Recent Research Articles from UNTHSC

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Updated: 1 hour 43 min ago

Kinetic comparison of older men and women during walk-to-stair descent transition.

Thu, 12/18/2014 - 3:29am
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Kinetic comparison of older men and women during walk-to-stair descent transition.

Gait Posture. 2014 Sep;40(4):600-4

Authors: Singhal K, Kim J, Casebolt J, Lee S, Han KH, Kwon YH

Abstract
Stair walking is one of the most challenging tasks for older adults, with women reporting higher incidence of falls. The purpose of this study was to investigate the gender differences in kinetics during stair descent transition. Twenty-eight participants (12 male and 16 female; 68.5 and 69.0 years of mean age, respectively) performed stair descent from level walking in a step-over-step manner at a self-selected speed over a custom-made three-step staircase with embedded force plates. Kinematic and force data were combined using inverse dynamics to generate kinetic data for gender comparison. The top and the first step on the staircase were chosen for analysis. Women showed a higher trail leg peak hip abductor moment (-1.0 Nm/kg), lower trail leg peak knee extensor moment and eccentric power (0.74 Nm/kg and 3.15 W/kg), and lower peak concentric power at trail leg ankle joint (1.29 W/kg) as compared to men (p<0.05; -0.82 Nm/kg, 0.89 Nm/kg, 3.83 W/kg, and 1.78 W/kg, respectively). The lead leg knee eccentric power was also lower in women (p<0.05). This decreased ability to exert knee control during stair descent transition may predispose women to a higher risk of fall.

PMID: 25082325 [PubMed - indexed for MEDLINE]

Cancer-associated isocitrate dehydrogenase 1 (IDH1) R132H mutation and d-2-hydroxyglutarate stimulate glutamine metabolism under hypoxia.

Thu, 12/18/2014 - 3:29am
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Cancer-associated isocitrate dehydrogenase 1 (IDH1) R132H mutation and d-2-hydroxyglutarate stimulate glutamine metabolism under hypoxia.

J Biol Chem. 2014 Aug 22;289(34):23318-28

Authors: Reitman ZJ, Duncan CG, Poteet E, Winters A, Yan LJ, Gooden DM, Spasojevic I, Boros LG, Yang SH, Yan H

Abstract
Mutations in the cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDH1) occur in several types of cancer, and altered cellular metabolism associated with IDH1 mutations presents unique therapeutic opportunities. By altering IDH1, these mutations target a critical step in reductive glutamine metabolism, the metabolic pathway that converts glutamine ultimately to acetyl-CoA for biosynthetic processes. While IDH1-mutated cells are sensitive to therapies that target glutamine metabolism, the effect of IDH1 mutations on reductive glutamine metabolism remains poorly understood. To explore this issue, we investigated the effect of a knock-in, single-codon IDH1-R132H mutation on the metabolism of the HCT116 colorectal adenocarcinoma cell line. Here we report the R132H-isobolome by using targeted (13)C isotopomer tracer fate analysis to trace the metabolic fate of glucose and glutamine in this system. We show that introduction of the R132H mutation into IDH1 up-regulates the contribution of glutamine to lipogenesis in hypoxia, but not in normoxia. Treatment of cells with a d-2-hydroxyglutarate (d-2HG) ester recapitulated these changes, indicating that the alterations observed in the knocked-in cells were mediated by d-2HG produced by the IDH1 mutant. These studies provide a dynamic mechanistic basis for metabolic alterations observed in IDH1-mutated tumors and uncover potential therapeutic targets in IDH1-mutated cancers.

PMID: 24986863 [PubMed - indexed for MEDLINE]

Between-centre variability in transfer function analysis, a widely used method for linear quantification of the dynamic pressure-flow relation: the CARNet study.

Thu, 12/18/2014 - 3:29am
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Between-centre variability in transfer function analysis, a widely used method for linear quantification of the dynamic pressure-flow relation: the CARNet study.

