A new species of the larger porcelaneous foraminifer Borelis provides novel insights into Neogene to recent Western Pacific palaeobiogeographical dispersal patterns

Only three species of alveolinoidean larger foraminifera occur in present-day tropical shallow-water marine settings. Alveolinella quoyi thrives in the Central Indo-Pacific and Eastern Indo-Pacific, Borelis pulchra in the Central and Eastern Indo-Pacific and in the central Atlantic, whereas Borelis schlumbergeri inhabits the IndoPacific Ocean. The northernmost record is that of Alveolinella quoyi from the shallow-water settings in Okinawa (central Ryukyu Islands, Japan). A new porcelaneous larger foraminiferal species, Borelis matsudai sp. nov. (Alveolinoidea, Borelinae), is established herein, based on specimens discovered in present-day shallow-water sediments from Sekisei Lagoon, southern Ryukyu Islands (Japan). This is the northernmost record of the genus in the western Indo-Pacific Warm Pool. The architectural characters of this species suggest its phylogenetic relationship with the Borelis pulchra group. A comprehensive literature survey of fossil and modern records of Borelis pulchra over the past 30 million years shows that the Middle Miocene constriction of the Indonesian Seaway and the Late Miocene-Early Pliocene restriction of the Indonesian Throughflow impacted the species-level dispersal of this species in the Indo-Australian Archipelago. Driven by the Kuroshio dispersal route Borelis matsudai sp. nov. likely appeared in the southern and central Ryukyu Islands at least from the Chibanian (Middle Pleistocene). This species represents a marginal part of a population in significant contact with its ancestor (B. pulchra), which is widespread southward since the Oligocene (Philippines). With ongoing global warming possible occurrences of Borelis matsudai sp. nov. in the northern Ryukyu Islands, where it has not yet been found, are expected. The Sekisei Lagoon represents, therefore, a biogeographical stepping stone relay station in northward migration of the shallow-water benthic organisms along the Kuroshio dispersal route

Endogenization and excision of human herpesvirus 6 in human genomes

Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% of humans, but it is not clear how this came about. It is also uncertain whether integrated HHV-6 can reactive into an infectious virus. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). As piRNAs block germline integration of transposons, piRNA-mediated repression of HHV-6 integration has been proposed to explain this association.In vitro, recombination of the HHV-6 genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected "solo-DR scar" has not been describedin vivo. Here we screened for integrated HHV-6 in 7,485 Japanese subjects using whole-genome sequencing (WGS). Integrated HHV-6 was associated with polymorphisms on chr22q. However, in contrast to prior work, we find that the reported MOV10L1 polymorphism is physically linked to an ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a solo-DR, supporting in vivo excision and possible viral reactivation. Together these results explain the recently-reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest potential exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact (non-retro)viral genome known to be present in human germlines

Material properties of a low contraction and resistivity silicon-aluminum composite for cryogenic detectors

We report on the cryogenic properties of a low-contraction silicon-aluminum composite, namely Japan Fine Ceramics SA001, to use as a packaging structure for cryogenic silicon devices. SA001 is a silicon--aluminum composite material (75% silicon by volume) and has a low thermal expansion coefficient ($\sim$1/3 that of aluminum). The superconducting transition temperature of SA001 is measured to be 1.18 K, which is in agreement with that of pure aluminum, and is thus available as a superconducting magnetic shield material. The residual resistivity of SA001 is 0.065 $\mathrm{\mu \Omega m}$, which is considerably lower than an equivalent silicon--aluminum composite material. The measured thermal contraction of SA001 immersed in liquid nitrogen is $\frac{L_{293\mathrm{K}}-L_{77\mathrm{K}}}{L_{293\mathrm{K}}}=0.12$%, which is consistent with the expected rate obtained from the volume-weighted mean of the contractions of silicon and aluminum. The machinability of SA001 is also confirmed with a demonstrated fabrication of a conical feedhorn array, with a wall thickness of 100 $\mathrm{\mu m}$. These properties are suitable for packaging applications for large-format superconducting detector devices.Comment: 8 pages, 4 figures, 1 table, accepted for the Journal of Low Temperature Physics for the LTD19 special issu

Variant Spectrum of von Hippel-Lindau Disease and Its Genomic Heterogeneity in Japan

Von Hippel-Lindau (VHL) disease is an autosomal dominant, inherited syndrome with variants in the VHL gene, causing predisposition to multi-organ neoplasms with vessel abnormality. Germline variants in VHL can be detected in 80-90% of patients clinically diagnosed with VHL disease. Here, we summarize the results of genetic tests for 206 Japanese VHL families, and elucidate the molecular mechanisms of VHL disease, especially in variant-negative unsolved cases. Of the 206 families, genetic diagnosis was positive in 175 families (85%), including 134 families (65%) diagnosed by exon sequencing (15 novel variants) and 41 (20%) diagnosed by multiplex ligation-dependent probe amplification (MLPA) (one novel variant). The deleterious variants were significantly enriched in VHL disease Type 1. Interestingly, five synonymous or non-synonymous variants within exon 2 caused exon 2 skipping, which is the first report of exon 2 skipping caused by several missense variants. Whole genome and target deep sequencing analysis were performed for 22 unsolved cases with no variant identified and found three cases with VHL mosaicism (variant allele frequency: 2.5-22%), one with mobile element insertion in the VHL promoter region, and two with a pathogenic variant of BAP1 or SDHB. The variants associated with VHL disease are heterogeneous, and for more accuracy of the genetic diagnosis of VHL disease, comprehensive genome and DNA/RNA analyses are required to detect VHL mosaicism, complicated structure variants and other related gene variants

