Network inference from perturbation time course data.

Networks underlie much of biology from subcellular to ecological scales. Yet, understanding what experimental data are needed and how to use them for unambiguously identifying the structure of even small networks remains a broad challenge. Here, we integrate a dynamic least squares framework into established modular response analysis (DL-MRA), that specifies sufficient experimental perturbation time course data to robustly infer arbitrary two and three node networks. DL-MRA considers important network properties that current methods often struggle to capture: (i) edge sign and directionality; (ii) cycles with feedback or feedforward loops including self-regulation; (iii) dynamic network behavior; (iv) edges external to the network; and (v) robust performance with experimental noise. We evaluate the performance of and the extent to which the approach applies to cell state transition networks, intracellular signaling networks, and gene regulatory networks. Although signaling networks are often an application of network reconstruction methods, the results suggest that only under quite restricted conditions can they be robustly inferred. For gene regulatory networks, the results suggest that incomplete knockdown is often more informative than full knockout perturbation, which may change experimental strategies for gene regulatory network reconstruction. Overall, the results give a rational basis to experimental data requirements for network reconstruction and can be applied to any such problem where perturbation time course experiments are possible.

Ageing and thought suppression performance: Its relationship with working memory capacity, habitual thought suppression and mindfulness.

A study investigated how the ability to suppress thoughts in the laboratory was affected by type of thought suppressed (positive, negative, neutral), participants' age and working memory capacity (WMC). Linked variables (Use of thought suppression, social desirability, and mindfulness) were measured to assess whether they modified susceptibility to thought intrusion. Younger, middle aged and older adults suppressed three different valenced thoughts in a counterbalanced order for 5-min per thought. Participants then completed a WMC task and questionnaire measures of the linked variables. Valence had no effect on intrusions. WMC was positively related to intrusions; higher WMC corresponded to greater intrusions. Age was negatively related to intrusions; with increasing age intrusions decreased. Hierarchical regression showed only age and backward digit span (WMC) significantly predicted intrusions. The relationship between WMC and intrusions was not moderated by age. WMC and age both independently predict level of intrusion, and no synergistic effect was found.

Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II.

INTRODUCTION: The purpose of this study was to determine whether macrophages migrated from the spleen are associated with angiotensin II-induced cardiac fibrosis and hypertension. METHODS: Sprague-Dawley rats were subjected to angiotensin II infusion in vehicle (500 ng/kg/min) for up to four weeks. In splenectomy, the spleen was removed before angiotensin II infusion. In the angiotensin II AT1 receptor blockade, telmisartan was administered by gastric gavage (10 mg/kg/day) during angiotensin II infusion. The heart and aorta were isolated for Western blot analysis and immunohistochemistry. RESULTS: Angiotensin II infusion caused a significant reduction in the number of monocytes in the spleen through the AT1 receptor-activated monocyte chemoattractant protein-1. Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively reduced the recruitment of macrophages into the heart. Associated with this change, transforming growth factor ß1 expression and myofibroblast proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated. Furthermore, interstitial/perivascular fibrosis was attenuated. These modifications occurred in coincidence with reduced blood pressure. At week 4, invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated and expression of endothelial nitric oxide synthase was upregulated, along with a reduction in aortic fibrosis. CONCLUSIONS: These results suggest that macrophages when recruited into the heart and aorta from the spleen potentially contribute to angiotensin II-induced cardiac fibrosis and hypertension.

A longitudinal investigation of repressive coping and ageing.

