Posttranslational modification of a neurofilament protein during axoplasmic transport: implications for regional specialization of CNS axons

The possibility that proteins are modified during axoplasmic transport in central nervous system axons was examined by analyzing neurofilament proteins (200,000, 140,000, and 70,000 mol wt) along the mouse primary optic pathway (optic nerve and optic tract). The major neurofilament proteins (NFPs) exhibited considerable microheterogeneity. At least three forms of the “ 140,000” neurofilament protein differing in molecular weight by SDS PAGE (140,000-145,000 mol wt) were identified. The “140,000” proteins, and their counterparts in purified neurofilament preparations, displayed similar isoelectric points and the same peptide maps. The “140,000” NFPs exhibited regional heterogeneity when consecutive segments of the optic pathway were separately examined on polyacrylamide gels. Two major species (145,000 and 140,000 mol wt) were present along the entire length of the optic pathway. The third protein (143,000 mol wt) was absent proximally but became increasingly prominent in distal segments. After intravitreal injection of [(3)H]proline, newly synthesized radiolabeled proteins in the “140,000” mol wt region entered proximal mouse retinal ganglion cell (RGC) axons as two major species corresponding to the 145,000 and 14,000 mol wt NFPs observed on stained gels. When transported NFPs reached more distal axonal regions (30 d postinjection or longer), a 143,000 mol wt protein appeared that was similar in isoelectric point and peptide map to the 145,000 and 140,000 mol wt species. The results suggest that (a) the composition of CNS neurofilaments, particularly the “140,000” component, is more complex than previously recognized, that (b) retinal ganglion cell axons display regional differentiation with respect to these cytoskeletal proteins, and that (c) structural heterogeneity of “140,000” NFPs arises, at least in part, from posttranslational modification during axoplasmic transport. When excised but intact optic pathways were incubated in vitro at pH 7.4, a 143,000 NFP was rapidly formed by a calcium-dependent enzymatic process active at endogenous calcium levels. Changes in major proteins other than those in the 145,000-140,000 mol wt region were minimal. In optic pathways from mice injected intravitreally with L-[(3)H]proline, tritiated 143,000 mol wt NFP formed rapidly in vitro if radioactively labeled NFPs were present in distal RGC axonal regions (31 d postinjection). By contrast, no 143,000 mol wt NFP was generated if radioactively labeled NFPs were present proximally in RGC axons (6 d postinjection). The enzymatic process that generates 143,000 mol wt NFP in vitro, therefore, appears to have a nonuniform distribution along the RGC axons. The foregoing results and other observations, including the accompanying report (J. Cell Biol., 1982, 94:159-164), imply that CNS axons may be regionally specialized with respect to structure and function

Can a blended learning approach enhance students transition into higher education? A study to explore perception , engagement and progression.

This paper is concerned with one programme‟s approach when using blended learning activities to support student transition into an English university. Its intention was to capture students‟ attention and curiosity whilst setting patterns for learning and study. The approach combined face-to-face sessions with on-line learning tasks. Research findings support the progress of students in regard to the level of attainment throughout the weekly tasks, although the students were initially challenged by the intensity of the use of ICT applications to support their learning. In conclusion this learning approach was found to be an effective method to support students during the initial weeks at university

Uranus's and Neptune’s stratospheric water abundance and vertical profile from Herschel-HIFI

Here we present new constraints on Uranus’s and Neptune’s externally sourced stratospheric water abundance using disk-averaged observations of the 557 GHz emission line from Herschel’s Heterodyne Instrument for the Far-Infrared. Derived stratospheric column water abundances are × 1014 cm−2 for Uranus and ×1014 cm−2 for Neptune, consistent with previous determinations using ISO-SWS and Herschel-PACS. For Uranus, excellent observational fits are obtained by scaling photochemical model profiles or with step-type profiles with water vapor limited to ≤0.6 mbar. However, Uranus’s cold stratospheric temperatures imply a ∼0.03 mbar condensation level, which further limits water vapor to pressures ≤0.03 mbar. Neptune’s warmer stratosphere has a deeper ∼1 mbar condensation level, so emission-line pressure broadening can be used to further constrain the water profile. For Neptune, excellent fits are obtained using step-type profiles with cutoffs of ∼0.3–0.6 mbar or by scaling a photochemical model profile. Step-type profiles with cutoffs ≥1.0 mbar or ≤0.1 mbar can be rejected with 4σ significance. Rescaling photochemical model profiles from Moses & Poppe to match our observed column abundances implies similar external water fluxes for both planets: × 104 cm−2 s−1 for Uranus and ×104 cm−2 s−1 for Neptune. This suggests that Neptune’s ∼4 times greater observed water column abundance is primarily caused by its warmer stratosphere preventing loss by condensation, rather than by a significantly more intense external source. To reconcile these water fluxes with other stratospheric oxygen species (CO and CO2) requires either a significant CO component in interplanetary dust particles (Uranus) or contributions from cometary impacts (Uranus, Neptune

ALMA Spectral Imaging of Titan Contemporaneous with Cassiniʼs Grand Finale

International audienc

International lease accounting reform and economic consequences: the views of UK users and preparers

In response to perceived difficulties with extant lease-accounting standards in operation worldwide, the G4+1 issued a discussion paper which proposes that all leases should be recognized on the balance sheet [ASB (1999). Leases: Implementation of a new approach, discussion paper. London: Accounting Standards Board]. Leasing is now on the active agenda of the IASB. A major difficulty faced by standard setters lies in overcoming the preparer/user lobbying imbalance and obtaining ex ante evidence on the likely impact of regulatory reform. This paper contributes to the ongoing international debate by conducting a questionnaire survey of U.K. users and preparers to assess their views on proposals for lease-accounting reform and on the potential economic consequences of their adoption. The results, based on 132 responses, indicate that both groups accept that there are deficiencies in the current rules, but they do not agree on the way forward and believe that the proposals would lead to significant economic consequences for key parties. The impact on respondents' views of familiarity with the proposals, level of lease usage, and company size, is also examined