Using time-to-contact information to assess potential collision modulates both visual and temporal prediction networks

Accurate estimates of the time-to-contact (TTC) of approaching objects are crucial for survival. We used an ecologically valid driving simulation to compare and contrast the neural substrates of egocentric (head-on approach) and allocentric (lateral approach) TTC tasks in a fully factorial, event-related fMRI design. Compared to colour control tasks, both egocentric and allocentric TTC tasks activated left ventral premotor cortex/frontal operculum and inferior parietal cortex, the same areas that have previously been implicated in temporal attentional orienting. Despite differences in visual and cognitive demands, both TTC and temporal orienting paradigms encourage the use of temporally predictive information to guide behaviour, suggesting these areas may form a core network for temporal prediction. We also demonstrated that the temporal derivative of the perceptual index tau (tau-dot) held predictive value for making collision judgements and varied inversely with activity in primary visual cortex (V1). Specifically, V1 activity increased with the increasing likelihood of reporting a collision, suggesting top-down attentional modulation of early visual processing areas as a function of subjective collision. Finally, egocentric viewpoints provoked a response bias for reporting collisions, rather than no-collisions, reflecting increased caution for head-on approaches. Associated increases in SMA activity suggest motor preparation mechanisms were engaged, despite the perceptual nature of the task.

Prediction of microRNAs affecting mRNA expression during retinal development.

Background: MicroRNAs (miRNAs) are small RNA molecules (similar to 22 nucleotides) which have been shown to play an important role both in development and in maintenance of adult tissue. Conditional inactivation of miRNAs in the eye causes loss of visual function and progressive retinal degeneration. In addition to inhibiting translation, miRNAs can mediate degradation of targeted mRNAs. We have previously shown that candidate miRNAs affecting transcript levels in a tissue can be deduced from mRNA microarray expression profiles. The purpose of this study was to predict miRNAs which affect mRNA levels in developing and adult retinal tissue and to confirm their expression.

Results: Microarray expression data from ciliary epithelial retinal stem cells (CE-RSCs), developing and adult mouse retina were generated or downloaded from public repositories. Analysis of gene expression profiles detected the effects of multiple miRNAs in CE-RSCs and retina. The expression of 20 selected miRNAs was confirmed by RT-PCR and the cellular distribution of representative candidates analyzed by in situ hybridization. The expression levels of miRNAs correlated with the significance of their predicted effects upon mRNA expression. Highly expressed miRNAs included miR-124, miR-125a, miR-125b, miR-204 and miR-9. Over-expression of three miRNAs with significant predicted effects upon global mRNA levels resulted in a decrease in mRNA expression of five out of six individual predicted target genes assayed.

Conclusions: This study has detected the effect of miRNAs upon mRNA expression in immature and adult retinal tissue and cells. The validity of these observations is supported by the experimental confirmation of candidate miRNA expression and the regulation of predicted target genes following miRNA over-expression. Identified miRNAs are likely to be important in retinal development and function. Misregulation of these miRNAs might contribute to retinal degeneration and disease. Conversely, manipulation of their expression could potentially be used as a therapeutic tool in the future.

Resting energy expenditure in non-ventilated, non-sedated patients recovering from serious traumatic brain injury: Comparison of prediction equations with indirect calorimetry values

Background & aims: Little is known about energy requirements in brain injured (TBI) patients, despite evidence suggesting adequate nutritional support can improve clinical outcomes. The study aim was to compare predicted energy requirements with measured resting energy expenditure (REE) values, in patients recovering from TBI.

Methods: Indirect calorimetry (IC) was used to measure REE in 45 patients with TBI. Predicted energy requirements were determined using FAO/WHO/UNU and Harris–Benedict (HB) equations. Bland– Altman and regression analysis were used for analysis.

Results: One-hundred and sixty-seven successful measurements were recorded in patients with TBI. At an individual level, both equations predicted REE poorly. The mean of the differences of standardised areas of measured REE and FAO/WHO/UNU was near zero (9 kcal) but the variation in both directions was substantial (range 591 to þ573 kcal). Similarly, the differences of areas of measured REE and HB demonstrated a mean of 1.9 kcal and range 568 to þ571 kcal. Glasgow coma score, patient status, weight and body temperature were signi?cant predictors of measured REE (p < 0.001; R²⁼ 0.47).

Conclusions: Clinical equations are poor predictors of measured REE in patients with TBI. The variability in REE is substantial. Clinicians should be aware of the limitations of prediction equations when estimating energy requirements in TBI patients.

Ligand and structure-based methodologies for the prediction of the activity of G protein-coupled receptor ligands

Accurate in silico models for the quantitative prediction of the activity of G protein-coupled receptor (GPCR) ligands would greatly facilitate the process of drug discovery and development. Several methodologies have been developed based on the properties of the ligands, the direct study of the receptor-ligand interactions, or a combination of both approaches. Ligand-based three-dimensional quantitative structure-activity relationships (3D-QSAR) techniques, not requiring knowledge of the receptor structure, have been historically the first to be applied to the prediction of the activity of GPCR ligands. They are generally endowed with robustness and good ranking ability; however they are highly dependent on training sets. Structure-based techniques generally do not provide the level of accuracy necessary to yield meaningful rankings when applied to GPCR homology models. However, they are essentially independent from training sets and have a sufficient level of accuracy to allow an effective discrimination between binders and nonbinders, thus qualifying as viable lead discovery tools. The combination of ligand and structure-based methodologies in the form of receptor-based 3D-QSAR and ligand and structure-based consensus models results in robust and accurate quantitative predictions. The contribution of the structure-based component to these combined approaches is expected to become more substantial and effective in the future, as more sophisticated scoring functions are developed and more detailed structural information on GPCRs is gathered.

SpaciMS: spatial and temporal operando resolution of reactions within catalytic monoliths

Monolithic catalysts are widely used as structured catalysts, especially in the abatement of pollutants. Probing what happens inside these monoliths during operation is, therefore, vital for modelling and prediction of the catalyst behavior. SpaciMS is a spatially resolved capillary-inlet mass spectroscopy system allowing for the generation of spatially resolved maps of the reactions within monoliths. In this study SpaciMS results combined with 3D CFD modelling demonstrate that SpaciMS is a highly sensitive and minimally invasive technique that can provide reaction maps as well as catalytic temporal behavior. Herein we illustrate this by examining kinetic oscillations during a CO oxidation reaction over a Pt/Rh on alumina catalyst supported on a cordierite monolith. These oscillations were only observed within the monolith by SpaciMS between 30 and 90% CO conversion. Equivalent experiments performed in a plug-flow reactor using this catalyst in a crushed form over a similar range of reaction conditions did not display any oscillations demonstrating the importance of intra monolith analysis. This work demonstrates that the SpaciMS offers an accurate and comprehensive picture of structured catalysts under operation.