OBJECTIVES: Two studies investigated the possibility that repressive coping is more prevalent in older adults and that this represents a developmental progression rather than a cohort effect. Study 1 examined repressive coping and mental health cross-sectionally in young and old adults. Study 2 examined whether there was a developmental progression of repressive coping prevalence rates in a longitudinal sample of older adults. METHOD: Study 1 compared younger adults (mean age 27.6 years) with older adults (mean age 74.2 years) on inventories of mental health and well-being and examined the prevalence of repressive coping in both samples. Study 2 re-tested a sample of older adults previously reported following an interval of 7 years. RESULTS AND CONCLUSION: Study 1 - in line with previous research older adults demonstrated greater psychological well-being and had a higher prevalence of repressive coping than younger adults (at 30% vs. 12% respectively). Study 2 - the data indicated that the prevalence of repressive coping rose from 41% at the first time of testing (2002) to 56.4% at the second testing interval (2009). These results suggest that repressive coping may increase across the lifespan in certain individuals and continue to increase throughout older adulthood. Furthermore, this increase in repressive coping with age appears to result in better well-being in those older adults who become repressive copers.

To suppress, or not to suppress? That is repression: controlling intrusive thoughts in addictive behaviour.

Research to understand how individuals cope with intrusive negative or threatening thoughts suggests a variety of different cognitive strategies aimed at thought control. In this review, two of these strategies--thought suppression and repressive coping--are discussed in the context of addictive behaviour. Thought suppression involves conscious, volitional attempts to expel a thought from awareness, whereas repressive coping, which involves the avoidance of thoughts without the corresponding conscious intention, appears to be a far more automated process. Whilst there has been an emerging body of research exploring the role of thought suppression in addictive behaviour, there remains a dearth of research which has considered the role of repressive coping in the development of, and recovery from, addiction. Based on a review of the literature, and a discussion of the supposed mechanisms which underpin these strategies for exercising mental control, a conceptual model is proposed which posits a potential common mechanism. This model makes a number of predictions which require exploration in future research to fully understand the cognitive strategies utilised by individuals to control intrusive thoughts related to their addictive behaviour.

The effectiveness of conjugate Haemophilus influenzae type B vaccine in The Gambia 14 years after introduction.

BACKGROUND: The Gambia was the first country in Africa to introduce conjugate Haemophilus influenzae type b (Hib) vaccine, which, as in other developing countries but unlike industrialized countries, is delivered as a 3-dose primary series with no booster. This study assessed its effectiveness 14 years after introduction. METHODS: Using methods standardized during >20 years in the study site, clinical and microbiological surveillance for invasive Hib disease (primarily meningitis) in the Western Region of The Gambia from 2007 to 2010 was complemented with studies of Hib carriage in children aged 1 to <2 years, Hib antibody levels in children aged <5 years, and Hib vaccine coverage and timing in children aged 1 to <2 years. RESULTS: The incidence of Hib meningitis remained low (averaging 1.3 per 100 000 children aged <5 years annually), as did the Hib oropharyngeal carriage rate (0.9%). Hib antibody levels were protective in >99% of those surveyed, albeit with lower titers in older children; and coverage of conjugate Hib vaccination was high (91% having 3 doses at 1-2 years of age) using a schedule that was delivered at median ages of 2.6 months, 4.3 months, and 6 months for the first, second, and third doses, respectively. CONCLUSIONS: Conjugate Hib vaccine was delivered on time in a 3-dose primary series without booster to a high proportion of eligible children and this was associated with effective disease control up to 14 years after introduction. It is important that surveillance continues in this first African country to introduce the vaccine to determine if effective control persists or if a booster dose becomes necessary as has been the case in industrialized countries.

Incidence of Haemophilus influenzae type b disease in The Gambia 14 years after introduction of routine Haemophilus influenzae type b conjugate vaccine immunization.

OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccine was first introduced in Africa in The Gambia in 1997 as a primary 3-dose course in infancy with no booster, and was followed by the disappearance of invasive Hib disease by 2002. A cluster of cases detected non-systematically in post-infant children in 2005-2006 raised the question of the need for a booster dose. The objective of this study was to determine the incidence of invasive Hib disease in Gambian children 14 years after the introduction of Hib conjugate vaccine. STUDY DESIGN: This hospital-based clinical and microbiological Hib disease surveillance in 3 hospitals in the western region of The Gambia was undertaken between October 2007 and December 2010 applying the same methods used in a previous Hib vaccine effectiveness study in 1997-2002. RESULTS: The annual incidences of Hib meningitis and all invasive Hib disease in children aged <5 years remained below 5 cases per 100,000 children during 2008-2010. The median age of patients with any invasive Hib disease was 5 months. CONCLUSION: Hib conjugate vaccination as a primary 3-dose course in The Gambia remains highly effective in controlling invasive Hib disease, and current data do not support the introduction of a booster dose.

