Faculty Bibliography

Stroke is a leading cause of mortality and disability. Emergent diagnosis and intervention are critical, and predicated upon initial brain imaging; however, existing clinical imaging modalities are generally costly, immobile, and demand highly specialized operation and interpretation. Low-energy microwaves have been explored as a low-cost, small form factor, fast, and safe probe for tissue dielectric properties measurements, with both imaging and diagnostic potential. Nevertheless, challenges inherent to microwave reconstruction have impeded progress, hence conduction of microwave imaging remains an elusive scientific aim. Herein, we introduce a dedicated experimental framework comprising a robotic navigation system to translate blood-mimicking phantoms within a human head model. An 8-element ultra-wideband array of modified antipodal Vivaldi antennas was developed and driven by a two-port vector network analyzer spanning 0.6-9.0 GHz at an operating power of 1 mW. Complex scattering parameters were measured, and dielectric signatures of hemorrhage were learned using a dedicated deep neural network for prediction of hemorrhage classes and localization. An overall sensitivity and specificity for detection >0.99 was observed, with Rayleigh mean localization error of 1.65 mm. The study establishes the feasibility of a robust experimental model and deep learning solution for ultra-wideband microwave stroke detection.

Glial cells in the peripheral nervous system (PNS), which arise from the neural crest, include axon-associated Schwann cells (SCs) in nerves, synapse-associated SCs at the neuromuscular junction, enteric glia, perikaryon-associated satellite cells in ganglia, and boundary cap cells at the border between the central nervous system (CNS) and the PNS. Here, we focus on axon-associated SCs. These SCs progress through a series of formative stages, which culminate in the generation of myelinating SCs that wrap large-caliber axons and of nonmyelinating (Remak) SCs that enclose multiple, small-caliber axons. In this work, we describe SC development, extrinsic signals from the axon and extracellular matrix (ECM) and the intracellular signaling pathways they activate that regulate SC development, and the morphogenesis and organization of myelinating SCs and the myelin sheath. We review the impact of SCs on the biology and integrity of axons and their emerging role in regulating peripheral nerve architecture. Finally, we explain how transcription and epigenetic factors control and fine-tune SC development and myelination.

Classic change blindness is the phenomenon where seemingly obvious changes that coincide with visual disruptions (such as blinks or brief blanks) go unnoticed by an attentive observer. Some early work into the causes of classic change blindness suggested that any pre-change stimulus representation is overwritten by a representation of the altered post-change stimulus, preventing change detection. However, recent work revealed that, even when observers do maintain memory representations of both the pre- and post-change stimulus states, they can still miss the change, suggesting that change blindness can also arise from a failure to compare the stored representations. Here, we studied slow change blindness, a related phenomenon that occurs even in the absence of visual disruptions when the change occurs sufficiently slowly, to determine whether it could be explained by conclusions from classic change blindness. Across three different slow change blindness experiments we found that observers who consistently failed to notice the change had access to at least two memory representations of the changing display. One representation was precise but short lived: a detailed representation of the more recent stimulus states, but fragile. The other representation lasted longer but was fairly general: stable but too coarse to differentiate the various stages of the change. These findings suggest that, although multiple representations are formed, the failure to compare hypotheses might not explain slow change blindness; even if a comparison were made, the representations would be too sparse (longer term stores) or too fragile (short-lived stores) for such comparison to inform about the change.

PURPOSE OF REVIEW/OBJECTIVE:Extremes of weather as a result of climate change are affecting social, economic and health systems. Kidney health is being threatened by global warming while treatment of kidney disease is contributing to increasing resource utilization and leaving a substantial carbon footprint. Improved physician awareness and patient education are needed to mitigate the risk. RECENT FINDINGS/RESULTS:Rising temperatures are changing kidney disease patterns, with increasing prevalence of acute kidney injury, chronic kidney disease and kidney stones. These issues disproportionately affect people suffering from social inequality and limited access to resources. SUMMARY/CONCLUSIONS:In this article, we review the effects of climate change on kidney stones, and acute and chronic kidney injury. Finally, we discuss the impact of renal replacement therapies on the environment and proposed ways to mitigate it.

