Antibiotic 167A

Two related antibiotics, 167-A and 167-B, were isolated from the fermentation broth of a mutant of an inactive wild strain of Amycolata autotrophica. Antibiotic 167-B was found to be cervinomycin A2; antibiotic 167-A is a new representative of the same group and has the structure of 18-O-demethyl cervinomycin A2.

Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by a congenital malformation of the lymphatic vessels of the small intestine causing insufficient drainage and leakage of lymph fluid. Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems. While the lymphatic system has been implicated in TSC through lymphangioleiomyomatosis (LAM) and lymphedema, this paper reports the first case of PIL in TSC, a female patient with a TSC2 mutation. She developed persistent and significant abdominal distension with chronic diarrhea during her first year of life. Due to lack of treatment options and the involvement of the mTOR pathway in TSC, a trial of an mTOR inhibitor, rapamycin, was initiated. This treatment was highly effective, with improvement in clinical symptoms of PIL as well as abnormal laboratory values including VEGF-C, which was elevated to over seven times the normal upper limit before treatment. This case suggests that PIL is a rare manifestation of TSC, warranting the use of mTOR inhibitors in future studies.

I present a framework to study the evolution of traits that allow an organism to survive life-threatening but rare risks. Specifically, I am concerned with risks so rare that any one individual in a population may not experience the risk-causing event in its lifetime. A theory of rare risk management is virtually absent in evolutionary biology, although it is well developed in economics. This is surprising because of the great influence economics had on evolutionary biology, and because biology is full of examples for evolved risk management traits. They include the ability of bacteria to sporulate, of pathogens to survive antibiotic treatment, of temperate bacteriophages to enter a lytic life cycle, as well as traits that allow higher organisms to survive rare environmental disasters, such as sporadic wildfires and irregular flooding. I make predictions about the sustenance of risk management traits under two scenarios, one where the catastrophic events cause individual deaths, and another one where catastrophic events cause population extinction. A well-developed theory of risk management will not only predict the distribution of risk management traits, but may also serve other purposes, such as to reconstruct the spectrum of environments that an organism encountered in its evolutionary history from the record stored in its genome's memory.