SHP-2 Promotes the Maturation of Oligodendrocyte Precursor Cells Through Akt and ERK1/2 Signaling In Vitro

Background: Oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes (OLs), which are responsible for myelination. Myelin is essential for saltatory nerve conduction in the vertebrate nervous system. However, the molecular mechanisms of maturation and myelination by oligodendrocytes remain elusive. Methods and Findings: In the present study, we showed that maturation of oligodendrocytes was attenuated by sodium orthovanadate (a comprehensive inhibitor of tyrosine phosphatases) and PTPi IV (a specific inhibitor of SHP-2). It is also found that SHP-2 was persistently expressed during maturation process of OPCs. Down-regulation of endogenous SHP-2 led to impairment of oligodendrocytes maturation and this effect was triiodo-L-thyronine (T3) dependent. Furthermore, overexpression of SHP-2 was shown to promote maturation of oligodendrocytes. Finally, it has been identified that SHP-2 was involved in activation of Akt and extracellular-regulated kinases 1 and 2 (ERK1/2) induced by T3 in oligodendrocytes

β1 Integrin Maintains Integrity of the Embryonic Neocortical Stem Cell Niche

IInteractions between laminins and integrin receptors hold neural stem cells in place at the ventricular surface of embryonic brain. Transient disruption leads to abnormal stem cell divisions and permanent cortical malformation

Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains Differentially Modulates Src Kinase Activity in Brain Maturation

Src family kinases (SFK) control multiple processes during brain development and function. We show here that the phosphoprotein associated with glycosphigolipid-enriched microdomains (PAG)/Csk binding protein (Cbp) modulates SFK activity in the brain. The timing and localization of PAG expression overlap with Fyn and Src, both of which we find associated to PAG. We demonstrate in newborn (P1) mice that PAG negatively regulates Src family kinases (SFK). P1 Pag1-/- mouse brains show decreased recruitment of Csk into lipid rafts, reduced phosphorylation of the inhibitory tyrosines within SFKs, and an increase in SFK activity of >/ = 50%. While in brain of P1 mice, PAG and Csk are highly and ubiquitously expressed, little Csk is found in adult brain suggesting altered modes of SFK regulation. In adult brain Pag1-deficiency has no effect upon Csk-distribution or inhibitory tyrosine phosphorylation, but kinase activity is now reduced (−20–30%), pointing to the development of a compensatory mechanism that may involve PSD93. The distribution of the Csk-homologous kinase CHK is not altered. Importantly, since the activities of Fyn and Src are decreased in adult Pag1-/- mice, thus presenting the reversed phenotype of P1, this provides the first in vivo evidence for a Csk-independent positive regulatory function for PAG in the brain

Neuregulin and BDNF Induce a Switch to NMDA Receptor-Dependent Myelination by Oligodendrocytes

<div><p>Myelination is essential for rapid impulse conduction in the CNS, but what determines whether an individual axon becomes myelinated remains unknown. Here we show, using a myelinating coculture system, that there are two distinct modes of myelination, one that is independent of neuronal activity and glutamate release and another that depends on neuronal action potentials releasing glutamate to activate NMDA receptors on oligodendrocyte lineage cells. Neuregulin switches oligodendrocytes from the activity-independent to the activity-dependent mode of myelination by increasing NMDA receptor currents in oligodendrocyte lineage cells 6-fold. With neuregulin present myelination is accelerated and increased, and NMDA receptor block reduces myelination to far below its level without neuregulin. Thus, a neuregulin-controlled switch enhances the myelination of active axons. <i>In vivo</i>, we demonstrate that remyelination after white matter damage is NMDA receptor-dependent. These data resolve controversies over the signalling regulating myelination and suggest novel roles for neuregulin in schizophrenia and in remyelination after white matter damage.</p></div

