New drug target for Rett syndrome

first_imgHarvard Stem Cell Institute (HSCI) researchers have identified a faulty signaling pathway that, when corrected in mice, ameliorates the symptoms of Rett syndrome, a devastating neurological condition. The findings could lead to the discovery of compounds or drugs that may benefit children affected by the disease, says neurobiologist Jeffrey Macklis, a member of the HSCI Executive Committee.The research was published recently in Nature Communications. Noriyuki Kishi and Jessica MacDonald, both recent postdoctoral fellows in the Macklis laboratory, are co-first authors. Macklis, who directed the work, is the Max and Anne Wien Professor of Life Sciences in the Department of Stem Cell and Regenerative Biology, and Center for Brain Science at Harvard University.Rett syndrome is a relatively common neurodevelopmental disorder, the second most common cause of intellectual disability in girls after Down syndrome; it is associated with a dysfunctional gene on the X chromosome. Boys with Rett syndrome are rare, because male fetuses who carry the mutations on their one X chromosome usually have prenatally lethal forms of the disease.Girls with Rett syndrome appear to develop relatively normally for the first six to 18 months of life, but then regress; they tend to lose their ability to speak and the purposeful use of their hands, withdraw from social situations, and wring their hands.Austrian physician Andreas Rett first described the disorder in 1966, but it wasn’t until 1999 that Huda Zoghbi and her lab at Baylor College of Medicine identified mutations in the gene MECP2 as the root cause of Rett syndrome. MECP2, however, turns a very large number of genes on and off throughout the entire body, so it has been a long-standing puzzle why children with Rett syndrome have this very specific and reproducible developmental cognitive brain disorder.“My view was that MECP2 mutation in Rett syndrome disrupts so many genes and their protein products that we weren’t going to find a single gene that we could fix to help girls with Rett,” said Macklis, former program head of HSCI’s Nervous System Diseases Program, and an Allen Distinguished Investigator of the Paul G. Allen Family Foundation. “But if we found a disrupted, improperly regulated signaling pathway that was ‘drug-able,’ that affected enough of the girls’ pathology, we might be able to make them dramatically functionally better with already available therapeutics — and that might make a real difference in their lives and their families’ lives.”Instead of concentrating on the MECP2 gene, Macklis’ group focused on neurons he knew were “abnormal and implicated in Rett syndrome and autism spectrum disorders,” and in 2004, his lab was the first to describe abnormal development in this type of neuron. These neurons, called inter-hemispheric callosal projection neurons (CPNs), have shorter, less-developed dendrites, or “receiving antennas,” in mice with the Rett gene mutations and in individuals with Rett syndrome.Building on their 2004 findings, the researchers were able to fluorescently label CPNs in mice with or without the Rett mutation, purify them from other types of neurons, and look at the levels at which many thousands of genes were active, and thus how much of the proteins coded for by those those genes was made.They found that one gene for IRAK1, which Macklis’ group identified as regulated by MECP2 and which is a well-known part of the NF-kB signaling pathway, was making about three times more protein than normal. They modified IRAK1 levels both in mice with Rett mutations and in mouse neurons in culture dishes. When they reduced the activity of its gene Irak1 by roughly half, and consequently the amount of IRAK1 protein made, the neurons and their dendrites developed substantially better, indistinguishable from normal by several assays. Further, mice with reduced levels of IRAK1 had significantly fewer symptoms, better function, and much longer lifespan. They had much-improved health, well beyond only these neurons.Now, Macklis said, the researchers have started looking into potential compounds and drugs that are already available and that might partially correct this pathway, and what dosages and timing might ultimately ameliorate the effects of Rett syndrome.last_img read more

