Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

A Spatial Distribution Study of Faunal Remains from Two Lower Magdalenian Occupation Levels in El Mirón Cave, Cantabria, Spain

Abstract: Human behaviour can be reconstructed by analysing specific activities and campsite organization using spatial analysis. The dense occupation layers of the Lower Cantabrian Magdalenian in the Northern Spain reveal varied aspects of Upper Palaeolithic lifeways, including evidence of specific localized activities. The outer vestibule of El Mirón cave has a particularly rich and intact Lower Magdalenian occupation horizon, Levels 15–17. The excavations in the outer vestibule “Cabin” area of the site revealed excellent bone preservation. Artefacts and faunal remains were individually recorded and sediments water-screened to yield a large sample of archaeological finds and spatial data. Zooarchaeological analysis provided the taxonomic, anatomic and taphonomic determination of the faunal individual finds. Smaller animal remains were categorized and counted; special attention was given to the identification of anthropogenic modifications such as burnt bones or bone flakes. These small refuse items are considered to be useful, in situ indicators of localized activities. The spatial distribution analysis of this dense and complex palimpsest of El Mirón Lower Cantabrian Magdalenian layers required GIS based methods including density analysis, heatmaps and cluster analysis. Based on the spatial distribution of Level 15 and 16 faunal remains, different activity areas were identified comprising hearth, working and dropping zones. These results imply the deliberately segregated use of space within the Lower Cantabrian Magdalenian site area, in which bone-processing activities played a central rol

Dissociable Influences of Auditory Object vs. Spatial Attention on Visual System Oscillatory Activity

Given that both auditory and visual systems have anatomically separate object identification (“what”) and spatial (“where”) pathways, it is of interest whether attention-driven cross-sensory modulations occur separately within these feature domains. Here, we investigated how auditory “what” vs. “where” attention tasks modulate activity in visual pathways using cortically constrained source estimates of magnetoencephalograpic (MEG) oscillatory activity. In the absence of visual stimuli or tasks, subjects were presented with a sequence of auditory-stimulus pairs and instructed to selectively attend to phonetic (“what”) vs. spatial (“where”) aspects of these sounds, or to listen passively. To investigate sustained modulatory effects, oscillatory power was estimated from time periods between sound-pair presentations. In comparison to attention to sound locations, phonetic auditory attention was associated with stronger alpha (7–13 Hz) power in several visual areas (primary visual cortex; lingual, fusiform, and inferior temporal gyri, lateral occipital cortex), as well as in higher-order visual/multisensory areas including lateral/medial parietal and retrosplenial cortices. Region-of-interest (ROI) analyses of dynamic changes, from which the sustained effects had been removed, suggested further power increases during Attend Phoneme vs. Location centered at the alpha range 400–600 ms after the onset of second sound of each stimulus pair. These results suggest distinct modulations of visual system oscillatory activity during auditory attention to sound object identity (“what”) vs. sound location (“where”). The alpha modulations could be interpreted to reflect enhanced crossmodal inhibition of feature-specific visual pathways and adjacent audiovisual association areas during “what” vs. “where” auditory attention

Predicting Transitions in Low and High Levels of Risk Behavior from Early to Middle Adolescence: The TRAILS Study

The present study examined the joint development of substance use and externalizing problems in early and middle adolescence. First, it was tested whether the relevant groups found in previous studies i.e., those with an early onset, a late onset, and no onset or low levels of risk behavior could be identified, while using a developmental model of a single, underlying construct of risk behavior. Second, departing from Moffitt’s taxonomy of antisocial behavior, it was tested if early, but not late, onset risk behavior is predicted by a problematic risk profile in childhood. Data were used from TRAILS, a population based cohort study, starting at age 11 with two follow-ups at mean ages of 13.6 and 16.3 years. Latent transition analyses demonstrated that, both in early and middle adolescence, a single underlying construct of risk behavior, consisting of two classes (labeled as low and high risk behavior), adequately represented the data. Respondents could be clearly classified into four possible transition patterns from early to middle adolescence, with a transition from high to low being almost non-existent (2.5 %), low to low (39.4 %) and low to high (41.8 %) being the most prevalent, and high to high (16.2 %) substantial. As hypothesized, only the high-high group was characterized by a clear adverse predictor profile in late childhood, while the low-high group was not. This study demonstrates that the development of substance use is correlated with externalizing problems and underscores the theory that etiologies of early and later onset risk behavior are different

