How Breast Cancer Arises

Breast cancer: polyploid giant cancer cell (PGCC)
Image Credit: National Cancer Institute

In what may turn out to be a long-missing piece in the puzzle of breast cancer, Harvard Medical School researchers have identified the molecular sparkplug that ignites cases of the disease currently unexplained by the classical model of breast-cancer development.

A report on the team’s work is published May 17 in Nature.

“We have identified what we believe is the original molecular trigger that initiates a cascade culminating in breast tumor development in a subset of breast cancers that are driven by estrogen,” said study senior investigator Peter Park, professor of Biomedical Informatics in the Blavatnik Institute at HMS.

The researchers said as many as one-third of breast cancer cases may arise through the newly identified mechanism.

The study also shows that the sex hormone estrogen is the culprit behind this molecular dysfunction because it directly alters a cell’s DNA.

Most, though not all, breast cancers are fueled by hormonal fluctuations. The prevailing view of estrogen’s role in breast cancer is that it acts as a catalyst for cancer growth because it stimulates the division and proliferation of breast tissue, a process that carries the risk for cancer-causing mutations. The new work, however, shows that estrogen causes mischief in a far more direct manner.

Genetic research offers new perspective on the early evolution of animals

Some representatives of comb jellies - (a) Beroe ovata, (b) Euplokamis sp., (c) Nepheloctena sp., (d) Bathocyroe fosteri, (e) Mnemiopsis leidyi, and (f) Ocyropsis sp.
Image Credits: a, b, e, f: Joseph F. Ryan; c: R. Griswold, National Oceanic and Atmospheric Administration; d: Marsh Youngbluth, National Oceanic and Atmospheric Administration.

Mapping gene linkages provides clear-cut evidence for comb jellies as sibling group to all other animals

A study published by University of Vienna and MBARI researchers and their collaborators today in Nature provides new insights into one of the earliest points in animal evolution that happened more than 700 million years ago.

For more than a century, scientists have been working to understand the pivotal moment when an ancient organism gave rise to the diverse array of animals in the world today. As technology and science have advanced, scientists have investigated two alternative hypotheses for which animals—sponges or comb jellies, also known as ctenophores—were most distantly related to all other animals. Identifying this outlier—known as the sibling group—has long eluded scientists.

In the new study, a team of researchers from MBARI, the University of Vienna, the University of California, Berkeley, and the University of California, Santa Cruz, mapped sets of genes that are always found together on a single chromosome, in everything from humans and hamsters to crabs and corals, to provide clear evidence that comb jellies are the sibling group to all other animals. Understanding the relationships among animals will help shape our thinking about how key features of animal anatomy, such as the nervous system or digestive tract, have evolved over time.

Scales or feathers? It all comes down to a few genes

From left to right: Rory Cooper, a post-doctoral researcher in Michel Milinkovitch’s laboratory, and Michel Milinkovitch, professor in the Department of Genetics and Evolution at the Faculty of Science of the UNIGE. 
Photo Credit: UNIGE

Scales, spines, feathers and hair are examples of vertebrate skin appendages, which constitute a remarkably diverse group of micro-organs. Despite their natural multitude of forms, these appendages share early developmental processes at the embryonic stage. Two researchers from the University of Geneva (UNIGE) have discovered how to permanently transform the scales that normally cover the feet of chickens into feathers, by specifically modifying the expression of certain genes. These results, published in the journal Science Advances, open new perspectives for studying mechanisms that have enabled radical evolutionary transitions in form among species.

The skin of terrestrial vertebrates is adorned with diverse keratinized appendages, such as hair, feathers, and scales. Despite the diversity of forms within and among species, the embryonic development of skin appendages typically begins in a very similar way. Indeed, all of these structures develop from cells that produce a localized thickening on the skin surface and express particular genes. One of these genes, called Sonic hedgehog (Shh), controls a signaling pathway - a communication system that allows the transmission of messages within and between cells. Shh signaling is involved in the development of diverse structures, including the neural tube, limb buds and skin appendages.

