A single beam acoustic device, with its relatively simple scheme and low intensity, can trap a single lipid droplet in a manner similar to optical tweezers. Forces in the order of hundreds of nanonewtons direct the droplet toward the beam focus, within the range of hundreds of micrometers. This trapping method, therefore, can be a useful tool for particle manipulation in areas where larger particles or forces are involved. © 2009 American Institute of Physics. ͓DOI: 10.1063/1.3206910͔Optical trapping of small objects has been used to quantitatively investigate the mechanism of biological particles. 1,2 Optical tweezers 3 typically output forces on the order of piconewtons, and displace micrometer-sized particles up to hundreds of nanometers from the trap. Despite its precision and wide range of biological applications, however, its use has been limited to either optically purified samples or shallow regions in a medium. The high energy of focused lasers, in addition, has often induced photodamage on target particles. 4 In acoustics, Wu 5 introduced the term of acoustic tweezers and showed that latex spheres or clusters of frog eggs could be trapped by applying two opposing sound waves at 3.5 MHz. Here we present a single beam acoustic trapping that is similar to optical tweezers and differs from Wu's 5 dual beam method, based on our theoretical findings in ray acoustics regime: the tight focusing, the acoustic impedance match of particles with surrounding medium, and the particle size greater than the ultrasonic wavelength. [6][7][8] Note that only the transverse trapping was demonstrated in the present experiment because an axial focusing as tight as the lateral focusing could not be achieved.A 30 MHz lithium niobate ͑LiNbO 3 ͒ single element transducer was built to trap lipid droplets and driven by sinusoidal bursts. Note that the transducer was allowed to move only in the direction perpendicular to the beam axis ͓see Fig. 1͑a͔͒. The excitation frequency was varied from 23 to 37 MHz, and its peak-to-peak voltages were 22, 32, and 41 V pp . Due to the need for sharp intensity gradients, the transducer was press focused 9 to obtain an F-number of 0.75. The transducer was mounted on a three-dimensional motorized positioner ͑LMG26 T50MM, OptoSigma, USA͒, and a series of control commands was sent to the positioner by the customized LABVIEW controller ͓see Fig. 1͑b͔͒. To evaluate generated forces by the transducer, the acoustic peak pressures at different frequencies were measured at the focus, by a calibrated PVDF needle hydrophone having an active element size of 40 m ͑HPM04/01, Precision Acoustics, U.K.͒, as shown in Fig. 2͑a͒.Oleic acid lipid droplets of 126.0Ϯ 5.6 m in diameter were synthesized using droplet-based microfluidic devices, a robust method of forming monodispersed droplets in the nanometer to micrometer size range. 10 A single droplet was used as a target particle because of its good acoustic impedance match with the de-ionized water. The droplets were then carefully loaded underneath an acoustica...

In the last 10 years, homocysteine has been regarded as a marker of cardiovascular disease and a definite risk factor for many other diseases. Homocysteine is biosynthesized from methionine through multiple steps and then goes through one of two major metabolic pathways: remethylation and transsulfuration. Hyperhomocysteinemia is a state in which too much homocysteine is present in the body. The main cause of hyperhomocysteinemia is a dysfunction of enzymes and cofactors associated with the process of homocysteine biosynthesis. Other causes include excessive methionine intake, certain diseases and side effects of some drugs. Hyperhomocysteinemia is a trigger for many diseases, such as atherosclerosis, congestive heart failure, age-related macular degeneration, Alzheimer's disease and hearing loss. There are many studies showing a positive relationship between homocysteine level and various symptoms. We speculate that a high level of homocysteine can be the sole reason or an aggravating factor in numerous diseases for which causal links are not fully understood.

