Fermentation of deproteinized cheese whey powder solutions to ethanol by engineered Saccharomyces cerevisiae : effect of supplementation with corn steep liquor and repeated-batch operation with biomass recycling by flocculation

The lactose in cheese whey is an interesting substrate for the production of bulk commodities such as bio-ethanol, due to the large amounts of whey surplus generated globally. In this work, we studied the performance of a recombinant Saccharomyces cerevisiae strain expressing the lactose permease and intracellular ß-galactosidase from Kluyveromyces lactis in fermentations of deproteinized concentrated cheese whey powder solutions. Supplementation with 10 g/l of corn steep liquor significantly enhanced whey fermentation, resulting in the production of 7.4% (v/v) ethanol from 150 g/l initial lactose in shake-flask fermentations, with a corresponding productivity of 1.2 g/l/h. The flocculation capacity of the yeast strain enabled stable operation of a repeated-batch process in a 5.5-l air-lift bioreactor, with simple biomass recycling by sedimentation of the yeast flocs. During five consecutive batches, the average ethanol productivity was 0.65 g/l/h and ethanol accumulated up to 8% (v/v) with lactose-toethanol conversion yields over 80% of theoretical. Yeast viability (>97%) and plasmid retention (>84%) remained high throughout the operation, demonstrating the stability and robustness of the strain. In addition, the easy and inexpensive recycle of the yeast biomass for repeated utilization makes this process economically attractive for industrial implementation.Fundação para a Ciência e a Tecnologia (FCT)LACTOGAL-Produtos Alimentares S.A.Companhia Portuguesa de Amidos, S.A

Prospect theory, mitigation and adaptation to climate change

Climate change is one of the most pressing challenges in current environmental policy. Appropriate policies intended to stimulate efficient adaptation and mitigation should not exclusively rely on the assumption of the homo oeconomicus, but take advantage of well-researched alternative behavioural patterns. Prospect theory provides a number of climate-relevant insights, such as the notion that evaluations of outcomes are reference dependent, and the relevance of perceived certainty of outcomes. This paper systematically reviews what prospect theory can offer to analyse mitigation and adaptation. It is shown that accounting for reference dependence and certainty effects contributes to a better understanding of some well-known puzzles in the climate debate, including (but not limited to) the different uptake of mitigation and adaptation amongst individuals and nations, the role of technical vs. financial adaptation, and the apparent preference for hard protection measures in coastal adaptation. Finally, concrete possibilities for empirical research on these effects are proposed

Relationship between the Sensory-Determined Astringency and the Flavanolic Composition of Red Wines

[EN] The relationship between the proanthocyanidin profile and the perceived astringency was assessed in 13 commercial Tempranillo red wines. The concentration and compositional information were obtained by liquid chromatography with diode array detection coupled to electrospray ionization mass spectrometry after acid-catalyzed depolymerization of wine proanthocyanidins in the presence of excess phloroglucinol. Statistical analysis of the results showed significant correlations between sensory and chemical determinations. Astringency was more affected by the subunit composition than by the total concentration or the average degree of polymerization of wine proanthocyanidins. Higher proportions of epicatechin (EC) subunits in extension positions and gallocatechin (GC) subunits in terminal positions were shown to increase astringency. On the contrary, the amount of epigallocatechin (EGC) in both extension and terminal positions was negatively correlated with the perceived astringency

Assessment of the reliability of the motor unit size index (MUSIX) in single subject “round-robin” and multi-centre settings

Objective The motor unit size index (MUSIX) is incorporated into the motor unit number index (MUNIX). Our objective was to assess the intra-/inter-rater reliability of MUSIX in healthy volunteers across single subject “round robin” and multi-centre settings. Methods Data were obtained from i). a round-robin assessment in which 12 raters (6 with prior experience and 6 without) assessed six muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis and abductor hallucis) and ii). a multi-centre study with 6 centres studying the same muscles in 66 healthy volunteers. Intra/inter-rater data were provided by 5 centres, 1 centre provided only intra-rater data. Intra/inter-rater variability was assessed using the coefficient of variation (COV), Bland-Altman plots, bias and 95% limits of agreement. Results In the round-robin assessment intra-rater COVs for MUSIX ranged from 7.8% to 28.4%. Inter-rater variability was between 7.8% and 16.2%. Prior experience did not impact on MUSIX values. In the multi-centre study MUSIX was more consistent than the MUNIX. Abductor hallucis was the least reliable muscle. Conclusions The MUSIX is a reliable neurophysiological biomarker of reinnervation. Significance MUSIX could provide insights into the pathophysiology of a range of neuromuscular disorders, providing a quantitative biomarker of reinnervation

