Citations
All
Search in:AllTitleAbstractAuthor name
Publications
(2K+)
Patents
Grants
Pathways
Clinical trials
Publication
Journal: Molecular Therapy
November/18/2017
Abstract
Unlike the epidermis, which regenerates continually, hair follicles anchored in the subcutis periodically regenerate by spontaneous repetitive cycles of growth (anagen), degeneration (catagen), and rest (telogen). The loss of hair follicles in response to injuries or pathologies such as alopecia endangers certain inherent functions of the skin. Thus, it is of interest to understand mechanisms underlying follicular regeneration in adults. In this work, a phytochemical rich in the natural vitamin E tocotrienol (TRF) served as a productive tool to unveil a novel epidermal pathway of hair follicular regeneration. Topical TRF application markedly induced epidermal hair follicle development akin to that during fetal skin development. This was observed in the skin of healthy as well as diabetic mice, which are known to be resistant to anagen hair cycling. TRF suppressed epidermal E-cadherin followed by 4-fold induction of β-catenin and its nuclear translocation. Nuclear β-catenin interacted with Tcf3. Such sequestration of Tcf3 from its otherwise known function to repress pluripotent factors induced the plasticity factors Oct4, Sox9, Klf4, c-Myc, and Nanog. Pharmacological inhibition of β-catenin arrested anagen hair cycling by TRF. This work reports epidermal E-cadherin/β-catenin as a novel pathway capable of inducing developmental folliculogenesis in the adult skin.
Publication
Journal: Journal of Neurology
December/5/2018
Abstract
Teriflunomide (TRF) and Dimethyl fumarate (DMF) are licensed drugs for relapsing-remitting Multiple Sclerosis (RRMS).We aimed to compare the rate and the time to discontinuation among persons with RRMS (pwRRMS), newly treated with TRF and DMF.A retrospective study on prospectively collected data was performed in nine tertiary MS centers, in Italy. The 24-month discontinuation rate in the two cohorts was the primary study outcome. We also assessed the time to discontinuation and reasons of therapy withdrawn. Discontinuation of TRF and DMF was defined as a gap of treatment ≥ 60 days.A cohort of 903 pwRRMS (316 on TRF and 587 on DMF) was analyzed. During 24 months of follow-up, pwRRMS on TRF and DMF showed similar discontinuation rates. The analysis of predictors with Cox regression model showed differences between the two groups (p for log-rank test = 0.007); male gender [HR 2.21 (1.00-4.90); p = 0.01] and the number of previous switches [HR 1.47 (1.16-1.86); p = 0.01] were associated with higher hazard of discontinuation in the DMF group.In a real-world setting, pwRRMS on TRF and DMF had similar discontinuation rates over 24 months. Male pwRRMS on DMF with a previous history of therapeutic failure are at more risk of discontinuation therapy.
Publication
Journal: Parkinsonism and Related Disorders
August/12/2019
Abstract
Parkinson's Disease (PD) is diagnosed clinically. Reliable non-invasive PD biomarkers are actively sought. Transfer RNAs produce short non-coding RNAs, the tRNA-derived fragments (tRF). tRF have been shown to play diverse roles, including in amyotrophic lateral sclerosis, and the response to ischemic stroke. Rich tRF populations are being reported in biofluids. We explored the possibility that tRF can serve as non-invasive biomarkers for PD.We collected existing RNA-seq samples and re-analyzed a total of 254 legacy datasets from 3 previous studies, from male and female PD patients and controls that belong to three categories: prefrontal cortex samples from 29 patients and 33 controls; cerebrospinal fluid (CSF) samples from 63 patients and 64 controls; and, serum samples from 34 patients and 31 controls. First, we identified tRF exhaustively and deterministically in every dataset. Second, we determined tRF that are differentially abundant (DA) between PD and control samples, using uncorrected t-tests. Lastly, we assessed all the DA tRF from the previous step with Partial Least Squares - Discriminant Analysis (PLS-DA) to stringently sub-select tRF that can distinguish PD patients from controls.We show that PLS-DA identified tRF from prefrontal cortex, CSF, and serum that can distinguish PD patients from controls. A handful of identified tRF were previously investigated in neurological contexts. Signatures built from relatively few tRF suffice to distinguish PD from control in each category of samples with high sensitivity (89-100%) and specificity (79-98%).tRF-based signatures are promising candidates that warrant further evaluation as non-invasive PD biomarkers.
