Recent Research Articles from UNTHSC

Subscribe to Recent Research Articles from UNTHSC  feed Recent Research Articles from UNTHSC
NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
Updated: 1 hour 18 min ago

Immune senescence: Significance of the stromal microenvironment.

Wed, 08/17/2016 - 14:30

Immune senescence: Significance of the stromal microenvironment.

Clin Exp Immunol. 2016 Aug 16;

Authors: Masters AR, Haynes L, Su DM, Palmer DB

Abstract
The immune system undergoes age-associated changes known as immunosenescence, resulting in increased susceptibility to infections, cancers and autoimmunity in the aged. The basis of our understanding of immunosenescence has been primarily derived from studies examining intrinsic defects within many of the cells of the immune system. While these studies have provided insight into the mechanisms of immunosenescence, a picture is now emerging that the stromal microenvironment within lymphoid organs also contributes significantly to the age-associated decline of immune function. These extrinsic defects appear to impact the functional activity of immune cells and may offer a potential target to recover immune activity. Indeed, rejuvenation studies which have targeted the stromal niche have successfully restored immune function in the aged, highlighting the impact of the microenvironment towards the aetiology of immunosenescence. This article is protected by copyright. All rights reserved.

PMID: 27529161 [PubMed - as supplied by publisher]

Blimp-1/PRDM1 regulates the transcription of human CS1 (SLAMF7) gene in NK and B cells.

Wed, 08/17/2016 - 14:30
Related Articles

Blimp-1/PRDM1 regulates the transcription of human CS1 (SLAMF7) gene in NK and B cells.

Immunobiology. 2016 Jan;221(1):31-9

Authors: Kim JR, Mathew SO, Mathew PA

Abstract
CS1 (CRACC/CD319/SLAMF7) is a member of SLAM (Signaling Lymphocyte Activation Molecule) family receptors and is expressed on NK cells, a subset of CD8(+) T lymphocytes, activated monocytes, mature dendritic cells and activated B cells. In NK cells, CS1 signaling induces cytolytic function of NK cells against targets whereas in B cells CS1 induces proliferation and autocrine cytokine production. CS1 is upregulated in multiple myeloma cells and contributes to clonogenic growth and tumorigenicity. However, the mechanism of CS1 upregulation is unknown. In this study, we analyzed the transcriptional regulation of human CS1 gene in NK and B cells. The promoter region of CS1 contains a Blimp-1/PRDM1 binding site and relative luciferase activities of successive deletion mutants of CS1 promoter were different between Blimp-1/PRDM1-positive and Blimp-1/PRDM1-negative cells. Proximal region of CS1 promoter contains a CAAT box and atypical TATA-box that might result in common transcription initiation at -29 nucleotides upstream of the ATG translation start codon. Electrophoretic Mobility Shift Assay (EMSA) and Chromatin Immunoprecipitation (ChIP) assays revealed Blimp-1/PRDM1 binds to the CS1 promoter region. Mutating the Blimp-1/PRDM1 site at -750 to -746 decreased the transcriptional activity of CS1 promoter implicating a trans-activating function of Blimp-1/PRDM1 in human CS1 gene regulation. The finding that Blimp-1/PRDM1 enhances transcription of CS1 gene in multiple myeloma cells may help in developing novel strategies for therapeutic intervention in multiple myeloma.

PMID: 26310579 [PubMed - indexed for MEDLINE]

The Impact of Race and Neighborhood Racial Composition on Preventable Readmissions for Diabetic Medicare Home Health Beneficiaries.

Tue, 08/16/2016 - 10:32
Related Articles

The Impact of Race and Neighborhood Racial Composition on Preventable Readmissions for Diabetic Medicare Home Health Beneficiaries.

J Racial Ethn Health Disparities. 2016 Aug 11;

