Imaging local diffusion in microstructures using NV-based pulsed field gradient NMR

Understanding diffusion in microstructures plays a crucial role in many scientific fields, including neuroscience, cancer or energy research. While magnetic resonance (MR) methods are the gold standard for diffusion measurements, spatial encoding in MR imaging has limitations. Here, we introduce nitrogen-vacancy (NV) center based nuclear magnetic resonance (NMR) spectroscopy as a powerful tool to probe diffusion with an optical readouts. We have developed an experimental scheme combining pulsed gradient spin echo (PGSE) with optically detected NV-NMR spectroscopy, which allows for the local quantification of molecular diffusion and flow within microscopic sample volumes. We demonstrate correlated optical imaging with spatially resolved PGSE NV-NMR experiments probing anisotropic water diffusion within a model microstructure. Our optically detected PGSE NV-NMR technique opens up prospects for extending the current capabilities of investigating diffusion processes with the future potential of probing single cells, tissue microstructures, or ion mobility in thin film materials for battery applications.Comment: 37 pages, 5 figures, 2 table

Programmable Ligand Detection System in Plants through a Synthetic Signal Transduction Pathway

There is an unmet need to monitor human and natural environments for substances that are intentionally or unintentionally introduced. A long-sought goal is to adapt plants to sense and respond to specific substances for use as environmental monitors. Computationally re-designed periplasmic binding proteins (PBPs) provide a means to design highly sensitive and specific ligand sensing capabilities in receptors. Input from these proteins can be linked to gene expression through histidine kinase (HK) mediated signaling. Components of HK signaling systems are evolutionarily conserved between bacteria and plants. We previously reported that in response to cytokinin-mediated HK activation in plants, the bacterial response regulator PhoB translocates to the nucleus and activates transcription. Also, we previously described a plant visual response system, the de-greening circuit, a threshold sensitive reporter system that produces a visual response which is remotely detectable and quantifiable.We describe assembly and function of a complete synthetic signal transduction pathway in plants that links input from computationally re-designed PBPs to a visual response. To sense extracellular ligands, we targeted the computational re-designed PBPs to the apoplast. PBPs bind the ligand and develop affinity for the extracellular domain of a chemotactic protein, Trg. We experimentally developed Trg fusions proteins, which bind the ligand-PBP complex, and activate intracellular PhoR, the HK cognate of PhoB. We then adapted Trg-PhoR fusions for function in plants showing that in the presence of an external ligand PhoB translocates to the nucleus and activates transcription. We linked this input to the de-greening circuit creating a detector plant.Our system is modular and PBPs can theoretically be designed to bind most small molecules. Hence our system, with improvements, may allow plants to serve as a simple and inexpensive means to monitor human surroundings for substances such as pollutants, explosives, or chemical agents

Langzeitbehandlung von Parkinsonpatienten mit tiefer Hirnstimulation. Long-term care of Parkinson patients with deep brain stimulation

For more than 15 years deep brain stimulation of the subthalamic nucleus and globus pallidus internus have become therapeutic options in advanced Parkinson's disease. The number of patients with long-term treatment is increasing steadily. This review focuses on issues of the long-term care of these Parkinson's patients, including differences of the available deep brain stimulation systems, recommendations for follow-up examinations, implications for medical diagnostics and therapies and an algorithm for symptom deterioration. Today, there is no profound evidence that deep brain stimulation prevents disease progression. However, symptomatic relief from motor symptoms is maintained during long-term follow-up and interruption of the therapy remains an exception

The impact of subthalamic deep brain stimulation on bradykinesia of proximal and distal upper limb muscles in Parkinson's disease

To assess the differential effects of bilateral deep brain stimulation of the subthalamic nucleus on proximal and distal muscle groups of the upper limb in Parkinson's disease.Eight parkinsonian subjects with chronic bilateral stimulation of the subthalamic nucleus performed index finger tapping (differentially drawing upon distal arm muscles), horizontal pointing (differentially drawing upon proximal arm muscles) and a complex reach-to-grasp task with cubes of different sizes, which involved both proximal and distal arm muscles. An ultrasound based system was used for kinematic motion analysis. Subjects were investigated in two clinical conditions: on and off subthalamic nucleus stimulation. Clinical symptom severity was rated with the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore.Stimulation of the subthalamic nucleus improved the UPDRS motor subscore (68 %). Bradykinesia of index finger tapping and horizontal pointing were equally improved by subthalamic nucleus stimulation. In contrast, in a complex reach-to-grasp task bradykinesia was differentially ameliorated for the grasp component.The data suggest that bilateral stimulation of the subthalamic nucleus improves bradykinesia of both distal and proximal muscles of the arm and hand in Parkinson's disease; however, dependent upon task complexity proximal and distal movement components may be affected differentially. Kinematic motion analysis is an efficient tool to objectively evaluate the beneficial effects of subthalamic nucleus stimulation on dexterity in Parkinson's disease

Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced PD

The authors retrospectively compared 1-year results of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN; n = 16) and internal pallidum (GPi) (n = 11) in advanced PD and found about equal improvements in "off" period motor symptoms, dyskinesias, and fluctuations. STN stimulation reduced medication requirements by 65% and required significantly less electrical power. These advantages contrasted with a need for more intensive postoperative monitoring and a higher incidence of adverse events related to levodopa withdrawal