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New research could lead to earlier diagnosis of Parkinson’s disease

05/07/2017

Suaad Abd-Elhadi wins Kaye Innovation Award for her work on a new diagnostic approach that could pave the way for early diagnosis of one of the most common and debilitating neurodegenerative disorders

Parkinson’s disease is the second most common neurodegenerative disorder in humans, after Alzheimer’s disease. It is typically characterized by changes in motor control such as tremors and shaking, but can also include non-motor symptoms, from the cognitive to the behavioral. An estimated seven to 10 million people worldwide are living with Parkinson's disease, with medication costing approximately $2,500 a year, and therapeutic surgery costing up to $100,000 dollars, per patient.

Making an accurate diagnosis of Parkinson’s, particularly in early stages and mild cases, is difficult, and there are currently no standard diagnostic tests other than clinical information provided by the patient and the findings of a neurological exam. One of the best hopes for improving diagnosis is to develop a reliable test for identifying changes in the severity of the disease. This will allow drug companies to test potential drugs at higher efficacy.

Now, a novel diagnostic approach developed at the Hebrew University of Jerusalem’s Faculty of Medicine could pave the way toward such a test. Working under the supervision of Dr. Ronit Sharon, at the Institute for Medical Research Israel-Canada (IMRIC), PhD student Suaad Abd-Elhadi developed the lipid ELISA, an approach that could lead to earlier detection of Parkinson’s, along with better tracking of the disease’s progression and a patient’s response to therapy.  

How the ELISA works

ELISA stands for “enzyme-linked immunosorbent assay.” An assay is a procedure used in laboratory settings to assess the presence, amount and activity of a target entity, such as a drug, cell or biochemical substance. ELISA is a common assay technique that involves targeting cellular secretions.

In the case of the lipid ELISA, the cellular secretion of interest is a specific protein called the alpha-Synuclin protein. This protein serves as a convenient biomarker that is closely associated with the tissues where Parkinson’s disease can be detected, along with the neurological pathways the disease travels along, causing its characteristic symptoms.

The development of a simple and highly sensitive diagnostic tool that can detect Parkinson’s biomarkers could lead to a minimally invasive and cost-effective way to improve the lives of Parkinson’s patients. Toward this end, Abd-Elhadi has recently demonstrated a proof of concept to the high potential of the lipid-ELISA assay in differentiating healthy and Parkinson’s affected subjects. She is now in the process of analyzing a large cohort of samples, including moderate and severe Parkinson's, and control cases, as part of a clinical study.

The Hebrew University, which holds granted patents on the technology through its technology transfer company Yissum, has signed an agreement with Integra Holdings for further development and commercialization.

2017 Kaye innovation Award

In recognition of her work, Suaad Abd-Elhadi was awarded the Kaye Innovation Award for 2017.

The Kaye Innovation Awards at the Hebrew University of Jerusalem have been awarded annually since 1994. Isaac Kaye of England, a prominent industrialist in the pharmaceutical industry, established the awards to encourage faculty, staff and students of the Hebrew University to develop innovative methods and inventions with good commercial potential, which will benefit the university and society. For more information about the 2017 Kaye Innovations Awards, visit http://bit.ly/kaye2017.

Suaad Abd-Elhadi is a direct-track Ph.D. student at the Department of Biochemistry and Molecular Biology of the institute for Medical Research Israel-Canada in the Hebrew University’s Faculty of Medicine. Under the supervision of Dr. Ronit Sharon, she conducts research that has been published in Scientific Reports and Analytical and Bioanalytical Chemistry. She completed her BSc in medical laboratory science at Hadassah Academic College, and was awarded a scholarship from the Liba and Manek Teich Endowment Fund for Doctoral Students and an Adrian Sucari Scholarship for Academic Excellence.

Photo for download: http://media.huji.ac.il/new/photos/hu170613_abdelhadi.jpg - Doctoral student and Kaye Innovation Award winner Suaad Abd-Elhadi (Credit: Hebrew University)

About the Hebrew University of Jerusalem

The Hebrew University of Jerusalem, Israel’s leading academic and research institution, is ranked among the top 100 universities in the world. Founded in 1918 by visionaries including Albert Einstein, the Hebrew University is a pluralistic institution where science and knowledge are advanced for the benefit of humankind. For more information, please visit http://new.huji.ac.il/en

New research could lead to earlier diagnosis of Parkinson’s disease
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Algorithm leads to dramatic improvement in drug discovery methods; Prof. Amiram Goldblum wins 2017 Kaye Innovation Award

22/06/2017

An algorithm developed at the Hebrew University cuts through the immense number of possible solutions to shorten drug discovery times from years to months

Discovery earns Prof. Amiram Goldblum a 2017 Kaye Innovation Award

Antibiotics for treating particularly resistant diseases, molecules that block immune system overreactions, molecules that inhibit the growth of cancer cells by removing excess iron, molecules that may increase the digestion of fats: all these and more have been discovered in recent years using a unique computerized approach to solving particularly complex problems.

Over the past five years, an Iterative Stochastic Elimination (ISE) algorithm developed in the laboratory of Prof. Amiram Goldblum, at the Hebrew University of Jerusalem’s Institute for Drug Research, has been applied to the discovery of potential drugs. The Institute is part of the School of Pharmacy in the Faculty Of Medicine. First tested to solve problems in the structure and function of proteins, the algorithm has since been used to reduce drug discovery times — from years to months and even to weeks.

