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BackgroundThe genes that produce antibodies and the immune receptors expressed on lymphocytes are not germline encoded; rather, they are somatically generated in each developing lymphocyte by a process called V(D)J recombination, which assembles specific, independent gene segments into mature composite genes. The full set of composite genes in an individual at a single point in time is referred to as the immune repertoire. V(D)J recombination is the distinguishing feature of adaptive immunity and enables effective immune responses against an essentially infinite array of antigens. Characterization of immune repertoires is critical in both basic research and clinical contexts. Recent technological advances in repertoire profiling via high-throughput sequencing have resulted in an explosion of research activity in the field. This has been accompanied by a proliferation of software tools for analysis of repertoire sequencing data. Despite the widespread use of immune repertoire profiling and analysis software, there is currently no standardized format for output files from V(D)J analysis. Researchers utilize software such as IgBLAST and IMGT/High V-QUEST to perform V(D)J analysis and infer the structure of germline rearrangements. However, each of these software tools produces results in a different file format, and can annotate the same result using different labels. These differences make it challenging for users to perform additional downstream analyses.ResultsTo help address this problem, we propose a standardized file format for representing V(D)J analysis results. The proposed format, VDJML, provides a common standardized format for different V(D)J analysis applications to facilitate downstream processing of the results in an application-agnostic manner. The VDJML file format specification is accompanied by a support library, written in C++ and Python, for reading and writing the VDJML file format.ConclusionsThe VDJML suite will allow users to streamline their V(D)J analysis and facilitate the sharing of scientific knowledge within the community. The VDJML suite and documentation are available from https://vdjserver.org/vdjml/ . We welcome participation from the community in developing the file format standard, as well as code contributions.

Heat causes protein misfolding and aggregation and, in eukaryotic cells, triggers aggregation of proteins and RNA into stress granules. We have carried out extensive proteomic studies to quantify heat-triggered aggregation and subsequent disaggregation in budding yeast, identifying >170 endogenous proteins aggregating within minutes of heat shock in multiple subcellular compartments. We demonstrate that these aggregated proteins are not misfolded and destined for degradation. Stable-isotope labeling reveals that even severely aggregated endogenous proteins are disaggregated without degradation during recovery from shock, contrasting with the rapid degradation observed for many exogenous thermolabile proteins. Although aggregation likely inactivates many cellular proteins, in the case of a heterotrimeric aminoacyl-tRNA synthetase complex, the aggregated proteins remain active with unaltered fidelity. We propose that most heat-induced aggregation of mature proteins reflects the operation of an adaptive, autoregulatory process of functionally significant aggregate assembly and disassembly that aids cellular adaptation to thermal stress.

Introduction: Demand for emergency ambulances is increasing every year. Traditionally, the only option for attending paramedics was to transport patients to the emergency department (ED) (Halter et al., 2011). However, the ED is now generally regarded as just one of a range of options available to paramedics to ensure that people receive the most appropriate care. Ambulance conveyance rates to ED in Northern Ireland (NI) have only occasionally fallen below 75% of incidents. A study examining a diabetic-specific Northern Ireland Ambulance Service (NIAS) referral pathway showed a much lower referral rate than comparable ambulance services, and data analysis has shown that over 70% of potentially eligible patients experiencing a fall are not receiving a falls referral (Bloomer, 2021; Scott, 2020). This study aimed to identify what paramedics perceive are the barriers and facilitators to the use of appropriate care pathways (ACPs) in NI. Methods: In this single-centre qualitative study, participants were recruited using convenience sampling. Data were collected through semi-structured interviews until data saturation was reached after 11 interviews. They were recorded, transcribed verbatim and thematically analysed. Results: Six main themes emerged during analysis. The participants discussed their perceptions of the barriers and facilitators of utilising ACPs under the auspices of clinical issues, cultural issues, risk, person-centred practice, inter-professional communication and operational infrastructure. Conclusions: The study provides insight into perceived barriers and facilitators to the use of ACPs. The themes identified are consistent with existing literature that calls for standardised pathways across regions. Future research should investigate the link between the NHS 111 service and ambulance demand. In order to facilitate the complex decision making involved in referral, relevant knowledge and skills should be embedded in paramedic education. Efforts should be made to improve inter-professional communication and awareness of the paramedic scope of practice and knowledge base. [ABSTRACT FROM AUTHOR]