One of the hallmarks of Parkinson Disease is a deficit in Complex I of the mitochondrial complex chain in the tyrosine hydroxylase (THf)+ neurons in the substantia nigra pars compacta (SNpc) of the brain. This situation allows the dopamine neuron to be put under oxidative stress, thus leaving the DA neuron vulnerable to free radical attack. In attempts to reverse the deficit in Complex I in the cell, in earlier experiments, we used a ketone body, D-beta- hydroxybutyrate (DBHB) in the presence of MPTP to increase oxidative phosphorylation. This change in phosphorylation state afforded protection to the SNpc TH+neurons. One drawback to the use of DBHB is that it is short- acting. In our present experiment, we used a DBHB analogue, glyceryl tris(3- hydroxybutyrate, G3HB) which is the basic DBHB structure that has been altered. Compared to DBHB which increased DBHB levels in plasma by almost 100%, G3HB increased plasma DBHB levels by less than 50%, Increasing the assay sample volume increases brain tissue DBHB levels . In the in vivo studies, the combination of MPTP and G3HB seemed to cause significant mortality in the two strains of mice that we used. This high mortality rate may be strain or breeding house dependent. More studies need to be done to sort this situation out.

关键词：羟基自由基；线粒体；帕金森氏症

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Despite the fact that there have been significant developments in anti-cancer technology, ovarian cancer still remains one of the leading causes of gynecological cancer deaths in the United States. To contribute towards novel approaches with minimal toxicity in treatment of ovarian cancer we proposed the present work, where we are integrating the field of nanotechnology with ovarian cancer cells unique property of overexpressing folic acid receptor alpha (FR- ) to specifically target ovarian cancer. A cerium oxide nanoparticle, called Nanoceria (NCe), that has the ability to act as an anti- oxidant in similar capacity as biological anti-oxidants was selected. NCe in our hands exhibited efficacy in inhibiting ovarian tumor growth in vivo. Taking advantage of the nanotechnology, NCe was conjugated with molecules of folic acid to specifically target ovarian tumors as they are known to over-express folate receptor. This would result in specific killing of ovarian cells by NCe while minimizing toxicity to normal tissue. Dr Seal s laboratory (UCF) was able to successfully conjugate NCe to folic acid to prepare folic acid tagged Nanoceria called FA-NCe. FA-NCe was tested in vitro and was observed to have higher anti-growth activity against ovarian cancer cells. When given in animals, FA-NCe was more potent in inhibiting ovarian tumor growth than NCe alone.

关键词：卵巢癌；抗氧化剂；细胞（生物学）；临床医学

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According to CDC data, racial and ethnic minorities in the United States--particularly Blacks/African-Americans and Hispanics/Latinos--have been disproportionately affected by HIV/AIDS, representing 72 percent of new HIV infections and 74 percent of all AIDS diagnoses in 2011. In addition to core funding programs through CDC and HRSA that are intended to provide services to all qualifying individuals affected by HIV/AIDS, MAI seeks to improve HIV-related health outcomes and reduce health disparities for minority communities through the provision of grant funds. MAI grants are distributed to a variety of entities. The Ryan White HIV/AIDS Treatment Extension Act of 2009 required GAO to (1) examine the services provided, population served, and administrative challenges faced by MAI grantees, and (2) describe the best practices identified by grantees and other stakeholders for community outreach and capacity building. GAO conducted a review of services reported in fiscal year 2011 MAI grantee annual reports from a generalizable sample of 100 grantees, and interviewed agency officials and other stakeholders. GAO also reviewed grant administrative requirements, and data on MAI grant amounts and populations served.

关键词：人类免疫缺陷病毒（HIV）；获得性免疫缺陷综合症；医药

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The Michigan State Police Vehicle Test Team is pleased to present the results of the 2013 model year Police Vehicle Evaluation. This year we tested thirteen vehicles in total, and four motorcycles. All of the cars were tested with a clean roof (no overhead light or light bar) and without A pillar mount spotlights. We believe this is the best way to ensure all of the vehicles are tested on an equal basis. Remember that once overhead lights, spotlights, radio antennas, sirens, and other emergency equipment are installed, overall performance may be somewhat lower than we report. Each vehicle was tested with the tires that are available as original equipment on the production model. Specific tire information for each vehicle is available in the Vehicle Description portion of this report. All vehicles listed in this report were equipped with electronic speed limiters. Motorcycles were tested with equipment installed as provided by their respective manufacturer. Harley-Davidson chose to test their bikes with minimal equipment. BMW, and Victory chose to test their bikes with the majority of the equipment installed.

