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Neuroprotective Effects of Asparagus officinalis Stem Extract in Transgenic Mice Overexpressing Amyloid Precursor Protein
Get PDFTo mimic Alzheimer\u27s disease, transgenic mice overexpressing the amyloid precursor protein (APP) were used in this study. We hypothesize that the neuroprotective effects of ETAS®50, a standardized extract of Asparagus officinalis stem produced by Amino Up Co., Ltd. (Sapporo, Japan), are linked to the inhibition of the apoptosis cascade through an enhancement of the stress-response proteins: heat shock proteins (HSPs). APP-overexpressing mice (double-transgenic APP and PS1 mouse strains with a 129s6 background), ages 6-8 weeks old, and weighing 20-24 grams were successfully bred in our laboratory. The animals were divided into 5 groups. APP-overexpressing mice and wild-type (WT) mice were pretreated with ETAS®50 powder (50% elemental ETAS and 50% destrin) at 200 mg/kg and 1000 mg/kg body weight. Saline, the vehicle for ETAS®50, was administered in APP-overexpressing mice and WT mice. ETAS®50 and saline were administered by gavage daily for 1 month. Cognitive assessments, using the Morris Water Maze, demonstrated that memory was recovered following ETAS®50 treatment as compared to nontreated APP mice. At euthanization, the brain was removed and HSPs, amyloid β, tau proteins, and caspase-3 were evaluated through immunofluorescence staining with the appropriate antibodies. Our data indicate that APP mice have cognitive impairment along with elevated amyloid β, tau proteins, and caspase-3. ETAS®50 restored cognitive function in these transgenic mice, increased both HSP70 and HSP27, and attenuated pathogenic level of amyloid β, tau proteins, and caspsase-3 leading to neuroprotection. Our results were confirmed with a significant increase in HSP70 gene expression in the hippocampus
The role of DND1 in cancers
Get PDFThe Ter mutation in Dead-End 1 (Dnd1), Dnd1Ter, which leads to a premature stop codon, has been determined to be the cause for primordial germ cell deficiency, accompanied with a high incidence of congenital testicular germ cell tumors (TGCTs) or teratomas in the 129/Sv-Ter mice. As an RNA-binding protein, DND1 can bind the 3′-untranslated region (3′-UTR) of mRNAs and function in translational regulation. DND1 can block microRNA (miRNA) access to the 3′-UTR of target mRNAs, thus inhibiting miRNA-mediated mRNA degradation and up-regulating translation or can also function to degrade or repress mRNAs. Other mechanisms of DND1 activity include promoting translation initiation and modifying target protein activity. Although Dnd1Ter mutation causes spontaneous TGCT only in male 129 mice, it can also cause ovarian teratomas in mice when combined with other genetic defects or cause germ cell teratomas in both genders in the WKY/Ztm rat strain. Furthermore, studies on human cell lines, patient cancer tissues, and the use of human cancer genome analysis indicate that DND1 may possess either tumor-suppressive or-promoting functions in a variety of somatic cancers. Here we review the involvement of DND1 in cancers, including what appears to be its emerging role in somatic cancers
Analysis of Vulnerabilities in IOT Devices and the Solutions
Get PDFThis thesis analyzes the insecurities in IOT devices, why these insecurities exist, and solutions to fix these vulnerabilities. IoT (Internet of Things) devices are nonstandard computing devices that connect wirelessly to a network that will transmit data. The amount of IOT devices continues to increase, as the demand for the items increases. It is predicted that there will be about 26 billion IOT devices installed by 2020. They have been improving on the amount of functionality they were previously able to do. For instance, Amazon’s Alexa is a speaker that can order items for you from the Amazon website, play your favorite music via Spotify, amazon music, or play music and much more. This requires Alexa to be logged into each one of those accounts to do this. With this information, there is a lot more personal information going in and out of the device. As the demand for the products increases, manufacturers begin to feel the pressure of having to push out products. They feel so much pressure that they skip important features of the IOT devices, including security. This lack of security opens users up to attacks and vulnerabilities from hackers that are trying to steal personal information. Therefore, consumers need to know the steps to take, in order to secure all their information, and the type of attacks and techniques hackers will use to get their private information
A Study of the Impact of Infrastructures on Public Bicycle-Sharing System Demand
Get PDFA bicycle-sharing system (public bicycle system, or bike-share scheme) is a service in which bicycles are made available for shared use to individuals on a short-term basis for a price or free. To study the impacts of bike infrastructures (particularly bike lanes and bike paths) on bicycle sharing system demand, autoregressive integrated moving average (ARIMA) models with exogenous factors are proposed to capture the relationships among the variables in a longitudinal analysis. The results show that every mile of bike lane added to the Houston bike share system will result in 38 average daily ridership increase in seven days of a week, 37 average daily ridership increase in weekdays (5 days of a week), and 82 average daily ridership increase on weekends. By adding every station to the public bikeshare system, the average daily ridership will increase by 16. The increase of average daily ridership will be 17 for weekdays, and 34 on weekends. It means that adding one bike station have less impact on average daily ridership of seven days of a week or five weekdays compared to the weekends. The impact of built environment on average daily ridership of weekends are almost two times more when compared to its impact on the average weekday ridership, resulting in more demand during weekends. Regarding the influence of the weather variables, temperature and wind speed had no impact on the average daily trip counts in Houston. However, precipitation displayed a significant negative impact on the average daily ridership
The Impact of Selective Cognitive and Non-Cognitive Factors on Academic Performance and Persistence Rate of First-Year College Students: Implications for Counseling.
