The Ronda Peridotite: Garnet-, Spinel-, and Plagioclase-Lherzolite Facies and the P-T Trajectories of a High-Temprature Mantle Intrusion

The Ronda peridotite is a high-temperature, alpine-type peridotite emplaced in the internal Zone of the Betic Cordilleras, southern Spain. Using the mineral assemblages of the peridotite and mafic layers, the peridotite mass has been subdivided into 4 zones of mineral facies: (1) garnet-lherzolite facies, (2) ariégite subfacies of spinel-lherzolite facies, (3) seiland subfacies of spinel-lherzolite facies, and (4) plagioclase-lherzolite facies. It is proposed that this mineralogical zonation developed through a syntectic recrystallization of a hot (1100 to 1200°C), solid mantle peridotite during its ascent into the Earth's crust. Coexisting minerals from 12 peridotites covering all the mineral facies above were analysed with an electron microprobe. Core compositions of pyroxene porphyroclasts are constant in all mineral facies and indicate that the peridotite was initially equilibrated at temperatures of 1100 to 1200 °C and pressures of 20 to 25 kb. In contrast, the compositions of pyroxene neoblasts and spinel grains (which appear to have grown during later recrystallization) are well correlated with mineral facies. They indicate that the recrystallization temperature throughout the mass is more or less constant, 800 to 900 °C, but that the pressure ranges from 5-7 kb in the plagioclase-lherzolite facies to 12-15 kb in the garnet-lherzolite facies. Therefore, variation in pressure appears to be primarily responsible for the four mineral facies types. A pressure range of at least 5 kb appears to be too large to have been maintained (at the same time) in a mass as small as the Ronda peridotite. Dynamic cooling may explain the observed variation in the recrystallization pressure; i.e. during the intrusion of the peridotite body, different parts of the body have followed different P-T paths in response to different local cooling rates. Comparing the inferred P-T paths for the peridotite with published melting temperature of peridotite and mafic rocks, it is concluded that the peridotite did not go through partial fusion during the ascent. A hypothetical, diapiric uprise that caused partial fusion and igneous differentiation of the mantle peridotite is considered to be a separate event prior to the ascent that started from about 70 km depth in the upper mantle. Estimates of cooling rates and of Al diffusion rates in pyroxenes suggest that the ascent rate of the peridotite body was greater than 1 meter/yea

Alteration in Murine Epidermal Langerhans Cell Population by Various UV Irradiations: Quantitative and Morphologic Studies on the Effects of Various Wavelengths of Monochromatic Radiation on Ia-Bearing Cells

The present study was undertaken in order to clarify the exact mode of the Langerhans cell (LC) depleting process caused by UV irradiation. Following irradiation with a single dose of various wavelengths of monochromatic UV radiation (UVR), we studied the number of Ia-positive cells in mouse epidermal sheets quantitatively, particularly with regard to dose-response relationship, action spectrum, and time course change. In addition, we studied morphologic alterations of these cells using electron- and immunoelectron microscopy (EM and IEM).We obtained the following results after a single dose of UVB radiation (200 mJ/cm2 of 300 nm) or PUVA (1% of 8-methoxypsoralen (8-MOP) 20 μ1 and 1 J/cm2 of 360 nm): (1) EM and IEM showed that while some LCs simply lost their Ia marker without any structural alterations, the majority of the LCs disappeared due to actual cell damage. (2) During an ‘injury phase,” the initial 48 h, and a “recovery phase,” lasting from 4–14 days after irradiation, enlargement of the size of remaining Ia-positive LCs occurred. The degree of enlargement was closely related to the degree of reduction in number, suggesting a process compensating for the loss of the LC population. (3) It was found that the recovery rate of LCs after irradiation damage was slower than that of keratinocytes, indicating different cell kinetics between these distinct cell populations in the epidermis, i.e., restoration of LCs after irradiation seems to be achieved at least partially through a repopulation process originating in the bone marrow.Studies with irradiation of various monochromatic wavebands, with or without topical 8-MOP, showed that the action spectrum for Ia-positive cell depletion activity lay within the spectrum shorter than 300 nm for UVR alone, and between 320–380 nm for 8-MOP plus UVR. Since the action spectra were similar to those for keratinocyte damage, i.e., sunburn cell formation, induction of unscheduled DNA synthesis, and to those for UVR-induced erythema, we conclude that common mechanisms underlie these types of tissue damage

