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Social support quality and availability affects risk behaviors in offenders.

Recent Research Articles from UNTHSC - Fri, 04/08/2016 - 06:29

Social support quality and availability affects risk behaviors in offenders.

Health Justice. 2016;4:2

Authors: Spohr SA, Suzuki S, Marshall B, Taxman FS, Walters ST

Abstract
BACKGROUND: People involved in the justice system are at 2.5 times the risk of HIV infection compared to the general population, which is further complicated by substance abuse. The purpose of this study was to evaluate the role of social network quality and quantity on unprotected sex, criminal risk, and substance use.
METHODS: We used data from 330 drug-involved offenders. Structural equation modeling (SEM) was used to model and test path directionality and magnitude between the latent constructs of social support quality and quantity on risky behaviors.
RESULTS: The SEM indicated the latent construct of social support quality was significantly associated with reduced sexual risk behavior (β = -0.27), criminal risk (β = -0.26), and reduced substance use (β = -0.33). Additionally, the proposed model found that social support quantity was significantly positively associated with increased sexual risk behavior (β = 0.40) and substance use (β = 0.20).
CONCLUSIONS: Social support quality is an important predictor of risky behaviors; as the quality of an offender's social support increases, engagement in risky behaviors decreases. Probationers who had broader social support availability also had increased substance use and unprotected sex. Probation systems may be able to reduce substance use and STD/HIV infection risk in offenders by strengthening the quality of social support networks.

PMID: 27054059 [PubMed - as supplied by publisher]

Dermatorynchus geneae: A seldom-described first branchial arch deformity.

Recent Research Articles from UNTHSC - Thu, 04/07/2016 - 10:36

Dermatorynchus geneae: A seldom-described first branchial arch deformity.

JAAD Case Rep. 2015 Sep;1(5):283-285

Authors: McIlwee BE, Hick RW, Weis SE

PMID: 27051754 [PubMed - as supplied by publisher]

Vestiges of an Ancient Border in the Contemporary Genetic Diversity of North-Eastern Europe.

Recent Research Articles from UNTHSC - Thu, 04/07/2016 - 10:36
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Vestiges of an Ancient Border in the Contemporary Genetic Diversity of North-Eastern Europe.

PLoS One. 2015;10(7):e0130331

Authors: Neuvonen AM, Putkonen M, Översti S, Sundell T, Onkamo P, Sajantila A, Palo JU

Abstract
It has previously been demonstrated that the advance of the Neolithic Revolution from the Near East through Europe was decelerated in the northernmost confines of the continent, possibly as a result of space and resource competition with lingering Mesolithic populations. Finland was among the last domains to adopt a farming lifestyle, and is characterized by substructuring in the form of a distinct genetic border dividing the northeastern and southwestern regions of the country. To explore the origins of this divergence, the geographical patterns of mitochondrial and Y-chromosomal haplogroups of Neolithic and Mesolithic ancestry were assessed in Finnish populations. The distribution of these uniparental markers revealed a northeastern bias for hunter-gatherer haplogroups, while haplogroups associated with the farming lifestyle clustered in the southwest. In addition, a correlation could be observed between more ancient mitochondrial haplogroup age and eastern concentration. These results coupled with prior archeological evidence suggest the genetic northeast/southwest division observed in contemporary Finland represents an ancient vestigial border between Mesolithic and Neolithic populations undetectable in most other regions of Europe.

PMID: 26132657 [PubMed - indexed for MEDLINE]

No association between global DNA methylation in peripheral blood and lung cancer risk in nonsmoking women: results from a multicenter study in Eastern and Central Europe.

Recent Research Articles from UNTHSC - Wed, 04/06/2016 - 06:38

No association between global DNA methylation in peripheral blood and lung cancer risk in nonsmoking women: results from a multicenter study in Eastern and Central Europe.

