Mitochondrial ferredoxin determines vulnerability of cells to copper excess

The essential micronutrient copper is tightly regulated in organisms, as environmental exposure or homeostasis defects can cause toxicity and neurodegenerative disease. The principal target(s) of copper toxicity have not been pinpointed, but one key effect is impaired supply of iron-sulphur (FeS) clusters to the essential protein Rli1 (ABCE1). Here, to find upstream FeS-biosynthesis/delivery protein(s) responsible for this, we compared copper sensitivity of yeast overexpressing candidate targets. Overexpression of the mitochondrial ferredoxin Yah1 produced copper hyper-resistance. 55Fe turnover assays revealed that FeS1-integrity of Yah1 was particularly vulnerable to copper among the test proteins. Furthermore, destabilization of the FeS domain of Yah1 produced copper hypersensitivity, and YAH1 overexpression rescued Rli1 dysfunction. This copper-resistance function was conserved in the human ferredoxin, Fdx2. The data indicate that the essential mitochondrial ferredoxin is an important copper target, determining a tipping point where plentiful copper supply becomes excess. This knowledge could help in tackling copper-related diseases

Impact of social anxiety on social cognition and functioning in patients with recent-onset schizophrenia spectrum disorders

Schizophrenia patients display important rates of comorbid social anxiety disorder (SAD) but few studies have directly examined how SAD affects the presentation of schizophrenia, notably social cognition deficits and functioning. Aims : To compare social cognition performance of schizophrenia patients who meet the diagnostic criteria for a comorbid SAD (SZ +) relative to patients without such comorbidity (SZ −) and to determine if the impact of social cognition performance on functioning is moderated by that comorbidity. Method : Social cognition performance (emotion recognition, social knowledge, and mentalizing), a control non-social reasoning task, as well as clinical symptoms and functioning were assessed in 26 patients with comorbid SAD (SZ +), 29 SZ − and 84 healthy controls. Results : Patient groups significantly differed from each other on social knowledge performance, but not in levels of symptoms or overall functioning. Relative to healthy controls, SZ + were impaired uniquely on mentalizing, whereas SZ − showed a more encompassing social cognition deficit that included mentalizing, social knowledge and non-social reasoning impairments. Mentalizing was the best predictor of functioning across both patient groups. Importantly, non-social reasoning negatively influenced mentalizing and in turn functioning only in the SZ − group. Conclusions : The overall pattern of results indicates common mentalizing deficits in SZ + and SZ −; however, these deficits appear linked to different underlying deficits and different pathways to functional impact in the two patient subgroups. This study highlights some distinctive characteristics of schizophrenia patients with comorbid SAD and signals a need for further investigations into the sources of the mentalizing and functioning impairments in SZ + patients

Radiomics strategies for risk assessment of tumour failure in head-and-neck cancer

Quantitative extraction of high-dimensional mineable data from medical images is a process known as radiomics. Radiomics is foreseen as an essential prognostic tool for cancer risk assessment and the quantification of intratumoural heterogeneity. In this work, 1615 radiomic features (quantifying tumour image intensity, shape, texture) extracted from pre-treatment FDG-PET and CT images of 300 patients from four different cohorts were analyzed for the risk assessment of locoregional recurrences (LR) and distant metastases (DM) in head-and-neck cancer. Prediction models combining radiomic and clinical variables were constructed via random forests and imbalance-adjustment strategies using two of the four cohorts. Independent validation of the prediction and prognostic performance of the models was carried out on the other two cohorts (LR: AUC = 0.69 and CI = 0.67; DM: AUC = 0.86 and CI = 0.88). Furthermore, the results obtained via Kaplan-Meier analysis demonstrated the potential of radiomics for assessing the risk of specific tumour outcomes using multiple stratification groups. This could have important clinical impact, notably by allowing for a better personalization of chemo-radiation treatments for head-and-neck cancer patients from different risk groups.Comment: (1) Paper: 33 pages, 4 figures, 1 table; (2) SUPP info: 41 pages, 7 figures, 8 table

