Probing the Catalytic Roles of Arg548 and Gln552 in the Carboxyl Transferase Domain of the \u3cem\u3eRhizobium etli\u3c/em\u3e Pyruvate Carboxylase by Site-directed Mutagenesis

The roles of Arg548 and Gln552 residues in the active site of the carboxyl transferase domain of Rhizobium etli pyruvate carboxylase were investigated using site-directed mutagenesis. Mutation of Arg548 to alanine or glutamine resulted in the destabilization of the quaternary structure of the enzyme, suggesting that this residue has a structural role. Mutations R548K, Q552N, and Q552A resulted in a loss of the ability to catalyze pyruvate carboxylation, biotin-dependent decarboxylation of oxaloacetate, and the exchange of protons between pyruvate and water. These mutants retained the ability to catalyze reactions that occur at the active site of the biotin carboxylase domain, i.e., bicarbonate-dependent ATP cleavage and ADP phosphorylation by carbamoyl phosphate. The effects of oxamate on the catalysis in the biotin carboxylase domain by the R548K and Q552N mutants were similar to those on the catalysis of reactions by the wild-type enzyme. However, the presence of oxamate had no effect on the reactions catalyzed by the Q552A mutant. We propose that Arg548 and Gln552 facilitate the binding of pyruvate and the subsequent transfer of protons between pyruvate and biotin in the partial reaction catalyzed in the active site of the carboxyl transferase domain of Rhizobium etli pyruvate carboxylase

Psycho-social factors influencing forest conservation intentions on the agricultural frontier

Remnant forest fragments are critical to conserve biological diversity yet these are lost rapidly in areas under agricultural expansion. Conservation planning and policy require a deeper understanding of the psycho-social factors influencing landholders’ intentions towards conserving forest fragments. We surveyed 89 landholders in an agricultural frontier of the South American Gran Chaco and employed survey data to test three social psychological models: the Theory of Planned Behavior (TPB) and two modified versions of it, one integrated to the Norm Activation Theory (TPB-NAT) and one including the effect of identity (TPB-NAT-Identity). The TPB was the most parsimonious model and explained a large variance of conservation intentions (41%). Social norms and attitudes had the largest direct influence on intentions across the three models, and identity had a significant role in shaping social norms and attitudes. Interventions aimed at building social capital within landholder networks provide the best hope for influencing pro-conservation norms.Fil: Mastrangelo, Matias Enrique. Victoria University of Wellington; Nueva Zelanda. Instituto Nacional de Tecnología Agropecuaria; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gavin, Michael C.. Colorado State University; Estados Unidos. Victoria University of Wellington; Nueva ZelandaFil: Laterra, Pedro. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Linklater, Wayne L.. Victoria University of Wellington; Nueva ZelandaFil: Milfont, Taciano L.. Victoria University of Wellington; Nueva Zeland

Crying and feeding problems in infancy and cognitive outcome in preschool children born at risk : a prospective population study

Objective: To investigate whether regulatory problems, i.e., crying and feeding problems in infants > 3 months of age, predict cognitive outcome in preschool children born at risk even when controlled for confounding factors. Methods: A prospective longitudinal study of children born in a geographically defined area in Germany. N = 4427 children of 6705 eligible survivors (66%) participated at all four assessment points (neonatal, 5, 20, and 56 months of age). Excessive crying and feeding problems were measured at 5 months. Mental development was assessed with the Griffiths Scale at 20 months, and cognitive assessments were conducted at 56 months. Neonatal complications, neurological, and psychosocial factors were controlled as confounders in structural equation modeling and analyses of variance. Results: One in five infants suffered from single crying or feeding problems, and 2% had multiple regulatory problems, i.e., combined crying and feeding problems at 5 months. In girls, regulatory problems were directly predictive of lower cognition at 56 months, even when controlled for confounders, whereas in boys, the influence on cognition at 56 months was mediated by low mental development at 20 months. Both in boys and girls, shortened gestational age, neonatal neurological complications, and poor parent-infant relationship were predictive of regulatory problems at 5 months and lower cognition at 56 months. Conclusion: Regulatory problems in infancy have a small but significant adverse effect on cognitive development