Justice Alito speaks on panel about Italian constitutional system

first_imgThe Kellogg Institute for International Studies and the Potenziani Program in Constitutional Studies hosted the book launch for the book, “Italian Constitutional Justice in Global Context,” on Wednesday afternoon. The book was co-authored by a group of four legal scholars that includes Paolo Carozza, a Notre Dame law professor, and Andrea Simoncini, a visiting fellow and professor of constitutional law at the University of Florence, and focuses on the Italian constitutional court system and the lessons it contains for constitutional legal studies around the world.As part of the launch, Kellogg and the Potenziani Program arranged a panel of speakers who were involved with the writing and editing of the book, including U.S. Supreme Court Justice Samuel Alito and the O’Toole Professor of Constitutional Law, Anthony J. Bellia. Simoncini also spoke on the panel.Alito, who wrote his senior thesis on the Italian constitutional courts, said the Italian court is particularly deserving of study by the English-speaking world.“One of the great opportunities I’ve had is to compare how I do things with other judges and justices,” he said.Simoncini said he and his co-authors realized there was a lack of Italian constitutional study in the English language, which is mainly due to the lack of translations available.“It was surprising to hear decisions from Albania and Zimbabwe talked about and studied, but the Italian counterparts were not,” he said, “I found this to be because Italy did not translate their decisions, and so they had no bearing on matters of global constitutionalism.”Alito said constitutional law procedure differs drastically in courts around the world, and these differences are a mechanism through which the American court system and it’s many unique facets can be evaluated.“Judicial review used to be unthinkable,” Alito said. “Here, in our idea of judicial review, the Constitution is law, but a higher form of the law. If the law clashes with the Constitution, constitutionality is debated and litigation arises.”Alito said this perception of judicial review may be derived from variances in how scholars and philosophers around the world think about rights, but that judicial review holds a very important place in American constitutional law.“Judicial review serves to protect against rights violations in the future,” Alito said.Alito said the idea of using legal precedent to substantiate legal decisions in the Supreme Court has become a topic of much debate by legal scholars, and he believes this practice does not account for differences in value systems between countries.“The point that emerges from looking at different cases, while Europe and America agree on certain values, it is simplistic to rely on counting up foreign decisions,” Alito said.Alito said in the U.S. justice system, there is at least a connection to the democratic process, as elected officials are still held accountable to their constituents for decisions to accept candidates for the Supreme Court or not.“Judges are appointed by an elected president and confirmed by elected members of congress, with only a majority,” Alito said.Alito said this contrasts sharply with other international courts, whose procedure helps to preserve courts as “judicial bodies and not political bodies.”Paolo Carozza, director of the Kellogg Institute for International Studies, said the book was a deeply collaborative venture that was the product of friendly discussion.“We didn’t take different chapters, each chapter was written by four pairs of hands,” Carozza said. “One person would write a chapter and then it was circulated for comments and editing.”Simoncini said the collaborative nature of the book is perfectly suited to the subject matter, as the global community can draw important lessons from comparing their varying modes of operation.“The dialogue between different constitutional scholars was not only the content of our work, but also the methodology,” Simoncini said.Carozza said the way the book was written was exemplar of Notre Dame “as a community of friendship and learning.”He also said the contributions the book will make to the study of comparative global constitutionalism “pales in comparison to the ways in which we, as a University, will impact the world.”Tags: Constitutional Studies, Kellogg Institue, Potenziani Minor in Constitutional Studies, SCOTUS, Supreme Court, U.S. Supreme Courtlast_img read more

Fintech Fantasies: Finovate fires up for 2015 with upcoming spring show in San Jose…

first_img 2SHARESShareShareSharePrintMailGooglePinterestDiggRedditStumbleuponDeliciousBufferTumblr For fintech folks it’s like Christmas in the spring, as Finovate fires up for 2015 displaying the latest in financial technology services. It’s always exciting. So we invited the ring leader himself, Mr. Eric Mattson, The Finovate Group’s CEO and host of FinovateSpring in San Jose (May 12-13), on the show to get a behind-the-scenes look at this year’s line up.We also talked about how Finovate has evolved over the last 8 or 9 years — adding shows and going global, capitalizing on what’s new in tech trends and answering issues with envelope-pushing solutions. Additionally, we discussed what makes a compelling 7-minute presentation, takeaways attendees can expect, and what’s new on the horizon — which happens to be Finovate’s latest show series: FinDEVr, taking place later this year in San Francisco. continue reading »last_img read more