Eur J Cancer Prev. 2016 Apr 4;

Authors: Davis A, Tao MH, Chen J, Scelo G, Bencko V, Fabianova E, Foretova L, Janout V, Lissowska J, Mates D, Mates IN, Rudnai P, Zaridze D, Boffetta P

Abstract
Alterations in global DNA methylation have been suggested to play an important role in cancer development. We evaluated the association of global DNA methylation in peripheral blood with the risk of lung cancer in nonsmoking women from six countries in Central and Eastern Europe. This multicenter case-control study included primary, incident lung cancer cases diagnosed from 1998 to 2001 and controls frequency-matched for geographic area, sex, and age. Global methylation was assessed in peripheral blood DNA from 83 nonsmoking female cases and 181 nonsmoking female controls using the luminometric methylation assay (LUMA). Unconditional logistic regression models were used to estimate associations between DNA methylation in the blood and the risk of lung cancer. LUMA methylation level was not associated with the risk of lung cancer in nonsmoking women. Associations were not significantly different according to different strata of age, BMI, alcohol drinking, or second-hand tobacco smoke exposure status. In our study of nonsmoking women, the LUMA methylation level in peripheral blood was not associated with the risk of lung cancer. Our findings do not support an association of global blood DNA methylation with the risk of lung cancer in nonsmoking women.

PMID: 27045934 [PubMed - as supplied by publisher]

Nanoparticle Effects on Human Platelets in Vitro: A Comparison between PAMAM and Triazine Dendrimers.

Recent Research Articles from UNTHSC - Tue, 04/05/2016 - 10:29
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Nanoparticle Effects on Human Platelets in Vitro: A Comparison between PAMAM and Triazine Dendrimers.

Molecules. 2016;21(4)

Authors: Enciso AE, Neun B, Rodriguez J, Ranjan AP, Dobrovolskaia MA, Simanek EE

Abstract
Triazine and PAMAM dendrimers of similar size and number of cationic surface groups were compared for their ability to promote platelet aggregation. Triazine dendrimers (G3, G5 and G7) varied in molecular weight from 8 kDa-130 kDa and in surface groups 16-256. PAMAM dendrimers selected for comparison included G3 (7 kDa, 32 surface groups) and G6 (58 kDa, 256 surface groups). The treatment of human platelet-rich plasma (PRP) with low generation triazine dendrimers (0.01-1 µM) did not show any significant effect in human platelet aggregation in vitro; however, the treatment of PRP with larger generations promotes an effective aggregation. These results are in agreement with studies performed with PAMAM dendrimers, where large generations promote aggregation. Triazine dendrimers promote aggregation less aggressively than PAMAM dendrimers, a factor attributed to differences in cationic charge or the formation of supramolecular assemblies of dendrimers.

PMID: 27043508 [PubMed - as supplied by publisher]

Carbon Disulfide (CS2) Interference in Glucose Metabolism from Unconventional Oil and Gas Extraction and Processing Emissions.

Recent Research Articles from UNTHSC - Tue, 04/05/2016 - 10:29
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Carbon Disulfide (CS2) Interference in Glucose Metabolism from Unconventional Oil and Gas Extraction and Processing Emissions.

Environ Health Insights. 2016;10:51-7

Authors: Rich AL, Patel JT, Al-Angari SS

Abstract
Carbon disulfide (CS2) has been historically associated with the manufacturing of rayon, cellophane, and carbon tetrachloride production. This study is one of the first to identify elevated atmospheric levels of CS2 above national background levels and its mechanisms to dysregulate normal glucose metabolism. Interference in glucose metabolism can indirectly cause other complications (diabetes, neurodegenerative disease, and retinopathy), which may be preventable if proper precautions are taken. Rich et al found CS2 and 12 associated sulfide compounds present in the atmosphere in residential areas where unconventional shale oil and gas extraction and processing operations were occurring. Ambient atmospheric concentrations of CS2 ranged from 0.7 parts per billion by volume (ppbv) to 103 ppbv over a continuous 24-hour monitoring period. One-hour ambient atmospheric concentrations ranged from 3.4 ppbv to 504.6 ppbv. Using the U.S. Environmental Protection Agency Urban Air Toxic Monitoring Program study as a baseline comparison for atmospheric CS2 concentrations found in this study, it was determined that CS2 atmospheric levels were consistently elevated in areas where unconventional oil and gas extraction and processing occurred. The mechanisms by which CS2 interferes in normal glucose metabolism by dysregulation of the tryptophan metabolism pathway are presented in this study. The literature review found an increased potential for alteration of normal glucose metabolism in viscose rayon occupational workers exposed to CS2. Occupational workers in the energy extraction industry exposed to CS2 and other sulfide compounds may have an increased potential for glucose metabolism interference, which has been an indicator for diabetogenic effect and other related health impacts. The recommendation of this study is for implementation of regular monitoring of blood glucose levels in CS2-exposed populations as a preventative health measure.

