Mitochondria use ‘toolkit’ when free radicals attack – Futurity: Research News

New research shows how mitochondriathe energy generators within cellscan withstand attacks on their DNA from rogue molecules.

The findings could pave the way for new treatments to tackle neurodegenerative diseases and cancer. The research could also have important implications for clinical advances in mitochondrial donationsometimes called a three-parent babyused to correct defects in faulty mitochondria.

The five-year study, published in Science Advances, reveals how the enzyme TDP1already known to have a role in repairing damaged DNA in the cells nucleusis also responsible for repairing damage to mitochondrial DNA (mtDNA).

During the process of energy production and making proteins, a large amount of rogue reactive oxygen species are produced which constantly attack the DNA in the mitochondria. These attacks break their DNA, however the new findings show mitochondria have their very own repair toolkits that are constantly active to maintain their own DNA integrity.

Each mitochondria repair toolkit has unique componentsenzymeswhich can cut, hammer, and seal the breaks. The presence of these enzymes is important for energy production, says lead author Sherif El-Khamisy, professor and chair of molecular medicine at the University of Sheffield.

Defects in repairing DNA breaks in the mitochondria affect vital organs that rely heavily on energy such as the brain. It also has implications on mitochondria replacement therapies recently approved in the UK and known as three parent babies.'

Although much research has focused on how free radicals damage the DNA in the cells nucleus, their effect on mitochondrial DNA is less well understood despite this damage to mtDNA being responsible for many different types of disease such as neurological disorders.

Having healthy mitochondria is also essential for tissue regeneration, making it particularly important for successful organ transplants.

The team further identified a mechanism through which mtDNA can be damaged and then fixed, via a protein called TOP1, which is responsible for untangling coils of mtDNA. When the long strands become tangled, TOP1 breaks and quickly repairs the strands to unravel the knots. If free radicals are also attacking the mitochondrial DNA, then TOP1 proteins can become trapped on the mitochondrial DNA strands, making repair even more difficult.

El-Khamisy believes the findings could pave the way for the development of new therapies for mitochondrial disease that boost their DNA repair capacity, or for cancer treatments which could use TDP1 inhibitors to prevent mtDNA repair selectively in cancer cells.

Cancer relies on cells dividing very quickly. That means they need a lot of energy, so will have really healthy mitochondria, says El-Khamisy.

If we can find a way to selectively damage the mitochondria in the cancer cells, by preventing or slowing its repair mechanism, this could be really promising.

The findings could also be important for new clinical advances such as the decision by the Human Fertilisation and Embryology Authority (HFEA) to allow mitochondrial donation, in which mtDNA from a female donor is introduced to an embryo to correct mitochondrial defects.

This research suggests that clinicians should assess the function of TDP1 and mitochondrial TOP1 before mitochondrial donation takes place, to ensure the success of this procedure, adds El-Khamisy.

Even if the new embryo has healthy mitochondrial DNA from the donor, it could still have defective TDP1 or mitochondrial TOP1 from the recipient, since they are both produced by the DNA in the cells nucleus, so mitochondrial DNA damage could still take place over time, and cause disease.

A Wellcome Trust Investigator Award and a Lister Institute of Preventative Medicine Fellowship supported the work. The University of Sheffield led the study in collaboration with the University of Newcastle, the University of Sussex, RAFT, Zewail City of Science and Technology in Egypt, and St Jude Childrens Research Hospital in the US.

Source: University of Sheffield

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Cheshunt fertility clinic under investigation for ‘paying poor women … – Hertfordshire Mercury

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A fertility clinic in Cheshunt is under investigation after it found itself at the centre of a sting by a national tabloid newspaper.

The Daily Mail alleged that the Herts and Essex Fertility Centre was one of three to offer financial incentives to poor women to donate their eggs - a practice which can be illegal.

The Human Fertilisation and Embryology Authority (HFEA), which regulates clinics, has contacted the facility and will be conducting an investigation.

Undercover reporters from the paper posed as couples seeking IVF treatment at the Cheshunt clinic, which lies a stone's throw from the Broxbourne Borough Council offices in Churchgate.

They claim they were offered cheap, or free, treatment in exchange for the donation of half the eggs the female partner would produce. Those eggs would then be used to provide IVF for other couples.

READ MORE: Brave Cheshunt boy comes through life-changing 75k operation

Clinics are restricted by law from offering financial incentives for donations, and one doctor at a clinic in Darlington told the reporter she should refrain from putting money on the consent form.