Value Chain Analysis of Native Chicken in Selected Barangay of Partido

The study aimed to analyze the existing value chain of native chicken in the Partido Camarines Sur. Specifically it aimed to describe the value chain in terms of actors, their roles, and links in the value chain map; relationship dynamics among actors; determine the cost and return of native chicken production and identify constraints and opportunities. The study utilized quantitative and qualitative research design. Surveyquestionnaire was used to gather the relevant data needed in the study. Value chain mapping was used to analyze the actors, their roles and relationship dynamics as well as the cost and return analysis to determine the cost and value added in the value chain. Findings revealed the main actors along this value chain are native chicken farmers/raisers, wholesalers/middlemen and retailers. The native chicken farmers directly sold their harvest to the wholesalers/middlemen and eventually to the consumers who directly visited their place. On the other hand, the wholesaler/middlemen sold the native chicken directly to the market. Findings revealed that all the three actors profited in the industry however, the wholesalers/middlemen profited a lot as compared to the producer/raisers and retailers. Results shows that in negotiating the price, the seller is the one sets the price in the value chain from raiser to the wholesalers/middlemen but when it comes to wholesalers/middlemen to consumers the buyers set the price

Alterations in the Thickness of Motor Cortical Subregions After Motor-Skill Learning and Exercise

Behavioral manipulations such as housing in an enriched environment have been shown to increase brain weight and visual cortical thickness. The present study was designed to test whether skill learning or repetitive movements can alter the thickness of the motor cortex. One group of 6-mo-old Long-Evans female rats learned motor skills on an obstacle course that increased in difficulty over training and required balance and coordination. A second group ran voluntarily in exercise wheels attached to their home cage but had little opportunity for skill learning. The third group was handled daily but received no opportunity for learning or exercise. Each condition lasted 26–29 d. The skill-learning and exercise conditions had greater heart weight, and the exercise condition had greater adrenal gland weights than controls. The thickness of the motor cortex was measured in four coronal planes between −2.33 mm to −0.3 mm from bregma. Regions of interest that corresponded to published maps of forelimb and hind-limb representations were analyzed together. Rats in the skill-learning condition had significantly thicker medial cortical areas in the two anterior planes (−0.8 and −0.3 mm from bregma). These regions correspond to previously mapped hind-limb representations. The exercise group had greater thickness of the medial region at −0.8 mm from bregma. Cortical thickness in all conditions varied significantly along the medial to lateral axis. For both treatments, the effects were restricted to medial and anterior regions of interest rather than posterior or lateral regions of interest. The results indicate that robust exercise, in addition to skill learning, is capable of altering the thickness of the motor cortex, but that the effects are restricted rather than distributed within the regions studied

Legal protection of the unborn child: A proposal to amend Articles 40 and 41 of the New Civil Code of the Philippines

The question of when human life begins is a profoundly intricate one, with widespread implications, ranging from abortion rights, to stem cell research and beyond. A key point in the debate rests on the way in which the concepts of humanity, life and human life are defined. What does it mean to be alive? What does it mean to be human? Is conception the starting point of human life? Is a zygote or an embryo alive? If it is, is it a human being? Is there really a difference between a human being and a person? These are complicated philosophical questions that often incite intense debate for their answers are used as evidence in the answers to questions about the moral and legal status of a zygote, embryo, fetus or unborn child. In the late nineteenth century, following the discovery of fertilization, the debate about abortion within the Church tipped in favor of its now familiar position that human life begins at conception, and is maintained to the present day. Although sharing the same nature with all human beings, the unborn individual, like each one of us, is unlike any that has been conceived before and unlike any that will ever be conceived again. The unborn child is not a becoming who is striving toward being. The unborn child is not a potential human life but a human life with great potentiality. It is right if it means that the physical facts of science, without any moral reflection on our part, cannot tell us what is right and wrong. But it is wrong if it means that the physical facts of science cannot tell us to whom we should apply the values of which are already aware. The interaction between the law and science is increasing, and the two disciplines must learn to work together for the good of society. The researchers believe that to be consistent with contemporary science, legal protection must be extended to the unborn entity from the moment of conception