Predicting the Future with a Scale-Invariant Temporal Memory for the Past

In recent years, it has become clear that the brain maintains a temporal memory of recent events stretching far into the past. This letter presents a neutrally inspired algorithm to use a scale-invariant temporal representation of the past to predict a scale-invariant future. The result is a scale-invariant estimate of future events as a function of the time at which they are expected to occur. The algorithm is time-local, with credit assigned to the present event by observing how it affects the prediction of the future. To illustrate the potential utility of this approach, we test the model on simultaneous renewal processes with different timescales. The algorithm scales well on these problems despite the fact that the number of states needed to describe them as a Markov process grows exponentially.

5-ALA fluorescence in indeterminate grade gliomas

5-Aminolevulinic acid (5-ALA) is a useful and well-established adjunct for glioblastoma surgery. A growing body of evidence has revealed the potential utility of 5-ALA in grade II and grade III glioma patients as well. However, reliable means of identifying in whom fluorescence will occur have not been established. The authors report the case of such an indeterminate-grade glioma highlighting two pearls of 5-ALA fluorescence in this subgroup of patients. Firstly, 5-ALA–guided tissue sampling helps to ensure that the true grade of the lesion is not underestimated. Secondly, intraoperative fluorescence can serve as a prognostic marker. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21196

The Roles of the Virome in Cancer

Viral infections as well as changes in the composition of the intestinal microbiota and virome have been linked to cancer. Moreover, the success of cancer immunotherapy with checkpoint inhibitors has been correlated with the intestinal microbial composition of patients. The transfer of feces—which contain mainly bacteria and their viruses (phages)—from immunotherapy responders to non-responders, known as fecal microbiota transplantation (FMT), has been shown to be able to convert some non-responders to responders. Since phages may also increase the response to immunotherapy, for example by inducing T cells cross-reacting with cancer antigens, modulating phage populations may provide a new avenue to improve immunotherapy responsiveness. In this review, we summarize the current knowledge on the human virome and its links to cancer, and discuss the potential utility of bacteriophages in increasing the responder rate for cancer immunotherapy.

Substrate multiplexed protein engineering facilitates promiscuous biocatalytic synthesis

Enzymes with high activity are readily produced through protein engineering, but intentionally and efficiently engineering enzymes for an expanded scope is a contemporary challenge. Measuring reaction outcomes on mixtures of substrates, called here SUbstrate Multiplexed Screening (SUMS), has long been used to rigorously quantitate enzyme specificity. Despite the potential utility of SUMS to guide engineering of promiscuous enzymes, this approach has not found widespread adoption in biocatalysis. Here, we develop principles of how to design robust SUMS methods that, rather than assess absolute specificity, use heuristic readouts of substrate promiscuity to identify hits for further investigation. This rich information enables engineering of activity for multiple substrates simultaneously and identifies enzyme variants with altered promiscuity, even when overall activity is lower. We demonstrate the effectiveness of SUMS by engineering two enzymes to produce pharmacologically active tryptamines from simple indole precursors in a biocatalytic cascade. These advances leverage common laboratory equipment and represent a highly accessible and customizable method for enzyme engineering.