The chairwoman of the HFEA Sally Cheshire said: "We are very concerned by the allegations made in this investigation. At the HFEA our priority is the best possible treatment and care for patients and donors.

"If any patients at these clinics have worries about their care, they should contact us while we investigate further. We have already contacted the clinics involved and our inspectors will investigate each allegation. If we find poor practice in a clinic, we will take regulatory action."

READ MORE: Watch Stavros Flatley lose seven inches from his waist with new treatment

Despite the HFEA confirming to the Mercury it has contacted the Herts and Essex Fertility Centre, the clinic's marketing manager Sally Day denied this is the case.

Consultant gynaecologist David Ogutu said the facility complies with all regulations and the scheme it offers is legal.

He added: "It is important to stress that egg share cycles involve treatment of only one recipient and one egg donor. Half the eggs received from an egg share donor are used to treat only one other patient, the recipient.

"The payment received from the recipient covers the donor's costs. At Herts & Essex Fertility Centre we are immensely proud to help hundreds of couples to have babies, who cannot afford fertility treatment and who through no fault of theirs, are not eligible for NHS funded treatment.

"Only through egg sharing can some couples hope to have a loving family and we have nothing to be ashamed of."

Health Secretary Jeremy Hunt said he would be watching the HFEA investigation very closely. He added: "I will be paying close attention to the findings and in the meantime urge anyone with concerns to contact the HFEA without delay.

"The Mail's findings are both serious and worrying and they are right to have brought them to public attention."

According to the Daily Mail report, a poster in the waiting room at the Herts and Essex clinic advertises the scheme to prospective parents who cannot get NHS funding.

IVF can cost couples tens of thousands of pounds so the scheme is likely to be a significant draw for the less well-off.

A nurse in Cheshunt allegedly told the reporters egg donation was "just like giving blood" and reassured them that "an egg isn't a baby".

Potential donors at the clinic are reportedly given one hour of counselling about the experience of another couple raising their genetic children.

Mr Ogutu said: "Research has clearly shown that egg sharing women have similar success rates to that of comparable non-egg sharing women undergoing IVF treatment.

"So those women are not compromising their chances of success and on top of that, are getting their treatment free.

"As far as the mandatory independent free counselling is concerned, we do not dictate how many sessions egg sharing couples have.

"It is purely between the counsellors and the couples to decide if they require more sessions as we have no limit as to the number of sessions."

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Cheshunt fertility clinic under investigation for 'paying poor women ... - Hertfordshire Mercury

Navigating the moral maze of driverless vehicles: Safety, risks and regulation – Lexology (registration)

Driverless vehicles continue to raise difficult legal and moral questions around safety. What are the regulatory implications for this fast-paced industry?

Autonomous vehicles (AV) that require no input from human occupants are currently being tested on public roads. Experimental prototypes, still closely supervised by people, are already mixing with ordinary traffic in parts of the US, Canada, UK, Sweden, Germany and Japan.

Technology giant Google alone has clocked up more than 2.2 million miles of autonomous testing[1] since it began developing its technology in 2009. It has now launched a new company, Waymo, to commercialise the technology. Other participants - including manufacturers like Volvo, parts suppliers such as Bosch and service providers like Uber - are pursuing their own ambitious development projects.

The arrival of autonomous vehicles as either purchasable products or hireable services now seems inevitable. However, in addition to the obvious technological challenges, driverless vehicles also raise a host of legal and moral questions. Our roads, our laws and our expectations have all been shaped by more than a century of vehicles controlled by human beings, with all their foibles and failings. Adding robotic cars, buses and trucks to the mix is not going to be trivial.

"There are certain areas of the law that are well equipped to deal with new technology, such as the patent system," notes Daniel Cole, an intellectual property partner at Gowling WLG. "But the archaic language of traffic laws that talk about a vehicle being under a person's control - that's all going to have to be completely revamped. And if you've ever watched anything move through a legislature, you'll know that's not happening in a month. That's years and years of work."

Setting the legal framework

Legal questions run from relatively minor issues, such as who pays for speeding fines, to deep moral questions about putting one life ahead of another in an accident.

One potentially tricky area is how to deal with rules that sometimes need to be broken. "Imagine an AV sitting at a red traffic light while an ambulance is trying to get through, refusing to move because it's been told it can't run through a red light. Meanwhile a patient is dying," says Cole. "There has to be a way to say it's OK to have that technical violation in these circumstances. But that's tricky because there are endless possibilities."