Goldblum’s solution is different from other algorithms called "heuristics," which are based on deriving solutions using logic and intuition, and suggests better solutions. In this instance, the algorithm produces a model for the activity of small molecules on one or more proteins known to cause the disease. A model is a set of filters of physico-chemical properties that distinguish between active and non-active molecules, or between more and less active ones. Millions of molecules can then be screened by the model, which enables the scoring of each molecule by a number that reflects its ability to pass through the filters based on its own physico-chemical properties.

A model of this type is usually built in a few hours and is capable of screening millions of molecules in less than a day. Therefore, within a few days or more, it is possible to make initial predictions about the candidate molecules for a specific activity to combat a disease. Most of those candidates have never been known before to have any biological activity.

For the development of this algorithm, Prof. Goldblum won an American Chemical Society Prize in 2000. Since then, the algorithm has solved many problems related to understanding various biological systems such as protein flexibility, proteins-small molecules interactions, and more. These and other discoveries stem from collaborations between Goldblum's laboratory, where his students employ the algorithm to solve various problems, and laboratories and pharmaceutical companies in the world that test Goldblum's predictions in Germany, Japan, the United States and of course in Israel.

On the strength of Goldblum’s technology, the company Pepticom was founded in 2011 by Yissum, the Technology Transfer arm of the Hebrew University, to revolutionize the discovery of novel peptide drug candidates. Pepticom’s key asset is an exceptional artificial intelligence platform aimed at designing peptide ligands based upon solved crystal structures of proteins.

Wide Applications

The algorithm can be applied to other types of problems, in which the number of possibilities is immense and are not solvable even if the world's most powerful computers would work on it together. These include problems in which the number of possible outcomes are 10 to the power of 100 and more, such as problems of land transport, aviation, communications and biological systems.

In the field of transportation, this could involve finding alternative ways to get from one point to another using traffic data on each of the alternative roads leading between the two points. In aviation, an optimal arrangement of landings and takeoffs at busy airports. In telecommunications, finding the least expensive routes within a complex array of communication cables. And in biology, a model that is constructed on the basis of a few dozen or hundreds of molecules serves to screen millions of molecules and to discover new drug candidates. These are then sent to experimental labs to be developed further, and in some cases have been crucial in furthering the development of treatment for Alzheimer’s disease and different forms of cancer.

Kaye Innovation Award

In recognition of his work, Prof. Amiram Goldblum was awarded the Kaye Innovation Award for 2017.

The Kaye Innovation Awards at the Hebrew University of Jerusalem have been awarded annually since 1994. Isaac Kaye of England, a prominent industrialist in the pharmaceutical industry, established the awards to encourage faculty, staff and students of the Hebrew University to develop innovative methods and inventions with good commercial potential, which will benefit the university and society. For more information about the 2017 Kaye Innovations Awards, visit http://bit.ly/kaye2017.

About the Hebrew University of Jerusalem

The Hebrew University of Jerusalem, Israel’s leading academic and research institution, is ranked among the top 100 universities in the world. Founded in 1918 by visionaries including Albert Einstein, the Hebrew University is a pluralistic institution where science and knowledge are advanced for the benefit of humankind. For more information, please visit http://new.huji.ac.il/en

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Algorithm leads to dramatic improvement in drug discovery methods; Prof. Amiram Goldblum wins 2017 Kaye Innovation Award
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Cannabis reverses aging processes in brains of mice

08/05/2017

Researchers restore the memory performance of Methuselah mice to a juvenile stage

Next step: clinical trials in humans to see whether THC reverses aging processes and increases cognitive ability

Memory performance decreases with increasing age. Cannabis can reverse these aging processes in the brain. This was shown in mice by scientists at the University of Bonn with their colleagues at the Hebrew University of Jerusalem. Old animals were able to regress to the state of two-month-old mice with a prolonged low-dose treatment with a cannabis active ingredient. This opens up new options, for instance, when it comes to treating dementia. The results are now presented in the journal Nature Medicine.

Like any other organ, our brain ages. As a result, our cognitive abilities decrease with increasing age. Thus it becomes more difficult to learn new things or devote attention to several things at the same time. This process is normal, but can also promote dementia. Researchers have long been looking for ways to slow down or even reverse this process.

Scientists at the University of Bonn and the Hebrew University of Jerusalem have now achieved this in mice. With their short life expectancy, these animals display pronounced cognitive deficits even at twelve months of age. The researchers administered a small quantity of THC, the active ingredient in the hemp plant (cannabis), to mice aged two, twelve and 18 months over a period of four weeks.

Afterwards, they tested learning capacity and memory performance in the animals – including, for instance, orientation skills and the recognition of other mice. Mice that were only given a placebo displayed natural age-dependent learning and memory losses. In contrast, the cognitive functions of the animals treated with cannabis were just as good as the two-month-old control animals. “The treatment completely reversed the loss of performance in the old animals,” reported Prof. Andreas Zimmer from the Institute of Molecular Psychiatry at the University of Bonn and member of the Cluster of Excellence ImmunoSensation.

Years of meticulous research

This treatment success is the result of years of meticulous research. First, the scientists discovered that the brain ages much faster when mice do not possess any functional receptors for THC. These cannabinoid 1 (CB1) receptors are proteins to which the substances dock and thus trigger a signal chain. CB1 is also the reason for the intoxicating effect of THC in cannabis products, such as hashish or marihuana, which accumulate at the receptor. THC imitates the effect of cannabinoids produced naturally in the body, which fulfil important functions in the brain. “With increasing age, the quantity of the cannabinoids naturally formed in the brain reduces,” says Prof. Zimmer. “When the activity of the cannabinoid system declines, we find rapid aging in the brain.”

