bluuebunny/crossref_metadata_2025_split huggingface dataset:
Procalcitonin and Bacterial Infections in the Human Body
Authors: Link Tina , Jacobson Reagan , Escorcia Isabella , Fisher Joseph , Nguyen Lan , Reddy Megan 
Published: April 2020

Procalcitonin (PCT), a member of the calcitonin (CT) superfamily, is a 116 amino acid, 13 kilodalton precursor protein produced in humans in the parafollicular cells of the thyroid as well as the neuroendocrine cells of the lungs and intestines of healthy individuals. PCT is coded for in the Calc‐I gene, located on chromosome 11. PCT is the precursor to the regulatory protein calcitonin but may have its own, separate role in the human body’s response to bacterial infection. There is a positive correlation between the concentration of PCT in the blood and the severity of a bacterial infection, making PCT an acute phase reactant. Under normal conditions, PCT undergoes proteolytic cleavage in the thyroid and is converted into CT, which then leaves the thyroid and enters the bloodstream; however, under inflammatory conditions, PCT is not cleaved and enters the bloodstream in a three‐section state comprising an amino terminus, immature calcitonin, and calcitonin carboxyl‐terminus peptide. Additionally, under inflammatory conditions, PCT is produced in other locations besides the parafollicular cells of the thyroid and the neuroendocrine cells of the lungs and intestines due to an increase in the expression of the Calc‐I gene. The reason for this increase may be related to potential anti‐inflammatory characteristics of PCT, including an ability to signal a reduction in the production of pro‐inflammatory proteins such as tumor necrosis factor‐alpha and interleukin 1‐beta. Furthermore, PCT in a specific concentration has been shown to reduce the reactivity of lipopolysaccharide (LPS) in gram‐negative bacteria. These properties of PCT have many potential applications in the medical field that are currently being studied or used. For example, detection of PCT in the blood can be used to determine if an infection is viral or bacterial or to evaluate the severity of infection in patients with sepsis. The determination of the pathogen allows for the correct course of appropriate treatment, potentially preventing the overprescription and overuse of antibiotics, a critical concern with the continued rise of bacterial antibiotic resistance. Additionally, as patients recover from a systemic bacterial infection, monitoring the level of PCT allows physicians to determine when the course of antibiotics may be stopped, once again minimizing antibiotic overuse. The Walton High School SMART Team has designed a 3D model of procalcitonin to investigate the relationship between procalcitonin’s structure and its function.Support or Funding InformationMSOE Center for Biomolecular Modeling
Activating Resident Neural Precursor Cells in the Spinal Cord to Promote Neural Repair
Authors: Gilbert Emily , Livingston Jessica , Khan Monoleena , Kandavel Harini , Kehtari Tarlan , Morshead Cindi 
Published: April 2020

Within the mammalian spinal cord there are two distinct populations of neural precursor cells: neural stem and progenitor cells (NSPCs) and oligodendrocyte progenitor cells (OPCs). NSPCs are located within the periventricular zone of the spinal cord and are relatively quiescent and non‐neurogenic under homeostatic conditions. OPCs are located throughout the grey and white matter of the spinal cord and give rise to new oligodendrocytes throughout life. Both of these populations are activated following injury, however, their response is not sufficient for functional recovery. We propose that enhancing resident precursor activation is a promising approach to improve structural and functional outcomes following SCI. The FDA‐approved drug metformin (MET) has demonstrated efficacy in promoting improved outcomes in the injured brain through pleiotropic effects including: decreased inflammation, enhanced precursor cell activation and increased neurogenesis and oligogenesis. Here, we seek to establish the influence of MET treatment on NSPC and OPC populations and explore whether MET can improve functional recovery following injury in the spinal cord. Our cellular data reveal that in uninjured animals, MET treatment significantly expands the NSPC pool in females, but not males; increases neurogenesis in males only and enhances oligogenesis across both sexes. Conversely, we observed no effect of MET treatment on the number of OPCs in uninjured mice, irrespective of sex. To test the efficacy of MET treatment following injury, we used two distinct models: (1) a dorsal column injury in the thoracic spinal cord (SCI), and (2), a model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE). In both models, MET was delivered to mice immediately following injury and for 14 days. Following SCI, mice were tested on a skilled walking test on post‐injury days (PID) 7 and 14. While all mice showed a significant deficit on PID7, by PID14, MET treated animals were not significantly impaired relative to pre‐injury performance and naive controls. In the EAE model, we evaluated the efficacy of MET treatment through both clinical scoring (based on degree of paralysis) and gait analysis. EAE resulted in significant clinical deficits 14 days following induction, which were mitigated in mice that received MET. Additionally, our gait analysis revealed improved metrics in MET treated mice. Across both injury models we observed significantly reduced inflammation. Taken together, our results support MET as a viable therapeutic strategy to expand and enhance NSPCs, improve the response of OPCs and support functional recovery following spinal cord injury.Support or Funding InformationCanadian Institute of Health ResearchMedicine by Design
Protein Binding to Lipid Droplets with Altered Ratios of Surface Phospholipids
Authors: Paetz Olivia , Renier Timothy , Vuong Sunny , Listenberger Laura 
Published: April 2020

