TGF beta type II receptor signaling controls Schwann cell death and proliferation in developing nerves

During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF)beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGF beta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGF beta signaling did not appear to affect other processes in which TGF beta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death

Cardiovascular magnetic resonance myocardial feature tracking detects quantitative wall motion during dobutamine stress

Contains fulltext : 96698.pdf (publisher's version ) (Open Access)BACKGROUND: Dobutamine stress cardiovascular magnetic resonance (DS-CMR) is an established tool to assess hibernating myocardium and ischemia. Analysis is typically based on visual assessment with considerable operator dependency. CMR myocardial feature tracking (CMR-FT) is a recently introduced technique for tissue voxel motion tracking on standard steady-state free precession (SSFP) images to derive circumferential and radial myocardial mechanics.We sought to determine the feasibility and reproducibility of CMR-FT for quantitative wall motion assessment during intermediate dose DS-CMR. METHODS: 10 healthy subjects were studied at 1.5 Tesla. Myocardial strain parameters were derived from SSFP cine images using dedicated CMR-FT software (Diogenes MRI prototype; Tomtec; Germany). Right ventricular (RV) and left ventricular (LV) longitudinal strain (EllRV and EllLV) and LV long-axis radial strain (ErrLAX) were derived from a 4-chamber view at rest. LV short-axis circumferential strain (EccSAX) and ErrSAX; LV ejection fraction (EF) and volumes were analyzed at rest and during dobutamine stress (10 and 20 mug . kg(1). min(1)). RESULTS: In all volunteers strain parameters could be derived from the SSFP images at rest and stress. EccSAX values showed significantly increased contraction with DSMR (rest: -24.1 +/- 6.7; 10 mug: -32.7 +/- 11.4; 20 mug: -39.2 +/- 15.2; p < 0.05). ErrSAX increased significantly with dobutamine (rest: 19.6 +/- 14.6; 10 mug: 31.8 +/- 20.9; 20 mug: 42.4 +/- 25.5; p < 0.05). In parallel with these changes; EF increased significantly with dobutamine (rest: 56.9 +/- 4.4%; 10 mug: 70.7 +/- 8.1; 20 mug: 76.8 +/- 4.6; p < 0.05). Observer variability was best for LV circumferential strain (EccSAX ) and worst for RV longitudinal strain (EllRV) as determined by 95% confidence intervals of the difference. CONCLUSIONS: CMR-FT reliably detects quantitative wall motion and strain derived from SSFP cine imaging that corresponds to inotropic stimulation. The current implementation may need improvement to reduce observer-induced variance. Within a given CMR lab; this novel technique holds promise of easy and fast quantification of wall mechanics and strain

Perinatal Asphyxia Affects Rat Auditory Processing: Implications for Auditory Perceptual Impairments in Neurodevelopmental Disorders

Perinatal asphyxia, a naturally and commonly occurring risk factor in birthing, represents one of the major causes of neonatal encephalopathy with long term consequences for infants. Here, degraded spectral and temporal responses to sounds were recorded from neurons in the primary auditory cortex (A1) of adult rats exposed to asphyxia at birth. Response onset latencies and durations were increased. Response amplitudes were reduced. Tuning curves were broader. Degraded successive-stimulus masking inhibitory mechanisms were associated with a reduced capability of neurons to follow higher-rate repetitive stimuli. The architecture of peripheral inner ear sensory epithelium was preserved, suggesting that recorded abnormalities can be of central origin. Some implications of these findings for the genesis of language perception deficits or for impaired language expression recorded in developmental disorders, such as autism spectrum disorders, contributed to by perinatal asphyxia, are discussed

Moving to capture children’s attention: developing a methodology for measuring visuomotor attention

