tag:www.urmc.rochester.edu,2009-01-01:/bme/2013-05-21T22:02:26-04:00 tag:www.urmc.rochester.edu,2009-01-01:/bme/235182272013-06-25T00:00:00Z

Spinal cord injury (SCI) initiates a cascade of processes that ultimately form a nonpermissive environment for axonal regeneration. Emerging evidence suggests that regenerative failure may be due in part to inhibitory factors expressed by reactive spinal cord glial cells and meningeal fibroblasts, such as the Eph receptor protein-tyrosine kinases and their corresponding ligands (ephrins). Here we sought to assess the role of ephrin B2, an inhibitory axonal guidance molecule, as an inhibitor of the recovery process following SCI. To determine the extent of ephrin B2 involvement in axonal regenerative failure, a SCI model was performed on a conditional ephrin B2 knockout mouse strain (ephrin B2(-/-)), in which the ephrin B2 gene was deleted under the GFAP promoter . The expression of ephrin B2 was significantly decreased in astrocytes of injured and uninjured ephrin B2(-/-) mice compared to wild-type mice. Notably, in the ephrin B2(-/-) mice, the deletion of ephrin B2 reduced astrogliosis, and accelerated motor function recovery after SCI. Anterograde axonal tracing on a hemisection model of SCI further showed that ephrin B2(-/-) mice exhibited increased regeneration of injured corticospinal axons and a reduced glial scar, when compared to littermate controls exposed to similar injury. These results were confirmed by an in vitro neurite outgrowth assay and ephrin B2 functional blockage, which showed that ephrin B2 expressed on astrocytes inhibited axonal growth. Combined these findings suggest that ephrin B2 ligands expressed by reactive astrocytes impede the recovery process following SCI. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Z RenX ChenJ YangBT KressJ TongH LiuT TakanoY ZhaoM Nedergaardhttp://www.urmc.rochester.edu/people/23788299-maiken-nedergaard tag:www.urmc.rochester.edu,2009-01-01:/bme/234347582013-06-15T00:00:00Z

Rapid, sensitive, and selective detection of viruses is critical for applications in medical diagnostics, biosecurity, and environmental safety. In this article, we report the application of a point-defect-coupled W1 photonic crystal (PhC) waveguide biosensor to label-free optical detection of viruses. Fabricated on a silicon-on-insulator (SOI) substrate using electron-beam (e-beam) lithography and reactive-ion-etching, the PhC sensing platform allows optical detection based on resonant mode shifts in response to ambient refractive index changes produced by infiltration of target biomaterial within the holes of the PhC structure. Finite difference time domain (FDTD) calculations were performed to assist with design of the sensor, and to serve as a theoretical benchmark against which experimental results could be compared. Using Human Papillomavirus virus-like particles (VLPs) spiked in 10% fetal bovine serum as a model system, we observed a limit of detection of 1.5 nM in simple (buffer only) or complex (10% serum) sample matrices. The use of anti-VLP antibodies specific for intact VLPs with the PhC sensors provided highly selective VLP detection. Copyright © 2013 Elsevier B.V. All rights reserved.

S PalAR YadavMA LifsonJE BakerPM FauchetBL Millerhttp://www.urmc.rochester.edu/people/21977435-benjamin-l-miller tag:www.urmc.rochester.edu,2009-01-01:/bme/236861722013-06-T00:00:00Z

The richness of perceptual experience, as well as its usefulness for guiding behaviour, depends on the synthesis of information across multiple senses. Recent decades have witnessed a surge in our understanding of how the brain combines sensory cues. Much of this research has been guided by one of two distinct approaches: one is driven primarily by neurophysiological observations, and the other is guided by principles of mathematical psychology and psychophysics. Conflicting results and interpretations have contributed to a conceptual gap between psychophysical and physiological accounts of cue integration, but recent studies of visual-vestibular cue integration have narrowed this gap considerably.

