New fecal microbiota for cancer patients: The composition of the gut microbiome influences the response of cancer patients to immunotherapies. Baruch et al. and Davar et al. report first-in-human clinical trials to test whether fecal microbiota transplantation (FMT) can affect how metastatic melanoma patients respond to anti–PD-1 immunotherapy (see the Perspective by Woelk and Snyder). Both studies observed evidence of clinical benefit in a subset of treated patients. This included increased abundance of taxa previously shown to be associated with response to anti–PD-1, increased CD8 ⁺ T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells, which are involved in immunosuppression. These studies provide proof-of-concept evidence for the ability of FMT to affect immunotherapy response in cancer patients. Science , this issue p. 602 , p. 595 ; see also p. 573

The parasite Trypanosoma brucei cycles between insect and mammalian hosts, and is the causative agent of sleeping sickness. Here, we performed genome-wide mapping of 2ʹ-O-methylations (Nms) on trypanosome rRNA using three high-throughput sequencing methods; RibOxi-seq, RiboMeth-seq and 2ʹ-OMe-seq. This is the first study using three genome-wide mapping approaches on rRNA from the same species showing the discrepancy among the methods. RibOxi-seq detects all the sites, but RiboMeth-seq is the only method to evaluate the level of a single Nm site. The sequencing revealed at least ninety-nine Nms guided by eighty-five snoRNAs among these thirty-eight Nms are trypanosome specific sites. We present the sequence and target of the C/D snoRNAs guiding on rRNA. This is the highest number of Nms detected to date on rRNA of a single cell parasite. Based on RiboMeth-seq, several Nm sites were found to be differentially regulated at the two stages of the parasite life cycle, the insect procyclic form (PCF) versus the bloodstream form (BSF) in the mammalian host.

Trypanosoma brucei, the parasite that causes sleeping sickness, cycles between an insect and a mammalian host. However, the effect of RNA modifications such as pseudouridinylation on its ability to survive in these two different host environments is unclear. Here, two genome-wide approaches were applied for mapping pseudouridinylation sites (Ψs) on small nucleolar RNA (snoRNA), 7SL RNA, vault RNA, and tRNAs from T. brucei. We show using HydraPsiSeq and RiboMeth-seq that the Ψ on C/D snoRNA guiding 2′-O-methylation increased the efficiency of the guided modification on its target, rRNA. We found differential levels of Ψs on these noncoding RNAs in the two life stages (insect host and mammalian host) of the parasite. Furthermore, tRNA isoform abundance and Ψ modifications were characterized in these two life stages demonstrating stage-specific regulation. We conclude that the differential Ψ modifications identified here may contribute to modulating the function of noncoding RNAs involved in rRNA processing, rRNA modification, protein synthesis, and protein translocation during cycling of the parasite between its two hosts.

Graph fragmentation aims to find the smallest vertex subset whose removal breaks a graph into components of bounded size. While this problem has applications in network dismantling and combinatorics, theoretical bounds on optimal solutions remain limited. We derive rigorous bounds for several graph classes, characterize hard instances, and illuminate the relationship between graph structure and optimal fragmentation strategies. Specifically, we show that for random d-regular graphs with n vertices, the minimal size of the fragmenting subset of nodes is asymptotically almost surely $\left|S\right|\ge {\displaystyle \frac{d-2}{2d-2}}n-o(n)$, and that asymptotically almost surely, $n-2\alpha (G)-o(n)\le \left|S\right|\le n-\alpha (G)+o(n)$, where $\alpha (G)$ is the independence number of G. For $d\gg 1$, we prove that asymptotically almost surely, $\left|S\right|/n\approx 1-logd/d$. However, we show that the line graphs of random regular graphs are considerably harder to fragment, with $\left|S\right|/n\ge 1-c/d$ for some constant c.