The use of optical emission spectroscopy for human 15N tracer studies.

Optical emission spectroscopy is a convenient method for determing ¹⁵N specific activity in a variety of metabolites following the administration of an ¹⁵N-labeled amino acid to humans. The only disadvantage, compared to the more conventional isotope ratio mass spectrometer analytical system is that more tracer is needed to give accurate results. When an ¹⁵N-labeled amino acid is used as the ¹⁵N carrier, the amount of ¹⁵N is not above a tracer dose. A suitable procedure is described for performing such studies using [¹⁵N]glycine as a tracer. As an experimental example, [¹⁵N]glycine was infused into a subject at a rate of 35 mg of N/hr for 8 hr. After 3 hr a meal was consumed by the subject. The urinary urea-¹⁵N, ammonia-¹⁵N and amino acid-¹⁵N profiles were determined.     

Effects of Polychlorinated Biphenyls on Macromolecular Synthesis by a Heterotrophic Marine Bacterium

Growth rates and final cell yields of a polychlorinated biphenyl (PCB)-sensitive pseudomonad isolated from the open ocean were reduced in a dose-dependent manner by 10 to 100 μg of Aroclor 1254 per liter, a commercial mixture of PCB isomers added to its culture medium. Effects on growth rates were detected within 1 h (approximately one doubling time) of treatment. By 4 h posttreatment, the amounts of deoxyribonucleic acid and ribonucleic acid per cell in exponentially growing populations treated with sublethal doses of Aroclor were detectably lower than in appropriate controls. Corresponding cell protein values were slightly higher than in controls. Selective degradation of cell proteins or nucleic acids was not detected in cells whose growth was totally suppressed for 4 h by PCBs. Cells whose growth rate was inhibited 20 to 50% by Aroclor synthesized protein at normal rates for periods in excess of 5 h from the time the chlorinated hydrocarbons were added. In contrast, rates per cell of adenine uptake and adenine incorporation into deoxyribonucleic acid and total nucleic acids by the cells treated with PCBs were significantly lower than in control cells. Intracellular adenine pools of cells whose growth was inhibited to 20% of the control rate by PCBs were 30% smaller and appeared to require a longer interval to equilibrate than those of untreated cells. This may indicate impaired transport and/or efflux of this nucleic acid precursor through the membrane of affected cells. Inhibition of nucleic acid synthesis in this sensitive bacterium by PCBs could explain the observed inhibitory effects of the chlorinated hydrocarbons on its growth.     

Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns

Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS₁₀) and showed it was an adequate instrumental variable (β = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 × 10⁻¹¹; N = 467). A higher GRS₁₀ was associated with lower methylation levels at cg12083122 located near LEP (β = −0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS₁₀ and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (β = −0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation.     

siRNA against presenilin 1 (PS1) down regulates amyloid β42 production in IMR-32 cells

Background  

One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid β protein (Aβ) within lesions known as senile plaques. Aβ is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aβ that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a β-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As γ-secretase catalyzes the final cleavage that releases the Aβ42 or 40 from amyloid β -protein precursor (APP), therefore, it is a potential therapeutic target for the treatment of AD. γ-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs), nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2) are critical components of a large enzyme complex that performs γ-secretase cleavage.     

Brain Response to a Humanoid Robot in Areas Implicated in the Perception of Human Emotional Gestures

Background

The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents.

Methodology

Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust) and silent speech respond to a humanoid robot impersonating the same emotions, while participants were instructed to attend either to the emotion or to the motion depicted.

Principal Findings

Increased responses to robot compared to human stimuli in the occipital and posterior temporal cortices suggest additional visual processing when perceiving a mechanical anthropomorphic agent. In contrast, activity in cortical areas endowed with mirror properties, like left Broca''s area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance.

Conclusions

Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions.

Significance

Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions.     

Unaffected perceptual thresholds for biological and non-biological form-from-motion perception in autism spectrum conditions

Background

Perception of biological motion is linked to the action perception system in the human brain, abnormalities within which have been suggested to underlie impairments in social domains observed in autism spectrum conditions (ASC). However, the literature on biological motion perception in ASC is heterogeneous and it is unclear whether deficits are specific to biological motion, or might generalize to form-from-motion perception.

Methodology and Principal Findings

We compared psychophysical thresholds for both biological and non-biological form-from-motion perception in adults with ASC and controls. Participants viewed point-light displays depicting a walking person (Biological Motion), a translating rectangle (Structured Object) or a translating unfamiliar shape (Unstructured Object). The figures were embedded in noise dots that moved similarly and the task was to determine direction of movement. The number of noise dots varied on each trial and perceptual thresholds were estimated adaptively. We found no evidence for an impairment in biological or non-biological object motion perception in individuals with ASC. Perceptual thresholds in the three conditions were almost identical between the ASC and control groups.

Discussion and Conclusions

Impairments in biological motion and non-biological form-from-motion perception are not across the board in ASC, and are only found for some stimuli and tasks. We discuss our results in relation to other findings in the literature, the heterogeneity of which likely relates to the different tasks performed. It appears that individuals with ASC are unaffected in perceptual processing of form-from-motion, but may exhibit impairments in higher order judgments such as emotion processing. It is important to identify more specifically which processes of motion perception are impacted in ASC before a link can be made between perceptual deficits and the higher-level features of the disorder.