A three-in-one-bullet for oesophageal cancer: replication fork collapse, spindle attachment failure and enhanced radiosensitivity generated by a ruthenium(ii) metallo-intercalator

[Ru(phen)2(tpphz)]2+ simultaneously inhibits DNA replication, blocks mitosis and enhances DNA-damaging ionising radiation in oesophageal cancer cells.

Nup132 modulates meiotic spindle attachment in fission yeast by regulating kinetochore assembly

During meiosis, the kinetochore undergoes substantial reorganization to establish monopolar spindle attachment. In the fission yeast Schizosaccharomyces pombe, the KNL1–Spc7-Mis12-Nuf2 (KMN) complex, which constitutes the outer kinetochore, is disassembled during meiotic prophase and is reassembled before meiosis I. Here, we show that the nucleoporin Nup132 is required for timely assembly of the KMN proteins: In the absence of Nup132, Mis12 and Spc7 are precociously assembled at the centromeres during meiotic prophase. In contrast, Nuf2 shows timely dissociation and reappearance at the meiotic centromeres. We further demonstrate that depletion of Nup132 activates the spindle assembly checkpoint in meiosis I, possibly because of the increased incidence of erroneous spindle attachment at sister chromatids. These results suggest that precocious assembly of the kinetochores leads to the meiosis I defects observed in the nup132-disrupted mutant. Thus, we propose that Nup132 plays an important role in establishing monopolar spindle attachment at meiosis I through outer kinetochore reorganization at meiotic prophase.

Design of a Retrofittable Spindle Attachment for High Frequency Vibration-Assisted Drilling

Conventional drilling of modern super alloys and composite material induces high stresses in the vicinity of drilled holes along with high thrust forces which lead to problems in terms of hole quality and accuracy as well as increased tool wear. A recent and promising technique to overcome these challenges is to introduce vibration assistance in the cutting zone by superimposing oscillating vibration in the feed direction of the tool. Two regimes of vibration excitation could be applied for this purpose: low frequency (<500 Hz) high amplitude (>100 μm) and high frequency (>500 Hz) low amplitude (<20 μm). Motivated by the advantages of the HF-VAD and the limited work available in the literature for this regime, a new system is developed by the authors where the rotating tool is excited to high frequency and low amplitude. The new design is based on the use of piezoelectric actuators to generate the motion and a high speed slip ring to ensure the transfer of sufficient power to the actuator. A novel concept was implemented by de-coupling the rotary motion of the spindle from the vibrational motion of the actuator to ensure a higher efficiency of power transmission without damaging either the actuator or the spindle. With this design, a retrofittable HSK 100A toolholder with high frequency excitation spindle attachment was manufactured to incorporate drill sizes up to 1/4 inches. Commissioning tests were performed under no load and spring loaded conditions and it was found that the system has a capability to excite the tool up to 100 μm at 900 Hz (resonance frequency) and up to 5 μm between 500–800 Hz and 1100–2500 Hz. HF-VAD tests were conducted using this new attachment on Aluminum 6061 and it was found that the system was able to successfully obtain the prescribed frequency and amplitude. Up to 50% reduction in thrust forces was obtained in HF-VAD in comparison to conventional drilling under same cutting parameters; this is associated with finer chips with break off serrations.

Recurrent loss of CenH3 is associated with independent transitions to holocentricity in insects

Faithful chromosome segregation in all eukaryotes relies on centromeres, the chromosomal sites that recruit kinetochore proteins and mediate spindle attachment during cell division. The centromeric histone H3 variant, CenH3, is the defining chromatin component of centromeres in most eukaryotes, including animals, fungi, plants, and protists. In this study, using detailed genomic and transcriptome analyses, we show that CenH3 was lost independently in at least four lineages of insects. Each of these lineages represents an independent transition from monocentricity (centromeric determinants localized to a single chromosomal region) to holocentricity (centromeric determinants extended over the entire chromosomal length) as ancient as 300 million years ago. Holocentric insects therefore contain a CenH3-independent centromere, different from almost all the other eukaryotes. We propose that ancient transitions to holocentricity in insects obviated the need to maintain CenH3, which is otherwise essential in most eukaryotes, including other holocentrics.