Mechanism Identified Linking ASD and Intellectual Disability, Opening Door To Development of Treatment Options

MedicalResearch.com Interview with:

Woo-Yang Kim, Ph.D Associate Professor Department of Developmental Neuroscience  Munroe-Meyer Institute University of Nebraska Medical Center Omaha, NE 68198-5960

Dr-Woo-Yang Kim

Woo-Yang Kim, Ph.D
Associate Professor
Department of Developmental Neuroscience
Munroe-Meyer Institute
University of Nebraska Medical Center
Omaha, NE 68198-5960

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  Autism impairs the ability of individuals to communicate and interact with others. About 75 percent of individuals with autism also have intellectual disability, which is characterized by significant limitations in cognitive functions and adaptive behaviors. While autism and intellectual disability are currently defined using behavioral criteria, little is known about the neuropathogenesis of these conditions.

Recent genetic studies have reported that haploinsufficiency of ARID1B causes autism and intellectual disability. However, the neurobiological function of ARID1B during brain development is unknown.

Our study investigated the neurobiological role of the gene in brain development. Using genetically-modified mice, we found that Arid1b haploinsufficiency leads to an excitation-inhibition imbalance by reducing the number of GABAergic interneurons in the cerebral cortex. Furthermore, we showed that treatment with a GABAA-receptor positive allosteric modulator rescues ASD-like behavior and cognitive dysfunction in Arid1b-haploinsufficient mice, suggesting an association between lower numbers of GABAergic interneurons and behavioral outcomes.

Our findings suggest a pathogenic mechanism for Autism Spectrum Disorder and intellectual disability.

Continue reading

Single Injection of Klotho Gene Protected Animals From Cognitive Decline

MedicalResearch.com Interview with:

Dr Miguel Chillon PhD Department of Biochemistry and Molecular Biology Universitat Autonoma Barcelona Spain

Dr. Chillon

Dr Miguel Chillon PhD
Department of Biochemistry and Molecular Biology
Universitat Autonoma Barcelona
Spain

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Klotho is a protein with an anti-aging and neuroprotective role. Recent studies show it prevents the development of cognitive problems associated with aging and Alzheimer’s disease. Klotho works mainly by inhibiting the insulin / IGF-1 signaling pathway and decreasing the damage caused by oxidative stress in the brain. One of the latest results revealed that the concentration of Klotho in cerebrospinal fluid is significantly lower in Alzheimer’s patients than in human controls of the same age; and it is lower in the elderly with respect to young adults.

Our study used a gene therapy strategy to introduce the Klotho gene into the Central Nervous System of adult animals. With just a single injection of the Klotho gene, young adult animals were protected over time from the cognitive decline associated with aging in old animals. These exciting results pave the way to further advances in research and the development of a neuroprotective therapy based on Klotho.

Continue reading

Multispecies Study Identifies Critical Genes in OCD Neurobiology

MedicalResearch.com Interview with:

Hyun Ji Noh PhD Postdoc in the Genome Sequencing and Analysis Program Broad Institute of MIT and Harvard

Dr. Hyun Ji Noh

Hyun Ji Noh PhD
Computational Scientist, Medical and Population Genetics
Broad Institute of MIT and Harvard

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder, characterized by intrusive thoughts and repetitive behaviors. OCD is estimated to affect roughly 80 million people worldwide, but its neurobiology remains poorly understood. To understand the disorder’s underpinnings, we searched for genetic mutations that are associated with OCD.

For this, we first identified 608 genes that were most likely to be important  in OCD – some that have previously been identified in OCD-like behaviors in dogs and mice, and others in human autism, which also involves repetitive behaviors. We compared these genes in 592 people with OCD and 560 people without OCD, and found that 4 of these genes were significantly different between people with and without OCD: NRXN1, HTR2A, CTTNBP2 and REEP3. All of these four genes have important functions in the brain. Specifically, we found that the variants in NRXN1 are likely to change its ability to bind other synaptic proteins. Synaptic proteins link neurons together, and are critical for transmitting signals through the brain. We also found that the variants in CTTNBP2 and REEP3 don’t actually change the proteins made by these genes, but instead probably affect gene regulation (for example, how much of the protein is made). These ‘regulatory’ variants disrupt the binding of transcription factors (proteins that regulate expression of genes in the body) near the gene.

Continue reading

Mouse Study Shows Intermittent Fasting Limits Obesity and Improves Metabolism

MedicalResearch.com Interview with:

Dr. Hoon-Ki Sung MD PhD Scientist at The Hospital for Sick Children (SickKids) and Assistant Professor in Laboratory Medicine & Pathobiology University of TorontoDr. Hoon-Ki Sung MD PhD Scientist at The Hospital for Sick Children (SickKids) and Assistant Professor in Laboratory Medicine & Pathobiology University of Toronto

Dr. Sung

Dr. Hoon-Ki Sung MD PhD
Scientist at The Hospital for Sick Children (SickKids) and
Assistant Professor in Laboratory Medicine & Pathobiology
University of Toronto 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Despite extensive research and medical interventions, the prevalence of obesity and associated metabolic disease is increasing. More and more studies show that obesity and its associated metabolic problems are often associated with unhealthy lifestyles and eating habits, including frequent eating (non-stop) throughout the day, resulting in a shorter period of physiological fasting. As such, various dietary approaches, such as calorie restriction and intermittent fasting have gained popularity as therapeutic strategies for obesity treatment. Intermittent-fasting is when one temporarily stops eating for a period of time, returns to normal food consumption, and then temporarily stops again.

In our study we examined the effect of an intermittent-fasting regimen, without restricting caloric intake, in mice. We found that an intermittent fasting regimen not only prevented obesity in mice, but also improved metabolism by changing the quality of fat in the body.

Our findings show that the health of the mice is significantly influenced by daily eating patterns. The addition of a ‘stop eating’ period converted inflammatory fat to brown-like (or beige) fat by anti-inflammatory immune cells, meaning it changed bad fat into good fat.

The results are exciting, because they show that weight loss is not the sole benefit of fasting. Fasting also restores the dual function of fat cells, which is to store energy and to release energy.

Continue reading

Studying Benign Pancreatic Tumors May Lead To Ability To Grow Beta Cells To Reverse Diabetes

MedicalResearch.com Interview with:

Andrew F. Stewart MD Irene and Dr. Arthur M. Fishberg Professor of Medicine Director, Diabetes, Obesity and Metabolism Institute Icahn School of Medicine at Mount Sinai New York, NY 10029

Dr. Stewart

Andrew F. Stewart MD
Irene and Dr. Arthur M. Fishberg Professor of Medicine
Director, Diabetes, Obesity and Metabolism Institute
Institute at the Icahn School of Medicine at Mount Sinai
New York, NY 10029

MedicalResearch.com: What is the background for this study?

Response: Diabetes results ultimately from an inadequate number of insulin-producing “beta” cell in the pancreas.  Ideally, these would regenerate when they are lost or damaged, but unfortunately inducing them to regenerate or proliferate has proven impossible until recently.

In 2015 and others we identified the first class of drugs – the harmine analogues – that are able to induce human beta cells to proliferate.  In this study, we wanted to identify additional pathways that can lead to human beta cell proliferation at higher rates than we had been able to induce with harmine.   For this we turned to a rare type of benign (i.e., not malignant, not cancer) tumor of the beta cells in the pancreas called “insulinomas”. These tiny tumors overproduce insulin and cause hypoglycemia (low blood glucose) which in turn causes seizures, loss of consciousness and confusion.  Once they are discovered, then can easily be removed via laparoscopic surgery, and the person is cured.  Since they are so rare, and since they are benign and easily cured, insulinomas have not been included in large genome sequencing studies of patients wit cancer.  However, we reasoned that they must hold the genomic recipe or wiring diagram for inducing human beta cells to replicate, so we perfumed next-generation DNA and RNA sequencing on a large series (38) of insulinomas.