A dual process account of creative thinking

This article explicates the potential role played by type 1 thinking (automatic, fast) and type 2 thinking (effortful, logical) in creative thinking. The relevance of Evans's (2007) models of conflict of dual processes in thinking is discussed with regards to creative thinking. The role played by type 1 thinking and type 2 thinking during the different stages of creativity (problem finding and conceptualization, incubation, illumination, verification and dissemination) is discussed. It is proposed that although both types of thinking are active in creativity, the extent to which they are active and the nature of their contribution to creativity will vary between stages of the creative process. Directions for future research to test this proposal are outlined; differing methodologies and the investigation of different stages of creative thinking are discussed. © Taylor & Francis Group, LLC

A Core Outcome Set for the Benefits and Adverse Events of Bariatric and Metabolic Surgery: The BARIACT Project.

This is the final version. Available from PLoS via the DOI in this record.BACKGROUND: Bariatric and metabolic surgery is used as a treatment for patients with severe and complex obesity. However, there is a need to improve outcome selection and reporting in bariatric surgery trials. A Core Outcome Set (COS), an agreed minimum set of outcomes reported in all studies of a specific condition, may achieve this. Here, we present the development of a COS for BARIAtric and metabolic surgery Clinical Trials-the BARIACT Study. METHODS AND FINDINGS: Outcomes identified from systematic reviews and patient interviews informed a questionnaire survey. Patients and health professionals were surveyed three times and asked to rate the importance of each item on a 1-9 scale. Delphi methods provided anonymised feedback to participants. Items not meeting predefined criteria were discarded between rounds. Remaining items were discussed at consensus meetings, held separately with patients and professionals, where the COS was agreed. Data sources identified 2,990 outcomes, which were used to develop a 130-item questionnaire. Round 1 response rates were moderate but subsequently improved to above 75% for other rounds. After rounds 2 and 3, 81 and 14 items were discarded, respectively, leaving 35 items for discussion at consensus meetings. The final COS included nine items: "weight," "diabetes status," "cardiovascular risk," "overall quality of life (QOL)," "mortality," "technical complications of the specific operation," "any re-operation/re-intervention," "dysphagia/regurgitation," and "micronutrient status." The main limitation of this study was that it was based in the United Kingdom only. CONCLUSIONS: The COS is recommended to be used as a minimum in all trials of bariatric and metabolic surgery. Adoption of the COS will improve data synthesis and the value of research data. Future work will establish methods for the measurement of the outcomes in the COS.Medical Research Council (MRC)National Institute for Health Research (NIHR)National Institute for Health Research (NIHR

Benign breast disease, recent alcohol consumption, and risk of breast cancer: a nested case–control study

INTRODUCTION: Alcohol consumption is a well-established risk factor for breast cancer. Some studies have suggested that the risk of breast cancer associated with alcohol consumption is greater for women with a history of benign breast disease (BBD). We hypothesized that among women with biopsy-confirmed BBD, recent alcohol consumption would increase the risk of breast cancer in women with proliferative breast disease to a greater extent than in women with nonproliferative breast disease. METHODS: We conducted a nested case–control study in the Nurses' Health Study I and II. The cases (n = 282) were women diagnosed with incident breast cancer, with a prior biopsy-confirmed breast disease. The controls (n = 1,223) were participants with a previous BBD biopsy, but without a diagnosis of breast cancer. Pathologists reviewed benign breast biopsy slides in a blinded fashion and classified the BBD as nonproliferative, proliferative without atypia, or atypical hyperplasia, according to standard criteria. RESULTS: Women with nonproliferative breast disease consuming ≥ 15 g of alcohol per day had a nonsignificant 67% increased risk of breast cancer (odds ratio = 1.67; 95% confidence interval 0.65 to 4.34) compared with nondrinkers. There was no evidence that recent alcohol consumption increased the risk of breast cancer to a greater extent in women with proliferative BBD than among women with nonproliferative BBD (P for interactio n = 0.20). CONCLUSION: Contrary to our a priori hypothesis, there was no evidence that recent alcohol consumption increased the risk of breast cancer to a greater extent among women with proliferative BBD than among women with nonproliferative BBD

