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Organic sludge has recently attracted attention as a renewable energy source. While the organic matter contained in sludge can be utilized as various renewable energy sources, its nitrogen component has limited use. In this study, subcritical water treatment was conducted to recover ammonia from digested sludge. While ammonia recovered via stripping is limited to soluble components, subcritical water treatment can convert solid components and dissolved organic nitrogen sludge into ammonia. Digested sludge was treated at several reaction temperatures, reaction pressures, treatment times, and oxygen ratios to determine the ammonia generation rate. Among the conditions tested in this study, an ammonium generation rate of 84.0% was obtained at 400 °C, 10 MPa, a treatment time of 5 min, and at an oxygen ratio of 1.2.

Railway structures applied to high-speed railways must achieve high performance in terms of strength and deformation characteristics. This requirement has led to the widespread use of geosynthetic-reinforced soil (GRS) structures. For the design of GRS structures, it is important to evaluate not only the tensile strength of the geosynthetic but also the pullout stiffness (spring constant of geosynthetic). Hence, a series of cyclic pullout loading tests were conducted to evaluate the pullout characteristics of various types of reinforcement embedded in the soil. Moreover, these test results were compared with the results of in-isolation tensile tests with the same loading histories. The experiments revealed that the pullout stiffness increased with an increase in the confining pressure and in-isolation tensile stiffness, but decreased with an increase in the relative displacement between the soil and reinforcement. Although the pullout stiffness was found to be affected by factors such as experimental conditions and type of reinforcement, a similar trend was observed in the results of several other tests when examining the relationship between the normalized pullout stiffness and the average strain generated in the reinforcement. This interesting correlation can be taken into account during the design of GRS structures that support bridge girders.

The restriction enzymes examined so far are phosphodiesterases, which cleave DNA strands by hydrolyzing phosphodiester bonds. Based on the mobility of restriction-modification systems, recent studies have identified a family of restriction enzymes that excise a base in their recognition sequence to generate an abasic (AP) site unless the base is properly methylated. These restriction glycosylases also show intrinsic but uncoupled AP lyase activity at the AP site, generating an atypical strand break. Action of an AP endonuclease at the AP site may generate another atypical break, rejoining/repairing of which is difficult. The PabI family of restriction enzymes contain a novel fold (HALFPIPE) and show unusual properties, such as non-requirement of divalent cations for cleavage. These enzymes are present in Helicobacteraceae/Campylobacteraceae and in few hyperthermophilic archaeal species. In Helicobacter genomes, their recognition sites are strongly avoided, and the encoding genes are often inactivated by mutations or replacement, indicating that their expression is toxic for the cells. The discovery of restriction glycosylases generalizes the concept of restriction-modification systems to epigenetic immune systems, which may use any mode of damage to DNA that are considered “non-self” based on epigenetic modifications. This concept will add to our understanding of immunity and epigenetics.

Vanadium atoms in layered LiVO2 form in-plane periodic vanadium trimers at low temperatures, but the trimers appear randomly in the stacking direction because there are many trimer configurations with comparable lattice energy. We detailed an original modeling scheme to represent glassy states with a completely disordered trimer configuration in the stacking structure. Through PDF analysis using this model, we show that the synthesis method can yield two types of low-temperature stacking structures: a completely disordered stacking structure and a short-range order in the stacking structure. The phase transition temperature of the former sample is about 15 K lower than that of the latter. We discuss that this is due to the strong trimer frustration that appears in the sample without short-range order, which suppresses the phase transition temperature, similar to the frustration effect in conventional spin systems., Comment: 6 pages, 4 figures

