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Alcohol Sales to Youth: Data from Rural Communities Within the Cherokee Nation.

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Alcohol Sales to Youth: Data from Rural Communities Within the Cherokee Nation.

Prev Sci. 2016 Jan;17(1):32-9

Authors: Lynne-Landsman SD, Kominsky TK, Livingston MD, Wagenaar AC, Komro KA

Abstract
Access to alcohol among individuals under 21 years of age continues to be a public health concern with approximately 5000 youth deaths attributable to alcohol each year (US Department of Health and Human Services 2007). To date, there is no research on youth access to alcohol from commercial sources within rural communities with large populations of Native American families. We evaluated commercial access to alcohol by underage-appearing female confederates in 4 rural towns within the Cherokee Nation, a non-reservation tribal jurisdiction that includes a high proportion of Native Americans embedded within a predominately White population. Alcohol purchase attempts were conducted approximately every 4 weeks on 10 occasions for a total of 997 alcohol purchase attempts. In addition to purchase attempt outcome, we collected data on characteristics of the outlets and clerks. Alcohol was sold to confederates without use of age identification on 23 % of all purchase attempts. Across repeated attempts, 76 % of outlets sold alcohol to a confederate at least once. Males and younger clerks were more likely to sell alcohol to the confederates. Grocery stores and gas stations were more likely to sell alcohol to the confederate than liquor stores, but this effect was no longer significant once seller age was accounted for in a multivariable model. Three out of 4 outlets sold alcohol to young-appearing buyers at least once across repeated attempts. Results reinforce the continuing need for regular enforcement of laws against selling alcohol to minors.

PMID: 26228479 [PubMed - indexed for MEDLINE]

Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing.

Recent Research Articles from UNTHSC - Fri, 09/30/2016 - 07:32

Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing.

Forensic Sci Int Genet. 2016 Sep 20;25:198-209

Authors: Wendt FR, Warshauer DH, Zeng X, Churchill JD, Novroski NM, Song B, King JL, LaRue BL, Budowle B

Abstract
Short tandem repeat (STR) loci are the traditional markers used for kinship, missing persons, and direct comparison human identity testing. These markers hold considerable value due to their highly polymorphic nature, amplicon size, and ability to be multiplexed. However, many STRs are still too large for use in analysis of highly degraded DNA. Small bi-allelic polymorphisms, such as insertions/deletions (INDELs), may be better suited for analyzing compromised samples, and their allele size differences are amenable to analysis by capillary electrophoresis. The INDEL marker allelic states range in size from 2 to 6 base pairs, enabling small amplicon size. In addition, heterozygote balance may be increased by minimizing preferential amplification of the smaller allele, as is more common with STR markers. Multiplexing a large number of INDELs allows for generating panels with high discrimination power. The Nextera™ Rapid Capture Custom Enrichment Kit (Illumina, Inc., San Diego, CA) and massively parallel sequencing (MPS) on the Illumina MiSeq were used to sequence 68 well-characterized INDELs in four major US population groups. In addition, the STR Allele Identification Tool: Razor (STRait Razor) was used in a novel way to analyze INDEL sequences and detect adjacent single nucleotide polymorphisms (SNPs) and other polymorphisms. This application enabled the discovery of unique allelic variants, which increased the discrimination power and decreased the single-locus random match probabilities (RMPs) of 22 of these well-characterized INDELs which can be considered as microhaplotypes. These findings suggest that additional microhaplotypes containing human identification (HID) INDELs may exist elsewhere in the genome.

PMID: 27685342 [PubMed - as supplied by publisher]

Nur77 exacerbates PC12 cellular injury in vitro by aggravating mitochondrial impairment and endoplasmic reticulum stress.

Recent Research Articles from UNTHSC - Fri, 09/30/2016 - 07:32

Nur77 exacerbates PC12 cellular injury in vitro by aggravating mitochondrial impairment and endoplasmic reticulum stress.

Sci Rep. 2016;6:34403

Authors: Gao H, Chen Z, Fu Y, Yang X, Weng R, Wang R, Lu J, Pan M, Jin K, McElroy C, Tang B, Xia Y, Wang Q