Publication
Journal: Journal of Enzyme Inhibition and Medicinal Chemistry
October/5/2016
Abstract
It has been reported that beta amyloid induces production of radical oxygen species and oxidative stress in neuronal cells, which in turn upregulates β-secretase (BACE-1) expression and beta amyloid levels, thereby propagating oxidative stress and increasing neuronal injury. A series of resveratrol derivatives, known to be inhibitors of oxidative stress-induced neuronal cell death (oxytosis) were biologically evaluated against BACE-1 using homogeneous time-resolved fluorescence (TRF) assay. Correlation between oxytosis inhibitory and BACE-1 inhibitory activity of resveratrol derivatives was statistically significant, supporting the notion that BACE-1 may act as pivotal mediator of neuronal cell oxytosis. Four of the biologically evaluated resveratrol analogs demonstrated considerably higher activity than resveratrol in either assay. The discovery of some "hits" led us to initiate detailed docking studies associated with Molecular Dynamics in order to provide a plausible explanation for the experimental results and understand their molecular basis of action.
Publication
Journal: ACS Applied Materials & Interfaces
October/11/2019
Abstract
Glioblastoma (GBM) is one of the deadliest primary brain malignant tumors with a bleak prognosis. Craniotomy surgical resection followed by radiotherapy and chemotherapy was still the standard therapeutic strategy for GBM. As a target alkylating agent, temozolomide (TMZ) was utilized in the therapy of GBM for decades. However, effective treatment for GBM is stymied by rapid acquired resistance and bone marrow suppression. Here, we synthesize a tetrahedral framework nucleic acid (tFNA) nanoparticle that can carry TMZ to enhance the lethality on four glioblastoma cell lines via activating the cell apoptosis and autophagy pathway. Our nanoparticle, namely tFNA-TMZ, show a more obvious efficacy in killing TMZ-sensitive cells (A172 and U87) than single agent TMZ. Besides, tFNA-TMZ was able to attenuate drug resistance in TMZ-resistant cells (T98G and LN-18) via downregulating the expression of O6-methylguanine-DNA-methyltransferase (MGMT). Furthermore, we modified the tFNA with GS24, a DNA aptamer which can specially bind to transferrin receptor (TRF) in cerebral vascular endothelial cell of mouse and enable tFNA nanoparticle to cross the blood brain barrier. In summary, our results demonstrated that tFNA-TMZ have a promising role as a nanoscale vehicle to deliver TMZ to enhance efficacy for glioblastoma.
Authors
Publication
Journal: Pigment Cell and Melanoma Research
July/8/2019
Abstract
Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults. With over 50% of patients developing metastatic disease, there is an unmet need for improved diagnostic and therapeutic options. Efforts to understand the molecular biology of the disease have revealed several markers that correlate with patient prognosis, including the copy number of chromosome 3, genetic alterations in the BAP1, EIF1AX and SF3B1 genes, and other transcriptional features. Here, we expand upon previous reports by comprehensively characterizing the short RNA-ome in 80 primary UVM tumor samples. In particular, we describe a previously unseen complex network involving numerous regulatory molecules that comprise microRNA (miRNAs), novel UVM-specific miRNA loci, miRNA isoforms (isomiRs), and tRNA-derived fragments (tRFs). Importantly, we show that the abundance profiles of isomiRs and tRFs associate with various molecular phenotypes, metastatic disease, and patient survival. Our findings suggest deep involvement of isomiRs and tRFs in the disease etiology of UVM. We posit that further study and characterization of these novel molecules will improve understanding of the mechanisms underlying UVM, and lead to the development of new diagnostic and therapeutic approaches.