Liability when things go wrong is another area that is expected to create challenges. "There's going to be a shift in liability from the driver to the manufacturer or the people who market these products," observes Andr Rivest, Gowling WLG partner and head of its automotive group in Canada. Especially in the early days of adoption, when AVs and human drivers interact, it may be difficult to establish exactly who is liable for what, he cautions.

Putting members of the public in driverless vehicles will also require crossing a Rubicon that manufacturers - and their lawyers and insurers - may find unnerving. "If you look at today's features, like lane departure warning, they all come with disclaimers warning that they don't replace the driver's responsibility," notes Cole. "At some point we're going to flip that on its head and say that manufacturers are in control of the car. That's a huge mind-shift."

Rivest agrees. "The transition from lower level autonomy to full autonomy is where it's really delicate, and that's what we are beginning to address," he notes. "How should an AV react if a small child runs out after a ball and the car can't stop in time, but if it veers to the side it will run down an elderly couple? Who will make these decisions?"

Redefining risk

People are fallible and human error accounts for an estimated 94% of crashes, according to figures published in the US. To limit the danger, we expect drivers to exercise good judgement and behave as responsibly as possible. Highway patrols, traffic cameras, fines and the threat of imprisonment back up that requirement, but we also acknowledge that human skill is variable. We simply live with the risk that some drivers will make fatal mistakes behind the wheel.

Yet we tend to be less willing to accept risks, even of a much lesser scale, when they are posed by machines. We expect dangers in equipment to be spotted and removed, preferably before anyone is hurt.

Similarly, the knowledge that computerised systems can react more quickly than human drivers in an emergency has led to hopes that AVs might dramatically reduce the overall frequency of accidents. But this potential has also fuelled speculation that driverless vehicles will need to include a "moral algorithm" to determine how they should react when human life is at stake. After all, an AV may need to decide whether to protect occupants at the expense of bystanders, for example.

"When cars crash today, people act instinctively - they don't make conscious decisions," points out Stuart Young, head of automotive at Gowling WLG in the UK. "But when you program a car, you are sitting at a computer writing the code, and you have every opportunity to make a calculated decision about what the car should do in given circumstances. I think there will be a moral judgement on someone who's been able to contemplate and come to a conclusion."

'Intelligent' software systems

However, the situation may not be so clear cut. It is likely that autonomous vehicles will rely on complex software techniques, such as neural networks or genetic algorithms, which can acquire expertise without human reasoning. For example, a software system might "learn" the capability to recognise a cyclist by being provided with many thousands of example images, rather than any formal definition composed by a programmer. Internally, the software will build up a complex mathematical model allowing it to successfully recognise new images of cyclists. However, there will be no step-by-step reasoning in the software that can be unravelled and understood.

Similar machine learning techniques are likely to be employed extensively within AV development, ultimately dictating how the vehicle will react to unfolding circumstances. A software model will be built up over millions of miles of testing, helping the AV to interpret any consciously coded set of rules.

What results is a mire of moral questions that include not just which decisions ought to be made but how they might be reached. Some types of programming might be subject to debate.

"Regulation needs to get on top of this," says Young. "It needs to get ahead of it. Because at the moment there's nothing giving a clear steer as to who's going to take responsibility for what, or whether all decisions are going to be left to manufacturers."

That path, as Cole notes, means waiting for things to go wrong to establish legal precedents that might provide a measure of clarity.

International regulation models

Gowling WLG is calling for an alternative approach that recognises the need for affirmative action by governments around the world. Pre-emptive regulation of autonomous vehicles need not hold back their development, argues Young. Instead, clarity over expectations and responsibilities would likely resolve some hard-to-quantify business risks that might otherwise stand as stumbling blocks.

"What we've been looking at is asking government to set up an independent agency to regulate the technology," says Young. "In the UK, we have the HFEA (Human Fertilisation and Embryology Authority), which may seem like an odd analogy, but it has been successful. There's a lot of ethics involved in embryology and development, but it was set up as an independent government agency with the right representation. It's broadly seen as having done a very good job of allowing development whilst tracking and reflecting ethical concerns in society. And that's what we need for the moral aspects of the algorithms that are going to be developed."

