Photophysiological and photosynthetic complex changes during iron starvation in Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942

Iron is an essential component in many protein complexes involved in photosynthesis, but environmental iron availability is often low as oxidized forms of iron are insoluble in water. To adjust to low environmental iron levels, cyanobacteria undergo numerous changes to balance their iron budget and mitigate the physiological effects of iron depletion. We investigated changes in key protein abundances and photophysiological parameters in the model cyanobacteria Synechococcus PCC 7942 and Synechocystis PCC 6803 over a 120 hour time course of iron deprivation. The iron stress induced protein (IsiA) accumulated to high levels within 48 h of the onset of iron deprivation, reaching a molar ratio of ~42 IsiA : Photosystem I in Synechococcus PCC 7942 and ~12 IsiA : Photosystem I in Synechocystis PCC 6803. Concomitantly the iron-rich complexes Cytochrome b6f and Photosystem I declined in abundance, leading to a decrease in the Photosystem I : Photosystem II ratio. Chlorophyll fluorescence analyses showed a drop in electron transport per Photosystem II in Synechococcus, but not in Synechocystis after iron depletion. We found no evidence that the accumulated IsiA contributes to light capture by Photosystem II complexes

Immune checkpoint inhibitors: new strategies to checkmate cancer

Immune checkpoint inhibitors (ICIs) targeting Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4) or Programmed cell Death protein 1 (PD-1) receptors have demonstrated remarkable efficacy in subsets of patients with malignant disease. This emerging treatment modality holds great promise for future cancer treatment and has engaged pharmaceutical research interests in tumour immunology. While ICIs can induce rapid and durable responses in some patients, identifying predictive factors for effective clinical responses has proven challenging. This review summarises the mechanisms of action of ICIs and outlines important pre-clinical work that contributed to their development. We explore clinical data that has led to disease-specific drug licensing, and highlight key clinical trials that have revealed ICI efficacy across a range of malignancies. We describe how ICIs have been used as part of combination therapies, and explore their future prospects in this area. We conclude by discussing the incorporation of these new immunotherapeutics into precision approaches to cancer therapy

Nonlinear dynamics of giant resonances in atomic nuclei

The dynamics of monopole giant resonances in nuclei is analyzed in the time-dependent relativistic mean-field model. The phase spaces of isoscalar and isovector collective oscillations are reconstructed from the time-series of dynamical variables that characterize the proton and neutron density distributions. The analysis of the resulting recurrence plots and correlation dimensions indicate regular motion for the isoscalar mode, and chaotic dynamics for the isovector oscillations. Information-theoretic functionals identify and quantify the nonlinear dynamics of giant resonances in quantum systems that have spatial as well as temporal structure.Comment: 24 pages, RevTeX, 15 PS figures, submitted Phys. Rev.

Self-Averaging, Distribution of Pseudo-Critical Temperatures and Finite Size Scaling in Critical Disordered Systems

The distributions $P(X)$ of singular thermodynamic quantities in an ensemble of quenched random samples of linear size $l$ at the critical point $T_c$ are studied by Monte Carlo in two models. Our results confirm predictions of Aharony and Harris based on Renormalization group considerations. For an Ashkin-Teller model with strong but irrelevant bond randomness we find that the relative squared width, $R_X$, of $P(X)$ is weakly self averaging. $R_X\sim l^{\alpha/\nu}$, where $\alpha$ is the specific heat exponent and $\nu$ is the correlation length exponent of the pure model fixed point governing the transition. For the site dilute Ising model on a cubic lattice, known to be governed by a random fixed point, we find that $R_X$ tends to a universal constant independent of the amount of dilution (no self averaging). However this constant is different for canonical and grand canonical disorder. We study the distribution of the pseudo-critical temperatures $T_c(i,l)$ of the ensemble defined as the temperatures of the maximum susceptibility of each sample. We find that its variance scales as $(\delta T_c(l))^2 \sim l^{-2/\nu}$ and NOT as $\sim l^{-d}. We find that$R_\chi$is reduced by a factor of$\sim 70$with respect to$R_\chi (T_c)$by measuring$\chi$of each sample at$T_c(i,l)$. We analyze correlations between the magnetization at criticality$m_i(T_c,l)$and the pseudo-critical temperature$T_c(i,l)$in terms of a sample independent finite size scaling function of a sample dependent reduced temperature$(T-T_c(i,l))/T_c$. This function is found to be universal and to behave similarly to pure systems.Comment: 31 pages, 17 figures, submitted to Phys. Rev.