SIGNIFICANCE/UNASSIGNED:Rapid acquisition of large imaging volumes with microscopic resolution is an essential unmet need in biological research, especially for monitoring rapid dynamical processes such as fast activity in distributed neural systems. AIM/UNASSIGNED:We present a multifocal strategy for fast, volumetric, diffraction-limited resolution imaging over relatively large and scalable fields of view (FOV) using single-camera exposures. APPROACH/UNASSIGNED:Our multifocal microscopy approach leverages diffraction to image multiple focal depths simultaneously. It is based on a custom-designed diffractive optical element suited to low magnification and large FOV applications and customized prisms for chromatic correction, allowing for wide bandwidth fluorescence imaging. We integrate this system within a conventional microscope and demonstrate that our design can be used flexibly with a variety of magnification/numerical aperture (NA) objectives. RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:Our study demonstrates the advantage of diffraction-based multifocal imaging techniques for 3D imaging of mm-scale objects from a single-camera exposure, with important applications in functional neural imaging and other areas benefiting from volumetric imaging.

Both cortical and cerebellar developmental differences have been implicated in attention-deficit/hyperactivity disorder (ADHD). Recently accumulating neuroimaging studies have highlighted hierarchies as a fundamental principle of brain organization, suggesting the importance of assessing hierarchy abnormalities in ADHD. A novel gradient-based resting-state functional connectivity analysis was applied to investigate the cerebro-cerebellar disturbed hierarchy in children and adolescents with ADHD. We found that the interaction of functional gradient between diagnosis and age was concentrated in default mode network (DMN) and visual network (VN). At the same time, we also found that the opposite gradient changes of DMN and VN caused the compression of the cortical main gradient in ADHD patients, implicating the co-occurrence of both low- (visual processing) and high-order (self-related thought) cognitive dysfunction manifesting in abnormal cerebro-cerebellar organizational hierarchy in ADHD. Our study provides a neurobiological framework to better understand the co-occurrence and interaction of both low-level and high-level functional abnormalities in the cortex and cerebellum in ADHD.

Perinatal white matter injury (WMI) is the leading cause of long-term neurological morbidity in infants born preterm. Neuroinflammation during a critical window of early brain development plays a key role in WMI disease pathogenesis. The mechanisms linking inflammation with the long-term myelination failure that characterizes WMI, however, remain unknown. Here, we investigate the role of astrocyte reactivity in WMI. In an experimental mouse model of WMI, we demonstrate that WMI disease outcomes are improved in mutant mice lacking secretion of inflammatory molecules TNF-α, IL-1α, and C1q known, in addition to other roles, to induce the formation of a neuroinflammatory reactive astrocyte substate. We show that astrocytes express molecular signatures of the neuroinflammatory reactive astrocyte substate in both our WMI mouse model and human tissue affected by WMI, and that this gene expression pattern is dampened in injured mutant mice. Our data provide evidence that a neuroinflammatory reactive astrocyte substate correlates with adverse WMI disease outcomes, thus highlighting the need for further investigation of these cells as potential causal players in WMI pathology.

While visual responses to familiar and novel stimuli have been extensively studied, it is unknown how neuronal representations of familiar stimuli are affected when they are interleaved with novel images. We examined a large-scale dataset from mice performing a visual go/no-go change detection task. After training with eight images, six novel images were interleaved with two familiar ones. Unexpectedly, we found that the behavioral performance in response to familiar images was impaired when they were mixed with novel images. When familiar images were interleaved with novel ones, the dimensionality of their representation increased, indicating a perturbation of their neuronal responses. Furthermore, responses to familiar images in the primary visual cortex were less predictive of responses in higher-order areas, indicating less efficient communication. Spontaneous correlations between neurons were predictive of responses to novel images, but less so to familiar ones. Our study demonstrates the modification of representations of familiar images by novelty.

Microsatellites are highly mutable sequences that can serve as markers for relationships among individuals or cells within a population. The accuracy and resolution of reconstructing these relationships depends on the fidelity of microsatellite profiling and the number of microsatellites profiled. However, current methods for targeted profiling of microsatellites incur significant "stutter" artifacts that interfere with accurate genotyping, and sequencing costs preclude whole-genome microsatellite profiling of a large number of samples. We developed a novel method for accurate and cost-effective targeted profiling of a panel of more than 150,000 microsatellites per sample, along with a computational tool for designing large-scale microsatellite panels. Our method addresses the greatest challenge for microsatellite profiling-"stutter" artifacts-with a low-temperature hybridization capture that significantly reduces these artifacts. We also developed a computational tool for accurate genotyping of the resulting microsatellite sequencing data that uses an ensemble approach integrating three microsatellite genotyping tools, which we optimize by analysis of de novo microsatellite mutations in human trios. Altogether, our suite of experimental and computational tools enables high-fidelity, large-scale profiling of microsatellites, which may find utility in diverse applications such as lineage tracing, population genetics, ecology, and forensics.