Our brain is home to different types of neurons, each with their own genetic signature that defines their function. These neurons are derived from progenitor cells, which are specialized stem cells that have the ability to divide to give rise to neurons. Neuroscientists from the Faculty of Medicine at the University of Geneva (UNIGE) shed light on the mechanisms that allow progenitors to generate neurons. By developing a novel technology called FlashTag that enables them to isolate and visualize neurons at the very moment they are born, they have deciphered the basic genetic code allowing the construction of a neuron. This discovery, which is published in Science, allows not only to understand how our brain develops, but also how to use this code to reconstruct neurons from stem cells. Researchers will now be able to better understand the mechanisms underlying neurological diseases such as autism and schizophrenia. Directed by Denis Jabaudon, a neuroscientist and neuroscientist at the Department of Basic Neurosciences at UNIGE Faculty of Medicine and neurologist at the University Hospitals Geneva (HUG), the researchers developed a technology termed FlashTag, which visualizes neurons as they are being born. Using this approach, at the very moment where a progenitor divides, it is tagged with a fluorescent marker that persists in its progeny. Scientists can then visualize and isolate newborn neurons in order to dynamically observe which genes are expressed in the first few hours of their existence. Over time, they can then study their evolution and changes in gene expression. "Previously, we only had a few photos to reconstruct the history of neurons, which left a lot of room for speculation. Thanks to FlashTag, there is now a full genetic movie unfolding before our eyes. Every instant becomes visible from the very beginning, which allows us to understand the developmental scenario at play, identify the main characters, their interactions and their incentives", notes Jabaudon. Working in the cerebral cortex of the mouse, the scientists have thus identified the key genesto neuronal development, and demonstrated that their expression dynamics is essential for the brain to develop normally. This discovery, by giving access to the primordial code of the formation of neurons, helps us to understand how neurons function in the adult brain. And it appears that several of these original genes are also involved in neurodevelopmental and neurodegenerative diseases, which can occur many years later. This suggests that a predisposition may be present from the very first moments in the existence of neurons, and that environmental factors can then impact on how diseases may develop later on. By understanding the genetic choreography of neurons, the researchers can therefore observe how these genes behave from the start, and identify potential anomalies predicting diseases. After successfully reading this genetic code, the scientists we able to rewrite it in newborn neurons. By altering the expression of certain genes, they were able to accelerate neuronal growth, thus altering the developmental script. With FlashTag, it is now possible to isolate newborn neurons and recreate cerebral circuits in vitro, which enables scientists to test their function as well as to develop new treatments. The UNIGE team posted a website where it is possible to enter the name of a gene and observe how it is expressed, and how it interacts with other genes. "Each research team can only focus on a handful of genes at a time, while our genome is made up of close to 20,000 genes. We therefore made our tool available for other researchers to use it, in a fully open way," highlights Jabaudon.
News Article | November 19, 2015
(Phys.org)—A team of researchers from institutions in the U.K. and Switzerland has identified a protein that is heavily involved in entrainment in fruit fly brains as part of coordinating the circadian clock. In their paper published in the journal Nature, the team describes how they engineered mutant flies to express differing amounts of the protein Ionotropic Receptor 25a, aka, IR25a and then tested the ability of the flies to adjust to light and temperature fluctuations. François Rouyer and Abhishek Chatterjee with Institut des Neurosciences Université Paris-Sud, offer a News & Views piece on the work done by the team in a companion piece published in the same journal edition.