Background DNA transposons are ubiquitous components of eukaryotic genomes. A major group of them encode a DDD/E transposase and contain terminal inverted repeats (TIRs) of varying lengths. The Kolobok superfamily of DNA transposons has been found in a wide spectrum of organisms. Results Here we report a new Kolobok lineage, designated KolobokP. They were identified in 7 animal phyla (Mollusca, Phoronida, Annelida, Nemertea, Bryozoa, Chordata, and Echinodermata), and are especially rich in bivalves. Unlike other Kolobok families, KolobokP adopts a composite-like architecture: an internal region (INT) flanked by two long terminal direct repeats (LTDRs), which exhibit their own short terminal inverted repeats ranging up to 18 bps. The excision of LTDRs was strongly suggested. The LTDR lengths seem to be constrained to be either around 450-bp or around 660-bp. The internal region encodes a DDD/E transposase and a small His-Me finger nuclease, which likely originated from the homing endonuclease encoded by a group I intron from a eukaryotic species. The architecture of KolobokP resembles composite DNA transposons, usually observed in bacterial genomes, and long terminal repeat (LTR) retrotransposons. In addition to this monomeric LTDR-INT-LTDR structure, plenty of solo LTDRs and multimers represented as (LTDR-INT)n-LTDR are also observed. Our structural and phylogenetic analysis supported the birth of KolobokP in the late stage of the Kolobok evolution. We propose KolobokP families propagate themselves in two ways: the canonical transposition catalyzed by their transposase and the sequence-specific cleavage by their endonuclease followed by the multimerization through the unequal crossover. Conclusions The presence of homing endonuclease and long terminal direct repeats of KolobokP families suggest their unique dual replication mechanisms: transposition and induced unequal crossover.

Background The short-term effects of teduglutide (TED) for short bowel syndrome with chronic intestinal failure (SBS–IF) in patients with Crohn’s disease (CD) remain unknown and real-world data have not been scarce. This study aimed to investigate the short-term efficacy and safety of TED in CD patients on parenteral support (PS) for SBS–IF. Methods We retrospectively investigated the medical records of CD patients with SBS–IF who initiated TED between January 2020 and October 2022 in Hyogo Medical University hospital. The primary outcomes were the change in PS volume and proportion of patients with a reduction of PS volume by ≥20% at week 4. Secondary outcomes were the changes in body mass index (BMI), estimated glomerular filtration rate (eGFR), albumin, hematocrit (Ht), PS calorie requirements, withdrawal from PS, and adverse events during the observation period. Results Of 605 CD patients, 23 who underwent home PS for SBS–IF were included in this study. Twenty patients continued TED throughout the observation period. The median PS duration was 11.6 (range 1.0-20.0) years and the observation period after starting TED was 48.0 (7.0-60.0) weeks. TED significantly reduced the PS volume from 17989(570-49000) mL/week to 14257(0-42000) mL/week at week 4 (p = 0.0013), and the PS volume decreased by ≥20% in 8 patients (40.0%) at week 4 and in 16 patients (80.0%) during the observation period after TED administration. The BMI significantly increased from 17.9 (12.9–23.9) kg/m2 before TED administration and 18.9 (14.6–25.4) kg/m2 after TED administration (p = 0.014). Although there were no significant differences in albumin (p = 0.53), eGFR (p = 0.66), and Ht (p = 0.089), the PS calorie /week was significantly decreased from 6581 (244–14000) kcal to 3747(0– 8820) kcal after TED administration (p = 0.0001). Ten patients (50.0%) experienced gastrointestinal stoma complications, including stoma swelling and/or prolapse during the observation period. Abdominal pain occurred in 7 cases (35.0%), catheter-related infection in five patients (25.0%), oedema in 4 patients (20.0%), nausea in 2 patients (10.0%), abdominal distension in 3 patients (15.0%), and upper respiratory tract infection in 1 patient (5.0%). All the symptoms were transient and tolerable. Although 3 patients discontinued TED due to nausea and abdominal pain and were excluded from this analysis, these symptoms improved after the discontinuation. Conclusion TED reduced PS volume at week 4 in CD patients with SBS–IF, and the BMI and the PS calorie requirement were improved during the observational period without serious adverse events.