Med Eng Phys. 2014 May;36(5):620-7

Authors: Meel-van den Abeelen AS, Simpson DM, Wang LJ, Slump CH, Zhang R, Tarumi T, Rickards CA, Payne S, Mitsis GD, Kostoglou K, Marmarelis V, Shin D, Tzeng YC, Ainslie PN, Gommer E, Müller M, Dorado AC, Smielewski P, Yelicich B, Puppo C, Liu X, Czosnyka M, Wang CY, Novak V, Panerai RB, Claassen JA

Abstract
Transfer function analysis (TFA) is a frequently used method to assess dynamic cerebral autoregulation (CA) using spontaneous oscillations in blood pressure (BP) and cerebral blood flow velocity (CBFV). However, controversies and variations exist in how research groups utilise TFA, causing high variability in interpretation. The objective of this study was to evaluate between-centre variability in TFA outcome metrics. 15 centres analysed the same 70 BP and CBFV datasets from healthy subjects (n=50 rest; n=20 during hypercapnia); 10 additional datasets were computer-generated. Each centre used their in-house TFA methods; however, certain parameters were specified to reduce a priori between-centre variability. Hypercapnia was used to assess discriminatory performance and synthetic data to evaluate effects of parameter settings. Results were analysed using the Mann-Whitney test and logistic regression. A large non-homogeneous variation was found in TFA outcome metrics between the centres. Logistic regression demonstrated that 11 centres were able to distinguish between normal and impaired CA with an AUC>0.85. Further analysis identified TFA settings that are associated with large variation in outcome measures. These results indicate the need for standardisation of TFA settings in order to reduce between-centre variability and to allow accurate comparison between studies. Suggestions on optimal signal processing methods are proposed.

PMID: 24725709 [PubMed - indexed for MEDLINE]

Age estimation via quantification of signal-joint T cell receptor excision circles in Koreans.

Thu, 12/18/2014 - 3:29am
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Age estimation via quantification of signal-joint T cell receptor excision circles in Koreans.

Leg Med (Tokyo). 2014 May;16(3):135-8

Authors: Cho S, Ge J, Seo SB, Kim K, Lee HY, Lee SD

Abstract
The estimation of age from biological samples (i.e., remains) at crime scenes could provide useful information about both victims and other persons related to criminal activities. Signal-joint T cell receptor excision circle (sjTREC) levels in peripheral blood decline with age, and negative correlations between sjTREC levels and age have been demonstrated in several ethnic groups. To validate the utility of sjTREC for age estimation in Koreans, Taqman qPCR was used to quantify the sjTREC level in samples obtained from 172 individuals ranging from 16 to 65 years old. We modified the previously reported method by using a shorter amplicon and confirmed the efficiency and utility of this method in this report. Our results showed that the linear negative regression curve between sjTREC levels and age was characterized by r=-0.807 and a standard error of 8.49 years. These results indicate that sjTREC level is an effective age estimation method in Koreans. The value of the standard error of quantification was not different from previous reports for other population groups.

PMID: 24524944 [PubMed - indexed for MEDLINE]

Label-free LC-MS/MS identification of phosphatidylglycerol-regulated proteins in Synechocystis sp. PCC6803.

Wed, 12/17/2014 - 3:29am
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Label-free LC-MS/MS identification of phosphatidylglycerol-regulated proteins in Synechocystis sp. PCC6803.

Proteomics. 2014 May;14(9):1053-7

Authors: Talamantes T, Ughy B, Domonkos I, Kis M, Gombos Z, Prokai L

Abstract
We present a proteomics dataset combining SDS-PAGE prefractionation and data-dependent LC-MS/MS that enables the identification of phosphatidylglycerol-regulated proteins in the pgsA(-) mutant of Synechocystis sp. PCC6803, a cyanobacterium strain that grows with this indispensable phospholipid added exogenously. We searched the acquired raw data against a composite protein sequence database of Synechocystis using MASCOT, and employed Progenesis LC-MS software for label-free quantification based on extracted peptide intensities to detect changes in protein abundances upon phospholipid withdrawal. Protein identifications were validated using rigorous criteria, and our analysis of the dataset revealed 80 phosphatidylglycerol-regulated proteins involved in various cellular processes including photosynthesis, respiration, metabolism, transport, transcription, and translation. The data have been deposited to the ProteomeXchange with identifier PXD000363 (http://proteomecentral.proteomexchange.org/dataset/PXD000363).

PMID: 24574175 [PubMed - indexed for MEDLINE]

The role of TGF-β2 and bone morphogenetic proteins in the trabecular meshwork and glaucoma.