Caught in a Wells Fargo web? Here’s how to get untangled

first_imgExcept that millions of Americans are second guessing their decision to bank with Wells Fargo, not much has changed since the Consumer Financial Protection Bureau announced the massive fake accounts scam perpetrated by Wells Fargo on its own customers. Predictably, a few proposed class action lawsuits have been filed by Wells Fargo customers, shareholders, and former employees alike.Americans expressed outrage over the first highly publicized banking scandal in a few years, and observers on both sides of the political aisle cheered Sen. Elizabeth Warren’s (D-Mass.) much-deserved verbal spanking of Wells Fargo CEO John Stumpf during a Senate Banking Committee hearing.That video never gets old.Industry analysts say that the Wells Fargo scandal has damaged the bank’s reputation, but there is no indication that a mass exodus has occurred among the bank’s customers. continue reading » 17SHARESShareShareSharePrintMailGooglePinterestDiggRedditStumbleuponDeliciousBufferTumblrlast_img read more

Women in leadership positions in credit unions: Are you hearing what I’m saying?

first_imgThink about this…as a speaker, you have an event coming up. You talk to the organizer or meeting planner about who the audience is, what their expectations are and what the message is that they want you to share and are prepared to accomplish that. You review your talking points and are excited to really offer the attendees exactly what you were told they needed.  You’re a bit nervous as you always are before a talk and then…you walk in and the audience is not who the planner told you they would be, the message you have is not relevant to them and you know that there is no way you will relate to them or them to you.  All you wanted was to connect with them and talk about what was important to them…any hope of them hearing your message is now out the window. You only hope you wake up from this nightmare of a dream.That scenario, as crazy as it sounds, really did happen to me. I always do my homework and know the audience, what the meeting planner wants and needs and provide some tips for immediate implementation so it isn’t simply a rah rah talk that will be forgotten as soon as everyone goes back into their own “real” world.  I should have realized when the planner didn’t have a lot of information and everything I asked had a “sounds great” response.  Any certain verbiage or examples I should use? “You’ve got this” and “sounds great” was all I received.  Even after doing research on the group, I didn’t find a lot to work with, but I knew the message she wanted…and so I was ready to connect and bring value.And then…I walked into the room that was to be 98% female and it was anything but that. The attendees were looking for something totally different than what I was prepared to share with them and although I did some amazing tap dancing, the majority of the room and I were not connecting and I left ready to throw in the towel. I have never felt so horrible.  I received a comment that I should never be invited back as I wasn’t prepared…and that was one of the good ones. I reached out to the planner and apologized for not giving the attendees what they were looking for and she told me she thought it was great and she loves having me and can’t wait to do this again. I wasn’t even sure if she was in the same room as I didn’t feel that at all.So, the question is, how important is communicating effectively? How about connecting to the people on your team? Are they hearing the message that you are intending to send? Unfortunately, for most of us, our communication goals are not consistently achieved; our message is not received as it was intended.  Communication is a necessary skill for all interpersonal relations, personal or professional. If a message is not understood, you have not communicated.Your role as a leader is:To make communication as simple as possibleTo be clearTo create understanding and meaningTo generate feedbackTo check for understandingHere are some ways to connect effectively:Be genuine. The only connections that work will be the ones that you truly care about; the world will see through anything short of that. If you don’t have a genuine interest in the person with whom you’re trying to connect with, then stop trying. As a leader, you must show that you are there to support someone’s goals and dreams. We don’t have to agree with their journey…you need to support it. It’s about them, not about you.Provide massive help. Most people never reach out to anyone above their level. Did you know that everyone needs help or support in something? You have more to offer than you realize and those on your team want to learn from you. For women especially, it’s hard enough to ask for help. When someone does, pay attention to them and be interested in them.Persistence is key. When you are looking to connect with someone, you can’t give up after one attempt. It’s the same with someone trying to get your attention. We are all busy and may not be able to jump when someone needs us. Sometimes a simple email or message letting them know when you are available will ease the situation. Communication is at an all-time high when they are trying to connect with you. Put yourself in their shoes…how would you want to be heard?  Make real connections. Think about how you’ve made the connections you have. That’s all this is. You only create relationships with people you genuinely want in your life. The same rule should apply with those reaching out to you. Don’t over-think it. Be human, be helpful and most humans will happily be human in return, regardless of who they are or what position they hold.Remain unforgettable, in other words, find ways to stand out. Remember birthdays or important events happening in your team. Give them your favorite book signed. Be genuinely helpful. You’d be surprised how the simplest things actually never get done. Being memorable isn’t as hard as some think! Be the leader or mentor that you wish you had. Imagine what that would feel like for someone else. Here is something to ponder… Think about a situation in which you experienced difficulty in communicating effectively with another person. If you had the opportunity for a second chance, what would you do differently? Was it the message or was it the way it was communicated? As a leader you need to understand what the other person is saying-not necessarily agreeing with it. Check in to make sure you both understand what is said and what is heard…and especially what isn’t said. As Steven Stowell said, “Great leaders find ways to connect with their people and help them fulfill their potential.” 15SHARESShareShareSharePrintMailGooglePinterestDiggRedditStumbleuponDeliciousBufferTumblr,Judy Hoberman Men and women sell, manage, recruit and supervise differently.  Judy Hoberman, creator of “Selling in a Skirt”, shares essential insights about gender differences and how to embrace and use those … Web: www.sellinginaskirt.com Detailslast_img read more