Authors: Chen HF, Homan S, Carlson E, Popoola T, Radhakrishnan K

Abstract
BACKGROUND: The recommended home health financial penalty program for preventable readmission does not factor race/ethnicity and neighborhood racial compositions into the determination of preventable readmission rates. Home health agencies may avoid beneficiaries from certain racial/ethnic groups and neighborhoods if these two factors have an effect on preventable readmissions. We examined the association between preventable readmissions with race/ethnicity and neighborhood racial composition.
METHODS: Several 2009 national data were used, such as the Master Beneficiary Summary File, Medicare Provider Analysis and Review File, and Outcome Assessment Information Set. Our sample consisted of diabetic Medicare home health beneficiaries (African-Americans and Whites only). We analyzed predictors of time-to-first 30-day preventable readmission, including short/long-term diabetic complications, chronic obstructive pulmonary disease/asthma, bacterial pneumonia, dehydration, urinary tract infection, hypertension, heart failure, angina without procedure, uncontrolled diabetes, and lower-extremity amputation.
RESULTS: There were 86,567, 17,262, and 11,392 observations in neighborhoods with low (6 % African-Americans), moderate (35 % African-Americans), and high (76 % African-Americans) density of African-Americans, respectively. Using Cox regression models, we found that in neighborhoods with moderate and high density of African-Americans, African-Americans had 21 % (hazard ratio (HR) 1.21; 95 % confidence interval (CI) 1.04-1.39) and 24 % (HR 1.24; 95 % CI 1.01-1.52) significantly higher hazards of 30-day preventable readmissions than Whites, respectively.
CONCLUSION: Race and neighborhood racial compositions are beyond home health providers' control. These two factors should be considered as covariates for the preventable readmissions in the recommended home health financial penalty program.

PMID: 27514389 [PubMed - as supplied by publisher]

Increased Partner Risk Characteristic Among Adolescents Using Alcohol In the Moment.

Fri, 08/12/2016 - 10:31

Increased Partner Risk Characteristic Among Adolescents Using Alcohol In the Moment.

Sex Transm Dis. 2016 Sep;43(9):537-541

Authors: Staras SA, Livingston MD, Komro KA

Abstract
BACKGROUND: Alcohol is a recognized risk factor for sexually transmitted diseases acquisition, but the mechanism is unclear. Potentially, adolescents using alcohol in the 2 hours before sex (in-the-moment use) have riskier sexual partners.
METHODS: We used multivariable logistic regression to examine the association between in-the-moment alcohol use and partner risk characteristics reported for the most recent sex among primarily 17- to 18-year-old adolescents originally recruited from a representative sample of Chicago public elementary schools. We created 3 composite partner risk profiles: partner familiarity risk (casual and unexpected), partner context risk (age discordance and met in public), and overall risk using all measures except partner alcohol use.
RESULTS: Teens who reported any in-the-moment alcohol use were more likely than nondrinking teens to report casual (adjusted odds ratio [AOR], 3.2; 95% confidence interval [95% CI], 2.1-4.9), unexpected (AOR, 1.6; 95% CI, 1.0-2.5), age discordant (AOR, 3.0; 95% CI, 2.0-4.6), or met in public partners (AOR, 1.4; 95% CI, 1.0 to 2.1). For each composite measure, the number of partner risk characteristics reported increased linearly with the percent of teens drinking in the moment (Cochran-Armitage trend, P < 0.0001). Compared with zero characteristics, in-the-moment alcohol use was associated with increased odds of reporting 1 (AOR, 2.8; 95% CI, 1.7-4.5), 2 (AOR, 4.6; 95% CI, 2.7, 7.6), or 3 to 4 characteristics (AOR, 7.1; 95% CI, 3.3-15.3).
CONCLUSIONS: Our findings expand the link between in-the-moment alcohol use and partner risk reported in prior studies to encompass adolescents' general sexual experiences and additional partner characteristics including the highly associated composite characteristics.

PMID: 27513378 [PubMed - as supplied by publisher]

Patient-centered medical home features and expenditures by medicare beneficiaries.

Fri, 08/12/2016 - 10:31
Related Articles

Patient-centered medical home features and expenditures by medicare beneficiaries.

Am J Manag Care. 2014 May;20(5):379-85

Authors: Stockbridge EL, Philpot LM, Pagán JA

Abstract
OBJECTIVES: To determine the impact of individual features of the patient-centered medical home (PCMH) care model on next-year healthcare expenditures including outpatient, inpatient, emergency department, pharmacy, and total healthcare expenditures among Medicare beneficiaries 65 years and older.
STUDY DESIGN: Analysis of retrospective longitudinal survey data. Methods Longitudinal files from the Medical Expenditure Panel Survey were analyzed. Differences in expenditures for individuals whose usual sources of care did or did not have different PCMH features were estimated using recycled predictions from generalized linear regression models.
RESULTS: Having little to no difficulty contacting the regular source of care over the telephone during regular business hours was associated with significantly lower total and inpatient expenditures over the next year (differences of $2867 and $3736, respectively). Having a regular source of care with office hours at night or on weekends was associated with significantly lower outpatient, emergency department, and other expenditures (differences of $535, $103, and $328, respectively). Pharmacy expenditures were significantly higher for individuals whose usual source of care inquired about medications and treatments prescribed by other doctors (difference of $362).
CONCLUSIONS: This study points out the need to identify how individual PCMH features impact healthcare expenditures across different policy-relevant categories. Practices that have not fully adopted a PCMH model can still make progress in improving quality and controlling costs by adopting even some modest features of the PCMH model.