To discover precisely what effect the THC treatment has in old mice, researchers at the Hebrew University of Jerusalem, led by Dr. Mona Dvir-Ginzberg and the late Prof. Itai Bab, examined the epigenetic changes in brains of aged mice treated with THC.

"The THC treatment induced molecular and epigenetic changes, which no longer corresponded to that of untreated old animals, but rather were similar to what we see in young animals," said Dr. Mona Dvir-Ginzberg from the Institute of Dental Sciences, in the Faculty of Dental Medicine at The Hebrew University of Jerusalem.

Moreover, the number of links between the nerve cells in the brain also increased again, which is an important prerequisite for learning ability. “It looked as though the THC treatment turned back the molecular clock,” says Zimmer.

Next step: clinical trial on humans

A low dose of the administered THC was chosen so that there was no intoxicating effect in the mice. Cannabis products are already permitted as medications, for instance as pain relief. As a next step, the researchers want to conduct a clinical trial to investigate whether THC also reverses aging processes in the brain in humans and can increase cognitive ability.

CITATION: A chronic low dose of delta9-tetrahydrocannabinol (THC) restores cognitive function in old mice, Nature Medicine, DOI: 10.1038/nm.4311 (link: https://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4311.html)

Cannabis reverses aging processes in brains of mice
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How stress controls hemoglobin levels in blood

04/04/2017

“Even at the cellular level, stress and the ability to mount a stress response are essential to our survival”

Our ability to breathe oxygen is critical to our survival. This process is mediated by the hemoglobin in our blood, which carries oxygen. Since air contains less oxygen on high mountains, the body is under pressure to make hemoglobin rapidly -- a stressful time. But what role does cellular stress play in the production of hemoglobin?

In a paper in the high-impact journal Cell Research, published April 4, 2017, researchers at the Hebrew University of Jerusalem report the discovery of an entirely new mechanism through which globin genes are expressed. Discovery of this hitherto unknown property of the hemoglobin genes shows that stress is absolutely needed to allow for the production of hemoglobin.

To produce a globin protein molecule, the DNA of the globin gene is first transcribed into a long RNA molecule from which internal segments must be excised, or spliced out, to generate the RNA template for protein synthesis in the red cell.

Now, a team of molecular biologists led by Prof. Raymond Kaempfer in the Hebrew University’s Faculty of Medicine reports that for each of the adult and fetal globin genes, the splicing of its RNA is strictly controlled by an intracellular stress signal.

The signal, which has been known for a long time, involves an enzyme present in every cell of the body, called PKR, which remains silent unless it is activated by a specific RNA structure thought to occur only in RNA made by viruses.

What Kaempfer and collaborators have discovered is that the long RNAs transcribed from the globin genes each contain a short intrinsic RNA element that is capable of strongly activating PKR. Unless the PKR enzyme is activated in this manner, the long RNA cannot be spliced to form the mature RNA template for globin protein synthesis.

“Surprisingly, we have revealed an entirely new mechanism through which hemoglobin gene expression is regulated by stress. An intracellular signal, essential for coping with stress, is absolutely necessary to allow for hemoglobin production. That stress signal is activated by the hemoglobin gene itself. Although we have long known that this signal strongly inhibits protein synthesis in general, during hemoglobin gene expression it first plays its indispensable, positive role before being turned off promptly to allow for massive hemoglobin formation needed for breathing,” said Prof. Raymond Kaempfer, the Dr. Philip M. Marcus Professor of Molecular Biology and Cancer Research at the Hebrew University of Jerusalem.

Once activated, PKR will place a phosphate (a process known as phosphorylation) onto a key initiation factor needed for the synthesis of all proteins, called eIF2-alpha. That in turn leads to inactivation of eIF2-alpha, resulting in a block in protein synthesis. This process is essential for coping with stress.

Most unexpectedly, they discovered that once activated, PKR must phosphorylate eIF2-alpha, and that phosphorylated eIF2-alpha is essential to form the machinery needed to splice globin RNA. In the splicing process, removal of an internal RNA segment causes the mature RNA product to refold such that it no longer will activate PKR, now allowing for unimpeded synthesis on this RNA of the essential globin protein chains at maximal rates, allowing for effective oxygen breathing. In other words, the ability to activate PKR remains transient, serving solely to enable splicing.

Thus, the team has demonstrated a novel, positive role for PKR activation and eIF2-alpha phosphorylation in human globin RNA splicing, in contrast to the long-standing negative role of this intracellular stress response in protein synthesis.  

The realization that stress is not only important but also essential may have important implications for how we understand hemoglobin expression. “What this boils down to is that even at the cellular level, stress and the ability to mount a stress response are essential to our survival. We have long known this in relation to other biological processes, and now we see that it is at play even for the tiny molecules that carry oxygen in our blood,” said Prof. Kaempfer.

Kaempfer's lab is in the Department of Biochemistry and Molecular Biology at IMRIC, the Institute for Medical Research-Israel Canada, in the Hebrew University's Faculty of Medicine. IMRIC is one of the most innovative biomedical research organizations in Israel and worldwide, bringing together brilliant scientific minds to find solutions to the world's most serious medical problems through a multidisciplinary approach to biomedical research. More information at http://imric.org.

