LINC00507 Is Specifically Expressed in the Primate Cortex and Has Age-Dependent Expression Patterns

Over the past decade, there has been an increase in the appreciation of the role of non-coding RNA in the development of organism phenotype. It is possible to divide the non-coding elements of the transcriptome into three categories: short non-coding RNAs, circular RNAs and long non-coding RNAs. Long non-coding RNAs are those transcripts that are greater than 200 nts in length and lack any significant open reading frames that produce proteins greater then 100 amino acids. Long intervening non-coding RNAs (lincRNAs) are a subclass of long non-coding RNAs. In contrast to protein coding RNAs, lincRNAs are expressed in a more tissue- and species-specific manner. In particular, many lincRNAs are only conserved amongst higher primates. This coupled with the propensity of many lincRNAs to be expressed in the brain, suggests that they are in fact one of the major drivers of organism complexity. We analysed 39 lincRNAs that are expressed in the frontal cortex and identified LINC00507 as being expressed in a cortex-specific manner in non-human primates and humans. The expression patterns of LINC00507 appear to be age-dependent, suggesting it may be involved in brain development of higher primates. Moreover, the analysis of LINC00507 potential to bind ribosomes revealed that this previously identified non-coding transcript may harbour a micropeptide

Anisotropic nanostructures directly written by fs pulses in wide-bandgap materials

The use of lasers to directly pattern optoelectronic devices primarily utilizes direct irradiation by UV light. We present here an alternative route using multi-photon absorption within a spherical focus in 3D space, thus allowing complex embedded structures to be directly written. In wide-bandgap materials such as chalcogenide, fluoride and silica glasses, our observations suggest free electrons are produced within the focus of a high-power infrared ultrashort pulse. The anisotropic interaction of this plasma with the incident pulse produces micron-sized DBR gratings of a 150nm pitch. An amplified Ti:S laser with 250kHz repetition rate, 150fs pulse duration, and wavelength tuned from 800-850nml is used to write embedded diffraction gratings and arrays of dots. The laser beam is focussed with a 50x objective into transparent polished samples, with pulse energies ranging from 0.1-1.1pJ (Fig.la). During the writing process broadband sub-bandgap UV light is emitted from a micron-sized spot at the sample focus. The written structures are permanent, typically with large refractive index changes on the order of Delta.n = +0.01 depending on the material

Upregulation of the pathogenic transcription factor SPI1/PU.1 in tuberous sclerosis complex and focal cortical dysplasia by oxidative stress

Tuberous sclerosis complex (TSC) is a congenital disorder characterized by cortical malformations and concomitant epilepsy caused by loss-of-function mutations in the mTOR suppressors TSC1 or TSC2. While the underlying molecular changes caused by mTOR activation in TSC have previously been investigated, the drivers of these transcriptional change have not been fully elucidated. A better understanding of the perturbed transcriptional regulation could lead to the identification of novel pathways for therapeutic intervention not only in TSC, but other genetic epilepsies in which mTOR activation plays a key role, such as focal cortical dysplasia 2b (FCD). Here, we analyzed RNA sequencing data from cortical tubers and a tsc2-/- zebrafish. We identified differential expression of the transcription factors (TFs) SPI1/PU.1, IRF8, GBX2, and IKZF1 of which SPI1/PU.1 and IRF8 targets were enriched among the differentially expressed genes. Furthermore, for SPI1/PU.1 these findings were conserved in TSC zebrafish model. Next, we confirmed overexpression of SPI1/PU.1 on the RNA and protein level in a separate cohort of surgically resected TSC tubers and FCD tissue, in fetal TSC tissue, and a Tsc1GFAP-/- mouse model of TSC. Subsequently, we validated the expression of SPI1/PU.1 in dysmorphic cells with mTOR activation in TSC tubers. In fetal TSC, we detected SPI1/PU.1 expression prenatally and elevated RNA Spi1 expression in Tsc1GFAP-/- mice before the development of seizures. Finally, in vitro, we identified that in astrocytes and neurons SPI1 transcription was driven by H2O2 -induced oxidative stress, independent of mTOR. We identified SPI1/PU.1 as a novel TF involved in the pro-inflammatory gene expression of malformed cells in TSC and FCD 2b. This transcriptional program is activated in response to oxidative stress and already present prenatally. Importantly, SPI1/PU.1 protein appears to be strictly limited to malformed cells, as we did not find SPI1/PU.1 protein expression in mice nor in our in vitro models