China approves its first H5N1 vaccine

first_imgApr 3, 2008 (CIDRAP News) – China’s State Food and Drug Administration (SFDA) yesterday approved the country’s first prepandemic H5N1 influenza vaccine, an inactivated whole-virus product made by Sinovac, a Beijing-based biotechnology company.China’s approval of Sinovac’s Panflu vaccine marks the third H5N1 vaccine to win approval from national or international regulatory bodies. In April 2007, the US Food and Drug Administration approved a Sanofi Pasteur H5N1 vaccine. A month later, the European Union approved a mock-up pandemic flu vaccine made by Novartis (it is designed to speed vaccine production when a pandemic emerges and will not be manufactured until then).Sinovac said its vaccine is approved only to supply China’s national vaccine stockpile and will not be available for commercial sale, according to a company press release yesterday. In 2006 the company said it planned to produce 20 million doses of the vaccine over the next few years, according to a previous report. The latest information gave no production estimate.”This vaccine is reserved for emergencies in the country and we have to get instructions on how much to produce,” Liu Peicheng, Sinovac’s publicity supervisor, told Reuters today.Vaccine experts say there is no guarantee that vaccines based on current H5N1 strains will be effective if a pandemic H5N1 virus emerges, but they hope such vaccines will provide some protection and buy time while a vaccine specifically matched to the pandemic strain is developed.The Sinovac vaccine contains an inactivated Vietnam strain of H5N1 virus and an aluminum hydroxide (alum) adjuvant. A phase 1 study of the vaccine, published in a 2006 issue of The Lancet, induced potentially protective immune responses in 78% of volunteers after two 10-microgram (mcg) doses.In late December 2007, Sinovac in a press release reported preliminary phase 2 results for the vaccine. The trial included 402 adults (aged 18 to 60). Groups received two doses of 5, 10, or 15 mcg of the vaccine.Each dosage induced varying degrees of immune response, but the 10- and 15-mcg dosages reached standards set by the EMEA to indicate good results for seasonal flu vaccines. Sinovac said the trial did not show any serious adverse reactions among the volunteers.The researchers who conducted the phase 1 trial said a whole-virus vaccine offers a dose-sparing advantage, because 20% to 23% of the vaccine antigen is lost during the preparation of split-virus vaccines. However, Iain Stephenson, MD, of the Infectious Disease Unit at Leicester Royal Infirmary in Leicester, England, had said in a Lancet editorial that though whole-virus vaccines usually produce a better response than split or subunit counterparts, it is difficult for manufacturers to switch production methods. Also, he said whole-virus vaccines are linked to febrile reactions in children.Sinovac has also completed a phase 1 trial of a split-virus H5N1 vaccine, which was found to be safe for children, adults, and elderly people, according to its December 2007 press release.Peicheng said Sinovac is also conducting trials to see if its H5N1 vaccine yields cross-protection against other strains, including those from Indonesia, Turkey, and Anhui province in China, Reuters reported.China has reported three H5N1 cases so far this year, all of them fatal.Vietnam starts H5N1 vaccine trialIn other vaccine developments, Vietnamese researchers said today that clinical trials have begun for an H5N1 vaccine that the country is developing, according