TGF beta type II receptor signaling controls Schwann cell death and proliferation in developing nerves

During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF)beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGF beta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGF beta signaling did not appear to affect other processes in which TGF beta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death

Diamond nucleation from the gas phase onto cold-worked Co-cemented tungsten carbide

Co-cemented tungsten carbide (WC–Co) substrates with fine (1 μm) and coarse (6 μm) grain size were sintered using 6 wt.% Co as a binder. The as-sintered samples were ground to the final geometry (10×10×3 mm3). After the grinding treatment, the full width at half maximum (FWHM) of the WC X-ray diffraction (XRD) peaks indicated a high level of strain in a few micrometers thick surface layer, according to the penetration depth of Cu Kα radiation. The as-ground substrates were submitted to a two-step etching procedure with Murakami's solution, to roughen the surface, and 10 s acid wash to etch surface cobalt out. The Murakami's etching time was varied between 1 and 20 min. Fine- and coarse-grained substrates submitted to different chemical etching times were characterized by scanning electron microscopy and XRD, and then submitted to short diamond nucleation runs in a Hot Filament Chemical Vapour Deposition reactor. Both FWHM of WC peaks and diamond nucleation density decreased by increasing the Murakami's etching duration, providing that the etched layer did not exceed 2 μm thickness. When a layer thicker than a couple of micrometers was removed by etching, diamond nucleation density was very low and no more dependent on etching time. This occurrence suggested that diamond nucleation density correlates well with the amount of residual strain at the substrate surface and can be tailored by a suitable control of strain-related defects produced by mechanical treatments

Dry turning of alumina/aluminum composites with CVD diamond coated Co-cemented tungsten carbide tools

Triangular (TPGN 160308) WC-6 wt.%Co inserts having different average grain sizes (1 and 3 µm) were submitted to surface roughening either by wet etching with Murakami's reagent or by a heat treatment in the hot filament chemical vapour deposition (HFCVD) reactor. The heat treatment was performed in a monohydrogen-rich atmosphere at substrate temperatures as high as 1000 degrees C. Scanning electron microscopy and energy-dispersive spectroscopy showed that this pre-treatment led to surface roughening of the as-ground inserts and to a lower surface Co concentration. Prior to deposition, all inserts were etched with an acid solution of hydrogen peroxide. Diamond coatings were deposited by HFCVD. The coated inserts were tested by dry machining of aluminum-matrix composite (Al-10%Al2O3) bars. Turning test results indicated that a proper combination of substrate pretreatment and microstructure can significantly improve tool life

Petrogenesis of Eocene oceanic basalts from the West Philippine Basin and Oligocene arc volcanics from the Palau-Kyushu Ridge drilled at 20°N, 135°E (Western Pacific Ocean).

The West Philippine Basin (WPB) is a back-arc basin that opened within the Philippine Sea Plate (PSP) between the current position of the Palau-Kyushu Ridge (PKR) and the margin of East Asia. Spreading occurred at the Central Basin Fault (CBF) mainly from 54 until 30 Ma. The PKR was active since ~ 48 to 35 Ma constituting a single volcanic arc with the Izu-Bonin-Mariana (IBM) Arc. At ~ 42 Ma ago spreading rate and direction changed from NE-SW to NS, stopping at ~ 30 Ma. A late phase of spreading and volcanism took place between 30 and 26 Ma. ODP Leg 195 Site 1201 is located in the WPB, ~ 100 km west of the PKR, on 49 Ma crust formed by NE-SW spreading at the CBF. From ~ 35 to 30 Ma, pelagic sedimentation at Site 1201 was followed by turbidite sedimentation, fed mostly by arc-derived volcanic clasts. The geochemical and isotopic features of Site 1201 basement rocks, which represent Eocene WPB oceanic crust, compared with those of Site 1201 volcanics from the turbidite sequence, representing products of the early Mariana Arc (PKR), provide some insights into the early history of the IBM subduction factory. The WPB basement is made up of aphyric to porphyritic basalts with altered olivine, and preserved plagioclase, clinopyroxene and opaques. The PKR volcanics are porphyritic basalts and andesites with plagioclase, clino- and orthopyroxene, hornblende, alkali feldspar and opaques. Variable textures, and degree of alteration suggesting zeolite facies metamorphic grade, characterize both groups of rocks. The mineralogical and geochemical characteristics of the investigated Site 1201 PKR volcanics highlight their calc-alkaline affinity. This feature is at variance with both other PKR rocks, having mostly boninitic and arc tholeiitic affinity, and WPB basement basalt, having tholeiitic affinity, with some characters transitional to arc-like, as expected for a back-arc basin. New Sr and Nd isotope data, coupled with published Sr, Nd, Pb and Hf isotope data (Savov et al., 2006), highlight the Indian Ocean MORB-like character of Site 1201 basement basalts. This suggests that WPB volcanism tapped an upper mantle domain distinct from that underlying the Pacific Plate. The isotopic features of Site 1201 PKR volcanics are more enriched relative to those of basement basalts reflecting higher amounts of subduction-derived component(s) in the source of arc magmas. Th-Nb relationships and isotope geochemistry of the WPB basement and overlaying arc volcanics suggest addition of subducted sediment mostly as siliceous melts, to the mantle source of the arc volcanics. In that respect, Site 1201 PKR volcanics resemble calc-alkaline volcanics of the currently active Mariana Arc. In addition, the calc-alkaline affinity, unradiogenic neodymium, and inferred Middle Oligocene age of PKR volcanics, suggest they might represent an evolved stage of arc volcanism at Palau-Kyushu Ridge, perhaps shortly before the end of its activity

