88 research outputs found
“We’ve Lost Sight of The Blue and White, and We Need To Find It Again.” Youth, Divergence of Memory, and Political Polarization in Post- Conflict Nicaragua
In this essay, I analyze the results from 20 interviews I completed in Managua, Matagalpa, and San Ramon, selecting 8 to delve into in depth. I conducted the interviews in pairs, asking parents about their memories of the Nicaraguan Contra war in the 1980s and then asking their children about the histories their parents shared with them and their personal views of Nicaragua. Through these interviews, I sought to understand in a Nicaraguan context the presence of historical memory, the politicization of historical memory, the diversity of youth activism, and the way that youth view reconciliation within their countries. My results reflect first that in the context of my interviews oral histories were in every case passed from parents to children, although in many cases children would understand and internalize these stories in a huge variety of ways regardless of the intended principles that the parents wanted to pass on. The second major finding of my research is that although parents are convinced that the current generation of Nicaraguan youth is more united than their own, their children almost universally argued the opposite. I conclude the paper by arguing that despite the prevailing idea amongst youth in my interviews that another Revolution is coming, I found many instances of hope in their responses; their dissent is but a reflection of that hope
The perceptions of the role of the school social worker by elementary school principals
Thesis (M.S.)--Boston Universit
Commercial Nuclear Power Plant Training Program Evaluation for Non-licensed Operators: a Delphi Approach
This study was concerned with the establishment of detailed qualification criteria on a generic basis for the position of non-licensed operator of a commercial nuclear power plant. The specific objectives included determining general educational requirements and specific technical areas of study necessary or desirable for the non-licensed operator, as well as the type of plant-specific orientation and training that he or she should receive during the first few months of employment. The additional education, training, and experience qualifications necessary for an individual filling the position of a non-licensed operator were also examined. A series of three questionnaires incorporating the Delphi Technique was used to gather data and opinions from commercial nuclear power plant training coordinators (both corporate and site), university educators in the nuclear power area, regulatory agencies auditing training programs for non-licensed operators and management personnel involved with non-licensed operators. Information thus collected was analyzed against majority opinion criteria, and specific qualification elements were identified and ranked in order of importance.Occupational and Adult Educatio
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Ascorbylation- the biological relevance of covalently bound ascorbic acid
Ascorbic acid, or vitamin C, is well known as a co-factor for proline-hydroxylase and as an anti-oxidant. However, it is also capable of forming covalent bonds, particularly in the role of a nucleophile, henceforth termed 'ascorbylation'.
The ascorbylation of electrophiles can occur under physiological conditions. Furthermore, there are a number of ascorbylated natural products found in plants and these compounds are reviewed here. Many of these natural products have biological activity. For example, the ascorbylated indole derivative ascorbigen, found in Brassica vegetables, can induce quinone reductase and thus may have a role in cancer chemoprevention.
Thus, we hypothesize that ascorbic acid has important biological relevance beyond the role of antioxidant and in the hydroxylation of proline. If ascorbic acid, which is present in cells and very high concentrations, ascorbylates electrophiles, this present a new pathway in the detoxification of toxic compounds. For example, acrolein is a toxic compound which alkylates DNA and protein, leading to cancer among other health issues. Acrolein also reacts rapidly with ascorbic acid. Once ascorbylated, acrolein is no longer electrophilic and furthermore, the ascorbyl-acrolein (AscACR) molecule is more hydrophilic and this could lead to improved elimination of the molecule. Essentially, ascorbylation could be a previously unrecognized form of phase II metabolism, analogous to glutathione conjugation. The first major goal of this research is to detect ascorbylated metabolites of electrophiles (i.e. AscACR) from biological samples.
Additionally, because ascorbylated compounds may have dramatically altered ADME characteristics compared to the non-ascorbylated compound, synthetically ascorbylated compounds may function as prodrugs. That is, a drug with poor pharmacokinetic parameters may be improved with the addition of an ascorbyl moiety, and that ascorbyl moiety may be cleaved via a retro-Michael reaction upon deliver to the site of action. The second goal of this work is to produce an ascorbylated prodrug. The candidate of choice was xanthohumol. Xanthohumol is a biologically active Michael acceptor which has very poor bioavailability due to low hydrophilicity- a characteristic which can be improved via ascorbylation.
AscACR is easily synthesized. However, it was exceedingly difficult to detect in any biological samples using LC-MS/MS. It was hypothesized originally that AscACR may be a product of oxidative stress but it could not be found in samples of human subjects exposed to oxidative stress. Samples of rats exposed to CCl₄, a well known inducer of oxidative stress, similarly contained no detectable amounts of AscACR. Even rat or cell cultures exposed to acrolein directly did not produce samples with detectable amounts of AscACR. In retrospect, this was likely due to the instability of AscACR in biological media.
However, a degradation product of AscACR was detected by LC-MS/MS in THP-1 cells exposed to acrolein diacetate (which was used to deliver acrolein intracellularly). This degradation product is produced via the hydrolysis of the lactone of AscACR, followed by decarboxylation and racemization to two stereoisomers, the mixture of which we term 5,6,7,8-tetrahydroxy-4-oxooctanal (THO). This same reaction scheme occurs with the natural product ascorbigen under certain conditions, and indeed is involved in the biosynthetic pathway of dactylose A and B.
