Differential and collaborative actions of Rad51 paralog proteins in cellular response to DNA damage

Metazoan Rad51 plays a central role in homologous DNA recombination, and its activity is controlled by a number of Rad51 cofactors. These include five Rad51 paralogs, Rad51B, Rad51C, Rad51D, XRCC2 and XRCC3. We previously hypothesized that all five paralogs participate collaboratively in repair. However, this idea was challenged by the biochemical identification of two independent complexes composed of either Rad51B/C/D/XRCC2 or Rad51C/XRCC3. To investigate if this biochemical finding is matched by genetic interactions, we made double mutants in either the same complex (rad51b/rad51d) or in both complexes (xrcc3/rad51d). In agreement with the biochemical findings the double deletion involving both complexes had an additive effect on the sensitivity to camptothecin and cisplatin. The double deletion of genes in the same complex, on the other hand, did not further increase the sensitivity to these agents. Conversely, all mutants tested displayed comparatively mild sensitivity to γ-irradiation and attenuated γ-irradiation-induced Rad51 foci formation. Thus, in accord with our previous conclusion, all paralogs appear to collaboratively facilitate Rad51 action. In conclusion, our detailed genetic study reveals a complex interplay between the five Rad51 paralogs and suggests that some of the Rad51 paralogs can separately operate in later step of homologous recombination

Development of Convolutional Neural Networks for an Electron-Tracking Compton Camera

Electron-tracking Compton camera, which is a complete Compton camera with tracking Compton scattering electron by a gas micro time projection chamber, is expected to open up MeV gamma-ray astronomy. The technical challenge for achieving several degrees of the point spread function is the precise determination of the electron-recoil direction and the scattering position from track images. We attempted to reconstruct these parameters using convolutional neural networks. Two network models were designed to predict the recoil direction and the scattering position. These models marked 41$~$degrees of the angular resolution and 2.1$~$mm of the position resolution for 75$~$keV electron simulation data in Argon-based gas at 2$~$atm pressure. In addition, the point spread function of ETCC was improved to 15$~$degrees from 22$~$degrees for experimental data of 662$~$keV gamma-ray source. These performances greatly surpassed that using the traditional analysis

New readout and data-acquisition system in an electron-tracking Compton camera for MeV gamma-ray astronomy (SMILE-II)

For MeV gamma-ray astronomy, we have developed an electron-tracking Compton camera (ETCC) as a MeV gamma-ray telescope capable of rejecting the radiation background and attaining the high sensitivity of near 1 mCrab in space. Our ETCC comprises a gaseous time-projection chamber (TPC) with a micro pattern gas detector for tracking recoil electrons and a position-sensitive scintillation camera for detecting scattered gamma rays. After the success of a first balloon experiment in 2006 with a small ETCC (using a 10$\times$10$\times$15 cm$^3$ TPC) for measuring diffuse cosmic and atmospheric sub-MeV gamma rays (Sub-MeV gamma-ray Imaging Loaded-on-balloon Experiment I; SMILE-I), a (30 cm)$^{3}$ medium-sized ETCC was developed to measure MeV gamma-ray spectra from celestial sources, such as the Crab Nebula, with single-day balloon flights (SMILE-II). To achieve this goal, a 100-times-larger detection area compared with that of SMILE-I is required without changing the weight or power consumption of the detector system. In addition, the event rate is also expected to dramatically increase during observation. Here, we describe both the concept and the performance of the new data-acquisition system with this (30 cm)$^{3}$ ETCC to manage 100 times more data while satisfying the severe restrictions regarding the weight and power consumption imposed by a balloon-borne observation. In particular, to improve the detection efficiency of the fine tracks in the TPC from $\sim$10\% to $\sim$100\%, we introduce a new data-handling algorithm in the TPC. Therefore, for efficient management of such large amounts of data, we developed a data-acquisition system with parallel data flow.Comment: 11 pages, 24 figure

