Transcription Factor Discovery Opens Up New Therapies For Glioblastoma Multiforme

Researchers from the Massachusetts General Hospital (MGH) have identified four transcription factors that distinguishes glioblastoma cells.

The four transcription factors identified were POU3F2, SOX2, SALL2 and OLIG2.

Transcription factors are proteins that regulates the expression of other genes. In this case, the transcription factors can zero in on a small ratio of glioblastoma cells responsible for the aggressiveness and treatment resistance of the deadly brain tumor.

A glioma is a tumor that commonly starts in the brain but can also manifest in the spine. These gliomas are categorized into grades from Grade I to Grade IV. Glioblastoma Multiforme is the most aggressive and deadly and is classified as a Grade IV Glioma.

Glioblastoma multiforme or GBM is the deadliest brain cancer around. It is also the most common. A patient diagnosed with GBM usually has one to two years to live.

By knowing the transcription factors responsible for the glioblastoma cells, therapies can be modeled that would target these factors. This discovery opens up the opportunity of finding new and alternative ways of treating this extremely difficult disease.

Engineered Antimicrobial Peptides Developed To Kill Antibiotic Resistant Bacteria

With antibiotic resistant bacteria becoming prevalent, reaching high levels, scientists are studying ways to counteract and address this serious problem. Using the drug resistant bacteria that causes Tuberculosis, researchers are testing a new therapy using antimicrobial peptides to overcome this. This research was presented at the 247th National Meeting & Exposition of the American Chemical Society (ACS).

The TB bacteria is slowly coming up with resistant strains that pose a real serious health risk. Scientists have developed a new way to destroy these organisms and similar ones that have built a resistance to antibiotics; drilling.

Using protein engineered antimicrobial peptides (AMP), the outer membrane of bacterial organisms are broken down removing its structural support and protection mechanism. Just like drill bits, the AMPs drill into the thick walls of the cells killing the bacteria. Using three synthesised strains of AMP, lab tests show that all three of these antimicrobial peptides were successful in killing the Mycobacterium tuberculosis and M. smegmatis bacteria .

This is just the first generation of AMPs produced and scientists are also studying another class of AMPs, picidin a and 3, to improve and expand its arsenal against this deadly trend.

New Process Developed To Image How The Brain Forms Memories

Researchers at Albert Einstein College of Medicine of Yeshiva University have imaged the brain while forming memories on the molecular level. This was achieved by tagging fluorescent beta-actin mRNA molecules using a mouse model.

The tagged molecules were observed by the scientists in real time while brain cells were forming memories. See embedded video.

They note that the stimulated individual hippocampal neurons caused a rapid transcription of the beta-actin gene within 10 to 15 minutes. The hippocampus is the region of the brain where where memories are made and stored. These beta-actin mRNA molecules continuously assemble and disassemble into large and small particles, respectively. These mRNA particles were seen traveling to their destinations in dendrites where beta-actin protein would be synthesized.

The neurons connect to each other through spines of dendrites where long-lasting synaptic connections form between neurons in contact with each other. The Beta-actin protein appears to strengthen these synaptic connections by altering the shape of dendritic spines.

SIGIRR Protein Found To Protect Gut Flora From Toxins

Credit: Barcroft/Fame Pictures/NPR

Scientists have discovered that the SIGIRR protein protects the beneficial bacteria in the gut (known as Gut Flora) from toxins and substances that can cause food poisoning and bowel inflammation. The Single Ig IL-1-Related Receptor (SIGIRR) is a protein encoded by the SIGIRR gene in humans.

The human body carries over a thousand species of bacteria. Most of these can be found in the human intestinal tract or the gut. These bacteria, collectively called Human Gut Flora comprises about 500 species and is beneficial to the body.

Gut flora performs important functions such as fermenting unused energy substrates, training the immune system, preventing growth of harmful, pathogenic bacteria, regulating the development of the gut, producing vitamins (such as biotin and vitamin K) for the host, and producing hormones to direct the host to store fats.

Although the positive relationship between gut flora and the human body, there are certain situations and conditions that bacteria can cause infections, disease, and even cancer.

Diabetes Patients Taking GLP-1 Based Medication Has Reduced Risk of Heart Failure

GLP-1 and Diabetes
Credit:Wikipedia

A study shows that diabetes patients taking a class of medication targeting the GLP-1 hormone has a reduced risk of heart disease.

Diabetes is one of the most serious health problems around. In the next 20 years, diabetes is expected to affect nearly 552 million people globally.

There are two types of diabetes, Type 1 and Type 2. Type 1 diabetes is a commonly hereditary condition where the immune system starts to attack insulin producing beta cells in the pancreas. Insulin is needed by the body to regulate the blood sugar levels in the bloodstream.

Type 2 diabetes is the most common of the two types. It accounts for 95% of cases of diabetes. In Type 2 diabetes, there is not enough insulin produced by the body or that the insulin produced is being rejected by the cells.

The growth of cases of Type 2 diabetes is generally associated with the rise of obesity. Every 10 seconds, 3 people will be diagnosed with Type 2 diabetes. Every 10 seconds, 1 person will die from it due to complications arising from it.

Heart disease, kidney failure, and stroke are the top diabetes related complications. There is no cure for diabetes. The disease can only be managed through glucose monitoring, insulin injections and other medications that help regulate blood sugar levels.

