. Scientific Frontline: Biology
Showing posts with label Biology. Show all posts
Showing posts with label Biology. Show all posts

Friday, February 3, 2023

Signal transmission in the immune and nervous system using NEMO

Jörg Tatzelt, Konstanze Winklhofer and Simran Goel (from left) carried out the investigations together.
 Photo Credit: RUB, Marquard

Certain biomolecules in the form of active complexes temporarily accumulate in cells. This can be crucial for their functionality.

When transmitting signals within cells, many individual steps interlock. Among other things, proteins are provided with certain building blocks that switch their function on or off. In order to ensure fast signal transmission, these building blocks accumulate in the cell at certain locations for a limited time; Researchers speak of biomolecular condensates. A team around Prof. Dr. Konstanze Winklhofer, head of the Molecular Cell Biology Chair at the Ruhr University Bochum, has shown that the NEMO protein also forms condensates and which mechanism underlies NEMO condensate formation. The findings are important for understanding signal transmissions in the immune and nervous systems. The researchers report in the Life Science Alliance journal.

Thursday, February 2, 2023

HudsonAlpha scientists make new discovery linked to Alzheimer’s disease

Senior Scientist Lindsay Rizzardi, PhD
Photo Credit: Courtesy of HudsonAlpha
HudsonAlpha scientists identify transcription factors that may be involved in altered gene expression seen in Alzheimer’s disease

The human brain contains many types of cells that work together to ensure it functions properly. As arguably the most important organ in the human body, if something goes amiss with any brain cells or their connections to other cells, varying levels of neurological dysfunction can occur. Many neurological disorders arise from damage to brain cells due to a build-up of misfolded or aggregated proteins in the brain, like the tau protein and the amyloid-beta protein. Specific genes contain the instructions cells need for producing proteins. Changes to those genes can affect the protein production cycle, causing a change in the amount of protein produced or the conformation or quality of that protein. 

Alterations to the DNA code itself are only one of the ways that protein production can go awry. A class of proteins called transcription factors are a key component of how genes are expressed, causing a protein product to be made at higher or lower amounts than needed. These transcription factors act without changing the genetic makeup of the gene. These factors bind to DNA and recruit repressors or activators like RNA polymerase that coordinate DNA transcription and, ultimately, translation into a protein. 

Genes decide the willow warbler’s migration routes

A young willow warbler
Photo Credit: sharkolot

Since antiquity, humans have been fascinated by birds’ intercontinental migratory journeys. A new study from Lund University in Sweden shows that two areas in their genome decide whether a willow warbler flies across the Iberian Peninsula to western Africa, or across the Balkans to eastern and southern Africa.

Researchers have long known that the behavior that causes songbirds to migrate in a specific direction towards a remote winter location is something they are born with. The recent study aims to further understanding of the genetics behind this behavior. With the help of modern technology, and 20 years of research into the genetics of songbirds and their migration routes, the researchers managed to identify which parts of the genome that determine the songbirds’ routes.

“The songbirds’ direction of travel is determined by two areas in the genome. Genes from the southern subspecies take the bird towards the southwest, across the Iberian peninsula to their wintering grounds in western Africa. Genes belonging to the northern subspecies instead lead the willow warblers towards the southeast, over the Balkans, to locations in eastern and southern Africa,” says Staffan Bensch, biology researcher at Lund University.

Reading out RNA structures in real time

The fluorescent blinking of cyanine dye (Alexa Fluor 647, pink star) bound to RNA changes depending on the structure of the RNA. When the RNA is folded like a hairpin, the fluorescent blinking is fast, and when the RNA switches to a G-quadruplex, the blinking is slow
Illustration Credit: Akira Kitamura

A new microscopic technique allows for the real-time study of RNA G-quadruplexes in living cells, with implications for the fight against amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease and Stephen Hawking’s disease, is a neurodegenerative disease that results in the gradual loss of control over the muscles in the body. It is currently incurable and the cause of the disease is unknown in over 90% of all cases — although both genetic and environmental factors are believed to be involved.

The research groups of Dr. Akira Kitamura at the Faculty of Advanced Life Science, Hokkaido University, and Prof. Jerker Widengren at the KTH Royal Institute of Technology, Sweden, have developed a novel technique that is able to detect a characteristic structure of RNA in real time in live cells. The technique, which is based on fluorescence-microscopic spectroscopy, was published in the journal Nucleic Acids Research.