It is also vital to recognise that the vehicle industry is a global one, where international agreements make more sense than local regulations. Given that vehicles can drive across national borders, useful models for regulation may also be found in the air transport industry, where international pacts govern corporate behaviour and limit liability for carriers.

Vehicles are already more heavily regulated than other consumer products, with type approval to ensure compliance with national and international regulations, and compulsory safety recalls to correct serious errors, so any move to regulate the programming of AVs would not be without precedent.

Today, most countries with a significant automotive manufacturing base have started to grapple with the issues raised by AVs, with varying levels of ambition. In the UK, for example, the Department for Transport recently carried out a consultation[2] to examine what changes might be needed to insurance, type approval regulations and the national Highway Code.

"The most comprehensive exercise I've seen is in the US," says Young. "The National Highway Traffic Safety Administration (NHTSA) has done a pretty thorough job with the Federal Automated Vehicles Policy[3], issued in September. It's a root and branch review of what needs to be done to create the right legal framework in the US (including a model state-by-state code), what should be retained at a federal level, and what needs to be set down in terms of vehicle safety. Of course, there have been critics of the policy, particularly around the data sharing aspects, and with the new Trump administration there is some doubt over whether it will get any further Federal support."

As technology advances, society is likely to recognise that AVs - even those without a verifiable moral algorithm - can save lives simply by reacting more swiftly, more decisively and more accurately to sudden unforeseen danger. The question that then arises is: how much safer than human drivers do AVs need to become before we are morally obliged to adopt them?

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New study: unborn baby experience pain during first trimester – The Global Dispatch

A new study is suggesting unborn babies in the first trimester may experience pain.

The scientific journal Cell, in a study etitled Tridimensional Visualization and Analysis of Early Human Development, published in March, sheds light on the advanced neurological development of the unborn.

Although the study comes to no definitive conclusion, embryologists now have a clearer picture of the extent of nerve development at early stages of gestation a greater level of development than previously thought. (Emphasis added, the Dispatch)

Human Fetus at 8 weeks photo Henry Gray

The study saysthat adult-like pattern of skin innervation is established before the end of the first trimester, showing important intra- and inter-individual variations in nerve branches.

Later they added that Sensory nerves and their branches in the hands of 14 embryos and fetuses were reconstructed in 3D using Prph detailing the process of examining the nerves in each hand.

The medical field has had much to say on the science of fetal pain, including as the unborn child moves in response to external stimuli such as touch as early as eight weeks.

The fetus starts to make movements in response to being touched from eight weeks, and more complex movements build up as detected by real time ultrasound over the next few weeks, said Vivette Glover of the Imperial College London in 2004.

After noting the incredible advancements in 3D and 4D imaging, the study the main limitations of our method are the availability of human embryos, the number of antibody combinations (a maximum of four at this time), the compatibility of the antibodies with our protocol (Table S1) and the storage of large size light-sheet image datasets. Nevertheless, the spectrum of future investigations and applications of this method in the field of embryology and fetology are countless.

Our work shows that it should be possiblein the near future to build a reference 3D atlas of the developing human. As a first step in this direction, all our 3D datasets aremade available on a dedicated website (https://transparent-human-embryo.com/) that will also serve as a repository for additional embryology 3D data generated from our laboratory and others. This reference 3D atlas of the developing human and specific organs and systems not only represents a powerful educational online tool for researchers, educators, and students worldwide, but will allow 3D printing of anatomical models for didactic purposes in health sciences education programs.

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photo Ivon19 via wikimedia commons

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Starvation causes atypical cell death – Phys.Org

May 3, 2017 The cover image of the MCB journal. Credit: IDIBELL

Researchers from the Cell death group of the Bellvitge Biomedical Research Institute (IDIBELL), led by Dr. Cristina Muoz-Pinedo, have characterized the cell death process due to starvation, in which the endoplasmic reticulum plays a leading role. Their work, chosen as the cover of the latest Molecular and Cellular Biology journal, was carried out within TRAIN-ERs, a European collaborative action that studies diseases associated with this cellular organelle.

"Usually, programmed cell deathalso called apoptosisfollows a biochemical pathway related to the permeabilization of mitochondria; However, we observed that in cases of cell death due to lack of glucose, cells die in an unexpected way, following a process similar to what we would expect from an immune response", explains Dr. Cristina Muoz-Pinedo, last author of the study.

