Inflammatory responses to sepsis

In an earlier post (TLR4) I discussed the TLR4 receptor. This receptor detects microbes and starts an inflammatory response. TLR4 is not the only receptor that detects microbes. There are many receptors the immune system uses. This redundancy prevents microbes going undetected and matches the response to the microbe. At least, when everything works. An excessive response can cause sepsis. In sepsis the response is so strong that it damages tissues and can even cause organ failure.

I have recently collaborated with Oliver Voss and John Coligan from the National Institute of Allergy and Infectious Diseases. They were studying CD300b. This is another receptor that binds lipopolysaccharides (LPS) like TLR4. CD300b then binds to TLR4 and enhances its signaling. This enhanced signaling can then cause more tissue damage, leading to sepsis.

Inhibiting TLR4 does not work well for treating sepsis in humans. This might be because some TLR4 signaling helps combat infecting microbes. Inhibiting CD300b might strike a healthy balance between continuing to fight the infection and the excessive signaling causing tissue injury.

Chronic kidney disease and lipid metabolism receptors

Lipids are very important molecules in the human body. Different types of lipids include fats and some vitamins. Lipids form the membranes in and around cells, store energy, and signal between cells. Lipids, like fats and oils, do not dissolve in water. To get them around the body they form complexes with proteins. These complexes include LDL and HDL.

Your doctor may have requested blood tests for these. They are important in cardiovascular disease. To get lipids into cells receptors must bind the lipoprotein complexes. Sometimes rather than supporting the cell, lipid uptake can cause stress and inflammation. This is why doctors often check the levels of LDL and HDL.

CD36 is a receptor for lipoproteins. We investigated the role of CD36 in chronic kidney disease (CKD). Breaking this receptor by changing the DNA that creates it protected against CKD. Similar protection happened with a small peptide inhibitor. This is important because it is easier to help patients by giving them a drug than by trying to change their DNA.

Chronic kidney disease and pathogen sensors

There are several receptors that detect microbial products. They are responsible for triggering an inflammatory response by the innate immune system. This is important to guard against infections. Sometimes inflammation can happen when it is not needed to protect against infection. A low level of inflammation is sometimes detected in chronic diseases.

Toll-like receptor 4 (TLR4) detects lipopolysaccharides (LPS). The outer layer of gram-negative bacteria contains LPS. TLR4 might also detect some molecules released during tissue damage. We investigated the role of TLR4 in chronic kidney disease (CKD).

Breaking TLR4 so it could not trigger the innate immune system protected against CKD.

Lightning talk slides on deep learning with keras

At the DCPython Office Hours event this month I gave a lightning talk on convolutional neural networks implemented with the keras library. The notebook is now up on github.

Deep neural networks are typically too slow to train on CPUs. Instead, GPUs are used. The example in the notebook uses a relatively small network so should be runnable on any hardware.

Lightning talk slides on web server log analysis with pandas

At the DCPython Office Hours event in May I gave a lightning talk on using pandas to analyse nginx access logs. The notebook is now up on github.