Supersymmetric Flaxion

Recently, a new minimal extension of the Standard Model has been proposed, where a spontaneously broken, flavor-dependent global U(1) symmetry is introduced. It not only explains the hierarchical flavor structure in the quark and lepton sector, but also solves the strong CP problem by identifying the Nambu-Goldstone boson as the QCD axion, which we call flaxion. In this work, we consider supersymmetric extensions of the flaxion scenario. We study the CP and flavor violations due to supersymmetric particles, the effects of R-parity violations, the cosmological gravitino and axino problems, and the cosmological evolution of the scalar partner of the flaxion, sflaxion. We also propose an attractor-like inflationary model where the flaxion multiplet contains the inflaton field, and show that a consistent cosmological scenario can be obtained, including inflation, leptogenesis, and dark matter.Comment: 30 pages, 2 figures; v2: version published in JHE

Frail patients with respiratory failure

Background : Older patients with severe respiratory failure have higher mortality rates and are more likely to experience impairments in activities of daily living (ADL). Methods : We retrospectively reviewed patients (≥ 75 years) who received intubation and artificial ventilation for respiratory failure at Shimane University Hospital between November 2014 and December 2020. We compared the outcomes of frail patients with those of self-sufficient patients. Results : Thirty-two patients were included. ADL ability before respiratory failure was rated self-sufficient in 18 patients (self-sufficient group) and not self-sufficient in 14 patients (frail group). None of the patients in either group underwent advanced care planning prior to the onset of respiratory failure. In the self-sufficient and frail groups, the in-hospital mortality rates were 33% and 50%, and the incidence of bedridden patients at discharge was 6% and 43%, respectively. Most patients in the frail group (93%) died or were bedridden. The median hospitalization cost was JPY 2,984,000 for the self-sufficient group and JPY 3,008,000 for the frail group. Conclusion : The overall prognosis of frail older patients who underwent intubation and artificial ventilation was poor. When providing intensive care to such patients, it is important to carefully consider their suitability for the treatment

Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood

The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α–dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood. Reduced DNA methylation is associated with enhanced induction of hepatic FGF21 expression after PPARα activation, which may partly explain the attenuation of diet-induced obesity in adulthood. We propose that Fgf21 methylation represents a form of epigenetic memory that persists into adulthood, and it may have a role in the developmental programming of obesity

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

治療回復後に十二指腸ポリープからの大量出血を生じたツツガムシ病の1例

関連する既往のない50歳代の男性が，7日前から生じた倦怠感，食思不振，呼吸困難を主訴に当院へ救急搬送された。敗血症性ショックと診断され救急科に入院となった。昇圧剤と抗菌薬による治療が開始されたが全身状態の改善がなく，入院翌日に原因精査のため当科に転科となった。身体診察では発熱と散在する紅斑性皮疹に加えて右腋窩に黒色痂皮を認め，ツツガムシ病が強く疑われた。血液検査では血小板とフィブリノーゲンが低下しており播種性血管内凝固（DIC）の状態だった。ミノサイクリンによる治療を開始し全身状態は改善傾向になったが低フィブリノーゲン血症は継続した。入院5日目に消化管出血による出血性ショックが発生し，緊急内視鏡では十二指腸の有茎性ポリープからの出血が生じており内視鏡的クリッピング術が行われた。しかしその後もDICとショックの状態が継続したため，入院7日目に十二指腸ポリープに対して緊急ポリペクトミーを行いショックとDICは改善した。ポリープは腺腫であり，ツツガムシ病で生じる消化管出血でみられる血管炎の所見はなかった。ツツガムシ病はリケッチアであるOrientia tsutsugamushiがツツガムシの刺咬により伝搬するダニ媒介感染症である。重症化は全身の血管炎によって生じ，全身状態が改善しないまま様々な合併症が生じ，消化管出血も稀な合併症の1つである。本症例は治療により一旦全身状態が回復した後に，遷延する凝固異常によって十二指腸ポリープから出血し緊急ポリペクトミーによって改善した。ポリープの病理に血管炎の所見はなく，遷延する凝固異常がもたらした出血であると考えられ，これまで報告されているツツガムシ病の消化管出血とは異なる機序で生じていたと考えられた。ツツガムシ病では治療により全身状態が回復しても，凝固異常が遷延している場合消化管出血の発症に注意する必要がある。A fifties man with no relevant medical history was transferred to our emergency department because of dyspnea, general malaise, and anorexia that began 7 days before. He was diagnosed with septic shock and hospitalized. Administration of vasopressors and antimicrobials did not improve his condition, and he was referred to our department for further investigation and management the day after admission. On physical examination, in addition to fever and erythematous rash, an eschar was noted at the right armpit. Scrub typhus was strongly suspected. Laboratory tests showed thrombocytopenia and hypofibrinogenemia, indicating disseminated intravascular coagulation (DIC). The administration of minocycline improved his condition, but DIC persisted. On the fifth day, he developed gastrointestinal hemorrhagic shock, and the endoscopic examination revealed bleeding from a duodenal polyp. Endoscopic clipping was performed, but hypotension and DIC were sustained. On the seventh day, emergency polypectomy was performed, and his condition improved. Some patients with scrub typhus lead to severe disease caused by vasculitis without temporal recovery, resulting in systemic complications. Gastrointestinal bleeding is one of the rare complications. Our case had prolonged coagulation abnormalities despite therapeutic recovery and developed bleeding from a duodenal polyp for which endoscopic polypectomy was required. Histopathological examination of the polyp specimen revealed no vasculitis. Therefore, the cause of bleeding was considered due to prolonged coagulation abnormalities, not due to vasculitis, which was reported to be a typical feature of gastrointestinal bleeding in patients with scrub typhus. The complication of gastrointestinal bleeding in patients with scrub typhus should be cautioned even after the patient's condition has recovered when the coagulation abnormalities persist

