Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

The Noradrenergic (alpha)2 Agonist Clonidine Modulates Behavioral And Neuroanatomical Correlates Of Human Attentional Orienting And Alerting

s. Introduction Arousal and selective attention are multidimensional psychological processes that interact closely with one another, both behaviourally and neuroanatomically. There is accumulating evidence that the noradrenergic (NA) system may contribute to both arousal and selective attention, as well as play an important role in mediating the interaction between these functions (Arnsten and Constant, 1992; Smith and Nutt, 1996; Coull et al., 1997). Visual spatial orienting tasks, originally developed by Posner (Posner et al., 1980), have provided an experimental paradigm with which to investigate both selective directed focal spatial expectations as well as general, unfocused alerting. Fernandez-Duque and Posner have recently demonstrated that the spatial orienting and alerting effects in the Posner task provide independent indices of attention and arousal, respectively (Fernandez-Duque and Posner, 1997). In spatial orienting tasks subjects de

Relation between cognitive dysfunction and pseudobulbar palsy in amyotrophic lateral sclerosis.

OBJECTIVES: To examine the relation between cognitive dysfunction and pseudobulbar features in patients with amyotrophic lateral sclerosis (ALS). METHODS: The performance of two patient groups, ALS with pseudobulbar palsy (n = 24) and ALS without pseudobulbar palsy (n = 28), was compared with 28 healthy age matched controls on an extensive neuropsychological battery. Tests used were the national adult reading test, short form of the WAIS-R, recognition memory test, Kendrick object learning test, paired associate learning, Wisconsin card sorting test, verbal fluency, Stroop and negative priming tests, a random movement joystick test, and a computerised Tower of Hanoi test. RESULTS: Tests of executive function showed a pronounced deficit on written verbal fluency in both ALS groups in comparison to controls, which tended to be more prominent in patients with ALS with pseudobulbar palsy. The random movement joystick test (a non-verbal test of intrinsic movement generation) showed an impairment in the generation of random sequences in patients with pseudobulbar palsy only. The computerised Tower of Hanoi showed a subtle planning impairment (shorter planning times) in all the patients with ALS compared with controls on trials requiring more complex solutions. In addition the pseudobulbar patients displayed shorter planning times on complex trials, and tended to solve these trials less accurately. There was also evidence of a deficit for all patients with ALS in comparison with controls on total errors and number of categories achieved on the Wisconsin card sorting test and a strong tendency towards an impairment on a task of selective attention and cognitive inhibition (negative priming). A word recognition memory deficit was showed across both ALS groups. CONCLUSIONS: This study elicited cognitive deficits (involving predominantly executive processes, with some evidence of memory impairment) in patients with ALS and further strengthened the link between ALS and frontal lobe dysfunction, this being more prominent in patients with pseudobulbar palsy. However, cognitive impairments suggestive of extramotor cortical involvement were not exclusive to this subgroup

Effects of artificial shade on attack by the mahogany shoot borer, Hypsipyla robusta (Moore)

Swietenia macrophylla King (Meliaceae: Swietenioideae) provides one of the premier timbers of the world. The mahogany shoot borer Hypsipyla robusta Moore (Lepidoptera: Pyralidae) is an economically important pest of S. macrophylla throughout Asia, Africa and the Pacific. No viable method of controlling this pest is known. Previous observations have suggested that the presence of overhead shade may reduce attack by H. robusta, but this has not been investigated experimentally. This research was therefore designed to assess the influence of light availability on shoot-borer attack on S. macrophylla, by establishing seedlings under three different artificial shade regimes, then using these seedlings to test oviposition preference of adult moths, neonate larval survival and growth and development of shoot borer larvae.\ud \ud \ud Oviposition preference of shoot borer moths was tested on leaves from seedlings grown under artificial shade for 63 weeks. A significant difference in choice was recorded between treatments, with 27.4 ± 1.5 eggs laid under high shade and 87.1 ± 1.8 under low shade.\ud \ud Neonate larval survival on early flushing leaflets of S. macrophylla did not differ significantly between shade treatments. Larval growth rate, estimated by measuring daily frass width, was significantly higher for those larvae fed on seedlings from the high and medium shade treatments (0.1 mm/day), than the low shade treatment (0.06 mm/day). In laboratory-reared larvae, the total mass of frass produced was significantly higher in the high shade treatment (0.4 g) than under the low shade treatment (0.2 g).\ud \ud Longer tunnel lengths were bored by larvae in plants grown under high shade (12.0 ± 2.4 cm) than under low shade (7.07 ± 1.9 cm). However, pupal mass under low shade was 48% higher than that under the high shade treatment, suggesting that plants grown under high shade were of lower nutritional quality for shoot borer larvae.\ud \ud These results indicate that shading of mahogany seedlings may reduce the incidence of shoot borer attack, by influencing both oviposition and larval development. The establishment of mahogany under suitable shade regimes may therefore provide a basis for controlling shoot borer attack using silvicultural approaches

Psychiatric and medical features of near fatal asthma.

BACKGROUND--The associations between psychiatric caseness, denial, and self reported measures of handicap and morbidity due to asthma in patients suffering a near fatal attack of asthma have not been fully explored. METHODS--Seventy seven consecutive subjects who presented to Adelaide teaching hospitals with a near fatal attack of asthma were assessed with a validated semi-structured interview following discharge from hospital. RESULTS--43% of the patients scored > or = 5 on the GHQ-28 questionnaire. There was a positive correlation between GHQ-28 score and limitation to daily activities due to asthma, and between GHQ-28 score and days lost from work, school or usual daily activities, both of which were retained after adjusting for age and sex. Asthma severity did not show a clear association with GHQ-28 score. The asthmatic patients reported high levels of denial, 57% scoring more than 3 out of 5 on the denial scale of the Illness Behaviour Questionnaire. Presentation with a history of progressive respiratory distress was negatively associated with denial score. This persisted after adjustment for age and sex--that is, those with high denial scores were more likely to report presentation as sudden collapse than progressive respiratory distress. CONCLUSIONS--Psychiatric caseness (GHQ score > or = 5) is associated with high levels of morbidity in asthmatic patients who survive a near fatal attack of asthma. High levels of denial in asthmatic subjects may be life threatening. The link between morbidity associated with asthma and psychiatric features, along with other psychosocial issues, warrants further investigation. A broader paradigm than the traditional medical model should be considered when assessing patients with asthma

The narrative construction of our (social) world: steps towards an interactive learning environment for children with autism

“The original publication is available at www.springerlink.com”. Copyright Springer. DOI: 10.1007/s10209-007-0076-x [Full text of this article is not available in the UHRA]Children with autism exhibit a deficit in narrative comprehension which adversely impacts upon their social world. The authors’ research agenda is to develop an interactive software system which promotes an understanding of narrative structure (and thus the social world) while addressing the needs of individual children. This paper reports the results from a longitudinal study, focussing on ‘primitive’ elements of narrative, presented as proto-narratives, in an interactive software game which adapts to the abilities of individual children. A correlation has been found with a real-world narrative comprehension task, and for most children a clear distinction in their understanding of narrative components.Peer reviewe