Effects of radiation damage and inelastic scattering on single-particle imaging of hydrated proteins with an X-ray Free-Electron Laser

We present a computational case study of X-ray single-particle imaging of hydrated proteins on an example of 2-Nitrogenase–Iron protein covered with water layers of various thickness, using a start-to-end simulation platform and experimental parameters of the SPB/SFX instrument at the European X-ray Free-Electron Laser facility. The simulations identify an optimal thickness of the water layer at which the effective resolution for imaging the hydrated sample becomes significantly higher than for the non-hydrated sample. This effect is lost when the water layer becomes too thick. Even though the detailed results presented pertain to the specific sample studied, the trends which we identify should also hold in a general case. We expect these findings will guide future single-particle imaging experiments using hydrated proteins

A Key Silencing Histone Mark on Chromatin Is Lost When Colorectal Adenocarcinoma Cells Are Depleted of Methionine by Methionine γ-Lyase

Methionine is an essential amino acid used, beyond protein synthesis, for polyamine formation and DNA/RNA/protein methylation. Cancer cells require particularly high methionine supply for their homeostasis. A successful approach for decreasing methionine concentration is based on the systemic delivery of methionine γ-lyase (MGL), with in vitro and in vivo studies demonstrating its efficacy in cancer therapy. However, the mechanisms explaining how cancer cells suffer from the absence of methionine more significantly than non-malignant cells are still unclear. We analyzed the outcome of the human colorectal adenocarcinoma cancer cell line HT29 to the exposure of MGL for up to 72 h by monitoring cell viability, proteome expression, histone post-translational modifications, and presence of spurious transcription. The rationale of this study was to verify whether reduced methionine supply would affect chromatin decondensation by changing the levels of histone methylation and therefore increasing genomic instability. MGL treatment showed a time-dependent cytotoxic effect on HT29 cancer cells, with an IC50 of 30 µg/ml, while Hs27 normal cells were less affected, with an IC50 of >460 µg/ml. Although the levels of total histone methylation were not altered, a loss of the silencing histone mark H3K9me2 was observed, as well as a decrease in H4K20me3. Since H3K9me2/3 decorate repetitive DNA elements, we proved by qRT-PCR that MGL treatment leads to an increased expression of major satellite units. Our data indicate that selected histone methylation marks may play major roles in the mechanism of methionine starvation in cancer cells, proving that MGL treatment directly impacts chromatin homeostasis

Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods

BACKGROUND: Accurate fusion transcript detection is essential for comprehensive characterization of cancer transcriptomes. Over the last decade, multiple bioinformatic tools have been developed to predict fusions from RNA-seq, based on either read mapping or de novo fusion transcript assembly. RESULTS: We benchmark 23 different methods including applications we develop, STAR-Fusion and TrinityFusion, leveraging both simulated and real RNA-seq. Overall, STAR-Fusion, Arriba, and STAR-SEQR are the most accurate and fastest for fusion detection on cancer transcriptomes. CONCLUSION: The lower accuracy of de novo assembly-based methods notwithstanding, they are useful for reconstructing fusion isoforms and tumor viruses, both of which are important in cancer research

