Truncated MEK1 is required for transient activation of MAPK signalling in G2 phase cells.

The primary endpoint of signalling through the canonical Raf-MEK-ERK MAP kinase cascade is ERK activation. Here we report a novel signalling outcome for this pathway. Activation of the MAP kinase pathway by growth factors or phorbol esters during G2 phase results in only transient activations of ERK and p90RSK, then suppression to below control levels.

A rare chromosome 3 imbalance and its clinical implications.

The duplication of chromosome 3q is a rare disorder with varying chromosomal breakpoints and consequently symptoms. Even rarer is the unbalanced outcome from a parental inv(3) resulting in duplicated 3q and a deletion of 3p. Molecular karyotyping should aid in precisely determining the length and breakpoints of the 3q+/3p- so as to better understand a child's future development and needs.

Menu-labeling policy in King County, Washington.

Background: Food eaten away from home now accounts for about one third of total calories consumed in the U.S. Policy change could lead to sustainable improvements in restaurant and other nutrition environments.

Myelopoiesis and myeloid leukaemogenesis in the zebrafish.

Over the past ten years, studies using the zebrafish model have contributed to our understanding of vertebrate haematopoiesis, myelopoiesis, and myeloid leukaemogenesis. Novel insights into the conservation of haematopoietic lineages and improvements in our capacity to identify, isolate, and culture such haematopoietic cells continue to enhance our ability to use this simple organism to address disease biology. Coupled with the strengths of the zebrafish embryo to dissect developmental myelopoiesis and the continually expanding repertoire of models of myeloid malignancies, this versatile organism has established its niche as a valuable tool to address key questions in the field of myelopoiesis and myeloid leukaemogenesis.

Measuring child rhythm.

Interval-based rhythm metrics were applied to the speech of English, Catalan and Spanish 2, 4 and 6 year-olds, and compared with the (adult-directed) speech of their mothers. Results reveal that child speech does not fall into a well-defined rhythmic class: for all three languages, it is more 'vocalic' (higher %V) than adult speech and has a tendency towards lower variability (when normalized for speech rate) in vocalic interval duration. Consonantal interval variability, however, is higher in child speech, particularly for younger children.

L-Leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway.

Haploinsufficiency of ribosomal proteins (RPs) has been proposed to be the common basis for the anemia observed in Diamond-Blackfan anemia (DBA) and myelodysplastic syndrome with loss of chromosome 5q [del(5q) MDS]. We have modeled DBA and del(5q) MDS in zebrafish using antisense morpholinos to rps19 and rps14, respectively, and have demonstrated that, as in humans, haploinsufficient levels of these proteins lead to a profound anemia. To address the hypothesis that RP loss results in impaired mRNA translation, we treated Rps19 and Rps14-deficient embryos with the amino acid L-leucine, a known activator of mRNA translation.

Thoracic myelopathy secondary to seizure following scoliosis surgery.

The incidence of spinal injuries is increased in people with epilepsy although compressive thoracic myelopathy has not been reported. We describe a 15-year-old girl with SCN1A mutation (Dravet syndrome), refractory generalized tonic-clonic seizures, and prior posterior instrumentation and fusion for scoliosis, who presented with progressive lower extremity weakness. Junctional kyphosis with disc herniation and spinal cord compression directly rostral to the instrumentation was apparent on imaging.

Alpers syndrome: the natural history of a case highlighting neuroimaging, neuropathology, and fat metabolism.

Mitochondrial diseases are increasingly being recognized as causes of encephalopathy and intractable epilepsy. There is no gold-standard test for diagnosing mitochondrial disease, and the current diagnosis relies on establishing a consistent pattern of evidence from clinical data, neuroimaging, tissue biopsy, and biochemical, genetic, and other investigations. Experience in the diagnosis and treatment of patients with certain forms of mitochondrial disease, such as Alpers syndrome, is largely gained from case reports or small case series.

Husbandry and growth rates of neonate epaulette sharks, Hemiscyllium ocellatum in captivity.

In this report, I describe husbandry techniques that are used to successfully hatch and raise epaulette sharks, Hemiscyllium ocellatum, in captivity. Egg cases and hatchlings were held in floating baskets within a 1,306-L tank, at water temperatures of 24.4-25.

An investigation to validate the grammar and phonology screening (GAPS) test to identify children with specific language impairment.

Background: The extraordinarily high incidence of grammatical language impairments in developmental disorders suggests that this uniquely human cognitive function is "fragile". Yet our understanding of the neurobiology of grammatical impairments is limited. Furthermore, there is no "gold-standard" to identify grammatical impairments and routine screening is not undertaken.

NUP98-HOXA9-transgenic zebrafish develop a myeloproliferative neoplasm and provide new insight into mechanisms of myeloid leukaemogenesis.

NUP98-HOXA9 [t(7;11) (p15;p15)] is associated with inferior prognosis in de novo and treatment-related acute myeloid leukaemia (AML) and contributes to blast crisis in chronic myeloid leukaemia (CML). We have engineered an inducible transgenic zebrafish harbouring human NUP98-HOXA9 under the zebrafish spi1(pu.1) promoter.

Multiple targets of nitric oxide in the tricarboxylic acid cycle of Salmonella enterica serovar typhimurium.

Host nitric oxide (NO⋅) production is important for controlling intracellular bacterial pathogens, including Salmonella enterica serovar Typhimurium, but the underlying mechanisms are incompletely understood. S. Typhmurium 14028s is prototrophic for all amino acids but cannot synthesize methionine (M) or lysine (K) during nitrosative stress.

Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia.

The MYC oncogenic transcription factor is overexpressed in most human cases of T cell acute lymphoblastic leukemia (T-ALL), often downstream of mutational NOTCH1 activation. Genetic alterations in the PTEN-PI3K-AKT pathway are also common in T-ALL. We generated a conditional zebrafish model of T-ALL in which 4-hydroxytamoxifen (4HT) treatment induces MYC activation and disease, and withdrawal of 4HT results in T-ALL apoptosis and tumor regression.

Ddx18 is essential for cell-cycle progression in zebrafish hematopoietic cells and is mutated in human AML.

In a zebrafish mutagenesis screen to identify genes essential for myelopoiesis, we identified an insertional allele hi1727, which disrupts the gene encoding RNA helicase dead-box 18 (Ddx18). Homozygous Ddx18 mutant embryos exhibit a profound loss of myeloid and erythroid cells along with cardiovascular abnormalities and reduced size. These mutants also display prominent apoptosis and a G1 cell-cycle arrest.

Assessment of a point-of-care cardiac troponin I test to differentiate cardiac from noncardiac causes of respiratory distress in dogs.

Objectives: To (1) determine a reference interval for cardiac troponin I (cTnI) using a point-of-care device in normal dogs and compare the results with those published by the manufacturer and (2) determine if cTnI differs among dogs with cardiogenic and noncardiogenic respiratory distress.

Design: Prospective observational study.

Setting: Emergency and referral veterinary hospital.

Apolipoprotein e4 genotype increases the risk of being diagnosed with posttraumatic fibromyalgia.

Objective: To determine whether the apolipoprotein E4 (Apo E4) allele may be a genetic risk factor for fibromyalgia syndrome (FMS).

Design: A retrospective assessment of associations between Apo E4 genotype and selected environmental exposures among a cohort diagnosed with FMS compared with control subjects.

Setting: Marshfield Clinic Research Foundation's Personalized Medicine Research Project (PMRP) biobank.

cpsf1 is required for definitive HSC survival in zebrafish.

A comprehensive understanding of the genes and pathways regulating hematopoiesis is needed to identify genes causally related to bone marrow failure syndromes, myelodysplastic syndromes, and hematopoietic neoplasms. To identify novel genes involved in hematopoiesis, we performed an ethyl-nitrosourea mutagenesis screen in zebrafish (Danio rerio) to search for mutants with defective definitive hematopoiesis. We report the recovery and analysis of the grechetto mutant, which harbors an inactivating mutation in cleavage and polyadenylation specificity factor 1 (cpsf1), a gene ubiquitously expressed and required for 3' untranslated region processing of a subset of pre-mRNAs.

Insonation frequency selection may assist detection and therapeutic delivery of targeted ultrasound contrast agents.

Background: Ultrasound-targeted drug delivery relies on the unique nature of ultrasound contrast agents--they are microbubbles that respond strongly to ultrasound. Intravenously injected microbubbles are smaller than a blood cell. By increasing the ultrasound power, the bubbles can be ruptured at the targeted endothelial wall, locally releasing any molecules in the bubble shell.

Inhibition of cervical cancer cell growth in vitro and in vivo with dual shRNAs.

RNA interference (RNAi)-based gene silencing is widely used in laboratories for gene function studies and also holds a great promise for developing treatments for diseases. However, in vivo delivery of RNAi therapy remains a key issue. Lentiviral vectors have been employed for stable gene transfer and gene therapy and therefore are expected to deliver a stable and durable RNAi therapy.

Zebrafish microRNA-126 determines hematopoietic cell fate through c-Myb.

Precise regulatory mechanisms are required to appropriately modulate the cellular levels of transcription factors controlling cell fate decisions during blood cell development. In this study, we show that miR-126 is a novel physiological regulator of the proto-oncogene c-myb during definitive hematopoiesis. We show that knockdown of miR-126 results in increased c-Myb levels and promotes erythropoiesis at the expense of thrombopoiesis in vivo.

Endothelial von Willebrand factor regulates angiogenesis.

The regulation of blood vessel formation is of fundamental importance to many physiological processes, and angiogenesis is a major area for novel therapeutic approaches to diseases from ischemia to cancer. A poorly understood clinical manifestation of pathological angiogenesis is angiodysplasia, vascular malformations that cause severe gastrointestinal bleeding. Angiodysplasia can be associated with von Willebrand disease (VWD), the most common bleeding disorder in man.

Driving under the influence of alcohol: examining ethno-specific rates and the mediating effects of psychological distress and harmful and problematic drinking.

This paper examines ethnic disparities in rates of driving under the influence of alcohol (DUIA) in a representative sample of Ontario adults. Data were drawn from the Centre for Addiction and Mental Health (CAMH) Monitor, a survey of 8276 Ontario adults aged 18 and older. We considered 19 distinct ethnic groups based on participants' self-identification of ethno-cultural heritage.

Expression of the cytoplasmic NPM1 mutant (NPMc+) causes the expansion of hematopoietic cells in zebrafish.

Mutations in the human nucleophosmin (NPM1) gene are the most frequent genetic alteration in adult acute myeloid leukemias (AMLs) and result in aberrant cytoplasmic translocation of this nucleolar phosphoprotein (NPMc+). However, underlying mechanisms leading to leukemogenesis remain unknown. To address this issue, we took advantage of the zebrafish model organism, which expresses 2 genes orthologous to human NPM1, referred to as npm1a and npm1b.