Comment

Comment by Dr. Krishna Kumari Challa on November 27, 2024 at 11:36am

This work also tells us how important it is to move away from a 'one-size-fits-all' approach to managing type 2 diabetes, and we hope that this will allow us to find ways to offer more precise treatments that treat the condition more effectively and reduces the development of diabetes complications.

Genes & Health will contribute to future efforts to ensure that precision medicine approaches are developed and bring real benefits to south Asian communities living with, and at risk of, type 2 diabetes.

Genetic basis of early onset and progression of type 2 diabetes in south Asians, Nature Medicine (2024). DOI: 10.1038/s41591-024-03317-8. www.nature.com/articles/s41591-024-03317-8 

Part 2

Comment by Dr. Krishna Kumari Challa on November 27, 2024 at 11:34am

Why are South Asians more diabetic prone?

A genetic predisposition to having lower insulin production and less healthy fat distribution are major causes of early-onset type 2 diabetes in  South Asian people, according to new research. These genetic factors also lead to quicker development of health complications, earlier need for insulin treatment, and a weaker response to some medications.

The findings, published in Nature Medicine, reinforce the need to understand how genetic variation across different population groups can influence the onset of diseases, treatment responses, and disease progression.

Key discoveries from the study include:

• Genetic signatures in South Asians: The younger age of onset in South Asians is strongly linked to genetic signatures that lead to both lower insulin production and unfavorable patterns of body fat distribution and obesity. The most significant genetic signature influencing whether a South Asian person develops type 2 diabetes, and at a young age, is a reduced ability of pancreatic beta cells to produce insulin. This genetic signature also increases the risk of gestational diabetes and the progression of gestational diabetes to type 2 diabetes after pregnancy.

• • Treatment responses: The genetic signatures identified in the study provide vital clues about how different people may respond to type 2 diabetes treatments. For example, individuals with high genetic risk for low insulin production were less likely to respond to common medications such as sodium-glucose co-transporter 2 inhibitors and were more likely to require insulin therapy.

  • High genetic-risk group identified: The study identified a subset of people with extreme genetic signatures for both low insulin production and unfavorable fat distribution. These individuals were found to develop type 2 diabetes an average of eight years earlier and at lower body mass index. Over time, these individuals were more likely to need insulin treatment and were at higher risk for diabetes complications such as eye and kidney disease.

Part 1

Comment by Dr. Krishna Kumari Challa on November 27, 2024 at 11:19am

To validate their findings further, the researchers used computer simulations to create different virtual tumors, some with surface growth and others with volume growth. The researchers compared the patterns of mutations from the simulations to the patterns found in the real tumor data.

They found that mutation patterns in the real tumors matched the patterns from the volume growth simulations but not the surface growth simulations.

One of the limitations of the study is that it focused on liver cancer, so the findings might not apply universally to all types of cancer. Another limitation is that the study mainly provides insights into the early stages of tumor growth, which might not fully capture the behavior of larger or metastatic types of cancer.

Arman Angaji et al, High-density sampling reveals volume growth in human tumours, eLife (2024). DOI: 10.7554/eLife.95338.2

Part 2

Comment by Dr. Krishna Kumari Challa on November 27, 2024 at 11:18am

Spatial genomics approach shows cancers grow uniformly, challenging the idea of 'two-speed' entities

Researchers have discovered that cancer grows uniformly throughout its mass, rather than at the outer edges. The work, published in the journal eLife, challenges decades-old assumptions about how the disease grows and spreads.

The researchers challenge the old idea  that a tumour is a 'two-speed' entity with rapidly dividing cells on the surface and slower activity in the core. For the last 50 years, researchers have hypothesized that tumors grow faster at their outer edges. Cancer cells on the surface are thought to have natural advantages compared to cells deep within. For example, peripheral cells have better access to nutrients and oxygen from surrounding healthy tissues. They can also get rid of their waste more easily. As a tumor grows, its center gets further and further away from the blood vessels in the area where it is growing. The cells in a tumor's core get less and less oxygen and nutrients. The cells are also under more mechanical pressure, with compression limiting their ability to divide.

Instead, this work shows they are uniformly growing masses, where every region is equally active and has the potential to harbour aggressive mutations.

These  findings have implications for tumor evolution. The constant churn of cells dying and being replaced by new ones throughout the tumour volume gives cancer many opportunities for evolutionary innovations, such as escaping from immune surveillance.

The researchers made the discovery thanks to spatial genomics, a technique used to study the genetic information of cells in their exact locations within a tissue.

The team obtained data from previous studies where hundreds of small samples were taken from different parts of liver tumors, both in two- and three-dimensional space. This provided a detailed map of the mutations throughout the tumor.
They looked at the mutations in each of the samples, and developed a method to measure the direction and spread of these mutations, allowing them to calculate the angles between the positions of parent cells and their mutated offspring.

