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The neurotoxic effect of manganese (Mn) establishes itself in a condition known as manganism or Mn induced parkinsonism. While this condition was first diagnosed about 170 years ago, the mechanism of the neurotoxic action of Mn remains unknown. Moreover, the possibility that Mn exposure combined with other genetic and environmental factors can contribute to the development of Parkinson's disease has been discussed in the literature and several epidemiological studies have demonstrated a correlation between Mn exposure and an elevated risk of Parkinson's disease. Here, we introduce X-ray fluorescence imaging as a new quantitative tool for analysis of the Mn distribution in the brain with high spatial resolution. The animal model employed mimics deficits observed in affected human subjects. The obtained maps of Mn distribution in the brain demonstrate the highest Mn content in the globus pallidus, the thalamus, and the substantia nigra pars compacta. To test the hypothesis that Mn transport into/distribution within brain cells mimics that of other biologically relevant metal ions, such as iron, copper, or zinc, their distributions were compared. It was demonstrated that the Mn distribution does not follow the distributions of any of these metals in the brain. The majority of Mn in the brain was shown to occur in the mobile state, confirming the relevance of the chelation therapy currently used to treat Mn intoxication. In cells with accumulated Mn, it can cause neurotoxic action by affecting the mitochondrial respiratory chain. This can result in increased susceptibility of the neurons of the globus pallidus, thalamus, and substantia nigra pars compacta to various environmental or genetic insults. The obtained data is the first demonstration of Mn accumulation in the substantia nigra pars compacta, and thus, can represent a link between Mn exposure and its potential effects for development of Parkinson's disease.

IntroductionVesatolimod is a Toll-like receptor-7 (TLR7) agonist in clinical development as part of a combination regimen for human immunodeficiency virus (HIV) cure. Influenza-like symptoms associated with TLR7-mediated immune activation have been reported in clinical trials of vesatolimod. Therefore, a broader understanding of the safety profile of vesatolimod and association with dose and mechanism of action will help inform future clinical studies.MethodsIn this analysis, data on flu-like adverse events of interest (AEIs) were pooled from eight clinical studies in which 606 participants either received single or multiple doses of vesatolimod (0.3–12 mg; n = 505) or placebo (n = 101). Vesatolimod pharmacokinetics, inflammatory responses, and pharmacodynamics were assessed.ResultsThe incidence of flu-like AEIs was higher with vesatolimod versus placebo (19% [96/505] vs. 8% [8/101]) and increased with vesatolimod dose and exposure. Most flu-like AEIs with vesatolimod were grade 1 or 2 severity (55% [53 of 96] grade 1; 35% [34 of 96] grade 2) with onset primarily after the first and second dose. Occurrence of flu-like AEIs after doses 1–3 was predictive of reoccurrence after later doses. Dose-dependent elevations of pharmacodynamic biomarkers (interferon-stimulated gene 15, 2′-5′-oligoadenylate synthetase 1, myxovirus resistance-1, interferon-α, interleukin-1 receptor antagonist, interferon-γ-induced protein 10, interferon-inducible T-cell-α chemoattractant) observed in participants with flu-like AEIs suggest a link with vesatolimod mechanism of action.ConclusionsFlu-like AEIs associated with vesatolimod administration were typically mild but increased with exposure, which may be predicted by the response to initial doses. The data suggest that adaptive clinical monitoring could help maximize pharmacodynamic responses and balance adverse events in future clinical trials of vesatolimod.

From color theory to the golden ratio, science is commonly integrated into art and has greatly benefited from technological advances. This project was inspired by the emerging field of Bio Art where biotechnology is used to create artwork that integrates biology, engineering, art, and photography. Initially, art principles were used to create a template for the artwork. Some designs utilized a 3D-printed stamp to help transfer their art onto the agar plate. LB Agar plates were used as our canvas and we used genetically modified E.coli strains as paint while integrating cell cultures. Bacterial colonies of different colors were produced from the transformation of E. coli with plasmids that contain genes for chromogens such as blue chromogen, pink chromogen, purple chromogen, and green fluorescent protein. For the bacteria to grow, the agar plate contained Ampicillin to maintain selective pressure and isopropyl B-D-thiogalactopyranoside to induce the expression of the chromogen gene. The plates were then incubated for 72 hours in a 37°C incubator, which led to the growth of bacteria into bacterial colonies which caused the color on the designs to be more visible. Finally, pictures of the bacterial designs were captured applying photography principles and were edited digitally, printed, and mounted for display. This interdisciplinary project served as a learning opportunity that uniquely integrated art, engineering, photography, and molecular and microbiology principles together.

DNA barcoding is a species identification technique that is useful within biodiversity studies, particularly in today's world, which is characterized by ever-increasing human activity. This technique is accessible to a broad range of individuals, including high school and undergraduate research students. As IB Diploma high school students interested in the biodiversity of our local Lake Wales Ridge ecosystem, we desired to gain hands-on DNA barcoding experience to broaden our molecular biology knowledge. For our investigation, we collected our sample from this ecosystem, which is a biodiversity hotspot. Using morphological characteristics, we identified the sample as a spider egg. However, using only morphology, it was not possible to identify the species that laid the egg. To resolve this issue, we performed DNA barcoding to identify the species of our spider egg. To do so, DNA from the sample was extracted, amplified using COI PCR primers, and sequenced through Sanger sequencing. Using the bioinformatic analysis platform DNA Subway and COI sequences from BLAST searches, we were able to determine that our spider egg most likely belonged to the species Emblyna roscida. Specifically, our BLAST searches showed that a COI gene sequence from Emblyna roscida had a sequence similarity value of approximately 98.5% with the sequence of our sample. Through this poster, we will discuss our taxonomic results, which showed how our Emblyna sequence related to COI sequences from other Emblyna species. Additionally, we will also discuss our experiences and perspectives with regard to this investigation.