Mechanomyographic activity in the human lateral pterygoid muscle during mandibular movement

The activity of the lateral pterygoid muscle has been regarded to be related to the pathological condition of the temporomandibular joint (TMJ) in the craniomandibular disorders. Because the lateral pterygoid muscle is a deep muscle, a needle electrode is necessary for EMG recordings. The purpose of this study was to establish a non-invasive method for the evaluation of muscle activity of the lateral pterygoid muscle using mechanomyogram (MMG). In three male subjects, surface electromyogram (EMG) in the left masseter muscle, left anterior and posterior belly of the temporal muscle, left anterior belly of the digastric muscle and needle EMG of the inferior head of the lateral pterygoid were recorded during mandibular movement tasks simultaneously with the MMG derived from a condenser microphone in the external ear canal. There were significant positive correlations between the needle EMG signal of the lateral pterygoid muscle and the MMG signal for the tasks of static jaw opened position of 30 mm of interincisal distance (p = 0.000, R(2)=0.725), static jaw opened position of 40 mm of interincisal distance (p = 0.000, R(2) = 0.753), 5 mm protruded mandibular position (p = 0.000, R(2) = 0.653), the most protruded mandibular position (p = 0.000, R(2) = 0803). On the contrary, for the task of maximal clenching, there was no significant correlation between the EMG signal of the lateral pterygoid muscle and the MMG signal. These results suggest that the activity of the lateral pterygoid muscle could be evaluated by the MMG signals recorded in the external ear canal, unless jaw closing major muscles show active contraction

高フェリチン血症を契機に成人Still 病と診断した不明熱症例

　成人Still 病は弛張熱，関節炎，発熱時に増強する発疹（サーモンピンク疹）を３徴とする疾患で，白血球増加，血清CRP やフェリチン値の上昇などの強い炎症所見を認め，しばしば不明熱の原因となる．高フェリチン血症を契機に成人Still 病と診断した症例を経験したので報告する．患者は57歳女性，入院３週間前から発熱とともに咽頭痛，関節痛が出現し，近医にて抗菌薬治療が行われた．抗菌薬不応の発熱で当院を紹介受診し，不明熱精査目的に入院した．入院時より前胸部や背部に淡い紅斑が出現し，採血で，白血球増加（11,480/μL），CRP 高値（12.98 mg/dL），フェリチン著明高値（5,511 ng/mL）を認めた．胸腹部CT 検査では腋窩・鼠径リンパ節の腫脹と脾腫大を認めた．血液培養検査は陰性で，骨髄生検や皮膚生検にて造血器腫瘍を示唆する所見を認めなかった．感染症や悪性腫瘍を除外し，Yamaguchi らの分類基準を満たし，成人Still 病と診断した．プレドニゾロンとメトトレキサートの併用療法を開始したところ，速やかに全身状態は改善した．不明熱の原因検索を行う際に，フェリチン値の測定は有用であると考えられる．　Adult-onset Still\u27s disease (AOSD) is a systemic inflammatory disorder which is responsible for a significant proportion of cases of fever of unknown origin. This disease is characterized by high spiking fevers, musculoskeletal disorders and salmon-colored rash. Here we report the case of a 57-year-old woman with fever of unknown origin who was diagnosed with AOSD. Hyperferritinemia contributed to her diagnosis. The patient was referred to our clinic with persistent spike fevers and arthralgia for 3 weeks despite antibiotic treatment. The patient also had a sore throat, and developed a skin rush on her trunk upon admission. Laboratory data indicated leukocytosis (11,480 /μL), elevated levels of CRP (12.98 mg/dL), and hyperferritinemia (5,511 ng/mL). To exclude infections and malignant diseases, systemic computed tomography scans and biopsy from bone marrow and skin were performed. From these examinations, and based on the criteria set by Yamaguchi et al. , the patient was given a diagnosis of AOSD. She was started on prednisone and methotrexate, and these treatments were effective. Serum ferritin levels should be checked for the evaluation of fever of unknown origin

Latitudinal cline in the foraging dichotomy of loggerhead sea turtles reveals the importance of East China Sea for priority conservation