DDD/E transposase gene is the most abundant gene in nature and many DNA transposons in all three domains of life use it for their transposition. A substantial number of eukaryotic DNA transposons show similarity to prokaryotic insertion sequences (ISs). The presence of IS481-like DNA transposons was indicated in the genome of Trichomonas vaginalis. Here, we surveyed IS481-like eukaryotic sequences using a bioinformatics approach and report a group of eukaryotic IS481-like DNA transposons, designated IS481EU, from parabasalids including T. vaginalis. The lengths of target site duplications (TSDs) of IS481EU are around 4 bps, around 15 bps, or around 25 bps, and strikingly, these discrete lengths of TSDs can be observed even in a single IS481EU family. Phylogenetic analysis indicated the close relationships of IS481EU with some of the prokaryotic IS481 family members. IS481EU was not well separated from IS3EU/GingerRoot in the phylogenetic analysis, but was distinct from other eukaryotic DNA transposons including Ginger1 and Ginger2. The unique characteristics of IS481EU in protein sequences and the distribution of TSD lengths support its placement as a new superfamily of eukaryotic DNA transposons.

The space-charge potential can be a source of various resonances in high-intensity hadron bunches traveling in linear accelerators at relatively low energy. Those natural resonances, which may occur even without external driving fields, have to be avoided carefully to minimize undesired beam loss. We perform self-consistent multiparticle simulations systematically to locate major resonance stop bands in the tune diagram, starting from equipartitioned and nonequipartitioned beams. Serious excitation of synchrobetatron resonances is confirmed, depending on the emittance condition at injection. It is demonstrated that a synchrobetatron difference resonance of any order can be suppressed strongly by controlling the ratio of the transverse and longitudinal projected emittances. The equipartitioned linac design is shown to broaden the usable operating area in the tune space, though that has almost nothing to do with thermodynamic effects.

Recently, many embankment disasters have occurred. The main causes of these disasters are natural hazards, such as earthquakes, rainfalls and the combination of these. We are proposing a sustainable seismic and rainfall countermeasures for railway and road embankments by means of geo-cells (made of HDPE) and soil reinforcement bars (Gc-Rb embankment). The soil reinforcement bar is inserted into an embankment, and the geo-cell is laid on the slope of the embankment. The characteristics of this method are the convenience of construction and the economy, in addition to the reinforcement against the natural hazards. The embankment of the Sanriku Railway Riasu Line was seriously damaged by the Tohoku Region Pacific Offshore Earthquake occurred on March 11, 2011 in Japan. Many civil structures were damaged not only in the Sanriku railway but also in Pacific ocean side of Tohoku area. In the restoration works of these structures, the shortage of the construction machine, the machine operator and related materials was the problem. Therefore easiness of construction and usual materials were demanded (such materials other than concrete and so on). The proposed method satisfies these required conditions. The operation of this railway line was restarted on April 3, 2013, two years after the earthquake. In this paper we report the current state of the embankment using this recovery method, including the maintenance, after 6 years from the restart of the service.

Study question Can a scoring model based on morphokinetic data developed to predict pregnancy rates of day–5 blastocyst transfers (KIDSCORE™D5) predict pregnancy rates of day–6 blastocyst transfers? Summary answer KIDSCORE™D5 was able to predict the clinical pregnancy rates of embryo transfers done on day 6 with an area under the curve (AUC) of 0.72. What is known already KIDSCORE™D5 is a scoring model based on morphokinetic data developed to predict the pregnancy rates of day–5 blastocysts. In 2019, Regnier et al. reported that the AUC of KIDSCORE™D5 for predicting clinical pregnancy rates of day–5 blastocyst transfers was 0.6. However, as KIDSCORE™D5 is constructed based on morphological characteristics and developmental dynamics of day–5 blastocysts, it is unclear whether KIDSCORE™D5 can predict pregnancy rates of day–6 blastocyst transfers. Since there are many cases of day–6 blastocyst transfers, it is important to know if KIDSCORE™D5 can predict pregnancy rates of day–6 blastocyst transfers. Study design, size, duration This retrospective single-center study, which included 162 day–5 and 72 day–6 blastocyst transfers, respectively, was conducted at Takahashi Women’s clinic from January to December 2019. Blastocysts derived from 146 patients who underwent intracytoplasmic sperm injection. All blastocysts were cryopreserved and were transferred singly. Participants/materials, setting, methods We used EmbryoScope+™ (Vitrolife) for in-vitro culture and calculated KIDSCORE™D5 (ver.3) using Embryoviewer™ (Vitrolife). Blastocyst scoring was done from 1.0 to 9.9. Clinical pregnancy was defined as the presence of a gestational sac confirmed by transvaginal ultrasonography. Statistical analysis was performed with JMP Pro 15.00 (SAS). The relationship between KIDSCORE™D5 and clinical pregnancy was evaluated by the AUC using ROC curve analysis and multivariate analysis adjusted for patient age. Main results and the role of chance The mean KIDSCORE™D5 of day–5 and day–6 blastocysts was 7.1±1.7 and 3.7±1.5, respectively. KIDSCORE™D5 of day–6 blastocysts was significantly lower than that of day–5 blastocysts (p Limitations, reasons for caution This study had a small sample size, and it was a retrospective single-center study. In addition, the relationship between KIDSCORE™D5 and clinical pregnancy rates may vary among facilities. Therefore, a prospective multicenter validation is necessary. Wider implications of the findings: Our study results indicated that KIDSCORE™D5 predicted clinical pregnancy and that morphokinetic parameters related to clinical pregnancy were similar between day–5 and day–6 blastocysts. Hence, morphokinetic evaluation can serve as a criterion for deciding which of multiple day–6 blastocysts can be transferred. Trial registration number Not applicable