PMID: 27042092 [PubMed]

Protein Modifications as Manifestations of Hyperglycemic Glucotoxicity in Diabetes and Its Complications.

Recent Research Articles from UNTHSC - Tue, 04/05/2016 - 10:29
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Protein Modifications as Manifestations of Hyperglycemic Glucotoxicity in Diabetes and Its Complications.

Biochem Insights. 2016;9:1-9

Authors: Zheng H, Wu J, Jin Z, Yan LJ

Abstract
Diabetes and its complications are hyperglycemic toxicity diseases. Many metabolic pathways in this array of diseases become aberrant, which is accompanied with a variety of posttranslational protein modifications that in turn reflect diabetic glucotoxicity. In this review, we summarize some of the most widely studied protein modifications in diabetes and its complications. These modifications include glycation, carbonylation, nitration, cysteine S-nitrosylation, acetylation, sumoylation, ADP-ribosylation, O-GlcNAcylation, and succination. All these posttranslational modifications can be significantly attributed to oxidative stress and/or carbon stress induced by diabetic redox imbalance that is driven by activation of pathways, such as the polyol pathway and the ADP-ribosylation pathway. Exploring the nature of these modifications should facilitate our understanding of the pathological mechanisms of diabetes and its associated complications.

PMID: 27042090 [PubMed]

Exosomes are unlikely involved in intercellular Nef transfer.

Recent Research Articles from UNTHSC - Tue, 04/05/2016 - 10:29
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Exosomes are unlikely involved in intercellular Nef transfer.

PLoS One. 2015;10(4):e0124436

Authors: Luo X, Fan Y, Park IW, He JJ

Abstract
HIV-1 Nef is an important pathogenic factor for HIV/AIDS pathogenesis. Several recent studies including ours have demonstrated that Nef can be transferred to neighboring cells and alters the function of these cells. However, how the intercellular Nef transfer occurs is in dispute. In the current study, we attempted to address this important issue using several complementary strategies, a panel of exosomal markers, and human CD4+ T lymphocyte cell line Jurkat and a commonly used cell line 293T. First, we showed that Nef was transferred from Nef-expressing or HIV-infected Jurkat to naïve Jurkat and other non-Jurkat cells and that the transfer required the membrane targeting function of Nef and was cell density-dependent. Then, we showed that Nef transfer was cell-cell contact-dependent, as exposure to culture supernatants or exosomes from HIV-infected Jurkat or Nef-expressing Jurkat and 293T led to little Nef detection in the target cells Jurkat. Thirdly, we demonstrated that Nef was only detected to be associated with HIV virions but not with acetylcholinesterase (AChE+) exosomes from HIV-infected Jurkat and not in the exosomes from Nef-expressing Jurkat. In comparison, when it was over-expressed in 293T, Nef was detected in detergent-insoluble AChE+/CD81 low/TSG101 low exosomes, but not in detergent-soluble AChE-/CD81 high/TSG101 high exosomes. Lastly, microscopic imaging showed no significant Nef detection in exosomal vesicle-like structures in and out 293T. Taken together, these results show that exosomes are unlikely involved in intercellular Nef transfer. In addition, this study reveals existence of two types of exosomes: AChE+/CD81 low/TSG101 low exosomes and AChE-/CD81 high/TSG101 high exosomes.

PMID: 25919665 [PubMed - indexed for MEDLINE]

A depressive endophenotype of poorer cognition among cognitively healthy community-dwelling adults: results from the Western Australia memory study.