关键词：汽车；警车；交通安全

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Based on the in vitro results in preliminary data and in year No. 2 of the proposal (1), we conducted an in vivo xenograft mouse experiment using prostate cancer cell lines containing specific levels (endogenous, shRNA, and Flag-MDH2 compensation) of MDH2.

关键词：化疗；前列腺癌；细胞（生物学）

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Androgen receptor (AR)-mediated transcription is modulated by interaction with co-regulatory proteins. We identified a novel AR repressor complex comprising of the androgen receptor co-repressor Art-27 and the transcriptional repressor URI. We found through chromatin immunoprecipitation experiments that URI depletion results in increased H3K9me3 at the promoter of the AR target gene Nkx3.1, suggesting that one mechanism of URI-mediated transcriptional repression is through chromatin modification. Art-27 was also found by ChiP to localize at the transcription start site of Nkx3.1 along with PolII. Previous results demonstrated a direct interaction between URI and the transcription factor KAP1. Because of the tight association of Art-27 with URI, we hypothesized that Art-27 also affects KAP1 activity. Immunoprecipitation of Art-27 with KAP1 revealed a direct interaction between the two proteins. Consistent with this result, knockdown of Art-27 resulted in increased expression of the KAP1 targets LINE1 and AluYa5. Overall, our findings demonstrate a new role for Art-27 in KAP1-mediated gene repression.

关键词：雄激素细胞（生物学）；生长（生理学）；受体位点

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The objectives of this document are: 1) to determine the extent to which Data and Safety Monitoring Boards (DSMBs) met National Institutes of Health (NIH) guidance in carrying out their responsibilities to monitor trials and 2) to identify any challenges to DSMB effectiveness. Clinical trials test experimental drugs, devices, and treatments to determine whether they are safe and effective. DSMBs are advisory committees of experts responsible for reviewing ongoing trial data. They play a unique role in ensuring the safety of human subjects enrolled in trials. They also play a critical role in ensuring the merit of these trials. To carry out these functions, DSMBs must have direct access to unmasked data during the course of a trial, meaning that members know which subjects are in which treatment group--something the researchers and subjects themselves do not generally know. NIH requires DSMBs to monitor all Phase III multi-site trials that entail potential risk.

关键词：临床试验；监测；数据库管理；委员会

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We have performed a high throughput, in vivo genetic screen to identify kinases that permitted androgen-dependent transformed prostate epithelial cells (LHSR-AR cells) to form tumors in female animals. In addition to known prostate cancer oncogenes, Never In Mitosis A (NIMA) related kinase 6 (NEK6) reproducibly yielded androgen-independent tumors in female mice. NEK6 can confer castration resistance to established tumors in male mice, and inactivating its expression can restore sensitivity to castration. Castration- resistant tumors generated through NEK6 overexpression are predominantly squamous in histology and AR-negative, and NEK6 does not activate AR signaling. NEK6 overexpression leads to phosphorylation of RPS6KB1 and SGK1, and these two genes along with a novel identified substrate, FOXJ2, are essential for NEK6- mediated androgen-independent tumor formation. NEK6 is located on a region of recurrent copy number gain on chromosome 9q33.3 in human prostate cancer, and NEK6 overexpression in tumor microarrays and the TCGA data set correlates with more aggressive disease. NEK6 and its downstream effectors are thus potential novel therapeutic targets in CRPC.

关键词：基因；荷尔蒙；体内的分析；前列腺癌

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Dystonia is the 3rd most common movement disorder, and some forms are brought on by stress. Investigators have not yet succeeded in making a genetic mouse model of dystonia by conventional approaches. A novel strategy was designed to combine three mutant mouse strains together by breeding to reduce the expression of a protein known to be mutated in an inherited human dystonia triggered by stress. There were problems with one of the mouse strains, however, which lost one of its genetic modifications, and a different strategy was adopted. This was successful, and a mouse with the desired dystonic symptoms was obtained. It has two mutations, one a dominantly inherited gene with 100% penetrance, and the other a strain-specific modifier gene that controls how strong the symptoms are. These genes were mapped to two loci on two different chromosomes. The behavior of the mouse was extensively characterized. Swim stress brought about very severe symptoms, but the mice fully recovered to a moderate dystonic baseline. As planned, electrophysiology and electromyography were performed, showing the co-contraction of opposing muscles, the hallmark of dystonia.

关键词：神经学；遗传学；突变；蛋白

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关键词：基于图形交互；图论；基于图的数据挖掘；医药

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