Publication
Journal: Database : the journal of biological databases and curation
November/18/2019
Abstract
Next-generation sequencing is increasing our understanding and knowledge of non-coding RNAs (ncRNAs), elucidating their roles in molecular mechanisms and processes such as cell growth and development. Within such a class, tRNA-derived ncRNAs have been recently associated with gene expression regulation in cancer progression. In this paper, we characterize, for the first time, tRNA-derived ncRNAs in NCI-60. Furthermore, we assess their expression profile in The Cancer Genome Atlas (TCGA). Our comprehensive analysis allowed us to report 322 distinct tRNA-derived ncRNAs in NCI-60, categorized in tRNA-derived fragments (11 tRF-5s, 55 tRF-3s), tRNA-derived small RNAs (107 tsRNAs) and tRNA 5' leader RNAs (149 sequences identified). In TCGA, we were able to identify 232 distinct tRNA-derived ncRNAs categorized in 53 tRF-5s, 58 tRF-3s, 63 tsRNAs and 58 5' leader RNAs. This latter group represents an additional evidence of tRNA-derived ncRNAs originating from the 5' leader region of precursor tRNA. We developed a public database, tRFexplorer, which provides users with the expression profile of each tRNA-derived ncRNAs in every cell line in NCI-60 as well as for each TCGA tumor type. Moreover, the system allows us to perform differential expression analyses of such fragments in TCGA, as well as correlation analyses of tRNA-derived ncRNAs expression in TCGA and NCI-60 with gene and miRNA expression in TCGA samples, in association with all omics and compound activities data available on CellMiner. Hence, the tool provides an important opportunity to investigate their potential biological roles in absence of any direct experimental evidence. Database URL: https://trfexplorer.cloud/.
Publication
Journal: Nucleic Acids Research
September/4/2020
Abstract
The fragments that derive from transfer RNAs (tRNAs) are an emerging category of regulatory RNAs. Known as tRFs, these fragments were reported for the first time only a decade ago, making them a relatively recent addition to the ever-expanding pantheon of non-coding RNAs. tRFs are short, 16-35 nucleotides (nts) in length, and produced through cleavage of mature and precursor tRNAs at various positions. Both cleavage positions and relative tRF abundance depend strongly on context, including the tissue type, tissue state, and disease, as well as the sex, population of origin, and race/ethnicity of an individual. These dependencies increase the urgency to understand the regulatory roles of tRFs. Such efforts are gaining momentum, and comprise experimental and computational approaches. System-level studies across many tissues and thousands of samples have produced strong evidence that tRFs have important and multi-faceted roles. Here, we review the relevant literature on tRF biology in higher organisms, single cell eukaryotes, and prokaryotes.
Publication
Journal: Canadian Journal of Psychiatry
October/18/2004
Abstract
OBJECTIVE
To determine whether Child Behavior Checklist/4-18 (CBCL) and Teacher Report Form (TRF) scores of children and adolescents with a first-time diagnosis of attention-deficit hyperactivity disorder (ADHD) are different and whether there is a similar difference in normal control subjects.
METHODS
We analyzed the CBCL and TRF scores of 146 patients (124 boys and 22 girls, aged 6 to 18 years; mean age 11.0 years, SD 3.6). We analyzed the same scores for 274 age and sex-matched control subjects recruited from a nationally representative sample.
RESULTS
Subjects with ADHD had significantly higher CBCL and TRF scores than control subjects. Age was significantly correlated with scores on the CBCL and TRF subscales Social Withdrawal, Somatic Complaints, and Internalization Problems; with scores on the CBCL subscale Attention Problems; and with scores on the TRF subscale Anxiety-Depression. In the group with ADHD, age was negatively correlated with scores on the CBCL and TRF subscale Externalizing Problems and with scores on the TRF subscale Aggressive Behavior. In the control group, the only significant correlation was between age and the CBCL subscale Somatic Complaints score.
CONCLUSIONS
These results indicate that underdiagnosis of ADHD in childhood may cause the emergence of greater internalization problems in adolescence.