Solution of the Nuclear Shell Model by Symmetry-Dictated Truncation

The dynamical symmetries of the Fermion Dynamical Symmetry Model are used as a principle of truncation for the spherical shell model. Utilizing the usual principle of energy-dictated truncation to select a valence space, and symmetry-dictated truncation to select a collective subspace of that valence space, we are able to reduce the full shell model space to one of manageable dimensions with modern supercomputers, even for the heaviest nuclei. The resulting shell model then consists of diagonalizing an effective Hamiltonian within the restricted subspace. This theory is not confined to any symmetry limits, and represents a full solution of the original shell model if the appropriate effective interaction of the truncated space can be determined. As a first step in constructing that interaction, we present an empirical determination of its matrix elements for the collective subspace with no broken pairs in a representative set of nuclei with $130\le A \le 250$. We demonstrate that this effective interaction can be parameterized in terms of a few quantities varying slowly with particle number, and is capable of describing a broad range of low-energy observables for these nuclei. Finally we give a brief discussion of extending these methods to include a single broken collective pair.Comment: invited paper for J. Phys. G, 57 pages, Latex, 18 figures a macro are available under request at [email protected]

Assessing Survival and Grading the Severity of Complications in Octogenarians Undergoing Pulmonary Lobectomy.

Introduction. Octogenarians are at increased risk for complications after lung resection. With alternatives such as radiation, understanding the risks of surgery and associated survival are valuable. Data grading the severity of complications and long-term survival in this population is lacking. We reviewed our experience with lobectomy in octogenarians, grading complications using a validated thoracic morbidity and mortality schema. Methods. We retrospectively reviewed consecutive patients aged ≥80 undergoing lobectomy between 2004 and 2012. Demographics, clinical/pathologic stage, complications, recurrence, and mortality were collected. Complications were graded by the Seely thoracic morbidity and mortality model. Results. 45 patients (mean age 82.2 years) were analyzed. The majority of patients (28/45, 62%) were clinical stage IA/IB. 62% (28/45) of patients experienced a complication. Only 15.6% (7/45) were considered significantly morbid (≥ grade IIIB) per the Seely model. Perioperative mortality was 2% and half of patients were living at a follow-up of 53 months. Overall five-year survival was 52%. Conclusions. In carefully selected octogenarians, lobectomy carries a 15.6% rate of significantly morbid complications with encouraging overall survival. These data provide the basis for a more complete discussion with patients regarding lobectomy for lung cancer

Assessing Survival and Grading the Severity of Complications in Octogenarians Undergoing Pulmonary Lobectomy

Introduction. Octogenarians are at increased risk for complications after lung resection. With alternatives such as radiation, understanding the risks of surgery and associated survival are valuable. Data grading the severity of complications and long-term survival in this population is lacking. We reviewed our experience with lobectomy in octogenarians, grading complications using a validated thoracic morbidity and mortality schema. Methods. We retrospectively reviewed consecutive patients aged ≥80 undergoing lobectomy between 2004 and 2012. Demographics, clinical/pathologic stage, complications, recurrence, and mortality were collected. Complications were graded by the Seely thoracic morbidity and mortality model. Results. 45 patients (mean age 82.2 years) were analyzed. The majority of patients (28/45, 62%) were clinical stage IA/IB. 62% (28/45) of patients experienced a complication. Only 15.6% (7/45) were considered significantly morbid (≥ grade IIIB) per the Seely model. Perioperative mortality was 2% and half of patients were living at a follow-up of 53 months. Overall five-year survival was 52%. Conclusions. In carefully selected octogenarians, lobectomy carries a 15.6% rate of significantly morbid complications with encouraging overall survival. These data provide the basis for a more complete discussion with patients regarding lobectomy for lung cancer

The Authoritarian Dynamic During the COVID-19 Pandemic: Effects on Nationalism and Anti-Immigrant Sentiment