PMID: 25181567 [PubMed - indexed for MEDLINE]

A sex difference in oxidative stress and behavioral suppression induced by ethanol withdrawal in rats.

Wed, 08/10/2016 - 06:30

A sex difference in oxidative stress and behavioral suppression induced by ethanol withdrawal in rats.

Behav Brain Res. 2016 Aug 5;

Authors: Jung ME, Metzger DB

Abstract
Ethanol withdrawal (EW) is referred to the abrupt termination of long-term heavy drinking, and provokes oxidative brain damage. Here, we investigated whether the cerebellum and hippocampus of female rats are less affected by prooxidant EW than male rats due to the antioxidant effect of 17β-estradiol (E2). Female and male rats received a four-week ethanol diet and three-week withdrawal per cycle for two cycles. Some female rats were ovariectomized with E2 or antioxidant (Vitamin E+Co-Q10) treatment. Measurements were cerebellum (Rotarod) and hippocampus (water-maze)-related behaviors, oxidative markers (O2•-, malondialdehyde, protein carbonyls), mitochondrial membrane swelling, and a key mitochondrial enzyme, cytochrome c oxidase (CcO). Separately, HT22 (hippocampal) cells were subjected to ethanol-exposure and withdrawal for two cycles to assess the effect of a CcO inhibitor on E2's protection for mitochondrial respiration and cell viability. Ethanol-withdrawn female rats showed a smaller increase in oxidative markers in cerebellum and hippocampus than male rats, and E2 treatment decreased the oxidative markers. Compared to male counterparts, ethanol-withdrawn female rats showed better Rotarod but poorer water-maze performance, accompanied by more severe mitochondrial membrane swelling and CcO suppression in hippocampus. E2 or antioxidant treatment improved Rotarod but not water-maze performance. In the presence of a CcO inhibitor, E2 treatment failed to protect mitochondrial respiration and cell viability from EW. These data suggest that antioxidant E2 contributes to smaller oxidative stress in ethanol-withdrawn female than male rats. They also suggest that EW-induced severe mitochondrial damage in hippocampus may blunt E2's antioxidant protection for hippocampus-related behavior.

PMID: 27503149 [PubMed - as supplied by publisher]

δ-Opioid receptors: Pivotal role in intermittent hypoxia-augmentation of cardiac parasympathetic control and plasticity.

Tue, 08/09/2016 - 06:31
Related Articles

δ-Opioid receptors: Pivotal role in intermittent hypoxia-augmentation of cardiac parasympathetic control and plasticity.

Auton Neurosci. 2016 Jul 25;

Authors: Estrada JA, Barlow MA, Yoshishige D, Williams AG, Downey HF, Mallet RT, Caffrey JL

Abstract
BACKGROUND: Intermittent hypoxia training (IHT) produces robust myocardial protection against ischemia-reperfusion induced infarction and arrhythmias. Blockade of this cardioprotection by antagonism of either β1-adrenergic or δ-opioid receptors (δ-OR) suggests autonomic and/or opioidergic adaptations.
PURPOSE: To test the hypothesis that IHT shifts cardiac autonomic balance toward greater cholinergic and opioidergic influence.
METHODS: Mongrel dogs completed 20d IHT, non-hypoxic sham training, or IHT with the δ-OR antagonist naltrindole (200μg/kgsc). The vagolytic effect of the δ-OR agonist met-enkephalin-arg-phe delivered by sinoatrial microdialysis was evaluated following IHT. Sinoatrial, atrial and left ventricular biopsies were analyzed for changes in δ-OR, the neurotrophic monosialoganglioside, GM-1, and cholinergic and adrenergic markers.
RESULTS: IHT enhanced vagal bradycardia vs. sham dogs (P<0.05), and blunted the δ2-OR mediated vagolytic effect of met-enkephalin-arg-phe. The GM-1 labeled fibers overlapped strongly with cholinergic markers, and IHT increased the intensity of both signals (P<0.05). IHT increased low and high intensity vesicular acetylcholine transporter labeling of sinoatrial nodal fibers (P<0.05) suggesting an increase in parasympathetic arborization. IHT reduced select δ-OR labeled fibers in both the atria and sinoatrial node (P<0.05) consistent with moderation of the vagolytic δ2-OR signaling described above. Furthermore, blockade of δ-OR signaling with naltrindole during IHT increased the protein content of δ-OR (atria and ventricle) and vesicular acetylcholine transporter (atria) vs. sham and untreated IHT groups. IHT also reduced the sympathetic marker, tyrosine hydroxylase in ventricle (P<0.05).
SUMMARY: IHT shifts cardiac autonomic balance in favor of parasympathetic control via adaptations in opioidergic, ganglioside, and adrenergic systems.