to a report from Reuters. The vaccine is based on a Vietnam strain of H5N1 virus.The vaccine is being tested in 11 volunteers, all of whom are researchers, the report said. They received their second dose of the vaccine today at the National Institute of Hygiene and Epidemiology in Hanoi.Nguyen Tuyet Nga, an epidemiologist and virologist who is leading the trial, told Reuters that the US Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have helped with the project, though no foreign pharmaceutical firms are involved in the study.Subjects in the trial are receiving two injections 28 days apart, with doses ranging from 3.75 to 45 mcg, Nga said. She also told Reuters that researchers would test the vaccine at a later date to see if it offers cross-protection against other H5N1 strains. The report did not say if the Vietnamese vaccine is a split- or whole-virus product or if it contains an adjuvant.Vietnam has reported five H5N1 cases this year, all of them fatal.See also:Sep 7, 2006, CIDRAP News story “Chinese report results for whole-virus H5N1 vaccine”Apr 2 Sinovac press releasehttp://www.sinovac.com/?optionid=754&auto_id=569Dec 24, 2007, Sinovac press releasehttp://www.sinovac.com/?optionid=754&auto_id=496Oct25 to Nov 2, 2007, CIDRAP News report “The pandemic vaccine puzzle: A seven-part series on the chances for immunizing the world against pandemic flu”last_img read more

The most beautiful and quietest rally in the world started from Istria. Follow live Nikola Tesla EV Rally Croatia livestream

first_imgNikola Tesla EV Rally Croatia – the most beautiful and quietest rally in the world marks its fifth edition and started in Rovinj.The rally traditionally starts in Istria and takes place from June 3 to 10, with the participation of a total of 60 teams that will run a 1550-kilometer route for eight days and end on June 10 in Zagreb. The route, officially named “Green Electric Highway” with charging stations allows you to experience the most beautiful parts of the Republic of Croatia and includes a visit to five islands and six national parks, with many attractions.Luxury tourist e-tour, which combines e-mobility, ecology and tourism, allows participants from Germany, Austria, Slovenia, Finland, Belgium, Norway, to show the best of Croatian cultural heritage and natural beauty with tasting of high quality wines and gastronomic delicacies and staying in luxury hotels.Every year, this innovative and unique tourist project pushes the boundaries and in the best way promotes the Republic of Croatia in Europe and the world by breaking records and setting new standards. Last year, the largest number of Tesla vehicles on the ferry and the largest number of vehicles that were being charged at one place were gathered. Between 4 and 5 MW of electricity was consumed daily, and the vehicles were charged at HEP’s substations, which delighted all competitors.Exploring the interior of Istria, through the islands of Cres, Lošinj, Krk and the island of Pag with wonderful lunar landscapes, the rally arrives in the city of Zadar where participants will have the opportunity to experience the cult installation of solar panels “Greeting to the Sun” and sea organ. In the final phase of the rally, a visit to the Plitvice Lakes National Park is planned, followed by the birthplace of Nikola Tesla in Smiljan and at the very end, Zagreb, where the end of the rally and the award ceremony will take place.Nikola Tesla EV Rally Croatia on the way from Istria to Zagreb can be followed live below on the linklast_img read more

