Biomedical Laboratory Science

Friday, July 8, 2016

The Pathophysiology of Defective Proteostasis in the Hypothalamus — From Obesity to Ageing

Hypothalamic dysfunction has emerged as an important mechanism involved in the development of obesity and its comorbidities, as well as in the process of ageing and age-related diseases, such as type 2 diabetes mellitus, hypertension and Alzheimer disease. In both obesity and ageing, inflammatory signalling is thought to coordinate many of the cellular events that lead to hypothalamic neuronal dysfunction. This process is triggered by the activation of signalling via the toll-like receptor 4 pathway and endoplasmic reticulum stress, which in turn results in intracellular inflammatory signalling. However, the process that connects inflammation with neuronal dysfunction is complex and includes several regulatory mechanisms that ultimately control the homeostasis of intracellular proteins and organelles (also known as 'proteostasis'). This Review discusses the evidence for the key role of proteostasis in the control of hypothalamic neurons and the involvement of this process in regulating whole-body energy homeostasis and lifespan.

Key points

Specialized neurons of the hypothalamus control caloric intake and energy expenditure in response to hormonal, nutritional and neural signals that reflect the energy stores in the body
Malfunction of the hypothalamus occurs in obesity and ageing, which leads to an imbalance between caloric intake and energy expenditure resulting in positive energy balance and reduced lifespan
The excessive consumption of certain nutrients and ageing affect different aspects of proteostasis in selected neurons of the hypothalamus, contributing to neuronal dysfunction in obesity and ageing
Inflammation is one of the most important outcomes of disturbed proteostasis to occur in the hypothalamus during obesity and ageing
Several genetic and pharmacological approaches used to correct the defects of proteostasis and reduce inflammation have proven effective in reducing obesity and increasing lifespan in experimental models

Figure 1: Control of energy balance and lifespan by the hypothalamic network. Neurons of the
medium hypothalamus respond to systemic signals of whole-body energy status. Blood levels of
insulin fluctuate acutely in response to carbohydrates present in food and chronically in response
to increased adiposity.

Source: Nature Reviews Endocrinology

What’s the point of the PhD thesis?

Doctoral courses are slowly being modernized. Now the thesis and viva need to catch up.

On the morning of Tom Marshall's PhD defence, he put on the suit he had bought for the occasion and climbed onto the stage in front of a 50-strong audience, including his parents and 6 examiners. He gave a 15-minute-long presentation, then faced an hour of cross-examination about his past 5 years of neuroscience research at the Donders Institute for Brain, Cognition and Behaviour in Nijmegen, the Netherlands. A lot was at stake: this oral examination would determine whether he passed or failed. “At the one-hour mark someone came in, banged a stick on the floor and said 'hora est',” says Marshall — the ceremonial call that his time was up. “But I couldn't. I had enjoyed the whole experience far too much, and ended up talking for a few extra minutes.”

Marshall's elaborate, public PhD assessment is very different from that faced by Kelsie Long, an Earth-sciences PhD candidate at the Australian National University (ANU) in Canberra. Her PhD will be assessed solely on her written thesis, which will be mailed off to examiners and returned with comments. She will do a public presentation of her work later this year, but it won't affect her final result. “It almost feels like a rite of passage,” she says.

Source: nature

Thursday, July 7, 2016

Viral Hepatitis Has Become a Leading Global Killer

Compared with most other communicable diseases, hepatitis has risen in global importance since the 1990s. It is now a leading cause of death and disability worldwide and kills at least as many people as tuberculosis, HIV/AIDS, or malaria.

This is the main finding of an international study - led by Imperial College London in the United Kingdom and the University of Washington in Seattle - published in The Lancet.

The study - which analyzes data from 1990-2013 on 183 countries - is timely, as the World Health Organization (WHO) launch a major new effort to tackle viral hepatitis.

The findings should prove of "crucial importance to global health policy," note the authors.

At 1.45 million deaths a year, viral hepatitis now ranks among the world'sleading
infectious diseases - such as TB, AIDS/HIV, and malaria.