Continue reading

Adverse Birth Outcomes and Agricultural Pesticide Use in the San Joaquin Valley of California

MedicalResearch.com Interview with:

Ashley Larsen, PhD Assistant professor Bren School of Environmental Science & Management University of California, Santa Barbara

Dr. Larsen

Ashley Larsen, PhD
Assistant professor
Bren School of Environmental Science & Management
University of California, Santa Barbara

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The relationship between pesticides and adverse birth outcomes has been recognized as an important question for quite some time, and there have been many good studies on the topic. Since randomly exposing people to different levels of pesticides is clearly unethical, researchers focused on the health consequences of non-occupational pesticide exposure often have to choose between detailed studies that follow a couple hundred or couple thousand individuals through pregnancy or larger scale studies that use easier to observe, but less accurate metrics of pesticide exposure (e.g. nearby crops or crop types). Here we tried to provide complementary insight by bridging the gap between detail and scale using detailed pesticide use data and individual birth certificate records for hundreds of thousands of births in an agriculturally dominated region of California. While we found negative effects of pesticide use on birth outcomes including low birth weight, preterm birth and birth abnormalities, these effects were generally in the magnitude of a 5-9% increase in probability of an adverse outcome, and only observed for individuals exposed to very high levels of pesticides.

Continue reading

H. pylori May Increase Risk of Stomach Cancer By Turning On Subset of Stem Cells

MedicalResearch.com Interview with:
Michael Sigal PhD

Clinical scientist of the Charité — Universitätsmedizin Berlin
Investigator at the Max Planck Institute for Infection Biology 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have previously found that H. pylori can colonize gastric glands and that in colonized glands the epithelial turnover was increased. We wanted to characterize the mechanisms that control the gland turnover in the stomach.

We found that Axin2, a classic Wnt target gene, marks two different subpopulations of cells with stem cell properties, one of which is Lgr5-positive and the other one Lgr5-negative. Both populations are affected by Rspondin 3, that is produced in myofibroblasts right beneath the stem cell compartment. Rspondin is crucial for stem cell signaling and knockout of Rspondin 3 in myofibroblasts results in loss of Lgr5 and Axin2 expression. Once we increased the bioavailability of Rspondin, that now could also interact with cells outside of the stem cell compartment, we noticed that the number of Axin2 positive stem cells dramatically increased. Of interest, only Lgr5-negative cells expanded in number and proliferate more, while the Lgr5-positive cells remained silenced.

Infection with Helicobacter pylori leads to an expansion of Axin2-positive cells which is driven by increased expression of Rspondin3. Expansion of the long lived stem cell pool could be an explanation for how H. pylori infection increases the risk for gastric cancer.

Continue reading

16 New Genetic Links To Longevity Discovered

MedicalResearch.com Interview with:

Dr. Zoltán Kutalik, PhD Group Leader Swiss Institute of Bioinformatics

Dr. Kutalik

Dr. Zoltán Kutalik, PhD
Group Leader
Swiss Institute of Bioinformatics
Assistant professor at the Institute of Social and Preventive Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Why do some of us live longer than others? While the environment in which we live – including our socio-economic status or the food we eat – plays the biggest part, about 20 to 30% of the variation in human lifespan comes down to our genome. Changes in particular locations in our DNA sequence, such as single-nucleotide polymorphisms (SNPs), could therefore hold some of the keys to our longevity. Until now, the most comprehensive studies had found only two hits in the genome.

Continue reading

Is Human Lifespan Really Limited to 100 Years?

MedicalResearch.com Interview with:

Pr. Siegfried Hekimi PhD McGill University

Prof. Hekimi

Pr. Siegfried Hekimi PhD
McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We analyzed data about the longest living individuals over the period of time during which the record can be trusted.

We found that there was no detectable plateauing of the maximum possible lifespan. This is consistent with not clearly observed plateau in the currently increasing average lifespan as well.

Continue reading

Rapid Improvements Coming to Gene Editing Techniques

MedicalResearch.com Interview with:

Michael Farzan PhD Co-chair and Professor Department of Immunology and Microbiology  Florida Campus  The Scripps Research Institute Jupiter, Florida

Dr. Farzan

Michael Farzan PhD
Co-chair and Professor
Department of Immunology and Microbiology
Florida Campus
The Scripps Research Institute
Jupiter, Florida

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: CRISPR is system for immune protection of bacteria.  It has now been widely adopted for use in editing mammalian cells.  The most commonly used CRISPR effector protein is Cas9.  Cas9 binds a guide RNA to recognize a DNA target, for example an incoming virus infecting a bacterium, or a gene in a human chromosome.  In bacteria, Cas9 requires a second protein to clear the guide RNA from a longer “CRISPR array”, basically a string of guide RNAs.

We have been studying a CRISPR effector protein related to Cas9 called Cpf1.  In bacteria it was know that, unlike Cas9, Cpf1 could cleave a CRISPR array by itself, without assistance from a second protein.  We knew that if it could do the same thing in human cells, it would help to simplify a number of gene-editing applications.  We were able to show that Cas9 could indeed excise multiple guide RNAs from a single message RNA in human cells.  We further showed that this approach was more efficient than the previous ways that guide RNAs were generated for gene editing, even more so when multiple guide RNAs were needed.

Continue reading

Baby Teeth Can Expose Toxic Levels of Minerals Associated With Autism

MedicalResearch.com Interview with:

Manish Arora, PhD Associate Professor Environmental Medicine & Public Health Icahn School of Medicine at Mount Sinai

Dr. Arora

Manish Arora, PhD
Associate Professor
Environmental Medicine & Public Health
Icahn School of Medicine at Mount Sinai

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Autism has both genetic and environmental risk factors. Our aim was to study if exposure to toxic metals, such as lead, or disruptions in the uptake of essential nutrient elements such as manganese or zinc would be related to autism risk. Furthermore, we were interested in not only understanding how much exposure had taken place but also which developmental periods were associated with increased susceptibility to autism risk.

Researchers suspect that the risk factors for autism start early in life, even prenatally, but measuring in utero exposures is technically very challenging. We used a newly developed technique that uses lasers to map growth rings in baby teeth (like growth rings in trees) to reconstruct the history of toxic metal and essential nutrient uptake. We applied this technology in samples collected from twins, including twins who were discordant for autism. This allowed us to have some control over genetic factors.

We found that twins with autism had higher levels of lead in their teeth compared to their unaffected twin siblings. They also had lower levels of zinc and manganese. The lower uptake of zinc was restricted to approximately 10 weeks before birth to a few weeks after birth, indicating that as a critical developmental period.

Continue reading

Metformin Reverses Some Autism Symptoms In Animal Model

MedicalResearch.com Interview with:
Ilse Gantois, PhD

Research Associate
Dr. Nahum Sonenberg’s laboratory
Department of Biochemistry
McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by cognitive impairment and affects 1 in 4000 males and 1 in 6000 females. About 60% of persons with Fragile X also have autism spectrum disorder. FXS is caused by absence of Fragile X protein (FMRP), which results in hyperactivation of ERK (extracellular signal-regulated kinase) and mTORC1 (mechanistic target of rapamycin complex 1) signaling. We show that treatment with metformin, the most widely used FDA-approved antidiabetic drug, suppresses translation by inhibiting the ERK pathway, and alleviates a variety of behavioural deficits, including impaired social interaction and excessive grooming. In addition, metformin also reversed defects in dendritic spine morphogenesis and synaptic transmission.
Continue reading

Beta-Blockers Reduce Heart Attack Size By Limiting Inflammation

MedicalResearch.com Interview with:

Borja Ibáñez MD Spanish National Centre for Cardiovascular Research Madrid

Dr. Ibáñez

Borja Ibáñez MD
Spanish National Centre for Cardiovascular Research
Madrid

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Acute myocardial infarction (heart attack) is a severe condition responsible for thousands of deaths every year and with important long-term consequences for survivors. Best treatment for acute myocardial infarction is a rapid coronary reperfusion.

Upon reperfusion, all inflammatory cells and mediators accumulated in the circulation during the infarction process, enter into the myocardium and causes an extra damage to the heart. Activated neutrophils play a critical role in this damage occurring upon reperfusion. The final size of infarction is the main determinant for mortality and long-term morbidity. The possibility of limiting the extent of infarcted tissue is of paramount importance.

Betablockers have been used in patients for more than 4 decades, mainly to treat arrhythmias and high blood pressure. Recently the same group of investigators demonstrated that the very early administration (i.e. during ambulance transfer to the hospital) of the betablocker “metoprolol” was able to reduce the size of infarction in patients. The mechanism by which metoprolol was protective in patients suffering a myocardial infarction was unknown.

Continue reading

Potential Drug-Binding Site Against Zika Virus Identified

MedicalResearch.com Interview with:

Dr. Jikui Song PhD Assistant professor of biochemistry University of California, Riverside.