Get PDFThe issue of first-year college students academic performance and persistence rate has recently become a focal point for policy discussions because researchers, administrators, counselors, and policymakers are increasingly interested in understanding why some students succeed while others fail. To help incoming freshmen accomplish their academic and career goals, college and universities must gain the necessary insight on how to retain these students and assist them in matriculating on their campuses. Selective cognitive and non-cognitive characteristics associated with incoming freshmen will have a significant impact on them remaining in school and graduating. The purpose of this study was to examine the impact of selected cognitive and non-cognitive factors on academic performance and persistence rate of first-year college students. This study is concerned with the predictable relationship between the cognitive and non-cognitive factors of high school GPA, SAT/ACT composite scores, first semester GPA, parents’ education level, ethnicity, SES, and gender on academic performance and persistence rate of first-year college students. A correlational research design was employed in this study. The population consisted of 1,532 first-time freshmen students who enrolled at the targeted institution of higher learning during the 2018-2019 academic year. The archival (secondary) data for the present empirical investigation was obtained from the target university’s office of Institutional, Assessment, Planning, and Effectiveness. A linear relationship was found between cognitive factors and academic performance among first-year college students. High school grade point average was found to be an independent predictor of academic performance among first-year college students. The first-semester grade point average was found to contribute significantly to the academic performance of first-year college students. A statistically linear relationship was found between non-cognitive factors and the academic performance of first-year college students. First-year college students’ gender was found to be independently related to their first-year final grade point average. The non-cognitive factors of their mothers’ education levels, their fathers’ education levels, ethnicity, SES, and gender were not significant predictors in distinguishing those first-year college students who would return to the university and those who would not return to the university. Moreover, a statistically linear relationship was found between the combination of cognitive and non-cognitive factors and the academic performance among first-year college students
Have Voucher Will Relocate? Poverty Deconcentration in a Large American City
Get PDFThe epic failure of fixed public housing projects supports the paradigm that poverty concentration makes poverty and the cycle of poverty intractable. Moreover, neoliberal, free-enterprise theorists interrogate the viability of the state as a provider of social goods and services and press the need for market-based schemes such as housing vouchers. However, how do you de-concentrate the poor voluntarily without government dictating residential choice? This article reports the results of the first ten years of a policy experiment leveraging a mobile voucher program to attempt to achieve voluntary dispersion and de-concentration of the poor in Phoenix, Arizona. Using Phoenix’s 308 census tracks as of 1998 as units of analysis, and examining the locational choices of the 5,139 families that received mobile housing vouchers between 1998 and 2009, this study finds that, although mobile voucher recipients dispersed somewhat throughout the research period, they were still geographically isolated in the southern poverty belt, housing mostly race and ethnic minority populations at the end of the ten-year period. The data suggest that race/ethnicity and patterns of residential segregation may hold some of the key to de-concentration. Ultimately, the level of de-concentration does not support the broader theory that mobile vouchers hold the key to poverty de-concentration
In vitro and in vivo characterization of potent antileishmanial methionine aminopeptidase 1 inhibitors
