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2.  Quantification of virus genes provides evidence for seed-bank populations of phycodnaviruses in Lake Ontario, Canada 
The ISME journal  2010;5(5):810-821.
Using quantitative PCR, the abundances of six phytoplankton viruses DNA polymerase (polB) gene fragments were estimated in water samples collected from Lake Ontario, Canada over 26 months. Four of the polB fragments were most related to marine prasinoviruses, while the other two were most closely related to cultivated chloroviruses. Two Prasinovirus-related genes reached peak abundances of >1000 copies ml−1 and were considered ‘high abundance', whereas the other two Prasinovirus-related genes peaked at abundances <1000 copies ml−1 and were considered ‘low abundance'. Of the genes related to chloroviruses, one peaked at ca 1600 copies ml−1, whereas the other reached only ca 300 copies ml−1. Despite these differences in peak abundance, the abundances of all genes monitored were lowest during the late fall, winter and early spring; during these months the high abundance genes persisted at 100–1000 copies ml−1 while the low abundance Prasinovirus- and Chlorovirus-related genes persisted at fewer than ca 100 copies ml−1. Clone libraries of psbA genes from Lake Ontario revealed numerous Chlorella-like algae and two prasinophytes demonstrating the presence of candidate hosts for all types of viruses monitored. Our results corroborate recent metagenomic analyses that suggest that aquatic virus communities are composed of only a few abundant populations and many low abundance populations. Thus, we speculate that an ecologically important characteristic of phycodnavirus communities is seed-bank populations with members that can become numerically dominant when their host abundances reach appropriate levels.
PMCID: PMC3105761  PMID: 21124493
algal viruses; phycodnaviruses; phytoplankton; DNA polymerase; quantitative PCR; freshwater
3.  Assessing Colonoscopy Training Outcomes Using Quality Indicators 
Training numbers for colonoscopy vary among specialties. Tracking colonoscopy quality indicators for program graduates may provide reliable outcome data to improve educational programs and establish training requirements. The purpose of this study was to measure specific colonoscopy quality indicators for a family medicine graduate to determine if outcome can be used to assess the quality of procedure training and contribute to more objective means of establishing training numbers.
We present a case series of the first 800 colonoscopies performed by a newly credentialed family physician who had performed 101 procedures during residency training. Procedure reports and medical records were reviewed for all patients receiving a colonoscopy by this physician from September 2003 to September 2007. Selected quality indicators were compared to recommended colonoscopy standards.
The overall reach-the-cecum rate was 98.6%. Adenomas were detected in 21.6% of females and 33.7% of males. All polyps measuring less than 2 cm were removed. Epinephrine was used for 3 patients with hemostasis after polypectomy. There were no perforations.
Quality indicators for colonoscopy were met after 101 supervised procedures. Postgraduate tracking of nationally recognized colonoscopy quality indicators can provide valuable outcome data to improve residency training and assist in establishing uniform training requirements among specialties.
PMCID: PMC2931191  PMID: 21975712
4.  Endurance Exercise as a Countermeasure for Aging 
Diabetes  2008;57(11):2933-2942.
OBJECTIVE— We determined whether reduced insulin sensitivity, mitochondrial dysfunction, and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity.
RESEARCH DESIGN AND METHODS— Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young (18–30 years old) and older (59–76 years old) subjects. Expression of proteins involved in fuel metabolism was measured by mass spectrometry. Citrate synthase activity, mitochondrial DNA (mtDNA) abundance, and expression of nuclear-encoded transcription factors for mitochondrial biogenesis were measured. SIRT3, a mitochondrial sirtuin linked to lifespan-enhancing effects of caloric restriction, was measured by immunoblot.
RESULTS— Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older subjects, but no age effect was noted. Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals. Although endurance-trained individuals exhibited higher expression of mitochondrial proteins, mtDNA, and mitochondrial transcription factors, there were persisting effects of age. SIRT3 expression was lower with age in sedentary but equally elevated regardless of age in endurance-trained individuals.
CONCLUSIONS— The results demonstrate that reduced insulin sensitivity is likely related to changes in adiposity and to physical inactivity rather than being an inevitable consequence of aging. The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction, although there are persisting effects of age on mtDNA abundance and expression of nuclear transcription factors and mitochondrial protein. Furthermore, exercise may promote longevity through pathways common to effects of caloric restriction.
PMCID: PMC2570389  PMID: 18716044
5.  Identification of a silencer module which selectively represses cyclic AMP-responsive element-dependent gene expression. 
Molecular and Cellular Biology  1995;15(11):6139-6149.
