Publications by authors named "Schaffer C"

Small-animal virtual reality (VR) systems have become invaluable tools in neuroscience for studying complex behavior during head-fixed neural recording, but they lag behind commercial human VR systems in terms of miniaturization, immersivity and advanced features such as eye tracking. Here we present MouseGoggles, a miniature VR headset for head-fixed mice that delivers independent, binocular visual stimulation over a wide field of view while enabling eye tracking and pupillometry in VR. Neural recordings in the visual cortex validate the quality of image presentation, while hippocampal recordings, associative reward learning and innate fear responses to virtual looming stimuli demonstrate an immersive VR experience.

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Microvascular endothelial dysfunction may provide insights into systemic diseases, such as carotid artery disease. Raster-scan optoacoustic mesoscopy (RSOM) can produce images of skin microvasculature during endothelial dysfunction challenges via numerous microvascular features. Herein, RSOM was employed to image the microvasculature of 26 subjects (13 patients with single carotid artery disease, 13 healthy participants) to assess the dynamics of 18 microvascular features at three scales of detail, i.

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Introduction: In microvascular breast reconstruction, the focus has shifted to achieving aesthetically pleasing results. Delayed breast reconstruction poses challenges such as ensuring natural ptosis and avoiding a "patch" effect. The Be.

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Article Synopsis
  • - Understanding the S-layer anchoring in bacteria involves non-covalent interactions between S-layer domains and secondary cell wall polymers (SCWPs), with specific roles for ManNAc ligands and the MnaA enzyme in SCWP biosynthesis.
  • - Research focused on producing MnaA and its variants to analyze their kinetic properties, test allosteric activation by UDP-GlcNAc, and explore the effects of tunicamycin as a potential inhibitor using crystal structure analysis and molecular docking.
  • - The study revealed the crystal structure of MnaA and confirmed the conservation of key residues, finding that UDP-GlcNAc boosts reaction rates but isn't essential for its function, while tunicamycin doesn't
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Here, we report a magnetogenetic system, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. Adeno-associated virus (AAV)-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine-2a receptor-Cre drivers resulted in motor freezing when placed in a magnetic resonance imaging machine or adjacent to a transcranial magnetic stimulation device. Functional imaging and fiber photometry confirmed activation in response to magnetic fields.

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Tannerella serpentiformis is a health-associated Gram-negative oral anaerobe, while its closest phylogenetic relative is the periodontal pathogen Tannerella forsythia. The pathogen employs glycan mimicry through protein O-glycosylation, displaying a terminal nonulosonic acid aiding in evasion of host immune recognition. Like T.

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Introduction: Degradation of host proteins by bacterial proteases leads to the subversion of the host response and disruption of oral epithelial integrity, which is considered an essential factor in the progression of periodontitis. High-temperature requirement A (HtrA) protease, which is critical for bacterial survival and environmental adaptation, is found in several oral bacteria, including the periodontal pathogen . This study investigated the proteolytic activity of HtrA from and its ability to modulate the host response.

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Coal mine drainage (CMD) in Appalachia is a widespread source of dissolved metals, SO, and acidity that can degrade aquatic habitats and water supplies for decades following mine closure and flooding. In the bituminous coalfield of Pennsylvania, the Irwin Coal Basin (ICB) contains a series of partly to completely flooded, abandoned underground mines separated by leaky barriers within the Pittsburgh coal seam. CMD originated throughout the basin from minepool aquifers that formed after mine closures dating from 1910 to 1957.

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, a member of the "red complex" bacteria implicated in severe periodontitis, employs various survival strategies and virulence factors to interact with the host. It thrives as a late colonizer in the oral biofilm, relying on its unique adaptation mechanisms for persistence. Essential to its survival are the type 9 protein secretion system and -glycosylation of proteins, crucial for host interaction and immune evasion.

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Article Synopsis
  • In partial onset epilepsy, seizures start in specific brain areas and can become resistant to medication, making neurosurgery a key treatment option that risks neurological deficits.
  • A study on mice with focal neocortical epilepsy applied precise cuts using femtosecond laser pulses around the seizure focus, significantly reducing seizure frequency by 87% and limiting the spread of seizures.
  • The surgical cuts led to minimal collateral damage and did not impair motor skills in reaching tasks, indicating potential for this method as an effective neurosurgical strategy for treating refractory focal epilepsy.
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Objective: The red-complex bacteria Porphyromonas gingivalis and Tannerella forsythia together with Fusobacterium nucleatum are essential players in periodontitis. This study investigated the bacterial interplay with human periodontal ligament mesenchymal stromal cells (hPDL-MSCs) which act in the acute phase of periodontal infection.

Design: The capability of the bacteria to induce an inflammatory response as well as their viability, cellular adhesion and invasion were analyzed upon mono- and co-infections of hPDL-MSCs to delineate potential synergistic or antagonistic effects.

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Nonlinear optical microscopy enables non-invasive imaging in scattering samples with cellular resolution. The spinal cord connects the brain with the periphery and governs fundamental behaviors such as locomotion and somatosensation. Because of dense myelination on the dorsal surface, imaging to the spinal grey matter is challenging, even with two-photon microscopy.

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The oral cavity harbors a diverse and dynamic bacterial biofilm community which is pivotal to oral health maintenance and, if turning dysbiotic, can contribute to various diseases. Glycans as unsurpassed carriers of biological information are participating in underlying processes that shape oral health and disease. Bacterial glycoinfrastructure-encompassing compounds as diverse as glycoproteins, lipopolysaccharides (LPSs), cell wall glycopolymers, and exopolysaccharides-is well known to influence bacterial fitness, with direct effects on bacterial physiology, immunogenicity, lifestyle, and interaction and colonization capabilities.