Avoiding burnout of white blood cells

The immune system (T cell) attacks a human tumor cell.
Image Credit: M. Oeggerli (Micronaut 2019), Marcel Philipp Trefny, and Prof. Alfred Zippelius, Translational Oncology, University Hospital Basel, supported by Pathology University Hospital Basel, and C-CINA, Biozentrum, University of Basel

A research group at the University of Basel has identified a gene that drives T lymphocytes to exhaustion. This finding opens up new approaches for more effective immunotherapies.

A tough battle requires endurance. This is also true for white blood cells as they tackle cancer – or more specifically for T lymphocytes or T cells, a group of white blood cells involved in the immune system’s fight against cancer cells. However, T cells can become exhausted during this fight.

Researchers from the Department of Biomedicine at the University of Basel and University Hospital Basel recently identified a gene that seems to contribute to this exhaustion. The findings of their research project, which was funded by the Swiss National Science Foundation, were published in the journal Nature Communications.

Wednesday, February 1, 2023

FAT4 Gene Mutations Cause Many Abnormalities in the Lymphatic System

A mutation in a gene can disrupt the lymphatic system
Photo Credit: Sangharsh Lohakare

Defects in this gene cause everything in the body to swell - even the brain

Mutations in the FAT4 gene can cause Hennekam syndrome, which is characterized by various abnormalities of the lymphatic system. An international team of scientists from Russia (Ural Federal University), Afghanistan, Pakistan and China used molecular dynamic modeling to demonstrate the pathogenicity of the identified mutations. The data obtained will help to determine the predisposition to diseases associated with FAT4 gene activation. The study was supported by the Ministry of Science and Higher Education of the Russian Federation in the framework of the Priority 2030 program and published in the journal Informatics in Medicine Unlocked.

"Hennekam syndrome is a relatively rare (less than 1,000 cases have been reported worldwide) inherited disorder caused by mutations in three different genes - FAT4, ADAMTS3, CCBE1. Abnormalities in the lymphatic system cause everything in the body - including the brain - to swell. This is due to impaired lymphatic transport and, as a result, a large accumulation of protein-rich fluid in the intercellular space. As a result, any affected organ can increase in volume. Signs of this syndrome can also be developmental disorders, strange body deformities, a flat face with swollen eyelids," says Mikhail Bolkov, Senior Researcher at the Department of Immunochemistry at the Ural Federal University and the Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences.

Tuesday, January 31, 2023

Understanding plants can boost wildland-fire modeling in uncertain future

How a fire burns and whether the vegetation survives or dies depend on how the live fuels — plants — use water and carbon. New research creates a framework for bringing those dynamics into wildland-fire models to more accurately predict wildfire and prescribed-burn behavior and resulting effects.
Photo Credit: Pixabay

A new conceptual framework for incorporating the way plants use carbon and water, or plant dynamics, into fine-scale computer models of wildland fire provides a critical first step toward improved global fire forecasting.

“Understanding the influences of vegetation structure and physiology on wildland fire is crucial to accurately predicting the behavior of fire and its effects,” said L. Turin Dickman, a plant ecophysiologist at Los Alamos National Laboratory. Dickman is corresponding author of a paper on plants and fire modeling in the journal New Phytologist. “Our research can be used to improve models that fire managers need to navigate an uncertain future.”

How to make hydrogels more injectable

MIT and Harvard researchers have developed computational models that can predict the properties of materials made from squishy hydrogel blocks.
Image Credit: Courtesy of the researchers

Gel-like materials that can be injected into the body hold great potential to heal injured tissues or manufacture entirely new tissues. Many researchers are working to develop these hydrogels for biomedical uses, but so far very few have made it into the clinic.

To help guide in the development of such materials, which are made from microscale building blocks akin to squishy LEGOs, MIT and Harvard University researchers have created a set of computational models to predict the material’s structure, mechanical properties, and functional performance outcomes. The researchers hope that their new framework could make it easier to design materials that can be injected for different types of applications, which until now has been mainly a trial-and-error process.

