Recent Research Articles from UNTHSC

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Updated: 59 min 47 sec ago

A weighted U statistic for association analyses considering genetic heterogeneity.

Wed, 02/03/2016 - 07:29
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A weighted U statistic for association analyses considering genetic heterogeneity.

Stat Med. 2016 Feb 1;

Authors: Wei C, Elston RC, Lu Q

Abstract
Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity-weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments dataset. The genome-wide analysis of nearly one million genetic markers took 7h, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. Copyright © 2016 John Wiley & Sons, Ltd.

PMID: 26833871 [PubMed - as supplied by publisher]

Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy.

Wed, 02/03/2016 - 07:29
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Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy.

Bioorg Med Chem Lett. 2015 Dec 11;

Authors: Acharya S, Rogers P, Krishnamoorthy RR, Stankowska DL, Dias HV, Yorio T

Abstract
Synthesis and bioactivity of novel dual acting nitric oxide releasing and reactive oxygen scavenging hybrid compound SA-2 is described. The hybrid molecule SA-2 significantly increased the superoxide dismutase enzyme level and protected the photoreceptor cells from H2O2 induced oxidative stress. Synthesis of ocular esterase sensitive aceloxy alkyl carbamate prodrug SA-4 with improved aqueous half-life is achieved to aid topical ocular formulation. This class of hybrid molecule and prodrug may have dual potential of improved IOP lowering and neuroprotection in glaucomatous optic neuropathy.

PMID: 26832784 [PubMed - as supplied by publisher]

Modified DOP-PCR for improved STR typing of degraded DNA from human skeletal remains and bloodstains.

Wed, 02/03/2016 - 07:29
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Modified DOP-PCR for improved STR typing of degraded DNA from human skeletal remains and bloodstains.

Leg Med (Tokyo). 2016 Jan;18:7-12

Authors: Ambers A, Turnbough M, Benjamin R, Gill-King H, King J, Sajantila A, Budowle B

Abstract
Forensic and ancient DNA samples often are damaged and in limited quantity as a result of exposure to harsh environments and the passage of time. Several strategies have been proposed to address the challenges posed by degraded and low copy templates, including a PCR based whole genome amplification method called degenerate oligonucleotide-primed PCR (DOP-PCR). This study assessed the efficacy of four modified versions of the original DOP-PCR primer that retain at least a portion of the 5' defined sequence and alter the number of bases on the 3' end. The use of each of the four modified primers resulted in improved STR profiles from environmentally-damaged bloodstains, contemporary human skeletal remains, American Civil War era bone samples, and skeletal remains of WWII soldiers over those obtained by previously described DOP-PCR methods and routine STR typing. Additionally, the modified DOP-PCR procedure allows for a larger volume of DNA extract to be used, reducing the need to concentrate the sample and thus mitigating the effects of concurrent concentration of inhibitors.

PMID: 26832369 [PubMed - in process]

Allosteric modulation of nicotinic acetylcholine receptors: the concept and therapeutic trends.

Wed, 02/03/2016 - 07:29
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Allosteric modulation of nicotinic acetylcholine receptors: the concept and therapeutic trends.

Curr Pharm Des. 2016 Jan 31;

Authors: Uteshev VV

Abstract
Expressing functional nicotinic acetylcholine receptors (nAChRs) may be beneficial to central neurons and neuronal networks because activation of nAChRs enhances neuronal resistance to injury, improves attention, cognitive performance, and produces robust anti-inflammatory and analgesic effects in mammals. Although exogenous orthosteric nAChR ligands present valuable tools in treatment of age- and trauma-related neurological deficits, therapeutic approaches that could amplify the brain's innate ability to maintain cholinergic homeostasis and resist injury may serve as intriguing and promising alternatives and have not been fully explored. One of these novel approaches utilizes positive allosteric modulators (PAMs) of nAChRs. Because of the ubiquitous expression of nAChRs in neuronal, glial and immune tissues, highly selective PAMs could amplify multiple endogenous neuroprotective, pro-cognitive, anti-inflammatory and anti-nociceptive cholinergic pathways to offset cholinergic hypofunction and generate therapeutic efficacy by targeting only a single player: i.e., nAChRs activated by endogenous cholinergic tone. In this article, I review the concept of allosteric modulation and current trends in therapeutic applications of nicotinic PAMs.