Publication
Journal: Behavioural and Cognitive Psychotherapy
June/1/2014
Abstract
BACKGROUND
For elementary school-children with aggressive behaviour problems, there is a strong need for effective preventive interventions to interrupt the developmental trajectory towards more serious behaviour problems.
OBJECTIVE
The aim of this RCT-study was to evaluate a school-based individual tailor-made intervention (Stay Cool Kids), designed to reduce aggressive behaviour in selected children by enhancing cognitive behavioural skills.
METHODS
The sample consisted of 48 schools, with 264 fourth-grade children selected by their teachers because of elevated levels of externalizing behaviour (TRF T-score>60), randomly assigned to the intervention or no-intervention control condition.
RESULTS
The intervention was found to be effective in reducing reactive and proactive aggressive behaviour as reported by children, mothers, fathers or teachers, with effect sizes ranging from .11 to .32. Clinically relevant changes in teacher-rated externalizing behaviour were found: the intervention reduced behaviour problems to (sub) clinical or normative levels for significantly more children than the control condition. Some aspects of problems in social cognitive functioning were reduced and children showed more positive self-perception. Ethnic background and gender moderated intervention effects on child and teacher reported aggression and child response generation.
CONCLUSIONS
The results of this study demonstrate the effectiveness on outcome behaviour and child cognitions of an individual tailor-made intervention across informants under real-world conditions.
Publication
Journal: Genes and Development
December/13/2019
Abstract
Small RNAs derived from mature tRNAs, referred to as tRNA fragments or "tRFs," are an emerging class of regulatory RNAs with poorly understood functions. We recently identified a role for one specific tRF-5' tRF-Gly-GCC, or tRF-GG-as a repressor of genes associated with the endogenous retroelement MERVL, but the mechanistic basis for this regulation was unknown. Here, we show that tRF-GG plays a role in production of a wide variety of noncoding RNAs-snoRNAs, scaRNAs, and snRNAs-that are dependent on Cajal bodies for stability and activity. Among these noncoding RNAs, regulation of the U7 snRNA by tRF-GG modulates heterochromatin-mediated transcriptional repression of MERVL elements by supporting an adequate supply of histone proteins. Importantly, the effects of inhibiting tRF-GG on histone mRNA levels, on activity of a histone 3' UTR reporter, and ultimately on MERVL regulation could all be suppressed by manipulating U7 RNA levels. We additionally show that the related RNA-binding proteins hnRNPF and hnRNPH bind directly to tRF-GG, and are required for Cajal body biogenesis, positioning these proteins as strong candidates for effectors of tRF-GG function in vivo. Together, our data reveal a conserved mechanism for 5' tRNA fragment control of noncoding RNA biogenesis and, consequently, global chromatin organization.
Publication
Journal: RNA Biology
October/15/2019
Abstract
Transfer RNA fragments (tRFs) are an emerging class of small RNA molecules derived from mature or precursor tRNAs. They are found across a wide range of organisms and tissues, in small RNA fraction or loaded to Argonaute in numbers comparable to microRNAs. Their functions and mechanisms of action are largely unknown, and results obtained on individual tRFs are often hard to generalize. Here we predicted binding mechanisms and specific target interaction sites of 26 human Argonaute-loaded tRFs of different types using large-scale meta-analyses of available experimental data. Strikingly, our findings matched all interaction sites detected in a recent experimental screen, confirming the validity of our computational approach. Such sites are primarily located on the 5' end of tRFs and often involve additional binding along the tRF length, similar to microRNAs. Indicative of multiple layers of regulation, diverse regulatory non-coding RNAs comprised a third of the tRF targets, with the rest being protein-coding transcripts. In the latter, coding sequence and 3' UTRs were the likely primary target regions, although we observed interactions of tRFs with 5' UTRs. Another novel phenomenon we report, a large number of putative interactions between tRFs and introns, is compatible with the roles of Argonaute in the nucleus. Further, observed tRF-intron binding modes suggest a mechanism of interaction of tRFs with Argonaute-dependent introns, and we predict here >20 candidate introns of this type. Taken together, these results present tRFs as regulatory molecules with a rich functional spectrum.
