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The Journal of Investigative Dermatology Feb 2024Physiological calcification of soft tissues is a common occurrence in aging and various acquired and inherited disorders. ABCC6 sequence variations cause the...
Physiological calcification of soft tissues is a common occurrence in aging and various acquired and inherited disorders. ABCC6 sequence variations cause the calcification phenotype of pseudoxanthoma elasticum (PXE) as well as some cases of generalized arterial calcification of infancy, which is otherwise caused by defective ENPP1. ABCC6 is primarily expressed in the liver, which has given the impression that the liver is central to the pathophysiology of PXE/generalized arterial calcification of infancy. The emergence of inflammation as a contributor to the calcification in PXE suggested that peripheral tissues play a larger role than expected. In this study, we investigated whether bone marrow-derived ABCC6 contributes to the calcification in PXE. In Abcc6 mice, we observed prevalent mineralization in several lymph nodes and surrounding connective tissues and an extensive network of lymphatic vessels within vibrissae, a calcified tissue in Abcc6 mice. Furthermore, we found evidence of lymphangiogenesis in patients with PXE and mouse skin, suggesting an inflammatory process. Finally, restoring wild-type bone marrow in Abcc6 mice produced a significant reduction of calcification, suggesting that the liver alone is not sufficient to fully inhibit mineralization. With evidence that ABCC6 is expressed in lymphocytes, we suggest that the adaptative immune system and inflammation largely contribute to the calcification in PXE/generalized arterial calcification of infancy.
PubMed: 38367909
DOI: 10.1016/j.jid.2024.01.026 -
BioRxiv : the Preprint Server For... Mar 2024Most mammals have specialized facial hairs known as vibrissae (whiskers), sensitive tactile structures that subserve both touch and flow sensing. Different animals have...
Most mammals have specialized facial hairs known as vibrissae (whiskers), sensitive tactile structures that subserve both touch and flow sensing. Different animals have different numbers and geometric arrangements of whiskers, and it seems nearly self-evident that these differences would correlate with functional and behavioral use. To date, however, cross-species comparisons of three-dimensional (3D) whisker array geometry have been limited because standard morphometric techniques cannot be applied. Our laboratory recently developed a novel approach to enable quantitative, cross-species vibrissal array comparisons. Here we quantify the 3D morphology of the vibrissal array of the harbor seal ( ), construct a CAD model of the array, and compare array morphologies of harbor seals, mice ( ) and rats ( ). In all three species whisker arclength decreases from caudal to rostral, whisker curvature increases from caudal to rostral, and whiskers emerge from the face in smooth orientation gradients. Two aspects of whisker orientation are strikingly consistent across species: the elevation angle is constant within a row, and the twist of the whisker about its own axis varies smoothly in a diagonal gradient across the array. We suggest that invariant whisker elevation within a row may aid localization behaviors, while variable twist-orientation may help the animal sense stimulus direction. We anticipate this work will serve as a starting point for quantitative comparisons of vibrissal arrays across species, help clarify the mechanical basis by which seal vibrissae enable efficient wake detection and following, and enable the creation of whole-body biomechanical models for neuroscience and robotics.
PubMed: 38293081
DOI: 10.1101/2024.01.15.575743 -
International Journal of Molecular... Jan 2024Peripheral nerve injuries (PNIs) occur frequently and can lead to devastating and permanent sensory and motor function disabilities. Systemic tacrolimus (FK506)...
Peripheral nerve injuries (PNIs) occur frequently and can lead to devastating and permanent sensory and motor function disabilities. Systemic tacrolimus (FK506) administration has been shown to hasten recovery and improve functional outcomes after PNI repair. Unfortunately, high systemic levels of FK506 can result in adverse side effects. The localized administration of FK506 could provide the neuroregenerative benefits of FK506 while avoiding systemic, off-target side effects. This study investigates the utility of a novel FK506-impregnated polyester urethane urea (PEUU) nerve wrap to treat PNI in a previously validated rat infraorbital nerve (ION) transection and repair model. ION function was assessed by microelectrode recordings of trigeminal ganglion cells responding to controlled vibrissae deflections in ION-transected and -repaired animals, with and without the nerve wrap. Peristimulus time histograms (PSTHs) having 1 ms bins were constructed from spike times of individual single units. Responses to stimulus onsets (ON responses) were calculated during a 20 ms period beginning 1 ms after deflection onset; this epoch captures the initial, transient phase of the whisker-evoked response. Compared to no-wrap controls, rats with PEUU-FK506 wraps functionally recovered earlier, displaying larger response magnitudes. With nerve wrap treatment, FK506 blood levels up to six weeks were measured nearly at the limit of quantification (LOQ ≥ 2.0 ng/mL); whereas the drug concentrations within the ION and muscle were much higher, demonstrating the local delivery of FK506 to treat PNI. An immunohistological assessment of ION showed increased myelin expression for animals assigned to neurorrhaphy with PEUU-FK506 treatment compared to untreated or systemic-FK506-treated animals, suggesting that improved PNI outcomes using PEUU-FK506 is mediated by the modulation of Schwann cell activity.