ノウコウソク ノ チリョウ セイセキ ワ ナゼ コウジョウ シナイ ノカ : 10ネンカン ノ ヤマガタケン ノウソッチュウ トウロク データ カラ ノ ヨゴ フリョウ インシ ノ ケントウ

　We studied ten years of stroke data registered with the Yamagata Society on Treatment for Cerebral Stroke（YSTCS）. The subjects included 16,407 cases of acute-phase cerebral infarction that were registered with the YSTCS during the ten years between 2002 and 2011. The cases were divided into two groups: the early phase group（2002-2006）and the late phase group（2007-2011）.　The clinical diagnoses included atherothrombotic cerebral infarction（AT）（n=7,196; 43.9%）, cardiogenic cerebral embolism（CE）（n=4,011; 24.4%）, and lacunar infarction（LI）（n=4,703; 28.7%）. The average age of the early phase group was 72.7±11.43 years, while that of the late phase group was 75.0±11.35 years; the difference was statistically significant. The proportion of CE cases increased in the late phase, while that of LI decreased. This phenomenon was more marked in cases involving patients of ≥80 years of age. In both the early and late phase groups, the AT and CE cases showed a significantly high proportion of poor outcomes. However, when age adjustment was implemented in the late phase group, the treatment outcomes improved across all clinical entities. A multiple logistic regression analysis revealed a significant association between old age, female sex, severe symptoms at onset, CE, a previous history of stroke, and a poor prognosis.　It is clear that developments in medicine have not kept pace with the advancement in the age at onset. The improvement of the outcomes of treatment for cerebral infarction requires further developments in acute-phase therapies and the primary prevention of cardiogenic cerebral embolism, many cases of which are severe

Spectral evolution of GRB 060904A observed with Swift and Suzaku -- Possibility of Inefficient Electron Acceleration

We observed an X-ray afterglow of GRB 060904A with the Swift and Suzaku satellites. We found rapid spectral softening during both the prompt tail phase and the decline phase of an X-ray flare in the BAT and XRT data. The observed spectra were fit by power-law photon indices which rapidly changed from $\Gamma = 1.51^{+0.04}_{-0.03}$ to $\Gamma = 5.30^{+0.69}_{-0.59}$ within a few hundred seconds in the prompt tail. This is one of the steepest X-ray spectra ever observed, making it quite difficult to explain by simple electron acceleration and synchrotron radiation. Then, we applied an alternative spectral fitting using a broken power-law with exponential cutoff (BPEC) model. It is valid to consider the situation that the cutoff energy is equivalent to the synchrotron frequency of the maximum energy electrons in their energy distribution. Since the spectral cutoff appears in the soft X-ray band, we conclude the electron acceleration has been inefficient in the internal shocks of GRB 060904A. These cutoff spectra suddenly disappeared at the transition time from the prompt tail phase to the shallow decay one. After that, typical afterglow spectra with the photon indices of 2.0 are continuously and preciously monitored by both XRT and Suzaku/XIS up to 1 day since the burst trigger time. We could successfully trace the temporal history of two characteristic break energies (peak energy and cutoff energy) and they show the time dependence of $\propto t^{-3} \sim t^{-4}$ while the following afterglow spectra are quite stable. This fact indicates that the emitting material of prompt tail is due to completely different dynamics from the shallow decay component. Therefore we conclude the emission sites of two distinct phenomena obviously differ from each other.Comment: 19 pages, 9 figures, accepted for publication in PASJ (Suzaku 2nd Special Issue

Essential anatomy for lateral lymph node dissection

In Western countries, the gold-standard therapeutic strategy for rectal cancer is preoperative chemoradiotherapy (CRT) following total mesorectal excision (TME), without lateral lymph node dissection (LLND). However, preoperative CRT has recently been reported to be insufficient to control lateral lymph node recurrence in cases of enlarged lateral lymph nodes before CRT, and LLND is considered necessary in such cases. We performed a literature review on aspects of pelvic anatomy associated with rectal surgery and LLND, and then combined this information with our experience and knowledge of pelvic anatomy. In this review, drawing upon research using a 3-dimensional anatomical model and actual operative views, we aimed to clarify the essential anatomy for LLND. The LLND procedure was developed in Asian countries and can now be safely performed in terms of functional preservation. Nonetheless, the longer operative time, hemorrhage, and higher complication rates with TME accompanied by LLND than with TME alone indicate that LLND is still a challenging procedure. Laparoscopic or robotic LLND has been shown to be useful and is widely performed; however, without a sufficient understanding of anatomical landmarks, misrecognition of vessels and nerves often occurs. To perform safe and accurate LLND, understanding the landmarks of LLND is essential