Wed, 12/17/2014 - 3:29am
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The role of TGF-β2 and bone morphogenetic proteins in the trabecular meshwork and glaucoma.

J Ocul Pharmacol Ther. 2014 Mar-Apr;30(2-3):154-62

Authors: Wordinger RJ, Sharma T, Clark AF

Abstract
Primary open-angle glaucoma (POAG) is the second leading cause of blindness worldwide. Elevated intraocular pressure (IOP) is a primary risk factor associated with POAG. Increased aqueous humor (AH) outflow resistance through the trabecular meshwork (TM) results in elevated IOP in POAG patients. Resistance to AH outflow is associated with increased accumulation of extracellular matrix (ECM) proteins in the TM. In addition, levels of transforming growth factor-beta2 (TGF-β2) are elevated in the AH and TM tissue of POAG patients. Elevated levels of TGF-β2 in other tissues have been associated with fibrosis and increased tissue stiffness. However, locally produced effectors that maintain homeostatic relationships must also be present. Bone morphogenetic proteins (BMPs) serve this purpose in the TM as they inhibit TGF-β2-induced ECM changes in TM cells. This review article first describes the TGF-β superfamily of growth factors including BMPs and their canonical and noncanonical signaling pathways. The article then addresses the role of TGF-β2 in the pathophysiology of POAG as related to the ECM and ECM crosslinking enzymes. This is followed by a discussion of potential homeostatic control mechanisms of TGF-β2 signaling in the TM including the inhibitory role of BMP-4 and BMP-7. We then describe the relationship of TGF-β2 and BMPs in TM fibrosis including the role of antagonists. Lastly, in future directions, we identify potential future studies that explore new and unique cellular interactions within the TM for potential therapeutic interventions.

PMID: 24517218 [PubMed - indexed for MEDLINE]

Role of the alternatively spliced glucocorticoid receptor isoform GRβ in steroid responsiveness and glaucoma.

Wed, 12/17/2014 - 3:29am
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Role of the alternatively spliced glucocorticoid receptor isoform GRβ in steroid responsiveness and glaucoma.

J Ocul Pharmacol Ther. 2014 Mar-Apr;30(2-3):121-7

Authors: Jain A, Wordinger RJ, Yorio T, Clark AF

Abstract
Glucocorticoid (GC)-induced ocular hypertension (OHT) is a serious side effect of GC therapy in susceptible individuals. This OHT is due to increased aqueous humor (AH) outflow resistance in the trabecular meshwork (TM) caused by GC-mediated changes in TM structure and function. GCs may also play a role in the development of primary open-angle glaucoma (POAG). Elevated cortisol levels in the AH or enhanced GC sensitivity may be one of the reasons for elevated intraocular pressure in POAG patients. The GC OHT responder population is at greater risk of developing POAG compared with non-responders. We recently have gained insight into the molecular mechanisms responsible for this differential GC responsiveness, which is attributed to differences in GC receptor isoform expression in the TM. This article summarizes current knowledge on alternative GC receptor splicing to generate GC receptor alpha (GRα) and GRβ and their roles in the regulation of GC responsiveness in normal and glaucoma TM.

PMID: 24506296 [PubMed - indexed for MEDLINE]

Lineage -CD34+CD31+ cells that appear in association with severe burn injury are inhibitory on the production of antimicrobial peptides by epidermal keratinocytes.

Wed, 12/17/2014 - 3:29am
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Lineage -CD34+CD31+ cells that appear in association with severe burn injury are inhibitory on the production of antimicrobial peptides by epidermal keratinocytes.

PLoS One. 2014;9(2):e82926

Authors: Yoshida S, Lee JO, Nakamura K, Suzuki S, Hendon DN, Kobayashi M, Suzuki F