CITATION: PKR activation and eIF2-alpha phosphorylation mediate human globin mRNA splicing at spliceosome assembly. Lena Ilan, Farhat Osman, Lise Sarah Namer, Einav Eliahu, Smadar Cohen-Chalamish, Yitzhak Ben-Asouli, Yona Banai, Raymond Kaempfer. Cell Research, advance online publication on April 4, 2017. doi: doi:10.1038/cr.2017.39

FUNDING: This work was supported by grants from the Israel Science Foundation.             

How stress controls hemoglobin levels in blood
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Hebrew University Launches Multidisciplinary Center on Cannabinoid Research

05/04/2017

The Hebrew University of Jerusalem has announced the launch of a Multidisciplinary Center on Cannabinoid Research (http://cannabinoids.huji.ac.il). The new Center will serve as one of the world’s leading institutes for conducting and coordinating research about cannabinoids, endocannabinoids and medical Cannabis. In addition, it will promote collaboration and disseminate information

Staffed by some of the world’s leading scientists and medical doctors from the Hebrew University and its affiliated Hadassah Medical Center, the Multidisciplinary Center is already supporting exciting new research. In February 2017, the Center awarded funding to three research projects:

"The establishment in Israel of the Multidisciplinary Center on Cannabinoid Research is of great relevance at this time since both academic institutions and pharmaceutical companies worldwide are channeling enormous efforts to basic and clinical research in this field," said Dr. Joseph (Yossi) Tam, Director of the Hebrew University’s Multidisciplinary Center on Cannabinoid Research, and Head of the Obesity and Metabolism Laboratory at the Hebrew University’s Institute for Drug Research in the Faculty of Medicine.

The Center’s research will focus on the following areas: Cancer; Pain; Inflammation & Stress Management; Immunity; Metabolism; Drug Delivery & Nanotechnology; Pharmaceutical Chemistry; Neuroscience; and Plant Science & Genetics.

Along with integrating the research activities of multiple Hebrew University research laboratories into interdisciplinary networks, the Center, which relies on the infrastructure of the Institute for Drug Research at the School of Pharmacy in the Faculty of Medicine, will also foster collaborations between its participating laboratories and other well-established research groups around the globe. 

"We feel incredibly fortunate to team up with a vast number of scientists working together on this expanding field of medicine with the significant potential to discover new therapies based on cannabinoids," said Dr. Tam.

Until very recently, the Cannabis plant and its extracts (popularly called marijuana, hashish, weed, grass, and so on) were mostly frowned upon as purely recreational drugs. However, over the last 50 years, Prof. Raphael Mechoulam at the Hebrew University has spearheaded a new scientific era of Cannabis research. Prof. Mechoulam with his colleagues isolated the active constituent of the Cannabis plant, tetrahydrocannabinol, elucidated its structure and synthesized it. Later he identified the endogenous cannabinoids (formed in the mammalian body) and thus pioneered the field of cannabinoid research.

"It has been shown that modulating endocannabinoid activity has therapeutic potential in a large number of human diseases, hence research on cannabinoids may lead to very significant advances, not only in basic science but also in therapeutics. Our Multidisciplinary Center addresses many aspects in this promising area, such as cancer, head injury, addiction, bone formation, obesity and others," said Prof. Raphael Mechoulam, Head of the Academic Committee of the Multidisciplinary Center, and the Lionel Jacobson Professor Emeritus of Medicinal Chemistry in the Hebrew University’s Faculty of Medicine.

The Center’s teams of highly qualified researchers comprise Heads of Labs and Research Groups ranging through Nano-Medicine & Nano Delivery Systems, Tumor Micro-environment, Neurobiology, Pain Relief & Plasticity, Molecular Modeling & Drug Design, Immuno-pharmacology, Free Radicals, Stress and Plant Pathogen Interactions. 

The Center’s informational resources include a World Calendar of Cannabinoids, featuring information about major upcoming events in the field of cannabinoid research.

Image for download: Hebrew University’s Multidisciplinary Center on Cannabinoid Research (Credit: Hebrew University) http://media.huji.ac.il/new/photos/hu170405_MDCR.jpg

Inquiries about the Multidisciplinary Center on Cannabinoid Research can be directed to Dr. Yossi Tam at yossit[at]ekmd.huji.ac.il.   

Hebrew University Launches Multidisciplinary Center on Cannabinoid Research
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‘Smart’ bacteria remodel their genes to infect our intestines

22/02/2017
Hebrew University researchers describe how infectious bacteria sense they’re attached to intestinal cells and remodel their gene expression to exploit our cells and colonize our gut

Infectious diarrhea, a common disease of children, is responsible for over 2 million infant deaths annually in developing counties alone. A primary cause of this and other devastating conditions is enteropathogenic bacteria, which attack the intestinal tract when contaminated food is consumed.

The infection process involves hundreds of genes and proteins, both in the infectious bacteria and the human host. However, the processes by which the pathogens establish themselves in our gut are poorly understood.

Now, a new study published in the prestigious journal Science, by researchers at the Hebrew University of Jerusalem’s Faculty of Medicine, describes how pathogens sense their host, and tailor their gene expression to exploit their host to cause disease. The research was led by led by Prof. Ilan Rosenshine, the Etta Rosensohn Professor of Bacteriology at the Hebrew University.

Working with a pathogenic strain of E. coli, the researchers found that the bacteria can sense attachment to the human intestinal cells and activate gene expression in response.  This was demonstrated by engineering one of these genes to express a protein that stains the expressing bacteria to appear green under the microscope. Under microscopic examination, the researchers observed that only the attached bacteria fluoresce in bright green, whereas non-attached bacteria remain dark.