Consistent Anisotropic Repulsions for Simple Molecules

We extract atom-atom potentials from the effective spherical potentials that suc cessfully model Hugoniot experiments on molecular fluids, e.g., $O_2$ and $N_2$. In the case of $O_2$ the resulting potentials compare very well with the atom-atom potentials used in studies of solid-state propertie s, while for $N_2$ they are considerably softer at short distances. Ground state (T=0K) and room temperatu re calculations performed with the new $N-N$ potential resolve the previous discrepancy between experimental and theoretical results.Comment: RevTeX, 5 figure

Projected sea surface temperatures over the 21st century: Changes in the mean, variability and extremes for large marine ecosystem regions of Northern Oceans

Global climate models were used to assess changes in the mean, variability and extreme sea surface temperatures (SSTs) in northern oceans with a focus on large marine ecosystems (LMEs) adjacent to North America, Europe, and the Arctic Ocean. Results were obtained from 26 models in the Community Model Intercomparison Project Phase 5 (CMIP5) archive and 30 simulations from the National Center for Atmospheric Research Large Ensemble Community Project (CESM-LENS). All of the simulations used the observed greenhouse gas concentrations for 1976–2005 and the RCP8.5 “business as usual” scenario for greenhouse gases through the remainder of the 21st century. In general, differences between models are substantially larger than among the simulations in the CESM-LENS, indicating that the SST changes are more strongly affected by model formulation than internal climate variability. The annual SST trends over 1976–2099 in the 18 LMEs examined here are all positive ranging from 0.05 to 0.5°C decade–1. SST changes by the end of the 21st century are primarily due to a positive shift in the mean with only modest changes in the variability in most LMEs, resulting in a substantial increase in warm extremes and decrease in cold extremes. The shift in the mean is so large that in many regions SSTs during 2070–2099 will always be warmer than the warmest year during 1976–2005. The SST trends are generally stronger in summer than in winter, as greenhouse gas heating is integrated over a much shallower climatological mixed layer depth in summer than in winter, which amplifies the seasonal cycle of SST over the 21st century. In the Arctic, the mean SST and its variability increases substantially during summer, when it is ice free, but not during winter when a thin layer of ice reforms and SSTs remain near the freezing point

Development of a patient reported outcome measure for fatigue in motor neurone disease: the Neurological Fatigue Index (NFI-MND).

BACKGROUND: The objective of this research was to develop a disease-specific measure for fatigue in patients with motor neurone disease (MND) by generating data that would fit the Rasch measurement model. Fatigue was defined as reversible motor weakness and whole-body tiredness that was predominantly brought on by muscular exertion and was partially relieved by rest. METHODS: Qualitative interviews were undertaken to confirm the suitability of a previously identified set of 52 neurological fatigue items as relevant to patients with MND. Patients were recruited from five U.K. MND clinics. Questionnaires were administered during clinic or by post. A sub-sample of patients completed the questionnaire again after 2-4 weeks to assess test-retest validity. Exploratory factor analyses and Rasch analysis were conducted on the item set. RESULTS: Qualitative interviews with ten MND patients confirmed the suitability of 52 previously identified neurological fatigue items as relevant to patients with MND. 298 patients consented to completing the initial questionnaire including this item set, with an additional 78 patients completing the questionnaire a second time after 4-6 weeks. Exploratory Factor Analysis identified five potential subscales that could be conceptualised as representing: 'Energy', 'Reversible muscular weakness' (shortened to 'Weakness'), 'Concentration', 'Effects of heat' and 'Rest'. Of the original five factors, two factors 'Energy' and 'Weakness' met the expectations of the Rasch model. A higher order fatigue summary scale, consisting of items from the 'Energy' and 'Weakness' subscales, was found to fit the Rasch model and have acceptable unidimensionality. The two scales and the higher order summary scale were shown to fulfil model expectations, including assumptions of unidimensionality, local independency and an absence of differential item functioning. CONCLUSIONS: The Neurological Fatigue Index for MND (NFI-MND) is a simple, easy-to-administer fatigue scale. It consists of an 8-item fatigue summary scale in addition to separate scales for measuring fatigue experienced as reversible muscular weakness and fatigue expressed as feelings of low energy and whole body tiredness. The underlying two factor structure supports the patient concept of fatigue derived from qualitative interviews in this population. All three scales were shown to be reliable and capable of interval level measurement