Misincorporation Proteomics Technologies: A Review.

Proteinopathies are diseases caused by factors that affect proteoform conformation. As such, a prevalent hypothesis is that the misincorporation of noncanonical amino acids into a proteoform results in detrimental structures. However, this hypothesis is missing proteomic evidence, specifically the detection of a noncanonical amino acid in a peptide sequence. This review aims to outline the current state of technology that can be used to investigate mistranslations and misincorporations whilst framing the pursuit as Misincorporation Proteomics (MiP). The current availability of technologies explored herein is mass spectrometry, sample enrichment/preparation, data analysis techniques, and the hyphenation of approaches. While many of these technologies show potential, our review reveals a need for further development and refinement of approaches is still required

Correction: Steele et al. Misincorporation Proteomics Technologies: A Review. Proteomes 2021, 9, 2.

In the original publication, there was a mistake in Table 2 as published [...]

An ultraviolet-optical flare from the tidal disruption of a helium-rich stellar core

The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two `relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report the discovery of a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decline of its light curve follows the predicted mass accretion rate, and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about 2 million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.Comment: To appear in Nature on May 10, 201

Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response

Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4g/kg or 0.8g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a “Go-stimulus” when it was followed by a “Stop-stimulus”. In the control variant (VSST_C), participants responded to the “Go-stimulus” even if it was followed by a “Stop-stimulus”. Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour

Applying the multi-threat framework of stereotype threat in the context of digital gaming.

Females often report experiencing stigmatisation pertaining to their competency in digital gaming communities. Employing the principles of the multi-Threat framework of stereotype threat, the current research examined the impact of gender-related stereotypes on females' gaming performance and related self-perceptions. In Experiment 1, 90 females were assigned to one of three conditions in which they were primed that their performance would be either diagnostic of their personal (self-As-Target) or gender group's ability (group-As-Target) or would be non-diagnostic of gaming ability (control). In Experiment 2, 90 females were primed that their performance would be judged by a group of other females (in-group source) or males (out-group source), or would be non-diagnostic of ability (control). Participants then completed a casual gaming task, as well as measures of competence beliefs, self-efficacy and self-esteem. Findings from Experiment 1 indicate that neither a self-As-Target nor a group-As-Target stereotype affected significantly gaming performance, or gamerelated self-efficacy, self-esteem and competency beliefs. Findings from Experiment 2 reveal further that females' gaming performance and associated self-perceptions were not impacted significantly by an in-group or out-group source of stereotype threat. The discussion turns to potential explanations for these findings, proposing that females may not perceive negative gender-gaming stereotypes to be an accurate representation of their personal or social group's gaming ability. We also discuss the implications of the experimental design and difficulty, as well as the potential for domain identification to moderate performance outcomes under stereotype threat

Large cell neuroendocrine lung carcinoma: consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists

Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies

Infection-mediated priming of phagocytes protects against lethal secondary Aspergillus fumigatus challenge

Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection

Objective and Subjective Factors as Predictors of Post-Traumatic Stress Symptoms in Parents of Children with Cancer – A Longitudinal Study

BACKGROUND: Parents of children with cancer report post-traumatic stress symptoms (PTSS) years after the child's successful treatment is completed. The aim of the present study was to analyze a number of objective and subjective childhood cancer-related factors as predictors of parental PTSS. METHODS: Data were collected from 224 parents during and after their child's cancer treatment. Data sources include self-report questionnaires and medical records. RESULTS: In a multivariate hierarchical model death of the child, parent's perception of child psychological distress and total symptom burden predicted higher levels of PTSS. In addition, immigrants and unemployed parents reported higher levels of PTSS. The following factors did not predict PTSS: parent gender, family income, previous trauma, child's prognosis, treatment intensity, non-fatal relapse, and parent's satisfaction with the child's care. CONCLUSIONS: Although medical complications can be temporarily stressful, a parent's perception of the child's distress is a more powerful predictor of parental PTSS. The vulnerability of unemployed parents and immigrants should be acknowledged. In addition, findings highlight that the death of a child is as traumatic as could be expected

FoxO and Stress Responses in the Cnidarian Hydra vulgaris

Background: In the face of changing environmental conditions, the mechanisms underlying stress responses in diverse organisms are of increasing interest. In vertebrates, Drosophila, and Caenorhabditis elegans, FoxO transcription factors mediate cellular responses to stress, including oxidative stress and dietary restriction. Although FoxO genes have been identified in early-arising animal lineages including sponges and cnidarians, little is known about their roles in these organisms. Methods/Principal Findings: We have examined the regulation of FoxO activity in members of the well-studied cnidarian genus Hydra. We find that Hydra FoxO is expressed at high levels in cells of the interstitial lineage, a cell lineage that includes multipotent stem cells that give rise to neurons, stinging cells, secretory cells and gametes. Using transgenic Hydra that express a FoxO-GFP fusion protein in cells of the interstitial lineage, we have determined that heat shock causes localization of the fusion protein to the nucleus. Our results also provide evidence that, as in bilaterian animals, Hydra FoxO activity is regulated by both Akt and JNK kinases. Conclusions: These findings imply that basic mechanisms of FoxO regulation arose before the evolution of bilaterians an