Dr. Jikui Song

Dr. Jikui Song PhD
Assistant professor of biochemistry
University of California, Riverside.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Recent outbreak of Zika virus (ZIKV) has become a wordwide health concern. However, no vaccines or antiviral drugs against ZIKV are currently available. To explore potential druggable sites for ZIKV, we set out to determine the crystal structure of full-length ZIKV NS5, the molecular machinery responsible for the genomic replication of ZIKV.

The major findings of our study include the identification of a conserved domain conformation within flavivirus NS5 family, which may be important for functional regulation of flavivirus NS5. Furthermore, our structural analysis revealed a potential drug-binding site of ZIKV NS5, providing basis for future development of novel antivirals against ZIKV.

Continue reading

26 Additional Genes Linked to Intellectual Disability Identified

MedicalResearch.com Interview with:
Dr. Muhammad Ayub MBBS, MRCPsych, MSc., MD

Professor of Psychiatry Chair Division of Developmental Disabilities
Department of Psychiatry Queens
University Kingston
Kingston ON Canada

MedicalResearch.com: What is the background for this study? 

Response: Intellectual Disability affects about 1 percent of the population worldwide. Genetics play a major role in its etiology. Better understanding of the genetic causes is a necessary step in development of improved diagnosis and treatment. Recessive inheritance where the affected child inherits a defective copy of a gene from both the parents is an important genetic mechanism for prevalence of the disease in populations where within family marriages are common. These types of marital bonds are common in South Asia and Middle Eastern countries. The families where parents are related are an effective resource to study recessive forms of Intellectual Disability.

Continue reading

Novel Viral Vector Allows Gene Transfer To Correct Hearing Loss

MedicalResearch.com Interview with:

Lukas Landegger MD Molecular Neurotology Laboratory (PI Konstantina Stankovic) Massachusetts Eye and Ear Infirmary

Dr. Landegger

Lukas Landegger MD
Molecular Neurotology Laboratory (PI Konstantina Stankovic)
Massachusetts Eye and Ear Infirmary

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Genetic hearing loss affects more than 125 million people worldwide and constitutes a major hurdle for language acquisition and child development in general. Technological advances over the last decades, such as cochlear implants, have made it possible for deaf children to partially regain their sense of hearing. However, these devices still have several shortcomings, especially when listeners attempt to understand speech in noise or listen to music.

In establishing Anc80L65 as a reliable vector for gene delivery in the inner ear and releasing the first data demonstrating convincing hearing and vestibular function rescue in mice, we provide a foundation for other researchers interested in assessing the benefits of gene therapy in animal models of human disease.

Continue reading

Doxycycline May Mute Painful Memories Associated With PTSD

MedicalResearch.com Interview with:
Dominik R Bach, PhD, MD

University of Zurich

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Posttraumatic stress disorder (PTSD) can occur after a psychological trauma such as physical violence, abuse, or natural disaster. It is characterised by increased arousal, flashbacks, and nightmares that reflect memories of the trauma. Current therapies include talking therapy, but it is costly and does not work in everybody. This is why we were looking for ways of reducing aversive memories with a drug. In the current study, we found that the antibiotic doxycycline impairs the formation of negative memories in healthy volunteers.

To form memories, the brain needs to strengthen connections between neurons. It has recently emerged that for strengthening such connections particular proteins are required that sit between nerve cells, so-called MMPs. They are involved in many disorders outside the brain, such as certain cancers and heart disease. This is how we already know that doxycycline suppresses the activity of MMPs. Since doxycycline is relatively safe and readily accessible, our research was relatively straightforward.

76 healthy volunteers – half women, half men – came to the laboratory and received either placebo (a sugar pill) or 200 mg doxycycline. They then took part in a computer test in which one screen color was often followed by a mildly painful electric shock and another color was not.

A week later, volunteers came back to the lab. They were shown the colors again , this time followed by a loud sound but never by shocks. The loud sounds made people blink their eyes – a reflexive response to sudden threat. This eye blink response was measured. Volunteers who had initially been under placebo had stronger eye blink after the color that predicted electric shock than after the other color. This “fear response” is a sensitive measure for memory of negative associations. Strikingly, the fear response was 60% lower in participants who had initially taken doxycycline.

Continue reading

Colorectal Cancer Risk Model Using Environmental and Genetic Factors

MedicalResearch.com Interview with:

Victor Moreno, PhD. Director of Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain Department of Clinical Sciences, Faculty of Medicine University of Barcelona Barcelona, Spain

Dr. Moreno

Victor Moreno, PhD.
Director of Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain
Department of Clinical Sciences, Faculty of Medicine
University of Barcelona
Barcelona, Spain

Gemma Ibáñez-Sanz, MD Gastroenterologist. *Cancer Prevention and Control Unit, Catalan Institute of Oncology. L’Hospitalet deLlobregat, Barcelona, SPAIN *Gastroenterology Department, Bellvitge University Hospital-IDIBELL,  L’Hospitalet de Llobregat, Spain

Dr. Ibáñez-Sanz

Gemma Ibáñez-Sanz, MD
Gastroenterologist.
*Cancer Prevention and Control Unit, Catalan Institute of Oncology. L’Hospitalet deLlobregat, Barcelona, SPAIN
*Gastroenterology Department, Bellvitge University Hospital-IDIBELL,
L’Hospitalet de Llobregat, Spain 

MedicalResearch.com: What is the background for this study?

Response: Colorectal cancer (CRC) screening by faecal occult blood testing has been demonstrated to reduce CRC incidence and mortality, as well as being a cost-effective strategy compared to no screening. Currently, the target population is defined basically by age (≥50 years old), which has been called a ‘one-size-fits-all’ strategy. This strategy implies performing unnecessary screening tests in low-risk people leading to avoidable risks for patients and extra costs for the healthcare system. On the other hand, high-risk patients may receive non-invasive testing, which is a suboptimal screening technique in their case. Several risk prediction models, either for  colorectal cancer or advanced neoplasia, have been previously developed, all with limited discriminating ability.

We have developed a risk stratification model that combines environmental factors with family history and genetic susceptibility. Furthermore, we have assessed the relative contribution of these factors and the utility of the model for risk stratification and public health intervention.

MedicalResearch.com: What are the main findings?

Response: Data from common genetic susceptibility loci could be useful to stratify colorectal cancer screening in average-risk population. Individuals in the top quintile of risk alleles have an 82% increased risk compared to those in the lower quintile. We have estimated the impact of determining an individual environmental and genetic risk score in a Spanish CRC screening population. In our model, although the genetic factors are significant contributors, the modifiable risk factors contribute more strongly. Risk assessment may increase screening participation and adoption of healthier lifestyles.

MedicalResearch.com: What should readers take away from your report?

Response: On average, each environmental risk factor increases CRC risk by 35%, while each risk allele only increases it by 7%. This implies that the change of one modifiable risk factor towards healthier lifestyle might offset the effect of 4 risk alleles. Given the fact that environmental factors explain part of the CRC risk, we believe it to be important to give thought to incorporating clinical data to encourage individuals to achieve a healthier lifestyle. As the European Code Against Cancer recommends, and our findings confirm, one should have a healthy diet, a healthy body weight, be physically active and should not smoke or a high consumption of alcohol.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Future prospective studies should aim to analyse if stratifying by genetic and lifestyle risk scores is useful and cost-effective to improve screening. Subjects with higher predicted risk should probably start screening earlier and decrease the intervals between tests, while low risk individuals could start later or space more the between test intervals.

MedicalResearch.com: Is there anything else you would like to add? 

Response: Population acceptability of genetic tests is not well known. We are currently recruiting subjects from colorectal cancer screening and gastroenterology clinics in a study called COLSCREEN to assess risk perception and attitudes regarding genetic testing to prevent cancer.

No disclosures

Citation:

Sci Rep. 2017 Feb 24;7:43263. doi: 10.1038/srep43263.

Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study.

Ibáñez-Sanz G1, Díez-Villanueva A1, Alonso MH1,2, Rodríguez-Moranta F2,3, Pérez-Gómez B2,4,5, Bustamante M2,6, Martin V2,7, Llorca J2,8, Amiano P2,9, Ardanaz E2,10, Tardón A2,11, Jiménez-Moleón JJ2,12, Peiró R2,13, Alguacil J2,14, Navarro C2,15, Guinó E1,2, Binefa G1,2, Navarro PF2,4,5, Espinosa A2,6, Dávila-Batista V7, Molina AJ2,7, Palazuelos C8, Castaño-Vinyals G2,6,16,17, Aragonés N2,4,5, Kogevinas M2,6,16,17,18, Pollán M2,4,5, Moreno V1,2,19.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Land-Based Salmon Farms Degrade Natural Waters With Dissolved Organic Materials

MedicalResearch.com Interview with:

Dr. Norbert Kamjunke Helmholtz-Centre for Environmental Research UFZ Department of River Ecology Magdeburg, Germany

Dr. Kamjunke

Dr. Norbert Kamjunke
Helmholtz-Centre for Environmental Research UFZ
Department of River Ecology
Magdeburg, Germany 

MedicalResearch.com: What is the background for this study?

