Scientists have discovered the genetic mutation that causes the rare skin disease, keratolytic winter erythema (KWE), or ‘Oudtshoorn skin’, in Afrikaners.

KWE causes a redness of the palms and soles with consecutive cycles of peeling of large sections of thick skin, often exacerbated during winter months. Oudtshoorn is a town in the Western Cape province of South Africa where the disorder was present in large families.

Afrikaners are Afrikaans-language speakers descended from predominantly Dutch, German and French settlers, who arrived in South Africa in the 17th and 18th centuries. Afrikaners have a high risk for several genetic disorders, the best known being familial hypercholesterolaemia (inherited high cholesterol leading to heart attacks early in life) and porphyria (sensitivity of the skin to ultra-violet exposure and adverse reactions to specific drugs).

These disorders are common because of founder mutations brought to South Africa by small groups of immigrants who settled in the Cape of Good Hope and whose descendants are now spread throughout the country. KWE is one of these less well-known founder genetic disorders.

KWE was first described as a unique and discrete skin disorder in 1977 by Wits dermatologist, Professor George Findlay. He noticed that it occurred in families and had a dominant mode of inheritance – i.e., on average, if a parent has the condition about half the children inherit it in every generation.

In addition to identifying the genetic mutation for scientific purposes, this research now enables dermatologists to make a definitive diagnosis of KWE in patients. It further enables researchers to understand similar skin disorders and is a starting point for developing possible treatments.

Wits Universitywww.wits.ac.za/news/latest-news/research-news/2017/2017-05/scientists-find-genetic-mutation-responsible-for-rare-skin-disease-in-afrikaners.html

What can’t graphene do? You can scratch “detect cancer” off of that list.
By interfacing brain cells onto graphene, researchers at the University of Illinois at Chicago have shown they can differentiate a single hyperactive cancerous cell from a normal cell, pointing the way to developing a simple, non-invasive tool for early cancer diagnosis.
“This graphene system is able to detect the level of activity of an interfaced cell,” says Vikas Berry, associate professor and head of chemical engineering at UIC, who led the research along with Ankit Mehta, assistant professor of clinical neurosurgery in the UIC College of Medicine.

“Graphene is the thinnest known material and is very sensitive to whatever happens on its surface,” Berry said. The nanomaterial is composed of a single layer of carbon atoms linked in a hexagonal chicken-wire pattern, and all the atoms share a cloud of electrons moving freely about the surface.
“The cell’s interface with graphene rearranges the charge distribution in graphene, which modifies the energy of atomic vibration as detected by Raman spectroscopy,” Berry said, referring to a powerful workhorse technique that is routinely used to study graphene.
The atomic vibration energy in graphene’s crystal lattice differs depending on whether it’s in contact with a cancer cell or a normal cell, Berry said, because the cancer cell’s hyperactivity leads to a higher negative charge on its surface and the release of more protons.

“The electric field around the cell pushes away electrons in graphene’s electron cloud,” he said, which changes the vibration energy of the carbon atoms. The change in vibration energy can be pinpointed by Raman mapping with a resolution of 300 nanometers, he said, allowing characterization of the activity of a single cell.

The study looked at cultured human brain cells, comparing normal astrocytes to their cancerous counterpart, the highly malignant brain tumour glioblastoma multiforme. The technique is now being studied in a mouse model of cancer, with results that are “very promising,” Berry said. Experiments with patient biopsies would be further down the road.
“Once a patient has brain tumour surgery, we could use this technique to see if the tumour relapses,” Berry said. “For this, we would need a cell sample we could interface with graphene and look to see if cancer cells are still present.”
The same technique may also work to differentiate between other types of cells or the activity of cells.

University of Illinois at Chicago news.uic.edu/first-use-of-graphene-to-detect-cancer-cells

New research suggests that GlycA, a newly identified blood marker, and C-reactive protein both independently predict major adverse cardiac events, including heart failure and death. Patients who have high levels of both biomarkers are at especially high risk.
 
That’s the finding of researchers from the Intermountain Medical Center Heart Institute in Salt Lake City, who teamed with LipoScience Laboratories to examine the markers to see if the two proteins, each previously linked to inflammation, are independent or related and whether either or both can identify patients at elevated risk for cardiovascular events.
 
The research grew out of an earlier analysis that paired plasma samples collected as part of the Intermountain Heart Collaborative Study with an assay developed by LipoScience that uses nuclear magnetic resonance technology to measure, among other things, the particle numbers in low-density lipoprotein (LDL) cholesterol, often called “bad” cholesterol. While scanning the plasma samples with the nuclear magnetic resonance technology, LipoScience had detected the GlycA and determined it to be a novel marker of inflammation.
 
Early research by the Intermountain Medical Center Heart Institute team showed that GlycA can predict heart attack risk; inflammation makes it more likely cholesterol plaques will rupture.
 
GlycA didn’t predict coronary artery disease nearly as well, said Brent Muhlestein, MD, co-director of cardiology research at Intermountain Medical Center and the study’s lead author.
 
C-reactive protein has already been shown to accurately predict adverse heart events and coronary artery disease, so the researchers wondered if the two are independent of each other, or if GLycA just offers another way to measure the effects of CRP.
 
Using the same plasma samples — part of more than 30,000 DNA samples collected over the course of 25 years by the Intermountain Medical Center Heart Institute— the researchers compared the value of both GlycA and CRP in predicting future heart attacks, strokes, or death.
 
For the study, nearly 3,000 patients undergoing coronary angiography were followed, two-thirds of them male. Sixty-five percent of them had been diagnosed with coronary artery disease, 42 percent with acute coronary syndrome, and 26 percent with diabetes.
 