Short interspersed elements (SINEs), which are nonautonomous transposable elements, require the transposition machinery of long interspersed elements (LINEs) to mobilize. SINEs are composed of two or more independently originating parts. The 5′ region is called the “head” and is derived mainly from small RNAs, and the 3′ region (“tail”) originates from the 3′ region of LINEs and is responsible for being recognized by counterpart LINE proteins. The origin of the middle “body” of SINEs is enigmatic, although significant sequence similarities among SINEs from very diverse species have been observed. Here, a systematic analysis of the similarities among SINEs and LINEs deposited on Repbase, a comprehensive database of eukaryotic repeat sequences was performed. Three primary findings are described: 1) The 5′ regions of only two clades of LINEs, RTE and Vingi, were revealed to have contributed to the middle parts of SINEs; 2) The linkage of the 5′ and 3′ parts of LINEs can be lost due to occasional tail exchange of SINEs; and 3) The previously proposed Ceph-domain was revealed to be a fusion of a CORE-domain and a 5′ part of RTE clade of LINE. Based on these findings, a hypothesis that the 5′ parts of bipartite nonautonomous LINEs, which possess only the 5′ and 3′ regions of the original LINEs, can contribute to the undefined middle part of SINEs is proposed.

Objective To reveal the relationship between canine corticosteroid-induced alkaline phosphatase isoenzyme activity and hepatobiliary diseases. Materials and Methods Retrospective analysis of the relationship between serum corticosteroid-induced alkaline phosphatase activity and diagnosis, serum cortisol concentration and alanine transferase activity in dogs with hepatobiliary diseases. Dogs with a history of glucocorticoid administration were excluded. Results Seventy-two dogs with hepatobiliary diseases were analysed. The serum corticosteroid-induced alkaline phosphatase concentration was increased in dogs with hepatobiliary diseases. There was no correlation between serum cortisol concentration and serum corticosteroid-induced alkaline phosphatase percentage or activity. Clinical Significance Dogs with hepatobiliary disease can exhibit high serum alkaline phosphatase activity even if the dogs have not been administrated glucocorticoids and the serum cortisol concentration is normal.

Although population characteristics and antimicrobial prescribing practices suggest that the hospitalized population in Japan is at high risk of Clostridioides difficile infection (CDI), the epidemiology of CDI in Japan is poorly understood.This prospective cohort study aimed to investigate the epidemiology of CDI at 12 hospitals in Japan.Patients with clinically significant diarrhoea (CSD) were enrolled. Stool specimens were tested for C. difficile by toxin A and/or B enzyme immunoassay (EIA) in the hospital laboratories, and a toxigenic culture and nucleic acid amplification tests were performed at a central laboratory. The risk factors of CDI and the impact of CDI on mortality were investigated.In total, 566 patients with CSD were included in the analyses. A total of 152 patients received the diagnosis of CDI by Toxin A/B EIA, toxigenic culture, or nucleic acid amplification test. Factors associated with CDI included low albumin (adjusted odds ratio (aOR): 1.56; 95% confidence interval (CI): 1.03-2.34) and length of hospital stay before stool collection18 days (aOR: 1.73; 95% CI: 1.09-2.75). CDI was associated with an increased mortality on univariate analysis (OR: 1.6, 95% CI: 1.0-2.6) but was not associated with an increased risk of mortality on multivariable analysis.Risk factors for CDI in Japan were similar to those identified in the USA and Europe. However, CDI was not associated with an increased risk of mortality in this population of patients with CSD.