Topics: Animals; Rats; Tacrolimus; Myelin Sheath; Neurons; Urethane; Nerve Regeneration; Amides; Carbamates; Urea; Esters
PubMed: 38255920
DOI: 10.3390/ijms25020847 -
Journal of Thermal Biology Jan 2024Enhanced vascular permeability at the site of injury is a prominent feature in acute inflammatory pain models, commonly assessed through the Evans Blue test. However,...
Enhanced vascular permeability at the site of injury is a prominent feature in acute inflammatory pain models, commonly assessed through the Evans Blue test. However, this invasive test requires euthanasia, thereby precluding further investigations on the same animal. Due to these limitations, the integration of non-invasive tools such as IRT has been sought. Here, we aimed to evaluate the use of thermography in a common orofacial pain model that employs formalin as a chemical irritant to induce local orofacial inflammation. Male Hannover rats (290-300 g, N = 43) were used. In the first approach, radiometric images were taken before and after formalin administration, assessing temperature changes and extravasated Evans Blue. The second approach included capturing pre- and post-formalin test radiometric images, followed by cytokine measurements in excised vibrissae tissue. Rats were anesthetized for vibrissae tissue collection, allowing correlations between thermographic patterns, nocifensive behavior duration, and cytokine levels in this area. Our findings revealed a positive correlation between local temperature, measured via thermography, and vascular permeability in the contralateral (r = 0.3483) and ipsilateral (r = 0.4502) side, measured using spectrophotometry. The obtained data supports the notion that thermography-based temperature assessment can effectively evaluate vascular permeability in the orofacial region.
Topics: Rats; Male; Animals; Formaldehyde; Thermography; Capillary Permeability; Evans Blue; Facial Pain; Cytokines
PubMed: 38176292
DOI: 10.1016/j.jtherbio.2023.103782 -
ENeuro Jan 2024The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and considered an...
The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in their connection strength with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS and, as a result, exert distinct influences on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution of striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1 in male and female mice and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex vivo patch clamp electrophysiology. We found that M1 and S1 dually innervate SPNs and FSIs; however, there is a consistent bias towards the M1 input in SPNs that is not found in FSIs. In addition, M1 and S1 inputs were distributed similarly across the proximal, medial, and distal regions of SPN and FSI dendrites. Notably, closely localized M1 and S1 clusters of inputs were more prevalent in SPNs than FSIs, suggesting that cortical inputs are integrated through cell-type specific mechanisms. Our results suggest that the stronger functional connectivity from M1 to SPNs compared to S1, as previously observed, is due to a higher quantity of synaptic inputs. Our results have implications for how sensorimotor integration is performed in the striatum through cell-specific differences in corticostriatal connections.
Topics: Mice; Male; Female; Animals; Vibrissae; Neurons; Interneurons; Corpus Striatum; Neostriatum
PubMed: 38164611
DOI: 10.1523/ENEURO.0503-23.2023 -
Cell Reports Jan 2024Goal-directed behaviors involve coordinated activity in many cortical areas, but whether the encoding of task variables is distributed across areas or is more...
Goal-directed behaviors involve coordinated activity in many cortical areas, but whether the encoding of task variables is distributed across areas or is more specifically represented in distinct areas remains unclear. Here, we compared representations of sensory, motor, and decision information in the whisker primary somatosensory cortex, medial prefrontal cortex, and tongue-jaw primary motor cortex in mice trained to lick in response to a whisker stimulus with mice that were not taught this association. Irrespective of learning, properties of the sensory stimulus were best encoded in the sensory cortex, whereas fine movement kinematics were best represented in the motor cortex. However, movement initiation and the decision to lick in response to the whisker stimulus were represented in all three areas, with decision neurons in the medial prefrontal cortex being more selective, showing minimal sensory responses in miss trials and motor responses during spontaneous licks. Our results reconcile previous studies indicating highly specific vs. highly distributed sensorimotor processing.
Topics: Mice; Animals; Somatosensory Cortex; Goals; Parietal Lobe; Neocortex; Neurons; Vibrissae
PubMed: 38150365
DOI: 10.1016/j.celrep.2023.113618 -
Mycologia 2024The marine basidiomycete has been regarded as a species complex, possibly including several species, because morphological variations in fruitbody, spore, and spore...