“The correlation between GlycA and CRP was only modest,” said Dr. Muhlestein. “Some patients had a high level of one and a low level of the other and vice versa. But the two proteins independently predicted future risk, and if you had both, it was the worst scenario completely. It tells us that GlycA is perhaps something important.”
 
How important will be the focus for future research. Dr. Muhlestein said his research team would like to identify exactly what GlycA is, what it does, and the underlying physiology of its connection to inflammation.

Intermountain Medical Center Heart Institute
intermountainhealthcare.org/news/2017/03/people-who-have-high-levels-of-two-cardiac-markers-at-high-risk-of-heart-failure-and-death/

Normally, the heart contracts and relaxes to a regular beat. In atrial fibrillation, the upper chambers of the heart beat irregularly, which affects blood flow into the two lower large chambers. This can lead to stroke, heart failure and other heart-related complications.
Atrial fibrillation triggers were first identified in the pulmonary veins. Hence, the isolation of these veins has become one of the standard treatments for atrial fibrillation. Subsequently, other sites in the heart have been found to trigger and/or drive atrial fibrillation, including the superior vena cava (SVC). Notably, patients with arrhythmogenic SVC have long myocardial sleeves (circularly and longitudinally oriented bundles of heart cells) around the SVC and high amplitude electrical potentials within them.
Although these anatomical features in arrhythmogenic SVC all point to the possibility of genetic factors being involved in atrial fibrillation, this topic has remained largely unstudied. Furthermore, findings of genetic studies previously conducted in people of European ancestry could not be generalized and transferred to those of Asian ancestry.
This critical knowledge gap drove a team of researchers from Tokyo Medical and Dental University(TMDU) in Japan to study the clinical and genetic factors associated with atrial fibrillation in an Asian population. The team discovered two variants of single-nucleotide polymorphism (SNP), a variation in a single nucleotide that occurs at a specific position in the genome, which were significantly associated with SVC arrhythmogenicity.
“We found that among six variants identified in a previous genome-wide association study in Japanese patients, SNPs rs2634073 and rs6584555 were associated with SVC arrhythmogenicity,” said Yusuke Ebana, first author of the study.
“We also determined that SVC arrhythmogenicity was conditionally dependent on age, body mass index, and left ventricular ejection fraction,” Ebana added.
To arrive at that conclusion, the research team conducted a meta-analysis of clinical and genetic factors of 2,170 atrial fibrillation patients with and without SVC arrhythmogenicity across three major hospitals in Japan. Surface electrocardiogram and bipolar intracardiac electrograms were continuously monitored. Additionally, a mapping catheter was placed in the SVC to map the circumferential SVC region using computed tomography (CT) or transesophageal echocardiography as a reference. All the patients were followed-up at least every three months.
“The genes closest to the two SVC variants we found were PITX2 and NEURL1, with the former reported as a left-right determinant in cardiac development,” said Tetsushi Furukawa, senior author of the study. “We speculate that the suppression of NEURL1 in SVC patients with the risk genotype could be the cause of arrhythmogenic SVC leading to atrial fibrillation,” Furukawa added.

Tokyo Medical and Dental University (TMDU)
www.tmd.ac.jp/english/press-release/20171018/index.html

A research team has revealed the intrinsic gene expression patterns of glioblastoma (GBM) tumours, insights that could drive more effective treatments for GBM, the most common and deadly malignant primary brain tumours in adults.
Jackson Laboratory (JAX) Professor Roel Verhaak, Ph.D., is the senior author of a paper showing tumour gene expression patterns distinct from those of the surrounding immune cells, and characterizing the effects of chemotherapy and radiation treatments.
Verhaak was the first author of a 2010 paper that established four subclasses of GBM — proneural, mesenchymal, neural and classical — based on molecular markers found in patient tumours. That paper was widely influential in the glioblastoma research field, observes Verhaak. “However, these four subtypes have not translated into differential treatment strategies. Every glioblastoma patient receives essentially the same treatment. We hope that our latest work will improve understanding of how to optimally stratify patients, another step towards precision medicine and more targeted, effective treatments.”
The cells that surround a tumour are known as its microenvironment, usually consisting of immune cells, supporting cells and other normal cells. Tumours donated to tissue banks consist of a mixture of microenvironment cells and cancer cells.
In the new paper, the research team isolated the intrinsic gene expression of 364 GBM tumours and observed the impact of the standard cancer treatment regimens of temozolomide and radiation on that expression after subtracting out the effects of therapy on the tumour-associated non-cancer cells.
“By separating out the contributions of the microenvironment, we developed a much clearer picture of the ‘ecosystem’ of hundreds of tumours,” Verhaak says. “We determined what types of cells are in the microenvironment and what their contributions are, and also assessed how treatment affects the microenvironment as well as the tumour cells themselves.”
Through this approach, the researchers found that the molecular markers defining the neural subtype of GBM was actually ascribed by the presence of normal neural tissue in the tumour margin, thus not representing a true tumour subtype.
By studying gene expression patterns in glioblastomas after treatment, their analysis also revealed that the presence of macrophages correlates with poorer outcomes for GBM patients receiving radiation therapy, and that tumours with a relatively high number of point mutations have an increased number of positive T cells, indicating they could respond to a kind of immunotherapy known as checkpoint inhibitors.
The resulting gene expression datasets, which are publicly available to researchers, provide comprehensive profiles of glioblastoma characteristics to more accurately guide immunotherapy trials.

Jackson Laboratory
www.jax.org/news-and-insights/2017/july/glioblastoma-ecosystem-redefined