Source: medicalnewstoday

New 'Mutation-Tracking' Blood Test Could Predict Breast Cancer Relapse Months in Advance

Scientists have developed a blood test for breast cancer able to identify which patients will suffer a relapse after treatment, months before tumours are visible on hospital scans.

The test can uncover small numbers of residual cancer cells that have resisted therapy by detecting cancer DNA in the bloodstream.

Researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust were able to track key mutations that cancer accumulates as it develops and spreads, without the need for invasive biopsy procedures.

They hope that by deciphering the DNA code found in blood samples, it should be possible to identify the particularly mutations likely to prove lethal to that patient - and tailor treatment accordingly.

Source: medicalxpress

Breathing New Life into Cystic Fibrosis Genetic Testing

New Research Has Broadened the Number of Clinically Relevant CFTR Gene Mutations.

Imagine yourself suspended a couple of hundred feet below the surface of the ocean. The sheer weight of the immense column of water pushing down on your chest makes each breath a harrowing task. Now picture that your only recourse to collect vital oxygen is to breathe laboriously throw a narrow straw that connects you to the atmosphere above. You slowly draw in air, cautiously trying not to collapse the straw from too forceful of suction—struggling just as much to exhale the expired air. Now repeat the entire cycle for the rest of your life.

If you were able to envision how the immense difficulties of breathing in this manner would be for just a few minutes, let alone your entire life, then you may have a minute sense of what a person afflicted with cystic fibrosis (CF) endures. Gasping for air while thick, sticky mucus lines the pulmonary system, seemingly threatening to drown and suffocate patients with each inhale.

Accurate genetic testing for cystic fibrosis can determine if a patient has the disease and provide
needed information for potential carrier couples, clinical actionability of identified mutations, and
potential severity. [Krishna Kumar/Getty]

Source: genengnews

Prostate Cancer And DNA Mutation: New Connections Revealed

Specific mutations in the DNA of men with metastatic prostate cancer have been shown to play a larger role in the disease than previously thought. Researchers hope that this finding will help change standard therapy guidelines and open the door to drugs currently being used for other cancers.

The new study, published in the New England Journal of Medicine, examined inherited mutations in DNA repair genes.

These gene mutations were already known to occur more frequently in prostate cancer patients than the general population.

However, the present study demonstrated that mutations in DNA repair genes were even more prevalent in people with metastatic prostate cancer, specifically.

Gene mutation research gives a new perspective on prostate cancer.

Source: medicalnewstoday

Wednesday, July 6, 2016

Top Signs There’s Something Wrong With Your Thyroid

One of the most important parts of our bodies is also one of the smallest ones. The thyroid, butterfly-shaped gland on the front of the neck below the Adam’s apple, releases hormones that have a huge impact on metabolism, among other processes.

Thyroid disorders can have a significant impact on your attitude and temperament. Hypothyroidism tends to make people feel depressed. This is due to the fact that too little thyroid hormones decreases the “happiness” hormone, serotonin, in the brain.

Source: https://youtu.be/XzTHxnKMFDs

Why is My Skin Itchy? Examining the Causes of Itchy Skin

For some people, itchy skin is a constant battle. It can be difficult to understand exactly what is causing the skin to itch.

Itchy skin can be the result of a rash or another skin condition. It can also be a symptom of a more serious condition such as liver disease or kidney failure. To get relief, it is important to identify the problem and treat the underlying cause.

Skin, rashes, and itches

Skin serves a vital purpose as a barrier, protecting the inside of the body.

Itching is one of the most common symptoms of all skin problems.

Source: medicalnewstoday

What It Feels Like to Live With an Incurable Bladder Disease

Nicole Abi-Najem, a 28-year old student from Toronto, has interstitial cystitis, an extremely painful bladder condition that has been likened to having a permanent urinary tract infection.

In 2012, I was working out and I went to the bathroom. When I finished peeing, I still felt like I had to go, but I knew that my bladder was empty. Doctors initially thought it was a urinary tract infection, but a test showed there wasn’t any bacteria. They gave me antibiotics, but the feeling didn’t go away. I went to a urologist, and he performed a cystoscopy to examine the inside of my bladder. He saw nothing. With both those tests clear, a specialist at Women’s College Hospital in Toronto eventually concluded that I had interstitial cystitis.