Genetics of Coronary Artery Disease: Discovery, Biology and Clinical Translation !

Genetics

Coronary artery disease is the leading global cause of mortality. Long recognized to be heritable, recent advances have started to unravel the genetic architecture of the disease. Common variant association studies have linked approximately 60 genetic loci to coronary risk. Large-scale gene sequencing efforts and functional studies have facilitated a better understanding of causal risk factors, elucidated underlying biology and informed the development of new therapeutics. Moving forwards, genetic testing could enable precision medicine approaches by identifying subgroups of patients at increased risk of coronary artery disease or those with a specific driving pathophysiology in whom a therapeutic or preventive approach would be most useful.

• Coronary artery disease is a heritable disorder that remains the leading cause of global mortality despite advances in treatment and prevention strategies. Human genetics studies have started to unravel the genetic underpinnings of this disorder.
• Gene discovery efforts have rapidly transitioned from family-based studies (for example, those that led to the discovery of familial hypercholesterolaemia) to large cohorts that facilitate both common and rare variant association studies.
• Common variant association studies have confirmed ∼60 genetic loci with a robust association with coronary disease, the majority of which are of modest effect size and in non-coding regions. Rare variant association studies have linked inactivating mutations in at least nine genes with risk of coronary artery disease.
• Human genetics and large-scale biobanks can facilitate drug development for coronary artery disease by highlighting causal biology and helping to understand the phenotypic consequences of lifelong deficiency of a given protein.
• Genomic medicine may provide patients and their health care providers with genetic data that will aid in coronary artery disease prevention and treatment.
• Genome editing to introduce mutations that are protective against coronary artery disease into the population could prove curative with a one-time injection, although substantial additional work is needed to confirm efficacy and safety, and to address the underlying ethics.

Observational epidemiology and translational research efforts have led to significant progress in improving the understanding of the pathophysiology underlying coronary artery disease (CAD). Prevention and treatment strategies developed on the basis of this knowledge led to a >50% decrease in age-adjusted CAD mortality rate in the United States between 1980 and 2000. However, despite these advances, CAD remains the leading global cause of mortality. Current predictions estimate that more than 900,000 individuals in the United States will suffer a myocardial infarction (heart attack) or die of CAD this year.

This review outlines research efforts to understand the genetic drivers of CAD, the role of human genetics in catalysing CAD drug discovery efforts and the promises and challenges of integrating genetic information into routine clinical practice.

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Study Sheds Light on How High Cholesterol Causes Cancer !

Cholesterol

New research from the University of California, Los Angeles has found a previously unknown molecular mechanism involving cholesterol that may promote tumor growth in the intestines.

A report on the study — published in the journal Cell Stem Cell — reveals how increasing levels of cholesterol in mice increased proliferation of intestinal stem cells and made tumors grow faster.

One of the methods that the researchers used to increase the availability of cholesterol to intestinal cells in the mice was to feed them a high-cholesterol diet.

"We were excited to find," says senior author Peter Tontonoz, a professor of pathology and laboratory medicine, "that cholesterol influences the growth of stem cells in the intestines, which in turn accelerates the rate of tumor formation by more than 100-fold."

He and his colleagues believe that their findings could pave the way to new treatments for gastrointestinal diseases, such as colon cancer.

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Kaplan MCAT Biology Review - Test Prep !

Exam Practice

MCAT Biology Review,

Test Prep for the MCAT Exam

KAPLAN pdf

Kaplan MCAT Biology Review, Test Prep pdf ebook

The MCAT is changing in 2015. With the addition of three semesters’ worth of material, more advanced critical thinking skills, a longer duration, and changes in Biology content, the new exam requires even more diligent prep with resources from Kaplan Test Prep.

Kaplan's MCAT Biology Review offers:

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Cancer: Four-Stranded DNA Could Help Develop Targeted Treatments

By taking a closer look at four-stranded versions of DNA inside the genome of human cells, scientists have discovered some potential new avenues for targeted cancer treatments. They found that the quadruple helix structures occur in DNA regions that control genes, especially cancer genes.

The researchers, from the University of Cambridge in the United Kingdom, report their findings in the journal Nature Genetics.