Recent Research Articles from UNTHSC - Tue, 04/05/2016 - 10:29
Related Articles

A depressive endophenotype of poorer cognition among cognitively healthy community-dwelling adults: results from the Western Australia memory study.

Int J Geriatr Psychiatry. 2015 Aug;30(8):881-6

Authors: Johnson LA, Sohrabi HR, Hall JR, Kevin T, Edwards M, O'Bryant SE, Martins RN

Abstract
OBJECTIVE: The objective was to evaluate in a cognitively normal population the utility of an endophenotype of the depression-cognition link previously shown to be related to cognitive functioning in mild cognitive impairment and Alzheimer's disease.
METHODS: The data of 460 cognitively normal adults aged 32-92 years (M = 63.5, standard deviation = 9.24) from the Western Australian Memory Study with the Cross-national comparisons of the Cambridge Cognitive Examination-revised (CAMCOG-R) scores and 30-item Geriatric Depression Scale (GDS) scores were analyzed to determine the relationship between the five-item depressive endophenotype (DepE) scale drawn from the GDS and level of performance on a measure of cognitive functioning.
RESULTS: For the entire sample, there was a nonsignificant trend toward a negative relationship between DepE and CAMCOG-R scores. When analyzed for those 65 years and older, there was a significant negative relationship between the two measures (p = 0.001) with DepE scores significantly increasing the risk for performing more poorly on the CAMCOG-R (odds ratio = 1.53). Analysis of data for those 70 years and older showed that DepE was the only predictor significantly related to poorer CAMCOG-R performance (p = 0.001). For the 70 years and older group, DepE scores significantly increased the risk of poorer CAMCOG-R scores (odds ratio = 2.23). Analysis of the entire sample on the basis of ApoEε4 carrier status revealed that DepE scores were significantly negatively related only to ApoEε4 noncarrier regardless of age.
CONCLUSIONS: Elevated DepE scores are associated with poor neuropsychological performance among cognitively normal older adults. Use of the DepE may allow for the identification of a subset of older adults where depression is a primary factor in cognitive decline and who may benefit from antidepressant therapies.

PMID: 25394326 [PubMed - indexed for MEDLINE]

U.S. Physicians' Opinions About Accommodating Religiously Based Requests for Continued Life-Sustaining Treatment.

Recent Research Articles from UNTHSC - Mon, 04/04/2016 - 06:31

U.S. Physicians' Opinions About Accommodating Religiously Based Requests for Continued Life-Sustaining Treatment.

J Pain Symptom Manage. 2016 Mar 30;

Authors: Ayeh DD, Tak HJ, Yoon JD, Curlin FA

Abstract
CONTEXT: Families of critically ill patients occasionally request that physicians continue life-sustaining treatment (LST), sometimes giving religious reasons.
OBJECTIVES: To examine whether U.S. physicians are more likely to accommodate requests for LST that are based on religious reasons.
METHODS: In 2010 we surveyed 1156 practicing U.S. physicians from specialties likely to care for adult patients with advanced illness. The questionnaire included two randomized experimental vignettes: one where a family asked that LST be continued for a patient that met brain death criteria and a second where the son of an elderly patient with cancer insists on continuing LST. In both, we experimentally varied the reasons that the family member gave to justify the request, to see if physicians are more likely to accommodate a request based on a religious requirement or hope for a miracle, compared to no mention of either. For physicians' religious characteristics, we assessed their religious affiliation and level of religiosity.
RESULTS: For the patient meeting brain death criteria, physicians were more likely to accommodate the request to continue LST when the family mentioned their Orthodox Jewish community (85% vs. 70%, P<0.001). For the patient with metastatic cancer, physicians were more likely to accommodate the request when the son said his religious faith does not permit discontinuing LST (65% vs. 46%, P<0.001), but not when he said he expected divine healing (50% vs. 46%).
CONCLUSION: Physicians appear more willing to accommodate requests to continue LST when those requests are based on particular religious communities or traditions, but not when based on expectations of divine healing.