Abstract
The nuclear orphan receptor, Nur77 plays important roles in neuroimflammation, apoptosis, and dopaminergic neurodegeneration. We conducted a further mechanistic investigation into the association of Nur77 with cell death. Cytosporone B (Csn-B), an agonist for Nur77, and Nur77 knockdown were adopted in the 6-hydroxydopamine (OHDA)-lesioned PC12 cells to investigate the mechanisms underlying Nur77-mediated injury. The 6-OHDA incubation caused Nur77 translocation from the nucleus to cytosol and Endoplasm reticulum (ER) and induced co-localization of Tom20/Nur77 and Protein Disulfide Isomerase (PDI)/Nur77. Nur77 activation further decreased cell viability, aggravated intracellular LDH release, intracellular Ca(2+), ROS levels, apoptosis, ER tress and, mitochondrial transmembrane potential (ΔΨm) decline. In addition, Nur77 activation significantly enhanced the efficiency of autophagy as indicated by an up-regulation of Beclin-1/LC-3 and downregulation of p62, and aggravated mitochondrial dysfunctions and ER stress as shown by increased HSP60/Cytochrome C (Cyt C) and CHOP-ATF3 levels respectively. These changes could be partially reversed by Nur77 knockdown. Moreover, Nur77 activation upregulated PINK1 and downregulated Parkin levels. We conclude that Nur77 exacerbates PC12 cell death at least partially by aggravating the mitochondrial impairment and ER stress and enhancing autophagy. We propose that Nur77 is likely a critical target in the PD therapy.

PMID: 27679973 [PubMed - as supplied by publisher]

Ecogeographic variation across morphofunctional units of the human nose.

Recent Research Articles from UNTHSC - Wed, 09/28/2016 - 07:31

Ecogeographic variation across morphofunctional units of the human nose.

Am J Phys Anthropol. 2016 Sep 27;

Authors: Maddux SD, Butaric LN, Yokley TR, Franciscus RG

Abstract
OBJECTIVES: Although the internal nose is overwhelmingly responsible for heat and moisture exchange during respiration, external nasal morphology is more commonly cited as evincing climatic adaptation in humans. Here, we assess variation across all four morphofunctional units of the complete nasorespiratory tract (external pyramid, nasal aperture, internal nasal fossa, and nasopharynx) to determine which units provide the strongest evidence of climatic adaptation.
MATERIALS AND METHODS: We employ 20 linear measurements collected on 837 modern human crania from major geographic (Arctic Circle, Asia, Australia, Europe, Africa) and climatic (polar, temperate, hot-arid, tropical) zones. In conjunction with associated climatic and geographic data, these morphological data are employed in multivariate analyses to evaluate the associations between each of these functional nasal units and climate.
RESULTS: The external pyramid and nasopharynx exhibit virtually no evidence of climate-mediated morphology across the regional samples, while apparent associations between climate and nasal aperture morphology appear influenced by the geographic (and likely genetic) proximities of certain populations. Only the internal nasal fossa exhibits an ecogeographic distribution consistent with climatic adaptation, with crania from colder and/or drier environments displaying internal nasal fossae that are longer, taller, and narrower (especially superiorly) compared to those from hotter and more humid environments.
CONCLUSIONS: Our study indicates that the internal nasal fossa exhibits a stronger association with climate compared to other aspects of the human nose. Further, our study supports suggestions that regional variation in internal nasal fossa morphology reflects demands for heat and moisture exchange via adjustment of internal nasal airway dimensions. Our study thus provides empirical support for theoretical assertions related to nasorespiratory function, with important implications for understanding human nasal evolution.

PMID: 27670377 [PubMed - as supplied by publisher]

Diversity of Gene Expression in Hepatocellular Carcinoma Cells.

Recent Research Articles from UNTHSC - Tue, 09/27/2016 - 07:35
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Diversity of Gene Expression in Hepatocellular Carcinoma Cells.

Genomics Proteomics Bioinformatics. 2015 Dec;13(6):377-82

Authors: Zhang F, Cui L, Kuo MD

Abstract
Understanding tumor diversity has been a long-lasting and challenging question for researchers in the field of cancer heterogeneity or tumor evolution. Studies have reported that compared to normal cells, there is a higher genetic diversity in tumor cells, while higher genetic diversity is associated with higher progression risks of tumor. We thus hypothesized that tumor diversity also holds true at the gene expression level. To test this hypothesis, we used t-test to compare the means of Simpson's diversity index for gene expression (SDIG) between tumor and non-tumor samples. We found that the mean SDIG in tumor tissues is significantly higher than that in the non-tumor or normal tissues (P<0.05) for most datasets. We also combined microarrays and next-generation sequencing data for validation. This cross-platform and cross-experimental validation greatly increased the reliability of our results.

PMID: 26779818 [PubMed - indexed for MEDLINE]

Initiation of calorie restriction in middle-aged male rats attenuates aging-related motoric decline and bradykinesia without increased striatal dopamine.