Vitamin C adequate THP-1 cells which are exposed to acrolein (via acrolein diacetate), produce THO. Thus, biologically, ascorbylation is involved in the detoxification of electrophiles; it is a new sort of phase II metabolism (albeit without an enzyme). The ascorbylation of acrolein itself is chemical; THO is also detected in the incubation of ascorbic acid and acrolein-diacetate no cell control. However, AscACR, the precursor of THO, was only detected in the no cell control. This is strong evidence that an enzyme, or some related biocatalyst, is involved in the conversion of AscACR to THO.
In the prodrug work, the ascorbylated form of xanthohumol (AscXN) failed to serve as a prodrug. The synthesis of AscXN was poor. AscXN itself was unstable. In a caco-2 cell study modeling intestinal absorption, AscXN failed to show any transport across the caco-2 monolayer. While AscXN failed to function as a prodrug, this may have been due to the choice in candidate, rather than failure of the hypothesis itself
Influenza D virus M2 protein exhibits ion channel activity in Xenopus laevis oocytes
A new type of influenza virus, known as type D, has recently been identified in cattle and pigs. Influenza D virus infection in cattle is typically asymptomatic; however, its infection in swine can result in clinical disease. Swine can also be infected with all other types of influenza viruses, namely A, B, and C. Consequently, swine can serve as a mixing vessel for highly pathogenic influenza viruses, including those with zoonotic potential. Currently, the only antiviral drug available targets influenza M2 protein ion channel is not completely effective. Thus, it is necessary to develop an M2 ion channel blocker capable of suppressing the induction of resistance to the genetic shift. To provide a basis for developing novel ion channel- blocking compounds, we investigated the properties of influenza D virus M2 protein (DM2) as a drug target
Heme Regulates Exocrine Peptidase Precursor Genes in Zebrafish
We previously determined that yquem harbors a mutation in the gene encoding uroporphyrinogen decarboxylase (UROD), the fifth enzyme in heme biosynthesis, and established zebrafish yquem (yqetp61) as a vertebrate model for human hepatoery-thropoietic porphyria (HEP). Here we report that six exocrine peptidase precursor genes, carboxypeptidase A, trypsin precursor, trypsin like, chymotrypsinogen B1, chymotrypsinogen 1-like, and elastase 2 like, are downregulated in yquem/urod (−/−), identified initially by microarray analysis of yquem/urod zebrafish and, subsequently, confirmed by in situ hybridization. We then determined downregulation of these six zymogens specifically in the exocrine pancreas of sauternes (sautb223) larvae, carrying a mutation in the gene encoding δ-amino-levulinate synthase (ALAS2), the first enzyme in heme biosynthesis. We also found that ptf1a, a transcription factor regulating exocrine zymogens, is downregulated in both yquem/urod (−/−) and sau/alas2 (−/−) larvae. Further, hemin treatment rescues expression of ptf1a and these six zymogens in both yquem/urod (−/−) and sauternes/alas2 (−/−) larvae. Thus, it appears that heme deficiency downregulates ptf1a, which, in turn, leads to downregulation of exocrine zymogens. Our findings provide a better understanding of heme deficiency pathogenesis and enhance our ability to diagnose and treat patients with porphyria or pancreatic diseases.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline
Acute Trauma Factor Associations With Suicidality Across the First 5 Years After Traumatic Brain Injury
AbstractObjectiveTo determine whether severity of head and extracranial injuries (ECI) is associated with suicidal ideation (SI) or suicide attempt (SA) after traumatic brain injury (TBI).DesignFactors associated with SI and SA were assessed in this inception cohort study using data collected 1, 2, and 5 years post-TBI from the National Trauma Data Bank and Traumatic Brain Injury Model Systems (TBIMS) databases.SettingLevel I trauma centers, inpatient rehabilitation centers, and the community.ParticipantsParticipants with TBI from 15 TBIMS Centers with linked National Trauma Data Bank trauma data (N=3575).InterventionsNot applicable.Main Outcome MeasuresSI was measured via the Patient Health Questionnaire 9 (question 9). SA in the last year was assessed via interview. ECI was measured by the Injury Severity Scale (nonhead) and categorized as none, mild, moderate, or severe.ResultsThere were 293 (8.2%) participants who had SI without SA and 109 (3.0%) who had SA at least once in the first 5 years postinjury. Random effects logit modeling showed a higher likelihood of SI when ECI was severe (odds ratio=2.73; 95% confidence interval, 1.55–4.82; P=.001). Drug use at time of injury was also associated with SI (odds ratio=1.69; 95% confidence interval, 1.11–2.86; P=.015). Severity of ECI was not associated with SA.ConclusionsSevere ECI carried a nearly 3-fold increase in the odds of SI after TBI, but it was not related to SA. Head injury severity and less severe ECI were not associated with SI or SA. These findings warrant additional work to identify factors associated with severe ECI that make individuals more susceptible to SI after TBI
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