PMID: 26831463 [PubMed - as supplied by publisher]

Effect of an acute increase in central blood volume on cerebral hemodynamics.

Tue, 02/02/2016 - 07:29
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Effect of an acute increase in central blood volume on cerebral hemodynamics.

Am J Physiol Regul Integr Comp Physiol. 2015 Oct 15;309(8):R902-11

Authors: Ogoh S, Hirasawa A, Raven PB, Rebuffat T, Denise P, Lericollais R, Sugawara J, Normand H

Abstract
Systemic blood distribution is an important factor involved in regulating cerebral blood flow (CBF). However, the effect of an acute change in central blood volume (CBV) on CBF regulation remains unclear. To address our question, we sought to examine the CBF and systemic hemodynamic responses to microgravity during parabolic flight. Twelve healthy subjects were seated upright and exposed to microgravity during parabolic flight. During the brief periods of microgravity, mean arterial pressure was decreased (-26 ± 1%, P < 0.001), despite an increase in cardiac output (+21 ± 6%, P < 0.001). During microgravity, central arterial pulse pressure and estimated carotid sinus pressure increased rapidly. In addition, this increase in central arterial pulse pressure was associated with an arterial baroreflex-mediated decrease in heart rate (r = -0.888, P < 0.0001) and an increase in total vascular conductance (r = 0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean) remained unchanged throughout parabolic flight (P = 0.30). During microgravity the contribution of cardiac output to MCA Vmean was gradually reduced (P < 0.05), and its contribution was negatively correlated with an increase in total vascular conductance (r = -0.683, P < 0.0001). These findings suggest that the acute loading of the arterial and cardiopulmonary baroreceptors by increases in CBV during microgravity results in acute and marked systemic vasodilation. Furthermore, we conclude that this marked systemic vasodilation decreases the contribution of cardiac output to CBF. These findings suggest that the arterial and cardiopulmonary baroreflex-mediated peripheral vasodilation along with dynamic cerebral autoregulation counteracts a cerebral overperfusion, which otherwise would occur during acute increases in CBV.

PMID: 26310936 [PubMed - indexed for MEDLINE]

Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function Sigma Factor in Stress Response.

Tue, 02/02/2016 - 07:29
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Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function Sigma Factor in Stress Response.

J Proteome Res. 2015 May 1;14(5):2158-68

Authors: Allen MS, Hurst GB, Lu TY, Perry LM, Pan C, Lankford PK, Pelletier DA

Abstract
Rhodopseudomonas palustris encodes 16 extracytoplasmic function (ECF) σ factors. To begin to investigate the regulatory network of one of these ECF σ factors, the whole proteome of R. palustris CGA010 was quantitatively analyzed by tandem mass spectrometry from cultures episomally expressing the ECF σ(RPA4225) (ecfT) versus a WT control. Among the proteins with the greatest increase in abundance were catalase KatE, trehalose synthase, a DPS-like protein, and several regulatory proteins. Alignment of the cognate promoter regions driving expression of several upregulated proteins suggested a conserved binding motif in the -35 and -10 regions with the consensus sequence GGAAC-18N-TT. Additionally, the putative anti-σ factor RPA4224, whose gene is contained in the same predicted operon as RPA4225, was identified as interacting directly with the predicted response regulator RPA4223 by mass spectrometry of affinity-isolated protein complexes. Furthermore, another gene (RPA4226) coding for a protein that contains a cytoplasmic histidine kinase domain is located immediately upstream of RPA4225. The genomic organization of orthologs for these four genes is conserved in several other strains of R. palustris as well as in closely related α-Proteobacteria. Taken together, these data suggest that ECF σ(RPA4225) and the three additional genes make up a sigma factor mimicry system in R. palustris.