Research has demonstrated that situational factors such as perceived threats to the social order activate latent authoritarianism. The deadly COVID-19 pandemic presents a rare opportunity to test whether existential threat stemming from an indiscriminate virus moderates the relationship between authoritarianism and political attitudes toward the nation and out-groups. Using data from two large nationally representative samples of adults in the United Kingdom (N = 2,025) and Republic of Ireland (N = 1,041) collected during the initial phases of strict lockdown measures in both countries, we find that the associations between right-wing authoritarianism (RWA) and (1) nationalism and (2) anti-immigrant attitudes are conditional on levels of perceived threat. As anxiety about the COVID-19 pandemic increases, so too does the effect of RWA on those political outcomes. Thus, it appears that existential threats to humanity from the COVID-19 pandemic moderate expressions of authoritarianism in society

Different Conspiracy Theories Have Different Psychological and Social Determinants: Comparison of Three Theories About the Origins of the COVID-19 Virus in a Representative Sample of the UK Population

COVID-19 conspiracy theories have proliferated during the global pandemic, and their rapid spread among certain groups may jeopardize the public health response (e.g., undermining motivation to engage in social distancing and willingness to vaccinate against the virus). Using survey data from two waves of a nationally representative, longitudinal study of life in lockdown in the United Kingdom (N = 1,406), we analyze the factors associated with belief in three origin theories related to COVID-19, namely that it 1) originated in a meat market in Wuhan, China; 2) was developed in a lab in Wuhan, China; and 3) is caused by 5G mobile networks. Our findings suggest that political-psychological predispositions are strongly associated with belief in conspiracy theories about the virus, though the direction and effect sizes of these predictors vary depending on the specific content of each origin theory. For instance, belief in the Chinese lab conspiracy theory is strongly associated with right-wing authoritarianism (RWA), social dominance orientation (SDO), and general conspiracy ideation, as well as less reliable news sources, distrust in scientists, and anxiety about the pandemic. Belief in the 5G network conspiracy theory is strongly associated with SDO, distrust in scientists, while less strongly with conspiracy ideation and information from social networks/media; RWA is strongly negatively associated with belief in the 5G conspiracy theory, with older and more wealthy individuals somewhat less likely to endorse it. The meat market origin theory is predicted by intolerance of uncertainty, ethnocentrism, COVID-19 anxiety, and less so by higher income, while distrust in scientists is negatively associated with this origin story. Finally, belief in COVID-19 conspiracy theories is associated with negative public health behaviors such as unwillingness to social distance and vaccinate against the virus. Crucially, our findings suggest that the specific content of COVID-19 conspiracy theories likely determines which individuals may be most likely to endorse them

Pandemic buying: Testing a psychological model of over-purchasing and panic buying using data from the United Kingdom and the Republic of Ireland during the early phase of the COVID-19 pandemic

The over-purchasing and hoarding of necessities is a common response to crises, especially in developed economies where there is normally an expectation of plentiful supply. This behaviour was observed internationally during the early stages of the Covid-19 pandemic. In the absence of actual scarcity, this behaviour can be described as ‘panic buying’ and can lead to temporary shortages. However, there have been few psychological studies of this phenomenon. Here we propose a psychological model of over-purchasing informed by animal foraging theory and make predictions about variables that predict over-purchasing by either exacerbating or mitigating the anticipation of future scarcity. These variables include additional scarcity cues (e.g. loss of income), distress (e.g. depression), psychological factors that draw attention to these cues (e.g. neuroticism) or to reassuring messages (eg. analytical reasoning) or which facilitate over-purchasing (e.g. income). We tested our model in parallel nationally representative internet surveys of the adult general population conducted in the United Kingdom (UK: N = 2025) and the Republic of Ireland (RoI: N = 1041) 52 and 31 days after the first confirmed cases of COVID-19 were detected in the UK and RoI, respectively. About three quarters of participants reported minimal over-purchasing. There was more over-purchasing in RoI vs UK and in urban vs rural areas. When over-purchasing occurred, in both countries it was observed across a wide range of product categories and was accounted for by a single latent factor. It was positively predicted by household income, the presence of children at home, psychological distress (depression, death anxiety), threat sensitivity (right wing authoritarianism) and mistrust of others (paranoia). Analytic reasoning ability had an inhibitory effect. Predictor variables accounted for 36% and 34% of the variance in over-purchasing in the UK and RoI respectively. With some caveats, the data supported our model and points to strategies to mitigate over-purchasing in future crises