Acceptable Risk

Perhaps the topic of acceptable risk never had a sexier and more succinct introduction than the one Edward Norton, playing an automobile company executive, gave it in Fight Club: “Take the number of vehicles in the field (A), multiply it by the probable rate of failure (B), and multiply the result by the average out of court settlement (C). A*B*C=X. If X is less than the cost of the recall, we don’t do one.” Of course, this dystopic scene also gets to the heart of the issue in another way: acceptable risk deals with mathematical calculations about the value of life, injury, and emotional wreckage, making calculation a difficult matter ethically, politically, and economically. This entry will explore the history of this idea, focusing on its development alongside statistics into its wide importance today

Increase in Ethanol Yield via Elimination of Lactate Production in an Ethanol-Tolerant Mutant of Clostridium Thermocellum

Large-scale production of lignocellulosic biofuel is a potential solution to sustainably meet global energy needs. One-step consolidated bioprocessing (CBP) is a potentially advantageous approach for the production of biofuels, but requires an organism capable of hydrolyzing biomass to sugars and fermenting the sugars to ethanol at commercially viable titers and yields. Clostridium thermocellum, a thermophilic anaerobe, can ferment cellulosic biomass to ethanol and organic acids, but low yield, low titer, and ethanol sensitivity remain barriers to industrial production. Here, we deleted the hypoxanthine phosphoribosyltransferase gene in ethanol tolerant strain of C. thermocellum adhE*(EA) in order to allow use of previously developed gene deletion tools, then deleted lactate dehydrogenase (ldh) to redirect carbon flux towards ethanol. Upon deletion of ldh, the adhE*(EA) Δldh strain produced 30% more ethanol than wild type on minimal medium. The adhE*(EA) Δldh strain retained tolerance to 5% v/v ethanol, resulting in an ethanol tolerant platform strain of C. thermocellum for future metabolic engineering efforts

Complete Genome Sequence of Salinisphaera sp. Strain LB1, a Moderately Halo-Acidophilic Bacterium Isolated from Lake Brown, Western Australia

Salinisphaera sp. strain LB1 was isolated from Lake Brown, Western Australia, surface water enriched at pH 4.0 and with 5% (wt/vol) NaCl. The complete genome sequence is presented in this report

Elimination of Hydrogenase Active Site Assembly Blocks H2 Production and Increases Ethanol Yield in Clostridium Thermocellum

Background: The native ability of Clostridium thermocellum to rapidly consume cellulose and produce ethanol makes it a leading candidate for a consolidated bioprocessing (CBP) biofuel production strategy. C. thermocellum also synthesizes lactate, formate, acetate, H2 , and amino acids that compete with ethanol production for carbon and electrons. Elimination of H2 production could redirect carbon flux towards ethanol production by making more electrons available for acetyl coenzyme A reduction to ethanol. Results: H2 production in C. thermocellum is encoded by four hydrogenases. Rather than delete each individually, we targeted hydrogenase maturase gene hydG, involved in converting the three [FeFe] hydrogenase apoenzymes into holoenzymes. Further deletion of the [NiFe] hydrogenase (ech) resulted in a mutant that functionally lacks all four hydrogenases. H2 production in ΔhydGΔech was undetectable, and the ethanol yield nearly doubled to 64% of the maximum theoretical yield. Genomic analysis of ΔhydG revealed a mutation in adhE, resulting in a strain with both NADH- and NADPH-dependent alcohol dehydrogenase activities. While this same adhE mutation was found in ethanol-tolerant C. thermocellum strain E50C, Δ hydG and ΔhydGΔech are not more ethanol tolerant than the wild type, illustrating the complicated interactions between redox balancing and ethanol tolerance in C. thermocellum. Conclusions: The dramatic increase in ethanol production suggests that targeting protein post-translational modification is a promising new approach for simultaneous inactivation of multiple enzymes

Cognitive mediation in people with dementia:Development, structural, and construct validity of the first dementia‐specific measure

OBJECTIVES: Anxiety and depression are common and deleterious comorbidities in people living with dementia (PLWD). Cognitive behavioural therapy (CBT) is one of the few promising treatments; however, it is unclear whether PLWD have the necessary prerequisites to engage in this. Having an understanding of cognitive mediation, that a thought mediates the relationship between an antecedent event and its emotional consequence, is key for engaging with CBT and is also a critical component of emotion regulation. There are no measures of this construct validated for PLWD. This study aims to adapt and validate an existing measure for this population. A secondary aim is to assess its applicability in older adults (OA) without a recognised neurocognitive impairment. // METHODS: A measure of cognitive mediation was adapted via expert and service user consultation for use in PLWD. A total of 102 PLWD and 77 OA without neurocognitive impairments completed the adapted measure along with two measures of emotion recognition and reasoning. Factor structure was examined separately in both samples, and the measure reduced, with convergent validity assessed. // RESULTS: A final measure of 10 items (named the CM-Dem) was subject to factor analysis yielding a single factor solution. The measure showed good psychometric properties in PLWD, including good model fit, high internal consistency, inter-rater reliability, and moderate convergent validity with related constructs. In contrast, poor validity was found in OA, especially a lack of convergent validity. // CONCLUSIONS: The CM-Dem has clinical and research utility as a measure of cognitive mediation in PLWD, but less so in OA

Characterization of Xylan Utilization and Discovery of a New Endoxylanase in Thermoanaerobacterium Saccharolyticum through Targeted Gene Deletions

The economical production of fuels and commodity chemicals from lignocellulose requires the utilization of both the cellulose and hemicellulose fractions. Xylanase enzymes allow greater utilization of hemicellulose while also increasing cellulose hydrolysis. Recent metabolic engineering efforts have resulted in a strain of Thermoanaerobacterium saccharolyticum that can convert C5 and C6 sugars, as well as insoluble xylan, into ethanol at high yield. To better understand the process of xylan solubilization in this organism, a series of targeted deletions were constructed in the homoethanologenic T. saccharolyticum strain M0355 to characterize xylan hydrolysis and xylose utilization in this organism. While the deletion of -xylosidase xylD slowed the growth of T. saccharolyticum on birchwood xylan and led to an accumulation of short-chain xylo-oligomers, no other single deletion, including the deletion of the previously characterized endoxylanase XynA, had a phenotype distinct from that of the wild type.This result indicates a multiplicity of xylanase enzymes which facilitate xylan degradation in T. saccharolyticum. Growth on xylan was prevented only when a previously uncharacterized endoxylanase encoded by xynC was also deleted in conjunction with xynA. Sequence analysis of xynC indicates that this enzyme, a low-molecular-weight endoxylanase with homology to glycoside hydrolase family 11 enzymes, is secreted yet untethered to the cell wall. Together, these observations expand our understanding of the enzymatic basis of xylan hydrolysis by T. saccharolyticum