The cyclic AMP (cAMP)-inducible promoter from the rat lactate dehydrogenase A subunit gene (LDH A) is associated with a distal negative regulatory element (LDH-NRE) that represses inherent basal and cAMP-inducible promoter activity. The element is of dyad symmetry, consisting of a palindromic sequence with two half-sites, 5'-TCTTG-3'. It represses the expression of an LDH A/chloramphenicol acetyltransferase (CAT) reporter gene in a dose-dependent, orientation- and position-independent fashion, suggesting that it is a true silencer element. Uniquely, it selectively represses cAMP-responsive element (CRE)-dependent transcription but has no effect on promoters lacking a CRE sequence. The repressing action of LDH-NRE could be overcome by cotransfection with LDH A/CAT vector oligonucleotides containing either the LDH-NRE or CRE sequence. This suggests that the reversal of repression was caused by the removal of functional active, limiting transacting factors which associate with LDH-NRE as well as with CRE. Gel mobility shift, footprinting, and Southwestern blotting assays demonstrated the presence of a 69-kDa protein with specific binding activity for LDH-NRE. Additionally, gel supershift assays with anti-CREB and anti-Fos antibodies indicate the presence of CREB and Fos or antigenically closely related proteins with the LDH-NRE/protein complex. We suggest that the LDH-NRE and CRE modules functionally interact to achieve negative modulation of cAMP-responsive LDH A transcriptional activity.
PMCID: PMC230865  PMID: 7565766
6.  Glioblastoma Behaviors in Three-Dimensional Collagen-Hyaluronan Composite Hydrogels 
ACS applied materials & interfaces  2013;5(19):9276-9284.
Glioblastoma multiforme (GBM) tumors, which arise from glia in the central nervous system (CNS), are one of the most deadly forms of human cancer with a median survival time of ~1 year. Their high infiltrative capacity makes them extremely difficult to treat, and even with aggressive multimodal clinical therapies, outcomes are dismal. To improve understanding of cell migration in these tumors, three-dimensional (3D) multicomponent composite hydrogels consisting of collagen and hyaluronic acid, or hyaluronan (HA), were developed. Collagen is a component of blood vessels known to be associated with GBM migration; whereas, HA is one of the major components of the native brain extracellular matrix (ECM). We characterized hydrogel microstructural features and utilized these materials to investigate patient tumor-derived, single cell morphology, spreading, and migration in 3D culture. GBM morphology was influenced by collagen type with cells adopting a rounded morphology in collagen-IV versus a spindle-shaped morphology in collagen-I/III. GBM spreading and migration were inversely dependent on HA concentration; with higher concentrations promoting little or no migration. Further, noncancerous astrocytes primarily displayed rounded morphologies at lower concentrations of HA; in contrast to the spindle-shaped (spread) morphologies of GBMs. These results suggest that GBM behaviors are sensitive to ECM mimetic materials in 3D and that these composite hydrogels could be used to develop 3D brain mimetic models for studying migration processes.
PMCID: PMC4333346  PMID: 24010546
glioblastoma multiforme; collagen; hyaluronic acid; hydrogel
7.  Vps74 gives phosphatase directions 
The Journal of Cell Biology  2014;206(4):453.
Study reveals how the Sac1 phosphatase removes PtdIns4P from early Golgi membranes.
Study reveals how the Sac1 phosphatase removes PtdIns4P from early Golgi membranes.
PMCID: PMC4137051
8.  Lasp brings a giant down to size 
The Journal of Cell Biology  2014;206(4):452.
PMCID: PMC4137053
9.  Sperm’s sensitive steering machinery 
The Journal of Cell Biology  2014;206(4):452.
PMCID: PMC4137054
10.  MagT1 helps a glycosylase gain acceptance 
The Journal of Cell Biology  2014;206(4):452.
PMCID: PMC4137063
11.  Pronounced and prevalent intersexuality does not impede the ‘Demon Shrimp’ invasion 
PeerJ  2015;3:e757.
Crustacean intersexuality is widespread and often linked to infection by sex-distorting parasites. However, unlike vertebrate intersexuality, its association with sexual dysfunction is unclear and remains a matter of debate. The ‘Demon Shrimp,’ Dikerogammarus haemobaphes, an amphipod that has invaded continental waterways, has recently become widespread in Britain. Intersexuality has been noted in D. haemobaphes but not investigated further. We hypothesise that a successful invasive population should not display a high prevalence of intersexuality if this condition represents a truly dysfunctional phenotype. In addition, experiments have indicated that particular parasite burdens in amphipods may facilitate invasions. The rapid and ongoing invasion of British waterways represents an opportunity to determine whether these hypotheses are consistent with field observations. This study investigates the parasites and sexual phenotypes of D. haemobaphes in British waterways, characterising parasite burdens using molecular screening, and makes comparisons with the threatened Gammarus pulex natives. We reveal that invasive and native populations have distinct parasitic profiles, suggesting the loss of G. pulex may have parasite-mediated eco-system impacts. Furthermore, the parasite burdens are consistent with those previously proposed to facilitate biological invasions. Our study also indicates that while no intersexuality occurs in the native G. pulex, approximately 50% of D. haemobaphes males present pronounced intersexuality associated with infection by the microsporidian Dictyocoela berillonum. This unambiguously successful invasive population presents, to our knowledge, the highest reported prevalence of male intersexuality. This is the clearest evidence to date that such intersexuality does not represent a form of debilitating sexual dysfunction that negatively impacts amphipod populations.