Study Finds Carrying Pollen Heats Up Bumble Bees, Raising New Climate Change Questions

Photo Credit: Malia Naumchik.

A new study from North Carolina State University finds carrying pollen is a workout that significantly increases the body temperature of bumble bees. This new understanding of active bumble bee body temperatures raises questions about how these species will be impacted by a warmer world due to climate change.

Spend a bit of time at a nearby flower patch and you will spot a fuzzy bumble bee with yellow bumps on her back legs. These yellow bumps are solid packets of pollen that have been carefully collected during the bees’ foraging trip for transport back to their nests. And while bees may seem to move from flower to flower with ease, these pollen packets can weigh up to a third of their body weight. This new study found that – after accounting for environmental temperature and body size – the body temperature of bumble bees carrying pollen was significantly hotter than the temperature of bees that were empty-legged.

Specifically, the researchers found that bee body temperatures rose 0.07°C for every milligram of pollen that they carried, with fully laden bees being 2°C warmer than unladen bees.

Mystery of important blood pressure drugs solved

Prof. Daniel Fuster, M.D. Department for BioMedical Research (DBMR) of the University of Bern and Department of Nephrology and Hypertension, Inselspital, Bern University Hospital.
Photo Credit: Courtesy of Daniel Fuster

Diuretic drugs from the thiazide group have been used for 60 years to treat high blood pressure. But they also increase the risk of developing diabetes. Researchers at the University of Bern and Inselspital have now pinpointed the cause of this side effect and in the process also gained new insights into the development of diabetes.

High blood pressure is a global health problem. In Switzerland, one in two people over the age of 65 has high blood pressure. This has been shown to increase the risk of serious secondary diseases such as dementia, stroke, cerebral hemorrhage, heart attack, and kidney failure. According to estimates by the World Health Organization, for example, around 54 percent of strokes are a direct result of high blood pressure. "Accordingly, there is a great need for effective, and also inexpensive and widely available antihypertensive drugs - particularly in light of our aging society," explains Prof. Daniel Fuster, M.D., from the Department for BioMedical Research at the University of Bern (DBMR) and Head Physician at the Department of Nephrology and Hypertension at Inselspital, Bern University Hospital.

UC Irvine research team identifies glycosylation enzyme critical in brain formation

Lisa Flanagan, professor of neurology
Photo Credit: Courtesy of University of California, Irvine

The MGAT5 glycosylation enzyme plays a crucial role in brain development, according to a study by University of California, Irvine researchers, a discovery that may contribute to new therapeutic purposes for neural stem cells.

Neurons, astrocytes and oligodendrocytes are the final mature cells of the brain and spinal cord formed by neural stem cells. Each has distinct and key functions. Neurons transmit signals, astrocytes help modify those signals, and oligodendrocytes keep the signals from degrading. When any cells make proteins or fats that end up on the cell surface, they often add small sugar molecules. The team tested whether this internal process – called glycosylation – affects how neural stem cells form mature brain cells.

The study, published in the journal Stem Cell Reports, found that during glycosylation, the MGAT5 enzyme significantly regulates the formation of neurons and astrocytes from neural stem cells. Neural stem cells that don’t have MGAT5 make more neurons and fewer astrocytes during the very early stages of brain development, altering its structure. These changes may contribute to later aberrant behavior patterns, including abnormal social interactions and repetitive actions.

Contraception, evolution and the genetic maintenance of same-sex sexual behavior

A gene is a basic unit of heredity. It is a segment of DNA that codes for a specific protein or RNA molecule. Genes are responsible for passing on traits from parents to their offspring. 
Image Credit: THAVIS 3D

Evolution depends on genes being passed down through the generations via reproduction, and same-sex sexual behavior does not result in offspring.

So, why haven’t the many genes associated with same-sex sexual behavior, known as SSB-associated genes, been purged from the human genome over time? It’s a question that has perplexed scientists for decades, one that’s explored anew in a Proceedings of the National Academy of Sciences study by two University of Michigan biologists.