PMID: 27039013 [PubMed - as supplied by publisher]

Conjunctival Lesions and Vision Impairment After Gastrointestinal Surgery.

Recent Research Articles from UNTHSC - Fri, 04/01/2016 - 06:43

Conjunctival Lesions and Vision Impairment After Gastrointestinal Surgery.

JAMA Ophthalmol. 2016 Mar 31;

Authors: Kirkland KA, Swann RE

PMID: 27031091 [PubMed - as supplied by publisher]

Locomotor, discriminative stimulus, and place conditioning effects of MDAI in rodents.

Recent Research Articles from UNTHSC - Thu, 03/31/2016 - 06:31

Locomotor, discriminative stimulus, and place conditioning effects of MDAI in rodents.

Behav Pharmacol. 2016 Mar 29;

Authors: Gatch MB, Dolan SB, Forster MJ

Abstract
5,6-Methylenedioxy-2-aminoindane (MDAI) has become a common substitute for (±)-3,4-methylenedioxymethamphetamine (MDMA) in Ecstasy. MDAI is known to produce MDMA-like discriminative stimulus effects, but it is not known whether MDAI has psychostimulant or hallucinogen-like effects. MDAI was tested for locomotor stimulant effects in mice and subsequently for discriminative stimulus effects in rats trained to discriminate cocaine (10 mg/kg, intraperitoneally), methamphetamine (1 mg/kg, intraperitoneally), ±MDMA (1.5 mg/kg, intraperitoneally), or (-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (0.5 mg/kg, intraperitoneally) from saline. The ability of MDAI to produce conditioned place preference was also tested in mice. MDAI (3 to 30 mg/kg) depressed locomotor activity from 10 to 60 min. A rebound stimulant effect was observed at 1 to 3.5 h following 30 mg/kg. Lethality occurred in 8/8 mice following 100 mg/kg MDAI. Similarly, MDMA depressed locomotor activity immediately following the administration of 0.25 mg/kg and stimulant effects were observed 50-70 min following the administration of 0.5 and 1 mg/kg. MDAI fully substituted for the discriminative stimulus effects of MDMA (2.5 mg/kg), (-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (5 mg/kg), and cocaine (7.5 mg/kg), but produced only 73% methamphetamine-appropriate responding at a dose that suppressed responding (7.5 mg/kg). MDAI produced tremors at 10 mg/kg in one methamphetamine-trained rat. MDAI produced conditioned place preference from 0.3 to 10 mg/kg. The effects of MDAI on locomotor activity and drug discrimination were similar to those produced by MDMA, having both psychostimulant-like and hallucinogen-like effects; thus, MDAI may have similar abuse potential as MDMA.

PMID: 27028902 [PubMed - as supplied by publisher]

N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects.

Recent Research Articles from UNTHSC - Thu, 03/31/2016 - 06:31

N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects.

Exp Physiol. 2016 Mar 1;101(3):387-396

Authors: Jouett NP, Moralez G, White DW, Eubank WL, Chen S, Tian J, Smith ML, Zimmerman MC, Raven PB

Abstract
NEW FINDINGS: What is the central question of this study? This study evaluated the following central question: does N-acetylcysteine (N-AC), an antioxidant that readily penetrates the blood-brain barrier, have the capability to reduce the increase in sympathetic nerve activity observed during hyperacute intermittent hypoxia? What is the main finding and its importance? We demonstrate that N-AC decreases muscle sympathetic nerve activity in response to hyperacute intermittent hypoxia versus placebo control. This finding suggests that antioxidants, such as N-AC, have therapeutic potential in obstructive sleep apnoea. This investigation tested the following hypotheses: that (i) N-acetylcysteine (N-AC) attenuates hyperacute intermittent hypoxia-induced sympathoexcitation, (ii) without elevating superoxide measured in peripheral venous blood. Twenty-eight healthy human subjects were recruited to the study. One hour before experimentation, each subject randomly ingested either 70 mg kg(-1) of N-AC (n = 16) or vehicle placebo (n = 12). Three-lead ECG and arterial blood pressure, muscle sympathetic nerve activity (n = 17) and whole-blood superoxide concentration (using electron paramagnetic resonance spectroscopy; n = 12) were measured. Subjects underwent a 20 min hyperacute intermittent hypoxia training (hAIHT) protocol that consisted of cyclical end-expiratory apnoeas with 100% nitrogen. N-AC decreased muscle sympathetic nerve activity after hAIHT compared with placebo (P < 0.02). However, N-AC did not alter superoxide concentrations in venous blood compared with placebo (P > 0.05). Moreover, hAIHT did not increase superoxide concentrations in the peripheral circulation as measured by electron paramagnetic resonance (P > 0.05). Based on these findings, we contend that (i) hAIHT and (ii) the actions of N-AC in hAIHT are primarily mediated centrally rather than peripherally, although central measurements of reactive oxygen species are difficult to obtain in human subjects, thus making this assertion difficult to verify. This investigation suggests the possibility of developing a pharmaceutical therapy to inhibit the sympathoexcitation associated with obstructive sleep apnoea.

