The critical role of water in spider silk and its consequence for protein mechanics

Due to its remarkable mechanical and biological properties, there is considerable interest in understanding, and replicating, spider silk's stress-processing mechanisms and structure-function relationships. Here, we investigate the role of water in the nanoscale mechanics of the different regions in the spider silk fibre, and their relative contributions to stress processing. We propose that the inner core region, rich in spidroin II, retains water due to its inherent disorder, thereby providing a mechanism to dissipate energy as it breaks a sacrificial amide-water bond and gains order under strain, forming a stronger amide-amide bond. The spidroin I-rich outer core is more ordered under ambient conditions and is inherently stiffer and stronger, yet does not on its own provide high toughness. The markedly different interactions of the two proteins with water, and their distribution across the fibre, produce a stiffness differential and provide a balance between stiffness, strength and toughness under ambient conditions. Under wet conditions, this balance is destroyed as the stiff outer core material reverts to the behaviour of the inner core.

Improving SEA procedures within Italian regions: Towards a more effective evaluation of urban sustainability

Sustainable urban development, a major issue at global scale, will become more relevant according to population growth predictions in developed and developing countries. Societal and international recognition of sustainability concerns led to the development of specific tools and procedures, known as sustainability assessments/appraisals (SA). Their effectiveness however, considering that global quality life indicators have worsened since their introduction, has promoted a re-thinking of SA instruments. More precisely, Strategic Environmental Assessment (SEA), – a tool introduced in the European context to evaluate policies, plans, and programmes (PPPs), – is being reconsidered because of several features that seem to limit its effectiveness. Over time, SEA has evolved in response to external and internal factors dealing with technical, procedural, planning and governance systems thus involving a shift of paradigm from EIA-based SEAs (first generation protocols) towards more integrated approaches (second generation ones). Changes affecting SEA are formalised through legislation in each Member State, to guide institutions at regional and local level. Defining SEA effectiveness is quite difficult. Its’ capacity-building process appears quite far from its conclusion, even if any definitive version can be conceptualized. In this paper, we consider some European nations with different planning systems and SA traditions. After the identification of some analytical criteria, a multi-dimensional cluster analysis is developed on some case studies, to outline current weaknesses.

Improving SEA prodedures within Italian regions: Towards a more effective evaluation of urban sustainability

Sustainable urban development, a major issue at global scale, will become more relevant according to population growth predictions in developed and developing countries. Societal and international recognition of sustainability concerns led to the development of specific tools and procedures, known as sustainability assessments/appraisals (SA). Their effectiveness however, considering that global quality life indicators have worsened since their introduction, has promoted a re-thinking of SA instruments. More precisely, Strategic Environmental Assessment (SEA), – a tool introduced in the European context to evaluate policies, plans, and programmes (PPPs), – is being reconsidered because of several features that seem to limit its effectiveness. Over time, SEA has evolved in response to external and internal factors dealing with technical, procedural, planning and governance systems thus involving a shift of paradigm from EIA-based SEAs (first generation protocols) towards more integrated approaches (second generation ones). Changes affecting SEA are formalised through legislation in each Member State, to guide institutions at regional and local level. Defining SEA effectiveness is quite difficult. Its’ capacity-building process appears quite far from its conclusion, even if any definitive version can be conceptualized. In this paper, we consider some European nations with different planning systems and SA traditions. After the identification of some analytical criteria, a multi-dimensional cluster analysis is developed on some case studies, to outline current weaknesses.

Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2x10(-201)), ABCG2 (p = 3.1x10(-26)), SLC17A1 (p = 3.0x10(-14)), SLC22A11 (p = 6.7x10(-14)), SLC22A12 (p = 2.0x10(-9)), SLC16A9 (p = 1.1x10(-8)), GCKR (p = 1.4x10(-9)), LRRC16A (p = 8.5x10(-9)), and near PDZK1 (p = 2.7x10(-9)). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0x10(-26)) and propionyl-L-carnitine (p = 5.0x10(-8)) concentrations, which in turn were associated with serum UA levels (p = 1.4x10(-57) and p = 8.1x10(-54), respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels.

Elevated levels of PFOS and PFHxS in firefighters exposed to aqueous film forming foam (AFFF)

Exposure to aqueous film forming foam (AFFF) was evaluated in 149 firefighters working at AFFF training facilities in Australia by analysis of PFOS and related compounds in serum. A questionnaire was designed to capture information about basic demographic factors, lifestyle factors and potential occupational exposure (such as work history and self-reported skin contact with foam). The results showed that a number of factors were associated with PFAA serum concentrations. Blood donation was found to be linked to low PFAA levels, and the concentrations of PFOS and PFHxS were found to be positively associated with years of jobs with AFFF contact. The highest levels of PFOS and PFHxS were one order of magnitude higher compared to the general population in Australia and Canada. Study participants who had worked ten years or less had levels of PFOS that were similar to or only slightly above those of the general population. This coincides with the phase out of 3M AFFF from all training facilities in 2003, and suggests that the exposures to PFOS and PFHxS in AFFF have declined in recent years. Self-reporting of skin contact and frequency of contact were used as an index of exposure. Using this index, there was no relationship between PFOS levels and skin exposure. This index of exposure is limited as it relies on self-report and it only considers skin exposure to AFFF, and does not capture other routes of potential exposure. Possible associations between serum PFAA concentrations and five biochemical outcomes were assessed. The outcomes were serum cholesterol, triglycerides, high-density lipoproteins, low density lipoproteins, and uric acid. No statistical associations between any of these endpoints and serum PFAA concentrations were observed.

"It's not the Jedi way!": Moral ambivalence and delivering the 'good' in Star Wars

This article examines the nature of good and evil through the prism of Star Wars, arguing that the ostensible dichotomy between the ‘good’ Jedi and the ‘evil’ Sith is false, and instead both the Jedi and the Sith engage in violence, which is evil. Anakin Skywalker then arrives as the Christ-figure who becomes evil and ‘dies’ to destroy the old rigid law of the letter adhered to by the Jedi, before resurrecting and sacrificing himself to defeat the Sith transgressors. As Milbank argues, the act of selfless love by Anakin as the Christ-figure therefore produces the good, the end of violent conflict which is ontological peace, and institutes the law of love which leads to life and peace.