Krox-20 inhibits Jun-NH2-terminal kinase/c-Jun to control Schwann cell proliferation and death

The transcription factor Krox-20 controls Schwann cell myelination. Schwann cells in Krox-20 null mice fail to myelinate, and unlike myelinating Schwann cells, continue to proliferate and are susceptible to death. We find that enforced Krox-20 expression in Schwann cells cell-autonomously inactivates the proliferative response of Schwann cells to the major axonal mitogen β–neuregulin-1 and the death response to TGFβ or serum deprivation. Even in 3T3 fibroblasts, Krox-20 not only blocks proliferation and death but also activates the myelin genes periaxin and protein zero, showing properties in common with master regulatory genes in other cell types. Significantly, a major function of Krox-20 is to suppress the c-Jun NH2-terminal protein kinase (JNK)–c-Jun pathway, activation of which is required for both proliferation and death. Thus, Krox-20 can coordinately control suppression of mitogenic and death responses. Krox-20 also up-regulates the scaffold protein JNK-interacting protein 1 (JIP-1). We propose this as a possible component of the mechanism by which Krox-20 regulates JNK activity during Schwann cell development

Determining the Extent of Soil Degradation Processes Using Trend Analyses at a Regional Multispectral Scale

In order to ensure the sustainability of production from agricultural lands, the degradation processes surrounding the fertile land environment must be monitored. Human-induced risk and status of soil degradation (SD) were assessed in the Northern-Eastern part of the Nile delta using trend analyses for years 2013 to 2023. SD hotspot areas were identified using time-series analysis of satellite-derived indices as a small fraction of the difference between the observed indices and the geostatistical analyses projected from the soil data. The method operated on the assumption that the negative trend of photosynthetic capacity of plants is an indicator of SD independently of climate variability. Combinations of soil, water, and vegetation’s indices were integrated to achieve the goals of the study. Thirteen soil profiles were dug in the hotspots areas. The soil was affected by salinity and alkalinity risks ranging from slight to strong, while compaction and waterlogging ranged from slight to moderate. According to the GIS-model results, 30% of the soils were subject to slight degradation threats, 50% were subject to strong risks, and 20% were subject to moderate risks. The primary human-caused sources of SD are excessive irrigation, poor conservation practices, improper utilisation of heavy machines, and insufficient drainage. Electrical conductivity (EC), exchangeable soil percentage (ESP), bulk density (BD), and water table depth were the main causes of SD in the area. Generally, chemical degradation risks were low, while physical risks were very high in the area. Trend analyses of remote sensing indices (RSI) proved to be effective and accurate tools to monitor environmental dynamic changes. Principal components analyses were used to compare and prioritise among the used RSI. RSI pixel-wise residual trend indicated SD areas were related to soil data. The spatial and temporal trends of the indices in the region followed the patterns of drought, salinity, soil moisture, and the difficulties in separating the impacts of drought and submerged on SD on vegetation photosynthetic capacity. Therefore, future studies of land degradation and desertification should proceed using indices as a factor predictor of SD analysis