PMID: 27498137 [PubMed - as supplied by publisher]

Phase 3 Evaluation of HP802-247 in the Treatment of Chronic Venous Leg Ulcers.

Tue, 08/09/2016 - 06:31
Related Articles

Phase 3 Evaluation of HP802-247 in the Treatment of Chronic Venous Leg Ulcers.

Wound Repair Regen. 2016 Aug 6;

Authors: Kirsner RS, Vanscheidt W, Keast DH, Lantis JC, Dove CR, Cazzell SM, Vartivarian M, Augustin M, Marston WA, McCoy ND, Cargill DI, Lee TD, Dickerson JE, Slade HB, HP802-247 Study Group

Abstract
In 2012 we reported promising results from a Phase 2 clinical trial of HP802-247, a novel spray-applied investigational treatment for chronic venous leg ulcers (VLU) consisting of human, allogeneic fibroblasts and keratinocytes. We now describe Phase 3 clinical testing of HP802-247, its failure to detect efficacy, and subsequent investigation into the root causes of the failure. Two randomized, controlled trials enrolled a total of 673 adult outpatients at 96 centers in North America and Europe. The primary endpoint was the proportion of ulcers with confirmed closure at the end of 12 weeks of treatment. An investigation into the root cause for the failure of HP802-247 to show efficacy in these two Phase 3 trials was initiated immediately following the initial review of the North American trial results. 421 patients were enrolled in the North American (HP802-247, 211; Vehicle 210) and 252 in the European (HP802-247, 131; Vehicle 121) trials. No difference in proportion of closed ulcers at week 12 was observed between treatment groups for either the North American (HP802-247, 61.1%; Vehicle 60.0%; P=0.5896) or the European (HP802-247, 47.0%; Vehicle 50.0%; P=0.5348) trials. Thorough investigation found no likelihood that design or execution of the trials contributed to the failure. Variability over time during the trials in the clinical response implicated the quality of the cells comprising HP802-247. Concordance between the two separate, randomized, controlled trials with distinct, non-overlapping investigative sites and independent monitoring teams renders the possibility of a Type II error vanishingly small and provides strong credibility for the unexpected lack of efficacy observed. The most likely causative factors for the efficacy failure in Phase 3 was phenotypic change in the cells (primarily keratinocytes) leading to batch to batch variability due to the age of the cell banks. This article is protected by copyright. All rights reserved.

PMID: 27495869 [PubMed - as supplied by publisher]

Treadmill exercise within lower body negative pressure protects leg lean tissue mass and extensor strength and endurance during bed rest.

Tue, 08/09/2016 - 06:31
Related Articles

Treadmill exercise within lower body negative pressure protects leg lean tissue mass and extensor strength and endurance during bed rest.

Physiol Rep. 2016 Aug;4(15)