Recent Research Articles from UNTHSC - Tue, 09/27/2016 - 07:35
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Initiation of calorie restriction in middle-aged male rats attenuates aging-related motoric decline and bradykinesia without increased striatal dopamine.

Neurobiol Aging. 2016 Jan;37:192-207

Authors: Salvatore MF, Terrebonne J, Fields V, Nodurft D, Runfalo C, Latimer B, Ingram DK

Abstract
Aging-related bradykinesia affects ∼ 15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacologic therapeutics, noninvasive lifestyle strategies should be identified to diminish its risk and identify the neurobiological targets to reduce aging-related bradykinesia. Early-life, long-term calorie restriction (CR) attenuates aging-related bradykinesia in rodents. Here, we addressed whether CR initiation at middle age could attenuate aging-related bradykinesia and motoric decline measured as rotarod performance. A 30% CR regimen was implemented for 6 months duration in 12-month-old male Brown-Norway Fischer 344 F1 hybrid rats after establishing individual baseline locomotor activities. Locomotor capacity was assessed every 6 weeks thereafter. The ad libitum group exhibited predictably decreased locomotor activity, except movement speed, out to 18 months of age. In contrast, in the CR group, movement number and horizontal activity did not decrease during the 6-month trial, and aging-related decline in rotarod performance was attenuated. The response to CR was influenced by baseline locomotor activity. The lower the locomotor activity level at baseline, the greater the response to CR. Rats in the lower 50th percentile surpassed their baseline level of activity, whereas rats in the top 50th percentile decreased at 6 weeks and then returned to baseline by 12 weeks of CR. We hypothesized that nigrostriatal dopamine tissue content would be greater in the CR group and observed a modest increase only in substantia nigra with no group differences in striatum, nucleus accumbens, or ventral tegmental area. These results indicate that initiation of CR at middle age may reduce aging-related bradykinesia, and, furthermore, subjects with below average locomotor activity may increase baseline activity. Sustaining nigral dopamine neurotransmission may be one component of preserving locomotor capabilities during aging.

PMID: 26610387 [PubMed - indexed for MEDLINE]

Implantable Medical Device Website Efficacy in Informing Consumers Weighing Benefits/Risks of Health Care Options.

Recent Research Articles from UNTHSC - Sat, 09/24/2016 - 07:36

Implantable Medical Device Website Efficacy in Informing Consumers Weighing Benefits/Risks of Health Care Options.

J Health Commun. 2016 Sep 23;:1-6

Authors: Wagner T, Lindstadt C, Jeon Y, Mackert M

Abstract
As more individuals turn to the Internet for health-related information and technology increases the availability and use of implantable medical devices (IMDs), the websites marketing these devices will increase. Healthy People 2020 mandates increased understandability and usability of health-related websites. This project used social cognitive theory (SCT) and health literacy constructs from the Institute of Medicine and National Institutes of Health to analyze eight IMD websites. Despite current recommendations, none of the websites considered for this study offered content of an appropriate reading level in conjunction with the United States average of eighth grade, and 75% of the sites failed to satisfy more than one health literacy construct. Most of the websites lacked many of the SCT constructs. More attention is needed to improve the usability of these and future IMD websites to simultaneously meet the goal of marketing IMDs and the Healthy People 2020 goals to educate patients and promote public health.

PMID: 27662117 [PubMed - as supplied by publisher]

The Increasing Prevalence in Intersex Variation from Toxicological Dysregulation in Fetal Reproductive Tissue Differentiation and Development by Endocrine-Disrupting Chemicals.

Recent Research Articles from UNTHSC - Sat, 09/24/2016 - 07:36

The Increasing Prevalence in Intersex Variation from Toxicological Dysregulation in Fetal Reproductive Tissue Differentiation and Development by Endocrine-Disrupting Chemicals.

Environ Health Insights. 2016;10:163-71

Authors: Rich AL, Phipps LM, Tiwari S, Rudraraju H, Dokpesi PO

Abstract
An increasing number of children are born with intersex variation (IV; ambiguous genitalia/hermaphrodite, pseudohermaphroditism, etc.). Evidence shows that endocrine-disrupting chemicals (EDCs) in the environment can cause reproductive variation through dysregulation of normal reproductive tissue differentiation, growth, and maturation if the fetus is exposed to EDCs during critical developmental times in utero. Animal studies support fish and reptile embryos exhibited IV and sex reversal when exposed to EDCs. Occupational studies verified higher prevalence of offspring with IV in chemically exposed workers (male and female). Chemicals associated with endocrine-disrupting ability in humans include organochlorine pesticides, poly-chlorinated biphenyls, bisphenol A, phthalates, dioxins, and furans. Intersex individuals may have concurrent physical disorders requiring lifelong medical intervention and experience gender dysphoria. An urgent need exists to determine which chemicals possess the greatest risk for IV and the mechanisms by which these chemicals are capable of interfering with normal physiological development in children.