Publication
Journal: Ageing Research Reviews
September/29/2020
Abstract
Aging is the most significant risk factor for vascular cognitive impairment (VCI), and the number of individuals affected by VCI is expected to exponentially increase in the upcoming decades. Yet, there are no current preventative or therapeutic treatments available against the development and progression of VCI. Therefore, there is a pressing need to better understand the pathophysiology underlying these conditions, for the development of novel tools and interventions to improve cerebrovascular health and delay the onset of VCI. There is strong epidemiological and experimental evidence that lifestyle factors, including nutrition and dietary habits, significantly affect cerebrovascular health and thereby influence the pathogenesis of VCI. Here, recent evidence is presented discussing the effects of lifestyle interventions against age-related diseases which in turn, inspired novel research aimed at investigating the possible beneficial effects of dietary interventions for the prevention of cognitive decline in older adults.
Keywords: Aging; Cognitive function; Dementia; Neurodegeneration Geroscience; Neurovascular coupling; Time restricted feeding.
Publication
Journal: Physiology and Behavior
June/29/2017
Abstract
A recent study reported that a special weekly scheduled time-restricted feeding regimen (TRF), i.e., no food consumption for 15h during the light (inactive) phase per day for 5 weekdays, attenuated the outcome of diverse nutritional challenges in response to high-fat diet in mice. In the present study, we wanted to further test whether this TRF could restrict body weight gain in both juvenile and adult animals when fed a high-fat diet. Fifty male Sprague-Dawley rats at ages from 5 to 27weeks were used. First, we found that freely fed rats with 60% fat diet gained weight significantly, which was associated with more calorie intake (particularly during light phase) than those fed standard food (7% fat). Secondly, we found that TRF restricted high-fat diet-induced weight gain in both groups of juvenile rats (5 and 13weeks of age) compared to freely fed rats with high-fat diet, despite the same levels of 24h-calorie intake during either weekdays or the weekend. Thirdly, we found that TRF did not restrict high-fat diet-induce weight gain in adult rats (27weeks of age). Thus, we suggest that this special TRF regimen could be further tested in humans (particularly young adults) for the purpose of obesity prevention.
Publication
Journal: Early Human Development
April/2/2008
Abstract
BACKGROUND
There is little information available concerning behavioural and functional health problems in children who had bronchopulmonary dysplasia (BPD).
OBJECTIVE
To compare behavioural problems and quality of life in a cohort of children at school age who had BPD with preterm and term controls.
METHODS
The cohort of 78 BPD children of 26 to 33 weeks' gestation was matched for birth weight with preterm controls. At school age follow-up, information was available for 66 BPD children and 60 preterm controls. (Three children with severe cerebral palsy were excluded). Parents completed the Child Behaviour Checklist (CBCL) and the Child Health Questionnaire (CHQ). The child's teacher completed the Teacher Report Form (TRF) of the CBCL, with the teachers of the BPD children completing a TRF on a classroom control. Parents completed a questionnaire on their levels of anxiety and depression.
RESULTS
The mean total problem score on the CBCL for the BPD children was similar to the controls, with the BPD children displaying more internalising behaviours. Little variation was seen between the BPD and preterm children on the TRF. Significant differences between classroom controls and the BPD children were found for the total problem scores (p=0.001), internalising behaviours (p=0.01) and social (p=0.047), attention (p=0.0001) and thought problems (0.047). Results from the CHQ showed no difference between the groups in their physical health or the impact of health problems on family life.
CONCLUSIONS
BPD children at school age display more internalising behaviour than preterm controls, with marked differences on comparison with classroom controls. Quality of life, however, does not seem to be adversely affected compared to the preterm controls.