Authors: Schneider SM, Lee SM, Feiveson AH, Watenpaugh DE, Macias BR, Hargens AR

Abstract
Leg muscle mass and strength are decreased during reduced activity and non-weight-bearing conditions such as bed rest (BR) and spaceflight. Supine treadmill exercise within lower body negative pressure (LBNPEX) provides full-body weight loading during BR and may prevent muscle deconditioning. We hypothesized that a 40-min interval exercise protocol performed against LBNPEX 6 days week(-1) would attenuate losses in leg lean mass (LLM), strength, and endurance during 6° head-down tilt BR, with similar benefits for men and women. Fifteen pairs of healthy monozygous twins (8 male and 7 female pairs) completed 30 days of BR with one sibling of each twin pair assigned randomly as the non-exercise control (CON) and the other twin as the exercise subject (EX). Before and after BR, LLM and isokinetic leg strength and endurance were measured. Mean knee and ankle extensor and flexor strength and endurance and LLM decreased from pre- to post-BR in the male CON subjects (P < 0.01), but knee extensor strength and endurance, ankle extensor strength, and LLM were maintained in the male EX subjects. In contrast, no pre- to post-BR changes were significant in the female subjects, either CON or EX, likely due to their lower pre-BR values. Importantly, the LBNPEX countermeasure prevents or attenuates declines in LLM as well as extensor leg strength and endurance. Individuals who are stronger, have higher levels of muscular endurance, and/or have greater LLM are likely to experience greater losses during BR than those who are less fit.

PMID: 27495299 [PubMed - in process]

Ischemia-induced Angiogenesis is Attenuated in Aged Rats.

Sun, 08/07/2016 - 10:33
Related Articles

Ischemia-induced Angiogenesis is Attenuated in Aged Rats.

Aging Dis. 2016 Aug;7(4):326-35

Authors: Tang Y, Wang L, Wang J, Lin X, Wang Y, Jin K, Yang GY

Abstract
To study whether focal angiogenesis is induced in aged rodents after permanent distal middle cerebral artery occlusion (MCAO), young adult (3-month-old) and aged (24-month-old) Fisher 344 rats underwent MCAO and sacrificed up to two months after MCAO. Immunohistochemistry and synchrotron radiation microangiography were performed to examine the number of newly formed blood vessels in both young adult and aged rats post-ischemia. We found that the number of capillaries and small arteries in aged brain was the same as young adult brain. In addition, we found that after MCAO, the number of blood vessels in the peri-infarct region of ipsilateral hemisphere in aged ischemic rats was significantly increased compared to the aged sham rats (p<0.05). We also confirmed that ischemia-induced focal angiogenesis occurred in young adult rat brain while the blood vessel density in young adult ischemic brain was significantly higher than that in the aged ischemic brain (p<0.05). Our data suggests that focal angiogenesis in aged rat brain can be induced in response to ischemic brain injury, and that aging impedes brain repairing and remodeling after ischemic stroke, possible due to the limited response of angiogenesis.

PMID: 27493831 [PubMed]

Fully Threaded Versus Partially Threaded Screws: Determining Shear in Cancellous Bone Fixation.

Sun, 08/07/2016 - 10:33
Related Articles

Fully Threaded Versus Partially Threaded Screws: Determining Shear in Cancellous Bone Fixation.

J Foot Ankle Surg. 2015 Nov-Dec;54(6):1021-4

Authors: Downey MW, Kosmopoulos V, Carpenter BB

Abstract
Many researchers have studied and compared various forms of intraosseous fixation. No studies have examined the effects of shear through stiffness and failure strength of a fully threaded versus a partially threaded screw. Our hypothesis was that the fully threaded lag screw technique would provide greater shear strength and resistance. Thirty-six synthetic sawbone blocks were used to test screw fixation. In group 1 (n = 9), 2 blocks were fixed together using a fully threaded 4.0-mm stainless steel cancellous bone screw and the lag technique. In group 2 (n = 8), 2 blocks were fixed together using the standard manufacturer-recommended method for inserting 4.0-mm partially threaded stainless steel cancellous bone screws. The constructs were then mechanically tested. Shear was applied by compressing each construct at an axial displacement rate of 0.5 mm/s until failure. The fully threaded screw had a significantly greater (p = .026) initial stiffness (106.4 ± 15.8 N/mm) than the partially threaded screw (80.1 ± 27.5 N/mm). The yield load and displacement for the fully threaded group (429.4 ± 11.7 N and 7.2 ± 0.35 mm) were 64% and 67% greater than those for the partially threaded screw group (261.4 ± 26.1 N and 4.3 ± 1.03 mm), respectively. The results of the present study have demonstrated the importance of a full-thread construct to prevent shear and to decrease strain at the fracture. The confirmation of our hypothesis questions the future need and use of partially threaded screws for cancellous bone fixation.

PMID: 26210079 [PubMed - indexed for MEDLINE]

Treatment with an orally bioavailable prodrug of 17β-estradiol alleviates hot flushes without hormonal effects in the periphery.

Tue, 08/02/2016 - 10:30

Treatment with an orally bioavailable prodrug of 17β-estradiol alleviates hot flushes without hormonal effects in the periphery.