CR FetschGC DeangelisDE Angelaki tag:www.urmc.rochester.edu,2009-01-01:/bme/236583822013-05-8T00:00:00Z

OBJECTIVE: The objective of this study was to determine which aspects of executive functions are most affected in behavioral variant frontotemporal dementia (bvFTD) and best differentiate this syndrome from Alzheimer disease (AD). METHODS: We compared executive functions in 22 patients diagnosed with bvFTD, 26 with AD, and 31 neurologically healthy controls using a conceptually driven and comprehensive battery of executive function tests, the NIH EXAMINER battery (http://examiner.ucsf.edu). RESULTS: The bvFTD and the AD patients were similarly impaired compared with controls on tests of working memory, category fluency, and attention, but the patients with bvFTD showed significantly more severe impairments than the patients with AD on tests of letter fluency, antisaccade accuracy, social decision-making, and social behavior. Discriminant function analysis with jackknifed cross-validation classified the bvFTD and AD patient groups with 73% accuracy. CONCLUSIONS: Executive function assessment can support bvFTD diagnosis when measures are carefully selected to emphasize frontally specific functions.

KL PossinD FeigenbaumKP RankinGE SmithAL BoxerK WoodSM HannaBL Millerhttp://www.urmc.rochester.edu/people/21977435-benjamin-l-millerJH Kramer tag:www.urmc.rochester.edu,2009-01-01:/bme/235411342013-05-2T00:00:00Z

For many tissue engineering applications and studies to understand how materials fundamentally affect cellular functions, it is important to have the ability to synthesize biomaterials that can mimic elements of native cell-extracellular matrix interactions. Hydrogels possess many properties that are desirable for studying cell behavior. For example, hydrogels are biocompatible and can be biochemically and mechanically altered by exploiting the presentation of cell adhesive epitopes or by changing hydrogel crosslinking density. To establish physical and biochemical tunability, hydrogels can be engineered to alter their properties upon interaction with external driving forces such as pH, temperature, electric current, as well as exposure to cytocompatible irradiation. Additionally, hydrogels can be engineered to respond to enzymes secreted by cells, such as matrix metalloproteinases and hyaluronidases. This review details different strategies and mechanisms by which biomaterials, specifically hydrogels, can be manipulated dynamically to affect cell behavior. By employing the appropriate combination of stimuli and hydrogel composition and architecture, cell behavior such as adhesion, migration, proliferation, and differentiation can be controlled in real time. This three-dimensional control in cell behavior can help create programmable cell niches that can be useful for fundamental cell studies and in a variety of tissue engineering applications.

K VatsDS Benoit/people/faculty/bio/?id=385 tag:www.urmc.rochester.edu,2009-01-01:/bme/236695582013-05-10T00:00:00Z

BACKGROUND: Infants in the newborn intensive care unit (NICU) are exposed to routine procedures that often cause distress and carry a negative burden or load on the infant's neurodevelopment. AIM: A ratio level index is introduced to estimate procedural load so as to begin to develop a system to monitor the intensity of distress associated with common NICU procedures. STUDY DESIGN: Two psychophysical methods, magnitude estimation (ME) and the general labeled magnitude scale (gLMS) were used to survey 86 clinicians via the internet to estimate the distress associated with 55 common NICU procedures. RESULTS: gLMS and ME estimations correlated highly across all procedures (r=0.97). gLMS values were used to derive the procedural load index (PLI) as a ratio level estimation of procedural distress. CONCLUSION: The PLI ranks and differentiates distress among common NICU procedures more precisely than current tools. This methodology, if correlated with infant physiological indices and health outcomes, may be operationalized at the bedside to measure procedural distress, and help to guide the ideal timing to perform procedures and minimize their negative consequence. Copyright © 2013 Elsevier Ltd. All rights reserved.

M SchiavenatoSA AntosFA BellBR FreedmanAJ KozakTB KrootEH LamKE RossBA SternfieldLH Carney/people/faculty/bio/?id=229 tag:www.urmc.rochester.edu,2009-01-01:/bme/236353582013-05-1T00:00:00Z

BACKGROUND: Neurodegenerative diseases such as Alzheimer's are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid beta. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. METHODS: Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30--180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. RESULTS: Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. CONCLUSION: Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans.

