Toxic DNA-protein crosslinks (DPCs) arise by ionizing irradiation and UV light, are particularly caused by endogenously produced reactive compounds such as formaldehyde, and also occur during ...compromised topoisomerase action. Although nucleotide excision repair and homologous recombination contribute to cell survival upon DPCs, hardly anything is known about mechanisms that target the protein component of DPCs directly. Here, we identify the metalloprotease Wss1 as being crucial for cell survival upon exposure to formaldehyde and topoisomerase 1-dependent DNA damage. Yeast mutants lacking Wss1 accumulate DPCs and exhibit gross chromosomal rearrangements. Notably, in vitro assays indicate that substrates such as topoisomerase 1 are processed by the metalloprotease directly and in a DNA-dependent manner. Thus, our data suggest that Wss1 contributes to survival of DPC-harboring cells by acting on DPCs proteolytically. We propose that DPC proteolysis enables repair of these unique lesions via downstream canonical DNA repair pathways.
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•The metalloprotease Wss1 targets DNA-protein crosslinks•Wss1 cleaves its substrates in a DNA-dependent manner•DNA-protein crosslink repair by Wss1 promotes genome stability•Wss1 action enables translesion synthesis of DNA-protein crosslinks
The metalloprotease Wss1 enables the repair of DNA-protein crosslinks by targeting their protein components in a DNA-dependent manner.
If mutual recognition is to be the 'cornerstone of judicial co‐operation' in the area of freedom, security and justice, mutual trust, on the other hand, must take a lead role as the normative glue ...that grounds and facilitates legal practices of recognition. Despite its topicality and practical relevance, the theoretical underpinnings of trust have been largely left untouched by legal scholarship. This article seeks to fill that void by unpacking trust's conceptual premises to prepare a critique of the legal principle of mutual trust and its underlying ideology as it emerged in the jurisprudence of the CJEU. It presents an enriched conceptualization of recognition trust, inquires into the potential and risks of trust‐based judicial cooperation and sheds light on the interplay of trust, distrust and the law. In drawing policy conclusions from the theoretical discussion, it also points to a new normative dimension of trust asking whether trust could feature as a form of mutual recognition.
We investigate the “generalized second-price” (GSP) auction, a new mechanism used by search engines to sell online advertising. Although GSP looks similar to the Vickrey-Clarke-Groves (VCG) ...mechanism, its properties are very different. Unlike the VCG mechanism, GSP generally does not have an equilibrium in dominant strategies, and truth-telling is not an equilibrium of GSP. To analyze the properties of GSP, we describe the generalized English auction that corresponds to GSP and show that it has a unique equilibrium. This is an ex post equilibrium, with the same payoffs to all players as the dominant strategy equilibrium of VCG. (JEL D44, L81, M37)
In the conversion problem, wealth has to be distributed between two assets with the objective to maximize the wealth at the end of the investment horizon. The bi-directional preemptive conversion ...problem with a constant price interval is the only problem, of the four main variants of the conversion problem, that has not yet been optimally solved by competitive analysis. Assuming a given number of monotonous price trends called runs, lower and upper bounds for the competitive ratio are given. In this work, the assumption of a given number of runs is rejected and lower and upper bounds for the bi-directional preemptive conversion problem with a constant price interval are given. Furthermore, an algorithm based on error balancing is given which at minimum achieves the given upper bound. It can also be shown that this algorithm is optimal for the single-period model.
The origin of sterile worker castes, resulting in eusociality, represents one of the major evolutionary transitions in the history of life. Understanding how eusociality has evolved is therefore an ...important issue for understanding life on earth. Here we show that in the large bee subfamily Xylocopinae, a simple form of sociality was present in the ancestral lineage and there have been at least four reversions to purely solitary nesting. The ancestral form of sociality did not involve morphological worker castes and maximum colony sizes were very small. True worker castes, entailing a life-time commitment to non-reproductive roles, have evolved only twice, and only one of these resulted in discrete queen-worker morphologies. Our results indicate extremely high barriers to the evolution of eusociality. Its origins are likely to have required very unusual life-history and ecological circumstances, rather than the amount of time that selection can operate on more simple forms of sociality.
In this paper, we consider a dynamic game of incomplete information used to sell sponsored search advertisements. We also consider a corresponding static game of complete information. We analyze the ...underlying dynamic game of incomplete information, and we establish an upper bound on the revenue of any equilibrium of any dynamic game in this environment. We then exclude equlibria of the corresponding static game with revenue that exceeds this upper bound. We characterize optimal reserve prices and show that the optimal reserve price is independent of the number of bidders and independent of the rate at which click-through rate declines over positions. We show that most of the incremental revenue from setting a reserve price optimally comes not from the low bidder's direct effect, and not from indirect effects of other low bidders, but rather from the indirect effects on high bidders.
Due to the relatively high tolerance and resistance to sanitizers, biofilms can persist in the environment resulting in cross-contamination. The overall goal of this study was to evaluate the impact ...of nanobubbles (NB) alone and in combination with neutral electrolyzed water (NEW) on different microbial biofilms including
Escherichia coli
O157:H7,
Vibrio parahaemolyticus
, and
Listeria innocua
on plastic and stainless steel (SS) coupons. NB alone completely removed
V. parahaemolyticus
biofilm on both plastic and SS coupons after 2 min. NB alone caused about a 1 to 3 log CFU/cm
2
reduction of
E. coli
and
L. innocua
biofilms, while a complete reduction was observed only after combining NB with NEW. The antiadhesion results of NB-treated plastic and SS coupons showed lower bacterial adhesion to NB-treated surfaces indicating that NB can attach to the surface and reduce the surface tension and bacterial adhesion. Surface-enhanced Raman spectroscopy spectra (SERS) and mapping results revealed the ability of NB to remove the bacterial biofilms. Raman spectra intensity was reduced at bands associated with carbohydrates, protein, and DNA indicating extracellular polymeric substance (EPS) disruption. This study demonstrates that NB could be a viable technology for removing microbial biofilms from surfaces and enhancing the efficacy of conventional sanitizers.
ABSTRACT
How sociality evolves and is maintained remains a key question in evolutionary biology. Most studies to date have focused on insects, birds, and mammals but data from a wider range of ...taxonomic groups are essential to identify general patterns and processes. The extent of social behaviour among squamate reptiles is under‐appreciated, yet they are a promising group for further studies. Living in aggregations is posited as an important step in the evolution of more complex sociality. We review data on aggregations among squamates and find evidence for some form of aggregations in 94 species across 22 families. Of these, 18 species across 7 families exhibited ‘stable’ aggregations that entail overlapping home ranges and stable membership in long‐term (years) or seasonal aggregations. Phylogenetic analysis suggests that stable aggregations have evolved multiple times in squamates. We: (i) identify significant gaps in our understanding; (ii) outline key traits which should be the focus of future research; and (iii) outline the potential for utilising reproductive skew theory to provide insights into squamate sociality.
Liver cirrhosis accounts for considerable morbidity and mortality worldwide and late presentation limits therapeutic options. We aimed to assess characteristics of patients with liver cirrhosis at ...the time of first presentation and during their clinical course. 476 patients were included (alcohol-related liver disease, ALD: 211, 44.3%; viral hepatitis: 163, 34.2%). Of these, 106 patients (22.3%) and 160 patients (33.6%) presented already with Child-Pugh C and MELD >15, respectively, and decompensation events were registered in 50% (238 patients) at baseline, and even in 75.4% of ALD patients. Half of the patients with cirrhosis had decompensated cirrhosis at presentation. This calls for increased awareness and strategies for earlier diagnosis of chronic liver disease and cirrhosis.
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