Event Begins: Thursday, November 14, 2024 12:00pm
Location: Dental & W.K. Kellogg Institute
Organized By: Office of Research School of Dentistry

Oral Health Sciences Seminar Series

Leveraging Focused Ultrasound to Drive Tissue Regeneration via On-Demand Modulation of Microenvironmental Cues

Mario L. Fabiilli, Ph.D.
Associate Professor
Department of Radiology
Department of Biomedical Engineering

Thursday, November 14, 2024
12:00 – 1:00pm
DENT G550
Host: Dr. Renny Franceschi
Sponsored by TEAM

*CE credit will be given to the School of Dentistry Faculty. If you would like CE credit, please sign in at the seminar

Endogenous reprogramming of glia into neurogenic progenitors holds great promise for neuron restoration therapies. Using lessons from regenerative species, we have developed strategies to stimulate mammalian Müller glia to regenerate neurons in vivo in the adult retina. We have demonstrated that the transcription factor Ascl1 can stimulate Müller glia neurogenesis. However, Ascl1 is only able to reprogram a subset of Müller glia into neurons. We have reported that neuroinflammation from microglia inhibits neurogenesis from Müller glia. Here we found that the peripheral immune response is a barrier to CNS regeneration. We show that monocytes from the peripheral immune system infiltrate the injured retina and negatively influence neurogenesis from Müller glia. Using CCR2 knock-out mice of both sexes, we found that preventing monocyte infiltration improves the neurogenic and proliferative capacity of Müller glia stimulated by Ascl1. Using scRNA-seq analysis, we identified a signaling axis wherein Osteopontin, a cytokine highly expressed by infiltrating immune cells is sufficient to suppress mammalian neurogenesis. This work implicates the response of the peripheral immune system as a barrier to regenerative strategies of the retina.

Part 6 of our series on 'The Holy Spirit' begins our look at 'The Work Of The Holy Spirit'. The Holy Spirit is the critical prime mover in the work of redemption. He established salvation for us but now He is also the One who applies salvation to us. In the next two studies, we will see how the Holy Spirit personally works in our lives to conform us to the image of Jesus. This episode will look at the Spirit's work of 'Conviction and Regeneration'. Why not share this message, which is available at https://www.preachtheword.com now in MP3 audio format and in HD video on our YouTube Channel (https://youtube.com/PreachTheWord)...

Wales has gained a reputation for urban regeneration thanks to areas of redevelopment that have taken place where the Welsh coal industry once stood.

Blackpool's £65m regeneration depends upon planning permission being granted, a public inquiry hears.

The Regeneration and Sustainability Award honors trailblazing work by Treehouse California Almonds and The Almond Project partners to advance sustainable farming methods in California’s almond industry.

Location: Electronic Resource- 

The cornea is densely innervated, mainly by sensory nerves of the ophthalmic branch of the trigeminal ganglia (TG). These nerves  are important to maintain corneal homeostasis, and nerve damage can lead to a decrease in wound healing, an increase in corneal ulceration and dry eye disease (DED), and neuropathic pain. Pathologies, such as diabetes, aging, viral and bacterial infection, as well as  prolonged use of contact lenses and surgeries to correct vision can produce nerve damage. There are no effective therapies to alleviate DED (a multifunctional disease) and several clinical trials using -3 supplementation show unclear and sometimes negative results. Using animal models of corneal nerve damage, we show that treating corneas with pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) increases nerve regeneration, wound healing, and tear secretion. The mechanism involves the activation of a calcium-independent phospholipase A2 (iPLA2) that releases the incorporated DHA from phospholipids and enhances the synthesis of docosanoids neuroprotectin D1 (NPD1) and a new resolvin stereoisomer  RvD6i. NPD1 stimulates the synthesis of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and of semaphorin 7A (Sema7A).  RvD6i treatment of injured corneas modulates gene expression in the TG resulting in enhanced neurogenesis; decreased neuropathic pain and increased sensitivity. Taken together, these results represent a promising therapeutic option to re-establish the homeostasis of the cornea.