Ultrasound and optical imagers are used widely in a variety of biological and medical applications. In particular, multimodal implementations combining light and sound have been actively investigated to improve imaging quality. However, the integration of optical sensors with opaque ultrasound transducers suffers from low signal-to-noise ratios, high complexity, and bulky form factors, significantly limiting its applications. Here, we demonstrate a quadruple fusion imaging system using a spherically focused transparent ultrasound transducer that enables seamless integration of ultrasound imaging with photoacoustic imaging, optical coherence tomography, and fluorescence imaging. As a first application, we comprehensively monitored multiparametric responses to chemical and suture injuries in rats’ eyes in vivo, such as corneal neovascularization, structural changes, cataracts, and inflammation. As a second application, we successfully performed multimodal imaging of tumors in vivo, visualizing melanomas without using labels and visualizing 4T1 mammary carcinomas using PEGylated gold nanorods. We strongly believe that the seamlessly integrated multimodal system can be used not only in ophthalmology and oncology but also in other healthcare applications with broad impact and interest.

AAA+ disaggregases solubilize aggregated proteins and confer heat tolerance to cells. Their disaggregation activities crucially depend on partner proteins, which target the AAA+ disaggregases to protein aggregates while concurrently stimulating their ATPase activities. Here, we report on two potent ClpG disaggregase homologs acquired through horizontal gene transfer by the species and subsequently abundant clone C. ClpG exhibits high, stand-alone disaggregation potential without involving any partner cooperation. Specific molecular features, including high basal ATPase activity, a unique aggregate binding domain, and almost exclusive expression in stationary phase distinguish ClpG from other AAA+ disaggregases. Consequently, ClpG largely contributes to heat tolerance of primarily in stationary phase and boosts heat resistance 100-fold when expressed in This qualifies ClpG as a potential persistence and virulence factor in .

Somatic sensory neuron somata are located within the dorsal root ganglia (DRG) and are mostly ensheathed by individual satellite glial cell sheets. It has been noted, however, that a subpopulation of these DRG somata are intimately associated, separated only by a single thin satellite glial cell membrane septum. We set out to test whether such neuron-glial cell-neuron trimers (NGlNs) are also linked functionally. The presence of NGlNs in chick DRGs was confirmed by electron microscopy. Selective satellite glial cell immunostains were identified and were used to image the inter-neuron septa in DRG frozen sections. We used a gentle, dispase-based enzymatic method to isolate chick and rat NGlNs in vitro for double patch clamp recordings. In the majority of pairs tested, an action potential-like stimulus train delivered to one soma resulted in a delayed, noisy and long-duration response in its idle partner. The response to a second stimulus train given minutes later was markedly facilitated. Both bidirectional and unidirectional transmission was observed between the paired neurons. Transmission was chemical and block by the general purinergic blocker suramin implicated ATP as a neurotransmitter. We conclude that the two neuronal somata in the NGlN can communicate by chemical transmission, which may involve a transglial, bi-synaptic pathway. This novel soma-to-soma transmission reflects a novel form of processing that may play a role in sensory disorders in the DRG and interneuron communication in the central nervous system.

Alzheimer’s disease (AD) is the most common cause of age-related dementia. Increasing evidence suggests that neuroinflammation mediated by microglia and astrocytes contributes to disease progression and severity in AD and other neurodegenerative disorders. During AD progression, resident microglia undergo proinflammatory activation, resulting in an increased capacity to convert resting astrocytes to reactive astrocytes. Therefore, microglia are a major therapeutic target for AD and blocking microglia-astrocyte activation could limit neurodegeneration in AD. Here we report that NLY01, an engineered exedin-4, glucagon-like peptide-1 receptor (GLP-1R) agonist, selectively blocks β-amyloid (Aβ)-induced activation of microglia through GLP-1R activation and inhibits the formation of reactive astrocytes as well as preserves neurons in AD models. In two transgenic AD mouse models (5xFAD and 3xTg-AD), repeated subcutaneous administration of NLY01 blocked microglia-mediated reactive astrocyte conversion and preserved neuronal viability, resulting in improved spatial learning and memory. Our study indicates that the GLP-1 pathway plays a critical role in microglia-reactive astrocyte associated neuroinflammation in AD and the effects of NLY01 are primarily mediated through a direct action on Aβ-induced GLP-1R+ microglia, contributing to the inhibition of astrocyte reactivity. These results show that targeting upregulated GLP-1R in microglia is a viable therapy for AD and other neurodegenerative disorders.

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