A Slow Dynamic RNA Switch Regulates Processing of microRNA-21.

The microRNAs are non-coding RNAs which post-transcriptionally regulate the expression of many eukaryotic genes, and whose dysregulation is a driver of human disease. Here we report the discovery of a very slow (0.1 s) conformational rearrangement at the Dicer cleavage site of pre-miR-21, which regulates the relative concentration of readily- and inefficiently-processed RNA structural states.

Impacts of tracer type, tracer selection, and source dominance on source apportionment with sediment fingerprinting.

Sediment fingerprinting estimates the proportional contribution of fine sediment from distinct catchment sources delivered to downstream receiving environments. Increased attention has focused on assessing the accuracy of source contribution estimates, particularly in relation to tracer selection and statistical un-mixing procedures. However, no studies have systematically tested the impact of source combination or dominance on the accuracy of source estimates.

The Use of Big Data to Improve Human Health: How Experience From other Industries Will Shape the Future.

'Data science' represents a set of mathematical and software development related techniques that are applied across a wide range of problems and industries. Practitioners of data science in human health-related domains typically see a world that differs substantially from practitioners in other domains such as advertising, finance, e-commerce, manufacturing, or social networking. This commentary discusses what those differences are (Project vs Product Focus, Independent vs Integrated Efforts, Causality vs Prediction Driven, Statistical vs Machine Learning Centricity) why they exist, and the future convergence that we believe is on the horizon.

Environmental Health Practice Challenges and Research Needs for U.S. Health Departments.

Background: Environmental health (EH) professionals, one of the largest segments of the public health workforce, are responsible for delivery of essential environmental public health services. The challenges facing these professionals and research needs to improve EH practice are not fully understood, but 26% of EH professionals working in health departments of the United States plan to retire in 5 y, while only 6% of public health students are currently pursuing EH concentrations.

Objectives: A groundbreaking initiative was recently launched to understand EH practice in health departments of the United States.

On The Potential of Dynamic Nuclear Polarization Enhanced Diamonds in Solid-State and Dissolution (13) C NMR Spectroscopy.

Dynamic nuclear polarization (DNP) is a versatile option to improve the sensitivity of NMR and MRI. This versatility has elicited interest for overcoming potential limitations of these techniques, including the achievement of solid-state polarization enhancement at ambient conditions, and the maximization of (13) C signal lifetimes for performing in vivo MRI scans. This study explores whether diamond's (13) C behavior in nano- and micro-particles could be used to achieve these ends.

Optimizing water hyperpolarization and dissolution for sensitivity-enhanced 2D biomolecular NMR.

A recent study explored the use of hyperpolarized water, to enhance the sensitivity of nuclei in biomolecules thanks to rapid proton exchanges with labile amide backbone and sidechain groups. Further optimizations of this approach have now allowed us to achieve proton polarizations approaching 25% in the water transferred into the NMR spectrometer, effective water T1 times approaching 40s, and a reduction in the dilution demanded for the cryogenic dissolution process. Further hardware developments have allowed us to perform these experiments, repeatedly and reliably, in 5mm NMR tubes.

Human health risks of geothermally derived metals and other contaminants in wild-caught food.

Arsenic (As) and mercury (Hg) associated with geothermally influenced lakes and rivers represent a potential health risk to communities where wild-caught food is consumed. The Rotorua Lakes region of New Zealand has extensive natural geothermal activity and a large proportion (35%) of indigenous Māori population, for whom wild food gathering is an important cultural activity. The aim of this study was to measure selected heavy metal and organochlorine (OC) concentrations in important local fish and shellfish species and assess the potential health risk to the local population of consuming these species.

A survey of emerging contaminants in the estuarine receiving environment around Auckland, New Zealand.

Increasing urbanisation in the future will put mounting stresses on the receiving environments around those urban centres due to increased sedimentation and contaminant runoff. Emerging contaminants (ECs) are an extensive array of chemicals and many are not under regulatory action. Within New Zealand likely future pressures from ECs will be in both urban centres and rural areas due to intensive agriculture, although at present there is a lack of information on the state of the environment in both sectors.

Adverse events in clinical islet transplantation: one institutional experience.

Islet transplantation is one of the most promising treatments for an unstable form of type 1 diabetes. However, islet transplantation still has some obstacles, such as low success rate of islet isolation, difficulty to obtain long-term insulin freedom, and adverse events related to transplant protocol. We describe the adverse events of current clinical islet transplantation at our institute in this report.

Organochlorines and heavy metals in wild caught food as a potential human health risk to the indigenous Māori population of South Canterbury, New Zealand.

Increasing concentrations of anthropogenic contaminants in wild kai (food) of cultural, recreational and economic importance to the indigenous Māori of New Zealand is a potential human health risk. Contaminants that are known to bioaccumulate through the food chain (e.g.

Body mass index reflects islet isolation outcome in islet autotransplantation for patients with chronic pancreatitis.

Total pancreatectomy with autologous islet cell transplantation (TP with AIT) is an effective treatment for chronic pancreatitis patients with severe abdominal pain. Body mass index (BMI) of the pancreatic donor is proven to be a useful predictor for islet isolation and transplantation outcomes in allogenic islet transplantation. However, the association between BMI and islet isolation outcome and/or metabolism after AIT was previously unclear.

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.

Monitoring tat peptide binding to TAR RNA by solid-state 31P-19F REDOR NMR.

Complexes of the HIV transactivation response element (TAR) RNA with the viral regulatory protein tat are of special interest due in particular to the plasticity of the RNA at this binding site and to the potential for therapeutic targeting of the interaction. We performed REDOR solid-state NMR experiments on lyophilized samples of a 29 nt HIV-1 TAR construct to measure conformational changes in the tat-binding site concomitant with binding of a short peptide comprising the residues of the tat basic binding domain. Peptide binding was observed to produce a nearly 4 A decrease in the separation between phosphorothioate and 2'F labels incorporated at A27 in the upper helix and U23 in the bulge, respectively, consistent with distance changes observed in previous solution NMR studies, and with models showing significant rearrangement in position of bulge residue U23 in the bound-form RNA.

Determination of DNA minor groove width in distamycin-DNA complexes by solid-state NMR.

We have performed solid-state 31P-19F REDOR nuclear magnetic resonance (NMR) experiments to monitor changes in minor groove width of the oligonucleotide d(CGCAAA2'FUTGGC)*d(GCCAAT(pS)TT GCG) (A3T2) upon binding of the drug distamycin A at different stoichiometries. In the hydrated solid-state sample, the minor groove width for the unbound DNA, measured as the 2'FU7-pS19 inter-label distance, was 9.4 +/- 0.