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Evolutionary repurposing of a sulfatase : A new Michaelis complex leads to efficient transition state charge offset

The recruitment and evolutionary optimization of promiscuous enzymes is key to the rapid adaptation of organisms to changing environments. Our understanding of the precise mechanisms underlying enzyme repurposing is, however, limited: What are the active-site features that enable the molecular recognition of multiple substrates with contrasting catalytic requirements? To gain insights into the mol

Empirical Valence Bond Simulations Suggest a Direct Hydride Transfer Mechanism for Human Diamine Oxidase

Diamine oxidase (DAO) is an enzyme involved in the regulation of cell proliferation and the immune response. This enzyme performs oxidative deamination in the catabolism of biogenic amines, including, among others, histamine, putrescine, spermidine, and spermine. The mechanistic details underlying the reductive half-reaction of the DAO-catalyzed oxidative deamination which leads to the reduced enz

Role of Ligand-Driven Conformational Changes in Enzyme Catalysis : Modeling the Reactivity of the Catalytic Cage of Triosephosphate Isomerase

We have previously performed empirical valence bond calculations of the kinetic activation barriers, Δ G‡calc, for the deprotonation of complexes between TIM and the whole substrate glyceraldehyde-3-phosphate (GAP, Kulkarni et al. J. Am. Chem. Soc. 2017 , 139 , 10514 - 10525 ). We now extend this work to also study the deprotonation of the substrate pieces glycolaldehyde (GA) and GA·HPi [HPi = pho

Challenges and advances in the computational modeling of biological phosphate hydrolysis

Phosphate ester hydrolysis is fundamental to many life processes, and has been the topic of substantial experimental and computational research effort. However, even the simplest of phosphate esters can be hydrolyzed through multiple possible pathways that can be difficult to distinguish between, either experimentally, or computationally. Therefore, the mechanisms of both the enzymatic and non-enz

Arbetsgivarens rehabiliteringsansvar vid alkoholmissbruk - Vilka skyldigheter har arbetsgivaren att genomföra rehabilitering då arbetstagaren har alkoholmissbruk och i vilken utsträckning behöver arbetstagaren delta i dessa?

Synen på alkoholmissbruk har skiftat genom tiderna. Till en början sågs missbruket som en samhällsfara där lösningen var att isolera individen från övriga samhället. Detta synsätt skiljer sig från det nuvarande där det finns ett samhällsintresse för en arbetstagare som lider av alkoholmissbruk för att denne ska få tidiga stödinsatser och förhoppningsvis med hjälp av dessa åtgärder kvarbli i arbetsThe perception of alcohol abuse has evolved over time. Initially, abuse was seen as a societal threat, with the solution being to isolate the individual from the rest of society. This perspective differs from the current approach, where there is a societal interest in supporting an employee suffering from alcohol abuse through early interventions, The aim is to support the employee to remain in th

Complex Genomic Landscape of Inversion Polymorphism in Europe’s Most Destructive Forest Pest

In many species, polymorphic genomic inversions underlie complex phenotypic polymorphisms and facilitate local adaptation in the face of gene flow. Multiple polymorphic inversions can co-occur in a genome, but the prevalence, evolutionary significance, and limits to complexity of genomic inversion landscapes remain poorly understood. Here, we examine genome-wide genetic variation in one of Europe’

Sociodemographic differences in the response to changes in COVID-19 testing guidelines

During the coronavirus disease 2019 (COVID-19) pandemic, Sweden emphasized voluntary guidelines over mandates. We exploited a rapid change and reversal of the Public Health Agency of Sweden's COVID-19 testing guidelines for vaccinated and recently infected individuals as a quasi-experiment to examine sociodemographic differences in the response to changes in pandemic guidelines. We analyzed daily

Identification of sentinel lymph node macrometastasis in breast cancer by deep learning based on clinicopathological characteristics

The axillary lymph node status remains an important prognostic factor in breast cancer, and nodal staging using sentinel lymph node biopsy (SLNB) is routine. Randomized clinical trials provide evidence supporting de-escalation of axillary surgery and omission of SLNB in patients at low risk. However, identifying sentinel lymph node macrometastases (macro-SLNMs) is crucial for planning treatment ta

Envisioning post-growth marketing : A dystopian-optimist’s guide

This article introduces a mode of thought called dystopian optimism in response to the question of how critical marketing can be made more optimistic. Dystopian optimism counters both the utopian-optimistic belief that the climate crisis can be solved from within the current growth-capitalist system, and the dystopian pessimism of terminal marketing. We propose degrowth as a means to revitalise cr

The association between working hours and working type with non-alcoholic fatty liver disease: results from the NHANES 1999-2014

Background: Previous research has indicated that long working hours are connected to a variety of health conditions, including nonalcoholic fatty liver disease (NAFLD). However, this association which has been observed in more population is limited. Our research is designed to evaluate the association between working hours, working type, and NAFLD.Methods: The study comprised adults with complete

Selection of random RNA fragments as method for searching for a site of regulation of translation of E. coli streptomycin mRNA by ribosomal protein S7

In E. coli cells ribosomal small subunit biogenesis is regulated by RNA-protein interactions involving protein S7. S7 initiates the subunit assembly interacting with 16S rRNA. During shift-down of rRNA synthesis level, free S7 inhibits self-translation by interacting with 96 nucleotides long specific region of streptomycin (str) mRNA between cistrons S12 and S7 (intercistron). Many bacteria do not

Instituting: How an archipelago is formed?

Instituting or How is an archipelago formed?Exhibition of contemporary art curated by Gigi Argyropoulou, Vassilis Noulas and Kostas TzimoulisEIGHT, cultural institute for arts and politics, Polytechnic 8, AthensParticipants: Dimitris Ioannou, Dionysis Kavallieratos, Panagiotis Kefalas, Chrysanthi Koumianaki, Maria Mavropoulou, Theano Metaxa, Maria Papadimitriou, Christina Petkopoulou, Poka-Yio, E.

Closed-loop design for scalable performance of vehicular formations

This paper presents a novel control design for vehicular formations as an alternative to alignment through conventional consensus protocols for second-order systems. The design is motivated by the closed-loop system, which we construct as first-order systems connected in series, and is therefore called serial consensus. The serial consensus design will guarantee the stability of the closed-loop sy

Hypercompetition in biomedical research evaluation and its impact on young scientist careers

Recent years have seen tremendous changes in the modes of publication and dissemination of biomedical information, with the introduction of countless new publishers and publishing models, as well as alternative modes of research evaluation. In parallel, we are witnessing an unsustainable explosion in the amount of information generated by each individual scientist, at the same time as many countri