The late-onset cerebellar ataxias (LOCAs) have largely resisted molecular diagnosis.
We sequenced the genomes of six persons with autosomal dominant LOCA who were members of three French Canadian ...families and identified a candidate pathogenic repeat expansion. We then tested for association between the repeat expansion and disease in two independent case-control series - one French Canadian (66 patients and 209 controls) and the other German (228 patients and 199 controls). We also genotyped the repeat in 20 Australian and 31 Indian index patients. We assayed gene and protein expression in two postmortem cerebellum specimens and two induced pluripotent stem-cell (iPSC)-derived motor-neuron cell lines.
In the six French Canadian patients, we identified a GAA repeat expansion deep in the first intron of
, which encodes fibroblast growth factor 14. Cosegregation of the repeat expansion with disease in the families supported a pathogenic threshold of at least 250 GAA repeats (GAA
). There was significant association between
(GAA)
expansions and LOCA in the French Canadian series (odds ratio, 105.60; 95% confidence interval CI, 31.09 to 334.20; P<0.001) and in the German series (odds ratio, 8.76; 95% CI, 3.45 to 20.84; P<0.001). The repeat expansion was present in 61%, 18%, 15%, and 10% of French Canadian, German, Australian, and Indian index patients, respectively. In total, we identified 128 patients with LOCA who carried an
(GAA)
expansion. Postmortem cerebellum specimens and iPSC-derived motor neurons from patients showed reduced expression of
RNA and protein.
A dominantly inherited deep intronic GAA repeat expansion in
was found to be associated with LOCA. (Funded by Fondation Groupe Monaco and others.).
Objective We sought to compare the Risk of Malignancy Index (RMI) to the Risk of Ovarian Malignancy Algorithm (ROMA) to predict epithelial ovarian cancer (EOC) in women with a pelvic mass. Study ...Design In all, 457 women with imaging results from ultrasound, computed tomography, magnetic resonance imaging, and serum HE4 and CA125 determined prior to surgery for pelvic mass were evaluable. RMI values were determined using CA125, imaging score, and menopausal status. ROMA values were determined using HE4, CA125, and menopausal status. Results At a set specificity of 75%, ROMA had a sensitivity of 94.3% and RMI had a sensitivity of 84.6% for distinguishing benign status from EOC ( P = .0029). In patients with stage I and II disease, ROMA achieved a sensitivity of 85.3% compared with 64.7% for RMI ( P < .0001). Conclusion The dual marker algorithm utilizing HE4 and CA125 to calculate a ROMA value achieves a significantly higher sensitivity for identifying women with EOC than does RMI.
•Assessment of the silver migration issue for high temperature die attaches.•A mitigation solution is proposed (fluorinated parylenes).•Lifetime with parylene exceeds 1000h at 275°C.
Silver sintering ...is a promising alternative to high melting point (HMP) solders which contain lead. Indeed, it offers better thermal and electrical properties and can operate at higher temperature. However, silver tends to migrate in presence of electric field, oxygen (or moisture) and high temperature, causing short circuits. In this paper, we assess the extent of this issue, and we evaluate the protective effect of a thin layer of parylene. It is shown that silver migration occurs rapidly (tens to hundreds of hours at 300°C), but that parylene offers a good mitigation of this issue.
We have conducted a search for L subdwarf candidates within the photometric catalogues of the UKIRT Infrared Deep Sky Survey and Sloan Digital Sky Survey. Six of our candidates are confirmed as L ...subdwarfs spectroscopically at optical and/or near-infrared wavelengths. We also present new optical spectra of three previously known L subdwarfs (WISEA J001450.17-083823.4, 2MASS J00412179+3547133, and ULAS J124425.75+102439.3). We examined the spectral type and metallicity classification of subclasses of known L subdwarfs. We summarized the spectroscopic properties of L subdwarfs with different spectral types and subclasses. We classify these new L subdwarfs by comparing their spectra to known L subdwarfs and L dwarf standards. We estimate temperatures and metallicities of 22 late-type M and L subdwarfs by comparing their spectra to BT-Settl models. We find that L subdwarfs have temperatures between 1500 and 2700 K, which are higher than similar-typed L dwarfs by around 100-400 K depending on different subclasses and subtypes. We constrained the metallicity ranges of subclasses of M, L, and T subdwarfs. We also discussed the spectral-type and absolute magnitude relationships for L and T subdwarfs.
Abstract
Classical mechanisms of volcanic eruptions mostly involve pressure buildup and magma ascent towards the surface
1
. Such processes produce geophysical and geochemical signals that may be ...detected and interpreted as eruption precursors
1–3
. On 22 May 2021, Mount Nyiragongo (Democratic Republic of the Congo), an open-vent volcano with a persistent lava lake perched within its summit crater, shook up this interpretation by producing an approximately six-hour-long flank eruption without apparent precursors, followed—rather than preceded—by lateral magma motion into the crust. Here we show that this reversed sequence was most likely initiated by a rupture of the edifice, producing deadly lava flows and triggering a voluminous 25-km-long dyke intrusion. The dyke propagated southwards at very shallow depth (less than 500 m) underneath the cities of Goma (Democratic Republic of the Congo) and Gisenyi (Rwanda), as well as Lake Kivu. This volcanic crisis raises new questions about the mechanisms controlling such eruptions and the possibility of facing substantially more hazardous events, such as effusions within densely urbanized areas, phreato-magmatism or a limnic eruption from the gas-rich Lake Kivu. It also more generally highlights the challenges faced with open-vent volcanoes for monitoring, early detection and risk management when a significant volume of magma is stored close to the surface.