The majority of eukaryotic genomes contain a large fraction of repetitive sequences that primarily originate from transpositional bursts of transposable elements (TEs). Repbase serves as a database for eukaryotic repetitive sequences and has now become the largest collection of eukaryotic TEs. During the development of Repbase, many new superfamilies/lineages of TEs, which include Helitron, Polinton, Ginger and SINEU, were reported. The unique composition of protein domains and DNA motifs in TEs sometimes indicates novel mechanisms of transposition, replication, anti-suppression or proliferation. In this review, our current understanding regarding the diversity of eukaryotic TEs in sequence, protein domain composition and structural hallmarks is introduced and summarized, based on the classification system implemented in Repbase. Autonomous eukaryotic TEs can be divided into two groups: Class I TEs, also called retrotransposons, and Class II TEs, or DNA transposons. Long terminal repeat (LTR) retrotransposons, including endogenous retroviruses, non-LTR retrotransposons, tyrosine recombinase retrotransposons and Penelope-like elements, are well accepted groups of autonomous retrotransposons. They share reverse transcriptase for replication but are distinct in the catalytic components responsible for integration into the host genome. Similarly, at least three transposition machineries have been reported in eukaryotic DNA transposons: DDD/E transposase, tyrosine recombinase and HUH endonuclease combined with helicase. Among these, TEs with DDD/E transposase are dominant and are classified into 21 superfamilies in Repbase. Non-autonomous TEs are either simple derivatives generated by internal deletion, or are composed of several units that originated independently.

A brief overview is given of the recent work done by the beam-physics group of Hiroshima University on resonant beam instabilities in high-intensity hadron rings. Emphasis is placed upon two essentially different instability mechanisms, namely, coherent and incoherent resonances that occur respectively in the beam core and in the beam tail. On the basis of a semi-empirical coherent resonance condition, a simple rule is introduced to construct a new type of stability map. The proposed diagram enables one to find the optimum operating region of any circular machine in the betatron tune space very easily and quickly.

Background In 2016 update of the EUALR recommendations for management of rheumatoid arthritis (RA), the poor prognostic factors include moderate to high disease activity according to composite measures and presence of Rheumatoid factor (RF) and/or anti-citrullinated peptide antibodies (ACPA), especially at high levels. Objectives In this retrospective study, we investigated the association between baseline clinical prognostic factors and inadequate response to methotrexate for early RA in clinical practice. Methods Patients aged 18 years or over whose date of clinical onset of RA was within the previous 12 months to the first visit to our hospital from 2009 to 2016, who had at least 6 months of follow-up data and composite measure score (DAS-SER, DAS-CRP, SDAI, CDAI) recorded at 12 months from MTX treatment were included. Data collected included baseline demographics, rheumatoid factor (RF), ACPA status and the level of its titer, time from symptom onset to treatment and disease activity at baseline. In this study, we define that it was inadequate response to MTX (MTX-IR) when the patient didn’t achieve low disease activity in at least three of four composite measures at 12 months after treatment, or was stopped to treat due to any reason or added biologic DMARDs (bDMARDs) in the observation period. Univariate and multivariate logistic regression of Inadequate response to MTX at 12 months after were performed. Results Data from 486 patients treated with MTX of 571 started to treat as early RA were analysed: 72.0% female; mean age 59.6 years (SD: 14.4); time from symptom onset to treatment is 7.3 months (SD 10.5); 66.1% RF-positive, 66.9% ACPA-positive. The number of patients is 138 (45.8% of ACPA positive) whose ACPA is in the higher level, over 150IU/ml. 411 patients were initially treated with MTX, and 75 were initially treated with other csDMARDs but added or changed to MTX within 1 years after treatment. Concomitant rate of corticosteroid at the start of MTX was 41.5% and mean dose of predonisolone was 5.7 mg/day. 270 (55.6%) patients were MTX-IR in 12 months after treatment. There is no significant difference between the dose of MTX at start in MTX-IR patients and that in others (6.70 versus 6.69 mg/week, respectively) but the dose at 12 months after treatment was 8.29 mg/w in MTX responders and significantly lower than that of MTX-IR, 8.68 mg/dl (p Conclusions In this observational study, patients with early RA at risk of inadequate response to MTX include only with high disease activity at baseline, and the level of ACPA titers or other baseline characteristics don’t predict it. Disclosure of Interest None declared