In cell-death-related treatments such as chemotherapy, the mitochondrial pathway is activated. Instead, when starved, cells activate the so-called "death receptors" on their membrane, which are normally used by the lymphocytes of the immune system to attack and destroy infected cells.

IDIBELL researchers have been able to relate the activation of these membrane receptors to the endoplasmic reticulum, a cellular organelle involved in protein synthesis and lipid metabolism, as well as intracellular transport. "Feeling the stress produced by the lack of nutrients, the reticulum send an alarm signal that triggers the appearance of death receptors in the membrane", says Dr. Muoz-Pinedo.

"According to our in vitro results, we assume that this is how the tumor cells located in the center of a tumorthe so-called necrotic coredie, because there are never enough nutrients in those areas", adds the IDIBELL researcher. "On the other hand, in ischemia, besides the lack of oxygen there is also cell death due to lack of glucose, so this process could also be related to the activity of the endoplasmic reticulum at a biochemical level".

Explore further: Scientists reveal alternative route for cell death

More information: Raffaella Iurlaro et al, Glucose Deprivation Induces ATF4-Mediated Apoptosis through TRAIL Death Receptors, Molecular and Cellular Biology (2017). DOI: 10.1128/MCB.00479-16

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Deans Vanderlick and Cooley among those honored by YSEA – Yale News

Yale deans Kyle Vanderlick and Lynn Cooley, faculty member Dr. Arthur Horwich, alumnus Jonathan Ayers, and outstanding undergraduates were honored at the 103rd annual meeting and awards dinner of the Yale Science & Engineering Association (YSEA), held on April 28 in the Presidents Room at the Quinnipiack Club.

At the event, YSEA officials announced that the organization had created the Dean Kyle Vanderlick Research Grantin recognition of the deans legacy in establishing the Yale School of Engineering and Applied Science as a bridge between the sciences and the humanities on the Yale campus and beyond. YSEA President John Siemon credited Vanderlick with greatly expanding the scope of the School of Engineering and Applied Science (SEAS) since she was appointed dean in 2008. Through this transformation, he said, interest and enrollment in Yales engineering programs and student groups have flourished.

He also cited the numerous cross-disciplinary collaborations between SEAS and other fields of research at Yale. The grant will be available annually to Yale science and engineering undergraduates who demonstrate the values that Dean Vanderlick has exemplified throughout her tenure at SEAS.

YSEA officials also announced the awardees for three honors:

Lynn Cooley, dean of the Graduate School of Arts and Sciences, theC.N.H. Long Professor of Genetics, and professor of cell biology and of molecular, cellular, and developmental biology, received the YSEA Award for Meritorious Service.

Cooley has focused her research on the mechanisms and regulation of oogenesis inthe fruit fly (drosophila). In her work, she has elucidated numerous aspects of Drosophila biology, utilizing techniques for genetic analysis in Drosophila that she has pioneered in her career.

At Yale, she has served as a member of the Biological Sciences Advisory Committee (20052007), director of the Combined Program in the Biological and Biomedical Sciences (20012014), director of the Medical Research Scholars Program (20062014), and director of the China Scholarship CouncilYale World Scholars Program (20062014).

Dr. Arthur Horwich, Sterling Professor of Genetics and Pediatrics at the Yale School of Medicine and an investigator at Howard Hughes Medical Institute, received the YSEA Award for Advancement of Basic & Applied Science

His research into protein foldingestablished the existence of a large class of proteins termed chaperonins, which help proteins fold correctly in various cellular locales. Previously, researchers believed that proteins folded into shape by themselves

In addition to their significance in fundamental biology, chaperonins have been recognized as being of great medical significance: Derangement of protein folding has been connected with numerous disorders, including neurodegenerative diseases. Most recently Horwichs laboratory has been studying the role of misfolding of the enzyme known as superoxide dismutatse I (SOD1), which leads to a specific type of amyotrophic laterals sclerosis (ALS).

Jonathan Ayers 78, chair, president and CEO of IDEXX Laboratories, Inc. received the YSEA Award for Distinguished Service to Industry, Commerce or Education

IDEXX is a leading innovator in veterinary medicine, producing test protocols, novel chemistry, diagnostic equipment, and software to deliver rapid and accurate results. IDEXX also protects water supplies for millions of people worldwide through their drinking water and wastewater quality tests. In addition, IDEXX tests help to protect dairy, poultry and livestock around the world.