PMID: 27660460 [PubMed]

Serum YKL-40, a prognostic marker in patients with large-artery atherosclerotic stroke.

Recent Research Articles from UNTHSC - Thu, 09/22/2016 - 07:35

Serum YKL-40, a prognostic marker in patients with large-artery atherosclerotic stroke.

Acta Neurol Scand. 2016 Sep 21;

Authors: Chen XL, Li Q, Huang WS, Lin YS, Xue J, Wang B, Jin KL, Shao B

Abstract
BACKGROUND AND PURPOSE: Inflammation comprises important aspects of large-artery atherosclerosis (LAA) stroke pathophysiology. YKL-40 is a new and emerging biomarker that is associated with both acute and chronic inflammations. Elevated serum concentrations of YKL-40 have been reported in patients with atherosclerosis and other cardiovascular diseases. This study investigates whether serum YKL-40 concentrations on admission can predict 3-month clinical outcomes after LAA stroke.
METHODS: We recruited control patients (n=85) and those with LAA stroke (n=141) according to the TOAST classification system. The modified Rankin scale at 3 months after stroke was used to evaluate the prognosis. The prognostic accuracy was assessed by the receiver operating characteristic curve.
RESULTS: Serum YKL-40 level was significantly higher for LAA patients than for controls (P<.001). Patients with poor outcomes (n=36) had significantly increased serum YKL-40 concentrations on admission (P=.01). High YKL-40 levels predicted poor functional outcome (OR=6.47, P=.02). Moreover, the combination of YKL-40 level and the NIHSS score could improve the prognostic accuracy of the NIHSS in predicting functional outcome (combined areas under the curve, 0.87; 95% CI, 0.80-0.94; P<.001).
CONCLUSIONS: The level of serum YKL-40 is a significant and independent biomarker to predict the clinical outcome of LAA stroke.

PMID: 27650381 [PubMed - as supplied by publisher]

Neurogenic mechanisms underlying the rapid onset of sympathetic responses to intermittent hypoxia.

Recent Research Articles from UNTHSC - Thu, 09/22/2016 - 07:35
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Neurogenic mechanisms underlying the rapid onset of sympathetic responses to intermittent hypoxia.

J Appl Physiol (1985). 2015 Dec 15;119(12):1441-8

Authors: Mifflin S, Cunningham JT, Toney GM

Abstract
Sleep apnea (SA) leads to metabolic abnormalities and cardiovascular dysfunction. Rodent models of nocturnal intermittent hypoxia (IH) are used to mimic arterial hypoxemias that occur during SA. This mini-review focuses on our work examining central nervous system (CNS) mechanisms whereby nocturnal IH results in increased sympathetic nerve discharge (SND) and hypertension (HTN) that persist throughout the 24-h diurnal period. Within the first 1-2 days of IH, arterial pressure (AP) increases even during non-IH periods of the day. Exposure to IH for 7 days biases nucleus tractus solitarius (NTS) neurons receiving arterial chemoreceptor inputs toward increased discharge, providing a substrate for persistent activation of sympathetic outflow. IH HTN is blunted by manipulations that reduce angiotensin II (ANG II) signaling within the forebrain lamina terminalis suggesting that central ANG II supports persistent IH HTN. Inhibition of the hypothalamic paraventricular nucleus (PVN) reduces ongoing SND and acutely lowers AP in IH-conditioned animals. These findings support a role for the PVN, which integrates information ascending from NTS and descending from the lamina terminalis, in sustaining IH HTN. In summary, our findings indicate that IH rapidly and persistently activates a central circuit that includes the NTS, forebrain lamina terminalis, and the PVN. Our working model holds that NTS neuromodulation increases transmission of arterial chemoreceptor inputs, increasing SND via connections with PVN and rostral ventrolateral medulla. Increased circulating ANG II sensed by the lamina terminalis generates yet another excitatory drive to PVN. Together with adaptations intrinsic to the PVN, these responses to IH support rapid onset neurogenic HTN.

PMID: 25997944 [PubMed - indexed for MEDLINE]

Correlation of Lipid Profile and Risk of Developing Type 2 Diabetes Mellitus in 10-14 Year Old Children.

Recent Research Articles from UNTHSC - Tue, 09/20/2016 - 07:32
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Correlation of Lipid Profile and Risk of Developing Type 2 Diabetes Mellitus in 10-14 Year Old Children.

