. Scientific Frontline

Monday, June 12, 2023

Study brings new understanding of multiple myeloma evolution

Elisabet Manasanch, M.D. | Linghua Wang, M.D., Ph.D.
Photo Credit: Courtesy of University of Texas MD Anderson Cancer Center

A new study by researchers at The University of Texas MD Anderson Cancer Center highlights novel insights into the evolution of multiple myeloma from precursor disease, which may help better identify patients likely to progress and develop new interventions.

Published today in Cancer Cell, the study integrates paired single-cell RNA sequencing and B cell receptor sequencing from 64 patients with multiple myeloma or precursor disease. The study achieved several notable milestones in the effort to better understand this evolutionary process and is believed to be the largest cohort of myeloma precursor patient samples analyzed at single-cell resolution.

How multiple myeloma, a deadly and incurable cancer of plasma cells in the bone marrow, evolves from precursor conditions like monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma remains largely a mystery. To help solve that mystery, this study was designed by Elisabet Manasanch, M.D., associate professor of Lymphoma/Myeloma, in collaboration with Linghua Wang, M.D., Ph.D., associate professor of Genomic Medicine, and Minghao Dang, Ph.D., postdoctoral fellow in the Wang lab.

“This research is a big step towards understanding the evolutionary roadmap that leads to myeloma,” Wang said. “Additionally, there is a significant clinical unmet need to find and validate novel biomarkers to identify patients at high-risk of progression who would benefit the most from early treatment interventions.”

Climate Change: Rising Rainfall, not Temperatures, Threaten Giraffe Survival

Masai giraffes in Tanzania have lower survival during seasons of heavier rainfall, which is predicted to increase under climate change.
Photo Credit: Mariola Grobelska

Giraffes in the East African savannahs are adapting surprisingly well to the rising temperatures caused by climate change. However, they are threatened by increasingly heavy rainfall, as researchers from the University of Zurich and Pennsylvania State University show.

Climate change is expected to cause widespread declines in wildlife populations worldwide. Yet, little was previously known about the combined climate and human effects on the survival rates not only of giraffes, but of any large African herbivore species. Now researchers from the University of Zurich and Pennsylvania State University have concluded a decade-long study – the largest to date – of a giraffe population in the Tarangire region of Tanzania. The study area spanned more than a thousand square kilometers, including areas inside and outside protected areas. Contrary to expectations, higher temperatures were found to positively affect adult giraffe survival, while rainier wet seasons negatively impacted adult and calf survival.

Cholera bacteria form aggressive biofilm to kill immune cells

The cholera-pathogen Vibrio cholerae (blue) forms an aggressive biofilm on the surface of immune cells (red).
Video Credit: University of Basel, Biozentrum

Scientific Frontline: Extended "At a Glance" Summary: Aggressive Biofilms in Vibrio cholerae

The Core Concept: Vibrio cholerae, the pathogen responsible for cholera, utilizes an aggressive, mesh-like biofilm on the surface of host immune cells to trigger cell death. This mechanism represents a shift from the traditional understanding of biofilms as strictly defensive structures.

Key Distinction/Mechanism: Unlike typical biofilms composed of a slimy matrix of sugars and proteins, this specific structure consists of intertwined bacterial appendages that encase macrophages. The bacteria secrete hemolysin, a toxin that creates pores in the macrophage membrane, directly resulting in cell lysis.

Major Frameworks/Components:

  • Bacterial Colonization: Vibrio cholerae uses "feeler" appendages to anchor onto the surface of macrophages.
  • Extracellular Meshwork: Bacteria divide and entwine these feelers to create a lethal cage around the immune cell.
  • Hemolysin Activity: This specific toxin is the primary agent identified in breaching the macrophage's protective membrane.
  • Human Intestinal Organoid Model: Used to replicate the infection environment, proving that the pathogen forms these lethal biofilms after disrupting the intestinal barrier.