Report of the 11th Liaison Meeting

The   11thLiaison   Meeting   between   the   Chairs   of   the   RCMs,   the   ICES   PGCCDBS,   PGMED  and  PGECON,  the  STECF  EWGs  on  the  DCF,  the  Regional  Database  Steering   Committees,  the  ICES  and  GFCM  representatives  and  the  European  Commission  was   held  at  the  DG  Maritime  Affairs  and  Fisheries,  Brussels  from  8th  to  9th  October  2014. The  11th  Liaison  meeting  was  held  in  Brussels  on  8th  and  9th  October  2014  to  address  the   following  terms  of  reference:     TOR  1.  Discussion  on  possible  follow-­‐‑up  to  the  main  outputs/recommendations  of:   • The  2014  RCMs  and  to  the   sp ecific  re commenda tions  a ddr e sse d  to  th e  Liaison   Meeting   • P G ECO N ,  PG CCDBS,  PG Med   –   ou tcome s  an d  r e commendation s  fr om  the ir   2014  meeting     • STECF  EWG  and  STEC F  Plen ary   -­‐‑   ou tcome s  a n d  r e commendation s  fr om  the ir   2014  meeting     • Data  end-­‐‑ users  (IC ES,  G F C M,  RC Ms)   TOR  2.  Compilation  of  recommendations  on  the  DCF   A  compilation  of  DCF  recommendations  will  be  established  by  the  COM  by  end  2014.   LM   needs   to   agree   on   which   recommendations   should   be   included   (i.e.   from   which   bodies)  &  covering  which  years.     TOR  3.  Regional  cooperation   • G r ants  for  str eng thene d  reg ion al  coop eration     • R e g ional  da ta b ases   o O ver view  of  use  of  the  Reg ional  Datab ases  for  R CMs  in  2014,  and  p rob lems   identified   o O ther  deve lop ments  (RDB  training s  in  2014,  RDB  Med&BS  develop ment)   o Chang es  for  the  fu tu re   –  an y  re commen da tions  from  th e  LM?   • R C M  data  calls   –  ove rview  of  h ow  MS  r esp onde d.   TOR  4.  Recommended  meetings/workshops   • P r ep a r e  a  list  of  r ecommen ded  me etin g s  for  2015  as  g u idance  for  MS   TOR  5.  Studies   • O ver view  of  p rocess   • LM  comme nts  and  p r ioritization  of  studies  p r op osed  b y  RC Ms,  PG ECO N ,  ICES,   GFCM   TOR  6.  AOB     1. The  DCF  website  has  been  revamped  by  the  JRC.  Any  comments  on  this?   2. Access  to  the  RCM  SharePoint   3. Derogations  –  List  of  derogations  by  Member  State  has  been  prepared  by  DG   MARE.  Have  any  RCMs  updated  this?     4. ICES  will  provide  an  update  on  their  plans  to  re-­‐‑evaluate  surveys.  Should  this   be  followed  by  STECF  work  on  surveys  to  be  included  in  future  EU  MAP?   5. Annual  reports  –  simplification:  presentation  of  process. 6. Data  transmission:   a. new   platform   for   information   exchanges   between   COM,   MS   and   end-­‐‑ users   b. new   tool   for   reporting   on   how   MS   complied   with   the   DG   MARE/JRC   data  calls     In   addition   to   the   above   Terms   of   Reference,   an   item   was   added   at   the   start   of   the   meeting,  regarding  the  implication  of  the  Landing  Obligation  on  data  collection  and   the  Discard  Plans.

Faceting Transition in an Exactly Solvable Terrace-Ledge-Kink model

We solve exactly a Terrace-Ledge-Kink (TLK) model describing a crystal surface at a microscopic level. We show that there is a faceting transition driven either by temperature or by the chemical potential that controls the slope of the surface. In the rough phase we investigate thermal fluctuations of the surface using Conformal Field Theory.Comment: 27 pages, 18 EPS figure

CORUM: the comprehensive resource of mammalian protein complexes

Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. The CORUM (http://mips.gsf.de/genre/proj/corum/index.html) database is a collection of experimentally verified mammalian protein complexes. Information is manually derived by critical reading of the scientific literature from expert annotators. Information about protein complexes includes protein complex names, subunits, literature references as well as the function of the complexes. For functional annotation, we use the FunCat catalogue that enables to organize the protein complex space into biologically meaningful subsets. The database contains more than 1750 protein complexes that are built from 2400 different genes, thus representing 12% of the protein-coding genes in human. A web-based system is available to query, view and download the data. CORUM provides a comprehensive dataset of protein complexes for discoveries in systems biology, analyses of protein networks and protein complex-associated diseases. Comparable to the MIPS reference dataset of protein complexes from yeast, CORUM intends to serve as a reference for mammalian protein complexes