Alcoholic Fatty Liver Disease (AFLD) is characterized by an increase in lipid droplets in the liver after acute ingestion of alcohol. Previous experiments with a rat model of AFLD show hepatic lipid droplets contain altered levels of the predominant classes of phospholipids. Specifically, hepatic lipid droplets from AFLD rats were found with lower amounts of phosphatidylcholine (PC) relative to phosphatidylethanolamine (PE). Our experiments aim to determine if the altered phospholipid composition of AFLD lipid droplets causes differences in the numbers or types of lipid droplet‐associated proteins. We selected proteins based on their membrane binding motifs and roles in lipid droplet homeostasis. AML12 cells cultured in choline‐deficient media simulate the altered phospholipid composition of AFLD lipid droplets. We isolated lipid droplets from AML12 cells cultured with and without choline and examined proteins of interest by SDS‐PAGE and western blotting. We found equivalent levels of rab18 and lanosterol synthase in lipid droplet fractions from cells grown with and without choline. Alternatively, perilipin 1, perilipin 2, and CIDE‐C are predominantly found in lipid droplet fractions from cells grown without choline (with lower ratios of PC:PE). The proteins that are most influenced by lipid droplet surface composition are all predicted to associate with lipid droplets through amphipathic alpha helices. By evaluating how altered phospholipid monolayer composition affects the binding of lipid droplet proteins, we seek to further elucidate the biochemical pathways that contribute to AFLD.Support or Funding InformationThis research was supported by St. Olaf College and the TRIO McNair Scholars Program.
Perfectionistic Cognitions and Interleukin‐6: The Moderating Role of Child Maltreatment
Authors: Molnar Danielle S. , MacNeil Adam J. , Moore Jessy , Maguire Aindriu R. R. , O’Leary Deborah D. , Wade Terrance J. 
Published: April 2020

Research is beginning to establish that perfectionism (i.e., the need to be absolutely perfect accompanied by harsh self‐criticism) contributes to poorer health and early mortality. Although few studies have addressed any personality/immune system links, there is growing evidence that personality can influence immune system functioning by altering cytokine production. Yet, to our knowledge, no study has examined the effect of perfectionism on immunological functioning. According to the Perfectionism Diathesis‐Stress Model, the deleterious effects of perfectionism on health should be further exacerbated by adverse childhood experiences (ACEs) such as maltreatment. However, this contention has yet to be tested empirically. The aim of this multidisciplinary research was to test how perfectionism is related to inflammatory analytes and whether these associations were moderated by child maltreatment. This study included a sample of young adults from the Niagara Longitudinal Heart Study (NLHS). Blood samples were collected, and serum was used to analyze levels of various immune biomarkers including Interleukin‐6 (IL‐6). Participants completed a self‐reported questionnaire that included the Childhood Trust Events Survey to identify exposure to sexual, physical, and emotional abuse before 18 years of age. Positive responses were then summed to create a count from 0 to 3 types of exposure. The Perfectionistic Cognitions Inventory assessed perfectionism. Results from multiple regression using Andrew Haye’s Process in which log‐transformed IL‐6 was regressed on perfectionistic cognitions, child maltreatment, and the interaction between perfectionistic cognitions and child maltreatment indicated that the relationship between perfectionistic cognitions and IL‐6 was moderated by child maltreatment. Specifically, higher perfectionistic cognitions were related to higher levels of IL‐6 under conditions of higher maltreatment. In sum, findings indicate that perfectionistic cognitions are related to immune system functioning and specifically to higher levels of IL‐6 when participants have experienced high levels of child maltreatment. These results support the Perfectionism Diathesis‐Stress Model and may provide key insights into both early prevention and intervention efforts aimed at reducing the toll of perfectionism on health.Support or Funding InformationThe NLHS is funded by the Canadian Institutes of Health Research (CIHR #s 363774, 399332). DSM is supported by an Early Researcher Award (Ministry of Research and Innovation, Government of Ontario). ARRM is supported by the Ontario Graduate Scholarship (OGS) Program.
Met‐β‐catenin induced hepatocellular cancer requires Ras but not Akt or Stat3 signaling
Authors: Tao Junyan , Liu Silvia , Bell Aaron , Chen Xin , Monga Satdarshan P. 
Published: April 2020