Targeted cancer therapies are currently the focus of much research and development into new anticancer treatments.

They are an important area of precision medicine - where information about an individual patient's genes and proteins are used to prevent, diagnose, and treat disease.

Read more: Cancer: Four-Stranded DNA Could Help Develop Targeted Treatments

The aim of targeted therapy is to attack cancer cells without affecting healthy cells.

Source: MedicalNewsToday

Melanoma May Be Stoppable With Drug That Halts Cancer Cell Proliferation

A drug already being tested in people as a treatment for cancer appears to show great promise in halting melanoma skin cancer. The drug - called pevonedistat - works in a way differently than intended and could also be effective against other cancers.

So says a new study from the University of Virginia School of Medicine in Charlottesville that was published in the journal EBioMedicine.

Lead researcher Tarek Abbas, assistant professor of radiation oncology, says:

"In fact, the drug is very effective on all melanomas, including those for which an effective therapeutic is lacking."

Melanoma is an aggressive skin cancer that develops when melanocytes - the cells that give skin its color - mutate and become cancerous.

Read more: Melanoma May Be Stoppable With Drug That Halts Cancer Cell Proliferation

Melanoma is an aggressive skin cancer that develops when cells that give skin its color mutate and
become cancerous. The researchers say they have found a drug that may stop the cancer progressing.

Source: MedicalNewsToday

Blood Vessel-Forming Protein Could Offer Alternative to Heart Bypass Surgery

For patients with severe coronary artery disease, heart bypass surgery can reduce the risk of heart attack and improve overall quality of life. Now, researchers report the possibility of a new treatment that may be even more beneficial, without the surgery.

Coronary artery disease (CAD) is the most common form of heart disease in the United States, responsible for more than 370,000 deaths in the country every year.

The condition arises when plaque builds up in the coronary arteries, partially or fully blocking the flow of oxygen-rich blood to the heart muscle. This blockage can cause heart attack, angina - severe chest pain - and, over time, heart failure.

While lifestyle changes - such as adopting a healthy diet and regular physical activity - are considered key to improving CAD, some patients may require heart bypass surgery, which can help restore blood flow to the heart.

But, as with all surgery, it has its risks. These include chest wound infection, bleeding, stroke, heart attack, and kidney or lung failure.

Read more: Blood Vessel-Forming Protein Could Offer Alternative to Heart Bypass Surgery

Researchers say the protein AGGF1 could be a promising treatment for coronary heart disease and
heart attack.

Source: medicalnewstoday

HIV: Newly Discovered Component Could Lead to More Effective Drugs

Scientists from the Medical Research Council Laboratory of Molecular Biology in Cambridge and University College London - both in the United Kingdom - have uncovered key components of HIV, which they believe could lead to new approaches for drugs to fight the infection.

HIV weakens a person's immune system by destroying important cells that fight disease and infection. Only certain body fluids - blood, semen, rectal fluids, vaginal fluids, and breast milk - from a person who has HIV can transmit HIV.

According to the Centers for Disease Control and Prevention (CDC), an estimated 1.2 million people are living with HIV in the United States. Although there is no cure for HIV infection, improved treatments allow people living with HIV to slow the virus' progression and stay relatively healthy for several years.

HIV is a part of a subtype of viruses called retroviruses, which means that the virus is composed of RNA - instead of normal DNA - and has the unique property of transcribing RNA into DNA after entering a cell.

Read more: HIV: Newly Discovered Component Could Lead to More Effective Drugs

Findings from the research could lead to future drugs that can enter human cells and block the pores
from within.

Source: medicalnewstoday

'Living' Cartilage Grown Using Stem Cells Could Prevent Hip Replacement Surgery

An alternative to hip replacement surgery may be in sight. In the Proceedings of the National Academy of Sciences, researchers reveal how it may be possible to use a patient's own stem cells to grow new cartilage in the shape of a hip joint.

Furthermore, the team - including researchers from Washington University School of Medicine in St. Louis, MO - says it is possible to program the newly grown cartilage to release anti-inflammatory molecules, which could stave off the return of arthritis - the most common cause of hip pain.