Response: Aquacultures are of great importance worldwide but pollute pristine headwater streams, lakes, and estuaries.

Chilean salmon production is economically important, contributing ~25% of the worldwide salmon yield
(Chile ranks second of the world’s salmon-producing countries). Salmon
farming has continuously increased in recent decades; the annual
salmonid production in Chile was 820,000 tons in 2012, representing a
value of 4.9 billion USD (32% of the total worldwide value of salmonid
production). Small salmon are reared in land-based aquacultures supplied
with stream water, whereas mid-sized fish are grown in cages in lakes
and adult fish in cages along the coast. The effluents from land-based
aquaculture pollute pristine streams with nutrients, antibiotics and
organic carbon, resulting in oxygen depletion and negative consequences
for the abundance and biodiversity of stream organisms. While
aquacultures have recently started to remove suspended matter from waste
water using sedimentation basins and rotating drum filters, dissolved
components are still discharged untreated. Nutrients and dissolved
organic matter (DOM) originating from the leaching of remaining food
pellets, fish faeces and fish excretions are major components released
by aquacultures. One aquaculture in northern Patagonia was estimated to
release DOM amounting to 21% of the carbon applied as feed and 76% of
the annual fish production.
Continue reading

Protective Bacteria May Reverse Inflammation In Some Forms of IBD

MedicalResearch.com Interview with:
Justin E. Wilson, Ph.D 
On behalf of the authors
Research Assistant Professor – Laboratory of Jenny Ting
Department of Genetics
Lineberger Comprehensive Cancer Center
The University of North Carolina at Chapel Hill
Chapel Hill, NC 27599

MedicalResearch.com: Could you provide me with some background on this project? Why did you decide to do this research project? What prior work led up to this latest paper?

Response: Previous work from our lab and others discovered two major points about NLRP12:
a) NLRP12 suppresses inflammation in response to bacterial components
b) NLRP12 provides protection against the inflammatory bowel disease colitis and colitis-associated colon cancer (i.e., Nlrp12-defcient mice have greater colon inflammation and inflammation-driven colon cancer).
Therefore, we wanted to know if Nlrp12 was regulating inflammation in the colon by responding to the trillions of intestinal microbes collective referred to as the microbiome. Mounting evidence also indicates that the immune system both responds to and influences the composition of the intestinal microbiome during intestinal health and disease, and we hypothesized that NLRP12 could be one of the important immune components during this process. Moreover, we were also interested in this topic because targeting the microbiome to treat inflammatory disorders and other diseases is an attractive method that has many advantages over immune suppression.

Continue reading

Gene “Decorations” Can Serve as Blood Biomarkers To Detect Cancer

MedicalResearch.com Interview with:

Kun Zhang, PhD Professor UCSD Department of Bioengineering La Jolla, CA 92093-0412

Dr. Kun Zhang

Kun Zhang, PhD
Professor
UCSD Department of Bioengineering
La Jolla, CA 92093-0412

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have been interested in a type of chemical modification on the DNA, called CpG methylation, for years. This is like a decoration of DNA molecules that is specific to the cell type or tissue type. We were particularly interested in studying how such decoration spread along the DNA molecules. In this study, we did a very comprehensive search of the entire human genome for various human cell types and tissue types, and found close to 150,000 regions (called MHB in this study) in which adjacent CpG share the same decoration. We then went on to find out how many of such regions are unique to each normal cell/tissue type, and how many are specific to cancers. Then we took some of these highly informative regions as “biomarkers”, and showed that we can detect the absence or presence of cancer, and, in the latter case, where the tumor grow, in a patient’s blood.

Continue reading

Genetic Variants Tied To Kidney Disease in African Americans

MedicalResearch.com Interview with:

Katalin Susztak MD, PhD Associate Professor of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia, PA 19104

Dr. Susztak

Katalin Susztak MD, PhD
Associate Professor of Medicine
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA 19104

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies showed an association between genetic variants in the APOL1 gene and kidney disease development, but it has not been confidently shown that this genetic variant is actually causal for kidney disease. For this reason we developed a mouse model that recapitulates the human phenotype.

Continue reading

Scientists Block Cocaine Addiction in Mice by Increasing Cadherin “glue” at Synapses

MedicalResearch.com Interview with:

Andrea K. Globa, Ph.D. Candidate Graduate Program in Neuroscience Life Sciences Institute University of British Columbia Vancouver, BC, Canada

Andrea Globa

Andrea K. Globa, Ph.D. Candidate
Graduate Program in Neuroscience
Life Sciences Institute
University of British Columbia
Vancouver, BC, Canada

MedicalResearch.com: What is the background for this study?

Response: Addiction is a complex disease, characterized by continued substance use despite serious negative consequences, increased drug tolerance, and withdrawal. In fact, the statistics show that over 40 million Americans abuse or are addicted to nicotine, alcohol or other drugs. This is a huge public health issue, so naturally, scientists are interested in figuring out why people get addicted, and in particular why certain people are more prone to addiction than others.

Studies examining genetic differences in addicted populations have shown that there are many mutations in genes that are important for brain function. One group of genes affected encode proteins that act as ‘glue’ to hold cells together. These proteins are called cadherins. In the brain, cadherins are important for holding brain cells together at spots where they communicate with one another – and these points where brain cells talk to one another are called synapses.

Many neuroscientists believe that addiction is actually a type of “pathological” learning, where there are changes at synapses in a brain circuit involved in reward and motivation. So we decided to examine the molecular mechanisms that are important for the strengthening of synapses in this brain circuit.

To put it very simply, to learn something you have to make your synapses stronger, and this involves adding more cadherin or ‘glue’ to the synapse. We wanted to see if these same rules held true in addiction.

Continue reading

Ketamine Before Stressful Event May Reduce Risk of PTSD

MedicalResearch.com Interview with:

Christine Ann Denny, Ph.D. Assistant Professor Department of Psychiatry Columbia University Division of Integrative Neuroscience Research Foundation for Mental Hygiene, Inc. New York, NY 10032-2695

Dr. Christine Ann Denny

Christine Ann Denny, Ph.D.
Assistant Professor
Department of Psychiatry
Columbia University
Division of Integrative Neuroscience
Research Foundation for Mental Hygiene, Inc.
New York, NY 10032-2695

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Post-traumatic stress disorder (PTSD) is one of the most common psychiatric illnesses, affecting about 8 million adult Americans, and an annual prevalence of about 3.5% worldwide. At-risk populations such as soldiers and veterans are at a higher risk to develop PTSD. Stress exposure is one of the major risk factors for PTSD and major depressive disorder (MDD), a disorder which is often co-morbid with PTSD.

There are currently very limited treatments for PTSD and MDD. In addition, these disorders are treated in a symptom-suppression approach, which only mitigate symptoms and work in only a small fraction of patients. Prevention is rarely an approach considered except in the form of behavioral intervention. However, pharmacological approaches to preventing psychiatric diseases has not yet been developed.

Our laboratory has previously found that ketamine, a general anesthetic and rapid-acting antidepressant, administered sub-anesthetically prior to stress can prevent against stress-induced depressive-like behaviors. We decided to delve into the literature to determine whether ketamine has any effects on PTSD in the clinic. We found numerous reports linking ketamine to PTSD, but the results were varied. We realized that the main difference in all of these studies was the timing of administration. We decided to systematically test the efficacy of ketamine in mice at various time points relative to a stressor to determine when would be the most effective window to buffer against heightened fear expression.

We found that ketamine administered 1 week, but not 1 month or 1 day, prior to a stressor was the most effective time point to administer the drug to buffer fear. This is critical, as it suggests that a pharmacological approach to enhance resilience can be more effective at protecting against PTSD symptoms than attempting to mitigate symptoms after it has already affected an individual.

