Dissociation Potential Curves of Low-Lying States in Transition Metal Hydrides. I. Hydrides of Group 4

The dissociation energy curves of low-lying spin-mixed states for Group 4 hydrides, TiH, ZrH, and HfH, have been calculated using both effective core potential and all-electron approaches. A comprehensive set of theoretical results including the dissociation energies, equilibrium distances, harmonic frequencies, anharmonicities, rotational constants, and dipole moments are reported for these molecules. We present results for both ground and a few excited states, filling a considerable gap in available data for these molecules. Absorption spectra are also predicted on the basis of the results. The present study uses three methods, all based on the multiconfigurational self-consistent field (MCSCF) method, augmented by second-order configuration interaction (SOCI), with either an effective core potential basis set (SBKJC) or a double-ζ basis set (MIDI):  (i) MCSCF+SOCI/SBKJC(f,p) with a one-electron approximation using effective nuclear charges, (ii) MCSCF+SOCI/MIDI(3p,3p) with the full Breit−Pauli Hamiltonian, and (iii) MCSCF +SOCI/MIDI(3p,3p) with the relativistic elimination of the small component scheme and full Breit−Pauli Hamiltonian. The results are compared with previous theoretical studies and available experimental data reported previously. Good agreement is obtained between the results obtained when the first and third methods are used

Dissociation Potential Curves of Low-Lying States in Transition Metal Hydrides. 2. Hydrides of Groups 3 and 5

The dissociation energy curves of low-lying spin-mixed states for Group 5 hydrides (VH, NbH, and TaH), as well as Group 3 hydrides (ScH, YH, and LaH), have been calculated by using both effective core potential (ECP) and all-electron (AE) approaches. The two approaches are based on the multiconfiguration self-consistent field (MCSCF) method, followed by second-order configuration interaction (SOCI) calculations:  the first method employs an ECP basis set proposed by Stevens and co-workers (SBKJC) augmented by a set of polarization functions, and spin−orbit coupling effects are estimated with a one-electron approximation, using effective nuclear charges. The second method employs a double-ζ basis set developed by Huzinaga (MIDI) and three sets of p functions are added to both transition element and hydrogen and one set of f functions is also added to the transition element. The relativistic elimination of small components (RESC) scheme and full Breit−Pauli Hamiltonian are employed in the AE approaches to incorporate relativistic effects. The present paper reports a comprehensive set of theoretical results including the dissociation energies, equilibrium distances, electronic transition energies, harmonic frequencies, anharmonicities, and rotational constants for several low-lying spin-mixed states in the hydrides, filling a considerable gap in available data for these molecules. Transition moments are also computed among the spin-mixed states, and qualitative agreement is obtained for Group 3 hydrides in comparison with the experimental results reported by Ram and Bernath. Peak positions of emission spectra in Group 5 hydrides are also predicted

Selective rab11 transport and the intrinsic regenerative ability of CNS axons.

Neurons lose intrinsic axon regenerative ability with maturation, but the mechanism remains unclear. Using an in-vitro laser axotomy model, we show a progressive decline in the ability of cut CNS axons to form a new growth cone and then elongate. Failure of regeneration was associated with increased retraction after axotomy. Transportation into axons becomes selective with maturation; we hypothesized that selective exclusion of molecules needed for growth may contribute to regeneration decline. With neuronal maturity rab11 vesicles (which carry many molecules involved in axon growth) became selectively targeted to the somatodendritic compartment and excluded from axons by predominant retrograde transport However, on overexpression rab11 was mistrafficked into proximal axons, and these axons showed less retraction and enhanced regeneration after axotomy. These results suggest that the decline of intrinsic axon regenerative ability is associated with selective exclusion of key molecules, and that manipulation of transport can enhance regeneration

Exclusion of integrins from CNS axons is regulated by Arf6 activation and the AIS.