Gentle cleansers kill viruses as effectively as harsh soaps

Photo Credit: Maria Lin Kim

Gentle cleansers are just as effective in killing viruses – including coronavirus – as harsh soaps, according to a new study from scientists at the University of Sheffield 

Healthcare professionals often substitute alcohol-based hand sanitizers and harsh soaps for skin-friendly cleansers in order to treat or prevent irritant contact dermatitis, which develops when chemical or physical agents damage the skin surface faster than the skin can repair

Incidence and severity of irritant contact dermatitis increased from 20 per cent to 80 per cent amongst healthcare professionals during the Covid-19 pandemic

Researchers also found non-enveloped viruses such as norovirus were resistant to all hand wash products tested, and were only killed with bleach disinfectants, which aren’t a feasible option for washing hands 

Gentle cleansers are just as effective in killing viruses – including coronavirus – as harsh soaps, a new study by University of Sheffield experts has found.

Twenty species of sea lettuce found along the coasts

Sea lettuce, which is a type of green alga, grows along the coasts and is interesting as potential food source. A new survey shows that there are 20 different species of sea lettuce along the Swedish coast.
Photo Credit: Sophie Steinhagen

The number of species of the green alga sea lettuce in the Baltic Sea region and Skagerak and is much larger than what was previously known. Researchers at the University of Gothenburg have surveyed 10,000 kilometers of coast and found twenty species of sea lettuce.

Green macroalgae of the genus Ulva, also known as sea lettuce, are almost ubiquitous in the wider Baltic Sea region and can be found from the Atlantic waters all the way up to the Bay of Bothnia in the Baltic Sea. Sea lettuce reproduces easily and grows quickly, which makes it interesting for an expanding aquaculture industry. Research is ongoing both in Sweden and abroad for utilizing sea lettuce in the food industry and for different biochemical applications.

There are multiple species, but until now it has not been known how many there are and previously only a handful had been identified.

Our visual perception is more rational than we think

Our visual perception adapts flexibly and unconsciously to the decision context when it’s to our advantage.
Photo Credit: Colin Lloyd

Our visual perception depends more strongly on the utility of information than previously thought. This has been demonstrated in a series of experiments conducted by researchers at the Neuroscience Center Zurich. Cognitive biases can begin at the retina.

Are our senses there to provide us with the most complete representation of the world, or do they serve our survival? For a long time, the former was the dominant view in neuroscience. “Was” is the operative word here. In the last 50 years, psychologists such as Nobel Prize winners Daniel Kahnemann and Amos Tversky have shown that human perception is often anything but complete and instead is highly selective.

Experiments have now verified that there is a whole list of examples of cognitive biases. One of the most important is confirmation bias: we often process new information in a way that confirms our beliefs and expectations.

But up until now, researchers haven’t been able to fully explain under what conditions these distortions come into play and when exactly in the perceptual process they begin. A study by researchers led by University of Zurich Professor Todd Hare and ETH Professor Rafael Polania, recently published in the journal Nature Human Behavior, now shows that the brain already adjusts the visual perception of things on the retina when it is in our interest to do so. Or, to put it another way, we unconsciously see things distorted when it comes to our survival, well-being, or other interests.

Sunday, June 11, 2023

Study examines role of metabolites in disease treatment

Phillip Owens, PhD
Photo Credit: Andrew Higley/UC Marketing + Brand

Each year, about 200,000 people in the United States are diagnosed with a bulge in the lower part of the aorta, the main artery in the body, called an abdominal aortic aneurysm (AAA).

New research from the University of Cincinnati examines the role a particular metabolite plays in the development of AAA and could lead to the first treatment of the condition.

The research was published in the journal Circulation.

“We started the study by examining whether AAA patients themselves had an increase in trimethylamine N-oxide (TMAO).  We examined an American and Swedish cohort with 354 human samples, and we compared those AAA patients to 1,775 control subjects,” says Phillip Owens, PhD, co-first author of the study along with Tyler Benson, PhD, both of the Division of Cardiovascular Health and Disease in the UC College of Medicine. “We started going into animal models after that, looking at what happens when we feed a high choline diet which leads to higher production of TMAO.”