PMID: 25853567 [PubMed - indexed for MEDLINE]

The cholinergic potential, the vagus nerve and challenges in treatment of traumatic brain injury.

Fri, 01/29/2016 - 06:33

The cholinergic potential, the vagus nerve and challenges in treatment of traumatic brain injury.

Curr Pharm Des. 2016 Jan 26;

Authors: Uteshev VV, Tenovuo O, Gaidhani N

Abstract
Existing treatments of traumatic brain injury (TBI) have failed to reverse tremendous losses in productivity, independence and overall quality of life among TBI victims and therefore, cannot be viewed as sufficient. Although there is no shortage of promising basic concepts that may translate to efficacious therapies after TBI, the accumulated knowledge has yet to deliver treatments that adequately meet clinical and social demands. In this article, we discuss novel concepts, recent advances and accompanying challenges in developing cholinergic and related therapies after TBI.

PMID: 26818869 [PubMed - as supplied by publisher]

Innovative diagnostic tools for early detection of Alzheimer's disease.

Fri, 01/29/2016 - 06:33
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Innovative diagnostic tools for early detection of Alzheimer's disease.

Alzheimers Dement. 2015 May;11(5):561-78

Authors: Laske C, Sohrabi HR, Frost SM, López-de-Ipiña K, Garrard P, Buscema M, Dauwels J, Soekadar SR, Mueller S, Linnemann C, Bridenbaugh SA, Kanagasingam Y, Martins RN, O'Bryant SE

Abstract
Current state-of-the-art diagnostic measures of Alzheimer's disease (AD) are invasive (cerebrospinal fluid analysis), expensive (neuroimaging) and time-consuming (neuropsychological assessment) and thus have limited accessibility as frontline screening and diagnostic tools for AD. Thus, there is an increasing need for additional noninvasive and/or cost-effective tools, allowing identification of subjects in the preclinical or early clinical stages of AD who could be suitable for further cognitive evaluation and dementia diagnostics. Implementation of such tests may facilitate early and potentially more effective therapeutic and preventative strategies for AD. Before applying them in clinical practice, these tools should be examined in ongoing large clinical trials. This review will summarize and highlight the most promising screening tools including neuropsychometric, clinical, blood, and neurophysiological tests.

PMID: 25443858 [PubMed - indexed for MEDLINE]

Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research.

Fri, 01/29/2016 - 06:33
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Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research.

Alzheimers Dement. 2015 May;11(5):549-60

Authors: O'Bryant SE, Gupta V, Henriksen K, Edwards M, Jeromin A, Lista S, Bazenet C, Soares H, Lovestone S, Hampel H, Montine T, Blennow K, Foroud T, Carrillo M, Graff-Radford N, Laske C, Breteler M, Shaw L, Trojanowski JQ, Schupf N, Rissman RA, Fagan AM, Oberoi P, Umek R, Weiner MW, Grammas P, Posner H, Martins R, STAR-B and BBBIG working groups

Abstract
The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement provides (1) a synopsis of selected preanalytical methods utilized in many international AD cohort studies, (2) initial draft guidelines/SOPs for preanalytical methods, and (3) a list of required methodological information and protocols to be made available for publications in the field to foster cross-validation across cohorts and laboratories.

PMID: 25282381 [PubMed - indexed for MEDLINE]

Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity.

Thu, 01/28/2016 - 06:33

Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity.