L YangBT KressHJ WeberM ThiyagarajanB WangR DeaneH BenvenisteJJ IliffM Nedergaardhttp://www.urmc.rochester.edu/people/23788299-maiken-nedergaard tag:www.urmc.rochester.edu,2009-01-01:/bme/232391612013-05-T00:00:00Z

A major challenge in cartilage tissue engineering is the need to recreate the native tissue's anisotropic extracellular matrix structure. This anisotropy has important mechanical and biological consequences and could be crucial for integrative repair. Here, we report that hydrodynamic conditions that mimic the motion-induced flow fields in between the articular surfaces in the synovial joint induce the formation of a distinct superficial layer in tissue engineered cartilage hydrogels, with enhanced production of cartilage matrix proteoglycan and Type II collagen. Moreover, the flow stimulation at the surface induces the production of the surface zone protein Proteoglycan 4 (aka PRG4 or lubricin). Analysis of second harmonic generation signature of collagen in this superficial layer reveals a highly aligned fibrillar matrix that resembles the alignment pattern in native tissue's surface zone, suggesting that mimicking synovial fluid flow at the cartilage surface in hydrodynamic bioreactors could be key to creating engineered cartilage with superficial zone features. Copyright © 2012 Wiley Periodicals, Inc.

T ChenMJ HiltonEB Brown/people/faculty/bio/?id=232MJ ZuscikHA Awad/people/faculty/bio/?id=240 tag:www.urmc.rochester.edu,2009-01-01:/bme/236558122013-05-T00:00:00Z

Detection of tones in reproducible noises provides detailed patterns of hit and false-alarm rates across sets of masker waveforms. Analysis of these detection patterns can identify the cues or combination of cues listeners use for detection in narrowband and wideband noise. Recent work has shown that diotic detection patterns of listeners with normal hearing (NH) are significantly correlated to energy and envelope cues; fine-structure cues also contribute for wideband maskers. Detection patterns are best predicted by an optimal cue-combination model based on signal-detection theory. In this study, listeners with mild to moderate sensorineural hearing loss (HL) were tested using the same waveforms. Their diotic detection patterns were best predicted by energy or envelope cues, with little contribution of fine-structure timing. Also, unlike NH patterns, predictions of HL patterns were rarely improved by an optimal combination of cues. For dichotic detection, NH patterns were better predicted by the slope of the interaural envelope difference (SIED) than by ITD or ILD cues. For HL patterns, the SIED cue, a nonlinear combination of ITD and ILD cues, generally did not predict detection patterns. These results illustrate differences between NH and HL listeners in the use and combination of cues for detection in noise.

LH Carney/people/faculty/bio/?id=229J MaoKJ KochKA Doherty tag:www.urmc.rochester.edu,2009-01-01:/bme/236545622013-05-T00:00:00Z

A formant-based approach to representing vowel quality is anchored in acoustic theory and is well documented in perception studies and in auditory modeling. This ongoing study investigates the representation of vowels in the responses of auditory models at the level of the midbrain (inferior colliculus). Previous modeling and physiological results have shown that formant structure is conveyed by changes in neural rates of midbrain cells that are tuned to amplitude modulations near voice pitch frequency. The current study examined model population responses to 20 speakers (10 males, 10 females) reciting 12 English vowel contrasts from the Hillenbrand et al. database [J. Acoust. Sci. Am. 97, 3099 (1995)]. Pairwise correlations across model population responses for each vowel were used to evaluate variability in the neural representations. Results show that the acoustical variability associated with the vowel contrasts is maintained in these neural representations. Thus, variability in the acoustic vowel space is maintained after the nonlinear responses of realistic auditory-nerve models and midbrain models for amplitude modulation tuning. Our goal is to extend our knowledge of the neural representation of the vowel space using a computational model for the responses of auditory neurons to ensembles of speech tokens.

LH Carney/people/faculty/bio/?id=229J LiT LiJM McDonough