The marine basidiomycete has been regarded as a species complex, possibly including several species, because morphological variations in fruitbody, spore, and spore appendage have been observed in materials from worldwide collections. Using more than 50 monosporic isolates of -like fungi mainly obtained from Japanese beach coasts, we investigated their molecular phylogeny, morphological characteristics, mating compatibility, nuclear behavior during spore formation, and life cycles. Molecular phylogenetic analyses separated the examined strains into seven clades. Each clade of fungi exhibited distinctive characteristics in fruitbodies and spores produced by culturing monokaryotic strains and mated dikaryotic strains; these characteristics included the color of fruitbodies, apical structure of peridial hair hyphae, spore shape, and apical structure of spore appendages. Mating tests of monokaryotic strains demonstrated mating compatibility between strains within a clade and incompatibility among clades. Therefore, each clade of fungi was phylogenetically, morphologically, and biologically recognized as a different species. Observation of the type specimen of revealed a tiny T-shaped apical structure of spore appendages-not mentioned in the original description-that is unique to the species. This finding, together with the original description, suggests that our studied strains include . aff. , whose morphology is mostly identical to sensu stricto, and three new species. Thus, we describe three new species and propose emendation of the descriptions of the genus . Culture-based studies have demonstrated that species have both sexual and asexual morphs that produce morphologically similar fruitbodies (basidiomata and conidiomata) and spores (basidiospores and conidia). Because it has both morphs forming appendaged waterborne basidiospores and conidia, must be the most well-adapted marine basidiomycete, ensuring the continuation of new generations by two morphs, while distributing in and inhabiting numerous marine environments.
Topics: Animals; Phylogeny; Spores, Fungal; Basidiomycota; Life Cycle Stages; Agaricales
PubMed: 38109665
DOI: 10.1080/00275514.2023.2276028 -
BioRxiv : the Preprint Server For... Dec 2023High-resolution awake mouse fMRI remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable...
High-resolution awake mouse fMRI remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radiofrequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Using a 14T scanner, high-resolution fMRI enabled brain-wide functional mapping of visual and vibrissa stimulation at 100×100×200μm resolution with a 2s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust BOLD responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 seconds prior to the air-puff in awake mice with repetitive stimulation, which was not detectable with the randomized stimulation paradigm. This early BC activation indicated learned anticipation through the vibrissa system and association cortices in awake mice under continuous training of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas.
PubMed: 38106227
DOI: 10.1101/2023.12.08.570803 -
Annual International Conference of the... Jul 2023This paper presents a high-speed rat whisker tracking and symmetry analysis system based on FPGA. The system utilizes high-speed image sensors recording rat face videos...
This paper presents a high-speed rat whisker tracking and symmetry analysis system based on FPGA. The system utilizes high-speed image sensors recording rat face videos at 120 and 1000 fps. The Xilinx Ultra96 single computer board is chosen as the platform to implement the system's processing system (PS) and the programmable logic (PL) part. The PL part is responsible for high-speed image processing and whisker tracking, while the PS part analyzes the symmetry of rat face using the tracking results from the PL part. With a processing speed FoM of 118.5 fps/GHz on the Xilinx Ultra96 single computer board and 275.47 fps/GHz on a laptop with Intel Core [email protected], the presented system achieves excellent performance. The proposed whisker detection method has a precision of 98.2% when a threshold with a 4-degree error is selected, with an average error angle of 0.98 degrees across more than 10,000 video frames. Moreover, the proposed system is capable of local video processing within millisecond delays. These results demonstrate the feasibility of developing a high-speed, accurate, and efficient whisker tracking and symmetry analysis system for rat behavior research.
Topics: Rats; Animals; Vibrissae; Image Processing, Computer-Assisted
PubMed: 38083760
DOI: 10.1109/EMBC40787.2023.10340867 -
Cell Reports Dec 2023Sensory cortical areas are organized into topographic maps representing the sensory epithelium. Interareal projections typically connect topographically matched...
Sensory cortical areas are organized into topographic maps representing the sensory epithelium. Interareal projections typically connect topographically matched subregions across areas. Because matched subregions process the same stimulus, their interaction is central to many computations. Here, we ask how topographically matched subregions of primary and secondary vibrissal somatosensory cortices (vS1 and vS2) interact during active touch. Volumetric calcium imaging in mice palpating an object with two whiskers revealed a sparse population of highly responsive, broadly tuned touch neurons especially pronounced in layer 2 of both areas. These rare neurons exhibited elevated synchrony and carried most touch-evoked activity in both directions. Lesioning the subregion of either area responding to the spared whiskers degraded touch responses in the unlesioned area, with whisker-specific vS1 lesions degrading whisker-specific vS2 touch responses. Thus, a sparse population of broadly tuned touch neurons dominates vS1-vS2 communication in both directions, and topographically matched vS1 and vS2 subregions recurrently amplify whisker touch activity.
Topics: Mice; Animals; Touch; Touch Perception; Neurons; Somatosensory Cortex; Vibrissae; Physical Stimulation
PubMed: 38064338
DOI: 10.1016/j.celrep.2023.113532