The wear of a wide range of material combinations has been studied in unlubricated conditions. Loads of 50 g to 10 Kg and speeds of 2 to 660 cm/s have been used. A representative selection of the results is given. As a broad classification two contrasting mechanisms of wear have been observed. In nearly all experiments, and for all types of wear mechanism, once equilibrium surface conditions are established the wear rate is independent of the apparent area of contact. The wear rate is accurately proportional to the load for only a limited number of combinations but there are many other examples for which the relation between wear rate and load shows only a small deviation from direct proportionality. It is suggested that with the same surface conditions the wear rate is proportional to the load; in practice this simple relation is modified because the surface conditions depend on the load. These rules of wear may be derived, on a priori grounds, from the experimental results, or from more detailed theoretical calculations.

Summary All organisms must replicate their genetic information accurately to ensure its faithful transmission. DNA polymerase errors provide an important source of genetic variation that can drive evolution. Understanding the origins of genetic variation will inform our understanding of evolution and the development of genetic diseases. A number of factors have been proposed to influence mutagenesis [1–10]. Here, we used mutation accumulation lines, whole-genome sequencing and whole-transcriptome analysis to study the locations and rate at which mutations arise in bacteria with as little selection bias as possible [11, 12]. Our analysis of greater than 7,000 replication errors in over 180 sequenced lines that underwent a total of more than 370,000 generations has provided new insights into how DNA polymerase errors sculpt genetic variation and drive evolution. Homopolymer run enrichment outside of genes causes insertions and deletions in these regions. Genes encoded in the lagging strand are transcribed such that RNA polymerase and DNA polymerase collide head-on. Head-on genes have been proposed to mutate at a higher rate than genes transcribed codirectionally with DNA polymerase progression due to conflicts between transcription and DNA replication [6, 10]. We did not detect associations between the number of base pair substitutions in genes and their orientation or expression. Strikingly, any higher mutation rate for head-on genes can be explained by differing sequence composition between the leading and lagging strands and the error bias for DNA polymerase in specific sequence contexts. Therefore, we find local sequence context is the major determinant of mutagenesis in bacteria.

The expansion of brain size in species with a large and gyrified cerebral cortex is triggered by a relative enlargement of the subventricular zone (SVZ) during development. Here, we uncover the key role of the novel interphase centrosome protein Akna in this process and show that it localizes mainly at subdistal appendages of the mother centriole in subtypes of neural stem and progenitor cells. Akna is necessary and sufficient to organize microtubules (MT) at the centrosome and regulate their polymerization. These processes show an unprecedented role of MT dynamics controlled by Akna in regulating entry to, and exit from, the SVZ by controlling delamination from the neuroepithelial ventricular zone and retention of cells in the SVZ. Importantly, Akna plays a similar role in mammary epithelial cells undergoing epithelial-to-mesenchymal transition (EMT), generalizing the importance of this new centrosomal protein in orchestrating MT polymerization to control cell delamination. Main Text Expansion of the SVZ is the developmental hallmark of enlarged and folded cerebral cortices, underpinning the importance of understanding the mechanisms that govern its formation. Epithelial-like neural stem cells (NSCs) divide in the ventricular zone (VZ), and mostly generate a new NSC and a committed progenitor cell at midneurogenesis. The latter delaminates and transforms into a basal progenitor (BP) which constitute the SVZ 1,2. Keeping cells for a defined temporal window in the SVZ is essential to control further amplification and fate determination 3,4. To identify novel regulators of these processes we compared the transcriptome of murine NSC sub-types that generate BPs from those that do not 5-7. We report here a novel and unexpected regulator of BP generation and SVZ formation, called Akna. Our work uncovers the function of this mis-annotated protein at the centrosome and reveals interphase centrosomal microtubule organizing center (MTOC) activity as a novel mechanism regulating EMT-like delamination of cells from the VZ to enter the SVZ and their retention therein. Akna is an integral component of the interphase centrosome In murine cerebral cortex, Akna mRNA levels correlate with the time of SVZ generation (low at embryonic day 11 (E11), high at E14, low at E18) and NSCs isolated at the peak of SVZ generation have higher Akna levels when transitioning to BPs 6 (Extended Data Fig. 1a,b). We therefore chose Akna as a candidate regulator of SVZ and BP generation and generated several rat and mouse monoclonal antibodies against Akna, validated by means of RNA interference, to test this hypothesis further (Extended Data Fig. 1c-f, information about clones Konno, D. et al. Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat Cell Biol 10, 93-101 (2008). Taverna, E., Gotz, M. & Huttner, W. B. The cell biology of neurogenesis: toward an understanding of the development and evolution of the neocortex. Annu Rev Cell Dev Biol 30, 465-502 (2014). Martinez-...

We tested the activity of four predicated RNase H enzymes including two RNase HI-type enzymes in addition to RNase HII (RnhB) and RNase HIII (RnhC) on several RNA:DNA hybrid substrates with different divalent metal cations. We found that the two RNase HI-type enzymes YpdQ and YpeP failed to show activity on the three substrates tested. RNase HII and RNase HIII cleaved all substrates tested although activity was dependent on the metal made available. We show that RNase HII and RNase HIII are both able to incise 5' to a single rNMP. We show that RNase HIII incision at a single rNMP occurs most efficiently with Mn, an activity we found to be conserved among other Gram-positive RNase HIII enzymes. Characterization of RNase HII and HIII with metal concentrations in the physiological range showed that RNase HII can cleave at single rNMPs embedded in DNA while RNase HIII is far less effective. Further, using metal concentrations within physiological range, RNase HIII efficiently cleaved longer RNA:DNA hybrids lacking an RNA:DNA junction while RNase HII is much less effective. Phenotypic analysis shows that cells with an deletion are sensitive to hydroxyurea (HU). In contrast, cells with an deletion show wild type growth in the presence of HU supporting the hypothesis that RNase HII and HIII have distinct substrate specificities This work demonstrates how metal availability influences substrate recognition and activity of RNase HII and HIII providing insight into their function Ribonuclease H (RNase H) represents a class of proteins that cleave RNA:DNA hybrids helping resolve R-loops and Okazaki fragments as well as initiating the process of ribonucleotide excision repair (RER). We investigated the activity of four RNase H enzymes finding that only RNase HII and HIII have activity and that their substrate preference is dependent on metal availability. To understand factors that contribute to RNase HII and RNase HIII substrate preference, we show that in the presence of metal concentrations within physiological range, RNase HII and HIII have distinct activities on different RNA:DNA hybrids. This work provides insight into how RNase HII and HIII repair the broad range of RNA:DNA hybrids that form in Gram-positive bacteria.