Recent Research Articles from UNTHSC

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Updated: 2 hours 12 min ago

Observational Study Fails to Demonstrate the Effectiveness of OMT in Decreasing Low Back Pain.

2 hours 12 min ago
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Observational Study Fails to Demonstrate the Effectiveness of OMT in Decreasing Low Back Pain.

J Am Osteopath Assoc. 2014 Nov;114(11):e119-20

Authors: Licciardone JC

PMID: 25352411 [PubMed - in process]

Impact of a community based implementation of REACH II program for caregivers of Alzheimer's patients.

2 hours 12 min ago
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Impact of a community based implementation of REACH II program for caregivers of Alzheimer's patients.

PLoS One. 2014;9(2):e89290

Authors: Lykens K, Moayad N, Biswas S, Reyes-Ortiz C, Singh KP

Abstract
BACKGROUND: In 2009 an estimated 5.3 million people in the United States were afflicted with Alzheimer's disease, a degenerative form of dementia. The impact of this disease is not limited to the patient but also has significant impact on the lives and health of their family caregivers. The Resources for Enhancing Alzheimer's Caregiver Health (REACH II) program was developed and tested in clinical studies. The REACH II program is now being delivered by community agencies in several locations. This study examines the impact of the REACH II program on caregiver lives and health in a city in north Texas.
STUDY DESIGN: Family caregivers of Alzheimer's patients were assessed using an instrument covering the multi-item domains of Caregiver Burden, Depression, Self-Care, and Social Support upon enrollment in the program and at the completion of the 6 month intervention. The domain scores were analyzed using a multivariate paired t-test and Bonferroni confidence interval for the differences in pre- and post-service domain scores.
RESULTS: A total of 494 families were enrolled in the program during the period January 1, 2011 through June 30, 2012. Of these families 177 completed the 6 month program and have pre - and post service domain scores. The median age for the caregivers was 62 years. The domain scores for Depression and Caregiver Burden demonstrated statistically significant improvements upon program completion.
CONCLUSION: The REACH II intervention was successfully implemented by a community agency with comparable impacts to those of the clinical trial warranting wider scale implementation.

PMID: 24586664 [PubMed - indexed for MEDLINE]

Characterization and reduction of cardiac- and respiratory-induced noise as a function of the sampling rate (TR) in fMRI.

2 hours 12 min ago
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Characterization and reduction of cardiac- and respiratory-induced noise as a function of the sampling rate (TR) in fMRI.

Neuroimage. 2014 Apr 1;89:314-30

Authors: Cordes D, Nandy RR, Schafer S, Wager TD

Abstract
It has recently been shown that both high-frequency and low-frequency cardiac and respiratory noise sources exist throughout the entire brain and can cause significant signal changes in fMRI data. It is also known that the brainstem, basal forebrain and spinal cord areas are problematic for fMRI because of the magnitude of cardiac-induced pulsations at these locations. In this study, the physiological noise contributions in the lower brain areas (covering the brainstem and adjacent regions) are investigated and a novel method is presented for computing both low-frequency and high-frequency physiological regressors accurately for each subject. In particular, using a novel optimization algorithm that penalizes curvature (i.e. the second derivative) of the physiological hemodynamic response functions, the cardiac- and respiratory-related response functions are computed. The physiological noise variance is determined for each voxel and the frequency-aliasing property of the high-frequency cardiac waveform as a function of the repetition time (TR) is investigated. It is shown that for the brainstem and other brain areas associated with large pulsations of the cardiac rate, the temporal SNR associated with the low-frequency range of the BOLD response has maxima at subject-specific TRs. At these values, the high-frequency aliased cardiac rate can be eliminated by digital filtering without affecting the BOLD-related signal.

PMID: 24355483 [PubMed - indexed for MEDLINE]

FRET based ratio-metric sensing of hyaluronidase in synthetic urine as a biomarker for bladder and prostate cancer.