Documentation FiFoSiM: Integrated Tax Benefit Microsimulation and CGE Model

ABSTRACT: This paper describes FiFoSiM, the integrated tax benefit microsimulation and computable general equilibrium (CGE) model of the Center of Public Economics at the University of Cologne. FiFoSiM consists of three main parts. The first part is a static tax benefit microsimulation module. The second part adds a behavioural component to the model: an econometrically estimated labour supply model. The third module is a CGE model which allows the user of FiFoSiM to assess the global economic effects of policy measures. Two specific features distinguish FiFoSiM from other tax benefit models: First, the simultaneous use of two databases for the tax benefit module and second, the linkage of the tax benefit model to a CGE model

Escherichia coli Frameshift Mutation Rate Depends on the Chromosomal Context but Not on the GATC Content Near the Mutation Site

Different studies have suggested that mutation rate varies at different positions in the genome. In this work we analyzed if the chromosomal context and/or the presence of GATC sites can affect the frameshift mutation rate in the Escherichia coli genome. We show that in a mismatch repair deficient background, a condition where the mutation rate reflects the fidelity of the DNA polymerization process, the frameshift mutation rate could vary up to four times among different chromosomal contexts. Furthermore, the mismatch repair efficiency could vary up to eight times when compared at different chromosomal locations, indicating that detection and/or repair of frameshift events also depends on the chromosomal context. Also, GATC sequences have been proved to be essential for the correct functioning of the E. coli mismatch repair system. Using bacteriophage heteroduplexes molecules it has been shown that GATC influence the mismatch repair efficiency in a distance- and number-dependent manner, being almost nonfunctional when GATC sequences are located at 1 kb or more from the mutation site. Interestingly, we found that in E. coli genomic DNA the mismatch repair system can efficiently function even if the nearest GATC sequence is located more than 2 kb away from the mutation site. The results presented in this work show that even though frameshift mutations can be efficiently generated and/or repaired anywhere in the genome, these processes can be modulated by the chromosomal context that surrounds the mutation site

TCR activation stimulates regulated intramembrane proteolysis of L-selectin by presenilin 1 and localized proteasomal degradation of the cytoplasmic tail

Leucocyte (L)-selectin is essential for mounting protective immunity to pathogens. As well as regulating leucocyte recruitment, it also regulates their activation and differentiation inside tissues thereby shaping local immune responses. The biochemical signals that regulate these diverse functions of L-selectin are poorly understood. Leucocyte activation induces proteolytic shedding of L-selectin ectodomain (ECD) but the impact of ECD shedding on signalling downstream of L-selectin is not known. In T cells there is substantial overlap between signalling downstream of L-selectin and the TCR. Cross-linking of L-selectin stimulates phosphorylation of the cytoplasmic tail and forward signalling via the non-receptor tyrosine kinases Lck and Zap70. Cross-linking of TCR induces phosphorylation-dependent binding of PKC isozymes to L-selectin cytoplasmic tail and PKCα dependent shedding of ectodomain (ECD). To further understand the role of L-selectin in T cell biology, we used T cells to dissect the crosstalk between L-selectin and physiological TCR activation. We used a combination of imaging flow cytometry and biochemistry to localise L-selectin ECD and intracellular domain (ICD) following engagement of the TCR. We show that following ADAM17 dependent ECD shedding from the plasma membrane, the ICD containing transmembrane retained fragment undergoes intramembrane proteolysis by PS1 containing γ-secretase. Subsequent degradation of L-selectin ICD occurs via the proteasome in the vicinity of the plasma membrane. Regulated intramembrane proteolysis and rapid degradation of L-selectin ICD following TCR activation suggests that the turnover of L-selectin cytoplasmic tail is an important regulator of T cell co-stimulation by L-selectin

Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia

Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course. Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy. Through a structure-activity relationship (SAR) study, we developed an HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers. KT-531 displayed strong HDAC6 inhibitory potency and selectivity, on-target biological activity, and a safe therapeutic window in nontransformed cell lines. In primary T-PLL patient cells, where HDAC6 was found to be overexpressed, KT-531 exhibited strong biological responses, and safety in healthy donor samples. Notably, combination studies in T-PLL patient samples demonstrated KT-531 synergizes with approved cancer drugs, bendamustine, idasanutlin, and venetoclax. Our work suggests HDAC inhibition in T-PLL could afford sufficient therapeutic windows to achieve durable remission either as standalone or in combination with targeted drugs.Peer reviewe