Many people in today's world suffer from uncomfortable tension in their bodies. This widespread issue not only affects daily lives but can also lead to long-term health problems. While there is a wide variety of mass-produced relief tools designed as one-size-fits-all solutions, these tools are fit for only a fraction of the population that comprises individuals with great variation in size. A personalized tension relief device will be a better option to cater to an individual's needs for tension relief. Having a customized device according to a person's body will improve the effectiveness of the device. To solve this problem, we propose to use a 3D printer and a computer-aided design to create a tension-relief prototype for alleviation along the upper to lower back, shoulders, hip flexors, and psoas muscles. We intend to utilize the SOLIDWORKS 3D CAD software to produce an efficient prototype with optimal results for the alleviation of muscles and tissue tension. A personalized design will be created according to an individual's body measurements. Factors such as weight, height, waist size, and body width can all affect the design of the relief tool's size and shape. The personalized product will be capable of soothing discomfort and tension along the upper body and hips. Due to its customization, the MEW-relief-tool will provide superior comfort and stress relief compared to generic, mass-produced products.

The Covid-19 pandemic has revealed myriad social, economic, and health inequities that disproportionately burden populations that have been made medically or socially vulnerable. Inspired by state and local governments that declared racism a public health crisis or emergency, the Anti-Racism in Public Health Act of 2020 reflects a shifting paradigm in which racism is considered a social determinant of health. Indeed, health inequities fundamentally rooted in structural racism have been exacerbated by the Covid-19 pandemic, which calls for the integration of antiracist praxis to promote ethical public health research processes. This commentary describes ways in which antiracist praxis—which emphasizes empowerment of traditionally marginalized populations—offers strategies to explicitly address power imbalance, stigmatization, and other consequences of structural racism in public health research.

Oxygen-ozone (O3) therapy serves as an alternative medical technique that increases the oxygen in the body along with the introduction of O3. O3 therapy has finally reached a level where the biological mechanisms of action have been understood, showing that they are in the domain of physiology, biochemistry, and pharmacology. Few clinical applications have been reviewed here as well as exemplifying that O3 therapy is particularly useful in musculoskeletal disorders. In the therapeutic range, O3 can be used as a more effective and safe substitute of standard medications. O3 therapy has been used for many years for its ability to inactivate various viruses, cancer, and acquired immune deficiency syndrome but is now making strides in the treatment of musculoskeletal disorders such as rheumatoid arthritis, lumbar facet joint syndrome, subacromial bursitis, carpal tunnel syndrome, osteoarthritis, hip bursitis, shoulder adhesive capsulitis, herniated disc, and temporomandibular joint disorder.

Our recent data suggest a high accumulation of copper (Cu) in the subventricular zone (SVZ) along the wall of brain ventricles. Anatomically, SVZ is in direct contact with cerebrospinal fluid (CSF), which is secreted by a neighboring tissue choroid plexus (CP). Changes in Cu regulatory gene expressions in the SVZ and CP as the function of aging may determine Cu levels in the CSF and SVZ. This study was designed to investigate the associations between age, Cu levels, and Cu regulatory genes in SVZ and plexus. The SVZ and CP were dissected from brains of 3-week, 10-week, or 9-month old male rats. Analyses by atomic absorption spectroscopy revealed that the SVZ of adult and old animals contained the highest Cu level compared with other tested brain regions. Significantly positive correlations between age and Cu levels in SVZ and plexus were observed; the SVZ Cu level of old animals was 7.5- and 5.8-fold higher than those of young and adult rats (p < 0.01), respectively. Quantitation by qPCR of the transcriptional expressions of Cu regulatory proteins showed that the SVZ expressed the highest level of Cu storage protein metallothioneins (MTs), while the CP expressed the high level of Cu transporter protein Ctr1. Noticeably, Cu levels in the SVZ were positively associated with type B slow proliferating cell marker Gfap (p < 0.05), but inversely associated with type A proliferating neuroblast marker Dcx (p < 0.05) and type C transit amplifying progenitor marker Nestin (p < 0.01). Dmt1 had significant positive correlations with age and Cu levels in the plexus (p < 0.01). These findings suggest that Cu levels in all tested brain regions are increased as the function of age. The SVZ shows a different expression pattern of Cu-regulatory genes from the CP. The age-related increase of MTs and decrease of Ctr1 may contribute to the high Cu level in this neurogenesis active brain region.

Harmane, a potent neurotoxin linked with several neurological disorders, is present in many foods, coffee, and cigarettes. We assessed whether morning food/coffee consumption and smoking were reflected in blood harmane concentrations (BHCs) we obtained in an epidemiologic sample (n=497). Participants who smoked on the morning of phlebotomy had similar logBHCs to those who had not smoked (P=.57); there was no correlation between logBHCs and number of cigarettes (P=.59). Among the coffee drinkers, there was no correlation between number of cups and logBHCs (P=.98). Participants who had eaten on the morning of phlebotomy had similar logBHCs to those who had not (P=.49); logBHCs did not correlate with the time latency between last food consumption and phlebotomy (P=.74). BHCs in this sample of ~500 individuals did not covary with recent smoking, coffee, or food consumption, suggesting that our inability to withhold these exposures on the morning of phlebotomy was not reflected in the BHCs we measured.