Publication
Journal: Anticancer Research
April/6/2019
Abstract
Obesity is a risk factor for cancer. Disruption of the daily feeding and fasting rhythm can contribute to obesity. This study tested the hypothesis that time-restricted feeding (TRF) attenuates obesity-enhanced metastasis.In a spontaneous metastasis model of Lewis lung carcinoma (LLC), male C57BL/6 mice were fed the standard AIN93G diet or a high-fat diet (HFD) with or without dark-phase restricted feeding (12 h per day) for 10 weeks. Pulmonary metastases from a subcutaneous tumor were quantified.The number and size of lung metastases were greater in the HFD group than in the AIN93G group, but did not differ between the TRF and AIN93G groups. TRF prevented HFD-induced increases in plasma concentrations of glucose, insulin, proinflammatory cytokines (leptin, monocyte chemotactic protein-1, plasminogen activator inhibitor-1), and angiogenic factors (angiopoietin-2, hepatic growth factor, vascular endothelial growth factor).TRF attenuates the HFD-enhanced spontaneous metastasis of LLC in mice.
Publication
Journal: European Journal of Immunology
April/22/1993
Abstract
Interleukin-6 (IL-6) is a late-acting differentiation factor for human B cells activated by polyclonal mitogens such as pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain I, but its role in specific antibody responses has not been established. We show here that IL-6 has no consistent effect on specific antibody responses by tonsillar mononuclear cells (TMC) stimulated with influenza virus. A blocking IL-6 antibody also had no effect on antibody production, suggesting that endogenous IL-6 production was not required. In control experiments, this antibody inhibited PWM-stimulated immunoglobulin secretion and proliferation of the IL-6-dependent B cell line B9. A requirement for IL-6 in responses of unfractionated TMC may have been disguised by the presence of T cells. To overcome this problem, we investigated the effect of IL-6 on specific antibody production by T-depleted B cells stimulated with antigen in the presence of IL-2, which is a T cell replacing factor (TRF) for human B cells. Specific antibody production was restored by IL-2, but not IL-6. Neither IL-6 nor anti-IL-6 antibody had any consistent effect on specific antibody production by purified B cells stimulated with antigen and TRF. These experiments show that IL-6 does not have a significant role in antigen (influenza virus)-specific antibody responses by human B lymphocytes.
Publication
Journal: FEBS Open Bio
August/15/2017
Abstract
Short RNAs derived from the cleavage of tRNA molecules are observed in most organisms. Their occurrence seems to be induced by stress conditions, but still little is known about their biogenesis and functions. We find that the recovery of tRNA fragments depends on the RNA isolation method. Using an optimized RNA extraction protocol and northern blot hybridization technique, we show that the tRNA-derived fragments in yeast are widespread in 12 different growth conditions. We did not observe significant stress-dependent changes in the amounts of tRNA fragments pool. Instead, we show the differential processing of almost all individual tRNAs. We also provide evidence that 3'-part-derived tRNA fragments are as abundant as the 5'- one in Saccharomyces cerevisiae. The resulting set of S. cerevisiae tRNA fragments provides a robust basis for further experimental studies on biological functions of tRFs.
Publication
Journal: Frontiers in Genetics
January/25/2015
Abstract
Tropical rain forests (TRF) are the most diverse terrestrial biome on Earth, but the diversification dynamics of their constituent growth forms remain largely unexplored. Climbing plants contribute significantly to species diversity and ecosystem processes in TRF. We investigate the broad-scale patterns and drivers of species richness as well as the diversification history of climbing and non-climbing palms (Arecaceae). We quantify to what extent macroecological diversity patterns are related to contemporary climate, forest canopy height, and paleoclimatic changes. We test whether diversification rates are higher for climbing than non-climbing palms and estimate the origin of the climbing habit. Climbers account for 22% of global palm species diversity, mostly concentrated in Southeast Asia. Global variation in climbing palm species richness can be partly explained by past and present-day climate and rain forest canopy height, but regional differences in residual species richness after accounting for current and past differences in environment suggest a strong role of historical contingencies in climbing palm diversification. Climbing palms show a higher net diversification rate than non-climbers. Diversification analyses of palms detected a diversification rate increase along the branches leading to the most species-rich clade of climbers. Ancestral character reconstructions revealed that the climbing habit originated between early Eocene and Miocene. These results imply that changes from non-climbing to climbing habits may have played an important role in palm diversification, resulting in the origin of one fifth of all palm species. We suggest that, in addition to current climate and paleoclimatic changes after the late Neogene, present-day diversity of climbing palms can be explained by morpho-anatomical innovations, the biogeographic history of Southeast Asia, and/or ecological opportunities due to the diversification of high-stature dipterocarps in Asian TRFs.