“It’s really exciting from a material standpoint and from a clinical application standpoint,” says Ellen Roche, an associate professor of mechanical engineering and a member of the Institute for Medical Engineering and Science at MIT. “More broadly, it’s a nice example of taking lab-based data and synthesizing it into something usable that can give you predictive guidelines that could be applied to things beyond these hydrogels.”

Groundbreaking Biomaterial Heals Tissues From the Inside Out

The biomaterial is based on a hydrogel that Christman's lab developed.
Photo Credit: University of California, San Diego

A new biomaterial that can be injected intravenously, reduces inflammation in tissue and promotes cell and tissue repair. The biomaterial was tested and proven effective in treating tissue damage caused by heart attacks in both rodent and large animal models. Researchers also provided proof of concept in a rodent model that the biomaterial could be beneficial to patients with traumatic brain injury and pulmonary arterial hypertension.

“This biomaterial allows for treating damaged tissue from the inside out,” said Karen Christman, a professor of bioengineering at the University of California San Diego, and the lead researcher on the team that developed the material. “It’s a new approach to regenerative engineering.”

A study on the safety and efficacy of the biomaterial in human subjects could start within one to two years, Christman added. The team, which brings together bioengineers and physicians, presented their findings in Nature Biomedical Engineering.

Focused ultrasound mediated liquid biopsy in a tauopathy mouse model

Hong Chen and her collaborators found that using focused-ultrasound-mediated liquid biopsy in a mouse model released more tau proteins and another biomarker for neurodegenerative disorders into the blood than without the intervention. This noninvasive method could facilitate diagnosis of neurodegenerative disorders.
Illustration Credit: Chen lab

Several progressive neurodegenerative disorders, including Alzheimer’s disease, are defined by having tau proteins in the brain. Researchers are seeking to identify the mechanisms behind these tau proteins to develop treatments, however, their efforts to detect biomarkers in blood has been hampered by the protective blood-brain barrier.

At Washington University in St. Louis, new research from the lab of Hong Chen, associate professor of biomedical engineering in the McKelvey School of Engineering and of radiation oncology in the School of Medicine, and collaborators found that using focused-ultrasound-mediated liquid biopsy in a mouse model released more tau proteins and another biomarker into the blood than without the intervention. This noninvasive method could facilitate diagnosis of neurodegenerative disorders, the researchers said.

The method, known as sonobiopsy, uses focused ultrasound to target a precise location in the brain. Once located, the researchers inject microbubbles into the blood that travel to the ultrasound-targeted tissue and pulsate, which safely opens the blood-brain barrier. The temporary openings allow biomarkers, such as tau proteins and neurofilament light chain protein (NfL), both indicative of neurodegenerative disorders, to pass through the blood-brain barrier and release into the blood.

Carnivorous plants change their diet: traps as toilet bowls

Pitcher plants of the genus Nepenthes on the island of Borneo.
Photo Credit: Antony van der Ent.

In tropical mountains, the number of insects declines with increasing altitude. This intensifies in high altitudes competition between plant species that specialize in catching insects as an important source of nutrients. How creatively some of these plant species have reacted to this situation is shown by an international research team with Prof. Dr. Gerhard Gebauer from the University of Bayreuth in the "Annals of Botany". In mountain regions on Borneo, some species of the pitcher plant Nepenthes have changed their diet: With their traps, which originally served to capture insects, they catch the excrement of mammals and are thus even better supplied with nutrients than before.

Monday, January 30, 2023

Short-term bang of fireworks has long-term impact on wildlife

Photo Credit: Jill Wellington

Popular fireworks should be replaced with cleaner drone and laser light shows to avoid the “highly damaging” impact on wildlife, domestic pets and the broader environment, new Curtin-led research has found.

The new research, published in Pacific Conservation Biology, examined the environmental toll of firework displays by reviewing the ecological effects of Diwali festivities in India, Fourth of July celebrations across the United States of America, and other events in New Zealand and parts of Europe.

Examples included fireworks in Spanish festivals impacting the breeding success of House Sparrows, July firework displays being implicated in the decline of Brandt’s Cormorant colonies in California, and South American sea lions changing their behavior during breeding season as a result of New Year’s fireworks in Chile.

Lead author Associate Professor Bill Bateman, from Curtin’s School of Molecular and Life Sciences, said fireworks remained globally popular despite the overwhelming evidence that they negatively impacted wildlife, domestic animals and the environment.