Special Issue: Biological traits, geographic distributions and species conservation in aquatic ecosystems[Aim]Quantifying the importance of habitat areas for conservation of highly migratory marine species with complex life histories can be challenging. For example loggerhead turtles (Caretta caretta) nesting in Japan forage both oceanically and neritically after their reproductive period. Here, we aimed to quantify the proportions of turtles using these two contrasting habitats (foraging dichotomy) to suggest priority conservation areas. [Location]North Pacific Ocean. [Methods]We examined the occurrence of foraging dichotomy at three nesting sites (Ishigaki, Okinoerabu Islands and Ichinomiya) based on stable isotope analysis of the egg yolks for 82 turtles and satellite tracking of post-nesting migration for 12 turtles. Moreover, we used the data of three other sites from previous studies (Yakushima Island, Minabe and Omaezaki). [Results]Two neritic foraging grounds (East China Sea and the coastal area of the Japanese archipelago), and an oceanic ground (North Pacific Ocean) were identified. We found a latitudinal cline with respect to the occurrence of foraging dichotomy; >84% of the females nesting at southern sites (Ishigaki and Okinoerabu Islands), 73% at middle sites (Yakushima Island and Minabe) and <46% at northern sites (Omaezaki and Ichinomiya) were neritic foragers; the proportion of oceanic foragers increased at northern sites. Based on the annual number of nests in the entire nesting region of Japan, satellite tracking and the latitudinal cline of foraging dichotomy, we estimated that 70% and 9% of annual nesting females in Japan utilize the neritic foraging habitat in the East China Sea and the coastal area of the Japanese archipelago, respectively, and that and 22% utilize the oceanic habitat of the North Pacific Ocean. [Main conclusions]The East China Sea represents a critical foraging habitat for the North Pacific populations of endangered loggerhead sea turtles. Our findings emphasize the need for international management to ensure their protection

妊娠を契機に血小板減少を来たし，子宮内胎児死亡に至った全身性エリテマトーデス及び抗リン脂質抗体症候群の一例

　抗リン脂質抗体症候群は，抗リン脂質抗体が産生されることで血栓症を主体とする病態を引き起こす自己免疫疾患である．動静脈血栓症に加え，習慣性流産，早産，妊娠高血圧症候群，胎児発育遅延，胎児機能不全などの妊娠合併症を高率に引き起こすとされている．また患者のうち約半数は全身性エリテマトーデスが併存していると言われている．我々は妊娠を契機に血小板減少を来たし，子宮内胎児死亡に至った全身性エリテマトーデス及び抗リン脂質抗体症候群の症例を経験した．　患者は20歳代女性，未経妊未経産．５年前に全身性エリテマトーデス及び抗リン脂質抗体症候群と診断された．プレドニゾロンとタクロリムス，アザチオプリンによる免疫抑制療法及び低用量アスピリン療法を開始され，数年間に渡りプレドニゾロン５mg/ 日＋タクロリムス３mg/ 日＋アザチオプリン50mg/ 日で病態は安定していた．妊娠を契機にプレドニゾロン10mg/ 日の単独治療に切り替えたが，徐々に血小板減少が進行してきたため入院し，プレドニゾロン30mg/ 日への増量及びタクロリムス３mg/ 日を再開した．また血栓予防治療として，低用量アスピリンに加えヘパリン療法を開始した．しかし妊娠16週５日で子宮内胎児死亡が判明したため，血栓予防治療を中止し児の娩出に至った．　抗リン脂質抗体症候群合併妊娠は，周産期管理に慎重を要する例も存在することを念頭に置き，特にハイリスク症例に対しては妊娠成立前から産婦人科と連携して治療にあたる必要がある．　Antiphospholipid syndrome is an autoimmune disease characterized by episodes of recurrent thrombosis. This syndrome is associated with not only recurrent arteriovenous thrombosis but also recurrent pregnancy loss, premature birth, pregnancyinduced hypertension, and fetal growth restriction. It has been reported that systemic lupus erythematosus coexists with antiphospholipid syndrome in as many as about 50% of patients. We report a case of intrauterine fetal death (IUFD) following thrombocytopenia in a patient with systemic lupus erythematosus and antiphospholipid syndrome. A woman in her 20s had difficulty conceiving and had been diagnosed as having systemic lupus erythematosus and antiphospholipid syndrome 5 years earlier. She was started on immunosuppressive therapy with prednisolone 5 mg/day, tacrolimus 3 mg/day, and azathioprine 50 mg/day, with low-dose aspirin therapy. Her disease was stable for several years. Thrombopenia gradually developed after treatment was changed to prednisolone 10 mg/day during pregnancy. She was admitted to hospital and treatment was started with prednisolone 30 mg/day, tacrolimus 3 mg/day, and heparin therapy in addition to low-dose aspirin therapy. However, IUFD was detected at a gestational age of 16 weeks 5 days, so we discontinued thromboprophylaxis treatment and administered a therapeutic abortion. In patients with antiphospholipid syndrome who need meticulous perinatal management, it is important to consult with the obstetrics and gynecology specialists before proceeding with a potentially high-risk pregnancy

Clinical Outcome of Patients with Pelvic and Retroperitoneal Bone and Soft Tissue Sarcoma : A Retrospective Multicenter Study in Japan

This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan