DETERMINING THE PATHOLOGICAL EFFECTS OF PRENATAL ALCOHOL EXPOSURE ON PERIPHERAL NEUROPATHY VIA SPINAL AND PERIPHERAL IMMUNE MECHANISMS

Previous studies have suggested that children with Fetal Alcohol Spectrum Disorder (FASD) display hypersensitivity to light touch. In support of this notion, we have demonstrated that applying a chronic constriction injury (CCI) to the sciatic nerve of rats that have prenatal alcohol exposure (PAE) results in heightened sensitivity to light touch, clinically termed allodynia. These observations coincided with heightened glial activation and enhanced peripheral immune reactivity. Considering allodynia is known to be mediated by both peripheral immune responses and spinal glial activation, it is reasonable to speculate that allodynia following PAE may be mediated through an alteration of immune reactivity. Thus, I hypothesized that PAE results in immune sensitization leading to enhanced susceptibility to developing allodynia. To address the possibility that PAE creates susceptibility to developing neuropathy, a minor CCI was applied to rats that have been prenatally exposed to saccharin (Sac) or alcohol (PAE). Induction of allodynia occurs only in PAE rats with a minor injury. Interestingly, data acquired by immunohistochemistry (IHC) and subsequent microscopy analyses show that spinal astrocyte activation was altered compared to Sac rats. Furthermore, pharmacological blockade of spinal cytokines leading to reduced allodynia also demonstrate an alteration in the proinflammatory cytokine profile at the spinal cord and the sciatic nerve. Strikingly, PAE resulted in downregulation of normal IL-10 responses within the spinal cord and dorsal root ganglia (DRG) as shown by IHC. Additionally, satellite glial cells were activated in the DRG compared to controls which coincided with heightened expression of the proinflammatory cytokine IL-1b. Spinal cord IHC analysis of glutamate transporters demonstrated that PAE alone is sufficient to upregulate both glutamate transporter 1 (GLT-1) and the astrocyte specific transporter glutamate aspartate transporter (GLAST) followed by a downregulation after minor CCI. These data suggest that an increase in synaptic and peri-synaptic glutamate develops following minor injury that is regulated predominantly by glia. Interestingly, no significant change was seen in the neuronal specific transporter EAAC1 or in NMDA receptor subunits. Collectively, the work described and presented in this dissertation demonstrates that PAE primes peripheral and spinal neuroimmune responses which lead to allodynia following minor CCI. Additionally, my data demonstrate that PAE may alter glutamate transporters in the spinal cord which may lead to continued heightened glial activation and increased cytokine actions following injury. Furthermore, our studies support the possibility that glial cells are sensitized as a consequence of PAE, which in turn influence neuronal activity. Taken together, the results from this work demonstrate that PAE leads to life-long susceptibility to developing allodynia

Spontaneous orbital polarization in the nematic phase of FeSe

The origin of nematicity in FeSe remains a critical outstanding question towards understanding unconventional superconductivity in proximity to nematic order. To understand what drives the nematicity, it is essential to determine which electronic degree of freedom admits a spontaneous order parameter independent from the structural distortion. Here, we use X-ray linear dichroism at the Fe K pre-edge to measure the anisotropy of the 3d orbital occupation as a function of in situ applied stress and temperature across the nematic transition. Along with X-ray diffraction to precisely quantify the strain state, we reveal a lattice-independent, spontaneously-ordered orbital polarization within the nematic phase, as well as an orbital polarizability that diverges as the transition is approached from above. These results provide strong evidence that spontaneous orbital polarization serves as the primary order parameter of the nematic phase.Comment: Main: 22 pages, 4 figures. Supp: 32 pages, 18 figure

Nitric Oxide Releasing Nanoparticles for Treatment of Candida Albicans Burn Infections

Candida albicans is a leading fungal cause of burn infections in hospital settings, and sepsis is one of the principle causes of death after a severe burn. The prevalence of invasive candidiasis in burn cases varies widely, but it accounts for 3–23% of severe infection with a mortality rate ranging from 14 to 70%. Therefore, it is imperative that we develop innovative therapeutics to which this fungus is unlikely to evolve resistance, thus curtailing the associated morbidity and mortality and ultimately improving our capacity to treat these infections. An inexpensive and stable nitric oxide (NO)-releasing nanoparticle (NO-np) platform has been recently developed. NO is known to have direct antifungal activity, modulate host immune responses and significantly regulate wound healing. In this study, we hypothesized that NO-np would be an effective therapy in the treatment of C. albicans burn infections. Using a murine burn model, NO-np demonstrated antifungal activity against C. albicans in vivo, most likely by arresting its growth and morphogenesis as demonstrated in vitro. NO-np demonstrated effective antimicrobial activity against yeast and filamentous forms of the fungus. Moreover, we showed that NO-np significantly accelerated the rate of wound healing in cutaneous burn infections when compared to controls. The histological evaluation of the affected tissue revealed that NO-np treatment modified leukocyte infiltration, minimized the fungal burden, and reduced collagen degradation, thus providing potential mechanisms for the therapeutics’ biological activity. Together, these data suggest that NO-np have the potential to serve as a novel topical antifungal which can be used for the treatment of cutaneous burn infections and wounds

Strain-Switchable Field-Induced Superconductivity

Field-induced superconductivity is a rare phenomenon where an applied magnetic field enhances or induces superconductivity. This fascinating effect arises from a complex interplay between magnetism and superconductivity, and it offers the tantalizing technological possibility of an infinite magnetoresistance superconducting spin valve. Here, we demonstrate field-induced superconductivity at a record-high temperature of T=9K in two samples of the ferromagnetic superconductor Eu(Fe$_{0.88}$Co$_{0.12}$)$_{2}$As$_{2}$. We combine tunable uniaxial stress and applied magnetic field to shift the temperature range of the zero-resistance state between 4K and 10K. We use x-ray diffraction and spectroscopy measurements under stress and field to demonstrate that stress tuning of the nematic order and field tuning of the ferromagnetism act as independent tuning knobs of the superconductivity. Finally, DFT calculations and analysis of the Eu dipole field reveal the electromagnetic mechanism of the field-induced superconductivity.Comment: Main text: 15 pages, 5 figures; Supplement: 15 pages, 10 supplementary figure

Signatures of pressure-enhanced helimagnetic order in van der Waals multiferroic NiI2_2

The van der Waals (vdW) type-II multiferroic NiI$_2$ has emerged as a candidate for exploring non-collinear magnetism and magnetoelectric effects in the 2D limit. Frustrated intralayer exchange interactions on a triangular lattice result in a helimagnetic ground state, with spin-induced improper ferroelectricity stabilized by the interlayer interactions. Here we investigate the magnetic and structural phase transitions in bulk NiI$_2$, using high-pressure Raman spectroscopy, optical linear dichroism, and x-ray diffraction. We obtain evidence for a significant pressure enhancement of the antiferromagnetic and helimagnetic transition temperatures, at rates of $\sim15.3/14.4$ K/GPa, respectively. These enhancements are attributed to a cooperative effect of pressure-enhanced interlayer and third-nearest-neighbor intralayer exchange. These results reveal a general path for obtaining high-temperature type-II multiferroicity via high pressures in vdW materials