Mating causes ‘jet lag’ in female fruit flies, changing behavior

A seminal fluid protein transferred from male to female fruit flies during mating changes the expression of genes related to the fly’s circadian clock, Cornell research has found.
Photo Credit: Erik Karits

A seminal fluid protein transferred from male to female fruit flies during mating changes the expression of genes related to the fly’s circadian clock, an innovative technique has revealed.

The finding, published in the Proceedings of the National Academy of Sciences, could help explain how this protein, called sex peptide, alters the female’s behavior.

Post-mating, sex peptide has been shown to elicit increased egg-laying, aggression, activity and feeding, while reducing sleep and interest in mating in previously unmated females.

“Flies like to eat at certain times of day,” said Mariana Wolfner ’74, professor of molecular biology and genetics and a Stephen H. Weiss Presidential Fellow in the College of Arts and Sciences, and one of the paper’s senior authors. “They sleep at certain times, and the circadian clock machinery controls when flies are likely to do these things.

Saturday, January 28, 2023

Ancestral variation guides future environmental adaptations

A sea campion in its natural habitat on the coast.
Photo Credit: Bangor University

The humble sea campion flower can show us how species adapt.

The speed of environmental change is very challenging for wild organisms. When exposed to a new environment individual plants and animals can potentially adjust their biology to better cope with new pressures they are exposed to - this is known as phenotypic plasticity.

Plasticity is likely to be important in the early stages of colonizing new places or when exposed to toxic substances in the environment. New research published in Nature Ecology & Evolution, shows that early plasticity can influence the ability to subsequently evolve genetic adaptations to conquer new habitats.

Friday, January 27, 2023

Machine learning identifies drugs that could potentially help smokers quit

Penn State College of Medicine researchers helped identify eight medications that may be repurposed to help people quit smoking. A team of more than 70 researchers contributed to the analysis of genetic and smoking behavior data from more than 1.3 million people.
Image Credit: Scientific Frontline

Medications like dextromethorphan, used to treat coughs caused by cold and flu, could potentially be repurposed to help people quit smoking cigarettes, according to a study by Penn State College of Medicine and University of Minnesota researchers. They developed a novel machine learning method, where computer programs analyze data sets for patterns and trends, to identify the drugs and said that some of them are already being tested in clinical trials.

Cigarette smoking is risk factor for cardiovascular disease, cancer and respiratory diseases and accounts for nearly half a million deaths in the United States each year. While smoking behaviors can be learned and unlearned, genetics also plays a role in a person’s risk for engaging in those behaviors. The researchers found in a prior study that people with certain genes are more likely to become addicted to tobacco.

Using genetic data from more than 1.3 million people, Dajiang Liu, Ph.D., professor of public health sciences, and of biochemistry and molecular biology and Bibo Jiang, Ph.D., assistant professor of public health sciences, co-led a large multi-institution study that used machine learning to study these large data sets — which include specific data about a person’s genetics and their self-reported smoking behaviors.

Thursday, January 26, 2023

Rapid plant evolution may make coastal regions more susceptible to flooding and sea level rise

Brady Stiller, University of Notre Dame
Photo Credit: Courtesy University of Notre Dame

Evolution has occurred more rapidly than previously thought in the Chesapeake Bay wetlands, which may decrease the chance that coastal marshes can withstand future sea level rise, researchers at the University of Notre Dame and collaborators demonstrated in a recent publication in Science.

 Jason McLachlan, an associate professor in the Department of Biological Sciences, evaluated the role evolution plays in ecosystems in the Chesapeake Bay by studying a type of grass-like plant, Schoenoplectus americanus, also called chairmaker’s bulrush. The research team used a combination of historical seeds found in core sediment samples, modern plants, and computational models to demonstrate that “resurrected” plants were allocating more resources in their roots below ground, allowing them to store carbon more quickly than modern plants.

Supplementation with amino acid serine eases neuropathy in diabetic mice

From left: Michal Handzlik and Christian Metallo
Photo Credit: Salk Institute

Approximately half of people with type 1 or type 2 diabetes experience peripheral neuropathy—weakness, numbness, and pain, primarily in the hands and feet. The condition occurs when high levels of sugar circulating in the blood damage peripheral nerves. Now, working with mice, Salk Institute researchers, in collaboration with the University of California San Diego, have identified another factor contributing to diabetes-associated peripheral neuropathy: altered amino acid metabolism.