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), osteoarthritis is the primary cause of hip joint damage that requires hip replacement surgery, causing severe pain and disability.

Hip replacement surgery, also known as arthroplasty, involves surgically removing the diseased part of the hip and replacing it with new, prosthetic parts. Each year in the United States, more than 332,000 hip replacement surgeries are performed.

Read more: 'Living' Cartilage Grown Using Stem Cells Could Prevent Hip Replacement Surgery

Researchers describe how they could use a patient's own stem cells to grow new cartilage that covers

a 3-D scaffold molded to the shape of their hip joint.

Source: medicalnewstoday

Osteoarthritis can be Caused by Senescent Cells

Researchers have uncovered evidence that cellular senescence - whereby cells stop dividing - is a cause of osteoarthritis, and they suggest targeting these cells could offer a promising way to prevent or treat the condition.

Study co-author Dr. James Kirkland, director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic in Rochester, MN, and colleagues publish their findings in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences.

Osteoarthritis (OA), also known as degenerative joint disease, is a condition in which cartilage - the tissue that protects the end of each bone in a joint - wears away, causing the underlying bones to rub together. This can cause pain, swelling, and poor joint movement.

As the condition worsens, the bones may lose shape. Additionally, growths called bone spurs may arise, and bits of bone and cartilage can break off and float around the space in the joint. This can trigger an inflammatory response that exacerbates pain, as well as cartilage and bone damage.

Read more: Osteoarthritis can be Caused by Senescent Cells

Researchers say that targeting senescent cells may have the potential to prevent or treat osteoarthritis.

Source: medicalnewstoday

Tibetans Inherited High-Altitude Gene From Ancient Human

A “superathlete” gene that helps Sherpas and other Tibetans breathe easy at high altitudes was inherited from an ancient species of human. That’s the conclusion of a new study, which finds that the gene variant came from people known as Denisovans, who went extinct soon after they mated with the ancestors of Europeans and Asians about 40,000 years ago. This is the first time a version of a gene acquired from interbreeding with another type of human has been shown to help modern humans adapt to their environment.

Researchers have long wondered how Tibetans live and work at altitudes above 4000 meters, where the limited supply of oxygen makes most people sick. Other high-altitude people, such as Andean highlanders, have adapted to such thin air by adding more oxygen-carrying hemoglobin to their blood. But Tibetans have adapted by having less hemoglobin in their blood; scientists think this trait helps them avoid serious problems, such as clots and strokes caused when the blood thickens with more hemoglobin-laden red blood cells.

Read more: Tibetans Inherited High-Altitude Gene From Ancient Human

Breathing easy. This Tibetan inherited a beneficial high-altitude gene from archaic Denisovan people.

Beijing Genomics Institute

Source: sciencemag

Cancer Breakthrough? Novel Insight into Metastasis Could Offer New Treatments

Researchers from the United Kingdom may have made a breakthrough in cancer treatment, after discovering an unusual mechanism by which cancer cells spread and survive in the body.

In a study published in Nature Communications, researchers reveal how two molecules join forces to help cancer cells survive as they metastasize.

Metastasis is the process by which cancer cells break away from the primary tumor and spread to other parts of the body through the bloodstream or lymph system.

Once cancer has spread, the disease becomes much more challenging to treat Chemotherapy, hormone therapy, radiotherapy, and other treatments can yield success for some metastatic cancers, but for most, the prognosis is poor.

Read more: Cancer Breakthrough? Novel Insight into Metastasis Could Offer New Treatments

Source: medicalnewstoday

Scientists Offer New View on Origins of Parkinson's Disease

The death of brain cells in Parkinson's disease is likely a result of stress in their endoplasmic reticulum or protein-folding machinery rather than just a general failure of their mitochondria or powerhouses.

So conclude researchers from the University of Leicester in the United Kingdom, who report their findings, based on research conducted in fruit flies, in the journal Cell Death and Disease.

Dr. Miguel Martins, who heads a group in the MRC Toxicology Unit at Leicester, says:

"This research challenges the current held belief the Parkinson's disease is a result of malfunctioning mitochondria."

Read more: Scientists Offer New View on Origins of Parkinson's Disease

Source: medicalnewstoday