IRS, as compared with IRS alone and with standard of care (SOC). Methods: The 32-month prospective controlled community trial enrolled an open cohort of residents (46,765 individuals, 1st enumeration and 52,133, 4th enumeration) in Katakwi District in northeastern Uganda. Consented participants were assigned to three arms based on residential subcounty: MDA+IRS, IRS, and SOC (insecticide treated bednets and case management). IRS with pirimiphos methyl and MDA with dihydroartemisinin- piperaquine were delivered in 4 co-timed campaign-style rounds 8 months apart. The primary endpoint was population prevalence of malaria, estimated by 6 cross-sectional surveys, starting at baseline and preceding each subsequent round. Results: Comparing malaria prevalence in MDA+IRS and IRS only arms over all 6 surveys (intention-to-treat analysis), roughly every 6 months, post-interventions, a geostatistical model found a significant additional 15.5% (95% confidence interval (CI): [13.7%, 17.5%], Z=9.6, p= 5e-20) decrease in the adjusted odds ratio (aOR) due to MDA for all ages, a 13.3% reduction in under 5’s (95% CI: [10.5%, 16.8%], Z=4.02, p= 5e-5), and a 10.1% reduction in children 5-15 (95% CI: [8.5%, 11.8%], Z=4.7, p= 2e-5). All ages residents of the MDA + IRS arm enjoyed an overall 80.1% reduction (95% CI: [80.0%,83.0%, p¡.0001] in odds of qPCR confirmed malaria compared with SOC residents. Secondary difference-in-difference analyses comparing surveys at different timepoints to baseline showed aOR (MDA + IRS vs IRS) of qPCR positivity between 0.28 and 0.66 (p<.001). Of three serious adverse events, one (nonfatal) was considered related to study medications. Limitations include the initial non-random assignment of MDA+IRS, which may have understated the impact of MDA, and lack of MDA-only arm, considered to violate equipoise. Conclusions: Despite being assessed at long timepoints 5-7 months post-round, MDA plus IRS provided significant additional protection from malaria infection over IRS alone. Future cohort studies of impact on incidence recommended.Item Intermediate Rate Atomic Trajectories of RNA by Solid State NMR Spectroscopy(Journal of the American Chemical Society, 2010) Olsen, Greg L.; Bardaro Jr., Michael F.; Echodu, Dorothy C.; Drobny, Gary P.; Varani, GabrieleMany RNAs undergo large conformational changes in response to the binding of proteins and small molecules. However, when RNA functional dynamics occur in the ns-μs time scale they become invisible to traditional solution NMR relaxation methods. Residual dipolar couplings methods have revealed the presence of extensive ns-μs domain motions in HIV-1 TAR RNA, but this technique lacks information on the rates of motions. We have used solid-state deuterium NMR to quantitatively describe trajectories of key residues in TAR by exploiting the sensitivity of this technique to motions that occur in the ns-μs regime. Deuterium lineshape and relaxation data were used to model motions of residues within the TAR binding interface. The resulting motional models indicate that two functionally essential bases within the single stranded bulge sample both the free and Tat-bound conformations on the microsecond timescale in the complete absence of the protein. Thus, our results strongly support a conformational capture mechanism for recognition: the protein does not induce a new RNA structure, but instead captures an already-populated conformation.Item Solid-State Deuterium NMR Studies Reveal μs-ns Motions in the HIV-1 TAR RNA Recognition Site(Journal of the American Chemical Society, 2008) Olsen, Greg L.; Echodu, Dorothy C.; Shajani, Zahra; Bardaro Jr., Michael F.; Varani, Gabriele; Drobny, Gary P.Solution and solid-state NMR measurements were used together to examine motion in three sites in the HIV-1 TAR RNA. We wished to investigate the dynamics facilitating the conformational rearrangements the TAR RNA must undergo for tat binding, and in particular to characterize the full range of motional timescales accessible to this RNA. Our results demonstrate that the dynamics in TAR involving residues essential to tat binding include not only the faster motions detected by solution relaxation measurements, but also a significant component in the μs-ns timescale.Item Synergy and timing: a concurrent mass medical campaign predicted to augment indoor residual spraying for malaria(African Journal of Agricultural Research, 2018) Elliott, Richard C.; Smith, David L.; Echodu, Dorothy C.Control programmes for high burden countries are tasked with charting effective multi-year strategies for malaria control within significant resource constraints. Synergies between different control tools, in which more than additive benefit accrues from interventions used together, are of interest because they may be used to obtain savings or to maximize health impact per expenditure. One commonly used intervention in sub-Saharan Africa is indoor residual spraying (IRS), typically deployed through a mass campaign. While possible synergies between IRS and long-lasting insecticide-treated nets (LLINs) have been investigated in multiple transmission settings, coordinated synergy between IRS and other mass medical distribution campaigns have not attracted much attention. Recently, a strong timing-dependent synergy between an IRS campaign and a mass drug administration (MDA) was theoretically quantified. These synergistic benefits likely differ across settings depending on transmission intensity and its overall seasonal pattern. Methods: High coverage interventions are modelled in different transmission environments using two methods: a Ross–Macdonald model variant and openmalaria simulations. The impact of each intervention strategy was measured through its ability to prevent host infections over time, and the effects were compared to the baseline case of deploying interventions in isolation. Results: By modelling IRS and MDA together and varying their deployment times, a strong synergy was found when the administered interventions overlapped. The added benefit of co-timed interventions was robust to differences in the models. In the Ross–Macdonald model, the impact compared was roughly double the sequential interventions in most transmission settings. Openmalaria simulations of this medical control augmentation of an IRS campaign show an even stronger response with the same timing relationship. Conclusions: The strong synergies found for these control tools between the complementary interventions demonstrate a general feature of effective concurrent campaign-style vector and medical interventions. A mass treatment campaign is normally short-lived, especially in higher transmission settings. When co-timed, the rapid clearing of the host parasite reservoir via chemotherapy is protected from resurgence by the longer duration of the vector control. An effective synchronous treatment campaign has the potential to greatly augment the impact of indoor residual spraying. Mass screening and treatment (MSAT) with highly sensitive rapid diagnostic tests may demonstrate a comparable trend while mass LLIN campaigns may similarly coordinate with MDA/MSAT.