Aging Dis. 2016 Jan;7(1):90-110

Authors: Luo X, Wu J, Jing S, Yan LJ

Abstract
Diabetes and its complications are caused by chronic glucotoxicity driven by persistent hyperglycemia. In this article, we review the mechanisms of diabetic glucotoxicity by focusing mainly on hyperglycemic stress and carbon stress. Mechanisms of hyperglycemic stress include reductive stress or pseudohypoxic stress caused by redox imbalance between NADH and NAD(+) driven by activation of both the polyol pathway and poly ADP ribose polymerase; the hexosamine pathway; the advanced glycation end products pathway; the protein kinase C activation pathway; and the enediol formation pathway. Mechanisms of carbon stress include excess production of acetyl-CoA that can over-acetylate a proteome and excess production of fumarate that can over-succinate a proteome; both of which can increase glucotoxicity in diabetes. For hyperglycemia stress, we also discuss the possible role of mitochondrial complex I in diabetes as this complex, in charge of NAD(+) regeneration, can make more reactive oxygen species (ROS) in the presence of excess NADH. For carbon stress, we also discuss the role of sirtuins in diabetes as they are deacetylases that can reverse protein acetylation thereby attenuating diabetic glucotoxicity and improving glucose metabolism. It is our belief that targeting some of the stress pathways discussed in this article may provide new therapeutic strategies for treatment of diabetes and its complications.

PMID: 26816666 [PubMed - as supplied by publisher]

Comparison of antioxidant and antiproliferative activity between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and fraction PII separated by column chromatography.

Wed, 01/27/2016 - 06:44

Comparison of antioxidant and antiproliferative activity between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and fraction PII separated by column chromatography.

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jan 8;

Authors: Jing S, Chai W, Guo G, Zhang X, Dai J, Yan LJ

Abstract
The aim of the present study was to compare the antioxidant and antiproliferative effects on cancer cells between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and its fraction PII that were separated by Biologic low pressure (LP) chromatography system followed by DEAE cellulose column chromatography. Results of in vitro experiments showed that the reducing power and the scavenging capacity of KCCP towards hydroxyl radicals (OH) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals increased in a concentration dependent manner and were stronger than that of fraction PII. Results of the antiproliferative effect of KCCP and fraction PII on cervical cancer HeLa cells, esophagus cancer Eca109 cells, and mouse ascites hepatomas H22 cells indicated that both KCCP and its fraction PII possessed inhibitory activity on all the tested cancer cells at a dose- and time-dependent manner, with KCCP showing higher inhibitory activity than that of fraction PII. The present study demonstrates that KCCP and its fraction PII have antioxidant properties that may help fight cancers.

PMID: 26809376 [PubMed - as supplied by publisher]

A triazine-based BODIPY trimer as a molecular viscometer.

Sat, 01/23/2016 - 06:34

A triazine-based BODIPY trimer as a molecular viscometer.

Phys Chem Chem Phys. 2016 Jan 21;

Authors: Raut SL, Kimball JD, Fudala R, Bora I, Chib R, Jaafari H, Castillo MK, Smith NW, Gryczynski I, Dzyuba SV, Gryczynski Z

Abstract
Photophysical behaviour of a novel trimeric BODIPY rotor with a high extinction coefficient is reported. Steady state and time resolved fluorescence measurements established that the trimer could be used as a viscometer for molecular solvents, membrane-like environments and several cancer cell lines.

PMID: 26795882 [PubMed - as supplied by publisher]

The Relationship Between Drug Use, Drug-related Arrests, and Chronic Pain Among Adults on Probation.

Sat, 01/23/2016 - 06:34
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The Relationship Between Drug Use, Drug-related Arrests, and Chronic Pain Among Adults on Probation.