Cell Physiol Biochem. 2016 Sep 19;39(5):1695-1704

Authors: Habiba NM, Fulda KG, Basha R, Shah D, Fernando S, Nguyen B, Xiong Y, Franks SF, Matches SJ, Magie RD, Bowman WP

Abstract
BACKGROUND/AIMS: The role of lipid profile in predicting the risk of Type 2 diabetes mellitus (T2DM) in children is not clearly established. Our aim is to screen non-diabetic children aged 10-14 years for risk of developing T2DM and evaluate the association of abnormal lipids and socioeconomic status (SES).
METHODS: Data on race/ethnicity, family history, body mass index percentile, blood pressure and presence of neck pigmentation (acanthosis nigricans) were collected from 149 non-diabetic children. Using these factors, children were classified into low risk (<3 risk factors) and high risk (>3 risk factors) groups. Logistic regression model and chi-square tests were used to evaluate the association of blood lipid profile and demographic variables. Independent t-test was used to compare the ratio of Total Cholesterol (TC) and High Density Lipids (HDL) with T2DM risk.
RESULTS: 60% of children were at high risk for developing T2DM. HDL (p<0.001), triglycerides (p=0.02) and TC/HDL ratio (p<.001) were significantly abnormal in high risk group. Low SES showed a marginal association with high risk group. There were no gender or age differences between high and low risk groups.
CONCLUSIONS: The significant determinants associated with high risk group were modifiable factors providing an opportunity for early intervention and prevention.

PMID: 27642750 [PubMed - as supplied by publisher]

Molecular markers of amnestic mild cognitive impairment among Mexican Americans.

Recent Research Articles from UNTHSC - Tue, 09/20/2016 - 07:32
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Molecular markers of amnestic mild cognitive impairment among Mexican Americans.

J Alzheimers Dis. 2015;49(1):221-8

Authors: Edwards M, Hall J, Williams B, Johnson L, O'Bryant S

Abstract
BACKGROUND: Mexican Americans face a significant health disparity when it comes to Alzheimer's disease (AD) as they present with higher rates of the disease and develop AD at an earlier age compared to other ethnic groups. Recent work identified a proteomic profile of AD among this population; however, no work to date has sought to examine the biological profile of pre-AD among Mexican Americans.
OBJECTIVE: This study aims to identify an amnestic mild cognitive impairment (aMCI) proteomic profile among Mexican Americans.
METHODS: Data were analyzed from 284 Mexican American participants (aMCI, n = 73; normal controls, n = 211) from the Health & Aging Brain among Latino Elders study. Fasting serum samples were analyzed using a multi-plex biomarker assay platform. A biomarker profile was generated using random forest analyses.
RESULTS: Among aMCI cases, the biomarker profile was found to be largely inflammatory with the top three markers shown to include TNFα, IL10, and TARC. The overall diagnostic accuracy of the biomarkers in detecting aMCI was 96% (sensitivity = 0.82; specificity = 0.97). Inclusion of clinical variables with the selected biomarkers did not impact the overall detection accuracy (area under the curve = 0.96) but led to a slight improvement in specificity (specificity = 0.99) and decrease in sensitivity (sensitivity = 0.74).
CONCLUSION: The biomarker profile of aMCI was shown to be different from our previously generated AD profile among Mexican Americans, which was largely metabolic in nature. The findings implicate a possible interplay between inflammatory and metabolic processes and additional work is needed to further examine this.

PMID: 26444793 [PubMed - indexed for MEDLINE]

Autoimmune therapeutic chloroquine lowers blood pressure and improves endothelial function in spontaneously hypertensive rats.

Recent Research Articles from UNTHSC - Mon, 09/19/2016 - 07:36

Autoimmune therapeutic chloroquine lowers blood pressure and improves endothelial function in spontaneously hypertensive rats.

Pharmacol Res. 2016 Sep 14;