PMID: 27027616 [PubMed - as supplied by publisher]

Effects of the Ion PGM™ Hi-Q™ sequencing chemistry on sequence data quality.

Recent Research Articles from UNTHSC - Thu, 03/31/2016 - 06:31

Effects of the Ion PGM™ Hi-Q™ sequencing chemistry on sequence data quality.

Int J Legal Med. 2016 Mar 30;

Authors: Churchill JD, King JL, Chakraborty R, Budowle B

Abstract
Massively parallel sequencing (MPS) offers substantial improvements over current forensic DNA typing methodologies such as increased resolution, scalability, and throughput. The Ion PGM™ is a promising MPS platform for analysis of forensic biological evidence. The system employs a sequencing-by-synthesis chemistry on a semiconductor chip that measures a pH change due to the release of hydrogen ions as nucleotides are incorporated into the growing DNA strands. However, implementation of MPS into forensic laboratories requires a robust chemistry. Ion Torrent's Hi-Q™ Sequencing Chemistry was evaluated to determine if it could improve on the quality of the generated sequence data in association with selected genetic marker targets. The whole mitochondrial genome and the HID-Ion STR 10-plex panel were sequenced on the Ion PGM™ system with the Ion PGM™ Sequencing 400 Kit and the Ion PGM™ Hi-Q™ Sequencing Kit. Concordance, coverage, strand balance, noise, and deletion ratios were assessed in evaluating the performance of the Ion PGM™ Hi-Q™ Sequencing Kit. The results indicate that reliable, accurate data are generated and that sequencing through homopolymeric regions can be improved with the use of Ion Torrent's Hi-Q™ Sequencing Chemistry. Overall, the quality of the generated sequencing data supports the potential for use of the Ion PGM™ in forensic genetic laboratories.

PMID: 27025714 [PubMed - as supplied by publisher]

Δ9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids found on the gray market.

Recent Research Articles from UNTHSC - Wed, 03/30/2016 - 06:40
Related Articles

Δ9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids found on the gray market.

Behav Pharmacol. 2015 Aug;26(5):460-8

Authors: Gatch MB, Forster MJ

Abstract
When synthetic cannabinoid compounds became controlled by state and federal governments, different, noncontrolled compounds began to appear as marijuana substitutes. Unlike the scheduled cannabinoids, the newer compounds have not been characterized for potency and efficacy in preclinical studies. The purpose of these experiments was to determine whether some of the more recent synthetic compounds sold as marijuana substitutes have behavioral effects similar to those of Δ-tetrahydrocannabinol (Δ-THC), the pharmacologically active compound in marijuana. The compounds UR-144, XLR-11, AKB-48 (APINACA), PB-22 (QUPIC), 5F-PB-22, and AB-FUBINACA were tested for locomotor depressant effects in male Swiss-Webster mice and subsequently for their ability to substitute for Δ-THC (3 mg/kg, intraperitoneally) in drug discrimination experiments with male Sprague-Dawley rats. UR-144, XLR-11, AKB-48, and AB-FUBINACA each decreased locomotor activity for up to 90 min, whereas PB-22 and 5F-PB-22 produced depressant effects lasting 120-150 min. Each of the compounds fully substituted for the discriminative stimulus effects of Δ-THC. These findings confirm the suggestion that these compounds have marijuana-like psychoactive effects and abuse liability.