IDEXXs growing global workforce of 7,000 includes over 700 veterinariansand Ph.D.s who bring a consistent stream of diagnostic and software innovations to the veterinary industry.

Siemon cited the companys sponsorship of STEM activities in local schools and universities, adding that IDEXX expands this culture of innovation far beyond its walls, both retaining and attracting top talent.

The YSEA Awards for Outstanding Academic Achievement were presented to the science and engineering undergraduates with the highest GPAs in their classes after five and seven terms, respectively. The winners are

Malini Gandhi 17 Molecular, cellular & developmental biology, GPA of 4.0

Anna Russo 17 Applied mathematics, GPA of 4.0

Christopher Chute 17 Mathematics, GPA of 3.99

Yumi Koga 17 Chemistry, GPA of 3.99

Stan Swidwinski 17 Electrical engineering/computer science, GPA of 3.99

Christopher Chute 17 Mathematics/computer science, GPA of 3.99

Julia Borowski 18 Chemistry, GPA of 4.00

Martin Lim 18 Economics/chemistry, GPA of 4.00

Adam Lowet 18 Cognitive science/molecular, cellular & developmental biology, GPA of 4.00

Scott Stankey 18 Mathematics, GPA of 4.00

Sara Meyers 18 Molecular, cellular & developmental biology, GPA of 3.99

Lionel Jin 18 Molecular, cellular & developmental biology, GPA of 3.99

Ilana Kaufman 18 Physics, GPA of 3.99

James Diao 18 Molecular biophysics & biochemistry, GPA of 3.99

Alexander Epstein 18 Molecular, cellular & developmental biology, GPA of 3.99

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Leading Protein Scientist Dr. Asya Grinberg Joins Dragonfly … – Markets Insider

CAMBRIDGE, Mass., May 1, 2017 /PRNewswire/ --Dragonfly Therapeutics, Inc. ("Dragonfly"), today announced the addition of Dr. Asya Grinberg to its senior team. Dr. Grinberg joins Dragonfly from Acceleron Pharma (Nasdaq: XLRN), where she led a multidisciplinary team in cell biology and protein chemistry. As Dragonfly's Head of Biologics, Dr. Grinberg leads its protein engineering, purification, characterization and structural biology team.

Dr. Grinberg brings to Dragonfly an extensive track record of scientific accomplishments and creativity in protein-based drug development. "Asya's experience developing multiple drug candidates from concept deep into the clinic represents a great addition to our company," stated Dragonfly co-founder and head of the Koch Institute for Integrative Cancer Research at MIT, Dr. Tyler Jacks.

Prior to joining Dragonfly, Dr. Grinberg spent 12 years at Acceleron Pharma discovering and developing novel protein therapeutics for treatment of hematopoietic diseases and cancer. She most recently served as Senior Director of Cell Biology and Protein Chemistry and has been a strong scientific and strategic driver of internal innovation. Dr. Grinberg's efforts were instrumental to the development of five clinical candidates, including Luspatercept (currently in Phase III testing) for treatment of beta-thalassemia and MDS. Dr. Grinberg is the key inventor of the IntelliTrap drug discovery platform targeting the TGF-beta superfamily. Dr. Grinberg received her M.Sc. in Bioorganic Chemistry from Moscow State University and did her Ph.D. studies at Max Delbrck Centre for Molecular Medicine in Germany. She completed her post-doctoral fellowship at the University of Michigan supported by the at Howard Hughes Medical Institute. Dr. Grinberg is a co-author of more than 40 scientific publications, and co-inventor on a number of patents.

"We are thrilled to welcome Dr. Grinberg to Dragonfly," said Dragonfly co-founder and CEO Bill Haney. "Her depth of understanding of protein therapeutics, coupled with her talent for innovation, will accelerate our development of novel cancer therapies, which use Natural Killer cells to both enhance the effectiveness of T cell performance and attack cancer directly."

About Dragonfly

Dragonfly Therapeutics is a discovery-stage company developing drugs to stimulate immune responses against cancer.

Our scientific founders are major figures in cancer biology and immunology and launched Dragonfly to harness the power of the innate immune system to provide breakthrough cancer treatments for patients.

For more information visit: http://www.dragonflytx.com, https://www.facebook.com/dragonflytherapeutics/, https://twitter.com/dragonflytx

Media Contact: Maura McCarthy 617-588-0086 x702 rel="nofollow">maura@dragonflytx.com

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SOURCE Dragonfly Therapeutics, Inc.

