Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
1,384
result(s) for
"Taylor, Barry"
Sort by:
Teen Titans. Volume 5, The trial of Kid Flash
\"When Titans Fall. He trained under the Dark Knight himself. But then Red Robin stepped out from under the Batman's shadow to start a new team of teenaged heroes like himself. As the Teen Titans, they battled against threats no other, older team could face. He never could have imagined that their greatest threats would come from within. Spinning out of the events of \"Forever Evil,\" the team is lost in the timestream, repeatedly slammed together only to be torn apart again. Superboy has been targeted by the murderous Son of Superman he was cloned from. Raven's deal with her devilish father Trigon--her freedom for the Titans' soul--has almost been sealed. And the carefree crimefighter called Kid Flash is about to be called to account for crimes that defy comprehension. As the trial of the friend and hero they thought they knew nears its dreaded verdict, the Teen Titans will be forced to make a fateful decision. Will they stand together-- or fall apart?\" -- page 4 of cover.
Book
deconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution
Background
Analysis of somatic mutations provides insight into the mutational processes that have shaped the cancer genome, but such analysis currently requires large cohorts. We develop deconstructSigs, which allows the identification of mutational signatures within a single tumor sample.
Results
Application of deconstructSigs identifies samples with DNA repair deficiencies and reveals distinct and dynamic mutational processes molding the cancer genome in esophageal adenocarcinoma compared to squamous cell carcinomas.
Conclusions
deconstructSigs confers the ability to define mutational processes driven by environmental exposures, DNA repair abnormalities, and mutagenic processes in individual tumors with implications for precision cancer medicine.
Journal Article
Automated Network Analysis Identifies Core Pathways in Glioblastoma
Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor in humans and the first cancer with comprehensive genomic profiles mapped by The Cancer Genome Atlas (TCGA) project. A central challenge in large-scale genome projects, such as the TCGA GBM project, is the ability to distinguish cancer-causing \"driver\" mutations from passively selected \"passenger\" mutations.
In contrast to a purely frequency based approach to identifying driver mutations in cancer, we propose an automated network-based approach for identifying candidate oncogenic processes and driver genes. The approach is based on the hypothesis that cellular networks contain functional modules, and that tumors target specific modules critical to their growth. Key elements in the approach include combined analysis of sequence mutations and DNA copy number alterations; use of a unified molecular interaction network consisting of both protein-protein interactions and signaling pathways; and identification and statistical assessment of network modules, i.e. cohesive groups of genes of interest with a higher density of interactions within groups than between groups.
We confirm and extend the observation that GBM alterations tend to occur within specific functional modules, in spite of considerable patient-to-patient variation, and that two of the largest modules involve signaling via p53, Rb, PI3K and receptor protein kinases. We also identify new candidate drivers in GBM, including AGAP2/CENTG1, a putative oncogene and an activator of the PI3K pathway; and, three additional significantly altered modules, including one involved in microtubule organization. To facilitate the application of our network-based approach to additional cancer types, we make the method freely available as part of a software tool called NetBox.
Journal Article
Homing in on genomic instability as a therapeutic target in cancer
While genomic instability is a hallmark of cancer, its genetic vulnerabilities remain poorly understood. Identifying strategies that exploit genomic instability to selectively target cancer cells is a central challenge in cancer biology with major implications for anti-cancer drug development.
Journal Article
Do More Active Children Sleep More? A Repeated Cross-Sectional Analysis Using Accelerometry
To determine whether levels of daytime physical activity are associated with sleep duration and night waking in children assessed using accelerometry, and if these associations change over time.
24-hour accelerometry data were obtained from 234 children at 3, 5 and 7 years of age for at least 5 days at each time. Sleep duration was estimated using the Sadeh algorithm. Time spent in sedentary, light and moderate-vigorous (MVPA) activity was established using published cut-points. Appropriate statistical techniques were utilised to account for the closed nature of the data (24-hour periods).
Time spent asleep was related more to sedentary or light activity and not to MVPA. The most active (95th percentile) children spent 55-84 fewer minutes asleep and 16-19 more minutes awake at night compared to the least active (5th percentile) children. Children with later bedtimes slept less at night (30-40 minutes) and undertook more sedentary (10-15 minutes) but also more light (18-23 minutes) activity during the day. However, no differences in MVPA were apparent according to bedtime. Children slept slightly less on weekend nights (11 minutes) compared with week-nights, but only at 3 years of age. Most relationships were broadly similar at 3, 5 and 7 years of age.
Children who are more physically active during the day have shorter total sleep time and are more awake at night than less active children. The protective effect of sleep on obesity does not appear to be mediated by increased physical activity.
Journal Article
Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers
Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are rare and frequently lethal tumors that so far have not been subjected to comprehensive genetic characterization.
We performed next-generation sequencing of 341 cancer genes from 117 patient-derived PDTCs and ATCs and analyzed the transcriptome of a representative subset of 37 tumors. Results were analyzed in the context of The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTC).
Compared to PDTCs, ATCs had a greater mutation burden, including a higher frequency of mutations in TP53, TERT promoter, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases. BRAF and RAS were the predominant drivers and dictated distinct tropism for nodal versus distant metastases in PDTC. RAS and BRAF sharply distinguished between PDTCs defined by the Turin (PDTC-Turin) versus MSKCC (PDTC-MSK) criteria, respectively. Mutations of EIF1AX, a component of the translational preinitiation complex, were markedly enriched in PDTCs and ATCs and had a striking pattern of co-occurrence with RAS mutations. While TERT promoter mutations were rare and subclonal in PTCs, they were clonal and highly prevalent in advanced cancers. Application of the TCGA-derived BRAF-RAS score (a measure of MAPK transcriptional output) revealed a preserved relationship with BRAF/RAS mutation in PDTCs, whereas ATCs were BRAF-like irrespective of driver mutation.