J Subst Abuse Treat. 2015 Jun;53:33-8

Authors: Reingle Gonzalez JM, Walters ST, Lerch J, Taxman FS

Abstract
The intersection between chronic health conditions, drug use, and treatment seeking behavior among adults in the criminal justice system has been largely understudied. This study examined whether chronic pain was associated with opiate use, other illicit drug use, and drug-related arrests in a sample of substance-using probationers. We expected that probationers with chronic pain-related diagnoses would report more opiate use and drug-related arrests. This study used baseline data from 250 adults on probation in Baltimore, Maryland and Dallas, Texas who were participating in a larger clinical trial. Eighteen percent of probationers in this sample reported suffering from chronic pain. In bivariate analyses, probationers with chronic pain reported more drug-related arrests (t=-1.81; p<0.05) than those without chronic pain. Multivariate analyses support the hypothesis that probationers who reported chronic pain were marginally more likely to use opiates (OR=2.37; 95% CI .89-1.05) and non-opiate illicit drugs (OR=3.11; 95% CI 1.03-9.39) compared to offenders without chronic pain. In summary, these findings suggest that adults under probation supervision who suffer from chronic pain may be involved in criminal activity (specifically, drug-related criminal activity) in an effort to self-medicate their physical health condition(s). Screening probationers for chronic pain in the probation setting and referring these adults to pain management treatment may be an important step in advancing public safety.

PMID: 25595302 [PubMed - indexed for MEDLINE]

A two-stage approach to genetic risk assessment in primary care.

Thu, 01/21/2016 - 06:37

A two-stage approach to genetic risk assessment in primary care.

Breast Cancer Res Treat. 2016 Jan 19;

Authors: Biswas S, Atienza P, Chipman J, Blackford AL, Arun B, Hughes K, Parmigiani G

Abstract
Genetic risk prediction models such as BRCAPRO are used routinely in genetic counseling for identification of potential BRCA1 and BRCA2 mutation carriers. They require extensive information on the counselee and her family history, and thus are not practical for primary care. To address this gap, we develop and test a two-stage approach to genetic risk assessment by balancing the tradeoff between the amount of information used and accuracy achieved. The first stage is intended for primary care wherein limited information is collected and analyzed using a simplified version of BRCAPRO. If the assessed risk is sufficiently high, more extensive information is collected and the full BRCAPRO is used (stage two: intended for genetic counseling). We consider three first-stage tools: BRCAPROLYTE, BRCAPROLYTE-Plus, and BRCAPROLYTE-Simple. We evaluate the two-stage approach on independent clinical data on probands with family history of breast and ovarian cancers, and BRCA genetic test results. These include population-based data on 1344 probands from Newton-Wellesley Hospital and mostly high-risk family data on 2713 probands from Cancer Genetics Network and MD Anderson Cancer Center. We use discrimination and calibration measures, appropriately modified to evaluate the overall performance of a two-stage approach. We find that the proposed two-stage approach has very limited loss of discrimination and comparable calibration as BRCAPRO. It identifies a similar number of carriers without requiring a full family history evaluation on all probands. We conclude that the two-stage approach allows for practical large-scale genetic risk assessment in primary care.

PMID: 26786860 [PubMed - as supplied by publisher]

Neonatal variables, altitude of residence and Aymara ancestry in northern Chile.

Thu, 01/21/2016 - 06:37
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Neonatal variables, altitude of residence and Aymara ancestry in northern Chile.

PLoS One. 2015;10(4):e0121834

Authors: Rothhammer F, Fuentes-Guajardo M, Chakraborty R, Lorenzo Bermejo J, Dittmar M