One possible explanation for the persistence of SSB-associated genes is that they have more than one function, a concept called pleiotropy. Perhaps SSB-associated genes are advantageous to heterosexuals in some way, helping them to have more children.

Support for this idea includes a 2021 Nature Human Behaviour study by University of Queensland biologist Brendan Zietsch and colleagues. They presented evidence that heterosexuals carrying SSB-associated genes have more sexual partners than those not carrying the genes. This could confer an evolutionary advantage, because more sexual partners could translate into more children, according to the Zietsch et al. study.

Scientists use X-ray beams to determine role of zinc in development of ovarian follicles

Elemental map of zinc measured by synchrotron-based X-ray fluorescence microscopy demonstrates the increase in total zinc content, and the differential distribution of zinc in ovarian follicles during primordial-through-secondary-stage development. The color scale bar represents the minimum and maximum zinc contents (µg/cm2). Scale bar=10 μm.
Image Credit: NIH/Yu-Ying Chen

To make a baby, first you need an egg. To have an egg, there needs to be a follicle. And in the very beginning of follicle development, there needs to be zinc.

The last of those statements represents the new findings reported recently by a team of researchers from Michigan State University, Northwestern University and the U.S. Department of Energy’s (DOE) Argonne National Laboratory. The research builds upon earlier work looking at the role of zinc in fertilization and uncovers the importance of the metal earlier in the process of ovulation.

The results were reported in a paper in the Journal of Biological Chemistry that looked at the role of zinc in follicle development. The researchers, led by Teresa Woodruff and Tom O’Halloran of Michigan State University, used the Bionanoprobe at Argonne’s Advanced Photon Source (APS) to examine zinc and other trace elements in the egg cell itself as well as surrounding somatic cells.

Mast cells have an important impact on the development of chronic myeloid leukemia

Microscopic image of bone marrow from a mouse with CML showing an unusually high number of mast cells (purple).
Image Source / Credit: Sebastian Halbach

Research team at the University of Freiburg traces the origin of proinflammatory cytokines

Chronic myeloid leukemia (CML) is a type of blood cancer that arises from malignant changes in blood-forming cells of the bone marrow. It mainly occurs in older individuals and represents about 20 percent of all adult leukemia cases. A research team led by Dr. Sebastian Halbach, Melanie Langhammer and Dr. Julia Schöpf from the Institute of Molecular Medicine and Cell Research at the University of Freiburg has now demonstrated for the first time that mast cells play a crucial role in the development of CML.  Mast cells could therefore serve as an additional therapeutic target in the clinic. “It was really impressive to see that mice lacking mast cells no longer developed severe CML,” says study leader Halbach. The results were recently published in the journal Leukemia.

Significantly elevated cytokine levels

Mast cells are cells of the immune system that play a decisive role in the defense against pathogens, but also in allergies. In this context, mast cells release inflammation inducing messenger molecules, so-called proinflammatory cytokines, which are crucial for the immune response. However, proinflammatory cytokines are also frequently found in the microenvironment of tumors and are suspected of decisively promoting cancer development. Using a mouse model for CML, the scientists were able to demonstrate for the first time that cytokines in CML could indeed originate from mast cells.

Brain research with organoids

Section of an electroporated brain organoid of a common marmoset. Green: electroporated cells that glow green due to the green fluorescent protein; magenta: neurons; gray: nuclei.
Photo Credit: Lidiia Tynianskaia

Scientists at the German Primate Center develop effective method to genetically modify brain organoids

Primates are among the most intelligent creatures with distinct cognitive abilities. Their brains are relatively large in relation to their body stature and have a complex structure. However, how the brain has developed over the course of evolution and which genes are responsible for the high cognitive abilities is still largely unclear. The better our understanding of the role of genes in brain development, the more likely it will be that we will be able to develop treatments for serious brain diseases. 