Abstract
Antimicrobial peptides are major host defense effectors against Pseudomonas aeruginosa skin infections. Due to the lack of such peptide production, severely burned hosts are greatly susceptible to P. aeruginosa burn wound infection. β-Defensin (HBD) production by normal human epidermal keratinocytes (NHEK) was inhibited by lineage(-)CD34(+) cells isolated from peripheral blood of severely burned patients. Lineage(-)CD34(+) cells obtained from severely burned patients were characterized as CD31(+), while healthy donor lineage(-)CD34(+) cells were shown to be CD31(-) cells. Lineage(-)CD34(+)CD31(-) cells did not show any inhibitory activities on HBD-1 production by NHEK. CCL2 and IL-10 released from lineage(-)CD34(+)CD31(+) cells were shown to be inhibitory on the peptide production by NHEK, while these soluble factors were not produced by lineage(-)CD34(+)CD31(-) cells. After treatment with a mixture of mAbs for CCL2 and IL-10, the culture fluids of lineage(-)CD34(+)CD31(+) cells did not show any inhibitory activities on HBD-1 production by NHEK. Lineage(-)CD34(+)CD31(+) cells that appear in association with burn injuries play a role on the inhibition of antimicrobial peptide production by skin keratinocytes through the production of CCL2 and IL-10.

PMID: 24498256 [PubMed - indexed for MEDLINE]

Real-time imaging of exocytotic mucin release and swelling in Calu-3 cells using acridine orange.

Wed, 12/17/2014 - 3:29am
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Real-time imaging of exocytotic mucin release and swelling in Calu-3 cells using acridine orange.

Methods. 2014 Mar 15;66(2):312-24

Authors: Shumilov D, Popov A, Fudala R, Akopova I, Gryczynski I, Borejdo J, Gryczynski Z, Grygorczyk R

Abstract
Mucus secretion is the first-line of defence against the barrage of irritants inhaled into human lungs, but abnormally thick and viscous mucus results in many respiratory diseases. Understanding the processes underlying mucus pathology is hampered, in part, by lack of appropriate experimental tools for labeling and studying mucin granule secretion from live cells with high sensitivity and temporal resolution. In this report we present original spectroscopic properties of acridine orange (AO) which could be utilized to study granule release and mucin swelling with various advanced fluorescence imaging approaches. Low concentration (<200 μM) AO solutions presented absorption maximum at 494 nm, emission maximum at 525 nm and only ∼1.76 ns fluorescence lifetime. By contrast at high concentrations (4-30 mM) favoring formation of AO aggregates, a very different absorption with maximum at ∼440 nm, dramatically red-shifted emission with maximum at 630 nm, and over 10-fold increased fluorescence lifetime (∼20 ns) was observed. To verify potential utility of AO for real-time imaging we have performed confocal, total internal reflection fluorescence (TIRF) and fluorescence lifetime imaging (FLIM) of AO-stained Calu-3 cells. We found similar red-shifted fluorescence spectra and long fluorescence lifetime in intracellular granules as compared to that in the cytoplasm consistent with granular AO accumulation. Mechanical stimulation of Calu-3 cells resulted in multiple exocytotic secretory events of AO-stained granules followed by post-exocytotic swelling of their fluorescently-labeled content that was seen in single-line TIRF images as rapidly-expanding bright-fluorescence patches. The rate of their size expansion followed first-order kinetics with diffusivity of 3.98±0.07×10(-7)c m(2)/s, as expected for mucus gel swelling. This was followed by fluorescence decrease due to diffusional loss of AO that was ∼10-fold slower in the secreted mucus compared to bulk aqueous solution. In summary, we showed that AO-staining could be utilized for real-time TIRF imaging of mucin granule exocytosis and mucin swelling with high sensitivity and temporal resolution. Considering unique AO fluorescence properties that permit selective excitation of AO monomers versus aggregates, our study lays the groundwork for future development of two-color excitation scheme and two-color fluorescence FLIM live-cell imaging assay with potentially many biological applications.

PMID: 24055436 [PubMed - indexed for MEDLINE]

Multiple-pulse pumping for enhanced fluorescence detection and molecular imaging in tissue.

Wed, 12/17/2014 - 3:29am
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Multiple-pulse pumping for enhanced fluorescence detection and molecular imaging in tissue.