Choline, found in a variety of foods with the richest sources being meat, fish, poultry, dairy and eggs, is processed into the organic compound TMAO when meat is digested by the bacteria in the gut.

Study reveals how treatment-resistant prostate cancer provides its own hormonal fuel

A new study from Washington University School of Medicine in St. Louis shows how prostate cancer creates its own hormonal fuel supply in response to anti-testosterone therapy. The study further suggests a strategy to block this process and potentially improve therapy options for treatment-resistant prostate cancer. Shown is a thin slice of a human prostate tumor. The dark staining throughout reveals the presence of histone acetylation promoting cholesterol production. Cholesterol is required to make testosterone, which fuels tumor growth.
Image Credit: Nupam Mahajan/School of Medicine

A new study in mice, led by researchers at Washington University School of Medicine in St. Louis, explains how prostate cancer senses a drop in testosterone levels due to common anti-hormone therapy and then begins making cholesterol — a necessary precursor to testosterone — to generate its own testosterone to fuel tumor growth. The study also points to a possible drug combination that may stop the cancer from feeding its own growth.

Healthy prostate cells do not produce testosterone, so the research provides long-sought answers to questions about how prostate cancer cells adapt to testosterone-deprivation therapy, a common therapeutic option, by developing an ability to supply their own hormonal fuel. Further, the research reveals that treating these aggressive prostate tumors with inhibitors that block aspects of the hormonal fuel supply chain slows tumor growth in mice. These findings suggest a novel treatment strategy for prostate cancer that has become resistant to the common anti-testosterone therapy abiraterone.

The study also may help explain why Black men are at higher risk of developing prostate cancer and tend to develop more aggressive forms of the cancer than white men of European ancestry.

Women feel the pain of losses more than men when faced with risky choices

Evaluating risk - are women more risk averse than men?
Photo Credit: Oleksandr Pidvalnyi

Women are less willing to take risks than men because they are more sensitive to the pain of any losses, they might incur than any gains they might make, new research from the University of Bath School of Management shows.

Published in the British Psychological Society’s British Journal of Psychology, the study – “Gender differences in optimism, loss aversion and attitudes toward risk" - also finds that men are ‘significantly’ more optimistic than women, making them more willing to take risks.

Researcher Dr Chris Dawson, associate professor in business economics at the University of Bath School of Management, said the findings were significant and could help explain sex-specific outcomes in different employment sectors, and in financial markets.

‘It is widely acknowledged that men, across many domains, take more risks than women. These differences in how the sexes view risk can have significant effects,” Dr Dawson says.

‘For instance, differences between the sexes in risk taking can explain why women are less likely to be entrepreneurs, are underrepresented in high-paying jobs and upper management, and less likely to invest their wealth in equities markets than men. Despite these important implications, we still know very little about why women take fewer risks than men.

Modified lactic acid bacteria provide faster wound healing

The lactic acid bacteria, or Limosilactobacillus reuteri, is genetically modified to produce the chemokine CXCL12 (ILP100-Topical). 
Photo Credit: Martina Sjaunja

Complicated, hard-to-heal wounds are a growing medical problem and there are currently only two drugs approved with proven efficacy. In a new study on humans, researchers at Uppsala University show that treatment with a specific type of modified lactic acid bacteria works well and has a positive effect on the healing of wounds.

In several controlled preclinical models, the research team behind the new study has previously demonstrated accelerated wound healing after topical treatment (treatment on the skin) using lactic acid bacteria, or Limosilactobacillus reuteri, genetically modified to produce the chemokine CXCL12 (ILP100-Topical).

The researchers can now show data from the first clinical study on humans, in which the main objective was to establish safety and tolerability. Other objectives were to see clinical and biological effects on wound healing using traditionally accepted methods, as well as more exploratory and traceable measurements.

36 healthy volunteers were included in the study with a total of 240 induced wounds studied. The study’s design and methodology are described in more detail below.

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