Neural stem cells (red) interact with their niche glial cells (green) to remain in quiescence. Credit: AG Berger Neural stem cells are responsible for the formation of differentiated daughter cells in the developing brain. If no new cells are needed, the stem cells may enter a resting phase called quiescence. Biologists at Johannes Gutenberg University Mainz (JGU) have now discovered that the phases of quiescence in the Drosophila fruit fly central nervous system are controlled by the Hippo signaling pathway. Drosophila serves as a model organism that helps geneticists to decode the molecular fundamentals of cellular biology and unravel mechanisms that are conserved in human beings and other vertebrates. Stem cells are undifferentiated cells able to produce specialized cell types. In the development and growth phases or during regeneration, stem cells provide backup and can generate sizeable amounts of daughter cells. Disruptions to the process can, in turn, result in tumor formation or early depletion of the stem cell reservoir. "In other words, the activity of stem cells needs to be precisely regulated to meet the needs of an organism. If no cell production is required, the stem cells remain in a quiescent state," explained Dr. Christian Berger of the Institute of Genetics at Mainz University. His work group has now been able to show how the resting phase is maintained in Drosophila neural stem cells. Protein interactions between niche glial cells and the stem cells activate the Hippo signaling pathway in the stem cells to repress growth and cell division. "The resting phases need to be actively triggered and maintained," added Berger. The Hippo signaling pathway, which is highly conserved up to humans, was known to play a critical role in organ size determination, like, for example, in the liver, but has not been demonstrated to influence neural stem cells in the central nervous system. The experiments were performed using Drosophila larvae. At the beginning of larval life, neural stem cells in the larval nervous system are naturally quiescent. Once the larvae take up food, the stem cells are activated and begin to grow. The Mainz-based team of geneticists working with Dr. Christian Berger has now discovered that growth starts earlier if the Hippo signaling pathway is deactivated, meaning the resting phase can no longer be correctly maintained. In addition, Berger's team has identified two surface proteins located on the neural stem cells and the surrounding niche glial cells that are responsible for the interactions between these cells. When the scientists remove these surface proteins from the niche glial cells, the stem cells begin to grow and prematurely form new daughter cells. In the physiological development process, this effect is regulated by the intake of nutrition. When the larvae begin to eat, the surface proteins Crumbs and Echinoid on the niche glial cells are deactivated about ten hours later and the stem cells begin to grow. The final component in this long series of signal sequences is the Yorkie effector protein that is the decisive factor at the end of the Hippo signaling pathway and determines the start of reactivation, growth, and division in the stem cells. "Our results with Drosophila exhibit surprising similarities in some respects to what we know about the regulation of resting phases in mammals, allowing for speculation as to whether the Hippo signaling pathway in neural stem cells functions in the same manner in both vertebrates and invertebrates," stated the paper's first author Rouven Ding. In order to strengthen the relevance of their results in mice, Berger's work group has started a joint project with Professor Benedikt Berninger of the Focus Program Translational Neurosciences (FTN) at the Mainz University Medical Center. Their findings may turn out to be important when it comes to research into cerebral cancer, since it is known that components of the Hippo signaling pathway, such as neurofibromin 2, are involved in the generation of brain tumors. Explore further: A Prkci gene keeps stem cells in check More information: Rouven Ding et al. The Hippo signalling pathway maintains quiescence in Drosophila neural stem cells, Nature Communications (2016). DOI: 10.1038/ncomms10510
News Article | March 1, 2015