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Streptococci are primary colonizers of the oral cavity where they are ubiquitously present and an integral part of the commensal oral biofilm microflora. The role oral streptococci play in the interaction with the host is ambivalent. On the one hand, they function as gatekeepers of homeostasis and are a prerequisite for the maintenance of oral health - they shape the oral microbiota, modulate the immune system to enable bacterial survival, and antagonize pathogenic species.

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Small animal studies in biomedical research often require anesthesia to reduce pain or stress experienced by research animals and to minimize motion artifact during imaging or other measurements. Anesthetized animals must be closely monitored for the safety of the animals and to prevent unintended effects of altered physiology on experimental outcomes. Many currently available monitoring devices are expensive, invasive, or interfere with experimental design.

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The blood-brain barrier (BBB) restricts the systemic delivery of messenger RNAs (mRNAs) into diseased neurons. Although leucocyte-derived extracellular vesicles (EVs) can cross the BBB at inflammatory sites, it is difficult to efficiently load long mRNAs into the EVs and to enhance their neuronal uptake. Here we show that the packaging of mRNA into leucocyte-derived EVs and the endocytosis of the EVs by neurons can be enhanced by engineering leucocytes to produce EVs that incorporate retrovirus-like mRNA-packaging capsids.

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Skin microangiopathy has been associated with diabetes. Here we show that skin-microangiopathy phenotypes in humans can be correlated with diabetes stage via morphophysiological cutaneous features extracted from raster-scan optoacoustic mesoscopy (RSOM) images of skin on the leg. We obtained 199 RSOM images from 115 participants (40 healthy and 75 with diabetes), and used machine learning to segment skin layers and microvasculature to identify clinically explainable features pertaining to different depths and scales of detail that provided the highest predictive power.

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Imaging plays a critical role in exploring the pathophysiology and enabling the diagnostics and therapy assessment in carotid artery disease. Ultrasonography, computed tomography, magnetic resonance imaging and nuclear medicine techniques have been used to extract of known characteristics of plaque vulnerability, such as inflammation, intraplaque hemorrhage and high lipid content. Despite the plethora of available techniques, there is still a need for new modalities to better characterize the plaque and provide novel biomarkers that might help to detect the vulnerable plaque early enough and before a stroke occurs.

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Laser speckle contrast imaging (LSCI) is a widefield imaging technique that enables high spatiotemporal resolution measurement of blood flow. Laser coherence, optical aberrations, and static scattering effects restrict LSCI to relative and qualitative measurements. Multi-exposure speckle imaging (MESI) is a quantitative extension of LSCI that accounts for these factors but has been limited to post-acquisition analysis due to long data processing times.

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RNA macromolecules, like proteins, fold to assume shapes that are intimately connected to their broadly recognized biological functions; however, because of their high charge and dynamic nature, RNA structures are far more challenging to determine. We introduce an approach that exploits the high brilliance of x-ray free-electron laser sources to reveal the formation and ready identification of angstrom-scale features in structured and unstructured RNAs. Previously unrecognized structural signatures of RNA secondary and tertiary structures are identified through wide-angle solution scattering experiments.

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Pyruvylation is a biologically versatile but mechanistically unexplored saccharide modification. 4,6-Ketal pyruvylated N-acetylmannosamine within bacterial secondary cell wall polymers serves as a cell wall anchoring epitope for proteins possessing a terminal S-layer homology domain trimer. The pyruvyltransferase CsaB from Paenibacillus alvei served as a model to investigate the structural basis of the pyruvyltransfer reaction by a combination of molecular modelling and site-directed mutagenesis together with an enzyme assay using phosphoenolpyruvate (PEP; donor) and synthetic β-D-ManNAc-(1 → 4)-α-D-GlcNAc-diphosphoryl-11-phenoxyundecyl (acceptor).

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Here we report a novel suite of magnetogenetic tools, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. AAV-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine 2a receptor-cre driver mice resulted in motor freezing when placed in an MRI or adjacent to a transcranial magnetic stimulation (TMS) device. Functional imaging and fiber photometry both confirmed activation of the target region in response to the magnetic fields.

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RNA macromolecules, like proteins, fold to assume shapes that are intimately connected to their broadly recognized biological functions; however, because of their high charge and dynamic nature, RNA structures are far more challenging to determine. We introduce an approach that exploits the high brilliance of x-ray free electron laser sources to reveal the formation and ready identification of Å scale features in structured and unstructured RNAs. New structural signatures of RNA secondary and tertiary structures are identified through wide angle solution scattering experiments.

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Two-photon excited fluorescence microscopy is a widely-employed imaging technique that enables the noninvasive study of biological specimens in three dimensions with sub-micrometer resolution. Here, we report an assessment of a gain-managed nonlinear (GMN) fiber amplifier for multiphoton microscopy. This recently-developed source delivers 58-nJ and 33-fs pulses at 31-MHz repetition rate.

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Laser speckle contrast imaging (LSCI) is a widefield imaging technique that enables high spatiotemporal resolution measurement of blood flow. Laser coherence, optical aberrations, and static scattering effects restrict LSCI to relative and qualitative measurements. Multi-exposure speckle imaging (MESI) is a quantitative extension of LSCI that accounts for these factors but has been limited to post-acquisition analysis due to long data processing times.

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