We have previously shown that co‐expression of hMet and mutant‐β‐catenin (S33Y or S45Y) using sleeping beauty transposon/transposase via hydrodynamic tail vein injection (SB‐HTVI) leads to HCC in mice referred to as Met‐b‐catenin model, which represented 11% of human HCC. Since Met signaling can activate downstream signaling including Ras, AKT/PI3K and STAT3, we next wanted to address if all these downstream components are equally or differentially required to lead to Met‐b‐catenin HCC. Recently, we replaced Met with G12D‐Kras to activate Ras/MAPK/Erk signaling and co‐expressed with mutant b‐catenin, which showed >90% gene expression similarity to Met‐b‐catenin HCC. Here, in leiu of Met, we co‐delivered mutant‐β‐catenin (S45Y/S33Y) with either myr‐AKT or H1047R‐PIK3CA or STAT3 via SB‐HTVI. Tumorigenesis was monitored at different stages after injection and molecular analysis was performed. Co‐injection of H1047R‐PIK3CA and S45Y/S33Y‐β‐catenin or myr‐ AKT and S45Y‐β‐catenin showed a notably slower tumor development as compared to Met‐b‐catenin or Kras‐b‐catenin model, taking >15 weeks post injection to develop appreciable tumor burden seen in the other 2 models at around 8 weeks. In fact, it took about 16 weeks and 22 weeks to induce comparable tumors for AKT‐S33Y‐β‐catenin group, and H1047R‐PIK3CA‐S33Y‐β‐catenin group, respectively. Co‐expression of active AKT/PI3K with mutant‐b‐catenin led to HCC displaying lipid accumulation in tumor cells. Co‐delivery of STAT3 and mutant‐catenin induced none or few small tumor nodules even around 34‐weeks post injection. There was evidence of increased p‐ERK, p‐AKT, and mTORC1/mTORC2 and downstream signaling including p‐EIF4E, p‐4E‐BP1 and p‐S6 Ribosomal protein as well as β‐catenin targets GS and CCND1 in AKT/PI3K‐b‐catenin. In conclusion, Ras signaling appears to be the most important downstream effector of Met signaling which cooperates with mutant β‐catenin for HCC development, while AKT/PI3K are of lesser relevance, and STAT3 of least relevance. These findings will have implications in biology as well as therapeutics for these subsets of human HCC as use of inhibitors of appropriate downstream effectors of Met may be more efficacious and with lesser off‐target effects than Met inhibition by itself in the Met‐b‐catenin HCC.Support or Funding InformationThis work was supported by NIH grants R01CA204586 to S.P.M
Role of the Candida albicans glycerophosphocholine acyltransferase, Gpc1, in phosphatidylcholine biosynthesis and cell physiology
Authors: King Will Ray , Patton-Vogt Jana 
Published: April 2020

Phosphatidylcholine (PC) is an abundant phospholipid in eukaryotic membranes. Our understanding of PC biosynthesis and acyl chain remodeling in Saccharomyces cerevisiae has been expanded with the identification of a glycerophosphosphocholine acyltransferase (GPCAT), Gpc1. Gpc1 acylates glycerophosphocholine (GPC), a product of complete deacylation of PC, to form lysophosphotidylcholine (LysoPC). LysoPC can subsequently be converted to PC by Ale1. This PC deacylation reacylation pathway (PC‐DRP) defines a novel route for PC biosynthesis and provides a potential mechanism to alter the acyl chain composition of a PC molecule. Changes in acyl chain composition can, in turn, affect physical properties of a membrane, such as fluidity, width, thickness and shape. Gpc1 displays no homology to known acyltransferases and defines a new gene family with members in plants, animals and fungi. The pathogenic fungus Candida albicans displays robust transport of GPC into the cell. We have previously shown that the inability of C. albicans to transport GPC results in decreased virulence in a mouse model of disseminated candidiasis, implying this metabolite plays a role during pathogenicity. We have created a C. albicans diploid knockout of Gpc1 homolog (orf19.998) using a transient CRISPR Cas‐9 system. Preliminary lipid analyses indicate that Gpc1 impacts PC biosynthesis in vivo. The physiological roles of CaGpc1 are being examined through growth and expression studies. Conditions to be examined include those associated with the human host and virulence, including elevated temperature, serum exposure, and hyphae inducing conditions.Support or Funding InformationNIH R15 GM104876
Inhibition of Oxidative DNA‐protein Crosslinking Via an Aqueous Extract of Kale
Authors: Gallano Alyssa Daniele , Nguyen Tanya , Lezo Daisy , Ramirez Ashley , Stemp Eric 
Published: April 2020

