Identifying a new intermediate polar using \u3cem\u3eXMM-Newton\u3c/em\u3e and \u3cem\u3eINTEGRAL\u3c/em\u3e

The bright X-ray source 2XMMi J180438.7-145647 is fortunate to have long baseline observations in INTEGRAL that complement observations taken by other missions. Optical spectroscopy of this object has suggested a distance of ˜7 kpc and an identification with a low-mass X-ray binary. We instead use the X-ray data from 0.3 to 40 keV to identify the source as a bright intermediate polar (IP) with an estimate for the white dwarf mass of ˜0.60 M⊙. This identification is supported by the presence of an iron triplet, the component lines of which are some of the strongest seen in IPs, and the signature of the spin period of the white dwarf at ˜24 min. We note that the lack of broad-band variability may suggest that this object is a stream-fed IP, similar in many respects to the well-studied IP, V2400 Oph. Phase binning has allowed us to create spectra corresponding to the peaks and troughs of the light curve from which we determine that the spectra appear harder in the troughs, consistent with the behaviour of other IPs binned on their spin periods. This work strongly suggests a misidentification in the optical due to the presence of large columns of enshrouding material. We instead propose a distance to the source of \u3c2.5 kpc to be consistent with the luminosities of other IPs in the dim, hard state. The considerable flux of the source together with the strength of the iron lines may, in future, allow the source to be used to diagnose the properties of the shock-heated plasma and the reflected component of the emission

Integrating ecology into macroevolutionary research

On 9 March, over 150 biologists gathered in London for the Centre for Ecology and Evolution spring symposium, ‘Integrating Ecology into Macroevolutionary Research’. The event brought together researchers from London-based institutions alongside others from across the UK, Europe and North America for a day of talks. The meeting highlighted methodological advances and recent analyses of exemplar datasets focusing on the exploration of the role of ecological processes in shaping macroevolutionary patterns

Comparison of in vitro and in situ plankton production determinations

Plankton production was measured using 8 techniques at 4 stations in the Celtic Sea, North Atlantic Ocean, in April 2002. Primary production (PP) was derived from 14C incorporation into particulate carbon after 24 h simulated in situ, PP(14CSIS), and 2 h photosynthesis-irradiance incubations, PP(14CPUR), and from 2 published satellite algorithms, PP(VGPM) and PP (M91). Gross production (GP) was calculated from O2 evolution, GP(O2), and 18O enrichment of dissolved O 2, GP(18O), after 24 h simulated in situ incubations, and from in situ active fluorescence measured by fast repetition rate fluorometry (FRRF). Net community production (NCP) was determined from changes in in situ dissolved oxygen, NCP(?O2), and from changes in oxygen during 24 h simulated in situ incubations, NCP(O2). Dark community respiration (DCR) was derived from changes in oxygen during a 24 h dark incubation, DCR(O2), and daily oxygen uptake, DOU(18O, O2), was calculated from the difference between GP(18O) and NCP(O2). Three stations were dominated by picoautotrophs and the fourth station was dominated by diatoms. While most of the comparisons between techniques fell within previously published ranges, 2 anomalies occurred only at the diatom-dominated station. Rates of PP(14CPUR) were oxygen uptake in the dark. The low rates of PP( 14CPUR) in relation to PP(14CSIS) may have resulted from the heterogeneous nature of the bloom and differences in sampling time. However, it is also possible that dissolved organic material (DOM) released by the stressed diatom population restricted the diffusion of 14C into the cells, thereby causing a greater underestimate of PP by techniques using short incubations. The significantly higher rates of oxygen uptake in the light are difficult to reconcile, and we do not know whether the light enhanced oxygen uptake was directly linked to carbon fixation. However, the release of DOM may also have provided substrate for enhanced respiration in the light. These anomalies were only revealed through the concurrent measurement of plankton production by this wide range of techniques. Further investigation of DOM excretion and light-enhanced respiration during diatom blooms is warranted

Mitochondrial Respiratory Capacity and Content Are Normal in Young Insulin-Resistant Obese Humans

Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in humans. Young (∼23 years) insulin-sensitive lean and insulin-resistant obese men and women were studied. Insulin resistance was confirmed through an intravenous glucose tolerance test. Measures of mitochondrial respiratory capacity and content as well as H(2)O(2) emitting potential and the cellular redox environment were performed in permeabilized myofibers and primary myotubes prepared from vastus lateralis muscle biopsy specimens. No differences in mitochondrial respiratory function or content were observed between lean and obese subjects, despite elevations in H(2)O(2) emission rates and reductions in cellular glutathione. These findings were apparent in permeabilized myofibers as well as in primary myotubes. The results suggest that reductions in mitochondrial respiratory capacity and content are not required for the initial manifestation of peripheral insulin resistance

Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review

OBJECTIVE: Determine the role of fluid-based biomarkers, advanced neuroimaging, genetic testing and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion (SRC). DESIGN: Systematic review. DATA SOURCES: Searches of seven databases from 1 January 2001 through 24 March 2022 using keywords and index terms relevant to concussion, sports and neurobiological recovery. Separate reviews were conducted for studies involving neuroimaging, fluid biomarkers, genetic testing and emerging technologies. A standardised method and data extraction tool was used to document the study design, population, methodology and results. Reviewers also rated the risk of bias and quality of each study. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they: (1) were published in English; (2) represented original research; (3) involved human research; (4) pertained only to SRC; (5) included data involving neuroimaging (including electrophysiological testing), fluid biomarkers or genetic testing or other advanced technologies used to assess neurobiological recovery after SRC; (6) had a minimum of one data collection point within 6 months post-SRC; and (7) contained a minimum sample size of 10 participants. RESULTS: A total of 205 studies met inclusion criteria, including 81 neuroimaging, 50 fluid biomarkers, 5 genetic testing, 73 advanced technologies studies (4 studies overlapped two separate domains). Numerous studies have demonstrated the ability of neuroimaging and fluid-based biomarkers to detect the acute effects of concussion and to track neurobiological recovery after injury. Recent studies have also reported on the diagnostic and prognostic performance of emerging technologies in the assessment of SRC. In sum, the available evidence reinforces the theory that physiological recovery may persist beyond clinical recovery after SRC. The potential role of genetic testing remains unclear based on limited research. CONCLUSIONS: Advanced neuroimaging, fluid-based biomarkers, genetic testing and emerging technologies are valuable research tools for the study of SRC, but there is not sufficient evidence to recommend their use in clinical practice. PROSPERO REGISTRATION NUMBER: CRD42020164558

Optimized polyepitope neoantigen DNA vaccines elicit neoantigen-specific immune responses in preclinical models and in clinical translation

BACKGROUND: Preclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation. METHODS: We developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer models through genome sequencing and in silico neoantigen prediction pipelines. Optimized polyepitope neoantigen DNA vaccines specific for the murine breast tumor E0771 and 4T1 were designed and their immunogenicity was tested in vivo. We also tested an optimized polyepitope neoantigen DNA vaccine in a patient with metastatic pancreatic neuroendocrine tumor. RESULTS: Our data support an optimized polyepitope neoantigen DNA vaccine design encoding long (≥20-mer) epitopes with a mutant form of ubiquitin (Ub CONCLUSIONS: We have developed and optimized a novel polyepitope neoantigen DNA vaccine platform that can target multiple neoantigens and induce antitumor immune responses in preclinical models and neoantigen-specific responses in clinical translation