Effect of thought suppression on desire to smoke and tobacco withdrawal symptoms.

RATIONALE: Suppressing smoking thoughts has been shown to result in elevated smoking. However, the effect of suppressing smoking thoughts on desire to smoke and withdrawal symptoms has not been investigated. OBJECTIVES: We examined the effects of suppressing smoking thoughts on the subsequent desire to smoke and on tobacco withdrawal symptoms, relative to groups that were either thinking about anything they wished or actively thinking about smoking. METHODS: A randomised experimental study compared the effects of three manipulations (suppressed smoking thoughts, expressed smoking thoughts and thoughts of anything they wished) on desire and withdrawal immediately after the manipulation and 5 and 10 min after. RESULTS: Suppressing smoking thoughts did not result in elevated subsequent desire to smoke, relative to the other manipulations. Suppressing smoking thoughts resulted in a significant elevation in hunger ratings, relative to the other manipulations, at all measurement times. There were no significant effects for the other withdrawal symptoms. Self-reported greater use of thought suppression in everyday life was significantly associated with greater desire to smoke at baseline and was associated with lower mindfulness scores. CONCLUSIONS: Laboratory-instructed suppression of smoking thoughts is associated with increased reports of hunger but did not lead to increases in other withdrawal symptoms or elevated desire to smoke. Reports of everyday use of thought suppression are associated with elevated desire to smoke at baseline. Further investigations need to assess the effect of suppressing smoking cravings, instead of general smoking thoughts, on desire to smoke and tobacco withdrawal.

I suppress, therefore I smoke: effects of thought suppression on smoking behavior.

Thought suppression is a method frequently employed by individuals who are trying to control their thoughts and behaviors. Although this strategy is known to actually increase unwanted thoughts, it is unclear whether thought suppression also results in behavioral rebound. The study presented in this article investigated the effects of suppressing thoughts of smoking in everyday life on the number of cigarettes subsequently smoked. Study participants recorded their daily cigarette intake and stress levels over a 3-week period. In Week 1 and Week 3, participants monitored intake and stress. During Week 2, in addition to monitoring intake and stress, participants in the experimental groups either suppressed or expressed smoking thoughts, whereas the control group continued monitoring. Our results showed a clear behavioral rebound: The suppression group smoked significantly more in Week 3 than the expression or control group did. Moreover, the tendency to suppress thoughts (measured by the White Bear Suppression Inventory) was positively related to the number of attempts to quit smoking. The implications of our findings for smoking cessation are discussed.

Effects of age on phenomenology and consistency of flashbulb memories of September 11 and a staged control event.

In two studies, the special status of flashbulb memories was investigated by contrasting the effects of age on the phenomenology and consistency of flashbulb memories of September 11, over a 2-year delay period, with those of a mundane staged control event: participants learning that they had not won a small prize. Flashbulb memories produced no significant age effects for either phenomenological characteristics or test-retest consistency, as predicted by Mather's (2004) emotional compensation hypothesis. By contrast, the control event resulted in significant age effects for phenomenological characteristics (e.g., specificity and the amount of detail recalled) but not for test-retest consistency. Furthermore, in both age groups, memories of September 11 were significantly more vivid, detailed, and consistent than control memories even though the test-retest interval was twice as long for flashbulb memories. In addition, correlations between consistency scores and ratings of rehearsal were positive for control memories but negative for flashbulb memories. The theoretical implications of these findings for research on cognitive aging and flashbulb memories are discussed.

Alcohol pharmacokinetics, decision making and folk wisdom: a reply to Moxnes and Jensen (2009).