HTC's new HTC One M9 will be available starting in mid-March. I was able to spend 24 hours with an early production unit this week and it looks like the M9 may top the M7 as my favorite smartphone. While I liked the M8 for the most part, there were a couple areas I wanted to see improved. With the M9, HTC looks to have improved in these areas, primarily in way of the in-hand feel and camera capability. Battery life should also be increased while the internal specs are top notch. I will soon have a retail unit for a full review and with just 24 hours of use under my belt, I cannot comment on battery life or longer term performance. That said, as soon as you take the new HTC One M9 out of the box you will understand what HTC means when it states the M9 is designed and built like a piece of fine jewelry. I fell in love with HTC One M7 the instant I held one in my hand. On the other hand, I nearly dropped the HTC One M8 as soon as I picked it up; the M8 never inspired the level of passion for me that the M7 did. HTC has reached a high level of emotional appeal again with the One M9 design. While the edges may be a bit sharp for some, the M9 feels much more secure in my hand than the M8. The dual color schemes, solid front panel, and premium materials set the bar for smartphone design. HTC moved from it UltraPixel rear camera to a more traditional 20 megapixel single lens variation. While I saw improvements over the M8 and my Sony Xperia Z3, HTC continues to tweak the final camera software and we are sure to see improvements over what I was able to capture this week. The rear UltraPixel was one reason I kept using other smartphones when I knew I would be capturing landscapes and I can now go with the HTC One M9 and rest assured I will capture good quality photos. One aspect of the camera that I need to further evaluate is the lack of optical image stabilization (OIS). I find this helps on the iPhone 6 Plus and Note 4 and wish HTC would have fit in some physical OIS technology. Back in October at the HTC Frequencies event, I recommended that HTC consider moving the UltraPixel to the front since people taking selfies don't need to zoom in and see great depth and detail. Several other attendees chimed in to say that was a good idea and it turns out HTC was considering that internally. Thus, I was very pleased to see the M9 roll out with an improved UltraPixel camera on the front. If you are in a low light situation and are not satisfied with the 20 megapixel rear camera, just turn the M9 around and use the UltraPixel front facing camera for your photo. I wrote an article about HTC likely sticking with a 1080p display and am pleased they did not give in to the specs war and attempt to one up the competition with a higher resolution display. HTC kept the same five inch size with 1080p and I am perfectly happy and support that decision. The display looks great and there is no need to sacrifice battery life for more pixels you can't even see. The M9 is also slightly shorter than the M8, by just 2 mm, but HTC also moved the power button from the top to the middle of the right side. While this will likely please many users, I don't like that the volume buttons are separate, one for up and one for down, so I hit them more often than the power button. HTC did provide support for customizing the software buttons, much like what LG did in the past, so you can have your notifications appear as a software button on the bottom and not have to stretch all the way up to the top. There are a couple things the HTC One M9 doesn't have that I would like to see in my daily smartphone, but I understand they are technically impossible and there are alternatives that I hope satisfy my needs. The HTC One M9 is not water resistant and while HTC could have incorporated some coating solution for a few areas, it was not possible with everything that is contained in the metal shell. However, HTC is releasing an Active case with IP68 rating and drop-resistant protection so there is a way for me to take it running in Washington State. The HTC One M9 doesn't have wireless charging due to the full metal casing. Granted this is more of a convenience for me than anything else and like my MoTR podcast co-host, Kevin Tofel, I am coming around to the belief that Quick Charging is a better solution than wireless charging. It is faster and easier to implement in today's smartphones. HTC Sense has always appealed to me and the few improvements in Sense 7 add a level of customization that I think will appeal to the masses who like to personalize their phones. It is now very easy to download or create your own theme, including the ability to share that theme with the community. I love how you can select a photo you have captured and apply that as the wallpaper while the HTC software creates several color, icon, and font options based on that selected photo. This is a rather brilliant way of helping people create completely personal devices in less than a minute. In the past HTC Sense has had the ability to select scenes (I think it was with Sense 3 or 4), yet I never knew a single person that actually switched scenes. HTC Sense 7 has a new widget, loaded out of the box, that acts as a 'smart launcher' where application shortcuts change based on your location. By default, there are work, home, and out locations, but you can customize this with places like the gym, commute, and more. The smart launcher widget can be resized and includes the applications you use most often in those particular geographic areas. You can pin apps you always use so they do not change in the future when you are in that location and also remove apps, although I have to test if those are removed permanently when I get a review unit. Since I have specific apps I use during my