Methods. 2014 Mar 15;66(2):292-8

Authors: Rich RM, Gryczynski I, Fudala R, Borejdo J, Stankowska DL, Krishnamoorthy RR, Raut S, Maliwal BP, Shumilov D, Doan H, Gryczynski Z

Abstract
Applications of fluorescence based imaging techniques for detection in cellular and tissue environments are severely limited by autofluorescence of endogenous components of cells, tissue, and the fixatives used in sample processing. To achieve sufficient signal-to-background ratio, a high concentration of the probe needs to be used which is not always feasible. Since typically autofluorescence is in the nanosecond range, long-lived fluorescence probes in combination with time-gated detection can be used for suppression of unwanted autofluorescence. Unfortunately, this requires the sacrifice of the large portion the probe signal in order to sufficiently filter the background. We report a simple and practical approach to achieve a many-fold increase in the intensity of a long-lived probe without increasing the background fluorescence. Using controllable, well separated bursts of closely spaced laser excitation pulses, we are able to highly increase the fluorescence signal of a long-lived marker over the endogenous fluorescent background and scattering, thereby greatly increasing detection sensitivity. Using a commercially available confocal microscopy system equipped with a laser diode and time correlated single photon counting (TCSPC) detection, we are able to enhance the signal of a long-lived Ruthenium (Ru)-based probe by nearly an order of magnitude. We used 80 MHz bursts of pulses (12.5 ns pulse separation) repeated with a 320 kHz repetition rate as needed to adequately image a dye with a 380 ns lifetime. Just using 10 pulses in the burst increases the Ru signal almost 10-fold without any increase in the background signal.

PMID: 23994243 [PubMed - indexed for MEDLINE]

Mitochondrial DNA deletions in Alzheimer's brains: a review.

Wed, 12/17/2014 - 3:29am
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Mitochondrial DNA deletions in Alzheimer's brains: a review.

Alzheimers Dement. 2014 May;10(3):393-400

Authors: Phillips NR, Simpkins JW, Roby RK

Abstract
Mitochondrial dysfunction and increased oxidative stress have been associated with normal aging and are possibly implicated in the etiology of late-onset Alzheimer's disease (AD). DNA deletions, as well as other alterations, can result from oxidative damage to nucleic acids. Many studies during the past two decades have investigated the incidence of mitochondrial DNA deletions in postmortem brain tissues of late-onset AD patients compared with age-matched normal control subjects. Published studies are not entirely concordant, but their differences might shed light on the heterogeneity of AD itself. Our understanding of the role that mitochondrial DNA deletions play in disease progression may provide valuable information that could someday lead to a treatment.

PMID: 23850329 [PubMed - indexed for MEDLINE]

Risk of future offense among probationers with co-occurring substance use and mental health disorders.

Wed, 12/17/2014 - 3:29am
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Risk of future offense among probationers with co-occurring substance use and mental health disorders.

Community Ment Health J. 2014 Apr;50(3):288-95

Authors: Balyakina E, Mann C, Ellison M, Sivernell R, Fulda KG, Sarai SK, Cardarelli R

Abstract
The criminal justice system is the primary service delivery system for many adults with drug and alcohol dependence, mental health, and other health service needs. The purpose of this study was to examine the relationship between risk of future offense, mental health status and co-occurring disorders in a large substance abuse diversion probationer population. A purposive sample of 2,077 probationers completed an assessment to screen for mental health disorders, substance use disorders, risk of future crime and violence, and several demographic characteristics. Probationers who screened positive for co-occurring substance use and mental health disorders were significantly more likely to be at higher risk of future crime and violence compared to probationers who screened positive for only substance use, only a mental health disorder, or no substance use or mental health disorder. Implications for substance use and mental health service delivery are discussed, and recommendations are made for further research.

PMID: 23765181 [PubMed - indexed for MEDLINE]

c-Jun NH2-terminal kinase-induced proteasomal degradation of c-FLIPL/S and Bcl2 sensitize prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine.

Wed, 12/17/2014 - 3:29am
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c-Jun NH2-terminal kinase-induced proteasomal degradation of c-FLIPL/S and Bcl2 sensitize prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine.