PMID: 26061356 [PubMed - indexed for MEDLINE]

ERG oncoprotein inhibits ANXA2 expression and function in prostate cancer.

Recent Research Articles from UNTHSC - Wed, 03/30/2016 - 06:40
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ERG oncoprotein inhibits ANXA2 expression and function in prostate cancer.

Mol Cancer Res. 2015 Feb;13(2):368-79

Authors: Griner NB, Young D, Chaudhary P, Mohamed AA, Huang W, Chen Y, Sreenath T, Dobi A, Petrovics G, Vishwanatha JK, Sesterhenn IA, Srivastava S, Tan SH

Abstract
UNLABELLED: Overexpression of ERG in the prostate epithelium, due to chromosomal translocations, contributes to prostate tumorigenesis. Here, genomic analysis of ERG siRNA-treated prostate cells harboring the endogenous TMPRSS2-ERG fusion revealed an inverse relationship between ERG and Annexin A2 (ANXA2) expression at both the RNA and protein level. ANXA2, a Ca(2+)-dependent and phospholipid-binding protein, is involved in various cellular functions, including maintenance of epithelial cell polarity. Mechanistic studies defined the prostate-specific transcription start site of ANXA2 and showed that the recruitment of ERG to the ANXA2 promoter is required for transcriptional repression by ERG. Knockdown of ERG enhanced the apical localization of ANXA2, the bundling of actin filaments at cell-cell junctions and formation of a polarized epithelial phenotype. ERG overexpression disrupted ANXA2-mediated cell polarity and promoted epithelial-mesenchymal transition (EMT) by inhibiting CDC42 and RHOA, and by activating cofilin. Immunohistochemistry demonstrated a reciprocal relationship of ANXA2 and ERG expression in a large fraction of primary prostate cancer clinical specimens. ANXA2 was absent or markedly reduced in ERG(+) tumors, which were mostly well differentiated. ERG(-) tumors, meanwhile, expressed moderate to high levels of ANXA2, and were either poorly differentiated or displayed subsets of poorly differentiated cells. Taken together, the transcriptional repression of ANXA2 by ERG in prostate epithelial cells plays a critical role in abrogating differentiation, promoting EMT, and in the reciprocal correlation of ERG and ANXA2 expression observed in human prostate cancer.
IMPLICATIONS: ANXA2 is a new component of the ERG network with potential to enhance biologic stratification and therapeutic targeting of ERG-stratified prostate cancers.

PMID: 25344575 [PubMed - indexed for MEDLINE]

Comparing biological markers of Alzheimer's disease across blood fraction and platforms: Comparing apples to oranges.

Recent Research Articles from UNTHSC - Tue, 03/29/2016 - 06:29

Comparing biological markers of Alzheimer's disease across blood fraction and platforms: Comparing apples to oranges.

Alzheimers Dement (Amst). 2016;3:27-34

Authors: O'Bryant SE, Lista S, Rissman RA, Edwards M, Zhang F, Hall J, Zetterberg H, Lovestone S, Gupta V, Graff-Radford N, Martins R, Jeromin A, Waring S, Oh E, King M, Baker L, Hampel H

Abstract
INTRODUCTION: This study investigated the comparability of potential AD biomarkers across blood fractions and assay platforms.
METHODS: Non-fasting serum and plasma samples from 300 participants (150 AD patients, 150 controls) were analyzed. Proteomic markers were obtained via electrochemiluminescence or Luminex technology. Comparisons were conducted via Pearson correlations. The relative importance of proteins within an AD diagnostic profile was examined using random forest importance plots.
RESULTS: On the MSD multi-plex platform, 10 out of the 21 markers shared >50% of the variance across blood fractions (SAA R(2)=0.99, IL10 R(2)=0.95, FABP R(2)=0.94, I309 R(2)=0.94, IL5 R(2)=0.94, IL6 R(2)=0.94, Eotaxin3 R(2)=0.91, IL18 R(2)=0.87, sTNFR1 R(2)=0.85, PPY R(2)=0.81). When examining protein concentrations across platforms, only five markers shared >50% of the variance (β2M R(2)=0.92, IL18 R(2)=0.80, FVII R(2)=0.78, CRP R(2)=0.74, FABP R(2)=0.70).
DISCUSSION: The current findings highlight the importance of considering blood fractions and assay platforms when searching for AD relevant biomarkers.