Report of the Regional Coordination Meeting for the North Atlantic (RCM NA) 2015

The 12th RCM North Atlantic was held in Hamburg (Germany) 14-18 September 2015. The main purpose of the RCM is to coordinate the National Programmes (NP) of the Member States (MS) in the North Atlantic region. National Programmes for 2011-2013 have been rolled over for the period 2014-2016. Therefore, the main focus at this year was to improve regional data collection, analysis and storage and the evolution towards Regional Coordination Groups (RCG).The impact of the introduction of the landing obligation and preparations for its implementation was also discussed taking into account possible changes in scientific sampling schemes. The participation of four National Correspondents make possible to address National administration issues related to the oncoming EU MAP. A data call was launched by the chairs of the RCM NA, RCM Baltic and RCM NS&EA where MS were requested to upload data for 2014 in the regional database (RDB Fishframe) hosted by ICES. All MS except France and Northern Ireland complied with this request on landings and effort data. All MS except France uploaded sample data for 2014. French data were available for the meeting using a web base interface. Evaluation of the data call for submission data to the RDB revealed the numbers of species in landings and sample data and the numbers of metiers in effort data are in general data stable. RCM NA see big improvements in the work MS are doing regarding data calls coming from a situation where some countries didn´t provide any data to a new scenario where everyone is providing data; at the same time the overall quality has significantly improved, which is a large step forward. Regional data collection, analysis, storage and the evolution towards Regional Coordination Groups (RCG). Optimizing and harmonizing fisheries management across MS is dependent on improving regional coordination. The group discussed various needs and aspects relevant for facilitating future work of the RCM. Future tasks for the RCM don’t differ much from the current tasks. The discussion was focused on the structure of the RCGs, funding and short term needs to address tasks in an efficient way in the future. Regional coordination encompasses many different aspects, ranging from regional cooperation, sampling design, quality control procedures, data storage and analysis to the actual coordination, reporting and accountancy. Current task sharing and coordination procedures as well as future mechanisms are partially covered under the current MARE study 2014/19 (FISHPI). The project and its progress were presented to the group. The outcomes of this study will demonstrate future procedures based on case studies. As substantial effort and costs are involved to facilitate the process of regional coordination, the group highlighted the importance to access to budgets to cover these costs. Development of the RDB is also crucial for future work of the RCGs; funds are needed for the development. Additionally, RCM NA identified 4 supra regional topics where work can be done intersesionally in cooperation with the rest of RCMs: (1) Cost sharing of funding surveys; (2) Impact of landing obligation; (3) reviewing the ICES list of data needs ; and (4) review and follow up on RDB upload logs. Due to the importance to moving to a regional catch sampling scheme, an exercise was realised using the distribution of landings by harbour and fleet segment as a proxy of sampling frames that could hypothetically operate in a regional probability based design. The exercise was based on landing weight, for the simple reason that this was the only complete variable that was available for all the various national data sets. A regional sampling design can however be optimized in any number of ways (e.g. by landings value, by métier diversity, by species diversity, by number of fishing trips). The aims and aspirations of the end users need to be defined to ascertain which is most appropriate. It is one of the overriding advantages of a regional sampling design (as opposed to the aggregation of national designs) that the overall coverage can be set out to achieve regional goals. The RCM NA analyzed and discussed the main achievements of WKISCON2. It was clear that concurrent sampling at-sea is a long-established practice in most MS and that, where it was applied, concurrent sampling of fishing trips on-shore resulted in substantial increases in species collected without jeopardizing the main uses of data. Stock assessment and discard estimation and management are the major current uses of concurrent sampling data. Concurrent sampling has also been providing other benefits than its initial reason, such as advice to local, national and international authorities, research on MSFD descriptors, mixed fisheries and gear interactions and on mortality of rare species, data-poor stocks and PETS. It was clear that concurrent sampling being a statistically valid method for species selection which has proven to fulfil different end-users needs, implementation constraints hinder concurrent sampling on-shore. Thus, in order to meet end-users needs and to overcome the constraints that may arise from the implementation of concurrent sampling in some countries, particularly on-shore, RCM NA considers that different statistically sound approaches other than concurrent sampling must be developed to be tested in the field, so they may provide useful alternatives. Introduction of the landing obligation and its impact in the implementation in scientific sampling schemes. In terms of evaluating the impact of the introduction of the Landing Obligation (LO) regulation on data collection, there is only limited experience as the current implementation only covers Pelagic and Industrial fisheries in this region but MS have or are preparing for the implementation where they can. It is currently perceived that this year is a transition period for the pelagic fisheries and that these fisheries and control agencies are not fully implementing the LO (managing but not enforcing). As a result MS did not have a lot of comments on the current year and are in general preparing for next year. During the meeting it was decided to gather further information to address this issue by getting member states who were present to fill in a table on “Monitoring the impact of the landing obligation on data collection in the North Atlantic region” outlining the current state of play. This table could be considered as a live document which should be filled in year by year as the Landing Obligation is phased in. This table will then serve to provide an historical record as countries can document the changes year by year and will also provide guidance and act as a learning tool to all member states on how other countries are implementing the LO. National administrations The group discussed the proposal for task sharing and criteria for joint surveys. RCM NS&EA and RCM NA 2014 discussed a cost model for the present joint MS financed surveys and for future joint surveys. In addition to this model, the RCM NA 2015 highlighted that four categories of surveys should be considered in relation to task sharing and criteria for joint surveys. In the light of cost sharing, the group commented that the current DCF recast proposal refers to ‘exploitation of stocks’ rather than EU TAC or landings. Given the relative stability, EU TAC shares are the preferred basis for sharing costs. The exploitation of stocks shall be interpreted as EU-TAC share as a default. In specific cases, RCGs can in the future agree on different interpretation where needed and feasible. Fully agreement among the group was concerning to the engagement and participation of National Correspondent (NC) in this meeting. The future role of the NCs in the RCG context was discussed, indicating a formal role for the NCs in the RCG process to approve and agree on regional arrangements. However, the current recast of the DCF doesn’t include the formal involvement of the NCs in the coordination procedures and meetings. RCM NA highlights this as potentially problematic for the foreseen formal role of the NCs. Other items on the agenda were the consideration of the follow up of relevant recommendations made last years by Liaison Meeting and presentations and relevant development from ICES, EC and SC-RDB