Neuroinflammation can positively influence axon regeneration following injury in the central nervous system. Inflammation promotes the release of neurotrophic molecules and stimulates intrinsic proregenerative molecular machinery in neurons, but the detailed mechanisms driving this effect are not fully understood. We evaluated how microRNAs are regulated in retinal neurons in response to intraocular inflammation to identify their potential role in axon regeneration. We found that miR-383-5p is downregulated in retinal ganglion cells in response to zymosan-induced intraocular inflammation. MiR-383-5p downregulation in neurons is sufficient to promote axon growth in vitro, and the intravitreal injection of a miR-383-5p inhibitor into the eye promotes axon regeneration following optic nerve crush. MiR-383-5p directly targets ciliary neurotrophic factor (CNTF) receptor components, and miR-383-5p inhibition sensitizes adult retinal neurons to the outgrowth-promoting effects of CNTF. Interestingly, we also demonstrate that CNTF treatment is sufficient to reduce miR-383-5p levels in neurons, constituting a positive-feedback module, whereby initial CNTF treatment reduces miR-383-5p levels, which then disinhibits CNTF receptor components to sensitize neurons to the ligand. Additionally, miR-383-5p inhibition derepresses the mitochondrial antioxidant protein peroxiredoxin-3 (PRDX3) which was required for the proregenerative effects associated with miR-383-5p loss-of-function in vitro. We have thus identified a positive-feedback mechanism that facilitates neuronal CNTF sensitivity in neurons and a new molecular signaling module that promotes inflammation-induced axon regeneration.

New findings from long-term research underscore the challenges managers face when trying to conserve Penn’s Woods. The seven-year study, conducted by a team of researchers from Penn State, the Pennsylvania Game Commission and Pennsylvania Department of Conservation and Natural Resources is the first to simultaneously assess how deer browsing, soil nutrients and competing vegetation affect tree regeneration in Keystone State forests.

An alternative remedy for restoring the lost tissue in the tooth cavity by inducing the body to regenerate it has been found by researchers at the Rutgers School of Dental Medicine.

Multiple sclerosis (MS) is a potentially disabling disease of the central nervous system in which the immune system attacks the protective sheath myelin that covers the nerve fibers.

Researchers at the Stowers Institute have established a definitive link between the makeup of the microbiome, the host immune response, and an organism's ability to heal itself.

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Brownfield regeneration and land use planning are complex issues which encompass many different environmental, economic and social dimensions. This Thematic Issue brings together quality research into brownfield regeneration, which highlights insights and successful strategies from across Europe and beyond.

A recent study highlights the role of the public sector in encouraging private investment in natural and cultural brownfield regeneration projects by analysing four models of financing: public-private partnerships, land value finance mechanisms, urban development funds and impact investment funds. Local governments, it is suggested, are well placed to identify and select the most suitable financing mechanisms for redevelopment projects.

A study has evaluated the Municipal Urbanisation Tax (MUT)—a specific tax for the construction, maintenance, and reinforcement of urban infrastructure—in the city of Tomar, Portugal. The city has a new formula for the tax which is simpler and reinforces efforts to contain urban sprawl. The MUT is a one-time charge applied to new development through land subdivision (Loteamento) or individual buildings, similar to an impact fee. Other municipalities aiming to direct urban regeneration towards their brownfield sites, for example, could learn from the Portuguese experiences.

A new study from Belgium has gathered community views of brownfield regeneration. Results indicate that the often overlooked aspect of landscape quality, such as green spaces, visually-attractive areas and cultural heritage, is important in people’s opinions of brownfield regeneration schemes.

The Ikes Fire moved into the northeast portion of the planning area that has a history of little to no fire activity in over two decades. This wildfire is consuming heavy fuel accumulations on the forest floor and is helping ensure the ecosystem will be healthier and more resilient in the future. https://www.nps.gov/grca/learn/news/ikes-fire-promotes-healthy-forest-regeneration-as-fire-activity-increases-20190807.htm

We monitored coarse woody debris dynamics and natural tree regeneration over a 14-year period after the 1991 Warner Creek Fire, a 3631-ha (8,972-ac) mixed severity fire in the western Cascade Range of Oregon. Rates for tree mortality in the fire, postfire mortality, snag fall, and snag fragmentation all showed distinct patterns by tree diameter and species, with Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) more likely to survive a fire, and to remain standing as a snag, than other common tree species. Natural seedling regeneration was abundant, rapid, and highly variable in space. Densities of seedlings >10 cm height at 14 years postfire ranged from 1,530 to 392,000 per ha. Seedling establishment was not concentrated in a single year, and did not appear to be limited by the abundant growth of shrubs. The simultaneous processes of mortality, snag fall, and tree regeneration increased the variety of many measures of forest structure. The singular event of the fire has increased the structural diversity of the landscape.

