A general neurologist\u27s perspective on the urgent need to apply resilience thinking to the prevention and treatment of Alzheimer\u27s disease

The goal of this article was to look at the problem of Alzheimer\u27s disease (AD) through the lens of a socioecological resilience-thinking framework to help expand our view of the prevention and treatment of AD. This serious and complex public health problem requires a holistic systems approach. We present the view that resilience thinking, a theoretical framework that offers multidisciplinary approaches in ecology and natural resource management to solve environmental problems, can be applied to the prevention and treatment of AD. Resilience thinking explains a natural process that occurs in all complex systems in response to stressful challenges. The brain is a complex system, much like an ecosystem, and AD is a disturbance (allostatic overload) within the ecosystem of the brain. Resilience thinking gives us guidance, direction, and ideas about how to comprehensively prevent and treat AD and tackle the AD epidemic

Structures of Sortase B from Staphylococcus aureus and Bacillus anthracis Reveal Catalytic Amino Acid Triad in the Active Site

Surface proteins attached by sortases to the cell wall envelope of bacterial pathogens play important roles during infection. Sorting and attachment of these proteins is directed by C-terminal signals. Sortase B of S. aureus recognizes a motif NPQTN, cleaves the polypeptide after the Thr residue, and attaches the protein to pentaglycine cross-bridges. Sortase B of B. anthracis is thought to recognize the NPKTG motif, and attaches surface proteins to m-diaminopimelic acid cross-bridges. We have determined crystal structure of sortase B from B. anthracis and S. aureus at 1.6 and 2.0 Å resolutions, respectively. These structures show a β-barrel fold with α-helical elements on its outside, a structure thus far exclusive to the sortase family. A putative active site located on the edge of the β-barrel is comprised of a Cys-His-Asp catalytic triad and presumably faces the bacterial cell surface. A putative binding site for the sorting signal is located nearby

The Immunomodulator 1-Methyltryptophan Drives Tryptophan Catabolism Toward the Kynurenic Acid Branch

Background: Animal model studies revealed that the application of 1-methyltryptophan (1-MT), a tryptophan (TRP) analog, surprisingly increased plasma levels of the TRP metabolite, kynurenic acid (KYNA). Under inflammatory conditions, KYNA has been shown to mediate various immunomodulatory effects. Therefore, the present study aims to confirm and clarify the effects of 1-MT on TRP metabolism in mice as well as in humans. Methods: Splenocytes from Balb/C or indoleamine 2,3-dioxygenase knockout (IDO1−/−) mice or whole human blood were stimulated with 1-MT for 6, 24, or 36 h. C57BL/6 mice received 1-MT in drinking water for 5 days. Cell-free supernatants and plasma were analyzed for TRP and its metabolites by tandem mass spectrometry (MS/MS). Results: 1-MT treatment induced an increase in TRP and its metabolite, KYNA in Balb/C, IDO−/− mice, and in human blood. Concurrently, the intermediate metabolite kynurenine (KYN), as well as the KYN/TRP ratio, were reduced after 1-MT treatment. The effects of 1-MT on TRP metabolites were similar after the in vivo application of 1-MT to C57BL/6 mice. Conclusions: The data indicate that 1-MT induced an increase of KYNA ex vivo and in vivo confirming previously described results. Furthermore, the results of IDO−/− mice indicate that this effect seems not to be mediated by IDO1. Due to the proven immunomodulatory properties of KYNA, a shift toward this branch of the kynurenine pathway (KP) may be one potential mode of action by 1-MT and should be considered for further applications

BIODEGRADATION OF PETROLEUM-WASTE BY BIOSURFACTANT-PRODUCING BACTERIA

The degradation of petroleum waste by mixed bacterial cultures which produce biosurfactants: Ralstonia pickettii SRS (BP-20), Alcaligenes piechaudii SRS (CZOR L-1B), Bacillus subtilis (1'- 1a), Bacillus sp. (T-1) and Bacillus sp. (T'-1) was investigated. The total petroleum hydrocarbons were degraded substantially (91 %) by the mixed bacterial culture in 30 days (reaching up to 29 % in the first 72 h). Similarly, the toxicity of the biodegraded petroleum waste decreased 3 times after 30 days as compared to raw petroleum waste. Thus, the mixed bacterial strains effectively clean-up the petroleum waste and they can be used in other bioremediation processes

