Rare and common genetic determinants of mitochondrial function determine severity but not risk of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving selective vulnerability of energy-intensive motor neurons (MNs). It has been unclear whether mitochondrial function is an upstream driver or a downstream modifier of neurotoxicity. We separated upstream genetic determinants of mitochondrial function, including genetic variation within the mitochondrial genome or autosomes; from downstream changeable factors including mitochondrial DNA copy number (mtCN). Across three cohorts including 6,437 ALS patients, we discovered that a set of mitochondrial haplotypes, chosen because they are linked to measurements of mitochondrial function, are a determinant of ALS survival following disease onset, but do not modify ALS risk. One particular haplotype appeared to be neuroprotective and was significantly over-represented in two cohorts of long-surviving ALS patients. Causal inference for mitochondrial function was achievable using mitochondrial haplotypes, but not autosomal SNPs in traditional Mendelian randomization (MR). Furthermore, rare loss-of-function genetic variants within, and reduced MN expression of, ACADM and DNA2 lead to ∼50 % shorter ALS survival; both proteins are implicated in mitochondrial function. Both mtCN and cellular vulnerability are linked to DNA2 function in ALS patient-derived neurons. Finally, MtCN responds dynamically to the onset of ALS independently of mitochondrial haplotype, and is correlated with disease severity. We conclude that, based on the genetic measures we have employed, mitochondrial function is a therapeutic target for amelioration of disease severity but not prevention of ALS.

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.

Distribution of selenium in zebrafish larvae after exposure to organic and inorganic selenium forms.

Selenium is an essential micronutrient for many organisms, and in vertebrates has a variety of roles associated with protection from reactive oxygen species. Over the past two decades there have been conflicting reports upon human health benefits and detriments arising from consumption of selenium dietary supplements. Thus, early studies report a decrease in the incidence of certain types of cancer, whereas subsequent studies did not observe any anti-cancer effect, and adverse effects such as increased risks for type 2 diabetes have been reported. A possible contributing factor may be that different chemical forms of selenium were used in different studies. Using larval stage zebrafish (Danio rerio) as a model organism, we report a comparison of the toxicities and tissue selenium distributions of four different chemical forms of selenium. We find that the organic forms of selenium tested (Se-methyl-l-selenocysteine and l-selenomethionine) show considerably more toxicity than inorganic forms (selenite and selenate), and that this appears to be correlated with the level of bioaccumulation. Despite differences in concentrations, the tissue specific pattern of selenium accumulation was similar for the chemical forms tested; selenium was found to be highly concentrated in pigment (melanin) containing tissues especially for the organic selenium treatments, with lower concentrations in eye lens, yolk sac and heart. These results suggest that pigmented tissues might serve as a storage reservoir for selenium.

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.

Role of maternal elimination diets and human milk IgA in the development of cow's milk allergy in the infants.

BACKGROUND: The role of maternal avoidance diets in the prevention of food allergies is currently under debate. Little is known regarding the effects of such diets on human milk (HM) composition or induction of infant humoral responses. OBJECTIVE: To assess the association of maternal cow's milk (CM) avoidance during breastfeeding with specific IgA levels in HM and development of cow's milk allergy (CMA) in infants. METHODS: We utilized HM and infant serum samples from a prospective birth cohort of 145 dyads. Maternal serum and HM samples were assessed for casein and beta-lactoglobulin (BLG)-specific IgA and IgG by ELISA; 21 mothers prophylactically initiated a strict maternal CM avoidance diet due to a sibling's history of food allergy and 16 due to atopic eczema or regurgitation/vomiting seen in their infants within the first 3 months of life. Infants' sera were assessed for casein and BLG-specific IgG, IgA and IgE; CMA was confirmed by an oral food challenge. The impact of HM on BLG uptake was assessed in transcytosis assays utilizing Caco-2 intestinal epithelial cell line. RESULTS: Mothers avoiding CM had lower casein- and BLG-specific IgA in HM than mothers with no CM restriction (P = 0.019 and P = 0.047). Their infants had lower serum casein- and BLG-specific IgG(1) (P = 0.025 and P < 0.001) and BLG-specific IgG(4) levels (P = 0.037), and their casein- and BLG-specific IgA levels were less often detectable than those with no CM elimination diet (P = 0.003 and P = 0.007). Lower CM-specific IgG4 and IgA levels in turn were associated with infant CMA. Transcytosis of BLG was impaired by HM with high, but not low levels of specific IgA. CONCLUSIONS: Maternal CM avoidance was associated with lower levels of mucosal-specific IgA levels and the development of CMA in infants. CLINICAL RELEVANCE: HM IgA may play a role in preventing excessive, uncontrolled food antigen uptake in the gut lumen and thereby in the prevention of CMA.

Digenean metacercariae of fishes from the lagoon flats of Palmyra Atoll, Eastern Indo-Pacific.

Although many studies on the taxonomy of digenean trematodes of marine fishes have been completed in the Eastern Indo-Pacific (EIP) marine ecoregion, only a few have considered metacercarial stages. Here, the results are presented of a taxonomic survey of the digenean metacercariae of fishes from Palmyra Atoll, a remote and relatively pristine US National Wildlife Refuge located 1680 km SSW of Hawaii. Up to 425 individual fish were collected, comprising 42 fish species, from the sand flats bordering the lagoon of the atoll. Quantitative parasitological examinations of each fish were performed. Morphological descriptions of the encountered digenean metacercariae are provided, together with their prevalence, mean intensities, host and tissue-use. Up to 33,964 individuals were recovered representing 19 digenean metacercaria species from eight families. The species composition of digeneans in lagoon fishes at Palmyra Atoll is a subset of what has previously been reported for the EIP. Further, the large diversity and abundance of metacercariae reported in this study highlight the utility of including this group in future ecological research in the EIP marine ecoregion.

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.

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.

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.

Voluntary involuntariness: thought suppression and the regulation of the experience of will.

Participants were asked to carry out a series of simple tasks while following mental control instructions. In advance of each task, they either suppressed thoughts of their intention to perform the task, concentrated on such thoughts, or monitored their thoughts without trying to change them. Suppression resulted in reduced reports of intentionality as compared to monitoring, and as compared to concentration. There was a weak trend for suppression to enhance reported intentionality for a repetition of the action carried out after suppression instructions had been discontinued.