This study describes the identification of an antibiotic class acting via LpxH, involved in lipopolysaccharide synthesis having potent in vivo efficacy against bloodstream infections caused by the critical Gram-negative pathogens E. coli and Klebsiella pneumoniae. Further development of this class of antibiotics could make an important contribution to the ongoing struggle against antibiotic resistance.

https://www.pnas.org/doi/10.1073/pnas.2317274121 (open access)

This study attempts to identify the “protective” genetic factors that can modify or reduce the effect of APOEε4 on Alzheimer’s disease risk and to identify new pathogenic mechanisms, proteins, and pathways that inform development of therapeutic targets and diagnostics.

https://link.springer.com/article/10.1007/s00401-024-02721-1 (open access).

Brief anger can temporarily impair blood vessel function, potentially heightening heart disease and stroke risks, finds new study in the Journal of the American Heart Association.

Scientists have created an infant ‘chimeric’ monkey by injecting a monkey embryo with stem cells from a genetically distinct donor embryo. The resulting animal is the first live-born chimeric primate to have a high proportion of cells originating from donor stem cells. However, the monkey had to be euthanized when it was only ten days old, due to health issues, thereby raising ethical concerns. DOI: 10.1016/j.cell.2023.10.005

Chinese Scientists have introduced an innovative, green alternative to nylon and Kevlar

Taking a look at how the use of solar energy has evolved, from ancient civilizations leveraging passive sunlight to modern photovoltaic milestones.

Astronomers have been closely monitoring Bennu, which swings close to Earth every six years. However, the real cause for concern arises from the possibility that on September 24, 2182, Bennu could collide with our planet with a force equivalent to 22 atomic bombs. While the odds of such a catastrophic strike are estimated at 1 in 2,700, NASA is not taking any chances.

The newly discovered letter, written by a German Jesuit to Pope Pius XII’s personal secretary, suggests that the pope knew of Hitler’s atrocities but chose to remain silent.

The nations are taking bold steps in the espionage shadow war to try to collect intelligence on leadership thinking and military capabilities.

Feline thief Gingee, a four-year-old Maine Coon, has been ransacking nearby homes in Buckley, Flintshire.

The most startling moment for owners Jay Phoenix, 43 and Mathew Westlake-Toms, 31, was when Gingee delivered a stolen knife to their bedroom at night.

The concrete dome of the Pantheon in Rome remains stable enough for visitors to walk beneath, and some Roman harbours have underwater concrete elements that have not been repaired for two millennia – even though they are in regions often shaken by earthquakes.

Whence this remarkable resilience of Roman concrete architecture? It’s all down to the chemistry.

A key function of our immune system is to detect and eliminate foreign pathogens such as bacteria and viruses. Immune cells like T cells do this by distinguishing between different types of proteins within cells, which allows them to detect the presence of infection or disease.

A type of T cell called cytotoxic T cells can recognize the mutated proteins on cancer cells and should therefore be able to kill them. However, in most patients, cancer cells grow unchecked despite the presence of T cells.

The current explanation scientists have as to why T cells fail to eliminate cancer cells is because they become “exhausted.” The idea is that T cells initially function well when they first face off against cancer cells, but gradually lose their ability to kill the cancer cells after repeated encounters.

Cancer immunotherapies such as immune checkpoint inhibitors and CAR-T cell therapy have shown remarkable promise by inducing long-lasting remission in some patients with otherwise incurable cancers. However, these therapies often fail to induce long-term responses in most patients, and T cell exhaustion is a major culprit.

We are researchers who study ways to harness the immune system to treat cancer. Scientists like us have been working to determine the mechanisms controlling how well T cells function against tumors. In our newly published research, we found that T cells become exhausted within hours after encountering cancer cells. T cells recognize tumor cells by the specific proteins called antigens they display on their surfaces. Timing T cell exhaustion

By the time most patients are diagnosed with cancer, their immune system has been interacting with developing cancer cells for months to years. We wanted to go back earlier in time to figure out what happens when T cells first encounter tumor cells.

To do this, we used mice genetically engineered to develop liver cancers as they age, similarly to how liver cancers develop in people. We introduced trackable cytotoxic T cells that specifically recognize liver cancer cells to analyze the T cells’ function and monitor which of the genes are activated or turned off over time.

We also used these same trackable T cells to study their response in mice infected with the bacteria Listeria. In these mice, we found that the T cells were highly functional and eliminated infected cells. By comparing the differences between dysfunctional T cells from tumors and highly functional T cells from infected mice, we can home in on the genes that code for critical proteins that T cells use to regulate their function.

In our previous work, we found that T cells become dysfunctional with dramatically altered genetic structure within five days of encountering cancer cells in mice. We had originally decided to focus on the very earliest time points after T cells encounter cancer cells in mice with liver cancer or metastatic melanoma because we thought there would be fewer genetic changes. That would have allowed us to identify the earliest and most critical regulators of T cell dysfunction.

Instead, we found multiple surprising hallmarks of T cell dysfunction within six to 12 hours after they encountered cancer cells, including thousands of changes in genetic structure and gene expression.