Continue reading

Gene Therapy Restores Hearing Down To A Whisper, in Mice

MedicalResearch.com Interview with:

Gwenaelle Geleoc, PhD Assistant Professor Department of Otolaryngology F.M. Kirby Neurobiology Center Children's Hospital and Harvard Medical School Boston, MA

Dr. Gwenaelle Geleoc

Gwenaelle Geleoc, PhD
Assistant Professor
Department of Otolaryngology
F.M. Kirby Neurobiology Center
Children’s Hospital and Harvard Medical School
Boston, MA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We seek to develop gene therapy to restore auditory and balance function in a mouse model of Usher syndrome. Usher syndrome is a rare genetic disorder which causes deafness, progressive blindness and in some cases balance deficits. We used a novel viral vector developed by Luk Vandenberghe and package gene sequences encoding for Ush1c and applied it to young mice suffering from Usher syndrome. These mice mimic a mutation found in patients of Acadian descent. We assessed recovery of hearing and balance function in young adult mice which had received the treatment. Otherwise deaf and dizzy, we found that the treated mice had recovered hearing down to soft sounds equivalent to a whisper and normal balance function.

Continue reading

Our ‘Motor Signature’ Is a Window Into Mental Health

MedicalResearch.com Interview with:

Dr. Piotr Słowiński</strong> Department of Mathematics College of Engineering Mathematics and Physical Sciences, Research Fellow University of Exeter

Dr. Piotr Słowiński

Dr. Piotr Słowiński
Department of Mathematics
College of Engineering
Mathematics and Physical Sciences,
Research Fellow
University of Exeter

MedicalResearch.com: What are the main findings?

Response: In an earlier study, we have found that every person has an individual style of moving (its own individual motor signature) and that people who have similar motor signatures are better in coordinating with each other (http://rsif.royalsocietypublishing.org/content/13/116/20151093). In the current study, we show that both these characteristics, own motor signature, and quality of interaction with others, have potential to give and insight into person’s mental health condition.

Assessment of motor symptoms is already a part of a clinical interview during a neurological evaluation by an expert psychiatrist. Our method, if confirmed in clinical trials, would speed up such examination and would allow for better allocation of the valuable time of medical professionals (for example, for more advanced tests in cases of diagnostic uncertainty). Additionally, it could allow for monitoring and personalization of treatment.

Continue reading

Key Gene Linked To Brain Plasticity and Learning Identified

MedicalResearch.com Interview with:

Keerthi Krishnan PhD</strong> Cold Spring Harbor Laboratory Cold Spring Harbor, New York 11724,

Dr. Keerthi Krishnan

Keerthi Krishnan PhD
Cold Spring Harbor Laboratory
Cold Spring Harbor, New York 11724

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Rett Syndrome is diagnosed as a neurodevelopmental disorder in girls, caused mainly by mutations in the gene MECP2. Many previous studies, including mine, have shown that mutations in MECP2 result in improper communication between nerve cells in the brain during sensitive periods of development. However, it was unclear if the same mechanisms were responsible for cognitive and behavioral problems found in adulthood.

In this paper, we have utilized a natural, learned response called pup retrieval behavior to study adult neural plasticity in a female mouse model of Rett Syndrome. With some learning, adult female mice will gather scattered pups to the nest, in response to distress calls from the pups. We found that the Rett Syndrome model mice with reduced MECP2 protein do not gather pups efficiently. This is due to the abnormal formation of structures called perineuronal nets on a specific type of neurons (called parvalbumin+ GABAergic neurons) that block plasticity and prevent learning of the appropriate response. Furthermore, the same neural and molecular mechanisms found earlier in development were also found to mediate learning in adulthood.

Continue reading

New Oncoprotein Offers Potential Therapeutic Target

MedicalResearch.com Interview with:

Dr. Hua Lu MS PhD Department of Biochemistry & Molecular Biology Reynolds and Ryan Families Chair in Translation Cancer Tulane Cancer Center Tulane University School of Medicine New Orleans, Louisiana 70112

Dr. Hua Lu

Dr. Hua Lu MS PhD
Department of Biochemistry & Molecular Biology
Reynolds and Ryan Families Chair in Translation Cancer
Tulane Cancer Center
Tulane University School of Medicine
New Orleans, Louisiana 70112

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It has been well appreciated and acknowledged that p53 is the most important tumor suppressor in human body. However, approximately 50% of human cancers still sustain the wild type form of its gene, and also oddly, some cancers, such as breast cancer, which contain wild type p53, are often less sensitive to chemotherapy than those harbor mutated p53. Although a number of oncoproteins, including MDM2 and MDMX (MDM4), have been shown to be highly expressed and to inactivate p53 in those wild type p53-containing cancers, more molecules need to be discovered to keep p53 in control in order to let cancer cells to proliferate and growth.

Our study as described in our recent publication in Nature Communications unveils a new p53 target gene that encodes pleckstrin homology domain-containing protein (PHLDB3) as another p53 inhibitor in a negative feedback fashion. Interestingly and mechanistically, PHLDB3 can work with MDM2 by boosting its E3 ubiquitin ligase activity, consequently leading to degradation of p53. Biologically, PHLDB3 can promote cancer cell proliferation and growth in culture and in xenograft tumor models by in part inactivating p53 activity. More interestingly, PHLDB3 is highly amplified and expressed in a number of human cancers, such as pancreatic, prostate, colon and breast cancers. High expression of PHLDB3 is well correlated with the wild type status of p53 in certain portion of breast cancer. These findings uncover PHLDB3 as another oncoprotein that can promote cancer growth by partially inactivate p53, and thus might serve as a potential target for future development of anti-cancer therapy. Our study also suggests that PHLDB3 has a p53-independent function important for cancer growth.

Continue reading

Craniofacial Abnormalities and Rare Muscular Dystrophy Linked To Same Gene

MedicalResearch.com Interview with:
Natalie Shaw, MD, MMSc
National Institute of Environmental Health Sciences
Research Triangle Park, North Carolina and
Harrison Brand, PhD
Molecular Neurogenetics Unit and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research
Massachusetts General Hospital, Boston
Massachusetts, USA.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Congenital arhinia, or absence of the nose and olfactory system, is an extremely rare malformation, often accompanied by defects in the eyes and reproductive system. Arhinia has been reported in only 80 patients in the past century and though a genetic cause had been suspected, no previous study had identified a plausible genetic candidate.

Through an international collaboration among clinicians and investigators spanning 10 different countries, we were able to assemble a cohort of 40 arhinia patients. Using whole-exome sequencing, we found that 84% of the patients had rare mutations in the same gene – SMCHD1. Further, modeling studies based on patient cells and SMCHD1 knockdown in zebrafish strongly support a role for the gene in arhinia.

We were surprised by this discovery because mutations that impair SMCHD1 function are known to interact with other regions of the genome to cause a type of muscular dystrophy (FSHD2) that does not affect the bones or cartilage of the face. Deep phenotyping of our cohort revealed that individuals with arhinia can in fact develop FSHD2, but it is still unclear why individuals with FSHD2 do not have arhinia.

Continue reading

Most Biomedical PostDocs Lose Out on Salary and Tenure

MedicalResearch.com Interview with:

Prof. Shulamit (Shu) Kahn Department of Markets, Public Policy and Law Questrom School of Business Boston University

Prof. Shulamit Kahn

Prof. Shulamit (Shu) Kahn
Department of Markets, Public Policy and Law
Questrom School of Business
Boston University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We started this research because Donna Ginther (Kansas) and I had an NIH R01 to study gender differences in biomedical careers. We quickly discovered that a major problem for women was the fact that between many years of graduate study and long postdocs, their biological clocks had almost expired before they would have a decent amount of time in their lives to think about having children.

Continue reading

Low Vitamin D Linked To Increased Risk of Chronic Headache

MedicalResearch.com Interview with:

Dr-Jyrki-Virtanen.jpg

Dr. Jyrki Virtanen

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Formation of vitamin D in the skin with UVB light from the sun is a main source of vitamin D during summer months, but in the winter months the UVB light is too weak for vitamin D production. Headache prevalence has been suggested to be related to increasing latitude (less UVB light throughout the year) and possibly to be less prevalent during summer (more UVB light), which suggests a possible role for vitamin D exposure.

Some previous small studies have suggested that low serum vitamin D levels might be associated with more frequent headache or migraine. Our study included 2601 men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) from eastern Finland, aged 42-60 years in 1984-1989, which makes it one of the largest studies so far regarding vitamin D and headache.

In our study chronic headache (occurring weakly or daily) was reported by 250 men, and men reporting chronic headache had lower serum vitamin D levels than others.

When we divided the study population into four groups based on their serum vitamin D levels, the group with the lowest levels had over a twofold risk of chronic headache in comparison to the group with the highest levels. Chronic headache was also more frequently reported by men who were examined outside the summer months of June through September.