In the surface growth model, these angles would point outwards. Instead, the researchers found the angles were spread evenly in all directions, showing uniform growth throughout the tumor.

The study also looked at how mutations were spread within the tumor. If cancer cells grew mostly at the edges, mutations would be more clustered. They found that mutations were spread out, suggesting that cells were dividing all over the tumor.
Part 1

Comment by Dr. Krishna Kumari Challa on November 27, 2024 at 11:06am

Tumor cell death can backfire, strengthening cancer's defenses and limiting immunotherapy success

A new study has uncovered an unexpected way cancer cells can escape the immune system, making it harder for treatments to work. The study, published in Cancer Cell, explains how a type of cancer cell death can actually make tumors grow faster by turning off the immune system's ability to fight the cancer.

Researchers  focused on a form of cell death called necroptosis. Previously thought to help the immune system fight cancer, researchers found that when cancer cells die in this way, they can release a molecule called interleukin-1α.

This molecule helps create an environment in the tumor that weakens the immune response, preventing T cells from attacking the cancer.

People thought necroptosis would help the immune system fight cancer, but instead, it seems to make things worse by helping tumors grow. This study shows that interleukin-1α is key to this process, and by blocking it, we might be able to help the immune system do its job.

The study also found that interleukin-1α is released by cancer cells responding to chemotherapy, which could explain why some treatments don't work as well as expected. But there's good news: By blocking interleukin-1α, researchers were able to improve the immune response and make cancer treatments like chemotherapy and immunotherapy more effective in animal models.

By blocking the actions of interleukin-1α, we could make current cancer treatments more successful. Additionally, targeting interleukin-1α can reduce the toxicity associated with chemotherapy, meaning this approach could help patients respond to and better tolerate therapy.

Researchers also discovered that lower levels of interleukin-1α are linked to better outcomes, especially in patients treated with chemotherapy. This suggests that interleukin-1α could be used as a marker to predict how well cancer treatments might work for different patients.

Kay Hänggi et al, Interleukin-1α release during necrotic-like cell death generates myeloid-driven immunosuppression that restricts anti-tumor immunity, Cancer Cell (2024). DOI: 10.1016/j.ccell.2024.10.014

Comment by Dr. Krishna Kumari Challa on November 27, 2024 at 10:48am

Using a mouse model, this study used global metabolic analysis to investigate changes in metabolites during an enteric infection. The mice were infected with one of two pathogens, L. monocytogenes, which replicates in the intestine, liver and gall bladder, or C. rodentium, which replicates in the caecum and colon.

The different infection groups led to both shared and specific changes in bile metabolites. Moreover, hundreds of new metabolites that are in the bile metabolome were described. More specifically, the researchers found that enteric infection dynamically changes the composition of bile in order to provide intestinal defense.
While these findings bridge a large gap in knowledge regarding bile composition, the researchers note that the 812 bile metabolites identified in this study likely only represent a subset of all bile metabolites.

Ting Zhang et al, Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis, Nature Microbiology (2024). DOI: 10.1038/s41564-024-01862-z

Part 2

Comment by Dr. Krishna Kumari Challa on November 27, 2024 at 10:47am

Intestinal infections can change bile composition, leading to changes in immune function

Intestinal infections can change the composition of liver bile, leading to changes in immune function and gut bacteria, potentially helping fight off harmful bacteria.

Researchers have identified a new axis of host defense by studying what happens during enteric infection—a term that encompasses all types of intestinal infections including so-called "stomach flu."

A new study from infectious disease investigators 

uncovers how bile, a solution produced by the liver and responsible for the absorption of fat, plays a role in the fight against infections.

While the study was conducted in mice, the researchers anticipate that the findings likely apply to humans as well. Results are published in Nature Microbiology.

The changes the researchers  detected in the composition of bile with infection are beneficial for the intestine to clear infection. 

These findings findings reveal the intricate and dynamic nature of bile composition, shedding new light on the liver's critical role in defending the intestine from infection. These insights enhance our understanding of the liver's broader functions in regulating physiological stability and metabolic processes.

Part 1

Comment by Dr. Krishna Kumari Challa on November 27, 2024 at 9:32am

How cancer cells fend off starvation and death from chemotherapy

Laboratory experiments with cancer cells have revealed two ways in which tumors evade drugs designed to starve and kill them.

While chemotherapies successfully treat cancers and extend patients' lives, they are known not to work for everyone for long, as cancer cells rewire the process by which they convert fuel into energy (metabolism) to outmaneuver the drugs' effects. Many of these drugs are so-called antimetabolics, disrupting cell processes needed for tumor growth and survival.

Three such drugs used in the study—raltitrexed, N-(phosphonacetyl)-l-aspartate (PALA), and brequinar—work to prevent cancer cells from making pyrimidines, molecules that are an essential component to genetic letter codes, or nucleotides, that make up RNA and DNA.