DISC1 genetics, biology and psychiatric illness

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain

Adult Type 3 Adenylyl Cyclase–Deficient Mice Are Obese

Background: A recent study of obesity in Swedish men found that polymorphisms in the type 3 adenylyl cyclase (AC3) are associated with obesity, suggesting the interesting possibility that AC3 may play a role in weight control. Therefore, we examined the weight of AC3 mice over an extended period of time. Methodology/Principal Findings: We discovered that AC3 2/2 mice become obese as they age. Adult male AC3 2/2 mice are about 40 % heavier than wild type male mice while female AC3 2/2 are 70 % heavier. The additional weight of AC3 2/2 mice is due to increased fat mass and larger adipocytes. Before the onset of obesity, young AC3 2/2 mice exhibit reduced physical activity, increased food consumption, and leptin insensitivity. Surprisingly, the obesity of AC3 2/2 mice is not due to a loss of AC3 from white adipose and a decrease in lipolysis. Conclusions/Significance: We conclude that mice lacking AC3 exhibit obesity that is apparently caused by low locomotor activity, hyperphagia, and leptin insensitivity. The presence of AC3 in primary cilia of neurons of the hypothalamus suggests that cAMP signals generated by AC3 in the hypothalamus may play a critical role in regulation of body weight

Manipulating the Biosynthesis of Bioactive Compound Alkaloids for Next-Generation Metabolic Engineering in Opium Poppy Using CRISPR-Cas 9 Genome Editing Technology

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated9 (Cas9) endonuclease system is a powerful RNA-guided genome editing tool. CRISPR/Cas9 has been well studied in model plant species for targeted genome editing. However, few studies have been reported on plant species without whole genome sequence information. Currently, no study has been performed to manipulate metabolic pathways using CRISPR/Cas9. In this study, the type II CRISPR/SpCas9 system was used to knock out, via nonhomologous end-joining genome repair, the 4′OMT2 in opium poppy (Papaver somniferum L.), a gene which regulates the biosythesis of benzylisoquinoline alkaloids (BIAs). For sgRNA transcription, viral-based TRV and synthetic binary plasmids were designed and delivered into plant cells with a Cas9 encoding-synthetic vector by Agrobacterium-mediated transformation. InDels formed by CRISPR/Cas9 were detected by sequence analysis. Our results showed that the biosynthesis of BIAs (e.g. morphine, thebaine) was significantly reduced in the transgenic plants suggesting that 4′OMT2 was efficiently knocked-out by our CRISPR-Cas9 genome editing approach. In addition, a novel uncharacterized alkaloid was observed only in CRISPR/Cas9 edited plants. Thus, the applicabilitiy of the CRISPR/Cas9 system was demonstrated for the first time for medicinal aromatic plants by sgRNAs transcribed from both synthetic and viral vectors to regulate BIA metabolism and biosynthesis

New approaches to the treatment of orphan genetic disorders: Mitigating molecular pathologies using chemicals

With the advance and popularization of molecular techniques, the identification of genetic mutations that cause diseases has increased dramatically. Thus, the number of laboratories available to investigate a given disorder and the number of subsequent diagnosis have increased over time. Although it is necessary to identify mutations and provide diagnosis, it is also critical to develop specific therapeutic approaches based on this information. This review aims to highlight recent advances in mutation-targeted therapies with chemicals that mitigate mutational pathology at the molecular level, for disorders that, for the most part, have no effective treatment. Currently, there are several strategies being used to correct different types of mutations, including the following: the identification and characterization of translational readthrough compounds; antisense oligonucleotide-mediated splicing redirection; mismatch repair; and exon skipping. These therapies and other approaches are reviewed in this paper