Thu, 10/30/2014 - 8:05am
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FRET based ratio-metric sensing of hyaluronidase in synthetic urine as a biomarker for bladder and prostate cancer.

Curr Pharm Biotechnol. 2013;14(4):470-4

Authors: Chib R, Raut S, Fudala R, Chang A, Mummert M, Rich R, Gryczynski Z, Gryczynski I

Abstract
Elevated hyaluronidase levels are found in the urine of bladder and prostate cancer patients. Therefore, HA-ase is regarded as an important biomarker for the detection of these cancers. In this report, we use a FRET based ratiometric sensing approach to detect the level of HA-ase in synthetic urine. For this, we have used a HA-FRET probe (hyaluronan) labeled with fluorescein as a donor and rhodamine as an acceptor. We monitor the digestion of our HA-FRET probe with different concentrations of HA-ase in synthetic urine via fluorescence emission. The extent to which FRET is released depends on the concentration of HA-ase. Our fluorescence intensity results are also supported with time resolved fluorescence decay data. This assay can be used to develop a non-invasive technique for the detection of bladder and/or prostate cancer progression.

PMID: 23360262 [PubMed - indexed for MEDLINE]

Are you bleeding? Validation of a machine-learning algorithm for determination of blood volume status: application to remote triage.

Wed, 10/29/2014 - 4:06am
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Are you bleeding? Validation of a machine-learning algorithm for determination of blood volume status: application to remote triage.

J Appl Physiol (1985). 2014 Mar 1;116(5):486-94

Authors: Rickards CA, Vyas N, Ryan KL, Ward KR, Andre D, Hurst GM, Barrera CR, Convertino VA

Abstract
Due to limited remote triage monitoring capabilities, combat medics cannot currently distinguish bleeding soldiers from those engaged in combat unless they have physical access to them. The purpose of this study was to test the hypothesis that low-level physiological signals can be used to develop a machine-learning algorithm for tracking changes in central blood volume that will subsequently distinguish central hypovolemia from physical activity. Twenty-four subjects underwent central hypovolemia via lower body negative pressure (LBNP), and a supine-cycle exercise protocol. Exercise workloads were determined by matching heart rate responses from each LBNP level. Heart rate and stroke volume (SV) were measured via Finometer. ECG, heat flux, skin temperature, galvanic skin response, and two-axis acceleration were obtained from an armband (SenseWear Pro2) and used to develop a machine-learning algorithm to predict changes in SV as an index of central blood volume under both conditions. The algorithm SV was retrospectively compared against Finometer SV. A model was developed to determine whether unknown data points could be correctly classified into these two conditions using leave-one-out cross-validation. Algorithm vs. Finometer SV values were strongly correlated for LBNP in individual subjects (mean r = 0.92; range 0.75-0.98), but only moderately correlated for exercise (mean r = 0.50; range -0.23-0.87). From the first level of LBNP/exercise, the machine-learning algorithm was able to distinguish between LBNP and exercise with high accuracy, sensitivity, and specificity (all ≥90%). In conclusion, a machine-learning algorithm developed from low-level physiological signals could reliably distinguish central hypovolemia from exercise, indicating that this device could provide battlefield remote triage capabilities.

PMID: 24408992 [PubMed - indexed for MEDLINE]

ERG Oncoprotein Inhibits ANXA2 Expression and Function in Prostate Cancer.

Tue, 10/28/2014 - 4:06am

ERG Oncoprotein Inhibits ANXA2 Expression and Function in Prostate Cancer.

Mol Cancer Res. 2014 Oct 24;

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

Abstract
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 Ca2+-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 (IHC), 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 biological stratification and therapeutic targeting of ERG stratified prostate cancers.

PMID: 25344575 [PubMed - as supplied by publisher]

Evidence for the exclusive expression of functional homomeric α7 nAChRs in hypothalamic histaminergic tuberomammillary neurons in rats.