The researchers also deciphered how upon sensing that it has attached to intestinal cells, the pathogen reorganizes its gene expression, including genes involved in virulence and metabolism, to exploit the host cell. These findings may lead to the development of new strategies to combat bacterial infection.

"The next steps include mapping in detail the genes that change their expression upon attachment, and describing the precise effects of this expression remodeling,” said Prof. Ilan Rosenshine. “Another important issue is testing whether similar regulation is involved in the infection processes of other pathogens."

CITATION: Host cell attachment elicits posttranscriptional regulation in infecting enteropathogenic bacteria. Naama Katsowich, Netanel Elbaz, Ritesh Ranjan Pal, Erez Mills, Simi Kobi, Tamar Kahan, Ilan Rosenshine. Science, 17 Feb 2017: Vol. 355, Issue 6326, pp. 735-739. DOI: 10.1126/science.aah4886. Link: http://science.sciencemag.org/content/355/6326/735

FUNDING: The work was funded by a grant from the Israel Academy of Sciences and Humanities. N.K. is a recipient of a fellowship from the Carol and Leonard Berall Endowment.

The Hebrew University of Jerusalem is Israel’s leading academic and research institution, producing one-third of all civilian research in Israel. For more information, visit http://new.huji.ac.il/en.

- Dov Smith

‘Smart’ bacteria remodel their genes to infect our intestines
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Higher BMI in Adolescence May Affect Cognitive Function in Midlife

11/12/2016

Study of Israeli adolescents also looks at impact of socioeconomic position on subsequent cognitive impairment

Overweight and obesity in adolescents have increased substantially in recent decades, and today affect a third of the adolescent population in some developed countries. While the dangers posed by high adult BMI on cognitive function in later life have been documented, the association of adolescent BMI with cognitive function in midlife has not yet been reported. (BMI, or Body Mass Index, is a calculation of a person’s weight in kilograms divided by the square of their height in meters.)

To shed light on this issue, scientists at the Hebrew University-Hadassah Braun School of Public Health and Community Medicine set out to determine the association between cumulative life course burden of high-ranked body mass index (BMI), and cognitive function in midlife. The research, which will appear in the Journal of Alzheimer’s Disease 55(3), was led by Prof. Jeremy Kark from the Braun School, in the Hebrew University of Jerusalem’s Faculty of Medicine, working with colleagues in Israel and the United States.

The researchers used weight and height data from 507 individuals tracked from over 33 years starting at age 17. The participants completed a computerized cognitive assessment at ages 48–52, and their socioeconomic position was assessed by multiple methods. Using mixed models the researchers calculated the life-course burden of BMI from age 17 to midlife, and used multiple regression to assess associations of BMI and height with global cognition and its five component domains.

In this population-based study of a Jerusalem cohort, followed longitudinally from adolescence for over 33 years, we found that higher BMI in late adolescence and the long-term cumulative burden of BMI predicted poorer cognitive function later in life. Importantly, this study shows that an impact of obesity on cognitive function in midlife may already begin in adolescence, independently of changes in BMI over the adult life course,” said the paper’s senior author, Prof.  Jeremy Kark of the Hebrew University-Hadassah Braun School of Public Health and Community Medicine.

“Our results also show that taller stature was associated with better global cognitive function, independent of childhood and adult socioeconomic position, and that height increase in late adolescence, reflecting late growth, conferred a protective effect, but among women only,” added Irit Cohen-Manheim, doctoral candidate at the Braun School and lead author.

The researchers point out that while socioeconomic position may have a particularly important role in the trajectory of a person’s lifetime cognitive function, it has rarely been adequately taken into account: “To the best of our knowledge, the association between BMI and cognition as a function of childhood and adult socioeconomic position has not been previously reported. Childhood household socioeconomic position appears to strongly modify the association between adolescent BMI and poorer cognition in midlife, the inverse association being restricted to low childhood socioeconomic position,” said Prof. Kark.

"Our results are consistent with the hypothesis that childhood living conditions, as reflected also by height, influence cognitive function later in life; however, our study is unique in showing that an adverse association of higher BMI with cognitive function appears to begin in adolescence and that it appears to be restricted to adults with lower childhood socioeconomic position,” said Prof.  Kark.

Evidence for the association between impaired cognitive function in midlife and subsequent dementia supports the clinical relevance of our results. Findings of the relation of BMI in adolescence with poorer midlife cognitive status, particularly in light of the ongoing epidemic of childhood obesity, require confirmation," said Irit Cohen-Manheim.

Scientists involved in this research are affiliated with the Hebrew University-Hadassah Braun School of Public Health and Community Medicine, Jerusalem, Israel; Department of Clinical Research, NeuroTrax Corporation, Modiin, Israel; Centre for Medical Decision Making, Ono Academic College, Kiryat Ono, Israel; Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA; Biostatistics Unit, Gertner Institute for Epidemiology and Health Policy Research, Tel-Hashomer, Israel.

FUNDING: The research was supported by grants from the Chief Scientist of the Israel Ministry of Health, the Israel Science Foundation, and the US-Israel Binational Science Foundation to Prof. Jeremy Kark.

REFERENCE: Irit Cohen-Manheim, Glen M. Doniger, Ronit Sinnreich, Ely S. Simon, Havi Murad, Ronit Pinchas-Mizrachi and Jeremy D. Kark. Body Mass Index, Height, and Socioeconomic Position in Adolescence, Their Trajectories into Adulthood, and Cognitive Function in Midlife. The Journal of Alzheimer's Disease 55(3), article pre-published on December 6, 2016, DOI: 10.3233/JAD-160843.