Moxnes and Jensen (2009) present a study of decision making under conditions of uncertainty using a computerised simulation of alcohol pharmacokinetics. In their article, they conclude that their findings challenge the 'folk wisdom' that advises against drinking on an empty stomach. We contend that this is a problematic conclusion for three reasons: (1) the study and findings presented in their paper are simply not sufficient to allow one to, even tentatively, draw such a conclusion; (2) the conclusion is contrary to basic pharmacological knowledge concerning alcohol absorption, metabolism and the implications for peak blood alcohol concentration; and (3) the implications for understanding the process of decision making while alcohol intoxicated are not considered in the study. The Moxnes and Jensen (2009) study did not involve alcohol administration and is therefore an examination of decision making in situations of uncertainty rather than a specific exploration of drinking-related decision making. Recent formulations of the effects of alcohol on cognitive processing would lead to different conclusions than those presented by Moxnes and Jensen (2009). We conclude by suggesting our understanding of the implications of the study.

Effects of thought suppression on eating behaviour in restrained and non-restrained eaters.

Recent research has shown that suppressing food related thoughts can cause a subsequent increase in consumption relative to groups not suppressing, or thinking about food. The present study examined whether the effects of thought suppression on subsequent eating behaviour would interact with participants restrained eating status. One hundred and sixteen female participants were split into three groups. One third suppressed thoughts of chocolate, one third thought about chocolate and the final third thought about anything they wished. Following this, participants took part in a task where they rated two brands of chocolate on several taste characteristics. Participants were unaware that the dependent variable was the amount of chocolate consumed and not taste preference. Participants also completed measures of dietary restraint, craving, guilt and thought suppression. Results indicated that restrained eaters in the suppression condition consumed significantly more chocolate than restrained eaters in the expression or control condition. Participants low on restraint ate statistically equivalent amounts in all three groups. In addition, participants reporting frequent use of thought suppression (assessed by the White Bear Suppression Inventory) reported greater chocolate cravings.

Universal electromotive force induced by domain wall motion.

The electromotive force induced by a moving magnetic domain wall in a nanostrip has been calculated theoretically and detected experimentally. It is found that the emf depends only on the domain wall transformation frequency through a universal Josephson type relation, which is closely related to the topological nature of the domain wall. Our experimental measurements confirm the theoretical prediction.

Resistance can be futile: investigating behavioural rebound.

One hundred and thirty-four non-dieting participants spent 5 min thinking aloud under three different conditions. Participants either suppressed or expressed thoughts of eating chocolate, or verbalised with no further instructions. After thinking aloud, all participants took part in a taste preference task where they tried two brands of chocolate and answered questions about their preference. Unbeknownst to participants the variable of interest was the amount of chocolate eaten, not their preference. Results indicated an interaction between condition (suppression vs. expression vs. control) and gender. Both male and female participants showed a behavioural rebound effect, consuming significantly more chocolate after suppression than participants in the verbalise only control group. However, in the expression group, a clear difference between males and females was manifested, while females ate a similar amount of chocolate in the expression and verbalise only control groups, males ate the most chocolate in the expression group and this was significantly greater than the amount eaten after suppression or the verbalise only control group.

The effects of age on psychopathology, well-being and repressive coping.

The present study was conducted to test the hypothesis that the increased psychological well-being and positivity effect in old age can be related to a high prevalence of repressive coping in healthy older adults. Both older (mean age 73) and younger (mean age 20) adults completed a range of indices measuring psychopathology and repressive coping. Results showed that older adults scored lower than younger adults on almost all indices of psychopathology, and were more likely to be classed as repressive copers than younger adults (41% versus 11%, respectively). Furthermore, when the repressive copers and borderline repressors were removed from both samples, age effects on several, but not all, measures of psychopathology disappeared, indicating that even older non-repressors showed better mental health than young non-repressors. Possible mechanisms of increased positivity, in terms of repressive coping and reductions in intrusive thoughts and rumination in old age, are discussed.