Oxidative damage is involved in the formation of free radicals, and if deregulated, can ultimately facilitate a variety of diseases ranging from Alzheimer’s disease to cancer. DNA‐protein crosslinking is a recognized form of oxidative stress that involves proteins interacting with radical‐induced lesions in the DNA molecule. In DNA, this damage is observed primarily at guanine (G) since it is the most easily oxidized base. Studies on oxidative stress show that substances – the most familiar being kale and spinach – high on antioxidants aid in protection from the excessive oxidizing effects of free radical species. The exact mechanism of inhibition has been hypothesized as a redox mechanism between the antioxidant and the radical. Therefore, the primary counteraction used to observe this mechanism and to reverse oxidative DNA‐protein crosslinking in this experiment was
kale.The flash‐quench technique is a method used for guanine oxidation and can induce DNA‐protein crosslinking. The intercalator, Ru(phen)2dppz2+[phen = phenanthroline, dppz = dipyridophenazine], is excited with a laser and gives an electron to the quencher, Co(NH3)5Cl2+. The intercalator then takes an electron from guanine, creating the guanine radical, which then reacts with protein. Samples containing Ru(phen)2dppz2+, Co(NH3)5Cl2+, histone protein, PUC19 DNA and kale were irradiated with blue laser light for 0 to 140 seconds to induce guanine damage. The extent of crosslinking was determined by the gel shift assay where SDS was added to the samples to disrupt the noncovalent interactions between the DNA and protein. Furthermore, the samples were compared with the control which substituted water for the kale extract. The inhibition of oxidative DNA damage by kale was studied further by focusing on kaempferol, a component of kale. Likewise, the gel shift assay was performed on samples containing water and two different concentrations – 50 μM and 200 μM – of the antioxidant. The interaction between kaempferol and the guanine radical was then displayed through transient absorption spectroscopy. Since kaempferol holds known antioxidative properties, the inhibition of DNA oxidation at the guanine site was also expected. Indeed, upon comparison, minimal DNA protein crosslinking was observed when kale or kaempferol were present in the samples. Specifically, as the irradiation time increased, the absorption of free DNA was low, assuming that a redox mechanism between the antioxidant and the guanine radical occurred.Future directions include determining the lowest concentration at which kaempferol is active, assessing the effects of additional antioxidants from kale, and examining a pure sample of kaempferol via high performance liquid chromatography (HPLC).Support or Funding InformationSupported and Funded by:Loring‐Denault Endowed Chair in Chemistry, Dr. Eleanor Siebert, and Professor Emeritus
HPV: The Power of Vaccination
Authors: Gite Jasmine , Ramanathan Siddharth , Hussein Inaya Hajj 
Published: April 2020