Aspects of the invention relate to several methods to deposit and regenerate target materials in neutron generators and similar nuclear reaction devices. In situ deposition and regeneration of a target material reduces tube degradation of the nuclear reaction device and covers impurities on the surface of the target material at the target location. Further aspects of the invention include a method of designing a target to generate neutrons at a high efficiency rate and at a selected neutron energy from a neutron energy spectrum.

A hydraulic actuator system including an actuator and a valve assembly configured for bi-directional regeneration. The actuator may include a hollow body and a rod disposed within and extending outwardly from the hollow body. The rod may include a first chamber within the rod and a piston disposed at one end of the rod, defining a second chamber and a third chamber within the hollow body. A valve assembly may be in fluid communication with a first conduit, a second conduit, the first chamber, the second chamber, and the third chamber, wherein the valve assembly is configured to selectively couple one of the first conduit and the second conduit to one or more of the first port, the second port, and the third port, wherein one of the first conduit and the second conduit is configured as a pressure source.

There is described a machine (1) for regeneration of pneumatic tires (2) comprising a beading device (5) for axial locking of the pneumatic tire to be regenerated in the direction of the revolving axis of the pneumatic tire (2) which provides an untranslatable bead (6) and a translatable bead (7) in said direction, a work rasp (9) mounted on a spindle (25), inflation means (66) of the pneumatic tire and a discharge cochlea (77). Said machine further comprises a roughing miller (8) suitable to prepare the pneumatic tire to a subsequent finishing by means of the rasp (9), said miller (8) being mounted on the same spindle (25) of the rasp (9) and after it, and constituted of a monoblock (27) with discharge channels (28) for chips produced by inserts (29) with a curved profile (30) providing a plurality of planar blades (31) joined by discharge grooves (32) of the chips produced.

A hydraulic motor/pump regenerator system for recovering energy from the moving vehicle having high efficiency and precise control, thereby allowing the maximum amount of energy to be recovered and reused, is described. Three, fixed-displacement pump/motors are used to enable the system to recover and reapply energy at efficiencies expected to be above 70% in most circumstances. The invention is not limited to the use of three fixed displacement hydraulic units since using more units may in some drive cycles further improve efficiency. By selecting an appropriate combination of pump/motor units for providing the driveshaft torque required by the driver, embodiments of the present invention generate high recovery efficiency at any speed.

The storing and destocking of hydrogen in a hydride tank (10) comprises purification performed in at least one trap (1, 1A, 1B) filtering the impurities contained in the hydrogen entering the tank to be stored and regeneration of said at least one trap, using the heat carried by the hydrogen exiting the tank after it has been destocked.

Process for the combined regeneration of at least two soluble salts contained in a residue of an industrial process comprising heavy metals, comprising: adding an amount of reactive aqueous solution needed to completely dissolve the salts which are desired to be regenerated to the residue; subjecting the resulting aqueous suspension to a separation to obtain an aqueous production solution on the one hand and insoluble impurities on the other hand, which are removed; successively subjected the aqueous production solution to at least two selective crystallization steps intended to crystallize, separately, the at least two soluble salts which are desired to be regenerated, which are washed, dried and regenerated separately; and adjusting the concentration of at least one of the soluble salts to be regenerated in the aqueous production solution, at the moment when such solution is subjected to the step of crystallization of this salt, to give rise to the selective crystallization of this salt, by addition of a controlled amount of this salt to the aqueous production solution upstream of the crystallization step.

A short video on using feedback with analog tape.

Light to shine on historical Smethwick landmark - with a little help from its friends.