These data support a model of tumorigenesis whereby PDTCs and ATCs arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities, many of which have prognostic and possible therapeutic relevance. The widespread genomic disruptions in ATC compared with PDTC underscore their greater virulence and higher mortality.
This work was supported in part by NIH grants CA50706, CA72597, P50-CA72012, P30-CA008748, and 5T32-CA160001; the Lefkovsky Family Foundation; the Society of Memorial Sloan Kettering; the Byrne fund; and Cycle for Survival.
Journal Article
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity
Detection of recurrently mutated nucleotides identifies novel cancer hotspots in an analysis of >11,000 human tumor samples.
Mutational hotspots indicate selective pressure across a population of tumor samples, but their prevalence within and across cancer types is incompletely characterized. An approach to detect significantly mutated residues, rather than methods that identify recurrently mutated genes, may uncover new biologically and therapeutically relevant driver mutations. Here, we developed a statistical algorithm to identify recurrently mutated residues in tumor samples. We applied the algorithm to 11,119 human tumors, spanning 41 cancer types, and identified 470 somatic substitution hotspots in 275 genes. We find that half of all human tumors possess one or more mutational hotspots with widespread lineage-, position- and mutant allele–specific differences, many of which are likely functional. In total, 243 hotspots were novel and appeared to affect a broad spectrum of molecular function, including hotspots at paralogous residues of Ras-related small GTPases
RAC1
and
RRAS2
. Redefining hotspots at mutant amino acid resolution will help elucidate the allele-specific differences in their function and could have important therapeutic implications.
Journal Article
Changes in Physical Activity over Time in Young Children: A Longitudinal Study Using Accelerometers
Previous research has suggested that marked declines in physical activity occur during the preschool years, and across the transition into school. However, longitudinal studies using objective measures of activity have been limited by sample size and length of follow-up. The aims of this study were to determine how overall activity and time in different intensities of activity change in children followed from 3 to 7 years. Children (n = 242) wore Actical accelerometers at 3, 4, 5, 5.5, 6.5 and 7 years of age during all waking and sleeping hours for a minimum of 5 days. Time in sedentary (S), light (L), moderate (M), and vigorous (V) physical activity was determined using available cut points. Data were analyzed using a mixed model and expressed as counts per minute (cpm, overall activity) and the ratio of active time to sedentary time (LMV:S), adjusted for multiple confounders including sex, age, time worn, and weather. At 5 years, physical activity had declined substantially to around half that observed at 3 years. Although starting school was associated with a further short-term (6-month) decline in activity (cpm) in both boys (difference; 95% CI: -98; -149, -46) and girls (-124; -174, -74, both P<0.001), this proved to be relatively transient; activity levels were similar at 6-7 years as they were just prior to starting school. Boys were more physically active than girls as indicated by an overall 12% (95% CI: 2, 22%) higher ratio of active to sedentary time (P = 0.014), but the pattern of this difference did not change from 3 to 7 years. Time worn and weather variables were significant predictors of activity. In conclusion, both boys and girls show a marked decline in activity from 3 to 4 years of age, a decrease that is essentially maintained through to 7 years of age. Factors driving this marked decrease need to be determined to enable the development of targeted interventions.
Journal Article
Parenting style and family type, but not child temperament, are associated with television viewing time in children at two years of age
Determines how the factors of parenting style, infant temperament, and family type are associated with television viewing in two-year-old children. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Journal Article
Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma
Yu Chen and colleagues describe a new constitutively activating mutation in the G-protein-coupled receptor
CYSLTR2
in patients with uveal melanoma lacking mutations in the G-protein-encoding genes
GNAQ
and
GNA11
. They find that expression of the mutant leads to increased expression of melanocyte-lineage signature genes and promotes tumorigenesis
in vivo
.
Uveal melanomas are molecularly distinct from cutaneous melanomas and lack mutations in
BRAF
,
NRAS
,
KIT
, and
NF1
. Instead, they are characterized by activating mutations in
GNAQ
and
GNA11
, two highly homologous α subunits of G
αq/11
heterotrimeric G proteins, and in
PLCB4
(phospholipase C β4), the downstream effector of G
αq
signaling
1
,
2
,
3
. We analyzed genomics data from 136 uveal melanoma samples and found a recurrent mutation in
CYSLTR2
(cysteinyl leukotriene receptor 2) encoding a p.Leu129Gln substitution in 4 of 9 samples that lacked mutations in
GNAQ
,
GNA11
, and
PLCB4
but in 0 of 127 samples that harbored mutations in these genes. The Leu129Gln CysLT
2
R mutant protein constitutively activates endogenous G
αq
and is unresponsive to stimulation by leukotriene. Expression of Leu129Gln CysLT
2
R in melanocytes enforces expression of a melanocyte-lineage signature, drives phorbol ester–independent growth
in vitro
, and promotes tumorigenesis
in vivo
. Our findings implicate
CYSLTR2
as a uveal melanoma oncogene and highlight the critical role of G
αq
signaling in uveal melanoma pathogenesis.
Journal Article