Sun, 10/26/2014 - 4:05am
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Evidence for the exclusive expression of functional homomeric α7 nAChRs in hypothalamic histaminergic tuberomammillary neurons in rats.

Neurosci Lett. 2014 Mar 20;563:107-11

Authors: Tischkau S, Mhaskar Y, Uteshev VV

Abstract
Hypothalamic histaminergic tuberomammillary (TM) neurons in rats express high densities of nicotinic acetylcholine receptors (nAChRs) whose Ca(2+) permeability, kinetic and pharmacological properties are similar to those of heterologous homomeric α7 nAChRs. However, native α7 nAChR subunits can co-assemble with β or α5 nAChR subunits to form functional heteromeric α7-containing α7β or α7α5 nAChRs with kinetics and pharmacology similar to those of α7 homomers. Therefore, although TM nAChRs have been used as an ex vivo model of functional α7 homomers, the molecular makeup of TM nAChRs has not been determined and the expression of functional α7-containing heteromers in TM neurons has not been excluded. To determine the profile of TM nAChR subunit transcripts, we have conducted single-cell qRT-PCR experiments using acutely dissociated TM neurons in rats. TM neurons were found to express transcripts of only principal α3, α6 and α7 nAChR subunits. Transcripts of other known mammalian neuronal subunits (α2, α4-5, α9-10, β2-4) were not detected. In the absence of β and α5 subunits, the expression of functional α7-containing heteromers in TM neurons is highly unlikely because principal α3, α6 and α7 nAChR subunits alone are not known to form functional heteromeric nAChRs. These results support the exclusive expression of native functional α7 homomers in rat TM neurons and introduce these neurons as a unique reliable source of native functional homomeric α7 nAChRs suitable for ex vivo and in vitro pharmacological assays in developing selective α7 nAChR agents.

PMID: 24486841 [PubMed - indexed for MEDLINE]

Methylene blue promotes quiescence of rat neural progenitor cells.

Sat, 10/25/2014 - 4:08am
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Methylene blue promotes quiescence of rat neural progenitor cells.

Front Cell Neurosci. 2014;8:315

Authors: Xie L, Choudhury GR, Wang J, Park Y, Liu R, Yuan F, Zhang CL, Yorio T, Jin K, Yang SH

Abstract
Neural stem cell-based treatment holds a new therapeutic opportunity for neurodegenerative disorders. Here, we investigated the effect of methylene blue on proliferation and differentiation of rat neural progenitor cells (NPCs) both in vitro and in vivo. We found that methylene blue inhibited proliferation and promoted quiescence of NPCs in vitro without affecting committed neuronal differentiation. Consistently, intracerebroventricular infusion of methylene blue significantly inhibited NPC proliferation at the subventricular zone (SVZ). Methylene blue inhibited mTOR signaling along with down-regulation of cyclins in NPCs in vitro and in vivo. In summary, our study indicates that methylene blue may delay NPC senescence through enhancing NPCs quiescence.

PMID: 25339866 [PubMed]

Validation of a self-administered computerized system to detect cognitive impairment in older adults.

Fri, 10/24/2014 - 4:05am
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Validation of a self-administered computerized system to detect cognitive impairment in older adults.

J Appl Gerontol. 2014 Dec;33(8):942-62

Authors: Brinkman SD, Reese RJ, Norsworthy LA, Dellaria DK, Kinkade JW, Benge J, Brown K, Ratka A, Simpkins JW

Abstract
There is increasing interest in the development of economical and accurate approaches to identifying persons in the community who have mild, undetected cognitive impairments. Computerized assessment systems have been suggested as a viable approach to identifying these persons. The validity of a computerized assessment system for identification of memory and executive deficits in older individuals was evaluated in the current study. Volunteers (N = 235) completed a 3-hr battery of neuropsychological tests and a computerized cognitive assessment system. Participants were classified as impaired (n = 78) or unimpaired (n = 157) on the basis of the Mini Mental State Exam, Wechsler Memory Scale-III and the Trail Making Test (TMT), Part B. All six variables (three memory variables and three executive variables) derived from the computerized assessment differed significantly between groups in the expected direction. There was also evidence of temporal stability and concurrent validity. Application of computerized assessment systems for clinical practice and for identification of research participants is discussed in this article.

