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 quasi-experimental controlled before-and-after trial in northeastern Uganda.

Background: Declines 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).

Synergy and timing: a concurrent mass medical campaign predicted to augment indoor residual spraying for malaria.

Background: 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.

Slow exchange model of nonrigid rotational motion in RNA for combined solid-state and solution NMR studies.

Functional RNA molecules are conformationally dynamic and sample a multitude of dynamic modes over a wide range of frequencies. Thus, a comprehensive description of RNA dynamics requires the inclusion of a broad range of motions across multiple dynamic rates which must be derived from multiple spectroscopies. Here we describe a slow conformational exchange theoretical approach to combining the description of local motions in RNA that occur in the nanosecond to microsecond window and are detected by solid-state NMR with nonrigid rotational motion of the HIV-1 transactivation response element (TAR) RNA in solution as observed by solution NMR.

Intermediate rate atomic trajectories of RNA by solid-state NMR spectroscopy.

Many RNAs undergo large conformational changes in response to the binding of proteins and small molecules. However, when RNA functional dynamics occur in the nanosecond-microsecond time scale, they become invisible to traditional solution NMR relaxation methods. Residual dipolar coupling methods have revealed the presence of extensive nanosecond-microsecond domain motions in HIV-1 TAR RNA, but this technique lacks information on the rates of motions.

Hydration dependent dynamics in RNA.

The 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.

Solid-state deuterium NMR studies reveal micros-ns motions in the HIV-1 transactivation response RNA recognition site.

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.