Biochem Pharmacol. 2014 Oct 15;91(4):457-73

Authors: Chaudhary P, Vishwanatha JK

Abstract
Tetrandrine, a constituent of Chinese herb Stephania tetrandra, causes cell death in prostate cancer, but the molecular mechanisms leading to apoptosis is not known. Here we demonstrated that tetrandrine selectively inhibits the growth of prostate cancer PC3 and DU145 cells compared to normal prostate epithelial PWR-1E cells. Tetrandrine-induced cell death in prostate cancer cells is caused by reactive oxygen species (ROS)-mediated activation of c-Jun NH2-terminal kinase (JNK1/2). JNK1/2-mediated proteasomal degradation of c-FLIPL/S and Bcl2 proteins are key events in the sensitization of prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine. Tetrandrine-induced JNK1/2 activation caused the translocation of Bax to mitochondria by disrupting its association with Bcl2 which was accompanied by collapse of mitochondrial membrane potential (MMP), cytosolic release of cytochrome c and Smac, and apoptotic cell death. Additionally, tetrandrine-induced JNK1/2 activation increased the phosphorylation of Bcl2 at Ser70 and facilitated its degradation via the ubiquitin-mediated proteasomal pathway. In parallel, tetrandrine-mediated ROS generation also caused the induction of ligand-independent Fas-mediated apoptosis by activating procaspase-8 and Bid cleavage. Inhibition of procaspase-8 activation attenuated the cleavage of Bid, loss of MMP and caspase-3 activation suggest that tetrandrine-induced Fas-mediated apoptosis is associated with the mitochondrial pathway. Furthermore, most of the signaling effects of tetrandrine on apoptosis were significantly attenuated in the presence of antioxidant N-acetyl-l-cysteine, thereby confirming the involvement of ROS in these events. In conclusion, the results of the present study indicate that tetrandrine-induced apoptosis in prostate cancer cells is initiated by ROS generation and that both intrinsic and extrinsic pathway contributes to cell death.

PMID: 25181458 [PubMed - indexed for MEDLINE]

M2b Macrophage Elimination and Improved Resistance of Mice with Chronic Alcohol Consumption to Opportunistic Infections.

Wed, 12/10/2014 - 3:29am

M2b Macrophage Elimination and Improved Resistance of Mice with Chronic Alcohol Consumption to Opportunistic Infections.

Am J Pathol. 2014 Dec 5;

Authors: Ohama H, Asai A, Ito I, Suzuki S, Kobayashi M, Higuchi K, Suzuki F

Abstract
Alcohol abuse was found to predispose persons to opportunistic infections. In this study, we tried to improve the host antibacterial resistance of chronic alcohol-consuming (CAC) mice to opportunistic infections. Bactericidal macrophages with functions to produce IL-12 and to express mRNAs for CXCL9 and inducible nitric oxide synthase (M1 macrophages) were characterized as the main effector cells in host antibacterial innate immunities against infections with opportunistic pathogens. However, CAC mice were found to be carriers of M2b macrophages [macrophages with functions to produce IL-10 and to express mRNAs for CD163, chemokine ligand (CCL)1, and LIGHT (homologous to lymphotoxin, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for high-voltage electron microscopy on T cells)], which were inhibitory on macrophage conversion from resident macrophages to M1 macrophages. Under treatment with CCL1 antisense oligodeoxynucleotides, a specific inhibitor of M2b macrophages, CAC mouse macrophages reverted to resident macrophages, and M1 macrophages were induced by a bacterial antigen from macrophages of CAC mice that were previously treated with the oligodeoxynucleotides. Opportunistic infections (enterococcal translocation and Klebsiella pneumonia) in CAC mice were completely controlled by CCL1 antisense oligodeoxynucleotides. These results indicate that certain opportunistic infections in alcoholics are controllable through the modulation of M2b macrophages.

PMID: 25485859 [PubMed - as supplied by publisher]

Abuse liability of the dietary supplement dimethylamylamine.

Tue, 12/09/2014 - 3:29am

Abuse liability of the dietary supplement dimethylamylamine.

Drug Alcohol Depend. 2014 Nov 25;

Authors: Dolan SB, Gatch MB

Abstract
BACKGROUND: Dimethylamylamine (DMAA) is a component of many dietary supplements and has recently been associated with numerous adverse effects, prompting the US military and World Anti-Doping Agency to ban its use as a supplement. The current study aimed to elucidate the abuse liability profile of DMAA.
METHODS: Dose-response studies of DMAA were performed with Swiss-Webster mice in locomotor and conditioned place-preference assays. The discriminative stimulus effects of DMAA were investigated in Sprague-Dawley rats trained to discriminate either cocaine or methamphetamine from saline.
RESULTS: DMAA produced dose-dependent locomotor depression and fully substituted for cocaine and partially substituted for methamphetamine. In the conditioned place-preference assay, DMAA produced an inverted-U-shaped dose-response curve, with intermediate doses producing significant place preference.
CONCLUSIONS: The cocaine- and methamphetamine-like discriminative stimulus effects and the conditioned place preference produced by DMAA suggest that is has potential for abuse. These findings in combination with reports of substantial adverse effects of DMAA in humans suggest that control of DMAA may warrant further consideration.