Cancer cells must have access to pyrimidine supplies to produce more cancer cells and to produce uridine nucleotides, a primary fuel source for cancer cells as they rapidly reproduce, grow, and die. Disrupting the fast-paced but fragile pyrimidine synthesis pathways, as some chemotherapies are designed to do, can rapidly starve cancer cells and spontaneously lead to them dying (apoptosis).

This new  study shows how cancer cells survive in an environment made hostile by the persistent shortage of the energy from glucose (the chemical term for blood sugar) needed to drive tumor growth.

This better understanding of how cancer cells evade the drugs' attempts to kill them in a low-glucose environment, the researchers say, could lead to the design of better or more effective combination therapies.

Publishing in the journal Nature Metabolism online Nov. 26, study results showed that the low-glucose environment inhabited by cancer cells, or tumor microenvironment, stalls cancer cell consumption of existing uridine nucleotide stores, making the chemotherapies less effective.

Normally, uridine nucleotides would be made and consumed to help make the genetic letter codes and fuel cell metabolism. But when DNA and RNA construction is blocked by these chemotherapies, so too is the consumption of uridine nucleotide pools, the researchers found, as glucose is needed to change one form of uridine, UTP, into another usable form, UDP-glucose.

The irony, researchers say, is that a low-glucose tumor microenvironment is in turn slowing down cellular consumption of uridine nucleotides and presumably slowing down rates of cell death. Researchers say cancer cells need to run out of pyrimidine building blocks, including uridine nucleotides, before the cells will self-destruct.

In other experiments, low-glucose tumor microenvironments were also unable to activate two proteins, BAX and BAK, sitting on the surface of mitochondria, a cell's fuel generator. Activation of these trigger proteins disintegrates the mitochondria, and instantly sets off a series of caspase enzymes that help initiate apoptosis (cell death).

Conclusion of the study:  low glucose slows down the consumption and exhaustion of uridine nucleotides needed to fuel cancer cell growth and hinders resulting apoptosis, or death, in cancer cells.

Glucose limitation protects cancer cells from apoptosis induced by pyrimidine restriction and replication inhibition, Nature Metabolism (2024). DOI: 10.1038/s42255-024-01166-w

Comment by Dr. Krishna Kumari Challa on November 26, 2024 at 7:26am

The study identified a quadratic relationship between rainfall and divorce rates, with the highest rates of divorce occurring in years with either extremely low or high rainfall during the breeding season.

An extreme rainfall event in 1997 was a significant outlier in the data, with exceptionally high rainfall correlating with a sharp increase in divorce rates. When this event was excluded from the analysis, a clearer negative relationship between rainfall and divorce emerged.

Despite rainfall impacting divorce rates, the study found no direct link between reproductive success (i.e., the number of offspring produced) and the likelihood of divorce, suggesting that other, as yet unidentified, factors may be influencing partnership stability.

This study adds to the growing body of evidence showing how environmental factors, particularly those linked to climate change, can directly influence the social dynamics and reproductive strategies of wildlife.

As climate change intensifies, it is critical to understand how fluctuations in environmental conditions, such as rainfall, affect the stability of socially monogamous species.

This research not only enhances our understanding of animal behavior in the face of climate variability but also provides valuable insights that could inform conservation efforts for species vulnerable to the effects of climate change.

 A. A. Bentlage et al, Rainfall is associated with divorce in the socially monogamous Seychelles warbler, Journal of Animal Ecology (2024). DOI: 10.1111/1365-2656.14216

Part 2

Comment by Dr. Krishna Kumari Challa on November 26, 2024 at 7:25am

Did you know that birds are separating and divorcing too?

Bird divorce rates may be linked to fluctuations in rainfall

A 16-year study on a closed population of Seychelles warblers (Acrocephalus sechellensis) on Cousin Island, Seychelles, has uncovered significant findings about how environmental factors—specifically rainfall—affect the stability of pair bonds in birds.

An international team of researchers  found that fluctuations in rainfall prior to and during the breeding season significantly influence the likelihood of "divorce" between mates, highlighting the broader implications of climate cahnge for animal reproduction and conservation. The study is published in the Journal of Animal Ecology.

Divorce, in the context of socially monogamous species, refers to the termination of a pair bond while both individuals are still alive. This mating strategy is often associated with poor reproductive success and has been observed in various bird species. However, the relationship between environmental factors, particularly climate fluctuations, and divorce is the new way of studying the problem.

Social monogamy implies that two birds have formed a pair bond and associate with the same partner, usually over many years and even lifetimes. Pair-bonded birds usually live and raise young together.

Researchers analyzed 16 years of data and found a complex, non-linear relationship between  rainfall patterns and divorce rates, with divorce being more likely during years of both low and high rainfall.

This relationship was notably influenced by an extreme climatic event—the 1997 El Niño-induced rainfall spike.

Part 1

• ‹ Previous
• 1
• …
• 12
• 13
• 14
• 15
• 16
• …
• 992
• Next ›
• Page