Continue reading

Salt-Impregnated Surgical Masks Make Viruses Harmless

MedicalResearch.com Interview with:

Hyo-Jick Choi, PhD Assistant Professor, Department of Chemical and Materials Engineering University of Alberta Edmonton, AB, Canada T6G 1H9

Dr. Hyo-Jick Choi

Hyo-Jick Choi, PhD
Assistant Professor,
Department of Chemical and Materials Engineering
University of Alberta
Edmonton, AB, Canada T6G 1H9

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Respiratory diseases such as influenza transmitted either through breathing aerosols exhaled/coughed out by an infected person or through direct contact. Despite controversy over its efficacy, surgical mask has been widely used by general public during the past respiratory disease outbreaks because of low cost, easy wearability, and widespread use in normal day-to-day situation. Critical issue is that virus captured on the filter of the mask still maintains infectivity for long time, raising concerns of secondary infections and transmissions.

This led us to develop a strain-nonspecific and reusable airborne virus deactivation system based on salt recrystallization principle. Salt recrystallization is hypothesized to cause deactivation of viruses transmitted through aerosols via two successive processes:

1) salt on filter fiber dissolves upon exposure to the pathogenic aerosols and
2) salt crystallizes as aerosols evaporate.

To demonstrate the concept, we coated the fiber of the surgical mask filter with sodium chloride (NaCl) salt crystal and tested its performance using three different types of influenza viruses. Salt-treated filter provided higher filtration efficiency compared to non-treated regular filter and successfully destroyed multiple subtypes of influenza viruses trapped on the filter within few minutes, leading to significant infectivity loss.

Continue reading

Genetic Factors Link Communication Competence in Childhood With Autism and Schizophrenia

MedicalResearch.com Interview with:

Dr. Beate St Pourcain MSc, PhD(Cardiff) Genetic Epidemiology School of Oral and Dental Sciences MRC Integrative Epidemiology Unit University of Bristol

Dr. Beate St Pourcain

Dr. Beate St Pourcain MSc, PhD(Cardiff)
Genetic Epidemiology
School of Oral and Dental Sciences
MRC Integrative Epidemiology Unit
University of Bristol

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: People with autism and with schizophrenia both have problems interacting and communicating with other people, because they cannot easily initiate social interactions or give appropriate responses in return. On the other hand, the disorders of autism and schizophrenia develop in very different ways. The first signs of Autism Spectrum Disorder (ASD) typically occur during infancy or early childhood, whereas the symptoms of schizophrenia usually do not appear until early adulthood. The researchers asked whether it is possible to disentangle the apparent symptom overlap in ASD and schizophrenia through genetic analyses.

As clinical diagnoses relate to the age of onset of a disorder and do not capture multiple developmental stages, the researchers used a trick. They assumed that there is a continuum between normal and abnormal behaviour and captured social communicative competence – the ability to socially engage with other people successfully – in participants of a population-based birth cohort during development.

Specifically, the researchers studied the genetic overlap between the risk of having these psychiatric disorders and these measures of social communicative competence. Investigating thousands of genetic variants with small effects across the genome, they showed that genes influencing social communication problems during childhood overlap with genes conferring risk for autism, but that this relationship wanes during adolescence. In contrast, genes influencing risk for schizophrenia were most strongly interrelated with genes affecting social competence during later adolescence, in line with the natural history of the disorder.

“The findings suggest that the risk of developing these contrasting psychiatric conditions is strongly related to distinct sets of genes, both of which influence social communication skills, but exert their maximum influence during different periods of development”, explained Beate St Pourcain, senior investigator at the Max Planck Institute and lead author of the study. This is consistent with studies showing that genetic factors underlying social communication behaviour also change to some degree during childhood and adolescence.

Continue reading

Vaccine Nanodiscs Can Trigger More Cancer Fighting Immune Cells

MedicalResearch.com Interview with:

James Moon, PhD John Gideon Searle Assistant Professor University of Michigan Dept. of Pharmaceutical Sciences and Biomedical Engineering Biointerfaces Institute Ann Arbor, MI, 48109

Dr. James Moon

James Moon, PhD
John Gideon Searle Assistant Professor
University of Michigan
Dept. of Pharmaceutical Sciences and Biomedical Engineering
Biointerfaces Institute
Ann Arbor, MI, 48109

MedicalResearch.com: What is the background for this study?

Response: The field of cancer immunotherapy has recently made a breakthrough with the clinical success of immune checkpoint inhibitors, which work by removing the brakes on immunosuppressed T-cells. However, these approaches generally work by augmenting pre-existing T-cell immunity and benefit only a subset of patients. In addition, because the majority of somatic mutations in cancer cells are unique to each patient, cancer immunotherapy may benefit from a personalized approach.

Continue reading

Newly Identified Molecule Turns Fat Storage Gene Off

MedicalResearch.com Interview with:

Prof. Jamal Tazi Institut de Génétique Moléculaire de Montpellier University of Montpellier Montpellier, Cedex, France

Prof. Jamal Tazi

Prof. Jamal Tazi
Institut de Génétique Moléculaire de Montpellier
University of Montpellier
Montpellier, Cedex, France

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. In this study we have used a novel approach to uncover novel drugs to treat obesity. Our approach is based on the finding that in humans the energy expenditure balance can be controlled by a single gene LMNA gene that can produce two different proteins with opposing effect on energy expenditure. We identified a molecule ABX300 that targets the expression of LMNA gene and favors energy expenditure leading to fat loss.

Continue reading

A Neuronal Network of Mitochondrial Dynamics Regulates Cancer Metastasis

MedicalResearch.com Interview with:
Cecilia Caino, Ph.D.
The Wistar Institute
3601 Spruce Street
Philadelphia, PA 19104

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Mitochondria have recently experienced a resurgence of interest in the field of cellular biology. Traditionally known for their role in energy production and in programmed cell death, mitochondria are more broadly recognized as signaling hubs and biosynthetic factories. Not surprisingly, mitochondria have been linked to several hallmarks of cancer, including evasion of apoptosis, tissue invasion and metastasis and abnormal metabolic pathways. It has become clear that mitochondria quality control and metabolism-regulated shape changes are dysregulated in cancer. Recent studies identified a novel therapy-resistance mechanism that involves mitochondrial subcellular re-localization and is responsible for enhanced metastatic potential of cancer cells. In this context, the molecular regulators of mitochondrial trafficking in cancer are largely unknown.

Through analysis of shRNA screening results, we identified Syntaphilin (SNPH), which is considered to moderate mitochondrial trafficking in neurons, as a non-neuronal tissue specific factor to suppress cancer cell invasion. Using multi-disciplinary cell biological, real time imaging, in vivo studies and human clinical studies, SNPH was revealed to block cell motility and tumor metastasis by regulation of reprogramming of mitochondrial dynamics. We provided evidence from public databases and clinical samples that SNPH levels are decreased in different types of human tumors and low SNPH levels correlate with worse patient prognosis. Overall this study demonstrated a new mechanism by which tumor cell invasion is regulated by a SNPH-mediated pathway.

Continue reading

How Does Candida Elude the Immune System?

MedicalResearch.com Interview with:

Professor Alistair J P Brown DSc FSB FAAM FRSE Aberdeen Fungal Group, MRC Centre for Medical Mycology, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen UK

Prof. Al Brown

Professor Alistair J P Brown  DSc FSB FAAM FRSE
Aberdeen Fungal Group, MRC Centre for Medical Mycology,
University of Aberdeen, Institute of Medical Sciences,
Foresterhill, Aberdeen UK 

MedicalResearch.com: What is the background for this study?

Response: Most of us harbor the yeast Candida albicans, and most of the time it does us no harm.  However, under certain circumstances it can break out to cause nasty infections of the mouth or genitalia (thrush), or potentially fatal infections in vulnerable intensive care patients.  Indeed, over half of women will suffer at least one episode of vulvovaginal candidiasis in their lifetime, and over 5% of women suffer recurrent episodes (four or more episodes per annum).  Also, it has been estimated that there are over 400,000 life-threatening systemic Candida infections worldwide per annum, of which over 40% are fatal (see Science Translational Medicine (2012) vol. 4, 165rv13).  A key to this is the potency of our immunological defenses: the weaker our defenses the more vulnerable we are to fungal infection.  Therefore, we in the Medical Research Council (MRC) Centre for Medical Mycology – and other groups worldwide – are studying the mechanisms by which our immune cells recognize and kill invading Candida cells, thereby protecting us from infection.

