[Sm(CH3COO)3 (H2O)2] · CH3COOH, ein Essigsäureaddukt des Samarium(III)-acetatdihydrate

The crystal structure of the acetic acid adduct of the so far unknown samarium(III) acetate dihydrate was determined from single-crystal four-circle diffractometer data. It has the composition [Sm (CH3COO)3(H2O)2] CH3COOH containing {[Sm(CH3COO)3(H2O)2]}2 dimers and crystallizes in the trigonal system, R3̄̄̄̄, a = 2695.1(3), c = 1030.8(4) pm, Vm = 216.97(5) cm3/mol, R = 0.041, Rw = 0.030

Spitzer observations of extragalactic H II regions - III. NGC 6822 and the hot star, H II region connection

Using the short-high module of the Infrared Spectrograph on the Spitzer Space Telescope, we have measured the [S IV] 10.51, [Ne II] 12.81, [Ne III] 15.56, and [S III] 18.71-micron emission lines in nine H II regions in the dwarf irregular galaxy NGC 6822. These lines arise from the dominant ionization states of the elements neon (Ne$^{++}$, Ne$^+$) and sulphur (S$^{3+}$, S$^{++}$), thereby allowing an analysis of the neon to sulphur abundance ratio as well as the ionic abundance ratios Ne$^+$/Ne$^{++}$ and S$^{3+}$/S$^{++}$. By extending our studies of H II regions in M83 and M33 to the lower metallicity NGC 6822, we increase the reliability of the estimated Ne/S ratio. We find that the Ne/S ratio appears to be fairly universal, with not much variation about the ratio found for NGC 6822: the median (average) Ne/S ratio equals 11.6 (12.2$\pm$0.8). This value is in contrast to Asplund et al.'s currently best estimated value for the Sun: Ne/S = 6.5. In addition, we continue to test the predicted ionizing spectral energy distributions (SEDs) from various stellar atmosphere models by comparing model nebulae computed with these SEDs as inputs to our observational data, changing just the stellar atmosphere model abundances. Here we employ a new grid of SEDs computed with different metallicities: Solar, 0.4 Solar, and 0.1 Solar. As expected, these changes to the SED show similar trends to those seen upon changing just the nebular gas metallicities in our plasma simulations: lower metallicity results in higher ionization. This trend agrees with the observations.Comment: 22 pages, 13 figures. To be published in MNRAS. reference added and typos fixed. arXiv admin note: text overlap with arXiv:0804.0828, which is paper II by Rubin et al. (2008

The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (Wld(S)) nerves

BACKGROUND: The progressive nature of Wallerian degeneration has long been controversial. Conflicting reports that distal stumps of injured axons degenerate anterogradely, retrogradely, or simultaneously are based on statistical observations at discontinuous locations within the nerve, without observing any single axon at two distant points. As axon degeneration is asynchronous, there are clear advantages to longitudinal studies of individual degenerating axons. We recently validated the study of Wallerian degeneration using yellow fluorescent protein (YFP) in a small, representative population of axons, which greatly improves longitudinal imaging. Here, we apply this method to study the progressive nature of Wallerian degeneration in both wild-type and slow Wallerian degeneration (Wld(S)) mutant mice. RESULTS: In wild-type nerves, we directly observed partially fragmented axons (average 5.3%) among a majority of fully intact or degenerated axons 37–42 h after transection and 40–44 h after crush injury. Axons exist in this state only transiently, probably for less than one hour. Surprisingly, axons degenerated anterogradely after transection but retrogradely after a crush, but in both cases a sharp boundary separated intact and fragmented regions of individual axons, indicating that Wallerian degeneration progresses as a wave sequentially affecting adjacent regions of the axon. In contrast, most or all Wld(S )axons were partially fragmented 15–25 days after nerve lesion, Wld(S )axons degenerated anterogradely independent of lesion type, and signs of degeneration increased gradually along the nerve instead of abruptly. Furthermore, the first signs of degeneration were short constrictions, not complete breaks. CONCLUSIONS: We conclude that Wallerian degeneration progresses rapidly along individual wild-type axons after a heterogeneous latent phase. The speed of progression and its ability to travel in either direction challenges earlier models in which clearance of trophic or regulatory factors by axonal transport triggers degeneration. Wld(S )axons, once they finally degenerate, do so by a fundamentally different mechanism, indicated by differences in the rate, direction and abruptness of progression, and by different early morphological signs of degeneration. These observations suggest that Wld(S )axons undergo a slow anterograde decay as axonal components are gradually depleted, and do not simply follow the degeneration pathway of wild-type axons at a slower rate

Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies.

NAMPT may represent a novel target for drug discovery in various therapeutic areas, including oncology and inflammation. Additionally, recent work has suggested that targeting NAMPT has potential in treating axon degeneration. In this work, publicly available X-ray co-crystal structures of NAMPT and the structures of two known NAMPT inhibitors were used as the basis for a structure- and ligand-based virtual screening campaign. From this, two novel series of NAMPT inhibitors were identified, one of which showed a statistically significant protective effect when tested in a cellular model of axon degeneration

Axonal transport declines with age in two distinct phases separated by a period of relative stability.