Report of the 12th Liaison Meeting

The 12th Liaison meeting was held in Brussels on 8th and 9th October 2015 to address the following Terms of Reference: TOR 1. Discussion on possible follow-­‐‑up to the main outputs/recommendations of: • The 2015 RCMs -­‐‑ specific recommendations addressed to the Liaison Meeting • PGECON, PGDATA, PGMed – outcomes and recommendations from their 2015 meeting • STECF EWG and STECF Plenary -­‐‑ outcomes and recommendations from their 2015 meetings • Data end users (ICES, STECF, RFMOs – GFCM, IATTC, ICCAT, IOTC, WCPFC, NAFO, SPRFMO, CECAF, WECAFC) TOR2. End user feedback on data transmission and related issues • Discuss feedback received from data end-­‐‑users on data transmission: main issues and possible harmonization of end user feedback to the Commission • JRC data transmission IT platform: experience gained and future steps • Discuss best practices on automatization of data upload by MS: data validation tools used by end users • Discussion on new set-­‐‑up for STECF evaluation of AR2014 & data transmission 2014 used in 2015 – continue like this next year? • Harmonisation and dissemination of DCF metadata: codelists, metiers, nomenclatures, best practices, standards • RCM data calls – overview of how MS responded TOR 3. Regional cooperation • Call for proposals MARE/2014/19 'ʹStrengthening Regional Cooperation in the area of fisheries data collection– state of play'ʹ. Presentation by a representative of the two RCG grants and discussions by LM thereafter. What should be the way forward? • Regional databases • Overview of use of the Regional Databases for RCMs in 2015 and problems identified • Other developments (RDB trainings in 2015, RDB Med&BS development) • Changes for the future – any recommendations from the LM? • Future role of RCMs and DCF-­‐‑related meetings: best practices, coordination, cohesion and common structure in line with emerging needs of DCF TOR 4. EU MAP • Discuss recommendations/ output of RCMs: List of proposed stocks, landing obligation, metiers • Discuss design-­‐‑based sampling in relation to DCF: does it fulfil DCF requirements? TOR 5. Availability of data • Overview of latest developments (DCF Database Feasibility Study and plans for a follow-­‐‑up study to this) TOR 6. AOB • Agree on a list of recommendations relating to DCF (that MS will need to report on in their AR2015) – COM will provide a compilation of proposed recommendations from LM & STECF Plenaries in 2014 as input • Prepare a list of recommended meetings for 2016 as guidance for MS • Review and prioritize DCF-­‐‑related study proposals from RCMs, PGECON, EGs etc • ICES update on workshop on concurrent sampling and plans to re-­‐‑evaluate survey