Publication
Journal: Journal of Child Psychology and Psychiatry and Allied Disciplines
November/18/2002
Abstract
BACKGROUND
This study focuses on a novel observational paradigm (SNAP) involving a rigged competitive card game (Murray, Woolgar, Cooper, & Hipwell, 2001) designed to expose children to the threat of losing. Recent work suggests that this paradigm is useful for assessing disruptive behaviour in young children (Hughes, Cutting, & Dunn, 2001).
METHODS
We report on a large study (involving 800 five-year-olds) that compares observational ratings of disruptive behaviour on the SNAP game with mother and teacher reports of externalising behaviour on the CBCL and TRF (Achenbach, 1991a, 1991b). To ensure independence of data, playmates were randomly assigned to two different sub-samples. The validity of this rigged game for examining individual differences in disruptive behaviour was supported (in both sub-samples) by modest but significant correlations with both mother and teacher ratings of externalising problems, and by significantly elevated SNAP ratings among children rated by mothers and teachers as showing extreme >> or = 95th%) levels of externalising problems, compared with the remaining majority of children.
RESULTS
Significant gender differences in disruptive behaviour were found on all three measures: observational SNAP ratings and mother/teacher questionnaire ratings. Factors that may contribute to this gender difference are discussed.
CONCLUSIONS
Our findings emphasise the importance of multi-method, multi-informant measures of disruptive behaviour, and suggest that the rigged card game used in this study is a valuable adjunct to more standard methods of rating disruptive behaviour.
Publication
Journal: Clinical and Experimental Immunology
March/16/1983
Abstract
5-Fluorouracil (5-FU) administered in daily injections to mice (15-60 mg/kg; subcutaneous) was differentially toxic to helper T cells. Precursors for both antibody forming cells and cytotoxic T lymphocytes (CTL) were spared. 5-FU suppressed the in vitro T cell-dependent antibody response to sheep red blood cells (SRBC). This low response was restored to normal levels by the addition of T cell replacing factor (TRF) or mixed lymphocyte culture (MLC) supernatants to the culture system. T cell-independent antibody responses to TNP-Ficoll or TNP-LPS were not eliminated by 5-FU but, in contrast, were elevated two-four-fold. These results indicate that precursors for antibody forming cells for T cell-dependent and -independent antibody responses were not eliminated by 5-FU, 5-FU administered in the same regimen did not reduce the number of CTL precursors as shown by limiting dilution analysis, but did cause a reduction in the capacity of lymphocytes from pre-treated mice to generate a CTL response in vitro. This low CTL response was restored to control levels by adding Lyt 1+2- T cells or sources of interleukin 2 (IL2) to the culture system, indicating that 5-FU similarly eliminated helper cells for CTL precursor differentiation as well as helper cells for antibody synthesis.