Sci Rep. 2016;6:30721

Authors: Merchenthaler I, Lane M, Sabnis G, Brodie A, Nguyen V, Prokai L, Prokai-Tatrai K

Abstract
Estrogen deprivation has a profound effect on the female brain. One of the most obvious examples of this condition is hot flushes. Although estrogens relieve these typical climacteric symptoms, many women do not want to take them owing to unwanted side-effects impacting, for example, the uterus, breast and blood. Therefore, there is a need for developing safer estrogen therapies. We show here that treatment with 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), a novel brain-targeting bioprecursor prodrug of the main human estrogen, 17β-estradiol, alleviates hot flushes in rat models of thermoregulatory dysfunction of the brain. Oral administration of DHED elicits a significant reduction of tail skin temperature (TST) rise representing hot flushes in the morphine-dependent ovariectomized rat model and results in the restoration of estrogen deprivation-induced loss of diurnal rhythm in TST. These beneficial effects occur without detrimental peripheral hormonal exposure; thus, the treatment avoids potentially harmful stimulation of estrogen-sensitive peripheral organs, including the uterus and the anterior pituitary, or the proliferation of MCF-7a breast cancer cell xenografts. Our promising preclinical assessments warrant further considerations of DHED for the development of a brain-selective 17β-estradiol therapy to relieve hot flushes without undesirable peripheral side-effects.

PMID: 27477453 [PubMed - in process]

A Depressive Endophenotype for Predicting Cognitive Decline among Mexican American Adults and Elders.

Sat, 07/30/2016 - 06:32

A Depressive Endophenotype for Predicting Cognitive Decline among Mexican American Adults and Elders.

J Alzheimers Dis. 2016 Jul 25;

Authors: Johnson LA, Gamboa A, Vintimilla R, Edwards M, Hall J, Weiser B, Yadav M, Dickensheets T, O'Bryant SE

Abstract
BACKGROUND: Late life depression is a prodromal feature and a risk factor for Alzheimer's disease (AD) and mild cognitive impairment (MCI). We identified five items in the Geriatric Depression scale (DepE) that are important as a risk for MCI and AD: memory problems, feeling blue, crying, feeling worthless, and trouble concentrating.
OBJECTIVE: Our goal was to examine the relationship between DepE and cognition in a cohort of Mexican Americans.
METHODS: Data from 317 Mexican Americans from the HABLE study were analyzed. DepE scores were dichotomized into two groups: endorsement of 1 item or less, and endorsement of 2 or more items. Cognition was assessed via neuropsychological tests, and diagnosis was based on consensus review. We utilized linear regression to examine the association between DepE and cognitive performance, and logistic regression to examine the utility of DepE in predicting MCI. To examine the impact of DepE on memory over 12 months, we performed ANOVA analysis.
RESULTS: Elevated DepE scores were associated with poorer performance on various measures of memory and cognition, but not executive or visual spatial skills. Over 12 months, we found a decline in immediate memory among women but not men. Those with high scores were 4 times more likely to have MCI. ANOVA of total scores revealed differences between groups on immediate memory (p < 0.05) in women, with no significant differences on delay recall in either gender.
CONCLUSION: DepE can be utilized in Mexican Americans to identify those at risk of memory related cognitive decline.

PMID: 27472872 [PubMed - as supplied by publisher]

Genome Sequence of a Proteus mirabilis Strain Isolated from the Salivary Glands of Larval Lucilia sericata.

Sat, 07/30/2016 - 06:32

Genome Sequence of a Proteus mirabilis Strain Isolated from the Salivary Glands of Larval Lucilia sericata.

Genome Announc. 2016;4(4)

Authors: Yuan Y, Zhang Y, Fu S, Crippen TL, Visi DK, Benbow ME, Allen MS, Tomberlin JK, Sze SH, Tarone AM

Abstract
We announce a draft genome sequence of a Proteus mirabilis strain derived from Lucilia sericata salivary glands. This strain is demonstrated to attract and induce oviposition by L. sericata, a common blow fly important to medicine, agriculture, and forensics. The genome sequence will help dissect interkingdom communication between the species.

PMID: 27469950 [PubMed]

Tip110: Physical properties, primary structure, and biological functions.

Fri, 07/29/2016 - 06:31
Related Articles

Tip110: Physical properties, primary structure, and biological functions.