Researchers are approaching these questions by knocking out or activating individual genes and thus drawing conclusions about their role in brain development. To avoid animal experiments as far as possible, brain organoids are used as an alternative. These three-dimensional cell structures, which are only a few millimeters in size, reflect different stages of brain development and can be genetically modified. However, such modifications are usually very complex, lengthy and costly. Researchers at the German Primate Center (DPZ) – Leibniz Institute for Primate Research in Göttingen have now succeeded in genetically manipulating brain organoids quickly and effectively. 

Deficiency causes appetite for meat

A carnivorous leaf of Triphyophyllum peltatum with glands excreting a sticky liquid to capture insect prey.
Photo Credit: Traud Winkelmann / Universität Hannover

Under certain circumstances, a rare tropical plant develops into a carnivore. A research team from the universities of Hannover and Würzburg has now deciphered the mechanism responsible for this.

Triphyophyllum peltatum is a unique plant. Native to the tropics of West Africa, the liana species is of great interest for medical and pharmaceutical research due to its constituents: In the laboratory, this show promising medically useful activities against pancreatic cancer and leukemia cells, among others, as well as against the pathogens that cause malaria and other diseases.

However, the plant species is also interesting from a botanical perspective: Triphyophyllum peltatum is the only known plant in the world that can become a carnivore under certain circumstances. Its menu then includes small insects, which it captures with the help of adhesive traps in the form of secretion drops and digests with synthesized lytic enzymes.

Most species, including humans, who experience early life adversity suffer as adults. How are gorillas different?

Experienced the loss of her mother and father and the disintegration of her family group before the age of 5. Now 20, she has become a successful mother, raising three offspring.
Photo Credit: Dian Fossey Gorilla Fund

There’s something most species—from baboons to humans to horses—have in common: When they suffer serious adversity early in life, they’re more likely to experience hardship later on in life.

When researchers from the Dian Fossey Gorilla Fund and the University of Michigan decided to look at this question in gorillas, they weren’t sure what they would find.

Previous studies by the Fossey Fund revealed that young gorillas are surprisingly resilient to losing their mothers, in contrast to what has been found in many other species. But losing your mother is only one of many potential bad things that can happen to young animals.

“Assuming that you survive something that we consider early life adversity, it’s often still the case that you will be less healthy or you will have fewer kids or your lifespan will be shorter—no matter what species you are,” said Stacy Rosenbaum, U-M assistant professor of anthropology and senior author of the study. “There’s this whole range of things that happens to you that seems to just make your life worse in adulthood.”

Gene-edited calf may reduce reliance on antimicrobials against cattle disease

 Brian Vander Ley, associate professor in the University of Nebraska–Lincoln’s School of Veterinary Medicine and Biomedical Sciences, works with Ginger, a Gir cow gene-edited with resistance to bovine viral diarrhea virus.
Photo Credit: Craig Chandler | University Communication and Marketing

Cattle worldwide face major health threats from a highly infectious viral disease that decades of vaccinations and other precautions have failed to contain. Federal, private-sector and Husker scientists are collaborating on a new line of defense, by producing a gene-edited calf resistant to the virus.

If follow-up research confirms its efficacy, the gene-editing approach offers long-term potential to reduce antimicrobial and antibiotic use in the cattle industry.

The bovine viral diarrhea virus devastates the bovine immune system and can cause severe respiratory and intestinal harm to infected beef and dairy cattle, said veterinary epidemiologist Brian Vander Ley, an associate professor in the University of Nebraska–Lincoln’s School of Veterinary Medicine and Biomedical Sciences.

In utero calves are especially vulnerable to infection. If they survive, they can remain infected for life, repeatedly spreading the virus to other cattle.

“They show up as normal cattle but really, they’re shedding a tremendous amount of virus. They’re the ‘Typhoid Marys’ of BVDV spread,” said Vander Ley, assistant director of UNL’s Great Plains Veterinary Educational Center in Clay Center.

New Research Unveils Mechanisms for Removal of Strong Replication-Blocking Lesions Generated by the Human HMCES Protein

Image Credit: ANIRUDH

Researchers at Nagoya University and Osaka University in Japan have found novel repair pathways of apurinic/apyrimidinic (AP) sites of DNA. Repair of the base excision, which repairs AP sites, is an essential mechanism for cell survival. Its dysfunction causes genome instability disorders, including various cranial nerve diseases. The findings of this study should lead to a better understanding of the molecular mechanisms to repair AP sites that are the causes of unexplained and intractable genomic instability diseases.