Corundum-bearing mafic granulites in the Horoman (Japan) and Ronda (Spain) peridotite massifs: Possible remnants of recycled crustal materials in the mantle

金沢大学理工研究域自然システム学

Successful Repeated Transcatheter Arterial Embolization (TAE) for Multiple Liver Metastases from Breast Cancer

A 46-year-old female was successfuly treated with repeated transcatheter arterial embolization (TAE) for multiple liver metastases from breast cancer. TAE using mitomycin C and epirubicin hydrochloride with lipiodol emulsion and gelatin sponge particles has been administered to the patient eight times over 4 years. She has also received systemic chemotherapy. She has survived for 6 years and 3 months after the detection of liver metastases

The SNP rs6508974 in AXL is a functional polymorphism and a promising biomarker for gefitinib treatment

Somatic mutations in epidermal growth factor receptor (EGFR) found in lung adenocarcinomas are used as biomarkers for the treatment with EGFR-tyrosine kinase inhibitors, including gefitinib. The bypass tracks with amplification of AXL is one of the mechanisms underlying the resistance to gefitinib. We, therefore, carried out a candidate gene approach method to identify AXL polymorphisms associated with the effectiveness of gefitinib. EGFR mutations were first dentified by mutantenriched PCR-restriction fragment length polymorphism (RFLP), and then 2 tag single nucleotide olymorphisms (SNPs) of AXL were examined by PCR-RFLP in 62 Japanese patients with advanced lung adenocarcinoma and treated with gefitinib in two general hospitals in Nagasaki. Subsequently, the association of EFGR mutations and the AXL polymorphism with the effectiveness of gefitinib was examined in these patients. We next examined the effect of the AXL polymorphism on the expression and function of this gene. It is worthy of note that EGFR mutations and the AXL polymorphism rs6508974 independently contributed to the effectiveness of gefitinib, and the polymorphism was proved to be a possible biomarker for selecting non-responders and responders to gefitinib treatment even in the absence of EGFR mutations. Furthermore, this SNP increased the transcriptional activity of the AXL transcript variant 3, one of the three AXL transcript variants, which to some extent increased the epithelial-mesenchymal transition in cancer cells. Taken together, AXL is one of the genes that determine the effectiveness of gefitinib and a biomarker for selecting non-responders and responders among lung adenocarcinoma patients with no EGFR mutations, suggesting that rs6508974 in AXL might be a functional SNP in lung denocarcinoma

Novel prospective umbrella-type lung cancer registry study for clarifying clinical practice patterns: CS-Lung-003 study protocol

Introduction Conventional cancer registries are suitable for simple surveillance of cancer patients, including disease frequency and distribution, demographics, and prognosis; however, the collected data are inadequate to clarify comprehensively diverse clinical questions in daily practice. Methods We constructed an umbrella‐type lung cancer patient registry (CS‐Lung‐003) integrating multiple related prospective observational studies (linked studies) that reflect clinical questions about lung cancer treatment. The primary endpoint of this registry is to clarify daily clinical practice patterns in lung cancer treatment; a key inclusion criterion is pathologically diagnosed lung cancer. Under this registry, indispensable clinical items are detected in advance across all active linked studies and gathered prospectively and systematically to avoid excessive or insufficient data collection. Researchers are to input information mutually, irrespective of the relevance to each researcher's own study. Linked studies under the umbrella of the CS‐Lung‐003 registry will be updated annually with newly raised clinical questions; some linked studies will be newly created, while others will be deleted after the completion of the analysis. Enrollment began in July 2017. Discussion We successfully launched the umbrella‐type CS‐Lung‐003 registry. Under this single registry, researchers collaborate on patient registration and data provision for their own and other studies. Thus, the registry will produce results for multiple domains of study, providing answers to questions about lung cancer treatment raised by other researchers. Through such analysis of each linked study, this registry will contribute to the comprehensive elucidation of actual daily practice patterns in lung cancer treatment. Key points CS‐Lung‐003 registry directly integrates multiple linked studies created under the umbrella of this cancer registry to solve various clinical questions regarding daily practice patterns of lung cancer treatment

Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy

The ubiquitin fold modifier 1 (UFM1) cascade is a recently identified evolutionarily conserved ubiquitin-like modification system whose function and link to human disease have remained largely uncharacterized. By using exome sequencing in Finnish individuals with severe epileptic syndromes, we identified pathogenic compound heterozygous variants in UBAS, encoding an activating enzyme for UFM1, in two unrelated families. Two additional individuals with biallelic UBAS variants were identified from the UK-based Deciphering Developmental Disorders study and one from the Northern Finland Intellectual Disability cohort. The affected individuals (n = 9) presented in early infancy with severe irritability, followed by dystonia and stagnation of development. Furthermore, the majority of individuals display postnatal microcephaly and epilepsy and develop spasticity. The affected individuals were compound heterozygous for a missense substitution, c.1111G>A (p.A1a371Thr; allele frequency of 0.28% in Europeans), and a nonsense variant or c.164G>A that encodes an amino acid substitution p.Arg5SHis, but also affects splicing by facilitating exon 2 skipping, thus also being in effect a loss-of-function allele. Using an in vitro thioester formation assay and cellular analyses, we show that the p.A1a371Thr variant is hypomorphic with attenuated ability to transfer the activated UFM1 to UFC1. Finally, we show that the CNS-specific knockout of Ufml in mice causes neonatal death accompanied by microcephaly and apoptosis in specific neurons, further suggesting that the UFM1 system is essential for CNS development and function. Taken together, our data imply that the combination of a hypomorphic p.A1a371Thr variant in trans with a loss-of-function allele in UBAS underlies a severe infantile-onset encephalopathy.Peer reviewe

ヒト皮膚培養線維芽細胞に対する紫外線(UVA)照射が不定期DNA 合成およびCollagen 合成に対する影響に関する検討-年齢別の細胞応答-

我々が生活紫外線として通常最も多く浴びる紫外線である長波長紫外線(UVA)の皮膚真皮の主要構成細胞(Fibroblast)に対する影響について検討を行った。照射エネルギー設定のため,ヒトが日常生活で表皮を透過し,皮膚の構成細胞に浴びる種々の光電磁波を測定する目的で,50μmのヒト新鮮皮膚を用い,波長特性別光源の皮膚透過率を測定した。UVA光源ランプの皮膚層を透過するエネルギーは56.6%,UVB光源ランプでは45.7%であった。若年者と高齢者に与えるUVA商社の影響の違いについて検討するため,若年者(4ヶ月,8ヶ月,2才)由来細胞3種と高齢者(63才,85才,88才)由来細胞3種の非露光部の皮膚真皮より樹立し,継代培養した細胞を使用して実験を行った。UVAのエネルギー強度は,通常我々が晴天時に暴露されると推定される最大量(4000μw/cm2/sec)を各細胞に照射した。細胞へのUVA商社による影響の測定は,DNA剛性の変化を見るため,3H-thymidineの取り込みにより,総DNA量の測定およびラジオオートグラフィーによる不定期DNA合成測定実験を行った。また,Collagen剛性の変化を見るため、3H-thymidineの取り込みとCollagenase消化法によるCollagen合成活性試験を行った。若年者と高齢者の比較では,高齢者細胞に有意なDNAの合成量と合成率の低下が見られ,UVA照射による不定期DNA合成応答も低下していた。Collagen合成に関する比較で,高齢者細胞に有意なCollagen合成活性の低下が見られた。若年者細胞には照射後に有意なCollagen合成の増加応答が見られたが,高齢者細胞ではほとんど見られなかった。これらの結果より,皮膚がUVA暴露により生涯を受けた場合,その真皮細胞の不定期DNA合成応答と,一時的Collagen合成増加の反応性応答は,高齢者は若年者と比べ,細胞単位レベルでの低下が明らかとなった

The Ronda Peridotite: Garnet-, Spinel-, and Plagioclase-Lherzolite Facies and the P-T Trajectories of a High-Temprature Mantle Intrusion

ISSN:0022-3530ISSN:1460-241