Amino Acid Starvation Induced by Invasive Bacterial Pathogens Triggers an Innate Host Defense Program

SummaryAutophagy, which targets cellular constituents for degradation, is normally inhibited in metabolically replete cells by the metabolic checkpoint kinase mTOR. Although autophagic degradation of invasive bacteria has emerged as a critical host defense mechanism, the signals that induce autophagy upon bacterial infection remain unclear. We find that infection of epithelial cells with Shigella and Salmonella triggers acute intracellular amino acid (AA) starvation due to host membrane damage. Pathogen-induced AA starvation caused downregulation of mTOR activity, resulting in the induction of autophagy. In Salmonella-infected cells, membrane integrity and cytosolic AA levels rapidly normalized, favoring mTOR reactivation at the surface of the Salmonella-containing vacuole and bacterial escape from autophagy. In addition, bacteria-induced AA starvation activated the GCN2 kinase, eukaryotic initiation factor 2α, and the transcription factor ATF3-dependent integrated stress response and transcriptional reprogramming. Thus, AA starvation induced by bacterial pathogens is sensed by the host to trigger protective innate immune and stress responses

Prediction of Severe Complications and Mortality in Patients Admitted to a Coronary Care Unit

The aim of this study was to design a statistical model which will predict death or life-threatening complications in patients admitted to Coronary Care Unit using data which is available at the time of presentation. The study included 3721 consecutive admissions over a period four year period. Predictive models were developed using logistic regression analysis (with data from 1000 patients) and their performance was assessed using receiver operating characteristic (ROC) curve analysis. The most useful model included nine data items and was tested on data from 2721 patients. These could be divided into four groups according to their calculated probability of developing a serious complication. The lowest risk group had a mortality of 0.05%, compared with 3.5%, 6.4% and 18.1% respectively in the higher risk groups (p1000 U/1) in the four groups was 14.1%, 21.2%, 46.9% and 51.5% respectively (p<0.001). The overall complication rates were 16.9%, 35.4%, 75.4% and 71.8% respectively (p<0.001)

What do young athletes implicitly understand about psychological skills?

One reason sport psychologists teach psychological skills is to enhance performance in sport; but the value of psychological skills for young athletes is questionable because of the qualitative and quantitative differences between children and adults in their understanding of abstract concepts such as mental skills. To teach these skills effectively to young athletes, sport psychologists need to appreciate what young athletes implicitly understand about such skills because maturational (e.g., cognitive, social) and environmental (e.g., coaches) factors can influence the progressive development of children and youth. In the present qualitative study, we explored young athletes’ (aged 10–15 years) understanding of four basic psychological skills: goal setting, mental imagery, self-talk, and relaxation. Young athletes (n = 118: 75 males and 43 females) completed an open-ended questionnaire to report their understanding of these four basic psychological skills. Compared with the older youth athletes, the younger youth athletes were less able to explain the meaning of each psychological skill. Goal setting and mental imagery were better understood than self-talk and relaxation. Based on these findings, sport psychologists should consider adapting interventions and psychoeducational programs to match young athletes’ age and developmental level

Assessing gender mainstreaming in the education sector: depoliticised technique or a step towards women's rights and gender equality?

In 1995 the Beijing Conference on Women identified gender mainstreaming as a key area for action. Policies to effect gender mainstreaming have since been widely adopted. This special issue of Compare looks at research on how gender mainstreaming has been used in government education departments, schools, higher education institutions, international agencies and NGOs .1 In this introduction we first provide a brief history of the emergence of gender mainstreaming and review changing definitions of the term. In the process we outline some policy initiatives that have attempted to mainstream gender and consider some difficulties with putting ideas into practice, particularly the tensions between a technical and transformative interpretations . Much of the literature about experiences with gender mainstreaming tends to look at organizational processes and not any specificities of a particular social sector. However, in our second section, we are concerned to explore whether institutional forms and particular actions associated with education give gender mainstreaming in education sites some distinctive features. In our last section we consider some of the debates about global and local negotiations in discussions of gender policy and education and the light this throws on gender mainstreaming. In so doing, we place the articles that follow in relation to contestations over ownership, political economy, the form and content of education practice and the social complexity of gender equality

The Dark Sides of Social Policy: From Neoliberalism to Resurgent Right-wing Populism

This Forum Debate explores the confluence of neoliberal, populist, conservative and reactionary influences on contemporary ideologies and practices of social policy, with a focus on the poorer peripheries of global