Enjoyment of the shopping experience:impact on customers’ repatronage intentions and gender influence

In this paper the authors investigate enjoyment of the shopping experience, its influence on consumers’ intention to repatronise a regional shopping centre and the effect of gender differences on shopping enjoyment. Four dimensions of shopping enjoyment are proposed and a 16-item measure is developed to assess 536 consumer perceptions of the shopping experience across five counties in the United Kingdom. Findings indicate that shopping experience enjoyment has a significant positive influence upon customers’ repatronage intentions. Furthermore, men are found to have a stronger relationship of enjoyment with repatronage than women. The implications of these results are discussed, together with managerial implications, study limitations, and future research directions

Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia

Abstract Cardiac ischaemia-reperfusion (I/R) injury has been attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which include redox imbalance, metabolic stalling and excessive production of reactive oxygen species (ROS). The alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool to reduce oxygen to water, thereby restoring electron flux when impaired and, in the process, blunting ROS production. Hence, AOX represents a natural rescue mechanism from respiratory stress. This study aimed to determine how respiratory restoration through xenotopically expressed AOX affects the re-perfused post-ischaemic mouse heart. As expected, AOX supports ETC function and attenuates the ROS load in post-anoxic heart mitochondria. However, post-ischaemic cardiac remodelling over 3 and 9 weeks was not improved. AOX blunted transcript levels of factors known to be up-regulated upon I/R such as the atrial natriuretic peptide (Anp) whilst expression of pro-fibrotic and pro-apoptotic transcripts were increased. Ex vivo analysis revealed contractile failure at nine but not 3 weeks after ischaemia whilst label-free quantitative proteomics identified an increase in proteins promoting adverse extracellular matrix remodelling. Together, this indicates an essential role for ETC-derived signals during cardiac adaptive remodelling and identified ROS as a possible effector.Peer reviewe

Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia

Abstract Cardiac ischaemia-reperfusion (I/R) injury has been attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which include redox imbalance, metabolic stalling and excessive production of reactive oxygen species (ROS). The alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool to reduce oxygen to water, thereby restoring electron flux when impaired and, in the process, blunting ROS production. Hence, AOX represents a natural rescue mechanism from respiratory stress. This study aimed to determine how respiratory restoration through xenotopically expressed AOX affects the re-perfused post-ischaemic mouse heart. As expected, AOX supports ETC function and attenuates the ROS load in post-anoxic heart mitochondria. However, post-ischaemic cardiac remodelling over 3 and 9 weeks was not improved. AOX blunted transcript levels of factors known to be up-regulated upon I/R such as the atrial natriuretic peptide (Anp) whilst expression of pro-fibrotic and pro-apoptotic transcripts were increased. Ex vivo analysis revealed contractile failure at nine but not 3 weeks after ischaemia whilst label-free quantitative proteomics identified an increase in proteins promoting adverse extracellular matrix remodelling. Together, this indicates an essential role for ETC-derived signals during cardiac adaptive remodelling and identified ROS as a possible effector.Peer reviewe

Strangelet search at RHIC

Two position sensitive Shower Maximum Detector (SMDs) for Zero-Degree Calorimeters (ZDCs) were installed by STAR before run 2004 at both upstream and downstream from the interaction point along the beam axis where particles with small rigidity are swept away by strong magnetic field. The ZDC-SMDs provides information about neutral energy deposition as a function of transverse position in ZDCs. We report the preliminary results of strangelet search from a triggered data-set sampling 100 million Au+Au collisions at top RHIC energy.Comment: Strange Quark Matter 2004 conference proceedin

Correlations in STAR: interferometry and event structure

STAR observes a complex picture of RHIC collisions where correlation effects of different origins -- initial state geometry, semi-hard scattering, hadronization, as well as final state interactions such as quantum intensity interference -- coexist. Presenting the measurements of flow, mini-jet deformation, modified hadronization, and the Hanbury Brown and Twiss effect, we trace the history of the system from the initial to the final state. The resulting picture is discussed in the context of identifying the relevant degrees of freedom and the likely equilibration mechanism.Comment: 8 pages, 6 figures, plenary talk at the 5th International Conference on Physics and Astrophysics of Quark Gluon Plasma, to appear in Journal of Physics G (http://www.iop.org