The Hebrew University of Jerusalem is Israel’s leading academic and research institution, producing one-third of all civilian research in Israel. For more information, visit http://new.huji.ac.il/en.

Higher BMI in Adolescence May Affect Cognitive Function in Midlife
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Canada's Governor General Visits Hebrew University's Faculty of Medicine, Mrs. Johnston Visits Early Childhood Programs

03/11/2016

Governor General discusses collaborative medical research partnerships between Canada and Israel at IMRIC, the Institute for Medical Research Israel-Canada

The Governor General of Canada, David Johnston, and his wife Sharon Johnston visited the Hebrew University of Jerusalem’s Faculty of Medicine today. The 28th Governor General of Canada, and the first to make a state visit to Israel, Johnston was accompanied by a delegation that discussed collaborative medical research partnerships between Canada and Israel.

The delegation visited IMRIC, the Institute for Medical Research Israel-Canada — one of the most innovative biomedical research organizations worldwide, bringing together Canadian and Israeli scientists to find solutions to the world's most serious medical problems through a multidisciplinary approach (www.imric.org).

The President of the Hebrew University, Prof. Menahem Ben-Sasson, welcomed The Governor General and Mrs. Johnston, saying: “When you travel abroad you want to feel at home, and here at the Hebrew University’s Faculty of Medicine you can feel right at home. At the Institute for Medical Research Israel-Canada, Canadians are directly involved in the translational medicine taking place here. Together, Israel and Canada are translating science into medicine and, ultimately, healing the world.”

Governor General Johnston replied, “You greeted us by saying ‘Welcome home,’ and you explained why: the common ground we have, and the sharing of knowledge. The diplomacy of knowledge is very enabling, and that is what we celebrate at an institute like this, a Canada-Israel institute of medicine.”

Prof. Haya Lorberboum-Galski, Chair of the Institute for Medical Research Israel-Canada, described the numerous collaborative medical research partnerships between Canada and Israel taking place at the Institute for Medical Research-Israel Canada. Among these are the Alex U. Soyka Pancreatic Cancer Research Project (link); the Joseph and Wolf Lebovic Cancer Genomics and Immunotherapy Program; the Canada-Israel International Fetal Alcohol Syndrome Consortium (link); and a collaboration with the Montreal Neurological Institute. Prof. Abraham Fainsod and Prof. Ehud Cohen then described their research into Fetal Alcohol Spectrum Disorder and Alzheimer's Disease, respectively.

Sharon Johnston Holds Round-Table Discussion with Early Childhood Program and HIPPY Israel Leaders:

On Wednesday, Sharon Johnston visited the National Council of Jewish Women Research Institute for Innovation in Education to meet with leaders of various Early Childhood Programs. As honorary patron of HIPPY (Home Instruction for Parents of Preschool Youngsters) Canada (http://hippycanada.ca/wordpress), she met with leaders of the HIPPY Israel program (http://hippy-international.org/israel) to learn about services offered by the organization. She heard from several mothers who said that participating in HIPPY has helped them become more effective parents, and she discussed common challenges, lessons and experiences among the Canadian and Israeli programs.

HIPPY Israel and its sibling early childhood programs serve some 3,000 families among Israel’s native-born Arab and Jewish communities and immigrant communities from Ethiopia, Eastern Europe and Central Asia. Operating in over 70 sites, HIPPY Israel is part of the government’s New Beginnings initiative designed to extricate preschoolers and school-age children from risk and poverty.  The Ministry of Education, education and social services departments of local authorities and the Hebrew University of Jerusalem all contribute to the operation of HIPPY in Israel. Founded in the late 1960s, HIPPY Israel is the most veteran of all HIPPY programs worldwide (http://hippy-international.org), which are dedicated to the principles of equal educational opportunity and social inclusion, working with communities and families who face socio-economic challenges, helping parents and carers to nurture children’s readiness for school and their motivation to reach their highest potential. 

The visits to the Hebrew University come in the context of forging greater ties between Canadian and Israeli innovation and educational institutions. Prior to visiting Israel, the Governor General wrote in an op-ed, "We are looking beyond our borders for ideas and innovation – and what better place to look than Israel, a leader in new ideas and innovative thinking. We have much to learn from each other."

The Hebrew University of Jerusalem is Israel's leading academic and research institution and is ranked among the top 100 universities in the world. Founded in 1918 by visionaries including Albert Einstein, the Hebrew University is a pluralistic institution where science and knowledge are advanced for the benefit of humankind. The Hebrew University produces one third of all civilian research in Israel. For more information, please visit http://new.huji.ac.il/en.