Geochemical and isotopic insights into the assembly, evolution and disruption of a magmatic plumbing system before and after a cataclysmic caldera-collapse eruption at Ischia volcano (Italy)

New geochemical and isotopic data on volcanic rocks spanning the period ~75–50 ka BP on Ischia volcano, Italy, shed light on the evolution of the magmatic system before and after the catastrophic, caldera-forming Monte Epomeo Green Tuff (MEGT) eruption. Volcanic activity during this period was influenced by a large, composite and differentiating magmatic system, replenished several times with isotopically distinct magmas of deep provenance. Chemical and isotopic variations highlight that the pre-MEGT eruptions were fed by trachytic/phonolitic magmas from an isotopically zoned reservoir that were poorly enriched in radiogenic Sr and became progressively less radiogenic with time. Just prior to the MEGT eruption, the magmatic system was recharged by an isotopically distinct magma, relatively more enriched in radiogenic Sr with respect to the previously erupted magmas. This second magma initially fed several SubPlinian explosive eruptions and later supplied the climactic, phonolitic-to-trachytic MEGT eruption(s). Isotopic data, together with erupted volume estimations obtained for MEGT eruption(s), indicate that >5–10 km3 of this relatively enriched magma had accumulated in the Ischia plumbing system. Geochemical modelling indicates that it accumulated at shallow depths (4–6 km), over a period of ca. 20 ka. After the MEGT eruption, volcanic activity was fed by a new batch of less differentiated (trachyte-latite) magma that was slightly less enriched in radiogenic Sr. The geochemical and Sr–Nd-isotopic variations through time reflect the upward flux of isotopically distinct magma batches, variably contaminated by Hercynian crust at 8–12 km depth. The deep-sourced latitic to trachytic magmas stalled at shallow depths (4–6 km depth), differentiated to phonolite through crystal fractionation and assimilation of a feldspar-rich mush, or ascended directly to the surface and erupted

A population approach to characterise amisulpride pharmacokinetics in older people and Alzheimer's disease

Introduction Current prescribing guidelines for the antipsychotic amisulpride are based largely on pharmacokinetic (PK) studies in young adults, and there is a relative absence of data on older patients, who are at greatest risk of developing adverse events. Methods This study aimed to develop a population PK model for amisulpride specifically in older people, by combining data from a richly sampled phase 1, single (50 mg) dose study in healthy older people (n = 20, 65–79 years), with a clinical dataset obtained during off label, low-dose (25–75 mg daily) amisulpride prescribing in older people with Alzheimer’s disease (AD) (n = 25, 69–92 years), as part of an observational study. Results After introducing a scaling factor based on body weight, age accounted for 20 % of the inter-individual variability in drug clearance (CL), resulting in a 54 % difference in CL between those aged 65 and those aged 85 years, and higher blood concentrations in older patients. Discussion These findings argue for the consideration of age and weight-based dose stratification to optimise amisulpride prescribing in older people, particularly in those aged 85 years and above

All-sky search of NAUTILUS data

A search for periodic gravitational-wave signals from isolated neutron stars in the NAUTILUS detector data is presented. We have analyzed half a year of data over the frequency band $$Hz, the spindown range$$ Hz/s and over the entire sky. We have divided the data into 2 day stretches and we have analyzed each stretch coherently using matched filtering. We have imposed a low threshold for the optimal detection statistic to obtain a set of candidates that are further examined for coincidences among various data stretches. For some candidates we have also investigated the change of the signal-to-noise ratio when we increase the observation time from two to four days. Our analysis has not revealed any gravitational-wave signals. Therefore we have imposed upper limits on the dimensionless gravitational-wave amplitude over the parameter space that we have searched. Depending on frequency, our upper limit ranges from $3.4 \times 10^{-23}$ to $1.3 \times 10^{-22}$. We have attempted a statistical verification of the hypotheses leading to our conclusions. We estimate that our upper limit is accurate to within 18%.Comment: LaTeX, 12 page