Innate lymphoid cells (ILCs) have been implicated in multiple pathologic conditions, including atherogenesis, as documented in experimental mice studies, however, their role in atherosclerosis in ...humans remains unexplored.
Here, we identify ILCs and their dynamics in early, advanced, and complicated human carotid- and aortic atherosclerotic plaques, using a multiplex immunohistochemical quadruple-staining technique with prototypic transcription factors T-bet, GATA3, or RORgt for identification of the ILC1, ILC2 and ILC3 subsets, respectively, in combination with lineage markers CD3, CD20/ CD79a and CD56 to exclude other lymphoid cell types. ILC subsets were quantified, and to put this in perspective, their numbers were expressed as percentage of the total number of infiltrated lymphoid cells and related to the frequency of conventional T cells, B cells, NK cells, and NKT cells.
All ILC subsets were present in every different stage of atherogenesis. ILC1s were the most abundant ILC subset, and their numbers significantly increased in the course of plaque development, but paradoxically, their relative frequency was reduced because of a higher increment of T cells and B cells. The numbers of ILC2s and ILC3s also gradually increased, but this trend did not achieve significance. T cell subsets always significantly outnumbered their ILC counterparts, except for the early lesions where the proportion of ILC1s was markedly higher, albeit not significant.
The high abundance of ILC1s in the early stages and further significant enrichment in later stages, suggest they may participate in the initiation and development of atherogenesis, and thus, may represent a novel target to prevent or treat atherosclerosis.
This study demonstrates inducible transgenic expression in the exceptionally short‐lived turquoise killifish Nothobranchius furzeri, which is a useful vertebrate model for ageing research. Transgenic ...N. furzeri bearing a green fluorescent protein (Gfp) containing construct under the control of a heat shock protein 70 promoter were generated, heat shock‐induced and reversible Gfp expression was demonstrated and germline transmission of the transgene to the F1 and F2 generations was achieved. The availability of this inducible transgenic expression system will make the study of ageing‐related antagonistically pleiotropic genes possible using this unique vertebrate model organism.
The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community ...has no way to share data other than in published papers. Although mass spectrometry (MS) techniques are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Molecular Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of 'living data' through continuous reanalysis of deposited data.
Tower CO2 flux measurements from 20 European grasslands in the EUROGRASSFLUX data set covering a wide range of environmental and management conditions were analyzed with respect to their ...ecophysiological characteristics and CO2 exchange (gross primary production, P(g), and ecosystem respiration, R(e)) using light-response function analysis. Photosynthetically active radiation (Q) and top-soil temperature (T(s)) were identified as key factors controlling CO2 exchange between grasslands and the atmosphere at the 30-min scale. A nonrectangular hyperbolic light-response model P(Q) and modified nonrectangular hyperbolic light-temperature-response model P(Q, T(s)) proved to be flexible tools for modeling CO2 exchange in the light. At night, it was not possible to establish robust instantaneous relationships between CO2 evolution rate rn and environmental drivers, though under certain conditions, a significant relationship r(n)=r(0) e(k)T(T)s was found using observation windows 7-14 days wide. Principal light-response parameters--apparent quantum yield, saturated gross photosynthesis, daytime ecosystem respiration, and gross ecological light-use efficiency, epsilon= P(g)/Q, display patterns of seasonal dynamics which can be formalized and used for modeling. Maximums of these parameters were found in intensively managed grasslands of Atlantic climate. Extensively used semi-natural grasslands of southern and central Europe have much lower production, respiration, and light-use efficiency, while temperate and mountain grasslands of central Europe ranged between these two extremes. Parameters from light-temperature-response analysis of tower data are in agreement with values obtained using closed chambers and free-air CO2 enrichment. Correlations between light-response and productivity parameters provides the possibility to use the easier to measure parameters to estimate the parameters that are more difficult to measure. Gross primary production (P(g)) of European grasslands ranges from 1700 g CO2 m-2 year-1 in dry semi-natural pastures to 6900 g CO2 m-2 year-1 in intensively managed Atlantic grasslands. Ecosystem respiration (R(e)) is in the range 1800 < R(e) < 6000 g CO2 m-2 year-1. Annual net ecosystem CO2 exchange (NEE) varies from significant net uptake (>2400 g CO2 m-2 year-1) to significant release (<-600 g CO2 m-2 year-1), though in 15 out of 19 cases grasslands performed as net CO2 sinks. The carbon source was associated with organic rich soils, grazing, and heat stress. Comparison of P(g), R(e), and NEE for tower sites with the same characteristics from previously published papers obtained with other methods did not reveal significant discrepancies. Preliminary results indicate relationships of grassland P(g) and R(e) to macroclimatic factors (precipitation and temperature), but these relationships cannot be reduced to simple monofactorial models.
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