Life Sci. 2016 Mar 15;149:79-95

Authors: Whitmill A, Timani KA, Liu Y, He JJ

Abstract
HIV-1 Tat-interacting protein of 110kDa (Tip110), also referred to as squamous cell carcinoma antigen recognized by T cells 3 (Sart3), p110 or p110(nrb), was initially identified as a cDNA clone (KIAA0156) without annotated functions. Over the past twenty years, several functions have been attributed to this protein. The proposed biological functions include roles for Tip110 in pre-mRNA splicing, gene transcription, stem cell biology, and development. Dysregulation of Tip110 is also a contributing factor in the development of cancer and other human diseases. It is clear that our understanding of this protein is rapidly evolving. In this review, we aimed to provide a summary of all the existing literature on this gene/protein and its proposed biological functions.

PMID: 26896687 [PubMed - indexed for MEDLINE]

MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics.

Thu, 07/28/2016 - 06:31

MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics.

Oncotarget. 2016 Jul 23;

Authors: Kpetemey M, Chaudhary P, Van Treuren T, Vishwanatha JK

Abstract
Migration and invasion enhancer 1 (MIEN1) is an important regulator of cell migration and invasion. MIEN1 overexpression represents an oncogenic event that promotes tumor cell dissemination and metastasis. The underlying mechanism by which MIEN1 regulates migration and invasion has yet to be deciphered. Here, we demonstrate that MIEN1 acts as a cytoskeletal-signaling adapter protein to drive breast cancer cell migration. MIEN1 localization is concentrated underneath the actin-enriched protrusive structures of the migrating breast cancer cells. Depletion of MIEN1 led to the loss of actin-protrusive structures whereas the over-expression of MIEN1 resulted in rich and thick membrane extensions. Knockdown of MIEN1 also decreased the cell-substratum adhesion, suggesting a role for MIEN1 in actin cytoskeletal dynamics. Our results show that MIEN1 supports the transition of G-actin to F-actin polymerization and stabilizes F-actin polymers. Additionally, MIEN1 promotes cellular adhesion and actin dynamics by inducing phosphorylation of FAK at Tyr-925 and reducing phosphorylation of cofilin at Ser-3, which results in breast cancer cell migration. Collectively, our data show that MIEN1 plays an essential role in maintaining the plasticity of the dynamic membrane-associated actin cytoskeleton, which leads to an increase in cell motility. Hence, targeting MIEN1 might represent a promising means to prevent breast tumor metastasis.

PMID: 27462783 [PubMed - as supplied by publisher]

Function of Ubiquitin (Ub) Specific Protease 15 (USP15) in HIV-1 Replication and Viral Protein Degradation.

Thu, 07/28/2016 - 06:31

Function of Ubiquitin (Ub) Specific Protease 15 (USP15) in HIV-1 Replication and Viral Protein Degradation.

Virus Res. 2016 Jul 23;

Authors: Pyeon D, Timani KA, Gulraiz F, Park IW

Abstract
HIV-1 Nef is necessary and may be sufficient for HIV-1-associated AIDS pathogenicity, in that knockout of Nef alone can protect HIV-infected patients from AIDS. We therefore investigated the feasibility of physical knockout of Nef, using the host ubiquitin proteasome system in HIV-1-infected cells. Our co-immunoprecipitation analysis demonstrated that Nef interacted with ubiquitin specific protease 15 (USP15), and that USP15, which is known to stabilize cellular proteins, degraded Nef. Nef could also cause decay of USP15, although Nef-mediated degradation of USP15 was weaker than USP15-mediated Nef degradation. Direct interaction between Nef and USP15 was essential for the observed reciprocal decay of the proteins. Further, USP15 degraded not only Nef but also HIV-1 structural protein, Gag, thereby substantially inhibiting HIV-1 replication. However, Gag did not degrade USP15, indicating that the Nef and USP15 complex, in distinction to other viral proteins, play an integral role in coordinating viral protein degradation and hence HIV-1 replication. Moreover, Nef and USP15 globally suppressed ubiquitylation of cellular proteins, indicating that these proteins are major determinants for the stability of cellular as well as viral proteins. Taken together, these data indicate that Nef and USP15 are vital in regulating degradation of viral and cellular proteins and thus HIV-1 replication, and specific degradation of viral, not cellular proteins, by USP15 points to USP15 as a candidate therapeutic agent to combat AIDS by eliminating viral proteins from the infected cells via USP15-mediated proteosomal degradation.