Identification of hydrocarbon generating source rocks and evaluation of their potential are essential in the exploration and development of hydrocarbon resources. For an offshore oil field in Abu Dhabi, we conducted geochemical study using crude oil and core samples from Upper Cretaceous Cenomanian carbonate rocks. The study objectives are 1) correlation of crude oil and source rock with biomarker, and 2) evaluation of the source rock potential. The Cenomanian carbonate rocks of the oil field are composed of shallow marine porous limestone and deep marine lime mudstone. This Cenomanian lime mudstone was believed as source rock of the crude oil in the interfingered Cenomanian porous limestone reservoirs. However, the origin of crude oil has been poorly constrained with geochemistry yet. In this study, we carried out geological description and RockEval pyrolysis analysis of core samples to evaluate source rock potential of the lime mudstone. Then, biomarkers such as hopane, sterane and compound specific isotopic ratio of n-alkane were analyzed to correlate the source rock and the crude oil samples with GC/MS, GC/MS/MS and GC/C/IRMS for high resolution biomarker measurements and robust interpretation. As a result, the biomarker fingerprints of the crude oil in porous limestone and the organic material in the lime mudstone show significant similarity. It proves that the crude oil in the porous limestone is migrated from interfingered organic rich Cenomanian lime mudstone. In addition, the lime mudstone shows excellent source rock property (Total Organic Carbon exceeding 4%, Hydrogen Index > 600mg/g TOC) and categorized as Type I/II source rock deposited in marine environment. Furthermore, the biomarkers effectively constrain the maturity of source rock which is difficult to evaluate with Vitrinite Reflectance and RockEVAL analysis. Consequently, the timing of hydrocarbon generation and the area of effective source rock will be interpreted based on our study result with higher confidence. This study deepens understanding of Cenomanian petroleum system in offshore Abu Dhabi. The result suggests the advantage of biomarker application not only in oil-source correlation but also in source rock maturity analysis.

Apoptotic cell death plays a pivotal role in the development and/or maintenance of several tissues including thymus. Deregulated thymic cell death is associated with autoimmune diseases including experimental autoimmune encephalomyelitis (EAE), a prototype murine model for analysis of human multiple sclerosis. Because Thy28 expression is modulated during thymocyte development, we tested whether Thy28 affects induction of EAE as effectively as antigen-induced thymocyte deletion using Thy28 transgenic (TG) mice. Thy28 TG mice showed partial resistance to anti-CD3 monoclonal antibody (mAb)-induced thymic cell death in vivo, as assessed by annexin V-expression and loss of mitochondrial membrane potential. The resistance to anti-CD3 mAb-induced cell death in Thy28 TG mice appeared to correlate with a decreased c-Jun N-terminal kinase phosphorylation and reduced down-regulation of Bcl-xL. Moreover, thymic hyperplasia was detected in Thy28 TG mice, although thymocyte development was unaltered. Development of peripheral lymphoid tissues including spleen and lymph nodes was also unaltered. Thy28 TG spleen T cells showed an increased production of IFN-γ, but not IL-17, in response to both anti-CD3 and anti-CD28 mAbs. Finally, Thy28 TG mice displayed accelerated induction of EAE as assessed by disease incidence, clinical score, and pathology following immunization with myelin oligodendrocyte glycoprotein compared with control WT mice. These findings suggest that modulation of Thy28 expression plays a crucial role in the determination of thymic cell fate, which may contribute to the development of EAE through proinflammatory cytokine production.

