SummaryEndogenous formaldehyde is produced by numerous biochemical pathways fundamental to life, and it can crosslink both DNA and proteins. However, the consequences of its accumulation are unclear. Here we show that endogenous formaldehyde is removed by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), and Adh5−/− mice therefore accumulate formaldehyde adducts in DNA. The repair of this damage is mediated by FANCD2, a DNA crosslink repair protein. Adh5−/−Fancd2−/− mice reveal an essential requirement for these protection mechanisms in hematopoietic stem cells (HSCs), leading to their depletion and precipitating bone marrow failure. More widespread formaldehyde-induced DNA damage also causes karyomegaly and dysfunction of hepatocytes and nephrons. Bone marrow transplantation not only rescued hematopoiesis but, surprisingly, also preserved nephron function. Nevertheless, all of these animals eventually developed fatal malignancies. Formaldehyde is therefore an important source of endogenous DNA damage that is counteracted in mammals by a conserved protection mechanism.

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This work addresses the fundamental problem of distinguishing between a driver and passenger using a mobile phone, which is the critical input to enable numerous safety and interface enhancements. Our detection system leverages the existing car stereo infrastructure, in particular, the speakers and Bluetooth network. Our acoustic approach has the phone send a series of customized high frequency beeps via the car stereo. The beeps are spaced in time across the left, right, and if available, front and rear speakers. After sampling the beeps, we use a sequential change-point detection scheme to time their arrival, and then use a differential approach to estimate the phone's distance from the car's center. From these differences a passenger or driver classification can be made. To validate our approach, we experimented with two kinds of phones and in two different cars. We found that our customized beeps were imperceptible to most users, yet still playable and recordable in both cars. Our customized beeps were also robust to background sounds such as music and wind, and we found the signal processing did not require excessive computational resources. In spite of the cars' heavy multi-path environment, our approach had a classification accuracy of over 90%, and around 95% with some calibrations. We also found we have a low false positive rate, on the order of a few percent.

In this work, we have focused on the influence of Gd 3+ substitution in structural, magnetic and electrical properties of cobalt ferrite synthesized by using sol-gel auto combustion method. The powder x-ray diffraction analysis reveals that the Gd-substituted cobalt ferrites crystallize in single phase spinel structure for lower concentrations of Gd 3+ , while a trace of GdFeO 3 appears as a minor phase for higher concentrations. Raman and Fourier transform infrared spectra confirm the formation of spinel structure. Furthermore, Raman analysis shows that the inversion degree of cobalt ferrite decreases with Gd 3+ doping. The field emission scanning electron microscopy images show that the substitution of small amount of Gd 3+ causes considerable reduction of grain size. Studies on magnetic properties reveal that the coercivity of Gdsubstituted cobalt ferrites enhances from 1265 Oe to 1635 Oe and the saturation magnetization decreases monotonically from 80 emu/g to 53.8 emu/g and the magnetocrystalline anisotropy constant increases from 5.8x10 5 erg/cm 3 to 2.23 x10 6 erg/cm 3 at 300 K. The electrical properties show that the Gd 3+ doped samples exhibit the high values of dielectric constant (616 at 100 Hz) and ac conductivity (4.83x10 -5 S/cm at 100 Hz) at room temperature. The activation energy is found to decrease from 0.408 to 0.347 eV in for the rise of Gd 3+ content. The impedance study 2 brings out role of bulk grain and grain-boundary towards the electrical resistance and capacitance of cobalt ferrite. Gd-substitution and nano size of cobalt ferrite enhance the electrical and magnetic properties which could ensure a higher memory storage capability. IntroductionSpinel ferrites with the general formula MFe 2 O 4 (M-Co, Ni, Mn and Zn etc.) are the most interesting magnetic oxides due to their superior electrical, magnetic and optical properties 1-8 .Among the spinel ferrites, cobalt ferrite is an attractive candidate due to its significant properties such as high coercivity, high electrical resistivity, moderate saturation magnetization, large magnetocrystalline anisotropy (~4x10 6 ergs/cm 3 ), good chemical stability and high Curie temperature (793 K) 9-16 . It is of significant technological interests due to its potential applications in targeted drug delivery systems 17, 18 , microwave devices 19, 20 , sensors 21 , catalysis 22, 23 and magnetic recording applications 9, 24 etc. Recently, the doping of small amount of trivalent rare earth cations in spinel ferrite has emerged as a promising strategy to improve the magnetic and electrical properties. Moreover, these properties are governed by the antiferromagnetic super exchange interaction between Fe 3+ -Fe 3+ ions; introducing small amount of trivalent rare earth (RE) ions into the spinel ferrite lattices will also induce RE 3+ -Fe 3+ interactions 25-30 . It is well known that the intrinsic properties of the spinel ferrite nanoparticles depend on the chemical composition and preparative methods 31, 32 . Spinel ferrites are prepared using several methods s...

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Numerical centrosome aberrations underlie certain developmental abnormalities and may promote cancer. A cell maintains normal centrosome numbers by coupling centrosome duplication with segregation, which is achieved through sustained association of each centrosome with a mitotic spindle pole. Although the microcephaly- and primordial dwarfism-linked centrosomal protein CEP215 has been implicated in this process, the molecular mechanism responsible remains unclear. Here, using proteomic profiling, we identify the minus end-directed microtubule motor protein HSET as a direct binding partner of CEP215. Targeted deletion of the HSET-binding domain of CEP215 in vertebrate cells causes centrosome detachment and results in HSET depletion at centrosomes, a phenotype also observed in CEP215-deficient patient-derived cells. Moreover, in cancer cells with centrosome amplification, the CEP215–HSET complex promotes the clustering of extra centrosomes into pseudo-bipolar spindles, thereby ensuring viable cell division. Therefore, stabilization of the centrosome–spindle pole interface by the CEP215–HSET complex could promote survival of cancer cells containing supernumerary centrosomes.

Despite the growing number of therapies that target cancer-specific pathways, cytotoxic treatments remain important clinical tools. The rationale for targeting cell proliferation by chemotherapeutic agents stems from the assumption that tumours harbour a greater fraction of actively dividing cells than normal tissues. One such group of cytotoxic drugs impair microtubule polymers, which are cytoskeletal components of cells essential for many processes including mitosis. However, in addition to their antimitotic action, these agents cause debilitating and dose-limiting neurotoxicity because of the essential functions of microtubules in neurons. To overcome this limitation, drugs against mitosis-specific targets have been developed over the past decade, albeit with variable clinical success. Here we review the key lessons learnt from antimitotic therapies with a focus on inhibitors of microtubule motor proteins. Furthermore, based on the cancer genome data, we describe a number of motor proteins with tumour type-specific alterations, which warrant further investigation in the quest for cytotoxic targets with increased cancer specificity.