PMID: 25481853 [PubMed - as supplied by publisher]

Novel Split Chest Tube Improves Post-Surgical Thoracic Drainage.

Tue, 12/09/2014 - 3:29am
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Novel Split Chest Tube Improves Post-Surgical Thoracic Drainage.

J Clin Exp Cardiolog. 2014;5

Authors: Olivencia-Yurvati AH, Cherry BH, Gurji HA, White DW, Newton JT, Scott GF, Hoxha B, Gourlay T, Mallet RT

Abstract
OBJECTIVE: Conventional, separate mediastinal and pleural tubes are often inefficient at draining thoracic effusions.
DESCRIPTION: We developed a Y-shaped chest tube with split ends that divide within the thoracic cavity, permitting separate intrathoracic placement and requiring a single exit port. In this study, thoracic drainage by the split drain vs. that of separate drains was tested.
METHODS: After sternotomy, pericardiotomy, and left pleurotomy, pigs were fitted with separate chest drains (n=10) or a split tube prototype (n=9) with internal openings positioned in the mediastinum and in the costo-diaphragmatic recess. Separate series of experiments were conducted to test drainage of D5W or 0.58 M sucrose, an aqueous solution with viscosity approximating that of plasma. One litre of fluid was infused into the thorax, and suction was applied at -20 cm H2O for 30 min.
RESULTS: When D5W was infused, the split drain left a residual volume of 53 ± 99 ml (mean value ± SD) vs. 148 ± 120 for the separate drain (P=0.007), representing a drainage efficiency (i.e. drained vol/[drained + residual vol]) of 95 ± 10% vs. 86 ± 12% for the separate drains (P = 0.011). In the second series, the split drain evacuated more 0.58 M sucrose in the first minute (967 ± 129 ml) than the separate drains (680 ± 192 ml, P<0.001). By 30 min, the split drain evacuated a similar volume of sucrose vs. the conventional drain (1089 ± 72 vs. 1056 ± 78 ml; P = 0.5). Residual volume tended to be lower (25 ± 10 vs. 62 ± 72 ml; P = 0.128) and drainage efficiency tended to be higher (98 ± 1 vs. 95 ± 6%; P = 0.111) with the split drain vs. conventional separate drains.
CONCLUSION: The split chest tube drained the thoracic cavity at least as effectively as conventional separate tubes. This new device could potentially alleviate postoperative complications.

PMID: 25478289 [PubMed - as supplied by publisher]

Postmortem medicolegal genetic diagnostics also require reporting guidance.

Fri, 12/05/2014 - 7:30pm

Postmortem medicolegal genetic diagnostics also require reporting guidance.

Eur J Hum Genet. 2014 Dec 3;

Authors: Sajantila A, Budowle B

PMID: 25469540 [PubMed - as supplied by publisher]

The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades.

Fri, 12/05/2014 - 7:30pm

The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades.

Mol Biol Evol. 2014 Dec 2;

Authors: Hallast P, Batini C, Zadik D, Maisano Delser P, Wetton JH, Arroyo-Pardo E, Cavalleri GL, de Knijff P, Destro Bisol G, Myhre Dupuy B, Eriksen HA, Jorde LB, King TE, Larmuseau MH, López de Munain A, López-Parra AM, Loutradis A, Milasin J, Novelletto A, Pamjav H, Sajantila A, Schempp W, Sears M, Tolun A, Tyler-Smith C, Van Geystelen A, Watkins S, Winney B, Jobling MA