Chicken repeat 1 (CR1) retroposons are long interspersed elements (LINEs) that are ubiquitous within amniote genomes and constitute the most abundant family of transposed elements in birds, crocodilians, turtles, and snakes. They are also present in mammalian genomes, where they reside as numerous relics of ancient retroposition events. Yet, despite their relevance for understanding amniote genome evolution, the diversity and evolution of CR1 elements has never been studied on an amniote-wide level. We reconstruct the temporal and quantitative activity of CR1 subfamilies via presence/absence analyses across crocodilian phylogeny and comparative analyses of 12 crocodilian genomes, revealing relative genomic stasis of retroposition during genome evolution of extant Crocodylia. Our large-scale phylogenetic analysis of amniote CR1 subfamilies suggests the presence of at least seven ancient CR1 lineages in the amniote ancestor; and amniote-wide analyses of CR1 successions and quantities reveal differential retention (presence of ancient relics or recent activity) of these CR1 lineages across amniote genome evolution. Interestingly, birds and lepidosaurs retained the fewest ancient CR1 lineages among amniotes and also exhibit smaller genome sizes. Our study is the first to analyze CR1 evolution in a genome-wide and amniote-wide context and the data strongly suggest that the ancestral amniote genome contained myriad CR1 elements from multiple ancient lineages, and remnants of these are still detectable in the relatively stable genomes of crocodilians and turtles. Early mammalian genome evolution was thus characterized by a drastic shift from CR1 prevalence to dominance and hyperactivity of L2 LINEs in monotremes and L1 LINEs in therians.

This chapter describes the current state of cartilage tissue engineering and its application in reconstructive and cosmetic plastic surgery. It explains why tissue engineering is a promising approach to solving the problem of tissue deficit for reconstructive procedures, the desired properties of the created neotissue, and the advances that have been made in the field to date. It then outlines important considerations in the selection of cell sources and scaffolding materials, including donor morbidity and recipient compatibility. The results of using different scaffolding materials in both in vitro and in vivo studies are presented. Finally, some of the current challenges in the field of cartilage tissue engineering, as well as considerations for its future trajectory, are discussed.

SummaryBackground Drug-induced pemphigus (DIP) shows clinical, histopathological and immunological features of pemphigus. However, little is known about immunological profiles in DIP. Objectives To characterize clinical and immunological profiles in patients with DIP. Methods We studied 17 Japanese patients with DIP who were treated at Kurume University Hospital or who consulted from other hospitals between 1997 and 2012. Complicated diseases, clinical and histopathological manifestations, responsible drugs and findings in immunofluorescence, enzyme-linked immunosorbent assays (ELISAs), immunoblotting (IB) and prognosis were analysed. Results Eight of the 17 patients with DIP showed pemphigus foliaceus-like appearance, three showed pemphigus herpetiformis-like appearance, and six showed atypical bullous lesions. Responsible drugs were thiol-containing drugs in 16 patients (bucillamine in nine cases, d-penicillamine in four cases, and cetapril, thiopronine and captopril in one patient each), and a nonthiol drug, sulfasalazine, in one patient. By ELISAs and/or IB analyses, nine patients reacted only with desmoglein 1 (Dsg1), four reacted with Dsg1 and Dsg3, and four showed no specific reactivity. By IB of normal human epidermal extracts, in addition to positive reactivity with Dsg1, four patients with no detectable malignancy showed paraneoplastic pemphigus-like reactivity with the 210-kDa envoplakin and the 190-kDa periplakin. Four cases showed anti-Dsg3 antibodies without mucosal lesions. While 11 cases recovered after discontinuation of the causative drugs, six patients had a very protracted or intractable disease course, and might develop true pemphigus. Conclusions The present study indicated that the majority of the patients with DIP studied showed a pemphigus foliaceus-type phenotype with anti-Dsg1 autoantibodies, caused by thiol-containing drugs.