Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2

Cerebellar-dependent delay eyeblink conditioning in adolescents with Specific Language Impairment

Cerebellar impairments have been hypothesized as part of the pathogenesis of Specific Language Impairment (SLI), although direct evidence of cerebellar involvement is sparse. Eyeblink Conditioning (EBC) is a learning task with well documented cerebellar pathways. This is the first study of EBC in affected adolescents and controls. 16 adolescent controls, 15 adolescents with SLI, and 12 adult controls participated in a delay EBC task. Affected children had low general language performance, grammatical deficits but no speech impairments. The affected group did not differ from the control adolescent or control adult group, showing intact cerebellar functioning on the EBC task. This study did not support cerebellar impairment at the level of basic learning pathways as part of the pathogenesis of SLI. Outcomes do not rule out cerebellar influences on speech impairment, or possible other forms of cerebellar functioning as contributing to SLI

Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms

Measurements of photo-nuclear jet production in Pb plus Pb collisions with ATLAS

Ultra-peripheral heavy ion collisions provide a unique opportunity to study the parton distributions in the colliding nuclei via the measurement of photo-nuclear jet production. An analysis of jet production in ultra-peripheral Pb+Pb collisions at √sNN = 5.02 TeV performed using data collected with the ATLAS detector in 2015 is described. The data set corresponds to a total Pb+Pb integrated luminosity of 0.38 nb−1. The ultra-peripheral collisions are selected using a combination of forward neutron and rapidity gap requirements. The cross-sections, not unfolded for detector response, are compared to results from Pythia Monte Carlo simulations re-weighted to match a photon spectrum obtained from the STARlight model. Qualitative agreement between data and these simulations is observed over a broad kinematic range suggesting that using these collisions to measure nuclear parton distributions is experimentally realisable

Measurements of photo-nuclear jet production in Pb + Pb collisions with ATLAS

Ultra-peripheral heavy ion collisions provide a unique opportunity to study the parton distributions in the colliding nuclei via the measurement of photo-nuclear jet production. An analysis of jet production in ultra-peripheral Pb+Pb collisions at √sNN = 5.02 TeV performed using data collected with the ATLAS detector in 2015 is described. The data set corresponds to a total Pb+Pb integrated luminosity of 0.38 nb⁻¹. The ultra-peripheral collisions are selected using a combination of forward neutron and rapidity gap requirements. The cross-sections, not unfolded for detector response, are compared to results from Pythia Monte Carlo simulations re-weighted to match a photon spectrum obtained from the STARlight model. Qualitative agreement between data and these simulations is observed over a broad kinematic range suggesting that using these collisions to measure nuclear parton distributions is experimentally realisable