commute compared to when I am at home or work I look forward to using this dynamic launcher widget. A download folder and suggested apps folder are also included by default in this smart launcher, but these may have limited utility for those reading this blog. Thankfully, there is a setting to quickly and easily hide these folders from appearing. In addition to improvements in the camera hardware, HTC spent some time improving its photo editor. New effects include double exposure, prismatic, particle elements, and mirroring. I used some of these and look forward to getting artistic with my photos. You will also be able to create and order photo books and cards right from your HTC One M9. There are other minor changes in HTC BlinkFeed, lock screen notifications, and other areas, but I will go into more detail when I have a review unit in hand. You can see some of the new HTC Sense 7 aspects in my screenshot gallery. I dropped the HTC One M8 quite a bit and still find the need to carry it in a case since it is very slippery. The M9 fixed that with less back curvature and sharper edges while also improving the rock solid feel of the hardware. You can't bend an HTC One M9 and may actually hurt yourself trying. The M9 is extremely responsive, the display still looks fantastic, BoomSound speakers perform well, and the improvements in the design are easily worth an upgrade from a M7. If you own a M8, upgrading to the M9 may be harder to justify and I will have to spend more time with the M9 to make that determination. Some may have wished for a radical change in the design, but I think HTC's strategy of improving an iconic design is the right approach. You can't mistake an HTC One you may see sitting on a table and the latest continues the evolution. With Samsung looking to launch a flagship without its signature removable battery and microSD card, Android enthusiasts may get behind the HTC One M9 with its continued support for microSD expansion combined with nearly everything else one may want in a high end smartphone.
Waelchli R.,Paediatric Dermatology |
Aylett S.E.,Neurosciences |
Aylett S.E.,University College London |
Atherton D.,Paediatric Dermatology |
And 4 more authors.
British Journal of Dermatology | Year: 2015
Background The spectrum of central nervous system (CNS) abnormalities described in association with congenital melanocytic naevi (CMN) includes congenital, acquired, melanotic and nonmelanotic pathology. Historically, symptomatic CNS abnormalities were considered to carry a poor prognosis, although studies from large centres have suggested a much wider variation in outcome. Objectives To establish whether routine MRI of the CNS is a clinically relevant investigation in children with multiple CMN (more than one at birth), and to subclassify radiological abnormalities. Methods Of 376 patients seen between 1991 and 2013, 289 fulfilled our criterion for a single screening CNS MRI, which since 2008 has been more than one CMN at birth, independent of size and site of the largest naevus. Cutaneous phenotyping and radiological variables were combined in a multiple regression model of long-term outcome measures (abnormal neurodevelopment, seizures, requirement for neurosurgery). Results Twenty-one per cent of children with multiple CMN had an abnormal MRI. Abnormal MRI was the most significant predictor of all outcome measures. Abnormalities were subclassified into group 1 'intraparenchymal melanosis alone' (n = 28) and group 2 'all other pathology' (n = 18). Group 1 was not associated with malignancy or death during the study period, even when symptomatic with seizures or developmental delay, whereas group 2 showed a much more complex picture, requiring individual assessment. Conclusions For screening for congenital neurological lesions a single MRI in multiple CMN is a clinically relevant strategy. Any child with a stepwise change in neurological/developmental symptoms or signs should have an MRI with contrast of the brain and spine to look for new CNS melanoma. What's already known about this topic? Multiple congenital melanocytic naevi (CMN; more than one lesion at birth) can be associated with abnormalities of the central nervous system (CNS). The spectrum of these abnormalities includes congenital and acquired pathologies, melanotic and nonmelanotic lesions, rendering the term 'CMN syndrome' more appropriate than 'neurocutaneous melanosis'. Symptomatic CNS abnormalities were previously thought to carry a universally poor prognosis, although cohort data in the last decade have argued against this. What does this study add? A single CNS magnetic resonance imaging scan in multiple CMN, independent of projected adult size or site of the largest naevus, and ideally in the first 6 months of life, is currently an appropriate screening strategy. An abnormal result is a better statistical predictor of clinical outcome than cutaneous phenotype. Clinical management is altered as a result of the radiological result. © 2015 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.