PMCID: PMC4327250
Amphipoda; Crustacea; Invasive species; Intersexuality; Microsporidia
12.  Low Salt Intake Down-regulates the Guanylin Signaling Pathway in Rat Distal Colon 
Gastroenterology  1996;111(6):1714-1721.
Background & Aims
Guanylin, an endogenous gastrointestinal peptide, causes the translocation of NaCl from interstitial fluid to the intestinal lumen. The aim of this study was to examine whether changes in dietary salt intake lead to compensatory changes in expression of the guanylin signaling pathway.
Rats received low-, normal-, or high-sodium diets for 1 week. Colonic guanylin expression was evaluated by Western and Northern blotting, rates of guanylin secretion by measuring biologically active guanylin released into the medium from colon explants, and expression of the guanylin receptor (C-type guanylate cyclase) by Northern blotting and bioassay.
By every criterion, the low-salt diet reduced expression of guanylin to 30%–40% of the level found in control animals. Guanylin receptor expression was also decreased, although less dramatically and with a lower statistical significance. For both guanylin and guanylin receptor, the high-salt diet had no significant effect on expression.
The data support the hypothesis that the guanylin pathway is down-regulated as an adaptive response to salt restriction.
PMCID: PMC4321892  PMID: 8942754
13.  Once-Daily, Single-Tablet Regimens For the Treatment of HIV-1 Infection 
Pharmacy and Therapeutics  2015;40(1):44-55.
Once-daily, single-tablet regimens have become integral to the management of human immunodeficiency virus type 1 infection, partly because they may improve adherence due to a lower pill burden. This article reviews the single-tablet options.
PMCID: PMC4296592  PMID: 25628507
14.  Protective effects of polyunsatutared fatty acids supplementation against testicular damage induced by intermittent hypobaric hypoxia in rats 
Intermittent hypobaric hypoxia (IHH) induces changes in the redox status and structure in rat testis. These effects may be present in people at high altitudes, such as athletes and miners. Polyunsaturated fatty acids (PUFA) can be effective in counteracting these oxidative modifications due to their antioxidants properties. The aim of the work was to test whether PUFA supplementation attenuates oxidative damage in testis by reinforcing the antioxidant defense system. The animals were divided into four groups (7 rats per group): normobaric normoxia (~750 tor; pO2 156 mmHg; Nx); Nx + PUFA, supplemented with PUFA (DHA: EPA = 3:1; 0.3 g kg−1 of body weight per day); hypoxic hypoxia (~428 tor; pO2 90 mmHg; Hx) and, Hx + PUFA. The hypoxic groups were exposed in 4 cycles to 96 h of HH followed by 96 h of normobaric normoxia for 32 days. Total antioxidant capacity (FRAP) and lipid peroxidation (malondialdehyde, MDA) in plasma and reduced (GSH)/oxidized glutathione (GSSG) ratio, tissue lipid peroxidation (TBARS) and antioxidant enzymes activity were assessed at the end of the study in testis. Also, SIRTUIN 1 and HIF-1 protein expression in testis were determined.
IHH increased lipid peroxidation in plasma and HIF-1 protein levels in testis. In addition, IHH reduced FRAP levels in plasma, antioxidant enzymes activities and SIRTUIN 1 protein levels in testis. PUFA supplementation attenuated these effects, inducing the increases in FRAP, in the antioxidant enzymes activity and HIF-1 levels.
These results suggest that the IHH model induces a prooxidant status in plasma and testis. The molecular protective effect of PUFA may involve the induction of an antioxidant mechanism.
PMCID: PMC4307138  PMID: 25613908
Intermittent hypoxia; Testis; Oxidative stress; PUFA; SIRTUIN 1
15.  Exploring the LINC to nuclear envelope spacing 
The Journal of Cell Biology  2014;206(2):146.
PMCID: PMC4107784
16.  Lipids help epithelia stand tall 
The Journal of Cell Biology  2014;206(2):147.
Palmitoylation and phosphoinositides target ankyrin-G/βII-spectrin network to lateral membranes.
Palmitoylation and phosphoinositides target ankyrin-G/βII-spectrin network to lateral membranes.
PMCID: PMC4107785
17.  GAAC pathway limits autophagy to a light snack 
The Journal of Cell Biology  2014;206(2):146.