Publication
Journal: Research in Developmental Disabilities
December/12/2016
Abstract
Current evidence on the co-occurrence of Developmental Coordination Disorder (DCD) and psychosocial problems mainly concerns parent-reported information, but rarely includes teacher information. The aim of this study was (1) to investigate the teachers' identification of emotional and behavioral problems in children with DCD and (2) to examine the performance of the teacher version of the Strengths and Difficulties Questionnaire (SDQ-T) compared with the Teacher Report Form (TRF) in children with DCD. We assessed primary school children (202 boys, 200 girls, range 4-10.8 years, mean age 7.2 years) for DCD following the DSM IV-TR criteria. Emotional and behavioral problems were measured with the TRF (n=327) and the SDQ-T (n=361). DCD was established in 23 (5.7%) children, 16 boys and 7 girls (mean age 7.0 years). Children with DCD had a higher proportion of clinical scores on both the TRF Total Problem Scale (TRF TPS) and SDQ-T Total Difficulties Score (SDQ-T TDS). Children with DCD had increased odds on the TRF domains Thought (odds ratio, OR: 5.39), Externalizing (OR: 4.12) and Internalizing (OR: 4.42) problems, and on all SDQ-T-domains and Total Difficulties score (OR: 7.30). In the DCD group the SDQ-T TDS correlated strongly (Spearman's rho 0.80) with the TRF TPS and demonstrated a moderate agreement (Cohen's Kappa 0.53). In conclusion, teachers identified significantly more emotional and behavioral problems in children with DCD compared with their peers. The SDQ-T showed moderate agreement with the TRF in identifying emotional and behavioral problems in children with DCD.
Publication
Journal: Journal of Physical Chemistry B
April/24/2016
Abstract
The reaction center core (RCC) complex and the RCC with associated Fenna-Matthews-Olson protein (FMO-RCC) complex from the green sulfur bacterium Chlorobaculum tepidum were studied comparatively by steady-state and time-resolved fluorescence (TRF) and femtosecond time-resolved transient absorption (TA) spectroscopies. The energy transfer efficiency from the FMO to the RCC complex was calculated to be ∼40% based on the steady-state fluorescence. TRF showed that most of the FMO complexes (66%), regardless of the fact that they were physically attached to the RCC, were not able to transfer excitation energy to the reaction center. The TA spectra of the RCC complex showed a 30-38 ps lifetime component regardless of the excitation wavelengths, which is attributed to charge separation. Excitonic equilibration was shown in TA spectra of the RCC complex when excited into the BChl a Qx band at 590 nm and the Chl a Qy band at 670 nm, while excitation at 840 nm directly populated the low-energy excited state and equilibration within the excitonic BChl a manifold was not observed. The TA spectra for the FMO-RCC complex excited into the BChl a Qx band could be interpreted by a combination of the excited FMO protein and RCC complex. The FMO-RCC complex showed an additional fast kinetic component compared with the FMO protein and the RCC complex, which may be due to FMO-to-RCC energy transfer.
Publication
Journal: Journal of Magnetic Resonance Imaging
November/17/2014
Abstract
OBJECTIVE
To develop and demonstrate the feasibility of a new formulation for quantitative perfusion modeling in the liver using interrupted DCE-MRI data acquired during multiple sequential breathholds.
METHODS
A new mathematical formulation to estimate quantitative perfusion parameters using interrupted data was developed. Using this method, we investigated whether a second degree-of-freedom in the tissue residue function (TRF) improves quality-of-fit criteria when applied to a dual-input single-compartment perfusion model. We subsequently estimated hepatic perfusion parameters using DCE-MRI data from 12 healthy volunteers and 9 cirrhotic patients with a history of hepatocellular carcinoma (HCC); and examined the utility of these estimates in differentiating between healthy liver, cirrhotic liver, and HCC.
RESULTS
Quality-of-fit criteria in all groups were improved using a Weibull TRF (2 degrees-of-freedom) versus an exponential TRF (1 degree-of-freedom), indicating nearer concordance of source DCE-MRI data with the Weibull model. Using the Weibull TRF, arterial fraction was greater in cirrhotic versus normal liver (39 ± 23% versus 15 ± 14%, P = 0.07). Mean transit time (20.6 ± 4.1 s versus 9.8 ± 3.5 s, P = 0.01) and arterial fraction (39 ± 23% versus 73 ± 14%, P = 0.04) were both significantly different between cirrhotic liver and HCC, while differences in total perfusion approached significance.
CONCLUSIONS
This work demonstrates the feasibility of estimating hepatic perfusion parameters using interrupted data acquired during sequential breathholds.
load more...