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Recent Study Published in Nature Unravels a Novel Pathway for … – Business Wire (press release)

PLEASANTON, Calif.--(BUSINESS WIRE)--10x Genomics, a company focused on enabling the mastery of biology by accelerating genomic discovery, today announced publication of an article in the journal Nature of a collaborative research study with researchers at the Stanford University School of Medicine. The article entitled, Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal, utilizes the 10x Genomics Single Cell 3 Solution for single-cell RNA-seq (scRNA-seq) to unravel the priming and self-renewal mechanisms of intestinal stem cells (ISCs).

The renewal and differentiation of Lgr5+ ISCs is critical to the continuous regeneration of the epithelial lining of the gut, which enables us to absorb nutrients and provides a barrier to protect us from the external environment. Disruptions in this process can lead to or worsen human intestinal disorders such as inflammatory bowel disease (IBD), gastrointestinal cancer and Celiac disease.

This carefully regulated process occurs within a stem-cell niche called the intestinal crypt, and depends on Wnt signaling, which can be turned up by Wnt and R-spondin (RSPO) ligands. The authors sought to identify the unique functional roles of Wnt and RSPO ligands for regulating Lgr5+ ISCs and the relative contributions of both ligands to in vivo Wnt signaling and stem-cell biology.

The authors were able to show using in vivo experiments that Wnt and RSPO are not redundant signals. RSPO was shown to expand stem cell number. Although Wnt was needed to maintain Lgr5+ ISCs in the presence of RSPO, Wnt was not sufficient to induce additional numbers of Lgr5+ ISCs above a certain threshold, demonstrating that RSPO, and not Wnt, establishes the set point for Lgr5+ ISC number. The authors performed single-cell RNA-seq to definitively show that the signaling contributions of Wnt and RSPO elicited distinct effects on ISCs, by fully characterizing the expression profile for each unique cellular subtype on a cell-by-cell basis upon perturbation of those signals in vivo.

By characterizing gene expression from 13,102 single cells, Yan and colleagues were able to show that Lgr5- control cells represented differentiated cell types of the small intestinal lineages, including Paneth, goblet, enteroendocrine, enterocyte, pre-enterocyte, and tuft cells. The Lgr5+ cells consisted of three cellular sub-populations, corresponding to cycling stem cells, non-cycling stem cells, and transit amplifying cells. The authors were able to further show that these three distinct sub-populations of Lgr5+ cells were each uniquely affected by perturbations in Wnt and RSPO signaling, conclusively demonstrating that Wnts are priming factors that enable stem cells to be competent by expressing RSPO receptors on their cell surface, whereas RSPOs are actual self-renewal factors that expand stem cell number.

Single-cell analysis provided conclusive evidence for the unique roles of Wnt and RSPO signaling to their respective function, either co-operatively priming Lgr5+ cells for competency, or for RSPO-mediated self-renewal. said Grace Zheng, Ph.D., research scientist at 10x Genomics. This powerfully illustrates the utility of single-cell RNA-seq to monitor discrete stem-cell states and their dynamic perturbation. To do this with any other technology would have been extremely cumbersome, if not impossible.

We are very excited about this result, and it opens up the possibility that analogous multi-tiered regulation by priming and self-renewal factors may be a generalized property of stem cells across other organ systems, either through Wnt and RSPO or functionally equivalent stem-cell niche components, said Ben Hindson, Ph.D., president, co-founder, and chief scientific officer of 10x Genomics. This could have wide reaching implications for stem-cell research and potentially yield new insight towards therapeutic applications in the future.

The lead author of the study is Kelley Yan, M.D. Ph.D., lead author of the study, formerly a postdoctoral fellow at Stanford and now an Assistant Professor of Medicine and of Genetics and Development in the Columbia Center for Human Development at Columbia University Medical Center. The senior author is Calvin Kuo, M.D. Ph.D., Professor of Medicine at Stanford.

The article entitled, Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal, can be accessed from Nature online: http://dx.doi.org/10.1038/nature22313

For more information about this research, visit the Kuo Lab at Stanford: http://kuolab.stanford.edu/index.html

About 10x Genomics

10x Genomics is changing the definition of sequencing by providing an innovative genomics platform that dramatically upgrades the capabilities of existing sequencing technologies. This is achieved through a combination of new microfluidic science, chemistry and bioinformatics. By implementing GemCode Technology within the Chromium System, researchers can now, for the first time, find new structural variants, haplotypes and other valuable genomic information with comprehensive workflows for Single Cell, V(D)J, Genome, Exome and de novo Assembly applications that incorporate their pre-existing sequencing technologies. http://www.10xGenomics.com.