Photos available for download:

Governor General’s Visit to Hebrew University Faculty of Medicine

—Photo 1: http://media.huji.ac.il/new/photos/hu161103_johnston1.JPG The President of the Hebrew University, Prof. Menahem Ben-Sasson, welcomes the Governor General of Canada, David Johnston (Photo: Bruno Charbit for Hebrew University)

—Photo 2: http://media.huji.ac.il/new/photos/hu161103_johnston2.jpg From left: IMRIC researcher Prof. Ehud Cohen; Governor General David Johnston; the President of the Hebrew University, Prof. Menahem Ben-Sasson; Chair of the Institute for Medical Research Israel-Canada, Prof. Haya Lorberboum-Galski; Mrs. Sharon Johnston; Dean of the Hebrew University’s Faculty of Medicine, Prof. David Lichtstein; and IMRIC researcher Prof. Abraham Fainsod.  (Photo: Bruno Charbit for Hebrew University)

Mrs. Johnston’s Visit to Hebrew University Early Childhood Programs

—Photo 1: http://media.huji.ac.il/new/photos/hu161102_hippy1.jpg: Prof. Gad Yair, Director of the NCJW Research Center for Innovation in Education at the Hebrew University, discusses the HIPPY Israel program with Mrs. Johnston. (Photo: Dov Smith/Hebrew University)

—Photo 2: http://media.huji.ac.il/new/photos/hu161102_hippy2.jpg: Hayat Abd Elhak, an instructor for the past 18 years in the HIPPY Israel program, presents Mrs. Johnston with a bracelet she made for her, inscribed with the Hebrew University early education programs’ motto, “From Birth to University.” “I will wear this to the state dinner tonight,” said Mrs. Johnston. (Photo: Dov Smith/Hebrew University)

Canada's Governor General Visits Hebrew University's Faculty of Medicine, Mrs. Johnston Visits Early Childhood Programs
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Columbia University Awards Top Honor to Hebrew University & NIH Epigenetics Pioneers

07/09/2016
Research led to the new field of Epigenetics, yielded insights into how cells and embryos develop

Research led to the new field of Epigenetics, yielded insights into how cells and embryos develop

Columbia University has announced that its top honor for achievement in biological and biochemical research will be awarded to two researchers from the Hebrew University of Jerusalem and a colleague from the United States.

The 2016 Louisa Gross Horwitz Prize will be presented to Prof. Howard Cedar and Prof. Aharon Razin of the Hebrew University’s Faculty of Medicine, and Dr. Gary Felsenfeld of the National Institutes of Health.

Since the Horwitz Prize was first awarded in 1967, 43 of the 94 winners have gone on to win Nobel Prizes, most recently in 2014.

The researchers will be awarded for their fundamental work on how molecules regulate the structure, behavior, and activity of DNA without modifying its genetic code. Their research has yielded key insights into how cells and embryos develop, and led to the formation of a new field of biology called Epigenetics.

Among the innovations attributed to Profs. Cedar and Razin is the concept of epigenetic reprogramming, a key process in development that erases and re-establishes the ability of cells to transform into different types.

The awards ceremony will be held in New York on November 22, 2016, following the 2016 Louisa Gross Horwitz Prize Lectures. The Columbia University announcement is at http://newsroom.cumc.columbia.edu/?p=37120.

  • Howard (Chaim) Cedar is an emeritus professor of molecular biology, and the Edmond J. Safra Distinguished Professor (Emeritus), at the Hebrew University of Jerusalem’s Faculty of Medicine.
  • Aharon Razin is an emeritus professor of biochemistry, and the Dr. Jacob Grunbaum Chair of Medical Science (Emeritus), at the Hebrew University of Jerusalem’s Faculty of Medicine.
  • Gary Felsenfeld is a senior investigator of the Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and an NIH Distinguished Investigator.

“These three scientists have advanced our understanding of how gene regulation works and what happens when the processes go wrong,” said Lee Goldman, MD, Harold and Margaret Hatch Professor of Columbia University, dean of the Faculties of Health Sciences and Medicine, and chief executive of Columbia University Medical Center. “These are fundamental medical discoveries that may lead to innovative treatments for a range of diseases.”

“These researchers laid the foundation for an important new field of study,” said Gerard Karsenty, MD, PhD, chair of the Horwitz Prize Committee and chair of the Department of Genetics and Development at Columbia University Medical Center. “As our cells divide and become more specialized they need instructions on which genes to use and which to ignore. Epigenetics adds these annotations to our biological textbook; it’s a process that is crucial to our development and continues throughout our lives.”

The Louisa Gross Horwitz Prize was established under the will of the late S. Gross Horwitz through a bequest to Columbia University. It is named in honor of the donor’s mother, Louisa Gross Horwitz, who was the daughter of Dr. Samuel David Gross (1805–89), a prominent Philadelphia surgeon who served as president of the American Medical Association and wrote Systems of Surgery. For more information, please see the Columbia University website at http://www.cumc.columbia.edu/research/horwitz-prize.

About the Hebrew University’s Faculty of Medicine

The Hebrew University’s Faculty of Medicine is a comprehensive training and research institution. Its mission is to educate Israel's finest medical personnel and deliver biomedical research breakthroughs that alleviate human suffering and improve healthcare throughout the world. The Faculty encompasses five schools: in addition to the Hebrew University-Hadassah Medical School, the Schools of Pharmacy, Nursing, Occupational Therapy and the Braun School of Public Health and Community Medicine provide the training that enable graduates to deliver the highest standards of research and treatment in Israel and around the world. At two major Institutes, the Institute for Medical Research Israel-Canada (IMRIC) and the Institute of Drug Research, the Faculty of Medicine conducts fundamental and applied research essential to understanding and finding therapies for the illnesses that challenge medical science, among them cancer, cardiovascular disease, diabetes, neurodegenerative diseases, and infectious diseases.​ For more information, visit https://medicine.ekmd.huji.ac.il/En.