PMID: 25332303 [PubMed - in process]

Electrophoretic Characterization of the Mammalian Nuclear Matrix Proteome, Nuclear Envelope, Nucleoli and Covalently Bound ADP-Ribose Polymers: Potential Applications to Cancer.

Fri, 10/24/2014 - 4:05am
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Electrophoretic Characterization of the Mammalian Nuclear Matrix Proteome, Nuclear Envelope, Nucleoli and Covalently Bound ADP-Ribose Polymers: Potential Applications to Cancer.

Cancer Genomics Proteomics. 2014 09-10;11(5):217-223

Authors: Aranda XG, Racho RG, Pacheco-Rodríguez G, Alvarez-González R

Abstract
Background/Aim: Nucleic acid metabolism is biochemically compartmentalized to the nucleus. Thus, it is necessary to define the proteome of the various macromolecular structures within this organelle. Materials and Methods: We isolated the nuclear matrix (NM) fraction from rat liver by sequential centrifugation steps at 13,000 rpm, staggered between endogenous nuclease treatment for 2 h at 37°C, followed by high-salt (H.S.; 2.0 M NaCl) and non-ionic detergent extractions (0.1%- or 1.0% Triton X-100) to eliminate the bulk of chromosomal DNA/RNA, histone proteins and the nuclear envelope (NE). Results: Integrity of the NM and NE structures was confirmed by electron microscopy. Next, we analyzed the NM proteome on a 20% polyacrylamide gel using the PhastSystem. We observed the absence of histone proteins and the characteristic presence of the lamins by Coomassie blue staining. By contrast, upon silver staining, following electrophoretic separation with a Tris-Borate-EDTA buffer, we observed the NM-associated nucleic RNA and protein-free ADP-ribose polymers. While polymers are found in much lower concentration than RNA in NM, they were purified by affinity chromatography on boronate resin prior to electrophoresis. We observed the electrophoretic resolution of free ADP-ribose chains (5-25 units) by silver staining. Conclusion: The significance of our observations to cancer studies and carcinogenesis is discussed.

PMID: 25331794 [PubMed - as supplied by publisher]

A Weighted U-Statistic for Genetic Association Analyses of Sequencing Data.

Fri, 10/24/2014 - 4:05am
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A Weighted U-Statistic for Genetic Association Analyses of Sequencing Data.

Genet Epidemiol. 2014 Oct 20;

Authors: Wei C, Li M, He Z, Vsevolozhskaya O, Schaid DJ, Lu Q

Abstract
With advancements in next-generation sequencing technology, a massive amount of sequencing data is generated, which offers a great opportunity to comprehensively investigate the role of rare variants in the genetic etiology of complex diseases. Nevertheless, the high-dimensional sequencing data poses a great challenge for statistical analysis. The association analyses based on traditional statistical methods suffer substantial power loss because of the low frequency of genetic variants and the extremely high dimensionality of the data. We developed a Weighted U Sequencing test, referred to as WU-SEQ, for the high-dimensional association analysis of sequencing data. Based on a nonparametric U-statistic, WU-SEQ makes no assumption of the underlying disease model and phenotype distribution, and can be applied to a variety of phenotypes. Through simulation studies and an empirical study, we showed that WU-SEQ outperformed a commonly used sequence kernel association test (SKAT) method when the underlying assumptions were violated (e.g., the phenotype followed a heavy-tailed distribution). Even when the assumptions were satisfied, WU-SEQ still attained comparable performance to SKAT. Finally, we applied WU-SEQ to sequencing data from the Dallas Heart Study (DHS), and detected an association between ANGPTL 4 and very low density lipoprotein cholesterol.