PMCID: PMC4107790
18.  Deubiquitination helps Rad18 grow more tolerant 
The Journal of Cell Biology  2014;206(2):146.
PMCID: PMC4107792
19.  The Neural Correlates of the Face Attractiveness Aftereffect: A Functional Near-infrared Spectroscopy (fNIRS) Study 
NeuroImage  2013;85(0 1):10.1016/j.neuroimage.2013.04.092.
Extensive behavioral evidence shows that our internal representation of faces, or face prototype, can be dynamically updated by immediate experience. This is illustrated by the robust attractiveness aftereffect phenomenon whereby originally unattractive faces become attractive after we are exposed to a set of unattractive faces. Although behavioral evidence suggests this effect to have a strong neural basis, limited neuroimaging evidence exists. Here we used functional near-infrared spectroscopy methodology (fNIRS) to bridge this gap. During the pre-adaptation trials, participants judged the attractiveness of three sets of faces: normal/undistorted faces, compressed faces (the internal features and distances between them were compressed), and expanded faces (the internal features and distances between them were stretched). Then, participants were shown extremely compressed faces for 5 minutes as adaptation stimuli, after which participants judged the same three sets of faces in post-adaptation trials. Behaviorally, after the adaptation trials, participants rated the compressed faces more attractive whereas they judged the other two sets of faces as less attractive, replicating the robust adaptation effect. fNIRS results showed that short-term exposure to compressed faces led to significant decreases in neural activity to all face types, but in a more extended network of cortical regions in the frontal and occipital cortexes for undistorted faces. Taken together, these findings suggest that the face attractiveness aftereffect mainly reflects changes in the neural representation of the face prototype in response to recent exposures to new face exemplars.
PMCID: PMC3795914  PMID: 23648964
face processing; face perception; fNIRS; attractiveness aftereffects; norm-based
20.  A short Anillin opens the way for germline development 
PMCID: PMC4085704
21.  The fluid dynamics of collective cell migration 
PMCID: PMC4085699
22.  Budding yeast do the Cdc42 two-step 
PMCID: PMC4085706
23.  Defining the kinetochore’s rules of engagement 
Quantitative analyses and computer modeling reveal how a “molecular lawn” fine-tunes the interactions between kinetochores and microtubules.
Quantitative analyses and computer modeling reveal how a “molecular lawn” fine-tunes the interactions between kinetochores and microtubules.
PMCID: PMC4085710
24.  Development of Thalamocortical Connectivity during Infancy and Its Cognitive Correlations 
The Journal of Neuroscience  2014;34(27):9067-9075.
Although commonly viewed as a sensory information relay center, the thalamus has been increasingly recognized as an essential node in various higher-order cognitive circuits, and the underlying thalamocortical interaction mechanism has attracted increasing scientific interest. However, the development of thalamocortical connections and how such development relates to cognitive processes during the earliest stages of life remain largely unknown. Leveraging a large human pediatric sample (N = 143) with longitudinal resting-state fMRI scans and cognitive data collected during the first 2 years of life, we aimed to characterize the age-dependent development of thalamocortical connectivity patterns by examining the functional relationship between the thalamus and nine cortical functional networks and determine the correlation between thalamocortical connectivity and cognitive performance at ages 1 and 2 years. Our results revealed that the thalamus–sensorimotor and thalamus–salience connectivity networks were already present in neonates, whereas the thalamus–medial visual and thalamus–default mode network connectivity emerged later, at 1 year of age. More importantly, brain–behavior analyses based on the Mullen Early Learning Composite Score and visual–spatial working memory performance measured at 1 and 2 years of age highlighted significant correlations with the thalamus–salience network connectivity. These results provide new insights into the understudied early functional brain development process and shed light on the behavioral importance of the emerging thalamocortical connectivity during infancy.
PMCID: PMC4078084  PMID: 24990927
development; functional connectivity; Mullen scores; resting state; thalamus; working memory
25.  Electron Cryo‐Microscopy of TPPS4⋅2HCl Tubes Reveals a Helical Organisation Explaining the Origin of their Chirality† 
Chemphyschem  2013;14(14):3209-3214.
A widely studied achiral porphyrin, which is highly soluble in aqueous solutions (TPPS4), is shown to self‐assemble into helical nanotubes. These were imaged by electron cryo‐microscopy and a state‐of‐the‐art image analysis allows building a map at ∼5 Å resolution, one of the highest obtained so far for molecular materials. The authors were able to trace the apparent symmetry breaking to existing nuclei in the “as received samples”, while carefully purified samples show that both handnesses occur in equal amounts.magnified image
PMCID: PMC4281918  PMID: 23908093
chirality; electron cryo‐microscopy; helical reconstruction; J‐aggregates/H‐aggregates; porphyrinoids; self‐assembly

Results 1-25 (1058)