Moved to Trichoplax neuropeptide
All posts by bk
Caspases 4, 5 and 11 are Intracellular LPS Receptors
A LPS receptor has already been identified by Beutler and colleagues. This finding was awarded the NOBEL prize in 2011. In the actual issue of Nature (doi:10.1038/nature13683) Shi and colleagues describe the role of caspases – enzymes triggerung cell death called apoptosis – as intracellular receptors for LPS.
When LPS is delived intracellarly into macrophages, epithelial cells or keratinocytes these cells undergo necrosis. The process is specific for intact Lipid A. Murine caspase-11 as well as human caspases 4 and 5 bind to LPS and Lipid A. They induce what is called pyroptosis. The paper is nicely done, however, one might wonder when and how LPS is released from the phagolysosome and becomes available within a cell.
Dogs Smell Cancer?!
It has been already published in May this year, but I think it is still worth mentioning here:
Bloomberg (klick on the link to see the orginal article) reports that dogs can be trained to sniff whether a person has breast cancer or prostate cancer. The selectivity, by which dogs discriminate between positive and negative samples is 90% and more. If we could train our dogs to do so, all mamma screening e.g. would become obsolete. We do not know what substances the dogs smell, but we can envisage that once they are identified we could train enough dogs to do the job or analytical chemistry might be able to do so. One would hope that dogs will be used because the test would be ultimately cheaper and emotionally closer than in the case of chemistry.
A treatment for Ebola?
CNN reports today that the two Americans which were infected with Ebola while fighting the disease in Africa received an experimental drug from Mapp Biopharmaceutical Inc (San Diego) and improved. There are obviously other untested drug ready to test. This drug is a mouse monoclonal antibody which raises many question about safety and rejection.
Even a vaccine is in the pipeline, but will only be tested from September on. Since the patients are usually not able to pay for the treatment and profit not at all expected, few companies dare to develop a medicine. But hopefully this is the beginning of fighting this devasting infection.
From Dinos to Birds – a problem of size
In the Science journal there is a remarkable report (DOI: 10.1126/science.1252243) by Lee et al. on the evolution of birds from dinosauri. A lineage is depicted which comprises 12 different independent steps in size reduction. These steps occurred mostly long before the first flying animal hatched. A Perspective article (DOI: 10.1126/science.1257633) by M.J. Benton puts this paper in its context: 20 years ago the evolution of birds was believed to occur within 10 Millions of years. This article summarizes the research done since: Around 50 Millions of year were necessary to the steps to reduce the animal to the size of Archeopteryx and further to that e.g. of a swallow. Some of the intermediate species had feathers, some were “paragliders”, but only Archaeopteryx developed free-flying.
Benton argues that the minaturization was caused by an environmental change i.e. that they tried to live on trees. The gain when living in a tree environment would be safety from predators and a wealth of additional food. Possible.
The authors sampled 120 therapods and early birds. That by itself is a tremendous achievement and makes their analysis fairly sound. Excellent work!
Epigenetics to Define a Cell
A nice analysis of the trimethylation of histon 3 at lysine 4 (H3K4me3) appears in Cell this week (http://dx.doi.org/10.1016/j.cell.2014.06.027). Benayoun and Pollina et al. claim that this marker labels preferentially those proteins that are essential for the cell’s function. The marker has been found at the start of most transcribed genes, but Benayoun and Pollina argue that not its mere presence, but the intensity of its presence is a sign that this protein is relevant for lineage specifity. If this intensity is disturbed, that function is not maintained.
This is a metaanalysis of a very broad range including human, mammalian, protostomes, plants and fungi. Nicely done!
Studies on the Epigenom in Human Early Embryos
Epigenetic modification of DNA, mostly methylation, is the way which ensures lineage specity in mammalian organization and propagation of cell types. It is inherited while cells multiply.
In Nature this week (doi:10.1038/nature13648) Reik and Kelsey describe two article ( et al. Nature 511, 606–610 (2014) and et al. Nature 511, 611–615 (2014)) where the methylation patterns in egg, sperm, fertilized eggs and blastocysts are analyzed. As has been found in mice before, blastocysts lose most of their methylation. Later in development the DNA gets remethylated again. This has been suggested but formal proof was lacking. The imprinting – methylated gene regions due to maternal or paternal origin – is not as much removed for maternal genes, but for paternal ones.
Whether these papers will improve human stem cell research is to be seen.
Gerald Maurice Edelman 1929 -2014
Gerald Maurice Edelman died in La Jolla California at the age of 84.
Immunologist worldwide recognize him for his contribution to the antibody enigma. Trained in medicine and chemistry his first publication on antibodies established that these molecules can be subjected to urea and sulfhydryl treatment and yield smaller chains as we know now very well but was new in 1959 when first published. For his work on antibody strucuture which e.g. lead to the first sequence of Ig γ-chain he was awarded the Nobel Prize in 1972 together with Rodney R. Porter.
The antibody enigma was only solved by Susumu Tonegawa who showed that recombination of the same DNA could lead to millions of different mRNAs from which finally antibody molecules are translated. He obtained the Nobel Prize in 1987 as well.
Translation Errors – not so bad at all
Faithfull translation of mRNA into proteins is one of the hallmarks of life. It is generally accepted that any deviation from this pathway leads to missformed proteins and is considered deleterious per se.
A very enlightning review in Trends in Biological Sciences (TIBS; DOI: 10.1016/j.tibs.2014.06.002) shows that errors in translation are dealt with in a productive way. First of all mistranslation are obviously regulated due to species and environnement which is by itself showing that mistranslation is beneficial for the organism, at least part of it. Furthermore mistranslation is well tolerated and not deleterious for the organism. Different organisms have evolved strategies to deal with it. It seems clear that by mistranslation the organism generates alternative proteins which may help to adapt the different environmental challenges.
Recommended!
Beta-cell development and genetics
Two reviews in Trends in Endocrinology and Metabolism (DOI: http://dx.doi.org/10.1016/j.tem.2014.05.001 and DOI: http://dx.doi.org/10.1016/j.tem.2014.03.013) address the development and the pathogenesis of pancreatic β-cells. Conrad, Stein and Hunter describe the transcription factors in mice and man which lead to β-cell genesis while Thomsem and Gloyn focus their attention to malfunction leading diabetes mellitus. Both reviews together show the actual status in β-cell research.