Recently, it was discovered that the HMCES protein prevents DNA cleavage by forming the DNA-protein crosslink with the AP site and that the DNA-HMCES crosslink protects cells from the toxicity of the AP sites. However, the mechanism by which the DNA-HMCES crosslinks when secondary DNA damage is repaired remains to be elucidated. In this study, the research team determined the repair mechanisms of DNA-HMCES crosslink damage.

This research is important because endogenous DNA damage induced by intracellular metabolites causes aging and carcinogenesis. One of the most frequently generated endogenous DNA damages is the AP site. Although AP sites in double-stranded DNA are repaired by base excision repair, human tissues accumulate between 50,000 and 200,000 AP sites per single cell. The AP site is a site in which genetic information is lost and is susceptible to DNA strand breakage through a chemically unstable structure. During DNA replication, the exposed AP site on the single strand of the template DNA impedes the progress of DNA polymerases because of the loss of genetic information. It also causes serious DNA double-strand break due to AP site breakage, which would induce cell death.

Zinnia Elegans will Help Strengthen Plants

Zinnia is one of the most common flower crops.
Photo Credit: Jeana Bala

Biologists at Ural Federal University and Inner Mongolia University (Hohhot, China) have identified a group of genes that are responsible for the strength of the stem in dicotyledonous plants. The results of the study are described in the journal Horticulturae, and will be useful for agriculture. 

"During plant development, specific changes occur at the level of cells, tissues, whole organs, as well as in metabolism and physiological processes. All these changes are controlled at the genetic level and by environmental conditions. These changes lead to the formation of anatomo-morphological structures that ensure the effective fulfillment of the main functions of the stem - water, mineral and photosynthetic transport, and maintenance of the shoot in an upright position. These processes are connected with deposition of lingin in cell walls of vessels and fibers. There is no lingin in the cells of the bark or in the center of the stem", - explains Anastasia Tugbaeva, co-author of the study, Junior Researcher at the UrFU Research Laboratory "Biotechnology of Components Maintenance and Restoration of Natural and Transformed Biosystems".

Brain-Belly Connection: Gut Health May Influence Likelihood of Developing Alzheimer’s

UNLV study pinpoints 10 bacterial groups associated with Alzheimer’s disease, provides new insights into the relationship between gut makeup and dementia.
Illustration Credit: Julien Tromeur

Could changing your diet play a role in slowing or even preventing the development of dementia? We’re one step closer to finding out, thanks to a new UNLV study that bolsters the long-suspected link between gut health and Alzheimer’s disease.

The analysis — led by a team of researchers with the Nevada Institute of Personalized Medicine (NIPM) at UNLV and published this spring in the Nature journal Scientific Reports — examined data from dozens of past studies into the belly-brain connection. The results? There’s a strong link between particular kinds of gut bacteria and Alzheimer’s disease.

Between 500 and 1,000 species of bacteria exist in the human gut at any one time, and the amount and diversity of these microorganisms can be influenced by genetics and diet.

The UNLV team’s analysis found a significant correlation between 10 specific types of gut bacteria and the likelihood of developing Alzheimer’s disease. Six categories of bacteria — Adlercreutzia, Eubacterium nodatum group, Eisenbergiella, Eubacterium fissicatena group, Gordonibacter, and Prevotella9 — were identified as protective, and four types of bacteria — Collinsella, Bacteroides, Lachnospira, and Veillonella — were identified as a risk factor for Alzheimer’s disease.

A multiomics approach provides insights into flu severity

Photo Credit: Andrea Piacquadio

Have you ever wondered why some people might get sicker than others, even when they catch the same virus? It is not yet clear why this is. Viral factors (such as differences in the strain of a virus) play a role in this variability, but they cannot account for the wide range of responses in different individuals infected by the same virus. A number of host factors have also been considered, including pre-existing immunity, age, sex, weight, and the microbiome.