Hypo-vascularised diabetic non-healing wounds are due to reduced number and impaired physiology of endogenous endothelial progenitor cell (EPC) population that, limits their recruitment and mobilization at the wound site. To enrich the EPC repertoire from non-endothelial precursors, abundantly available mesenchymal stromal cells (MSCs) were reprogrammed into induced-endothelial cells (iECs). We identified cell signaling molecular targets by meta-analysis of microarray datasets. BMP-2 induction leads to the expression of inhibitory Smad 6/7-dependent negative transcriptional regulation of ID1, rendering the latter's reduced binding to TWIST1 during transdifferentiation of WJ-MSC into iEC. TWIST1, in turn, regulates endothelial genes transcription, positively of pro-angiogenic-KDR and negatively, in part, of anti-angiogenic-SFRP4. Twist1 reprogramming enhanced the endothelial lineage commitment of WJ-MSC, increased the vasculogenic potential of reprogrammed EC (rEC). Transplantation of stable TWIST1-rECs into full-thickness type 1 and 2 diabetic-splinted wound healing murine model enhanced the microcirculatory blood flow and accelerated the wound tissue regeneration. An increased or decreased co-localization of GFP with KDR/SFRP4 and CD31 in the regenerated diabetic wound bed with TWIST1 overexpression or silencing (piLenti-TWIST1-shRNA-GFP), respectively further confirmed improved neovascularization. This study depicted the reprogramming of WJ-MSCs into rECs using unique transcription factors, TWIST1 for an efficacious cell transplantation therapy to induce neovascularization–mediated diabetic wound tissue regeneration.

Diabetic Keratopathy, a sight-threatening corneal disease, comprises several symptomatic conditions including delayed epithelial wound healing, recurrent erosions, and sensory nerve (SN) neuropathy. We investigated the role of neuropeptides in mediating corneal wound healing, including epithelial wound closure and SN regeneration. Denervation by Resiniferatoxin severely impaired corneal wound healing and markedly up-regulated pro-inflammatory gene expression. Exogenous neuropeptides CGRP, SP, and VIP partially reversed Resiniferatoxin’s effects, with VIP specifically inducing IL-10 expression. Hence, we focused on VIP and observed that wounding induced VIP and VIPR1 expression in normal (NL), but not diabetic (DM) mouse corneas. Targeting VIPR1 in NL corneas attenuated corneal wound healing, dampened wound-induced expression of neurotrophic factors, and exacerbated inflammatory responses while exogenous VIP had the opposite effects in DM corneas. Remarkably, wounding and diabetes also affected the expression of Sonic Hedgehog (SHH) in a VIP-dependent manner. Downregulating SHH expression in NL corneas decreased, while exogenous SHH in DM corneas increased the rates of corneal wound healing. Furthermore, inhibition of SHH signaling dampened VIP-promoted corneal wound healing. We conclude that VIP regulates epithelial wound healing, inflammatory response, and nerve regeneration in the corneas in a SHH-dependent manner, suggesting a therapeutic potential for these molecules in treating diabetic keratopathy.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor widely expressed in mammalian tissues, and it exerts critical protective effects on neurons and other cell types in various disease models, such as those for diabetes. However, to date, the expression and roles of MANF in the cornea, with or without diabetic keratopathy (DK), remain unclear. Here, we demonstrate that MANF is abundantly expressed in normal corneal epithelial cells; however, MANF expression was significantly reduced in both unwounded and wounded corneal epithelium in streptozotocin-induced type 1 diabetic C57BL/6 mice. Recombinant human MANF significantly promoted normal and diabetic corneal epithelial wound healing and nerve regeneration. Furthermore, MANF inhibited hyperglycemia-induced endoplasmic reticulum (ER) stress and ER stress–mediated apoptosis. Attenuation of ER stress with 4-phenylbutyric acid (4-PBA) also ameliorated corneal epithelial closure and nerve regeneration. However, the beneficial effects of MANF and 4-PBA were abolished by an Akt inhibitor and Akt-specific small interfering RNA (siRNA). Finally, we reveal that the subconjunctival injection of MANF-specific siRNA prevents corneal epithelial wound healing and nerve regeneration. Our results provide important evidence that hyperglycemia-suppressed MANF expression may contribute to delayed corneal epithelial wound healing and impaired nerve regeneration by increasing ER stress, and MANF may be a useful therapeutic modality for treating DK.