Abstract
Studies performed in the Andean plateau, one of the highest inhabited areas in the world, have reported that reduced availability of oxygen is associated to fetal growth retardation and lower birth weight, which are established predictors of morbidity and mortality during the first year of life. To test this hypothesis, perinatal variables of neonates born at the Juan Noé Hospital of Arica, Chile, were analyzed in relation to altitude of residence and Aymara ancestry of their mothers. The study population comprised the offspring of 5,295 mothers born between February 2004 and August 2010. Information included birth weight, height, head circumference, gestational age, altitude of residence and socioeconomic status, and was obtained from medical records. Mother´s ancestry was assessed based on surnames which were linked to percentages of Aymara admixture estimates relying on 40 selected ancestry informative markers. After correcting for the effect of multicollinearity among predictor variables, neonates born to mothers with an increased component of Aymara ancestry showed significantly higher birth weight and height at sea level, a marginally significant (p-value 0.06) decrease of birth weight and a significant decrease of height with altitude in comparison with the offspring of mothers with low Aymara ancestry. Since observed tendencies are suggestive of a possible genetic adaptation to hypoxia of the Chilean Aymara, we discuss briefly preliminary evidence related to fetal oxygen transport, particularly polymorphisms in the promoters of the HBG1 and HBG2 genes that are modulators of HbF synthesis, obtained in this ethnic group.

PMID: 25885573 [PubMed - indexed for MEDLINE]

Genetic and linguistic correlation of the Kra-Dai-speaking groups in Thailand.

Thu, 01/21/2016 - 06:37
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Genetic and linguistic correlation of the Kra-Dai-speaking groups in Thailand.

J Hum Genet. 2015 Jul;60(7):371-80

Authors: Srithawong S, Srikummool M, Pittayaporn P, Ghirotto S, Chantawannakul P, Sun J, Eisenberg A, Chakraborty R, Kutanan W

Abstract
The Kra-Dai linguistic family includes Thai and Lao as well as a great number of languages spoken by ethnic minorities in Southeast Asia. In Thailand, a dozen of other Kra-Dai languages are spoken in addition to Thai, the national language. The genetic structure of the Kra-Dai-speaking populations in Thailand has been studied extensively using uniparentally inherited markers. To extend this line of genetic investigation, this study used 15 autosomal microsatellites of 500 individuals from 11 populations, belonging to nine Kra-Dai ethnicities, namely, the Kaleung, Phu Thai, Saek, Nyo, Lao Isan, Yuan, Black Tai, Phuan and Lue. These ethnolinguistic groups are dispersed in three different geographic regions of Thailand, that is, Northern, Northeastern and Central. The results show a very low average of pairwised F(st) (0.0099), as well as no population substructure based on STRUCTURE analysis, indicating genetic homogeneity within the Kra-Dai-speaking group, possibly owing to shared linguistic ancestry. The Mantel test, an analysis of molecular variance, and the approximate Bayesian computation procedure employed to evaluate potential factors for driving genetic diversity revealed that language is the predominant factor affecting genetic variations, whereas geography is not. The result of distance-based clustering analyses and spatial analysis of molecular variance revealed genetic distinctions of some populations, reflecting the effects of genetic drift and gene flow on allele frequency within populations, in concordance with the result of R-matrix regression. The genetic and linguistic affiliations of the contemporary Kra-Dai-speaking groups are consistent with each other despite certain deviation due to various evolutionary factors that may have occurred during their migrations and resettlements.

PMID: 25833471 [PubMed - indexed for MEDLINE]

Direct Analysis in Real Time (DART) of an Organothiophosphate at Ultrahigh Resolution by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry.

Wed, 01/20/2016 - 06:33

Direct Analysis in Real Time (DART) of an Organothiophosphate at Ultrahigh Resolution by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry.

Int J Mol Sci. 2016;17(1)

Authors: Prokai L, Stevens SM

Abstract
Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Mass resolution was documented to be over 800,000 in full-scan MS mode and over 1,000,000 for an MS/MS product ion produced by collision-induced dissociation of the protonated analyte. Mass measurement accuracy below 1 ppm was obtained for all DART-generated ions that belonged to the test compound in the mass spectra acquired using only external mass calibration. This high mass measurement accuracy, achievable at present only through FTMS, was required for unequivocal identification of the corresponding molecular formulae.

PMID: 26784186 [PubMed - as supplied by publisher]

Aquaporins: their role in gastrointestinal malignancies.

Tue, 01/19/2016 - 06:34

Aquaporins: their role in gastrointestinal malignancies.