Another important factor is the molecular biology within your cells. DNA is shown as one long double-helical strand. So, you might expect that the cell would always read genetic information in order, starting at one end and going to the other. But this isn’t the case. DNA contains transposable elements, sometimes called “junk DNA,” which can change the regions of the genome that are being read at a given time.

The work published in Cell Genomics by an international team led by Dr. Guillaume Bourque, who studied the role of these transposable elements on the severity of illness after influenza A virus infection.

Delivery of antioxidants to liver mitochondria

Damage to the liver induced by acetaminophen (dotted blue outlines) is almost completely mitigated by CoQ10-MITO-Porter (right), compared to the effect of phosphate buffered saline (left) and direct administration of CoQ10(center).
Image Credit: Mitsue Hibino, et al. Scientific Reports. May 10, 2023

A new drug delivery system delivers an antioxidant directly to mitochondria in the liver, mitigating the effects of oxidative stress.

Mitochondria are microscopic organelles found within cells, and are well-known as the “powerhouse of the cell.” They are by far the largest producer of the molecule adenosine triphosphate (ATP), which provides energy to many processes in living cells. The process by which mitochondria synthesize ATP generates a large amount of reactive oxygen species (ROS), chemical groups that are highly reactive. 

In a healthy cell, the ROS is controlled by the mitochondria; however, when this balance is lost, the excess ROS damages the mitochondria and subsequently cells and tissues. This phenomenon, known as oxidative stress, can cause premature aging and disease. The ROS that causes oxidative stress can be controlled by antioxidants.

A research team led by Professor Yuma Yamada, Distinguished Professor Hideyoshi Harashima and Assistant Professor Mitsue Hibino at Hokkaido University have developed a system to deliver antioxidants to mitochondria to mitigate the effects of excess ROS. Their findings were published in Scientific Reports.

Researchers map the genome of the world’s grumpiest cat

The mighty roar of a grumpy and angry Pallas' cat (Otocolobus manul)
Photo Credit: Johannes Heel

University of Minnesota researchers recently led successful efforts to build the first genome for Pallas’s cat (Otocolobus manul), a small wild cat native to central Asia known for its grumpy facial expression. The cat, which faces growing challenges from climate change, habitat fragmentation, and poaching, had no available genetic resources to help with conservation prior to this study. 

The study, published in NAR Genomics and Bioinformatics, was led by Nicole Flack, a doctoral candidate in the College of Veterinary Medicine, along with Christopher Faulk, a professor in the College of Food, Agricultural, and Natural Resource Sciences. 

The researchers used blood samples from Tater, a 6-year-old Pallas’s cat who lives at the Utica Zoo in New York, to construct a high-quality diploid nuclear genome assembly, a representative map of genes for the species.

The study results include confirmation that the Pallas’s cat is more closely related to certain wild cat species and less related to house cat species than some previous studies have suggested. 

The bat's ability to convert energy into muscle power is affected by flight speed

Photo Credit: Anders Hedenström

Small bats are bad at converting energy into muscle power. Surprisingly, a new study led by Lund University reveals that this ability increases the faster they fly.

The researchers have studied the efficiency of migratory bats – a species that weighs about eight grams and is found in almost all of Europe. Efficiency, in this case, is the ability to convert supplied energy into something we need. For bats and birds, it’s the energy required to fly. In a new study published in the journal Proceedings of the Royal Society B, a research team in Lund states that the efficiency varies with the bats' flight speed. The faster the bats flew, the more energy they managed to convert into muscle power.

“Previously, we believed that efficiency is a constant. So, this is a bit of a breakthrough”, says Anders Hedenström, biology researcher at Lund University.

Using high-speed cameras, laser and smoke in a wind tunnel, the researchers have measured the bat's kinetic energy. They then compared these results with the animals' metabolism – a methodological breakthrough with technically advanced measurements. In the past, researchers have only measured either kinetic energy or metabolic rate and compared this to theories.