Nano Random Forests to mine protein complexes and their relationships in quantitative proteomics data

Ever-increasing numbers of quantitative proteomics data sets constitute an underexploited resource for investigating protein function. Multiprotein complexes often follow consistent trends in these experiments, which could provide insights about their biology. Yet, as more experiments are considered, a complex’s signature may become conditional and less identifiable. Previously we successfully distinguished the general proteomic signature of genuine chromosomal proteins from hitchhikers using the Random Forests (RF) machine learning algorithm. Here we test whether small protein complexes can define distinguishable signatures of their own, despite the assumption that machine learning needs large training sets. We show, with simulated and real proteomics data, that RF can detect small protein complexes and relationships between them. We identify several complexes in quantitative proteomics results of wild-type and knockout mitotic chromosomes. Other proteins covary strongly with these complexes, suggesting novel functional links for later study. Integrating the RF analysis for several complexes reveals known interdependences among kinetochore subunits and a novel dependence between the inner kinetochore and condensin. Ribosomal proteins, although identified, remained independent of kinetochore subcomplexes. Together these results show that this complex-oriented RF (NanoRF) approach can integrate proteomics data to uncover subtle protein relationships. Our NanoRF pipeline is available online

Measurements of Cosmic-ray Low-energy Antiproton and Proton Spectra in a Transient Period of the Solar Field Reversal

The energy spectra of cosmic-ray low-energy antiprotons and protons have been measured by BESS in 1999 and 2000, during a period covering the solar magnetic field reversal. Based on these measurements, a sudden increase of the antiproton to proton flux ratio following the solar magnetic field reversal was observed, and it generally agrees with a drift model of the solar modulation.Comment: 4 pages, 4 figures, revised version accepted for publication in Phys. Rev. Let

A nationwide, multi-center, retrospective study of symptomatic small bowel stricture in patients with Crohn\u27s disease.

BACKGROUND:Small bowel stricture is one of the most common complications in patients with Crohn\u27s disease (CD). Endoscopic balloon dilatation (EBD) is a minimally invasive treatment intended to avoid surgery; however, whether EBD prevents subsequent surgery remains unclear. We aimed to reveal the factors contributing to surgery in patients with small bowel stricture and the factors associated with subsequent surgery after initial EBD.METHODS:Data were retrospectively collected from surgically untreated CD patients who developed symptomatic small bowel stricture after 2008 when the use of balloon-assisted enteroscopy and maintenance therapy with anti-tumor necrosis factor (TNF) became available.RESULTS:A total of 305 cases from 32 tertiary referral centers were enrolled. Cumulative surgery-free survival was 74.0% at 1 year, 54.4% at 5 years, and 44.3% at 10 years. The factors associated with avoiding surgery were non-stricturing, non-penetrating disease at onset, mild severity of symptoms, successful EBD, stricture length < 2 cm, and immunomodulator or anti-TNF added after onset of obstructive symptoms. In 95 cases with successful initial EBD, longer EBD interval was associated with lower risk of surgery. Receiver operating characteristic analysis revealed that an EBD interval of ≤ 446 days predicted subsequent surgery, and the proportion of smokers was significantly high in patients who required frequent dilatation.CONCLUSIONS:In CD patients with symptomatic small bowel stricture, addition of immunomodulator or anti-TNF and smoking cessation may improve the outcome of symptomatic small bowel stricture, by avoiding frequent EBD and subsequent surgery after initial EBD