Columbia University Awards Top Honor to Hebrew University & NIH Epigenetics Pioneers
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Study of Israelis and Palestinians Calls for Rethinking How HDL Protects Against Coronary Heart Disease

03/08/2016

Small and medium sized HDL particles were more closely associated than HDL-C with protection against coronary atherosclerosis in a Jerusalem study

The idea that plasma high-density lipoprotein cholesterol (HDL-C) is protective against coronary heart disease has been part of medical conventional wisdom for five decades. HDL-C has traditionally been considered the most important component of so-called "good cholesterol" HDL. However, drug trials that increased HDL-C have failed to support a causal role for the amount of cholesterol carried in HDL in reducing the risk of coronary heart disease.

With advances in the separation of lipoproteins by size and functionality, research has intensified to identify HDL measures that may be better predictors of coronary heart disease than the traditional HDL-C.  Recent evidence suggests that small, dense, protein-rich particles in HDL may be more atheroprotective than large, buoyant cholesterol-rich particles.

To explore this further, 274 Arabs and 230 Jews residing in Jerusalem were recruited for a new study by researchers at the Braun School of Public Health in the Hebrew University of Jerusalem’s Faculty of Medicine. This work, led by Prof. Jeremy Kark of the Hebrew University-Hadassah Braun School of Public Health and Community Medicine, was undertaken by Dr. Chobufo Ditah, a physician from Cameroon, as his thesis for the Braun School’s International Masters of Public Health (IMPH) program. 

(Dr. Ditah, who received the Faculty of Medicine's award of excellence for his MSc thesis and graduated Magna Cum Laude from the IMPH  program, credits the Pears Foundation of Britain for enabling him to study at the Hebrew University. The IMPH program is made possible by donors who provide full scholarships to students from low-income countries, with the Pears Foundation endowing the largest number of scholarships and underpinning the associated alumni network. Dr. Ditah currently serves as a Medical Referent with the humanitarian NGO Doctors Without Borders (MSF), overseeing the implementation, evaluation and reorientation of medical interventions in host countries.)

The researchers used Nuclear Magnetic Resonance (NMR) spectroscopy to identify the numbers and sizes of plasma HDL particles, and helical CT-scanning to identify calcification in their coronary arteries, reflecting the overall burden of coronary atherosclerosis. With these data in hand, they looked for associations between the concentrations and sizes of different HDL particles, and coronary artery calcification.

Their findings, published in the prestigious journal Atherosclerosis, showed a statistically significant inverse association of both the number of HDL particles (HDL-P) and the concentration of small and medium-sized HDL particles (MS-HDL-P) with coronary artery calcification, after adjusting for age, statin use, smoking, and other factors. There was no association between large HDL-P and coronary artery calcification in either population group. The association with HDL-C was weaker and inconsistent between men and women.

"Our findings indicate that HDL-P and MS-HDL-P are better independent markers of coronary artery disease, as reflected by coronary artery calcification, than HDL-C, at least in this bi-ethnic population of Israelis and Palestinians," said Dr. Chobufo Ditah.

"With a better understanding of HDL's complexity and a better ability to measure its components, it is now possible to move past HDL-C to more refined measures that better reflect HDL's role in coronary heart disease risk. Based on the accumulating evidence, incorporation of MS-HDL-P or HDL-P into the routine prediction of coronary heart disease risk should be considered," said Prof. Jeremy Kark.

"These findings support previous reports, based on studies in other population groups, suggesting that small dense HDL particles are protectively associated with risk of coronary heart disease. The consistency of this finding in a new population of urban Arabs and Jews, using different disease outcomes and different separation methods, add more strength to those findings," added Dr. Ditah.

Participants in this research are affiliated with the following institutions: Hebrew University-Hadassah Braun School of Public Health and Community Medicine; Hebrew University Faculty of Medicine; Hadassah Medical Center, Ein Kerem, Jerusalem; Mankon Sub-Divisional Hospital, Cameroon; LipoScience, Laboratory Corporation of America Holdings, USA.

The Hebrew University-Hadassah Braun School of Public Health and Community Medicine (link), in the Hebrew University’s Faculty of Medicine, is the first school of public health in Israel. Its world-renowned International Master’s in Public Health (IMPH) program (link) graduated its 40th class in 2015, featuring a diverse student body ranging from Cameroon to Kosovo, the United States to Jerusalem. The International MPH degree has been awarded to more than 800 graduates from 92 low-income countries in Africa, Asia, Latin America, Eastern Europe, as well as developed countries of North America and Western Europe. The comprehensive multi-disciplinary 12-month training experience prepares graduates to take up key positions as leaders and teachers of public health in their home countries, and to initiate and participate in the promotion and development of public health practices and develop capacity-building programs for training public health personnel.

The Hebrew University of Jerusalem is Israel’s leading academic and research institution, producing one-third of all civilian research in Israel. For more information, visit http://new.huji.ac.il/en.

FUNDING: This study was supported by research grants from the USAID Middle Eastern Regional Cooperation (MERC) Program (grant no TA-MOU-01-M21-002) and from D-CURE-Diabetes Care in Israel to Jeremy Kark.

CITATION: Small and medium sized HDL particles are protectively associated with coronary calcification in a cross-sectional population-based sample. Atherosclerosis, Volume 251, August 2016, Pages 124–131.  Chobufo Ditah, James Otvos, Hisham Nassar, Dorith Shaham, Ronit Sinnreich, Jeremy D. Kark. doi:10.1016/j.atherosclerosis.2016.06.010 http://www.sciencedirect.com/science/article/pii/S0021915016302556

Study of Israelis and Palestinians Calls for Rethinking How HDL Protects Against Coronary Heart Disease
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