The diagnosis of delayed expanding traumatic pseudoaneurysm of thoracic aorta caused by self-inflicted penetrating injury with crossbow bolt: A case report

Introduction and importance: Penetrating chest trauma caused by a crossbow bolt is very rare. Herein, we report a successfully treated patient who attempted suicide by directing a crossbow to the chest cavity and developed an expanding pseudoaneurysm of the thoracic aorta during eight-day follow up. Case presentation: A 51-year-old male was admitted to the emergency department after firing a crossbow bolt twice into his left chest. At admission, the patient was hemodynamically stable and maintaining oxygenation. The bolt had already been removed from the body. Contrast-enhanced computed tomography (CT) revealed a cavity pseudoaneurysm 2.5 mm in size in the aortic arch. Three-dimensional reconstruction of the CT demonstrated wound tracts showing probable damage by the bolt. The patient was admitted to the emergency department for careful observation and transferred to the psychiatric ward on day two. Follow-up contrast-enhanced CT on day eight demonstrated rapid expansion of the pseudoaneurysm from 2.5 mm to 4.0 mm in size. We performed thoracic endovascular aortic repair (TEVAR) on day 13. The patient was uneventfully discharged on the 20th hospital day. Clinical discussion: Emergency physicians should be aware that damage to the surrounding tissue may be accompanied by delayed expansion of an aortic pseudoaneurysm, even if the bolts do not cause direct aortic wall injury. Conclusion: This case suggests that understanding the injury mechanism, confirming the tract of the bolts, and carefully exploring traumatic pseudoaneurysm can lead to a less invasive operation due to early detection

Analysis of Ribosomal Protein Gene Structures: Implications for Intron Evolution

Many spliceosomal introns exist in the eukaryotic nuclear genome. Despite much research, the evolution of spliceosomal introns remains poorly understood. In this paper, we tried to gain insights into intron evolution from a novel perspective by comparing the gene structures of cytoplasmic ribosomal proteins (CRPs) and mitochondrial ribosomal proteins (MRPs), which are held to be of archaeal and bacterial origin, respectively. We analyzed 25 homologous pairs of CRP and MRP genes that together had a total of 527 intron positions. We found that all 12 of the intron positions shared by CRP and MRP genes resulted from parallel intron gains and none could be considered to be “conserved,” i.e., descendants of the same ancestor. This was supported further by the high frequency of proto-splice sites at these shared positions; proto-splice sites are proposed to be sites for intron insertion. Although we could not definitively disprove that spliceosomal introns were already present in the last universal common ancestor, our results lend more support to the idea that introns were gained late. At least, our results show that MRP genes were intronless at the time of endosymbiosis. The parallel intron gains between CRP and MRP genes accounted for 2.3% of total intron positions, which should provide a reliable estimate for future inferences of intron evolution

Ribosomal Protein Gene Knockdown Causes Developmental Defects in Zebrafish

The ribosomal proteins (RPs) form the majority of cellular proteins and are mandatory for cellular growth. RP genes have been linked, either directly or indirectly, to various diseases in humans. Mutations in RP genes are also associated with tissue-specific phenotypes, suggesting a possible role in organ development during early embryogenesis. However, it is not yet known how mutations in a particular RP gene result in specific cellular changes, or how RP genes might contribute to human diseases. The development of animal models with defects in RP genes will be essential for studying these questions. In this study, we knocked down 21 RP genes in zebrafish by using morpholino antisense oligos to inhibit their translation. Of these 21, knockdown of 19 RPs resulted in the development of morphants with obvious deformities. Although mutations in RP genes, like other housekeeping genes, would be expected to result in nonspecific developmental defects with widespread phenotypes, we found that knockdown of some RP genes resulted in phenotypes specific to each gene, with varying degrees of abnormality in the brain, body trunk, eyes, and ears at about 25 hours post fertilization. We focused further on the organogenesis of the brain. Each knocked-down gene that affected the morphogenesis of the brain produced a different pattern of abnormality. Among the 7 RP genes whose knockdown produced severe brain phenotypes, 3 human orthologs are located within chromosomal regions that have been linked to brain-associated diseases, suggesting a possible involvement of RP genes in brain or neurological diseases. The RP gene knockdown system developed in this study could be a powerful tool for studying the roles of ribosomes in human diseases

Halogen‐Free πupiupi‐Conjugated Polymers Based on Thienobenzobisthiazole for Efficient Nonfullerene Organic Solar Cells: Rational Design for Achieving High Backbone Order and High Solubility

In π-conjugated polymers, a highly ordered backbone structure and solubility are always in a trade-off relationship that must be overcome to realize highly efficient and solution-processable organic photovoltaics (OPVs). Here, it is shown that a π-conjugated polymer based on a novel thiazole-fused ring, thieno[2′, 3′:5, 6]benzo[1, 2-d:4, 3-d′]bisthiazole (TBTz) achieves both high backbone order and high solubility due to the structural feature of TBTz such as the noncovalent interlocking of the thiazole moiety, the rigid and bent-shaped structure, and the fused alkylthiophene ring. Furthermore, based on the electron-deficient nature of these thiazole-fused rings, the polymer exhibits deep HOMO energy levels, which lead to high open-circuit voltages (VOCs) in OPV cells, even without halogen substituents that are commonly introduced into high-performance polymers. As a result, when the polymer is combined with a typical nonfullerene acceptor Y6, power conversion efficiencies of reaching 16% and VOCs of more than 0.84 V are observed, both of which are among the top values reported so far for “halogen-free” polymers. This study will serve as an important reference for designing π-conjugated polymers to achieve highly efficient and solution-processable OPVs

4-Carbomethoxybenzaldehyde as a highly sensitive pre-column fluorescence derivatization reagent for 9,10-phenanthrenequinone.