Attention underpins many activities integral to a child’s development. However, methodological limitations currently make large-scale assessment of children’s attentional skill impractical, costly and lacking in ecological validity. Consequently we developed a measure of ‘Visual Motor Attention’ (VMA) - a construct defined as the ability to sustain and adapt visuomotor behaviour in response to task-relevant visual information. In a series of experiments, we evaluated the capability of our method to measure attentional processes and their contributions in guiding visuomotor behaviour. Experiment 1 established the method’s core features (ability to track stimuli moving on a tablet-computer screen with a hand-held stylus) and demonstrated its sensitivity to principled manipulations in adults’ attentional load. Experiment 2 standardised a format suitable for use with children and showed construct validity by capturing developmental changes in executive attention processes. Experiment 3 tested the hypothesis that children with and without coordination difficulties would show qualitatively different response patterns, finding an interaction between the cognitive and motor factors underpinning responses. Experiment 4 identified associations between VMA performance and existing standardised attention assessments and thereby confirmed convergent validity. These results establish a novel approach to measuring childhood attention that can produce meaningful functional assessments that capture how attention operates in an ecologically valid context (i.e. attention's specific contribution to visuomanual action)

The benefit of directly comparing autism and schizophrenia for revealing mechanisms of social cognitive impairment

Autism and schizophrenia share a history of diagnostic conflation that was not definitively resolved until the publication of the DSM-III in 1980. Though now recognized as heterogeneous disorders with distinct developmental trajectories and dissociative features, much of the early nosological confusion stemmed from apparent overlap in certain areas of social dysfunction. In more recent years, separate but substantial literatures have accumulated for autism and schizophrenia demonstrating that abnormalities in social cognition directly contribute to the characteristic social deficits of both disorders. The current paper argues that direct comparison of social cognitive impairment can highlight shared and divergent mechanisms underlying pathways to social dysfunction, a process that can provide significant clinical benefit by informing the development of tailored treatment efforts. Thus, while the history of diagnostic conflation between autism and schizophrenia may have originated in similarities in social dysfunction, the goal of direct comparisons is not to conflate them once again but rather to reveal distinctions that illuminate disorder-specific mechanisms and pathways that contribute to social cognitive impairment

An ecological future for weed science to sustain crop production and the environment. A review

Sustainable strategies for managing weeds are critical to meeting agriculture's potential to feed the world's population while conserving the ecosystems and biodiversity on which we depend. The dominant paradigm of weed management in developed countries is currently founded on the two principal tools of herbicides and tillage to remove weeds. However, evidence of negative environmental impacts from both tools is growing, and herbicide resistance is increasingly prevalent. These challenges emerge from a lack of attention to how weeds interact with and are regulated by the agroecosystem as a whole. Novel technological tools proposed for weed control, such as new herbicides, gene editing, and seed destructors, do not address these systemic challenges and thus are unlikely to provide truly sustainable solutions. Combining multiple tools and techniques in an Integrated Weed Management strategy is a step forward, but many integrated strategies still remain overly reliant on too few tools. In contrast, advances in weed ecology are revealing a wealth of options to manage weedsat the agroecosystem levelthat, rather than aiming to eradicate weeds, act to regulate populations to limit their negative impacts while conserving diversity. Here, we review the current state of knowledge in weed ecology and identify how this can be translated into practical weed management. The major points are the following: (1) the diversity and type of crops, management actions and limiting resources can be manipulated to limit weed competitiveness while promoting weed diversity; (2) in contrast to technological tools, ecological approaches to weed management tend to be synergistic with other agroecosystem functions; and (3) there are many existing practices compatible with this approach that could be integrated into current systems, alongside new options to explore. Overall, this review demonstrates that integrating systems-level ecological thinking into agronomic decision-making offers the best route to achieving sustainable weed management

Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity

Notch signaling is central to vertebrate development, and analysis of Notch has provided important insights into pathogenetic mechanisms in the CNS and many other tissues. However, surprisingly little is known about the role of Notch in the development and pathology of Schwann cells and peripheral nerves. Using transgenic mice and cell cultures, we found that Notch has complex and extensive regulatory functions in Schwann cells. Notch promoted the generation of Schwann cells from Schwann cell precursors and regulated the size of the Schwann cell pool by controlling proliferation. Notch inhibited myelination, establishing that myelination is subject to negative transcriptional regulation that opposes forward drives such as Krox20. Notably, in the adult, Notch dysregulation resulted in demyelination; this finding identifies a signaling pathway that induces myelin breakdown in vivo. These findings are relevant for understanding the molecular mechanisms that control Schwann cell plasticity and underlie nerve pathology, including demyelinating neuropathies and tumorigenesi