To determine whether Cav1.2 voltage-gated Ca²⁺ channels contribute to astrocyte activation, we generated an inducible conditional knock-out mouse in which the Cav1.2 α subunit was deleted in GFAP-positive astrocytes. This astrocytic Cav1.2 knock-out mouse was tested in the cuprizone model of myelin injury and repair which causes astrocyte and microglia activation in the absence of a lymphocytic response. Deletion of Cav1.2 channels in GFAP-positive astrocytes during cuprizone-induced demyelination leads to a significant reduction in the degree of astrocyte and microglia activation and proliferation in mice of either sex. Concomitantly, the production of proinflammatory factors such as TNFα, IL1β and TGFβ1 was significantly decreased in the corpus callosum and cortex of Cav1.2 knock-out mice through demyelination. Furthermore, this mild inflammatory environment promotes oligodendrocyte progenitor cells maturation and myelin regeneration across the remyelination phase of the cuprizone model. Similar results were found in animals treated with nimodipine, a Cav1.2 Ca²⁺ channel inhibitor with high affinity to the CNS. Mice of either sex injected with nimodipine during the demyelination stage of the cuprizone treatment displayed a reduced number of reactive astrocytes and showed a faster and more efficient brain remyelination. Together, these results indicate that Cav1.2 Ca²⁺ channels play a crucial role in the induction and proliferation of reactive astrocytes during demyelination; and that attenuation of astrocytic voltage-gated Ca²⁺ influx may be an effective therapy to reduce brain inflammation and promote myelin recovery in demyelinating diseases.

SIGNIFICANCE STATEMENT Reducing voltage-gated Ca²⁺ influx in astrocytes during brain demyelination significantly attenuates brain inflammation and astrocyte reactivity. Furthermore, these changes promote myelin restoration and oligodendrocyte maturation throughout remyelination.

Whilst polarisation has become a familiar feature of national politics in recent months, on some key issues there is still a degree of political consensus. One of these is the need to rebalance the UK economy away from an overreliance on London and ...

The Chancellor announced yesterday his second budget aimed at achieving strong, sustainable and balanced growth, more evenly shared across the country and between industries. A number of measures are introduced that will significantly impact on dev...

Surendra Singh Patel, Sanyami Zunjarrao, and Beena Pillai

Eisenia fetida, the common vermicomposting earthworm, shows robust regeneration of posterior segments removed by amputation. During the period of regeneration, the newly formed tissue initially contains only undifferentiated cells but subsequently differentiates into a variety of cell types including muscle, nerve and vasculature. Transcriptomics analysis, reported previously, provided a number of candidate non-coding RNAs that were induced during regeneration. We found that one such long non-coding RNA (lncRNA) is expressed in the skin, only at the base of newly formed chaetae. The spatial organization and precise arrangement of the regenerating chaetae and the cells expressing the lncRNA on the ventral side clearly support a model wherein the regenerating tissue contains a zone of growth and cell division at the tip and a zone of differentiation at the site of amputation. The temporal expression pattern of the lncRNA, named Neev, closely resembled the pattern of chitin synthase genes, implicated in chaetae formation. We found that the lncRNA has 49 sites for binding a set of four microRNAs (miRNAs) while the chitin synthase 8 mRNA has 478 sites. The over-representation of shared miRNA sites suggests that lncRNA Neev may act as a miRNA sponge to transiently de-repress chitin synthase 8 during formation of new chaetae in the regenerating segments of Eisenia fetida.

S. Ghods, S. Waddell, E. Weller, C. Renteria, H.-Y. Jiang, J. M. Janak, S. S. Mao, T. J. Linley, and D. Arola

Fish scales serve as a dermal armor that provides protection from physical injury. Due to a number of outstanding properties, fish scales are inspiring new concepts for layered engineered materials and next-generation flexible armors. While past efforts have primarily focused on the structure and mechanical behavior of ontogenetic scales, the structure-property relationships of regenerated scales have received limited attention. In the present study, common carp (Cyprinus carpio) acquired from the wild were held live in an aquatic laboratory at 10° and 20°C. Ontogenetic scales were extracted from the fish for analysis, as well as regenerated scales after approximately 1 year of development and growth. Their microstructure was characterized using microscopy and Raman spectroscopy, and the mechanical properties were evaluated in uniaxial tension to failure under hydrated conditions. The strength, strain to fracture and toughness of the regenerated scales were significantly lower than those of ontogenetic scales from the same fish, regardless of the water temperature. Scales that regenerated at 20°C exhibited significantly higher strength, strain to fracture and toughness than those regenerated at 10°C. The regenerated scales exhibited a highly mineralized outer layer, but no distinct limiting layer or external elasmodine; they also possessed a significantly lower number of plies in the basal layer than in the ontogenetic scales. The results suggest that a mineralized layer develops preferentially during scale regeneration with the topology needed for protection, prior to the development of other qualities.

Temple University researchers discovered that boosting levels of a protein called Lin28 in injured spinal cords of mice prompts the regrowth of axons and repairs communication between the brain and body. They believe the discovery could be used to develop new treatments for both spinal cord and optic nerve injuries.