Axonal transport is critical for supplying newly synthesized proteins, organelles, mRNAs, and other cargoes from neuronal cell bodies into axons. Its impairment in many neurodegenerative conditions appears likely to contribute to pathogenesis. Axonal transport also declines during normal aging, but little is known about the timing of these changes, or about the effect of aging on specific cargoes in individual axons. This is important for understanding mechanisms of age-related axon loss and age-related axonal disorders. Here we use fluorescence live imaging of peripheral nerve and central nervous system tissue explants to investigate vesicular and mitochondrial axonal transport. Interestingly, we identify 2 distinct periods of change, 1 period during young adulthood and the other in old age, separated by a relatively stable plateau during most of adult life. We also find that after tibial nerve regeneration, even in old animals, neurons are able to support higher transport rates of each cargo for a prolonged period. Thus, the age-related decline in axonal transport is not an inevitable consequence of either aging neurons or an aging systemic milieu

Novel HDAC6 inhibitors increase tubulin acetylation and rescue axonal transport of mitochondria in a model of Charcot-Marie-Tooth Type 2F

Disruption of axonal transport causes a number of rare, inherited axonopathies and is heavily implicated in a wide range of more common neurodegenerative disorders, many of them age- related. Acetylation of α-tubulin is one important regulatory mechanism, influencing microtubule stability and motor protein attachment. Of several strategies so far used to enhance axonal transport, increasing microtubule acetylation through inhibition of the deacetylase enzyme HDAC6 has been one of the most effective. Several inhibitors have been developed and tested in animal and cellular models but better drug candidates are still needed. Here we report the development and characterisation of two highly potent HDAC6 inhibitors, which show low toxicity, promising pharmacokinetic properties, and enhance microtubule acetylation in the nanomolar range. We demonstrate their capacity to rescue axonal transport of mitochondria in a primary neuronal culture model of the inherited axonopathy Charcot- Marie-Tooth Type 2F, caused by a dominantly acting mutation in heat shock protein beta 1.Funding for this work was provided by Takeda Development Centre Europe Ltd. M.P.C. is funded by the John and Lucille van Geest Foundation

Interaction between a MAPT variant causing frontotemporal dementia and mutant APP affects axonal transport.

In Alzheimer's disease, many indicators point to a central role for poor axonal transport, but the potential for stimulating axonal transport to alleviate the disease remains largely untested. Previously, we reported enhanced anterograde axonal transport of mitochondria in 8- to 11-month-old MAPTP301L knockin mice, a genetic model of frontotemporal dementia with parkinsonism-17T. In this study, we further characterized the axonal transport of mitochondria in younger MAPTP301L mice crossed with the familial Alzheimer's disease model, TgCRND8, aiming to test whether boosting axonal transport in young TgCRND8 mice can alleviate axonal swelling. We successfully replicated the enhancement of anterograde axonal transport in young MAPTP301L/P301L knockin animals. Surprisingly, we found that in the presence of the amyloid precursor protein mutations, MAPTP301L/P3101L impaired anterograde axonal transport. The numbers of plaque-associated axonal swellings or amyloid plaques in TgCRND8 brains were unaltered. These findings suggest that amyloid-β promotes an action of mutant tau that impairs axonal transport. As amyloid-β levels increase with age even without amyloid precursor protein mutation, we suggest that this rise could contribute to age-related decline in frontotemporal dementia.This work was supported by Alzheimer’s Research UK (ART/PG2009/2 to R.A.), MRC project grant (MR/L003813/1 to R.A., S.G.), Medical Research Council studentship (S.M.), Alzheimer’s Research UK studentship (ARUKPhD2013-13 to C.D.), Biotechnology and Biological Sciences Research Council Institute Strategic Programme Grant (M.P.C.), the Foundation for Alzheimer Research (FRA/SAO) (JPB) and the Belgian F.N.R.S. (K.A and JPB)

Cultured dissociated primary dorsal root ganglion neurons from adult horses enable study of axonal transport

Neurological disorders are prevalent in horses, but their study is challenging due to anatomic constraints and the large body size; very few host-specific in vitro models have been established to study these types of diseases, particularly from adult donor tissue. Here we report the generation of primary neuronal dorsal root ganglia (DRG) cultures from adult horses: the mixed, dissociated cultures, containing neurons and glial cells, remained viable for at least 90 days. Similar to DRG neurons in vivo, cultured neurons varied in size, and they developed long neurites. The mitochondrial movement was detected in cultured cells and was significantly slower in glial cells compared to DRG-derived neurons. In addition, mitochondria were more elongated in glial cells than those in neurons. Our culture model will be a useful tool to study the contribution of axonal transport defects to specific neurodegenerative diseases in horses as well as comparative studies aimed at evaluating species-specific differences in axonal transport and survival