Authors: McCarthy CG, Wenceslau CF, Goulopoulou S, Ogbi S, Matsumoto T, Webb RC

Abstract
It has been suggested that hypertension results from a loss of immunological tolerance and the resulting autoimmunity may be an important underlying factor of its pathogenesis. This stems from the observations that many of the features involved in autoimmunity are also implicated in hypertension. Furthermore, the underlying presence of hypertension and cardiovascular disease are frequently observed in patients with autoimmune diseases. Antimalarial agents such as chloroquine are generally among the first line treatment options for patients with autoimmune diseases; however, whether they can improve a hypertensive phenotype in a genetic model of essential hypertension remains to be clarified. Therefore, we hypothesized that chloroquine treatment would improve endothelial function and lower blood pressure in spontaneously hypertensive rats (SHR). We treated adult SHR and Wistar-Kyoto rats (12 weeks old), as well as a group of young SHR (5 weeks old), with chloroquine (40mg/kg/day via intraperitoneal injection) for 21 days. Chloroquine lowered blood pressure in adult SHR, but did not impede the development of high blood pressure in young SHR. In isolated mesenteric resistance arteries from SHR of both ages, chloroquine treatment inhibited cyclooxygenase-dependent contraction to acetylcholine, lowered vascular and systemic generation of reactive oxygen species, and improved nitric oxide bioavailability. Overall, these data reveal the anti-hypertensive mechanisms of chloroquine in the vasculature, which may be important for lowering risk of cardiovascular disease in patients with autoimmune diseases. Furthermore, it adds to the growing body of evidence suggesting that autoimmunity underlies hypertension.

PMID: 27639600 [PubMed - as supplied by publisher]

HIV-1 Tat-shortened neurite outgrowth through regulation of microRNA-132 and its target gene expression.

Recent Research Articles from UNTHSC - Sat, 09/17/2016 - 07:36

HIV-1 Tat-shortened neurite outgrowth through regulation of microRNA-132 and its target gene expression.

J Neuroinflammation. 2016;13(1):247

Authors: Rahimian P, He JJ

Abstract
BACKGROUND: Synaptodendritic damage is a pathological hallmark of HIV-associated neurocognitive disorders, and HIV-1 Tat protein is known to cause such injury in the central nervous system. In this study, we aimed to determine the molecular mechanisms of Tat-induced neurite shortening, specifically the roles of miR-132, an important regulator of neurite morphogenesis in this process.
METHODS: The relationship between Tat expression and miR-132 expression was first determined using reverse transcription quantitative PCR (qRT-PCR) in Tat-transfected astrocytes and neurons, astrocytes from Tat-transgenic mice, and HIV-infected astrocytes. qRT-PCR and Western blotting were performed to determine Tat effects on expression of miR-132 target genes methyl CpG-binding protein 2, Rho GTPase activator p250GAP, and brain-derived neurotrophic factor. Exosomes were isolated from Tat-expressing astrocytes, and exosomal microRNA (miRNA) uptake into neurons was studied using miRNA labeling and flow cytometry. The lactate dehydrogenase release was used to determine the cytotoxicity, while immunostaining was used to determine neurite lengths and synapse formation. Tat basic domain deletion mutant and miR-132 mimic and inhibitor were used to determine the specificity of the relationship between Tat and miR-132 and its effects on astrocytes and neurons and the underlying mechanisms of Tat-induced miR-132 expression.
RESULTS: Tat significantly induced miR-132 expression, ensuing down-regulation of miR-132 target genes in astrocytes and neurons. miR-132 induction was associated with phosphorylation of cAMP response element-binding protein and required the basic domain of Tat. miRNA-132 induction had no effects on astrocyte activation or survival but was involved in the direct neurotoxicity of Tat. miR-132 was present in astrocyte-derived exosomes and was taken up by neurons, causing neurite shortening.
CONCLUSIONS: Tat-induced miR-132 expression contributes to both direct and astrocyte-mediated Tat neurotoxicity and supports the important roles of miR-132 in controlling neurite outgrowth.

PMID: 27634380 [PubMed - in process]

A novel Alzheimer disease locus located near the gene encoding tau protein.

Recent Research Articles from UNTHSC - Sat, 09/17/2016 - 07:36
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A novel Alzheimer disease locus located near the gene encoding tau protein.