Cancer Lett. 2016 Jan 15;

Authors: Nagaraju GP, Basha R, Rajitha B, Alese OB, Alam A, Pattnaik S, El-Rayes B

Abstract
Aquaporins (AQPs) are small (~30kDa monomers) integral membrane water transport proteins that allow water to flow through cell membranes in reaction to osmotic gradients in cells. In mammals, the family of AQPs has thirteen (AQP0-12) unique members that mediate critical biological functions. Since AQPs can impact cell proliferation, migration and angiogenesis, their role in various human cancers is well established. Recently, AQPs have been explored as potential diagnostic and therapeutic targets in gastrointestinal (GI) cancers. GI cancers encompass multiple sites including the colon, esophagus, stomach and pancreas. Research in the last three decades has revealed biological aspects and signaling pathways critical for the development of GI cancers. Since the majority of these cancers is very aggressive and rapidly metastasizes, identifying effective targets is crucial for treatment. Preclinical studies have utilized inhibitors of specific AQPs and knock down of AQP expression using siRNA. Although several studies have explored the role of AQPs in colorectal, esophageal, gastric, hepatocellular and pancreatic cancers, there is no comprehensive review compiling the available information on GI cancers as has been published for other malignancies such as ovarian cancer. Due to the similarities and association of various sites of GI cancers, it is helpful to consider these results collectively in order to better understand the role of specific AQPs in critical GI cancers. This review summarizes the current knowledge of the role of AQPs in GI malignancies with particular focus on diagnosis and therapeutic applications.

PMID: 26780474 [PubMed - as supplied by publisher]

Diversity of Gene Expression in Hepatocellular Carcinoma Cells.

Tue, 01/19/2016 - 06:34

Diversity of Gene Expression in Hepatocellular Carcinoma Cells.

Genomics Proteomics Bioinformatics. 2016 Jan 9;

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 - as supplied by publisher]

Systolic pressure response to voluntary apnea predicts sympathetic tone in obstructive sleep apnea as a clinically useful index.

Mon, 01/18/2016 - 06:32

Systolic pressure response to voluntary apnea predicts sympathetic tone in obstructive sleep apnea as a clinically useful index.

Auton Neurosci. 2015 Dec 9;

Authors: Jouett NP, Hardisty JM, Mason JR, Niv D, Romano JJ, Watenpaugh DE, Burk JR, Smith ML

Abstract
The present investigation tested the hypotheses that systolic arterial pressure (SAP) responses to voluntary apnea (a) serve as a surrogate of sympathetic nerve activity (SNA), (b) can distinguish Obstructive Sleep Apnea (OSA) patients from control subjects and (c) can document autonomic effects of treatment. 9 OSA and 10 control subjects were recruited in a laboratory study; 44 OSA subjects and 78 control subjects were recruited in a clinical study; and 21 untreated OSA subjects and 14 well-treated OSA subjects were recruited into a treatment study. Each subject performed hypoxic and room air voluntary apneas in triplicate. Muscle SNA (MSNA) and continuous AP were measured during each apnea in the laboratory study, while systolic arterial pressure (SAP) responses were measured continuously and by standard auscultation in the clinical and treatment studies. OSA subjects exhibited increased mean arterial pressure (MAP), SAP and MSNA responses to hypoxic apnea (all P<0.01) and the SAP response highly correlated with the MSNA response (R(2)=0.72, P<0.001). Clinical assessment confirmed that OSA subjects exhibited markedly elevated SAP responses (P<0.01), while treated OSA subjects had a decreased SAP response to apnea (P<0.04) compared to poorly treated subjects. These data indicate that (a) OSA subjects exhibit increased pressor and MSNA responses to apnea, and that (b) voluntary apnea may be a clinically useful assessment tool of autonomic dysregulation and treatment efficacy in OSA.

PMID: 26774324 [PubMed - as supplied by publisher]

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