The study, published in Nature, adds to growing evidence that some often-underappreciated, “non-essential” amino acids play important roles in the nervous system. The findings may provide a new way to identify people at high risk for peripheral neuropathy, as well as a potential treatment option. The team included UC San Diego bioengineering professor Prashant Mali, microbiome expert professor Rob Knight and pathologist Nigel A. Calcutt.

“We were surprised that dialing up and down a non-essential amino acid had such a profound effect on metabolism and diabetic complications,” says senior author Christian Metallo, a professor in Salk’s Molecular and Cell Biology Laboratory. “It just goes to show that what we think of as dogma can change under different circumstances, such as in disease conditions.”

Evolutionary Tuning of a Cellular “Powerhouse”

Profiles of the subunits of individual complexes (top) and overall representation of all around 5200 protein signals in MitCOM.
Image Source | Credit: AG Fackler/Pfanner/Becker

Mitochondria are membrane-enclosed structures found in all cells of higher organisms, where they produce most of the necessary energy (“powerhouses of the cell”). In addition, these organelles serve important functions in the synthesis and degradation of certain biomolecules as well as in numerous intercellular signaling processes. In close collaboration, a team of researchers led by Prof. Dr. Nikolaus Pfanner and Prof. Dr. Bernd Fakler from the University of Freiburg Institutes of Biochemistry and Physiology, respectively, and by Prof. Dr. Thomas Becker from the Institute of Biochemistry at the University of Bonn has now applied a newly developed analytical method to comprehensively map the structural organization of proteins in mitochondria. The results provide initial insight into the structure and organization of the mitochondrial proteins in protein machineries of varying complexity, thus laying the foundation for future studies of new protein functions and structures. This study was published in the journal Nature.

Comprehensive picture of the composition of protein complexes indispensable

Mechanical forces in the nervous system play a corrective role

The researchers visualized the forces acting on dendrites during pruning by measuring their lengths (blue/red) and the angles at dendritic branchpoints: A) before, B) after dendrite severing,
Image Credit: WWU - Rumpf Lab

Researchers at Münster University show in the fruit fly how mechanical tearing cuts neural connections

Nerve cells communicate with one another via long processes known as axons and dendrites, or, more generally, neurites. During development, these processes first grow and form connections with other cells, for example synapses with other nerve cells. Any neurites which are not properly linked, or are no longer needed, are removed by a corrective mechanism known as “pruning”. Such pruning processes can appear drastic, and neurites sometimes seem to be severed directly from the nerve cell. Researchers headed by Dr. Sebastian Rumpf from the Institute of Neuro- and Behavioral Biology at Münster University has now found the mechanism of neurite severing. In a study published in the Journal of Cell Biology, the team show that in sensory nerve cells of the fruit fly Drosophila melanogaster, pruning occurs through mechanical tearing.

Power of cancer drugs may see boost by targeting newly identified pathway

Proteins labeled with colored tags fill the main compartment — but not the nuclei (blue) — of human cervical cancer cells. Green cells contain the protein TRPV2, red cells contain STING, and yellow and orange cells contain a mixture of both. The proteins are part of a newly discovered DNA-protection pathway that potentially could be targeted to improve cancer therapies, according to researchers at Washington University School of Medicine in St. Louis.
Image Credit: Lingzhen Kong

Cells zealously protect the integrity of their genomes, because damage can lead to cancer or cell death. The genome — a cell’s complete set of DNA — is most vulnerable while it is being duplicated before a cell divides. Cancer cells constantly are dividing, so their genomes are constantly in jeopardy.

Researchers at Washington University School of Medicine in St. Louis has identified a previously unknown signaling pathway cells use to protect their DNA while it is being copied. The findings, published in the journal Molecular Cell, suggest that targeting this pathway potentially could boost the potency of cancer therapeutics.

“A cell that can’t protect its genome is going to die,” said senior author Zhongsheng You, a professor of cell biology and physiology. “This entire pathway we found exists to protect the genome so the cell can survive in the face of replication stress. By combining inhibitors of this pathway with chemotherapy drugs that target the DNA replication process, we potentially could make such drugs more effective.”

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