ón Científica Pulmón y Ventilación Mecánica. BACKGROUND GRECCAR 2 was the first multicentre, randomised trial to compare local excision with total mesorectal excision in downstaged low rectal cancer. Encouraging oncological results were noted at 3 years’ follow-up but needed to be corroborated with longer follow-up. In this study, we aimed to report the 5-year oncological outcomes, including local recurrence, metastatic disease, and survival. METHODS Patients age 18 years and older with T2T3 low rectal cancer, of maximum size 4 cm, who were clinically good responders after chemoradiotherapy (residual tumour ≤2 cm) were randomly assigned before surgery to either local excision or total mesorectal excision. Randomisation was centralised and not stratified and used permuted blocks of size eight. In the local excision group, a completion total mesorectal excision was performed if pathological tumour stage was ypT2-3. The primary objective of this study was to assess the 5-year oncological outcomes of local recurrence, metastatic disease, disease-free survivis, there was no difference between the local excision and total mesorectal excision groups in 5-year local recurrence (7% [95% CI 3-16] vs 7% [3-16]; adjusted hazard ratio [HR] 0·71 [95% CI 0·19-2·58]; p=0·60), metastatic disease (18% [CI 11-30] vs 19% [11-31]; 0·86 [0·36-2·06]; p=0·73), overall survival (84% [73-91] vs 82% [71-90]; 0·92 [0·38-2·22]; p=0·85), disease-free survival (70% [58-79] vs 72% [60-82]; 0·87 [0·44-1·72]; p=0·68), or cancer-specific mortality (7% [3-17] vs 10% [5-20]; 0·65 [0·17-2·49]; p=0·53). INTERPRETATION The 5-year results of this multicentre randomised trial corroborate the 3-year results, providing no evidence of difference in oncological outcomes between local excision and total mesorectal excision. Local excision can be proposed in selected patients having a small T2T3 low rectal cancer with a good clinical response after chemoradiotherapy. FUNDING National Cancer Institute of France. A new way to culture and image flowers is uncovering the processes that take place in reproductive cells buried deep in plants. © 2020, Wang and Dobritsa.Every movement ends in a period of stillness. Current models assume that commands that hold the limb at a target location do not depend on the commands that moved the limb to that location. Here, we report a surprising relationship between movement and posture in primates on a within-trial basis, the commands that hold the arm and finger at a target location depend on the mathematical integration of the commands that moved the limb to that location. Following damage to the corticospinal tract, both the move and hold period commands become more variable. However, the hold period commands retain their dependence on the integral of the move period commands. Thus, our data suggest that the postural controller possesses a feedforward module that uses move commands to calculate a component of hold commands. This computation may arise within an unknown subcortical system that integrates cortical commands to stabilize limb posture. plain-language-summary Moving an arm requires the brain to send electrical signals to n volunteers held a robot arm, and Albert et al. measured the forces they produced while reaching and holding still. Both the human and monkey experiments revealed a relationship between move signals and hold signals. Like for eye movements, hold signals for the arm could be calculated from the move signals. In further experiments with stroke patients where the brain had been damaged, the move signals were found to be deteriorated, but the way hold signals were calculated stayed the same. This suggests that there is an unknown structure within the brain that calculates hold signals based on move signals. Investigating how the brain holds the arm still may help scientists understand why some neurological conditions like stroke or dystonia cause unwanted movements or unusual postures. This might also lead scientists to develop new ways to treat these conditions. © 2020, Albert et al.The electrical connectivity in the inferior olive (IO) nucleus plays an important role in generating well-timed spiking activity. Here we combined electrophysiological and computational approaches to assess the functional organization of the IO nucleus in mice. Spontaneous fast and slow subthreshold events were commonly encountered during in vitro recordings. We show that whereas the fast events represent intrinsic regenerative activity, the slow events reflect the electrical connectivity between neurons (‘spikelets’). Recordings from cell pairs revealed the synchronized occurrence of distinct groups of spikelets; their rate and distribution enabled an accurate estimation of the number of connected cells and is suggestive of a clustered organization. This study thus provides a new perspective on the functional and structural organization of the olivary nucleus and a novel experimental and theoretical approach to study electrically coupled networks. © 2020, Lefler et al.Many biological features are conserved and thus considered to be resistant to evolutionary change. While rapid genetic adaptation following the removal of conserved genes has been observed, we often lack a mechanistic understanding of how adaptation happens. We used the budding yeast, Saccharomyces cerevisiae, to investigate the evolutionary plasticity of chromosome metabolism, a network of evolutionary conserved modules. We experimentally evolved cells constitutively experiencing DNA replication stress caused by the absence of Ctf4, a protein that coordinates the enzymatic activities at replication forks. Parallel populations adapted to replication stress, over 1000 generations, by acquiring multiple, concerted mutations. These mutations altered conserved features of two chromosome metabolism modules, DNA replication and sister chromatid cohesion, and inactivated a third, the DNA damage checkpoint. The selected mutations define a functionally reproducible evolutionary trajectory. We suggest that the evolutions in their replication machinery. Studying the rapid evolution that follows genetic perturbations could help researchers to better deal with challenges in cancer treatment and the development of antibiotic resistance in bacteria, as well as leading to a deeper understanding of both evolution and cell biology. AZD-5462 concentration © 2020, Fumasoni and Murray.