One medication used by diabetes patients to manage diabetes are DPP-4 inhibitors. DPP-4 inhibitors prevent DPP-4 (Dipeptidyl peptidase-4) from breaking down a hormone called GLP-1 (Glucagon-like peptide-1).

GLP-1 is a hormone released from the gut that travels to the pancreas and allows the increased production of insulin when glucose levels starts rising.

GLP-1 also holds back the production of a hormone called Glucagon. Glucagon encourages the liver to convert glucose reserves into active glucose. By holding back the production of glucagon, the levels of glucose in the bloodstream are minimized.

GLP-1 does not live long as DPP-4 breaks down the hormone. By inhibiting DPP-4, GLP-1 hormones lasts longer and insulin production and glucagon reduction continues.

Lipoxin A4 Discovered To Serve Dual Purpose In Treatment and Management of Asthma

Scientists from from Brigham and Women's Hospital have discovered a molecule that plays a dual role in the treatment and management of asthma.

Asthma is a breathing disorder wherein air passages start to swell and narrow which restricts the airflow to and from the lungs of the patient. The air passages, called bronchioles, start to swell up and tighten resulting in shortness of breath, coughing, tightening of the chest and a wheezing sound while trying to breath.

Asthma can be triggered by chemicals in the air or food, exercise, weather, stress, medicine, and other allergens. Also it is advised that people suffering from asthma to avoid exposure to cigarette smoke and other air born particles such as pollen.

Asthma is an incurable condition and can only be managed and controlled by medication such as inhaled corticosteroids. These help keep the swelling down and reduce the effects of an asthma attack.

The purpose of asthma medication is to reduce the swelling of the bronchioles. Recently, researchers from Brigham and Women's Hospital have discovered a molecule that can be used to effectively treat and manage asthma attacks by both cutting down on the swelling and also inhibiting further inflammation of the bronchioles.

Lipoxin A4's process of quelling airway inflammation is similar to putting out a forest fire, according to Bruce Levy, M.D., Pulmonary and Critical Care Medicine Division, BWH Department of Internal Medicine. Molecular image courtesy of Levy Lab.
Credit: Levy Lab

XPD Protein Discovered To Scan For Damaged DNA

The XPD scanner (green)is in close contact with a damaged point (red) on the DNA double helix. The damaged DNA strand lies in a deep pocket of the protein to enable a ferrous sensor (Fe) to come into contact with the damaged point, thereby halting the protein as it moves along the DNA.
Image: UZH

Xeroderma pigmentosum group D (XPD) protein, a protein associated with repairing DNA has been discovered to also scan for damaged DNA.

Deoxyribonucleic acid (DNA) is a molecule that contains genetic code or instructions used for the development and function of living organisms. DNA encodes its genetic information through the sequence of four nucleotides (guanine(G), adenine(A), thymine(T), and cytosine(C)).

Whenever DNA is damaged through ultra-violet light, cigarette smoke, toxic fumes, toxins, X-rays and radiation, and metabolic processes, it is repaired by proteins and enzymes such as Superoxide dismutases and methyl guanine methyl transferase (MGMT). Roles of these proteins and enzymes vary from recognizing damage, to correcting the damaged portions or remove them.

Unrecognized damage which does not get repaired, accelerates aging and causes cancer and genetic disorders. There are DNA disorders that involve the body having difficulty repairing DNA. Xeroderma pigmentosum (XP) and Trichothiodystrophy (TTD) are two of these disorders.

A team headed by veterinary pharmacologist and toxicologist Hanspeter Nägeli has now discovered that the protein XPD plays a key role in locating damaged DNA.

MIT News: Understanding Tumor Metastasis, Cancer, And Cellular Adhesion

A microscopic image of cancer cells adhering to a spot coated with molecules found in the extracellular matrix.
Image: Nathan Reticker-Flynn

Cancer researchers at MIT are focusing their attention on how tumor metastasis occurs. Metastasis is the spread of the tumor to other parts of the body and is the primary reason for ninety percent of all cancer deaths. Their findings are published in the October issue of Nature Communications.

When a tumor metastasize, cancerous cells detach from the primary tumor and spread to other organs through the blood stream. The team of researchers headed by Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, are studying how the anchoring process works within the tumor.

“As cancer cells become more metastatic, there can be a loss of adhesion to normal tissue structures. Then, as they become more aggressive, they gain the ability to stick to, and grow on, molecules that are not normally found in healthy tissues but are found in sites of tumor metastases,” says Bhatia, who is also a member of the David H. Koch Institute for Integrative Cancer Research at MIT. “If we can prevent them from growing at these new sites, we may be able to interfere with metastatic disease.”

Cells bind itself to a tissue surface or extracellular matrix because of cell adhesion. The extracellular matrix is a structural support system that holds cells in place and also regulates its behavior. On the surface of the matrix are cell adhesion molecules such as the protein Integrin that anchor the cells in place. Integrins can communicate with the cellular matrix both ways, meaning it can send signals from the matrix environment to the matrix and vice-versa.

The scientists tested eight hundred different protein pairs to find out how the cells will bind to them. They noticed that one pair of extracellular matrix molecules that metastatic tumors stuck to especially well was fibronectin and galectin-3, both made of proteins that contain or bind to sugars. Integrin works especially well with fibronectin.