Publications by authors named "Christina Schier"

Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin.

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Allicin is the main flavour component of crushed raw garlic. This plant defence molecule has strong antibiotic properties. While measurements in the liquid phase using LC-MS are established, accessing reactive organosulfur compounds in the gas phase is still a challenge due to heat-degradation in the gas chromatograph.

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Fungal infections of the lung are an increasing problem worldwide and the search for novel therapeutic agents is a current challenge due to emerging resistance to current antimycotics. The volatile defence substance allicin is formed naturally by freshly injured garlic plants and exhibits broad antimicrobial potency. Chemically synthesised allicin was active against selected fungi upon direct contact and via the gas phase at comparable concentrations to the pharmaceutically used antimycotic amphotericin B.

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To streamline and improve throughput, the agar-based multiplexed opsonophagocytic killing assay (MOPA) was optimized and validated on a microcolony platform for use in the Phase III clinical trial program for V114, an MSD 15-valent pneumococcal conjugate vaccine candidate. The precision, dilutional linearity and specificity of the microcolony MOPA (mMOPA) were assessed for each serotype in validation experiments. All prespecified acceptance criteria on assay performance were satisfied.

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The common foodstuff garlic produces the potent antibiotic defense substance allicin after tissue damage. Allicin is a redox toxin that oxidizes glutathione and cellular proteins and makes garlic a highly hostile environment for non-adapted microbes. Genomic clones from a highly allicin-resistant (AR-1), which was isolated from garlic, conferred allicin resistance to and even to Resistance-conferring genes had redox-related functions and were on core fragments from three similar genomic islands identified by sequencing and in silico analysis.

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Despite marked regional differences in HIV susceptibility within the CNS, there has been surprisingly little exploration into the differential vulnerability among neuron types and the circuits they underlie. The dorsal striatum is especially susceptible, harboring high viral loads and displaying marked neuropathology, with motor impairment a frequent manifestation of chronic infection. However, little is known about the response of individual striatal neuron types to HIV or how this disrupts function.

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Background: Medial prefrontal cortex (mPFC) dysfunction is present in heavy alcohol consumers. Dopamine signaling in mPFC is associated with executive functioning and affects drinking behavior; however, direct measurement of extracellular mPFC dopamine during appetitive and consummatory ethanol (EtOH) self-administration behavior has not been reported.

Methods: We used in vivo microdialysis in freely behaving, adult, male, Long Evans rats to determine extracellular dopamine concentration in the mPFC during operant self-administration of an EtOH-plus-sucrose or sucrose solution.

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Article Synopsis
  • Memory deficits in HIV-associated neurocognitive disorders (HAND) are linked to damage in hippocampal interneurons, particularly due to the HIV-1 Tat protein.
  • Research conducted on transgenic mice demonstrated that exposure to Tat led to impaired cognitive functions, such as decreased spatial memory and object recognition.
  • The study found significant reductions in specific types of interneurons (like nNOS-expressing, parvalbumin, and somatostatin-expressing cells) in the hippocampus, which play crucial roles in regulating the activity of pyramidal cells and may contribute to neurobehavioral deficits in HAND.
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Article Synopsis
  • Few preclinical studies have examined how different medications for opiate addiction affect neurotoxicity related to HIV-1 Tat in neuronal and glial co-cultures.
  • Exposure to Tat combined with morphine, methadone, or buprenorphine at 500 nM significantly increased neurotoxicity beyond that of Tat alone, while buprenorphine showed neurotoxic effects even at lower concentrations and demonstrated both neurotoxic and neuroprotective properties.
  • The study found that while all drugs elevated glial calcium levels when combined with Tat, they varied in their effects on neuroinflammation and toxicity, with buprenorphine potentially offering unique benefits due to its pharmacological profile at different opioid receptors.
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Rationale: Naltrexone, a non-selective opioid antagonist, decreases the euphoria and positive subjective responses to alcohol in heavy drinkers. It has been proposed that the μ-opioid receptor plays a role in ethanol reinforcement through modulation of ethanol-stimulated mesolimbic dopamine release.

Objectives: To investigate the ability of naltrexone and β-funaltrexamine, an irreversible μ-opioid specific antagonist, to inhibit ethanol-stimulated and morphine-stimulated mesolimbic dopamine release, and to determine whether opioid receptors on mesolimbic neurons contribute to these mechanisms.

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Background: Ethanol (EtOH) affects prefrontal cortex functional roles such as decision making, working memory, and behavioral control. Yet, the pharmacological effect of EtOH on dopamine, a neuromodulator in the medial prefrontal cortex (mPFC), is unclear. Past studies exploring this topic produced conflicting outcomes; however, a handful of factors (temporal resolution, method of drug administration, estrous cycle) possibly contributed to these discrepancies.

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Operant self-administration methods are commonly used to study the behavioral and pharmacological effects of many drugs of abuse, including ethanol. However, ethanol is typically self-administered orally, rather than intravenously like many other drugs of abuse. The pharmacokinetics of orally administered drugs are more complex than intravenously administered drugs.

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Background: Ethanol self-administration has been shown to increase dopamine in the nucleus accumbens; however, dopamine levels in the accumbal subregions (core, shell, and core-shell border) have not yet been measured separately in this paradigm. This study was designed to determine if dopamine responses during operant ethanol self-administration are similar in the core, core-shell border, and shell, particularly during transfer from the home cage to the operant chamber and during consumption of the drinking solution.

Methods: Six groups of male Long-Evans rats were trained to lever-press for either 10% sucrose (10S) or 10% sucrose + 10% ethanol (10S10E) (with a guide cannula above the core, core-shell border, or shell of the accumbens).

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