Niche market

first_imgTo access this article REGISTER NOWWould you like print copies, app and digital replica access too? SUBSCRIBE for as little as £5 per week. Would you like to read more?Register for free to finish this article.Sign up now for the following benefits:Four FREE articles of your choice per monthBreaking news, comment and analysis from industry experts as it happensChoose from our portfolio of email newsletterslast_img

The problem of family violence

first_imgEditorial – Otago Daily Times 12 Nov 2012A call to make domestic violence a stand-alone criminal offence provides a much-needed avenue for discussion about a problem still sadly prevalent. Departing Principal Family Court Judge Peter Boshier, who is beginning a term with the Law Commission, believes a separate charge of domestic violence would provide a more accurate gauge of the extent of the problem in New Zealand and provide a wider context for judges considering the criminal backgrounds of people appearing in court. “We all know that family violence is a huge problem, but we don’t know just how much of a huge problem it is,” Judge Boshier said in his final speech at the Women’s Refuge conference in Blenheim recently. The call follows others made in March, during a trip to Queenstown, including significant changes around protection orders. One of the difficulties calculating the extent of domestic violence is police estimate only 18% of cases are reported. Women’s Refuge figures show almost 25,000 women and children needed its help last year, and refuges provided safe beds to an average of 230 women and children each night. The refuge receives more than 60,000 calls to its Crisisline every year.…A police report released in September challenges some of the gender perceptions around family violence. The Family Violence Death Review found mothers were responsible for 45% of the child deaths subject to a family violence death review from 2004 to 2011. The report, which only involved deaths that were subject to a family violence death review, found victims of family violence were spread almost equally among men, women and children. It also found 81% of female victims and 29% of male victims were killed by a former or current spouse or partner, 64% of all deaths were in families where police had prior involvement, and in 55% of child deaths police had prior involvement with the family. Most suspects or offenders were in their 20s. Family First national director Bob McCoskrie said the statistics debunked the misleading popular perception “that women and children need to be protected from men”. “If we’re really serious about reducing family violence, we need to talk about … our violent culture and the role alcohol and drugs play in fuelling this environment.” Prof David Fergusson, of the University of Otago, said the public perception men were the perpetrators of most domestic violence was the result of biased publicity. “The proper message is that both gender groups have a capacity for domestic violence – women probably perpetrate more assaults on children then men do.” Prof Fergusson said the bottom line was “the importance of public policy being based on evidence”. There should be no argument there, but it is debatable whether such evidence – through more accurate statistics on the problem – will actually help solve the problem, particularly given the issue is complex, often involving intergenerational, ingrained and learned behaviours and a cocktail of social and environmental factors.http://www.odt.co.nz/opinion/editorial/234265/problem-family-violencelast_img read more

St. Louis 7th Grade Girls Team In School Tourney

first_imgThe 7th grade St Louis Girls basketball team finished with 1 win and 1 loss Saturday at their 2nd annual St Louis School Invitational.The win came against St Bartholmew by a final score of 24 to 17. Kate Burkhart finished with a game high 7 points. Avery Roell & Hanna Hurm scored 4 points each. Sarah Preston finished with 5 points. Stella Hillenbrand& Kate Poltrack rounded out the scoring each with 2 points. Harlee Masavage led the Lady Cards in rebounding. Hailey Mohr led defensively. Hanna Hurm scored 4 points, followed by Hailey Mohr, Kate Burkhart, & Stella Hillenbrand with 2 each. Avery Roell added a 3 pointer and Harlee Masavage a free throw.Submitted by STL Coach Mike Burkhart.center_img In the second game St Louis squared off against a much taller and more athletic Benjamin Rush team. Final score Ben Rush 44 St Louis 14.last_img read more