PMID: 27019866 [PubMed - as supplied by publisher]

Antiangiogenic mechanisms and factors in breast cancer treatment.

Recent Research Articles from UNTHSC - Sat, 03/26/2016 - 06:37

Antiangiogenic mechanisms and factors in breast cancer treatment.

J Carcinog. 2016;15:1

Authors: Castañeda-Gill JM, Vishwanatha JK

Abstract
Breast cancer is known to metastasize in its latter stages of existence. The different angiogenic mechanisms and factors that allow for its progression are reviewed in this article. Understanding these mechanisms and factors will allow researchers to design drugs to inhibit angiogenic behaviors and control the rate of tumor growth.

PMID: 27013929 [PubMed]

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

Recent Research Articles from UNTHSC - Sat, 03/26/2016 - 06:37

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

Alzheimers Dement. 2016 Mar;12(3):292-323

Authors: Dubois B, Hampel H, Feldman HH, Scheltens P, Aisen P, Andrieu S, Bakardjian H, Benali H, Bertram L, Blennow K, Broich K, Cavedo E, Crutch S, Dartigues JF, Duyckaerts C, Epelbaum S, Frisoni GB, Gauthier S, Genthon R, Gouw AA, Habert MO, Holtzman DM, Kivipelto M, Lista S, Molinuevo JL, O'Bryant SE, Rabinovici GD, Rowe C, Salloway S, Schneider LS, Sperling R, Teichmann M, Carrillo MC, Cummings J, Jack CR, Proceedings of the Meeting of the International Working Group (IWG) and the American Alzheimer's Association on “The Preclinical State of AD”; July 23, 2015; Washington DC, USA

Abstract
During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

PMID: 27012484 [PubMed - in process]

Large-scale recent expansion of European patrilineages shown by population resequencing.

Recent Research Articles from UNTHSC - Sat, 03/26/2016 - 06:37
Related Articles

Large-scale recent expansion of European patrilineages shown by population resequencing.

Nat Commun. 2015;6:7152

Authors: Batini C, Hallast P, Zadik D, Delser PM, Benazzo A, Ghirotto S, Arroyo-Pardo E, Cavalleri GL, de Knijff P, Dupuy BM, Eriksen HA, King TE, López de Munain A, López-Parra AM, Loutradis A, Milasin J, Novelletto A, Pamjav H, Sajantila A, Tolun A, Winney B, Jobling MA

Abstract
The proportion of Europeans descending from Neolithic farmers ∼ 10 thousand years ago (KYA) or Palaeolithic hunter-gatherers has been much debated. The male-specific region of the Y chromosome (MSY) has been widely applied to this question, but unbiased estimates of diversity and time depth have been lacking. Here we show that European patrilineages underwent a recent continent-wide expansion. Resequencing of 3.7 Mb of MSY DNA in 334 males, comprising 17 European and Middle Eastern populations, defines a phylogeny containing 5,996 single-nucleotide polymorphisms. Dating indicates that three major lineages (I1, R1a and R1b), accounting for 64% of our sample, have very recent coalescent times, ranging between 3.5 and 7.3 KYA. A continuous swathe of 13/17 populations share similar histories featuring a demographic expansion starting ∼ 2.1-4.2 KYA. Our results are compatible with ancient MSY DNA data, and contrast with data on mitochondrial DNA, indicating a widespread male-specific phenomenon that focuses interest on the social structure of Bronze Age Europe.

PMID: 25988751 [PubMed - indexed for MEDLINE]

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