Cyclooxygenase inhibitors impair CD4 T cell immunity and exacerbate Mycobacterium tuberculosis infection in aerosol-challenged mice

Tuberculosis, caused by infection with Mycobacterium tuberculosis (Mtb), kills over 1.6 million people each year despite availability of antibiotics. The increase in drug resistant Mtb strains is a major public health emergency and host-directed therapy as adjunct to antibiotic treatment has gained increased interest. Cyclooxygenase inhibitors (COXi) are frequently used drugs to alleviate tuberculosis related symptoms. Mouse studies of acute intravenous Mtb infection have suggested a potential benefit of COXi for host-directed therapy. Here we show that COXi treatment (ibuprofen and celecoxib) is detrimental to Mtb control in different mouse models of respiratory infection. This effect links to impairments of the Type-1 helper (Th1) T-cell response as CD4 T-cells in COXi-treated animals have significantly decreased Th1 differentiation, reduced IFNγ expression and decreased protective capacity upon adoptive transfer. If confirmed in clinical trials, these findings could have major impact on global health and question the use of COXi for host-directed therapy.publishedVersio

Trajectories of quality of life in early-stage dementia: individual variations and predictors of change

Background: Little evidence is available about how quality of life (QoL) changes as dementia progresses. Objectives: We explored QoL trajectories over a 20-month period and examined what predicted change in QoL. Method: Fifty-one individuals with a diagnosis of Alzheimer’s, vascular or mixed dementia (PwD) participating in the MIDAS study rated their QoL using the QoL-AD scale at baseline and at 20-month follow-up. PwD also rated their mood and quality of relationship with the carer. In each case the carer rated his/her level of stress and perceived quality of relationship with the PwD. Results: There was no change in mean QoL score. Nearly one-third of PwD rated QoL more positively at 20-month follow-up and nearly one-third rated QoL more negatively. These changes could be regarded as reliable in one-quarter of the sample. Participants taking AChEI medication at baseline were more likely to show a decline in QoL score. There were no other significant differences between those whose scores increased, decreased or stayed the same on any demographic or disease-related variables, or in mood or perceived quality of relationship with the carer. While baseline QoL score was the strongest predictor of QoL at 20 months, the quality of relationship with the carer as perceived by the PwD was also independently a significant predictor. Conclusions: There is a degree of individual variation in QoL trajectories. Use of AChEI medication appears linked to decline in QoL score, while positive relationships with carers play an important role in maintaining QoL in early-stage dementia

Shifting visual perspective during retrieval shapes autobiographical memories

The dynamic and flexible nature of memories is evident in our ability to adopt multiple visual perspectives. Although autobiographical memories are typically encoded from the visual perspective of our own eyes they can be retrieved from the perspective of an observer looking at our self. Here, we examined the neural mechanisms of shifting visual perspective during long-term memory retrieval and its influence on online and subsequent memories using functional magnetic resonance imaging (fMRI). Participants generated specific autobiographical memories from the last five years and rated their visual perspective. In a separate fMRI session, they were asked to retrieve the memories across three repetitions while maintaining the same visual perspective as their initial rating or by shifting to an alternative perspective. Visual perspective shifting during autobiographical memory retrieval was supported by a linear decrease in neural recruitment across repetitions in the posterior parietal cortices. Additional analyses revealed that the precuneus, in particular, contributed to both online and subsequent changes in the phenomenology of memories. Our findings show that flexibly shifting egocentric perspective during autobiographical memory retrieval is supported by the precuneus, and suggest that this manipulation of mental imagery during retrieval has consequences for how memories are retrieved and later remembered