Mol Psychiatry. 2016 Jan;21(1):108-17

Authors: Jun G, Ibrahim-Verbaas CA, Vronskaya M, Lambert JC, Chung J, Naj AC, Kunkle BW, Wang LS, Bis JC, Bellenguez C, Harold D, Lunetta KL, Destefano AL, Grenier-Boley B, Sims R, Beecham GW, Smith AV, Chouraki V, Hamilton-Nelson KL, Ikram MA, Fievet N, Denning N, Martin ER, Schmidt H, Kamatani Y, Dunstan ML, Valladares O, Laza AR, Zelenika D, Ramirez A, Foroud TM, Choi SH, Boland A, Becker T, Kukull WA, van der Lee SJ, Pasquier F, Cruchaga C, Beekly D, Fitzpatrick AL, Hanon O, Gill M, Barber R, Gudnason V, Campion D, Love S, Bennett DA, Amin N, Berr C, Tsolaki M, Buxbaum JD, Lopez OL, Deramecourt V, Fox NC, Cantwell LB, Tárraga L, Dufouil C, Hardy J, Crane PK, Eiriksdottir G, Hannequin D, Clarke R, Evans D, Mosley TH, Letenneur L, Brayne C, Maier W, De Jager P, Emilsson V, Dartigues JF, Hampel H, Kamboh MI, de Bruijn RF, Tzourio C, Pastor P, Larson EB, Rotter JI, O'Donovan MC, Montine TJ, Nalls MA, Mead S, Reiman EM, Jonsson PV, Holmes C, St George-Hyslop PH, Boada M, Passmore P, Wendland JR, Schmidt R, Morgan K, Winslow AR, Powell JF, Carasquillo M, Younkin SG, Jakobsdóttir J, Kauwe JS, Wilhelmsen KC, Rujescu D, Nöthen MM, Hofman A, Jones L, IGAP Consortium, Haines JL, Psaty BM, Van Broeckhoven C, Holmans P, Launer LJ, Mayeux R, Lathrop M, Goate AM, Escott-Price V, Seshadri S, Pericak-Vance MA, Amouyel P, Williams J, van Duijn CM, Schellenberg GD, Farrer LA

Abstract
APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10(-6)) and temporal cortex (P=2.6 × 10(-6)). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ɛ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted.

PMID: 25778476 [PubMed - indexed for MEDLINE]

Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction.

Recent Research Articles from UNTHSC - Thu, 09/15/2016 - 07:34

Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction.

Oncotarget. 2016 Sep 8;

Authors: Mathew SO, Chaudhary P, Powers SB, Vishwanatha JK, Mathew PA

Abstract
Prostate cancer is the most common type of cancer diagnosed and the second leading cause of cancer-related death in American men. Natural Killer (NK) cells are the first line of defense against cancer and infections. NK cell function is regulated by a delicate balance between signals received through activating and inhibitory receptors. Previously, we identified Lectin-like transcript-1 (LLT1/OCIL/CLEC2D) as a counter-receptor for the NK cell inhibitory receptor NKRP1A (CD161). Interaction of LLT1 expressed on target cells with NKRP1A inhibits NK cell activation. In this study, we have found that LLT1 was overexpressed on prostate cancer cell lines (DU145, LNCaP, 22Rv1 and PC3) and in primary prostate cancer tissues both at the mRNA and protein level. We further showed that LLT1 is retained intracellularly in normal prostate cells with minimal cell surface expression. Blocking LLT1 interaction with NKRP1A by anti-LLT1 mAb on prostate cancer cells increased the NK-mediated cytotoxicity of prostate cancer cells. The results indicate that prostate cancer cells may evade immune attack by NK cells by expressing LLT1 to inhibit NK cell-mediated cytolytic activity through LLT1-NKRP1A interaction. Blocking LLT1-NKRP1A interaction will make prostate cancer cells susceptible to killing by NK cells and therefore may be a new therapeutic option for treatment of prostate cancer.

PMID: 27626681 [PubMed - as supplied by publisher]

Feeling No Buzz or a Slight Buzz Is Common When Legally Drunk.

Recent Research Articles from UNTHSC - Thu, 09/15/2016 - 07:34

Feeling No Buzz or a Slight Buzz Is Common When Legally Drunk.

Am J Public Health. 2016 Oct;106(10):1761-1762

Authors: Rossheim ME, Thombs DL, Gonzalez-Pons KM, Killion JA, Clapp JD, Reed MB, Croff JM, Ruderman DE, Weiler RM

PMID: 27626346 [PubMed - as supplied by publisher]

Hospital and Health Plan Partnerships: The Affordable Care Act's Impact on Promoting Health and Wellness.

Recent Research Articles from UNTHSC - Thu, 09/15/2016 - 07:34

Hospital and Health Plan Partnerships: The Affordable Care Act's Impact on Promoting Health and Wellness.