Integrins are adhesion and survival molecules involved in axon growth during CNS development, as well as axon regeneration after injury in the peripheral nervous system (PNS). Adult CNS axons do not regenerate after injury, partly due to a low intrinsic growth capacity. We have previously studied the role of integrins in axon growth in PNS axons; in the present study, we investigate whether integrin mechanisms involved in PNS regeneration may be altered or lacking from mature CNS axons by studying maturing CNS neurons in vitro. In rat cortical neurons, we find that integrins are present in axons during initial growth but later become restricted to the somato-dendritic domain. We investigated how this occurs and whether it can be altered to enhance axonal growth potential. We find a developmental change in integrin trafficking; transport becomes predominantly retrograde throughout axons, but not dendrites, as neurons mature. The directionality of transport is controlled through the activation state of ARF6, with developmental upregulation of the ARF6 GEF ARNO enhancing retrograde transport. Lowering ARF6 activity in mature neurons restores anterograde integrin flow, allows transport into axons, and increases axon growth. In addition, we found that the axon initial segment is partly responsible for exclusion of integrins and removal of this structure allows integrins into axons. Changing posttranslational modifications of tubulin with taxol also allows integrins into the proximal axon. The experiments suggest that the developmental loss of regenerative ability in CNS axons is due to exclusion of growth-related molecules due to changes in trafficking.The authors thank Dr. Matthew N. Rasband for kindly providing the adenoviruses for ankG silencing experiment and Dr. Juan Bonifacino for AP-1 constructs. We also thank Menghon Cheah for his assistance. We acknowledge funding from the Medical Research Council, the Christopher and Dana Reeve Foundation, EU Framework 7 Project Plasticise, the European Research Council, the John and Lucille van Geest Foundation, and the NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from the Society for Neuroscience via http://dx.doi.org/10.1523/JNEUROSCI.2850-14.201

Characterization of Individuals with Sacroiliac Joint Bridging in a Skeletal Population: Analysis of Degenerative Changes in Spinal Vertebrae

Theaimof this study was to characterize the individualswith sacroiliac joint bridging (SIB) by analyzing the degenerative changes intheirwhole vertebral column and comparing themwith the controls.Atotal of 291modern Japanesemale skeletons,with an averageage at death of 60.8 years, were examined macroscopically. They were divided into two groups: individuals with SIB and thosewithout bridging (Non-SIB).The degenerative changes in their whole vertebral column were evaluated, and marginal osteophytescores (MOS) of the vertebral bodies and degenerative joint scores in zygapophyseal jointswere calculated. SIBwas recognized in 30individuals froma total of 291 males (10.3%).The average of age at death in SIB group was significantly higher than that in Non-SIBgroup. The values ofMOS in the thoracic spines, particularly in the anterior part of the vertebral bodies, were consecutively higherin SIB group than in Non-SIB group. Incidence of fused vertebral bodies intervertebral levels was obviously higher in SIB groupthan in Non-SIB group. SIB and marginal osteophyte formation in vertebral bodies could coexist in a skeletal population of men.Some systemic factors might act on these degenerative changes simultaneously both in sacroiliac joint and in vertebral column

Osteoclasts adapt to physioxia perturbation through DNA demethylation

Oxygen plays an important role in diverse biological processes. However, since quantitation of the partial pressure of cellular oxygen in vivo is challenging, the extent of oxygen perturbation in situ and its cellular response remains underexplored. Using two-photon phosphorescence lifetime imaging microscopy, we determine the physiological range of oxygen tension in osteoclasts of live mice. We find that oxygen tension ranges from 17.4 to 36.4 mmHg, under hypoxic and normoxic conditions, respectively. Physiological normoxia thus corresponds to 5% and hypoxia to 2% oxygen in osteoclasts. Hypoxia in this range severely limits osteoclastogenesis, independent of energy metabolism and hypoxia-inducible factor activity. We observe that hypoxia decreases ten-eleven translocation (TET) activity. Tet2/3 cooperatively induces Prdm1 expression via oxygen-dependent DNA demethylation, which in turn activates NFATc1 required for osteoclastogenesis. Taken together, our results reveal that TET enzymes, acting as functional oxygen sensors, regulate osteoclastogenesis within the physiological range of oxygen tension, thus opening new avenues for research on in vivo response to oxygen perturbation.Nishikawa K., Seno S., Yoshihara T., et al. Osteoclasts adapt to physioxia perturbation through DNA demethylation. EMBO Reports 22, e53035 (2021); https://doi.org/10.15252/embr.202153035