Annotation and analysis of a large cuticular protein family with the R&R Consensus in Anopheles gambiae

<p>Abstract</p> <p>Background</p> <p>The most abundant family of insect cuticular proteins, the CPR family, is recognized by the R&R Consensus, a domain of about 64 amino acids that binds to chitin and is present throughout arthropods. Several species have now been shown to have more than 100 CPR genes, inviting speculation as to the functional importance of this large number and diversity.</p> <p>Results</p> <p>We have identified 156 genes in <it>Anopheles gambiae </it>that code for putative cuticular proteins in this CPR family, over 1% of the total number of predicted genes in this species. Annotation was verified using several criteria including identification of TATA boxes, INRs, and DPEs plus support from proteomic and gene expression analyses. Two previously recognized CPR classes, RR-1 and RR-2, form separate, well-supported clades with the exception of a small set of genes with long branches whose relationships are poorly resolved. Several of these outliers have clear orthologs in other species. Although both clades are under purifying selection, the RR-1 variant of the R&R Consensus is evolving at twice the rate of the RR-2 variant and is structurally more labile. In contrast, the regions flanking the R&R Consensus have diversified in amino-acid composition to a much greater extent in RR-2 genes compared with RR-1 genes. Many genes are found in compact tandem arrays that may include similar or dissimilar genes but always include just one of the two classes. Tandem arrays of RR-2 genes frequently contain subsets of genes coding for highly similar proteins (sequence clusters). Properties of the proteins indicated that each cluster may serve a distinct function in the cuticle.</p> <p>Conclusion</p> <p>The complete annotation of this large gene family provides insight on the mechanisms of gene family evolution and clues about the need for so many CPR genes. These data also should assist annotation of other <it>Anopheles </it>genes.</p

アクセイ フクマク チュウヒシュ ニ タイスル cytoreductive surgery

海外では悪性腹膜中皮腫に対してcytoreductive surgery (CRS)と腹腔内温熱化学療法を含めた周術期化学療法が普及しているものの、本邦では悪性腹膜中皮腫に対する外科的治療の報告は乏しい。今回我々は当院でのCRSと周術期化学療法による悪性腹膜中皮腫に対する治療成績を報告する。2013年2月から2022年4月までの期間において、15例の悪性腹膜中皮腫に対してCRSを施行した。患者年齢の中央値は58歳(42-67)で、男性5例と女性10例であった。CRSは病変の存在する壁側腹膜と臓器切除を組み合わせて施行した。10例に対して術前化学療法を施行し、12例に対して術後化学療法を施行した。腹腔内温熱化学療法を8例に対して施行した。全生存期間の中央値は41か月であった。3年生存率57.7%で、5年生存率は34.6%であった。上皮型でperitoneal cancer index≦22であった6例については全例生存中であり、今後の長期生存が期待される結果であった。2.5cmより大きな腫瘍が遺残した場合でも術後化学療法の奏功により3年以上の生存が得られる症例も存在していた。単変量解析をおこなうも、生存に関する統計学的に有意な因子は認めなかった。手術合併症（Clavien-Dindo分類3以上）はGrade 3aが2例、Grade 3bが1例、Grade 4aが2例であった。悪性腹膜中皮腫に対して、これまで日本で施行されてきた化学療法単独療法では予後不良であることが知られている。一方、今回の我々が施行したCRSと周術期化学療法の治療成績は比較的予後良好であり、合併症も許容範囲内であると考えられた。悪性腹膜中皮腫に対する海外におけるCRSと化学療法による良好な治療成績の報告があることからも、本邦でのCRSと周術期化学療法の継続と症例の集積により、体系的な治療法確立と治療成績向上が期待できるであろう。Cytoreductive surgery and perioperative chemotherapy, including hyperthermic intraperitoneal chemotherapy, the standard treatments for malignant peritoneal mesothelioma worldwide are not yet widespread in Japan. We report the surgical outcomes of cytoreductive surgery with perioperative chemotherapy for patients with malignant peritoneal mesothelioma at our institution. We encountered 15 patients who required cytoreductive surgery from February 2013 to April 2022. Their median age was 58 (range 42–67) years, and there were 5 men and 10 women. Cytoreductive surgery was performed by combining extensive peritoneal resection and the resection of various organs. Ten patients underwent neoadjuvant chemotherapy. Hyperthermic intraperitoneal chemotherapy was performed in 8 patients, and 12 patients received postoperative systemic chemotherapy. The median overall survival period was 41 months for all patients. After the cytoreductive surgery, the 3- and 5-year survival rates were 57.7% and 34.6%, respectively. All six patients with epithelial-type peritoneal mesothelioma with a peritoneal cancer index of ≤22 are alive, with expected long-term survival. Furthermore, among patients with a cytoreduction completeness of 3, which indicates residual tumors of >2.5 cm in diameter, long-term survival was achieved in those who responded to chemotherapy. In the univariate analysis, no significant factor was identified for overall survival. For malignant peritoneal mesothelioma, the treatment outcome of chemotherapy alone, which is the standard treatment in Japan, is known to be poor. This study demonstrated that cytoreductive surgery with chemotherapy achieved better outcomes than known reports in Japan. The results of cytoreductive surgery with chemotherapy from across the world may improve treatment outcomes in Japan

Electron-bunch compression using a dynamical nonlinearity correction for a compact x-ray free-electron laser

We propose a novel method to achieve a highly brilliant electron bunch with a peak current of several kA in an x-ray free-electron laser (XFEL) by efficiently correcting nonlinearity of the bunch-compression system. In this method, a second-order positive energy chirp is imprinted to the electron bunch by a correction cavity installed at the beginning of the system, namely the nonlinearity is initially overcorrected. The imprinted chirp is enhanced in a compression process at a bunch compressor due to electron bunch rotation in longitudinal phase space, and then continuously corrects the second-order nonlinearity induced in the following sections. Since the frequency and field amplitude of the correction cavity can be significantly lowered to the available technology level, this method enables the use of a high-frequency accelerator, i.e., a high-gradient accelerator, which is indispensable to realize a compact XFEL facility

Brightness analysis of an electron beam with a complex profile

We propose a novel analysis method to obtain the core bright part of an electron beam with a complex phase-space profile. This method is beneficial to evaluate the performance of simulation data of a linear accelerator (linac), such as an x-ray free electron laser (XFEL) machine, since the phase-space distribution of a linac electron beam is not simple, compared to a Gaussian beam in a synchrotron. In this analysis, the brightness of undulator radiation is calculated and the core of an electron beam is determined by maximizing the brightness. We successfully extracted core electrons from a complex beam profile of XFEL simulation data, which was not expressed by a set of slice parameters. FEL simulations showed that the FEL intensity was well remained even after extracting the core part. Consequently, the FEL performance can be estimated by this analysis without time-consuming FEL simulations

Undulator commissioning by characterization of radiation in x-ray free electron lasers

In x-ray free electron lasers (XFELs) where a long undulator composed of many segments is installed, there exist a number of error sources to reduce the FEL gain such as the trajectory error, K value discrepancy, and phase mismatch, which are related to the segmented-undulator structure. Undulator commissioning, which refers to the tuning and alignment processes to eliminate the possible error sources, is thus an important step toward realization of lasing. In the SPring-8 angstrom compact free electron laser (SACLA) facility, the undulator commissioning has been carried out by means of characterization of x-ray radiation, i.e., measurements of the spatial and spectral profiles of monochromatized spontaneous undulator radiation as well as by probing the FEL intensity. The achieved tuning and alignment accuracies estimated from the statistics of actual measurements in SACLA show the effectiveness of this commissioning scheme