Elucidating the structure and function of the nucleus-The NIH Common Fund 4D Nucleome program.

Genomic architecture appears to play crucial roles in health and a variety of diseases. How nuclear structures reorganize over different timescales is elusive, partly because the tools needed to probe and perturb them are not as advanced as needed by the field. To fill this gap, the National Institutes of Health Common Fund started a program in 2015, called the 4D Nucleome (4DN), with the goal of developing and ultimately applying technologies to interrogate the structure and function of nuclear organization in space and time.

Spatial and temporal tools for building a human cell atlas.

Improvements in the sensitivity, content, and throughput of microscopy, in the depth and throughput of single-cell sequencing approaches, and in computational and modeling tools for data integration have created a portfolio of methods for building spatiotemporal cell atlases. Challenges in this fast-moving field include optimizing experimental conditions to allow a holistic view of tissues, extending molecular analysis across multiple timescales, and developing new tools for 1) managing large data sets, 2) extracting patterns and correlation from these data, and 3) integrating and visualizing data and derived results in an informative way. The utility of these tools and atlases for the broader scientific community will be accelerated through a commitment to findable, accessible, interoperable, and reusable data and tool sharing principles that can be facilitated through coordination and collaboration between programs working in this space.

Wearable technologies for active living and rehabilitation: Current research challenges and future opportunities.

This paper presents some recent developments in the field of wearable sensors and systems that are relevant to rehabilitation and provides examples of systems with evidence supporting their effectiveness for rehabilitation. A discussion of current challenges and future developments for selected systems is followed by suggestions for future directions needed to advance towards wider deployment of wearable sensors and systems for rehabilitation.

Toward mapping the human body at a cellular resolution.

The adult human body is composed of nearly 37 trillion cells, each with potentially unique molecular characteristics. This Perspective describes some of the challenges and opportunities faced in mapping the molecular characteristics of these cells in specific regions of the body and highlights areas for international collaboration toward the broader goal of comprehensively mapping the human body with cellular resolution.

The diuretic effect in human subjects of an extract of Taraxacum officinale folium over a single day.

BACKGROUND: Taraxacum officinale (L.) Weber (Asteraceae) has been extensively employed as a diuretic in traditional folk medicine and in modern phytotherapy in Europe, Asia, and the Americas without prior clinical trial substantiation. OBJECTIVES: In this pilot study, a high-quality fresh leaf hydroethanolic extract of the medicinal plant T. officinale (dandelion) was ingested by volunteers to investigate whether an increased urinary frequency and volume would result. DESIGN: Volume of urinary output and fluid intake were recorded by subjects. Baseline values for urinary frequency and excretion ratio (urination volume:fluid intake) were established 2 days prior to dandelion dosing (8 mL TID) and monitored throughout a 1-day dosing period and 24 hours postdosing. RESULTS: For the entire population (n = 17) there was a significant (p < 0.05) increase in the frequency of urination in the 5-hour period after the first dose. There was also a significant (p < 0.001) increase in the excretion ratio in the 5-hour period after the second dose of extract. The third dose failed to change any of the measured parameters. CONCLUSIONS: Based on these first human data, T. officinale ethanolic extract shows promise as a diuretic in humans. Further studies are needed to establish the value of this herb for induction of diuresis in human subjects.

Ipsilateral cortical fMRI responses after peripheral nerve damage in rats reflect increased interneuron activity.

In the weeks following unilateral peripheral nerve injury, the deprived primary somatosensory cortex (SI) responds to stimulation of the ipsilateral intact limb as demonstrated by functional magnetic resonance imaging (fMRI) responses. The neuronal basis of these responses was studied by using high-resolution fMRI, in vivo electrophysiological recordings, and juxtacellular neuronal labeling in rats that underwent an excision of the forepaw radial, median, and ulnar nerves. These nerves were exposed but not severed in control rats. Significant bilateral increases of fMRI responses in SI were observed in denervated rats. In the healthy SI of the denervated rats, increases in fMRI responses were concordant with increases in local field potential (LFP) amplitude and an increased incidence of single units responding compared with control rats. In contrast, in the deprived SI, increases in fMRI responses were associated with a minimal change in LFP amplitude but with increased incidence of single units responding. Based on action potential duration, juxtacellular labeling, and immunostaining results, neurons responding to intact forepaw stimulation in the deprived cortex were identified as interneurons. These results suggest that the increases in fMRI responses in the deprived cortex reflect increased interneuron activity.

Optical waveguiding in suspensions of dielectric particles.

An optical waveguide formed by a suspension of dielectric nanoparticles in a microchannel is described. The suspensions, chosen for their guiding and scattering properties, are silica and polystyrene particles that have diameters of 30-900 nm and are dispersed in water with volume fractions up to 10%. Changing the diameter and concentration of the particles causes the suspensions to transition from Rayleigh to Mie scattering and from single to multiple scattering. The threshold for optical guiding in a waveguide core composed of these suspensions is set by the numerical aperture of the effective refractive-index difference introduced by the suspension and not by the average interparticle distance.

A low-threshold, high-efficiency microfluidic waveguide laser.

This communication describes a long (1 cm), laser-pumped, liquid core-liquid cladding (L2) waveguide laser. This device provides a simple, high intensity, tunable light source for microfludic applications. Using a core solution of 2 mM rhodamine 640 perchlorate, optically pumped by a frequency-doubled Nd:YAG laser, we found that the threshold for lasing was as low as 22 muJ (16-ns pulse length) and had a slope efficiency up to 20%. The output wavelength was tunable over a 20-nm range by changing the ratio of solvent components (dimethyl sulfoxide and methanol) in the liquid core.

Dynamic control of liquid-core/liquid-cladding optical waveguides.

This report describes the manipulation of light in waveguides that comprise a liquid core and a liquid cladding (liq/liq waveguide). These waveguides are dynamic: Their structure and function depend on a continuous, laminar flow of the core and cladding liquids. Because they are dynamic, they can be reconfigured and adapted continuously in ways that are not possible with solid-state waveguides. The liquids are introduced into the channels of a microfluidic network designed to sandwich the flowing core liquid between flowing slabs of the cladding fluid. At low and moderate Reynolds numbers, flow is laminar, and the liq/liq interfaces are optically smooth. Small irregularities in the solid walls of the channels do not propagate into these interfaces, and liq/liq waveguides therefore exhibit low optical loss because of scattering. Manipulating the rate of flow and the composition of the liquids tunes the characteristics of these optical systems.