Abstract
Many studies of human populations have used the male-specific region of the Y chromosome (MSY) as a marker, but MSY sequence variants have traditionally been subject to ascertainment bias. Also, dating of haplogroups has relied on Y-specific short tandem repeats (STRs), involving problems of mutation rate choice, and possible long-term mutation saturation. Next-generation sequencing can ascertain single nucleotide polymorphisms (SNPs) in an unbiased way, leading to phylogenies in which branch-lengths are proportional to time, and allowing the times-to-most-recent-common-ancestor (TMRCAs) of nodes to be estimated directly. Here we describe the sequencing of 3.7 Mb of MSY in each of 448 human males at a mean coverage of 51 ×, yielding 13,261 high-confidence SNPs, 65.9% of which are previously unreported. The resulting phylogeny covers the majority of the known clades, provides date estimates of nodes, and constitutes a robust evolutionary framework for analysing the history of other classes of mutation. Different clades within the tree show subtle but significant differences in branch lengths to the root. We also apply a set of 23 Y-STRs to the same samples, allowing SNP- and STR-based diversity and TMRCA estimates to be systematically compared. Ongoing purifying selection is suggested by our analysis of the phylogenetic distribution of non-synonymous variants in 15 MSY single-copy genes.

PMID: 25468874 [PubMed - as supplied by publisher]

Positive oxidative stress in aging and aging-related disease tolerance.

Wed, 12/03/2014 - 11:30pm

Positive oxidative stress in aging and aging-related disease tolerance.

Redox Biol. 2014 Jan 9;2C:165-169

Authors: Yan LJ

Abstract
It is now well established that reactive oxygen species (ROS), reactive nitrogen species (RNS), and a basal level of oxidative stress are essential for cell survival. It is also well known that while severe oxidative stress often leads to widespread oxidative damage and cell death, a moderate level of oxidative stress, induced by a variety of stressors, can yield great beneficial effects on adaptive cellular responses to pathological challenges in aging and aging-associated disease tolerance such as ischemia tolerance. Here in this review, I term this moderate level of oxidative stress as positive oxidative stress, which usually involves imprinting molecular signatures on lipids and proteins via formation of lipid peroxidation by-products and protein oxidation adducts. As ROS/RNS are short-lived molecules, these molecular signatures can thus execute the ultimate function of ROS/RNS. Representative examples of lipid peroxidation products and protein oxidation adducts are presented to illustrate the role of positive oxidative stress in a variety of pathological settings, demonstrating that positive oxidative stress could be a valuable prophylactic and/or therapeutic approach targeting aging and aging-associated diseases.

PMID: 25460727 [PubMed - as supplied by publisher]

Sequencing the hypervariable regions of human mitochondrial DNA using massively parallel sequencing: Enhanced data acquisition for DNA samples encountered in forensic testing.

Wed, 12/03/2014 - 11:30pm

Sequencing the hypervariable regions of human mitochondrial DNA using massively parallel sequencing: Enhanced data acquisition for DNA samples encountered in forensic testing.

Leg Med (Tokyo). 2014 Oct 25;

Authors: Davis C, Peters D, Warshauer D, King J, Budowle B

Abstract
Mitochondrial DNA testing is a useful tool in the analysis of forensic biological evidence. In cases where nuclear DNA is damaged or limited in quantity, the higher copy number of mitochondrial genomes available in a sample can provide information about the source of a sample. Currently, Sanger-type sequencing (STS) is the primary method to develop mitochondrial DNA profiles. This method is laborious and time consuming. Massively parallel sequencing (MPS) can increase the amount of information obtained from mitochondrial DNA samples while improving turnaround time by decreasing the numbers of manipulations and more so by exploiting high throughput analyses to obtain interpretable results. In this study 18 buccal swabs, three different tissue samples from five individuals, and four bones samples from casework were sequenced at hypervariable regions I and II using STS and MPS. Sample enrichment for STS and MPS was PCR-based. Library preparation for MPS was performed using Nextera® XT DNA Sample Preparation Kit and sequencing was performed on the MiSeq™ (Illumina, Inc.). MPS yielded full concordance of base calls with STS results, and the newer methodology was able to resolve length heteroplasmy in homopolymeric regions. This study demonstrates short amplicon MPS of mitochondrial DNA is feasible, can provide information not possible with STS, and lays the groundwork for development of a whole genome sequencing strategy for degraded samples.

PMID: 25459369 [PubMed - as supplied by publisher]

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