Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain

Imaging techniques based on optical contrast analysis can be used to visualize dynamic and functional properties of the nervous system via optical signals resulting from changes in blood volume, oxygen consumption and cellular swelling associated with brain physiology and pathology. Here we report in vivo noninvasive transdermal and transcranial imaging of the structure and function of rat brains by means of laser-induced photoacoustic tomography (PAT). The advantage of PAT over pure optical imaging is that it retains intrinsic optical contrast characteristics while taking advantage of the diffraction-limited high spatial resolution of ultrasound. We accurately mapped rat brain structures, with and without lesions, and functional cerebral hemodynamic changes in cortical blood vessels around the whisker-barrel cortex in response to whisker stimulation. We also imaged hyperoxia- and hypoxia-induced cerebral hemodynamic changes. This neuroimaging modality holds promise for applications in neurophysiology, neuropathology and neurotherapy

Proteasomal Degradation of Proinsulin Requires Derlin-2, HRD1 and p97

Nephrolog

Ultrathin Gold Nanowire-Functionalized Carbon Nanotubes for Hybrid Molecular Sensing

Carbon nanotubes (CNTs) have shown great potential as sensing component in the electrochemical, field effect transistor and optical sensors, because of their extraordinary onedimensional electronic structure, thermal conductivity, tunable and stable near-infrared emission. However, the insolubility of CNTs due to strong van der Waals interactions limits their use in the field of nanotechnology. In this study, we demonstrate that non-covalent ultrathin gold nanowires functionalized multi-walled carbon nanotube (GNW-CNT) hybrid sensing agents show highly efficient and selective immune molecular sensing in electrochemical and near-infrared photoacoustic imaging methods. A detection limit of 0.01 ng/mL for the Alpha-Fetoprotein (AFP) antigen with high selectivity is shown. The extraordinary optical absorption, thermal and electric conductivity of hybrid GNW-CNTs presented in this study could be an effective tactic to integrate imaging, sensing and treatment functionalities

A practical guide to photoacoustic tomography in the life sciences

The life sciences can benefit greatly from imaging technologies that connect microscopic discoveries with macroscopic observations. One technology uniquely positioned to provide such benefits is photoacoustic tomography (PAT), a sensitive modality for imaging optical absorption contrast over a range of spatial scales at high speed. In PAT, endogenous contrast reveals a tissue's anatomical, functional, metabolic, and histologic properties, and exogenous contrast provides molecular and cellular specificity. The spatial scale of PAT covers organelles, cells, tissues, organs, and small animals. Consequently, PAT is complementary to other imaging modalities in contrast mechanism, penetration, spatial resolution, and temporal resolution. We review the fundamentals of PAT and provide practical guidelines for matching PAT systems with research needs. We also summarize the most promising biomedical applications of PAT, discuss related challenges, and envision PAT's potential to lead to further breakthroughs

A Chaperone Trap Contributes to the Onset of Cystic Fibrosis

Protein folding is the primary role of proteostasis network (PN) where chaperone interactions with client proteins determine the success or failure of the folding reaction in the cell. We now address how the Phe508 deletion in the NBD1 domain of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein responsible for cystic fibrosis (CF) impacts the binding of CFTR with cellular chaperones. We applied single ion reaction monitoring mass spectrometry (SRM-MS) to quantitatively characterize the stoichiometry of the heat shock proteins (Hsps) in CFTR folding intermediates in vivo and mapped the sites of interaction of the NBD1 domain of CFTR with Hsp90 in vitro. Unlike folding of WT-CFTR, we now demonstrate the presence of ΔF508-CFTR in a stalled folding intermediate in stoichiometric association with the core Hsps 40, 70 and 90, referred to as a ‘chaperone trap’. Culturing cells at 30 C resulted in correction of ΔF508-CFTR trafficking and function, restoring the sub-stoichiometric association of core Hsps observed for WT-CFTR. These results support the interpretation that ΔF508-CFTR is restricted to a chaperone-bound folding intermediate, a state that may contribute to its loss of trafficking and increased targeting for degradation. We propose that stalled folding intermediates could define a critical proteostasis pathway branch-point(s) responsible for the loss of function in misfolding diseases as observed in CF

Clinical implications of frequency-force relation

In order to assess the frequency-force relationship in man, the relation between RR intervals and timing of dosing and opening sounds of a prosthetic mitral valve was studied by means of cross-correlation techniques in eight patients with atrial fibrillation. The relation between RR intervals and aortic blood flow velocity was also studied with the same techniques in three patients with atrial fibrillation during thoracotomy. Frequency-force relation could be demonstrated in the cross-correlograms between RR interval and the interval between the occurrence of the R wave and the mitral valve dosing sound and also in the crosscorrelograms between RR interval and aortic blood flow parameters such as stroke volume

Treatment of chronic suppurative osteomyelitis of the mandible

Chronic suppurative osteomyelitis of the mandible is often considered difficult to treat and may lead to refractory osteomyelitis. Sixteen patients with chronic suppurative osteomyelitis of the mandible were treated with a relatively simple protocol, consisting of sequestrectomy or decortication and i.v. antimicrobial therapy for one week, followed by oral penicillin for three weeks. Only one case showed recurrence of symptoms, which was treated successfully in a second session. It is concluded that combined surgical and antimicrobial therapy should be sufficient to cure most cases of chronic suppurative osteomyelitis of the mandibl