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Recent Study Published in Nature Unravels a Novel Pathway for ... - Business Wire (press release)

Biochemistry Analyser Market to Reach a Valuation of US$ 4,625.3 … – MilTech

The clinical use of biochemistry analyzers in measurement solutions such as latex agglutination, ion-selective potentiometry, and colorimetric & photometric testing. In addition to this, accuracy of biochemistry analyzers in analyzing blood and urine samples has benefited pathology labs and diagnostic centers across the globe. Persistence Market Research predicts that the global demand for biochemistry analyzers will continue to soar on the grounds of such factors. A recent report published by Persistence Market Research projects that by the end of 2024, the global market for biochemistry analyzers will reach US$ 4,625.3 Mn in terms of value.

Key findings in the report cite that the use of chemistry analyzers spans from high-throughput clinical labs to point-of-care clinics, and its use for testing enzymes, electrolytes and proteins is gaining traction. The report current values the global biochemistry analyzer market at a little over US$ 3,000 Mn. During the forecast period, revenues generated through global sales of biochemistry analyzers are, thus, expected to soar at a steady CAGR of 5.5%.

Key Research Insights from the Report include:

Roche Diagnostics GmbH, Siemens AG, Beckman Coulter Inc., Abbott Diagnostics Inc., Shenzhen Mindray Bio-Medical Electronics Co., Ltd., Hologic, Inc., Randox Laboratories, Ltd., Awareness Technology, Inc., Transasia Biomedicals Ltd., and Nova Biomedical Corp. are profiled in the report as key players of global biochemistry analyzer market.

A Sample of this Report is Available Upon Request @http://www.persistencemarketresearch.com/samples/6451

The report further reveals that fully-automated biochemistry analyzers will remain in great demand in the years to come. In 2017 and beyond, more than 85% of global biochemistry analyzer revenues will be accounted by sales of fully-automated biochemistry analyzers. Moreover, clinical diagnostics will also remain the largest application of biochemistry analyzers throughout the forecast period. Revenues accounted by global sales of biochemistry analyzers in clinical diagnostics are anticipated to register speedy growth at 5.7% CAGR. The report further identifies diagnostic centers as largest end-users of biochemistry analyzers in the world. On the other hand, rising number of point-of-care diagnostic labs instated in hospitals will render a key end-user of biochemistry analyzers. Together, hospitals and diagnostics centers will be responsible for procure over two-third of global biochemistry analyzers revenues through 2024.

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The use of biochemistry analyzers in drug development applications is also expected to gain traction in the future. Based on modality, the report forecasts that in 2016, more than 70% of the market value was accounted by bench-top biochemistry analyzers. However, towards the end of the forecast period, the demand for bench-top modality will incur a marginal decline, while floor standing biochemistry analyzers will bring in over US$ 1,200 Mn revenues.

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Biochemistry Analyser Market to Reach a Valuation of US$ 4,625.3 ... - MilTech

‘Grey’s Anatomy’ Sneak Peek: Alex Battles Eliza Over a Kid’s Rights … – Yahoo TV (blog)

When it comes to the kids under his care, Dr. Alex Karev is as protective as a mama bear with her cubs. And as Greys Anatomy fans have seen before, hes willing to toe lines or even cross them to give them the best care.

But in this sneak peek from Thursdays new episode, Alex (Justin Chambers) runs into a new force of opposition Eliza Minnick (Marika Dominczyk). A boy named Liam comes into the hospital with a tumor, but his parents refuse surgery due to their religious beliefs.

The kid took a train all by himself to ask us for help, Alex pleads toEliza. Actual help, not prayers and olive oil on his head.

Eliza doesnt back down. No neurosurgeon will cut into a kids skull without parental consent, because its illegal, she replies.

And then, twisting the knife a bit, she notes that with his history assaulting DeLuca and almost going to prison for it perhaps he shouldnt be crossing any lines right now.

Greys Anatomy airs Thursdays at 8 p.m. on ABC.

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'Grey's Anatomy' Sneak Peek: Alex Battles Eliza Over a Kid's Rights ... - Yahoo TV (blog)