INTRODUCTIONGenital human papillomavirus (HPV) is a sexually transmitted infection (STI) that can lead to oropharyngeal, anal, cervical, vaginal, and penile cancers. It is the initiating event for malignant transformation and cervical dysplasia classified by the thickness of squamous intraepithelial lesions. Histologic evidence shows disorganized architecture and koilocytic changes in the epithelium, with a predilection for the squamocolumnar junction or transformation zone. Compared to heterosexual population, LGBTQIA+ subgroups may be at higher risk to HPV infections. This study aims to determine how knowledgeable Oakland University (OU) students are about HPV infection and vaccination, their perception and attitude towards it, and willingness to receive the vaccine, with a focus on gender and sexual orientation.METHODSA cross‐sectional survey collecting data on various parameters with measurable indicators such as: general non‐identifying information, knowledge of HPV vaccination, attitude towards HPV vaccination, and intent for receiving HPV vaccine was conducted. An information section regarding HPV and its vaccine was provided to assess change in knowledge of and attitude towards vaccination. Comparisons were analyzed with ANOVA and Chi‐Square tests.RESULTSOn average, heterosexual respondents agreed less than LGBTQIA+ respondents that the current vaccine is capable of preventing cervical, penile, or anal cancer (P = 0.0091). Vaccinated respondents agreed more than unvaccinated respondents that all gynecologists and personal physicians should recommend the vaccine to patients whether or not they come from conservative families (P = 0.0002), and that they would recommend this vaccine for their college friends (P = < 0.0001). Vaccinated respondents were significantly younger than unvaccinated respondents (P = 0.0005), but respondents who have heard of the HPV vaccine were significantly older than respondents who have not heard of the HPV vaccine (P = 0.0188). Adjusting for all factors, smokers have a significantly lower knowledge score than non‐smokers (P = 0.0290). A lower proportion of alcohol drinking respondents received the HPV vaccine as compared to non‐alcohol drinking respondents (P = 0.0358). On average, respondents who were unvaccinated were significantly more likely to undergo the HPV vaccine after taking the survey as compared to before taking the survey (P = 0.0016).CONCLUSIONDespite increasing social acceptance of the LGBTQIA+ community, few studies have addressed HPV infection and vaccination awareness among sexual minorities. Our findings show discrepancies in vaccine knowledge and vaccination status among different at‐risk groups. The findings also show increased likelihood of undergoing vaccination after reading an informational section within the survey, indicating the significant impact of and need to have widespread educational campaigns to influence behavioral perceptions and increase vaccine uptake.
Altered Redox Signalling in both Muscle and Nerve are Required for Neuromuscular Breakdown
Authors: Pollock Natalie , Hemmings Kay , Staunton Caroline A. , Owen Euan D. , Scalabrin Mattia , Macpherson Peter C. , Vasilaki Aphrodite , Van Remmen Holly , Richardson Arlan , Brooks Susan V. , McArdle Anne , Jackson Malcolm J. 
Published: April 2020

Our previous work has demonstrated that loss of superoxide dismutase1 (Sod1) in whole body KO mice (Sod1KO) results in an accelerated loss of muscle mass and function that is associated with a breakdown of neuromuscular junctions (NMJ). Deletion of Sod1 specifically in muscle or nerve caused a milder phenotype. These observations led us to hypothesise that altered redox signalling in muscle or nerve alone is not sufficient to induce sarcopenic changes but requires defects in both tissues. Inducible motor neuron Sod1 KO (i‐mnSod1KO) mice were created in order to examine whether loss of Sod1 in nerves in adult‐life affected age‐associated muscle wasting and weakness.This current work has examined changes in the neuromuscular system of Sod1KO, nerve rescue (SynTgSod1KO), i‐mnSod1KO mice and WT mice with advancing age.Hind limb skeletal muscles and sciatic nerves from adult (8–10 months), mid age (16–18 months) and old WT (24–27 months) mice, mid‐age and old i‐mnSod1KO mice, adult Sod1KO and adult SynTgSod1KO were used. Fixed and stained EDL muscles were used for NMJ analysis. Alterations in NMJ structure were quantified including pre‐and post‐synaptic overlap, fragmentation, complexity and area. Schwann cells were stained with fluorescently tagged s100 antibody. Western blot analysis of the sciatic nerves was performed to compare levels of oxidative damage assessed by the contents of 3‐NT and protein carbonylation. Electron paramagnetic resonance (EPR) analysis was carried out by infusing mice with a CPH spin probe and excising the gastrocnemius (GTN) muscle and sciatic nerve to examine the level of oxidised adducts. Samples were placed in Krebs buffer, frozen in liquid nitrogen and scanned on Bruker e‐scan EPR.A decline in NMJ structure was seen with advancing age. Despite some structural alterations, mid age mice showed no significant changes in NMJ structure in either WT or i‐mnSod1KO mice. There were significant alterations in all mice at 24 months and older. NMJs were substantially more disrupted in old i‐mnSod1Ko mice compared with old WT mice. Overlap and complexity of NMJs were both significantly reduced, but fragmentation was similar. The pattern of s100 staining was also altered with advancing age.The concentration of the 3‐carboxy‐proxyl radical (CP) measured by EPR in the sciatic nerve or GTN of adult WT, i‐mnSod1KO and SynTgSod1KO mice was not significantly different, although Sod1KO mice demonstrated a significant increase in CP concentration compared with adult WT.Data suggest that an accumulation of age‐related changes in the muscle alongside altered redox signalling in the nerve due to lack of Sod1 is needed to bring about a significant breakdown of the NMJ.Support or Funding InformationWith thanks to National Institute of Ageing (AG051442) and University of Liverpool for their support.