No full textLeishmania major is the causative agent of cutaneous leishmaniasis (CL). No human vaccine is available for CL, and current drug regimens present several drawbacks, such as emerging resistance, severe toxicity, medium effectiveness, and/or high cost. Thus, the need for better treatment options against CL is a priority. In the present study, we validate the enzyme methionine aminopeptidase 1 of L. major (MetAP1Lm), a metalloprotease that catalyzes the removal of N-terminal methionine from peptides and proteins, as a chemotherapeutic target against CL infection. The in vitro antileishmanial activities of eight novel MetAP1 inhibitors (OJT001 to OJT008) were investigated. Three compounds, OJT006, OJT007, and OJT008, demonstrated potent antiproliferative effects in macrophages infected with L. major amastigotes and promastigotes at submicromolar concentrations, with no cytotoxicity against host cells. Importantly, the leishmanicidal effect in transgenic L. major promastigotes overexpressing MetAP1Lm was diminished by almost 10-fold in comparison to the effect in wild-type promastigotes. Furthermore, the in vivo activities of OJT006, OJT007, and OJT008 were investigated in L. major-infected BALB/c mice. In comparison to the footpad parasite load in the control group, OJT008 decreased the footpad parasite load significantly, by 86%, and exhibited no toxicity in treated mice. We propose MetAP1 inhibitor OJT008 as a potential chemotherapeutic candidate against CL infection caused by L. major infection
Pre-clinical pharmacokinetics, tissue distribution and physicochemical studies of CLBQ14, a novel methionine aminopeptidase inhibitor for the treatment of infectious diseases
No full textIntroduction: CLBQ14, a derivative of 8-hydroxyquinoline, exerts its chemotherapeutic effect by inhibiting methionine aminopeptidase (MetAP), the enzyme responsible for the post-translational modification of several proteins and polypeptides. MetAP is a novel target for infectious diseases. CLBQ14 is selective and highly potent against replicating and latent Mycobacterium tuberculosis making it an appealing lead for further development. Methods: The physicochemical properties (solubility, pH stability and lipophilicity), in vitro plasma stability and metabolism, pre-clinical pharmacokinetics, plasma protein binding and tissue distribution of CLBQ14 in adult male Sprague-Dawley rats were characterized. Results: At room temperature, CLBQ14 is practically insoluble in water (80 mg/mL); it has a log P value of 3.03 ± 0.04. CLBQ14 exhibits an inverse Z-shaped pH decomposition profile; it is stable at acidic pH but is degraded at a faster rate at basic pH. It is highly bound to plasma proteins (\u3e91%), does not partition to red blood cells (B/P ratio: 0.83 ± 0.03), and is stable in mouse, rat, monkey and human plasma. CLBQ14 exhibited a bi-exponential pharmacokinetics after intravenous administration in rats, bioavailability of 39.4 and 90.0%, respectively from oral and subcutaneous route. We observed a good correlation between predicted and observed rat clearance, 1.90 ± 0.17 L/kg/h and 1.67 ± 0.08 L/kg/h, respectively. Human hepatic clearance predicted from microsomal stability data and from the single species scaling were 0.80 L/hr/kg and 0.69 L/h/kg, respectively. CLBQ14 is extensively distributed in rats; following a 5 mg/kg intravenous administration, lowest and highest concentrations of 15.6 ± 4.20 ng/g of heart and 405.9 ± 77.11 ng/g of kidneys, respectively, were observed. In vitro CYP reaction phenotyping demonstrates that CLBQ14 is metabolized primarily by CYP 1A2. Conclusion: CLBQ14 possess appealing qualities of a drug candidate. The studies reported herein are imperative to the development of CLBQ14 as a new chemical entity for infectious diseases
Examining Aspects of Obama’s Criminal Justice Legacy
Get PDFThis paper is primarily a theoretical discussion of some aspects of the criminal justice legacy of Barack Obama’s two-term presidency and its impact on minorities. The historic 2008 electoral victory of the first black US president was widely expected to usher the dawn of a post-racial America. Instead, race relations worsened. Some critics complained that there was no significant reduction in black-white disparity in probable arrest, court actions and imprisonment during Obama presidency and that whatever he achieved was too little and too late to reform the U.S. criminal justice system. Protagonists however argue that undue expectations failed to take account of deeply entrenched racism, racially toxic political environment and limitations on presidential powers which the Obama administration had to contend with. The two major criminal justice legislation of his administration were the 2009 Hate Crimes Prevention Act and the 2010 Fair Sentencing Act. Due to partisan politics, he could not get several critical bills passed into law due to stiff opposition from the Republican Party-dominated legislature. But many of those initiatives have become the cornerstone of the ongoing bipartisan criminal justice reform