PMID: 27460547 [PubMed - as supplied by publisher]

Identification and Characterization of Novel Matrix-Derived Bioactive Peptides: A Role for Collagenase from Santyl® Ointment in Post-Debridement Wound Healing?

Thu, 07/28/2016 - 06:31
Related Articles

Identification and Characterization of Novel Matrix-Derived Bioactive Peptides: A Role for Collagenase from Santyl® Ointment in Post-Debridement Wound Healing?

PLoS One. 2016;11(7):e0159598

Authors: Sheets AR, Demidova-Rice TN, Shi L, Ronfard V, Grover KV, Herman IM

Abstract
Debridement, the removal of diseased, nonviable tissue, is critical for clinicians to readily assess wound status and prepare the wound bed for advanced therapeutics or downstream active healing. Removing necrotic slough and eschar through surgical or mechanical methods is less specific and may be painful for patients. Enzymatic debridement agents, such as Clostridial collagenase, selectively and painlessly degrade devitalized tissue. In addition to its debriding activities, highly-purified Clostridial collagenase actively promotes healing, and our past studies reveal that extracellular matrices digested with this enzyme yield peptides that activate cellular migratory, proliferative and angiogenic responses to injury in vitro, and promote wound closure in vivo. Intriguingly, while collagenase Santyl® ointment, a sterile preparation containing Clostridial collagenases and other non-specific proteases, is a well-accepted enzymatic debridement agent, its role as an active healing entity has never been established. Based on our previous studies of pure Clostridial collagenase, we now ask whether the mixture of enzymes contained within Santyl® produces matrix-derived peptides that promote cellular injury responses in vitro and stimulate wound closure in vivo. Here, we identify novel collagen fragments, along with collagen-associated peptides derived from thrombospondin-1, multimerin-1, fibronectin, TGFβ-induced protein ig-h3 and tenascin-C, generated from Santyl® collagenase-digested human dermal capillary endothelial and fibroblastic matrices, which increase cell proliferation and angiogenic remodeling in vitro by 50-100% over controls. Using an established model of impaired healing, we further demonstrate a specific dose of collagenase from Santyl® ointment, as well as the newly-identified and chemically-synthesized ECM-derived peptides significantly increase wound re-epithelialization by 60-100% over saline-treated controls. These results not only confirm and extend our earlier studies using purified collagenase- and matrix-derived peptides to stimulate healing in vitro and in vivo, but these Santyl®-generated, matrix-derived peptides may also represent exciting new opportunities for creating advanced wound healing therapies that are enabled by enzymatic debridement and potentially go beyond debridement.

PMID: 27459729 [PubMed - in process]

Introduction to special issue on Advances in blood-based biomarkers of Alzheimer's disease.

Thu, 07/28/2016 - 06:31
Related Articles

Introduction to special issue on Advances in blood-based biomarkers of Alzheimer's disease.

Alzheimers Dement (Amst). 2016;3:110-2

Authors: O'Bryant SE

PMID: 27453933 [PubMed]

A blood screening test for Alzheimer's disease.

Thu, 07/28/2016 - 06:31
Related Articles

A blood screening test for Alzheimer's disease.

Alzheimers Dement (Amst). 2016;3:83-90

Authors: O'Bryant SE, Edwards M, Johnson L, Hall J, Villarreal AE, Britton GB, Quiceno M, Cullum CM, Graff-Radford NR

Abstract
INTRODUCTION: This study combined data across four independent cohorts to examine the positive and negative predictive values of an Alzheimer's disease (AD) blood test if implemented in primary care.
METHODS: Blood samples from 1329 subjects from multiple independent, multiethnic, community-based, and clinic-based cohorts were analyzed. A "locked-down" referent group of 1128 samples was generated with 201 samples randomly selected for validation purposes. Random forest analyses were used to create the AD blood screen. Positive (PPV) and negative (NPV) predictive values were calculated.
RESULTS: In detecting AD, PPV was 0.81, and NPV was 0.95 while using the full AD blood test. When detecting mild cognitive impairment, PPV and NPV were 0.74 and 0.93, respectively. Preliminary analyses were conducted to detect any "neurodegenerative disease". The full 21-protein AD blood test yielded a PPV of 0.85 and NPV of 0.94.
DISCUSSION: The present study creates the first-ever multiethnic referent sample that spans community-based and clinic-based populations for implementation of an AD blood screen.

PMID: 27453929 [PubMed]

Pages