PMID: 25331574 [PubMed - as supplied by publisher]

Long lived BSA Au clusters as a time gated intensity imaging probe.

Fri, 10/24/2014 - 4:05am
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Long lived BSA Au clusters as a time gated intensity imaging probe.

Nanoscale. 2014 Mar 7;6(5):2594-7

Authors: Raut SL, Fudala R, Rich R, Kokate RA, Chib R, Gryczynski Z, Gryczynski I

Abstract
The work presented here reports the use of long lifetime (>1 μs) BSA Au clusters as a cellular/tissue, time gated, intensity imaging probe. By collecting the emission signal 50 ns post excitation, one can off-gate the intense auto-fluorescence background, thereby greatly enhancing the clarity/specificity in fluorescence imaging.

PMID: 24469148 [PubMed - indexed for MEDLINE]

Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10.

Wed, 10/22/2014 - 4:06am

Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10.

Eur J Immunol. 2014 Oct 20;

Authors: Xie L, Choudhury GR, Winters A, Yang SH, Jin K

Abstract
Forkhead box P3 (Foxp3)(+) regulatory T (Treg) cells maintain the immune tolerance and prevent inflammatory responses in the periphery. However, the presence of Treg cells in the central nervous system under steady state has not been studied. Here, for the first time, we show a substantial TCRαβ (+) CD4(+) Foxp3(+) T-cell population (cerebral Treg cells) in the normal rat cerebrum, constituting more than 15% of the cerebral CD4(+) T-cell compartment. Cerebral Treg cells showed an activated/memory phenotype and expressed many Treg-cell signature genes at higher levels than peripheral Treg cells. Consistent with their activated/memory phenotype, cerebral Treg cells robustly restrained the LPS-induced inflammatory responses of brain microglia/macrophages, suggesting a role in maintaining the cerebral homeostasis by inhibiting the neuroinflammation. In addition, brain astrocytes were the helper cells that sustained Foxp3 expression in Treg cells through IL-2/STAT5 signaling, showing that the interaction between astrocytes and Treg cells contributes to the maintenance of Treg-cell identity in the brain. Taken together, our work represents the first study to characterize the phenotypic and functional features of Treg cells in the normal rat cerebrum. Our data have provided a novel insight for the contribution of Treg cells to the immunosurveillance and immunomodulation in the cerebrum under steady state. This article is protected by copyright. All rights reserved.

PMID: 25329858 [PubMed - as supplied by publisher]

Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice.

Tue, 10/21/2014 - 4:06am
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Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice.

Behav Pharmacol. 2014 Oct 16;

Authors: Gatch MB, Forster MJ

Abstract
A number of cannabinoid compounds are being sold in the form of incense as 'legal' alternatives to marijuana. The purpose of these experiments was to determine whether the most common of these compounds have discriminative stimulus effects similar to Δ-tetrahydrocannabinol (Δ-THC), the main active component in marijuana. Locomotor depressant effects of JWH-018, JWH-073, JWH-200, JWH-203, JWH-250, AM-2201, and CP 47,497-C8-homolog were tested in mice. The compounds were then tested for substitution in rats trained to discriminate Δ-THC (3 mg/kg, intraperitoneally). The time course of the peak dose of each compound was also tested. Each of the synthetic cannabinoids dose-dependently decreased locomotor activity for 1-2 h. Each of the compounds fully substituted for the discriminative stimulus effects of Δ-THC, mostly at doses that produced only marginal amounts of rate suppression. JWH-250 and CP 47,497-C8-homolog suppressed response rates at doses that fully substituted for Δ-THC. The time courses varied markedly between compounds. Most of the compounds had a shorter onset than Δ-THC, and the effects of three of the compounds lasted substantially longer (JWH-073, JWH-250, and CP 47,497-C8-homolog). Several of the most commonly used synthetic cannabinoids produce behavioral effects comparable with those of Δ-THC, which suggests that these compounds may share the psychoactive effects of marijuana responsible for abuse liability. The extremely long time course of the discriminative stimulus effects and adverse effects of CP 47,497-C8-homolog suggest that CP 47,497-C8-homolog may be associated with increased hazards among humans.