Continue reading

Non-Invasive Interface Allows Subjects To Control Objects With Just Thoughts

MedicalResearch.com Interview with:

Bin He, Ph.D. Director, Institute for Engineering in Medicine Director, Center for Neuroengineering Distinguished McKnight University Professor of Biomedical Engineering Medtronic-Bakken Endowed Chair for Engineering in Medicine University of Minnesota, Minneapolis, MN 55455

Dr. Bin He

Bin He, Ph.D.
Director, Institute for Engineering in Medicine
Director, Center for Neuroengineering
Distinguished McKnight University Professor of Biomedical Engineering
Medtronic-Bakken Endowed Chair for Engineering in Medicine
University of Minnesota, Minneapolis, MN 55455

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This work is aimed at developing a noninvasive brains-computer interface to allow disabled patients to control their environment by just thinking about it.

We found 8 human subjects were able to accomplish 3D reach and grasp tasks without using any muscle activities but just thinking about it.

Continue reading

Intermittent Fasting Inhibits Cancer Cells in Childhood Leukemia ALL

MedicalResearch.com Interview with:

Chengcheng (Alec) Zhang, Ph.D. Associate Professor Hortense L. and Morton H. Sanger Professorship in Oncology Michael L. Rosenberg Scholar for Medical Research Department of Physiology  UT Southwestern Medical Center

Dr. Alec Zhang

Chengcheng (Alec) Zhang, Ph.D.
Associate Professor
Hortense L. and Morton H. Sanger Professorship in Oncology
Michael L. Rosenberg Scholar for Medical Research
Department of Physiology
UT Southwestern Medical Center

MedicalResearch.com: What is the background for this study?

Response: New therapeutic targets and approaches are needed to effectively treat leukemia. Acute myeloid leukemia (AML) is the most common form of adult acute leukemia whereas acute lymphoblastic leukemia (ALL) is the most common form of cancer in children; ALL also occurs in adults. Although treatment of pediatric ALL is highly effective, a sizeable number of patients are non-responders who succumb to this disease. The outcome of ALL in adults is significantly worse than for pediatric ALL. Additionally, some types of ALL have a much poorer prognosis than others.

Dietary restriction, including fasting, delays aging and has prolonged effects in a wide range of organisms and has been considered for cancer prevention. In certain types of solid tumor,_ENREF_1 dietary restriction regimens are able to promote T cell-mediated tumor cytotoxicity and enhance anticancer immunosurveillance, and coordinate with chemotherapy to promote the anti-cancer effects. However, the responsiveness of hematopoietic malignancies to dietary restriction, including fasting, remains unknown. Furthermore, whether dietary restriction alone can inhibit cancer development is not clear.

Continue reading

Genes Linked To Ectopic Fat Deposition Identified

MedicalResearch.com Interview with:

Audrey Chu, Ph.D. Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health

Dr. Audrey Chu

Audrey Chu, Ph.D.
Division of Intramural Research
National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Body shape reflects the underlying adipose tissue distributed throughout different compartments of the body (ectopic fat). Variation in ectopic fat is associated with diabetes, hypertension and heart disease. This is mostly independent of overall adiposity. Ectopic fat can be measured using special x-rays procedures such as CT (“CAT scans”) or MRI and can give more information about fat distribution. Fat distribution characteristics can run in families, suggesting that a person’s genes can help determine the amount of fat that can accumulate in different parts of the body. Identifying genes that are associated with ectopic fat can provide insight into the biological mechanisms leading to differences in cardiometabolic disease risk.

In order to understand which genes might be involved, we examined genetic variants across the genome and their association with ectopic fat in the largest study of its kind including over 18,000 individuals of four different ancestral backgrounds.

Several new genetic regions were identified in association with ectopic fat in addition to confirming previously known regions. The association of the new regions was specific to ectopic fat, since the majority of the regions were not associated with overall or central adiposity. Furthermore, most of these regions were not associated with type 2 diabetes, lipids, heart disease or blood pressure. The major exception was the region surrounding the UBE2E2 gene, which was associated with diabetes.

Continue reading

Healthy Stem Cells Need Just Right Telomere Length

MedicalResearch.com Interview with:

Professor Jan Karlseder Molecular and Cell Biology Laboratory Donald and Darlene Shiley Chair Salk Institute for Biological Studies

Prof. Jan Karlseder

Professor Jan Karlseder
Molecular and Cell Biology Laboratory
Donald and Darlene Shiley Chair
Salk Institute for Biological Studies

MedicalResearch.com: What is the background for this study? 

Response: Telomeres are repetitive stretches of DNA at the ends of each chromosome whose length can be increased by an enzyme called telomerase. Our cellular machinery results in a little bit of the telomere becoming lopped off each time cells replicate their DNA and divide. As telomeres shorten over time, the chromosomes themselves become vulnerable to damage. Eventually the cells die. The exception is stem cells, which use telomerase to rebuild their telomeres, allowing them to retain their ability to divide, and to develop (“differentiate”) into virtually any cell type for the specific tissue or organ, be it skin, heart, liver or muscle—a quality known as pluripotency. These qualities make stem cells promising tools for regenerative therapies to combat age-related cellular damage and disease.

Continue reading

Platypus Venom May Lead To Better Understanding of Diabetes

MedicalResearch.com Interview with:

Platypus

Platypus

 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Platypus and Echidnas are the only representative of the unique group of egg-laying mammals. These peculiar animals are human’s most distant relatives amongst living mammals and they have allow unprecedented insights into the evolution of mammals. Many aspect of the biology of these extraordinary mammals are unusual. One of the most remarkable changes is that monotremes lack a functional stomach and lost many genes involved in digestion. This sparked our interest to investigate the Insulin release pathway as a key aspect of blood glucose regulation which is affected in Diabetes.

When we identified and characterised the hormone that is central to the release of insulin after a meal (called GLP-1)we were surprised to see it active in gut where is should be but also in the venom gland of platypus and echidna.

When we investigated the monotreme GLP-1 further we discovered that this hormone is not degraded in human serum. This is exciting as the human GLP-1 is degraded very rapidly (within minutes) and a major treatment approach in type 2 diabetes is to develop long-lasting GLP-1 variants like the one we discovered in platypus and echidna.

Continue reading

Microbiome Is Major Driver of Recurrent Obesity

MedicalResearch.com Interview with:
Dr. Eran Elinav. Principal investigator
Immunology Department
Weizmann Institute of Science
Rehovot, Israel

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Recurrent obesity is a very common yet poorly studied and under researched phenomenon. It is well known that many people diet, but then regain the weight they lost and even add more weight. We found that the gut microbiome is a major driver of this enhanced weight regain phenomenon. We found that in the obese state, the microbiome is altered, and these alterations are not reversed upon weight loss. And these alterations are sufficient to drive weight regain, since transferring them to germ-free mice also transferred the enhanced weight regain phenotype.

Moreover, we provide three different treatments for this condition:
(1) Antibiotics;
(2) transfer of bacteria from lean mice; and
(3) addition of specific molecules that we found to be lacking in the altered microbiome.

All of these treatments cured the mice we tested from enhanced weight regain.

Continue reading

Bacterial Nitric Oxide Essential For Staph Bacteria To Colonize Nose

MedicalResearch.com Interview with:

Ferric C. Fang, M.D. Professor of Laboratory Medicine and Microbiology Adjunct Professor of Medicine (Infectious Diseases) Director, Harborview Medical Center Clinical Microbiology Laboratory University of Washington School of Medicine Seattle, WA

Dr. Ferric C. Fang

Ferric C. Fang, M.D.
Professor of Laboratory Medicine and Microbiology
Adjunct Professor of Medicine (Infectious Diseases)
Director, Harborview Medical Center Clinical Microbiology Laboratory
University of Washington School of Medicine
Seattle, WA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Fang lab has a longstanding interest in the interaction between nitric oxide (NO·) and pathogenic bacteria. NO· is an important mediator of the host innate immune response that restricts the growth of invading bacterial pathogens. One of the known actions of NO· is the reversible inhibition of aerobic respiration that results from NO· binding to the heme centers of terminal oxidases.