9,10-Phenanthrenequinone (PQ) is harmful environmental pollutant that is detected in airborne particulates. The measurement of PQ in the air should be necessary to evaluate the potential adverse effects of PQ on human health. We have recently developed a determination method for PQ based on the fluorescence derivatization of PQ using benzaldehyde and ammonium acetate as a reagent. In this study, in order to obtain more sensitive and selective fluorescence derivatization reaction, we measured the fluorescence of the reaction mixture of PQ with 21 kinds of aromatic aldehydes in the presence of ammonium acetate. Among the tested aldehydes, 4-carbomethoxybenzaldehyde was found to be the best reagent in regard to fluorescence intensity and emission wavelength maximum. Based on the fluorescence derivatization with 4-carbomethoxybenzaldehyde, a highly sensitive chromatographic method was developed for the determination of PQ with the detection limit (S/N=3) of 1.2 fmol/injection

Five-dimensional Black Hole and Particle Solution with Non-Abelian Gauge Field

We study the 5-dimensional Einstein-Yang-Mills system with a cosmological constant. Assuming a spherically symmetric spacetime, we find a new analytic black hole solution, which approaches asymptotically "quasi-Minkowski", "quasi anti-de Sitter", or "quasi de Sitter" spacetime depending on the sign of a cosmological constant. Since there is no singularity except for the origin which is covered by an event horizon, we regard it as a localized object. This solution corresponds to a magnetically charged black hole. We also present a singularity-free particle-like solution and a non-trivial black hole solution numerically. Those solutions correspond to the Bartnik-McKinnon solution and a colored black hole with a cosmological constant in the 4-dimensions. We analyze their asymptotic behaviors, spacetime structures and thermodynamical properties. We show that there is a set of stable solutions if a cosmological constant is negative.Comment: 17 pages, 17 figures, submitted to PR

Intron Dynamics in Ribosomal Protein Genes

The role of spliceosomal introns in eukaryotic genomes remains obscure. A large scale analysis of intron presence/absence patterns in many gene families and species is a necessary step to clarify the role of these introns. In this analysis, we used a maximum likelihood method to reconstruct the evolution of 2,961 introns in a dataset of 76 ribosomal protein genes from 22 eukaryotes and validated the results by a maximum parsimony method. Our results show that the trends of intron gain and loss differed across species in a given kingdom but appeared to be consistent within subphyla. Most subphyla in the dataset diverged around 1 billion years ago, when the “Big Bang” radiation occurred. We speculate that spliceosomal introns may play a role in the explosion of many eukaryotes at the Big Bang radiation

microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity

褐色脂肪細胞の燃焼を促す新たなメカニズムを解明 --体の熱産生にマイクロRNA-33が関与--. 京都大学プレスリリース. 2021-02-17.Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33−/− mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33f/f dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)A receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33f/f DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress

Phamacogenomics of Clozapine-Induced Agranulocytosis

Background: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. Methods: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. Results: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10−9, odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10−8, OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10−5, OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. Conclusions: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated

Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells

BACKGROUND: We demonstrated that mouse embryonic stem (ES) cells-derived vascular endothelial growth factor receptor-2 (VEGF-R2) positive cells could differentiate into both endothelial cells (EC) and mural cells (MC), and termed them as vascular progenitor cells (VPC). Recently, we have established a method to expand monkey and human ES cells-derived VPC with the proper differentiation stage in a large quantity. Here we investigated the therapeutic potential of human VPC-derived EC and MC for vascular regeneration. METHODS AND RESULTS: After the expansion of human VPC-derived vascular cells, we transplanted these cells to nude mice with hindlimb ischemia. The blood flow recovery and capillary density in ischemic hindlimbs were significantly improved in human VPC-derived EC-transplanted mice, compared to human peripheral and umbilical cord blood-derived endothelial progenitor cells (pEPC and uEPC) transplanted mice. The combined transplantation of human VPC-derived EC and MC synergistically improved blood flow of ischemic hindlimbs remarkably, compared to the single cell transplantations. Transplanted VPC-derived vascular cells were effectively incorporated into host circulating vessels as EC and MC to maintain long-term vascular integrity. CONCLUSIONS: Our findings suggest that the combined transplantation of human ES cells-derived EC and MC can be used as a new promising strategy for therapeutic vascular regeneration in patients with tissue ischemia