Cytolytic Recombinant Vesicular Stomatitis Viruses Expressing STLV-1 Receptor Specifically Eliminate STLV-1 Env-Expressing Cells in an HTLV-1 Surrogate Model In Vitro

Human T-cell leukemia virus type 1 (HTLV-1) causes serious and intractable diseases in some carriers after infection. The elimination of infected cells is considered important to prevent this onset, but there are currently no means by which to accomplish this. We previously developed “virotherapy”, a therapeutic method that targets and kills HTLV-1-infected cells using a cytolytic recombinant vesicular stomatitis virus (rVSV). Infection with rVSV expressing an HTLV-1 primary receptor elicits therapeutic effects on HTLV-1-infected envelope protein (Env)-expressing cells in vitro and in vivo. Simian T-cell leukemia virus type 1 (STLV-1) is closely related genetically to HTLV-1, and STLV-1-infected Japanese macaques (JMs) are considered a useful HTLV-1 surrogate, non-human primate model in vivo. Here, we performed an in vitro drug evaluation of rVSVs against STLV-1 as a preclinical study. We generated novel rVSVs encoding the STLV-1 primary receptor, simian glucose transporter 1 (JM GLUT1), with or without an AcGFP reporter gene. Our data demonstrate that these rVSVs specifically and efficiently infected/eliminated the STLV-1 Env-expressing cells in vitro. These results indicate that rVSVs carrying the STLV-1 receptor could be an excellent candidate for unique anti-STLV-1 virotherapy; therefore, such antivirals can now be applied to STLV-1-infected JMs to determine their therapeutic usefulness in vivo

Cytolytic Recombinant Vesicular Stomatitis Viruses Expressing STLV-1 Receptor Specifically Eliminate STLV-1 Env-Expressing Cells in an HTLV-1 Surrogate Model In Vitro

Human T-cell leukemia virus type 1 (HTLV-1) causes serious and intractable diseases in some carriers after infection. The elimination of infected cells is considered important to prevent this onset, but there are currently no means by which to accomplish this. We previously developed “virotherapy”, a therapeutic method that targets and kills HTLV-1-infected cells using a cytolytic recombinant vesicular stomatitis virus (rVSV). Infection with rVSV expressing an HTLV-1 primary receptor elicits therapeutic effects on HTLV-1-infected envelope protein (Env)-expressing cells in vitro and in vivo. Simian T-cell leukemia virus type 1 (STLV-1) is closely related genetically to HTLV-1, and STLV-1-infected Japanese macaques (JMs) are considered a useful HTLV-1 surrogate, non-human primate model in vivo. Here, we performed an in vitro drug evaluation of rVSVs against STLV-1 as a preclinical study. We generated novel rVSVs encoding the STLV-1 primary receptor, simian glucose transporter 1 (JM GLUT1), with or without an AcGFP reporter gene. Our data demonstrate that these rVSVs specifically and efficiently infected/eliminated the STLV-1 Env-expressing cells in vitro. These results indicate that rVSVs carrying the STLV-1 receptor could be an excellent candidate for unique anti-STLV-1 virotherapy; therefore, such antivirals can now be applied to STLV-1-infected JMs to determine their therapeutic usefulness in vivo