PMID: 25325289 [PubMed - as supplied by publisher]

Resident Assistant Training Program for Increasing Alcohol, Other Drug, and Mental Health First-Aid Efforts.

Tue, 10/21/2014 - 4:06am
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Resident Assistant Training Program for Increasing Alcohol, Other Drug, and Mental Health First-Aid Efforts.

Prev Sci. 2014 Oct 17;

Authors: Thombs DL, Gonzalez JM, Osborn CJ, Rossheim ME, Suzuki S

Abstract
In college and university residence halls, resident assistants (RAs) are expected to serve as first-aid providers to students who may have alcohol, other drug, mental health, and academic problems. Despite this responsibility, evidence-based, first-aid programs have not been developed and tested for the RA workforce. The current study examined effects of an investigational first-aid program designed specifically for RAs. The online Peer Hero Training program is a novel approach to RA training in its use of interactive video dramatizations of incidents involving substance-using or distressed residents. A 9-month randomized trial conducted on eight US campuses compared RAs who participated in the Peer Hero Training program to RAs who received training-as-usual. Participation in the Peer Hero Training program significantly increased RA first-aid efforts for residential students who may have had alcohol, other drug, mental health, or academic problems 6 months after baseline. Compared with those in the training-as-usual condition, RAs in the Peer Hero Training program made more than 10 times as many first-aid efforts for possible alcohol problems, almost 14 times the number of first-aid efforts for possible drug use, almost 3 times the number of first-aid efforts for possible mental health problems, and 3 times the number of first-aid efforts for academic problems. There was no evidence that measured RA attitudes mediated the effects of the intervention. Results of this preliminary evaluation trial suggest that online training using interactive video dramatizations is a viable approach to strengthening RAs' ability to provide alcohol, other drugs, and mental health first-aid to undergraduates.

PMID: 25322950 [PubMed - as supplied by publisher]

Blood pressure regulation XI: overview and future research directions.

Tue, 10/21/2014 - 4:06am
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Blood pressure regulation XI: overview and future research directions.

Eur J Appl Physiol. 2014 Mar;114(3):579-86

Authors: Raven PB, Chapleau MW

Abstract
While the importance of regulating arterial blood pressure within a 'normal' range is widely appreciated, the definition of 'normal' and the means by which humans and other species regulate blood pressure under various conditions remain hotly debated. The effects of diverse physiological, pathological and environmental challenges on blood pressure and the mechanisms that attempt to maintain it at an optimal level are reviewed and critically analyzed in a series of articles published in this themed issue of the European Journal of Applied Physiology. We summarize here the major points made in these reviews, with emphasis on unifying concepts of regulatory mechanisms and future directions for research.

PMID: 24463603 [PubMed - indexed for MEDLINE]

Inhibition of triple-negative and Herceptin-resistant breast cancer cell proliferation and migration by Annexin A2 antibodies.

Sat, 10/18/2014 - 4:08am
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Inhibition of triple-negative and Herceptin-resistant breast cancer cell proliferation and migration by Annexin A2 antibodies.

Br J Cancer. 2014 Oct 16;

Authors: Chaudhary P, Thamake SI, Shetty P, Vishwanatha JK

Abstract
Background:Annexin A2 (AnxA2), a calcium-dependent phospholipid binding protein, is abundantly present at the surface of triple-negative and Herceptin-resistant breast cancer cells. Interactions between cell-surface AnxA2 and tyrosine kinase receptors have an important role in the tumour microenvironment and act together to enhance tumour growth. The mechanism supporting this role is still unknown.Methods:The membrane function of AnxA2 was blocked by incubating cells with anti-AnxA2 antibodies. Western blotting, immunoprecipitation, immunofluorescence, 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), flow cytometry, Clonogenic, and wound-healing assays were performed in this study.Results:We demonstrate that AnxA2 interacts with epidermal growth factor receptor (EGFR) at the cell surface and has an important role in cancer cell proliferation and migration by modulating EGFR functions. Blocking AnxA2 function at the cell surface by anti-AnxA2 antibody suppressed the EGF-induced EGFR tyrosine phosphorylation and internalisation by blocking its homodimerisation. Furthermore, addition of AnxA2 antibody significantly inhibited the EGFR-dependent PI3K-AKT and Raf-MEK-ERK downstream pathways under both EGF-induced and basal growth conditions, resulting in lower cell proliferation and migration.Conclusions:These findings suggest that cell-surface AnxA2 has an important regulatory role in EGFR-mediated oncogenic processes by keeping EGFR signalling events in an activated state. Therefore, AnxA2 could potentially be used as a therapeutic target in triple-negative and Herceptin-resistant breast cancers.British Journal of Cancer advance online publication 16 October 2014; doi:10.1038/bjc.2014.542 www.bjcancer.com.

PMID: 25321192 [PubMed - as supplied by publisher]

HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China.

Sat, 10/18/2014 - 4:08am
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HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China.

BMJ Open. 2014;4(10):e005886

Authors: Leng X, Liang S, Ma Y, Dong Y, Kan W, Goan D, Hsi JH, Liao L, Wang J, He C, Zhang H, Xing H, Ruan Y, Shao Y

Abstract
OBJECTIVE: To explore HIV virological failure and drug resistance among injecting drug users (IDUs) receiving first-line antiretroviral treatment (ART) in China.
DESIGN: A series of cross-sectional surveys from 2003 to 2012 from the Chinese National HIV Drug Resistance (HIVDR) Surveillance and Monitoring Network.
SETTING: China.
PARTICIPANTS: Data were analysed by the Chinese National (HIVDR) Surveillance and Monitoring Network from 2003 to 2012. Demographic, ART and laboratory data (CD4+ cell count, viral load and drug resistance) were included. Factors associated with virological failure were identified by logistic regression analysis.
RESULTS: 929 of the 8556 individuals in the Chinese HIVDR database were IDUs receiving first-line ART. For these 929 IDUs, the median duration of treatment was 14 months (IQR 6.0-17.8). 193 of the 929 IDUs (20.8%) experienced virological failure (HIV viral load ≥1000 copies/mL). The prevalence of HIVDR among patients with virological failure was 38.9% (68/175). The proportion of patients with drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTIs), nucleoside reverse transcriptase inhibitor (NRTIs) and protease inhibitors (PIs) was 52.9%, 76.5% and 4.4%, respectively. Factors independently associated with virological failure include: ethnic minorities, junior high school education or less, farmers, self-reported missing doses in the past month, CD4 cell count at survey from 200 to 349 cells/mm(3) or from 0 to 199 cells/mm(3), and residence of Guangxi and Yunnan provinces.
CONCLUSIONS: The proportion of virological failure was high among IDUs receiving first-line ART in China. However, better treatment outcomes were observed in Guangxi and Yunnan, which indicates the importance of ART education and adherence to intervention, especially for patients who are farmers, minorities or have a poor educational background.

PMID: 25319999 [PubMed - in process]

Involvement of p38 MAPK in reactive astrogliosis induced by ischemic stroke.

Fri, 10/17/2014 - 12:05pm
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Involvement of p38 MAPK in reactive astrogliosis induced by ischemic stroke.

Brain Res. 2014 Mar 10;1551:45-58

Authors: Roy Choudhury G, Ryou MG, Poteet E, Wen Y, He R, Sun F, Yuan F, Jin K, Yang SH

Abstract
Reactive astrogliosis is an essential feature of astrocytic response to all forms of central nervous system (CNS) injury and disease, which may benefit or harm surrounding neural and non-neural cells. Despite extensive study, its molecular triggers remain largely unknown in term of ischemic stroke. In the current study we investigated the role p38 mitogen-activated protein kinase (MAPK) in astrogliosis both in vitro and in vivo. In a mouse model of middle cerebral artery occlusion (MCAO), p38 MAPK activation was observed in the glia scar area, along with increased glial fibrillary acidic protein (GFAP) expression. In primary astrocyte cultures, hypoxia and scratch injury-induced astrogliosis was attenuated by both p38 inhibition and knockout of p38 MAPK. In addition, both knockout and inhibition of p38 MAPK also reduced astrocyte migration, but did not affect astrocyte proliferation. In a mouse model of permanent MCAO, no significant difference in motor function recovery and lesion volume was observed between conditional GFAP/p38 MAPK knockout mice and littermates. While a significant reduction of astrogliosis was observed in the GFAP/p38 knockout mice compared with the littermates. Our findings suggest that p38 MAPK signaling pathway plays an important role in the ischemic stroke-induced astrogliosis and thus may serve as a novel target to control glial scar formation.

PMID: 24440774 [PubMed - indexed for MEDLINE]

Ancient human genomes suggest three ancestral populations for present-day Europeans.

Thu, 10/16/2014 - 4:04am
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Ancient human genomes suggest three ancestral populations for present-day Europeans.

Nature. 2014 Sep 18;513(7518):409-13

Authors: Lazaridis I, Patterson N, Mittnik A, Renaud G, Mallick S, Kirsanow K, Sudmant PH, Schraiber JG, Castellano S, Lipson M, Berger B, Economou C, Bollongino R, Fu Q, Bos KI, Nordenfelt S, Li H, de Filippo C, Prüfer K, Sawyer S, Posth C, Haak W, Hallgren F, Fornander E, Rohland N, Delsate D, Francken M, Guinet JM, Wahl J, Ayodo G, Babiker HA, Bailliet G, Balanovska E, Balanovsky O, Barrantes R, Bedoya G, Ben-Ami H, Bene J, Berrada F, Bravi CM, Brisighelli F, Busby GB, Cali F, Churnosov M, Cole DE, Corach D, Damba L, van Driem G, Dryomov S, Dugoujon JM, Fedorova SA, Gallego Romero I, Gubina M, Hammer M, Henn BM, Hervig T, Hodoglugil U, Jha AR, Karachanak-Yankova S, Khusainova R, Khusnutdinova E, Kittles R, Kivisild T, Klitz W, Kučinskas V, Kushniarevich A, Laredj L, Litvinov S, Loukidis T, Mahley RW, Melegh B, Metspalu E, Molina J, Mountain J, Näkkäläjärvi K, Nesheva D, Nyambo T, Osipova L, Parik J, Platonov F, Posukh O, Romano V, Rothhammer F, Rudan I, Ruizbakiev R, Sahakyan H, Sajantila A, Salas A, Starikovskaya EB, Tarekegn A, Toncheva D, Turdikulova S, Uktveryte I, Utevska O, Vasquez R, Villena M, Voevoda M, Winkler CA, Yepiskoposyan L, Zalloua P, Zemunik T, Cooper A, Capelli C, Thomas MG, Ruiz-Linares A, Tishkoff SA, Singh L, Thangaraj K, Villems R, Comas D, Sukernik R, Metspalu M, Meyer M, Eichler EE, Burger J, Slatkin M, Pääbo S, Kelso J, Reich D, Krause J

Abstract
We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.

PMID: 25230663 [PubMed - indexed for MEDLINE]