Like mammalian hosts, many bacteria also possess the ability to enzymatically synthesize NO·. Our latest research investigated the physiological role of the Staphylococcus aureus nitric oxide synthase (saNOS). We discovered that endogenously produced NO· is able to target bacterial terminal oxidases under microaerobic conditions, allowing the bacteria to transition to nitrate respiration when oxygen concentrations are limited and helping to maintain the membrane potential. This process was found to be essential for S. aureus nasal colonization in a mouse model. Thus, a conserved mechanism is involved in both the antimicrobial actions of NO· and the physiological role of NO· in regulating bacterial electron transfer reactions. Interestingly, NO·-heme interactions have been shown to control mitochondrial respiration during hypoxia in mammalian cells.

Continue reading

Can Probiotics in Yogurt Protect Against Stress and Anxiety?

MedicalResearch.com Interview with:

Elizabeth Bryda, PhD Professor, Director, Rat Resource and Research Center Veterinary Pathobiology University of Missouri Columbia, Missouri

Dr. Elizabeth Bryda

Elizabeth Bryda, PhD
Professor, Director, Rat Resource and Research Center
Veterinary Pathobiology
University of Missouri
Columbia, Missouri

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A number of groups have demonstrated the ability of probiotics to benefit digestive health and there is a growing body of evidence to suggest an association between mental health and “gut health”. We were interested to see if probiotic bacteria could decrease anxiety- or stress-related behavior in a controlled setting using zebrafish as our model organism of choice for these studies.

We were able to show that Lactobacillus plantarum decreased overall anxiety-related behavior and protected against stress-induced dysbiosis (microbial imbalance). The fact that administration of probiotic bacteria also protected other resident gut bacteria from the dramatic changes seen in “stressed” fish not receiving the probiotic was unexpected and suggested that these bacteria may be working at the level of the GI tract and the central nervous system.

Continue reading

Therapies That Target Accessory Cells in a Tumor May Enhance Standard Care

MedicalResearch.com Interview with:

Sudarshan Anand, PhD Department of Cell, Developmental and Cancer Biology Department of Radiation Medicine Oregon Health and Science University Portland, Oregon

Dr. Sudarshan Anand

Sudarshan Anand, PhD
Department of Cell, Developmental and Cancer Biology
Department of Radiation Medicine
Oregon Health and Science University
Portland, Oregon

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Almost half of all cancer patients receive radiation therapy during the course of their disease.

While the impact of radiation on the cancer cells has been well studied in experimental models, its effects on the accessory cells that are present in the tumor are not well known. One of the major interests of our lab is studying these accessory cells of the tumor aka “the tumor microenvironment”. These group of cells consists of blood vessel cells, fibroblasts and immune cells that are normal cells that have been recruited by the tumor and generally support tumor growth.

The goal of this study was to understand the impact of radiation (and broadly DNA damaging agents) on the blood vessel cells in the tumor. We focused on a specific type of molecule called microRNAs (miRs) in these cells. miRs are small RNA molecules that bind to dozens of messenger RNAs and the production of proteins.

We discovered a group of microRNAs that was induced in blood vessel cells by radiation, a chemotherapy agent cisplatin and peroxide an agent that mimics oxidative stress that is often present in cancers. We found that the top candidate on this list was a microRNA that mimicked radiation by inducing DNA damage and eventually killing the blood vessel cells. Administering this microRNA, either within a tumor or using a specific nanoparticle that delivers cargo to the tumor blood vessels, decreased tumor growth in mouse models of breast cancer, brain cancer and colorectal cancer. We found that the efficacy of this agent was a result of its ability to suppress a protein TREX1, that is often mutated in human lupus.

In other words, this microRNA was able to create some of the immune and inflammatory features of lupus within a tumor and induce proteins that triggered cell death on tumor cells. Overall, our work illustrates how the tumor accessory cells respond to radiation and highlights the cross-talk between different accessory cells and the tumor cells.

Continue reading

Precise Structure of Cannabis Brain Receptor Defined

MedicalResearch.com Interview with:

(l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum

(l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum UT Southwestern

Dan Rosenbaum, Ph.D.
Principal Investigator
Department of Biophysics
The University of Texas Southwestern Medical Center
Dallas, Texas

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study focuses on the structure of the human CB1 cannabinoid receptor.

The CB1 protein is a membrane-embedded G protein-coupled receptor (GPCR) in the brain and peripheral tissues that responds to a variety of different compounds, including endogenous lipid messengers (‘endocannabinoids’), plant natural products (such as THC from the Cannabis sativa plant i.e. marijuana), and synthetic antagonists (such as the taranabant ligand used for this study). The CB1 receptor is involved in regulating neurotransmission in vertebrates, and is a potential therapeutic target for numerous conditions including obesity, pain, and epilepsy.

The main findings of this study entailed the solution of the high-resolution crystal structure of human CB1 receptor bound to the inhibitor taranabant. This structure revealed the precise shape of the inhibitor binding pocket, which is also responsible for binding THC and endocannabinoids. In addition to helping explain the mechanism of inhibitor and THC binding, our structure provides a framework for computational studies of binding to a large diversity of cannabinoid modulators of therapeutic importance.

Continue reading

Switch Stimulating New Insulin-Producing Cells Could Lead To Cure For Type I Diabetes

MedicalResearch.com Interview with:

Dr. Fred Levine MD PhD Professor & Director Sanford Children's Health Research Center Sanford Burnham Prebys Medical Discovery Institute La Jolla, CA

Dr. Fred Levine

Dr. Fred Levine MD PhD
Professor & Director
Sanford Children’s Health Research Center
Sanford Burnham Prebys Medical Discovery Institute
La Jolla, CA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study is the latest in a series that began in 2010 when we published that the combination of severe pancreatitis and ablation of preexisting pancreatic beta-cells led to the formation of new beta-cells by direct conversion of alpha-cells, which are the neighboring cells in the islets of Langerhans producing glucagon, which like insulin is also involved in glucose homeostasis.

The phenomenon of generating new beta-cells by islet cell transdifferentiation went against the conventional wisdom in the field, which is that most beta-cell neogenesis in adults occurs by differentiation from cells in the pancreatic ducts, similar to what happens during embryogenesis. Since then, we have shown that beta-cell neogenesis by islet cell transdifferentiation appears to occur in murine and human type I diabetes, making it highly translationally relevant.

Understanding the mechanism by which new beta-cells are formed from alpha-cells is required for eventual clinical translation. The current study describes that mechanism, which involves the activation of an atypical G protein coupled receptor called Protease Activated Receptor 2 (PAR2). Unlike most other GPCRs, it is activated by extracellular proteases such as are found in the exocrine pancreas or following tissue damage. PAR2 activation by an injectable peptide agonist was both necessary and sufficient to induce beta-cell neogenesis when preexisting beta-cells are absent, as occurs in type I diabetes.

Continue reading

Our Brain Makes Liars Even Better At Lying

MedicalResearch.com Interview with:
Neil Garrett PhD Student

Affective Brain Lab
Department of Experimental Psychology
University College London
London, UK

MedicalResearch.com: What is the background for this study? What are the main findings?

1. BEHAVIOURAL FINDING: The amount by which participants lied got larger and larger over the course of the block. Dishonesty escalation was observed only when participants lied for their own benefit, not when they did so solely for the benefit of others.

2. BRAIN FINDING: A network of brain regions associated with emotion responded strongly when participants lied initially. But as time went on, it would respond less and less to the same amount of lying. The greater the drop in sensitivity, the more a person increased their lying the next opportunity they got.

Continue reading

Vitiligo Susceptibility Genes Associated With Immune Regulation Identified

MedicalResearch.com Interview with:

Richard Spritz, Director of the Human Medical Genetics and Genomics Program at the University of Colorado School Medicine, led a recent study that explored the genetic links between eye color and serious skin conditions like vitiligo and melanoma. (Marla R. Keown/Aurora Sentinel)

Dr. Richard Spritz,

Richard A. Spritz, M.D.
Professor and Director,
Human Medical Genetics and Genomics Program
University of Colorado School of Medicine.
Aurora, CO 80045 USA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Vitiligo is an autoimmune disease in which depigmented skin results from destruction of skin melanocytes, with strong epidemiologic association with several other autoimmune diseases that include autoimmune thyroid disease, type 1 diabetes, rheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, and Addison’s disease.

In previous genetic linkage and genome-wide association studies (GWAS) of vitiligo patients of European-derived white ancestry (EUR), we identified 27 vitiligo susceptibility loci. In the present study, we carried out a third GWAS of vitiligo in EUR subjects. The combined analysis, with almost 5,000 vitiligo cases and 40,000 non-vitiligo controls, identified a total 23 new confirmed vitiligo loci, as well as seven with suggestive significance.

Continue reading