Am Health Drug Benefits. 2016 Jul;9(5):269-78

Authors: Vu M, White A, Kelley VP, Hopper JK, Liu C

Abstract
BACKGROUND: The Affordable Care Act (ACA) healthcare reforms, centered on achieving the Centers for Medicare & Medicaid Services (CMS) Triple Aim goals of improving patient care quality and satisfaction, improving population health, and reducing costs, have led to increasing partnerships between hospitals and insurance companies and the implementation of employee wellness programs. Hospitals and insurance companies have opted to partner to distribute the risk and resources and increase coordination of care.
OBJECTIVE: To examine the ACA's impact on the health and wellness programs that have resulted from the joint ventures of hospitals and health plans based on the published literature.
METHOD: We conducted a review of the literature to identify successful mergers and best practices of health and wellness programs. Articles published between January 2007 and January 2015 were compiled from various search engines, using the search terms "corporate," "health and wellness program," "health plan," "insurance plan," "hospital," "joint venture," and "vertical merger." Publications that described consolidations or wellness programs not tied to health insurance plans were excluded. Noteworthy characteristics of these programs were summarized and tabulated.
RESULTS: A total of 44 eligible articles were included in the analysis. The findings showed that despite rising healthcare costs, joint ventures prevent hospitals from trading-off quality and services for cost reductions. Administrators believed that partnering would allow the companies to meet ACA standards for improving clinical outcomes at reduced costs. Before the implementation of the ACA, some employers had wellness programs, but these were not standardized and did not need to produce measurable results. The ACA encouraged improvement of employee wellness programs by providing funding for expanded health services and by mandating quality care. Successful workplace health and wellness programs have varying components, but all include monetary incentives and documented outcomes.
CONCLUSION: The concurrent growth of hospital health plans (especially those emerging from vertical mergers and partnerships) and wellness programs in the United States provides a unique opportunity for employees and patient populations to promote wellness and achieve the Triple Aim goals as initiated by CMS.

PMID: 27625744 [PubMed]

Chloroquine Suppresses the Development of Hypertension in Spontaneously Hypertensive Rats.

Recent Research Articles from UNTHSC - Thu, 09/15/2016 - 07:34

Chloroquine Suppresses the Development of Hypertension in Spontaneously Hypertensive Rats.

Am J Hypertens. 2016 Sep 13;

Authors: McCarthy CG, Wenceslau CF, Goulopoulou S, Baban B, Matsumoto T, Webb RC

Abstract
BACKGROUND: Innate immune system responses to damage-associated molecular patterns (DAMPs) are involved in hypertension. However, the mechanisms of this contribution are not well understood. Circulating mitochondrial DNA is a DAMP that activates Toll-like receptor (TLR) 9 and is elevated in spontaneously hypertensive rats (SHR). Therefore, we hypothesized that lysosomotropic agent chloroquine (CQ) would impair TLR9 signaling, as well as prevent the development of hypertension and immune cell recruitment to the vasculature, in SHR.
METHODS: Initially, adult SHR and Wistar-Kyoto (WKY) rats (12 weeks old), as well as a group of young SHR (5 weeks old), were treated with CQ (40mg/kg/day) or vehicle (saline) via intraperitoneal injections for 21 days and then TLR9-myeloid differentiation primary response protein (MyD88) signaling proteins were assessed in mesenteric resistance arteries (MRA) via western blot. Subsequently, young SHR and WKY were treated from 5-8 weeks of age and then were allowed to mature without further treatment. Blood pressure was measured pretreatment, posttreatment, and after maturation, and immune cell recruitment to the vasculature was measured via flow cytometry after maturation.
RESULTS: In MRA from adult SHR, CQ increased the expression of MyD88-dependent proteins, whereas young SHR MRA exhibited a decrease. This inhibition was subsequently associated with suppression of blood pressure, as well as decreased counts of circulating T cells and vascular infiltrating leukocytes in SHR, when CQ was administered during the prehypertensive phase.
CONCLUSIONS: These data bring into question the participation of TLRs during the maintenance phase of hypertension and promote the exploration of innate immune system therapy during the critical developmental phase.

PMID: 27623761 [PubMed - as supplied by publisher]

A Survey of the Impact of Deyolking on Biological Processes Covered by Shotgun Proteomic Analyses of Zebrafish Embryos.

Recent Research Articles from UNTHSC - Wed, 09/14/2016 - 07:35
Related Articles

A Survey of the Impact of Deyolking on Biological Processes Covered by Shotgun Proteomic Analyses of Zebrafish Embryos.

Zebrafish. 2015 Dec;12(6):398-407

Authors: Rahlouni F, Szarka S, Shulaev V, Prokai L

Abstract
Deyolking, the removal of the most abundant protein from the zebrafish (Danio rerio) embryo, is a common technique for in-depth exploration of proteome-level changes in vivo due to various environmental stressors or pharmacological impacts during embryonic stage of development. However, the effect of this procedure on the remaining proteome has not been fully studied. Here, we report a label-free shotgun proteomics survey on proteome coverage and biological processes that are enriched and depleted as a result of deyolking. Enriched proteins are involved in cellular energetics and development pathways, specifically implicating enrichment related to mitochondrial function. Although few proteins were removed completely by deyolking, depleted molecular pathways were associated with calcium signaling and signaling events implicating immune system response.

PMID: 26439676 [PubMed - indexed for MEDLINE]

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