Recent years have witnessed an explosion of interest in understanding the role of conformational dynamics both in the evolution of new enzymatic activities from existing enzymes and in facilitating the emergence of enzymatic activity de novo on scaffolds that were previously non-catalytic. There are also an increasing number of examples in the literature of targeted engineering of conformational d

Structural and biochemical studies on diverse enzymes have highlighted the importance of ligand-gated conformational changes in enzyme catalysis, where the intrinsic binding energy of the common phosphoryl group of their substrates is used to drive energetically unfavorable conformational changes in catalytic loops, from inactive open to catalytically competent closed conformations. However, compu

GTP hydrolysis is a biologically crucial reaction, being involved in regulating almost all cellular processes. As a result, the enzymes that catalyze this reaction are among the most important drug targets. Despite their vital importance and decades of substantial research effort, the fundamental mechanism of enzyme-catalyzed GTP hydrolysis by GTPases remains highly controversial. Specifically, ho

Genetic variation among orthologous proteins can cause cryptic phenotypic properties that only manifest in changing environments. Such variation may impact the evolvability of proteins, but the underlying molecular basis remains unclear. Here, we performed comparative directed evolution of four orthologous metallo-β-lactamases toward a new function and found that different starting genotypes evolv

Throughout adulthood and ageing our brains undergo structural loss in an average pattern resembling faster atrophy in Alzheimer’s disease (AD). Using a longitudinal adult lifespan sample (aged 30-89; 2–7 timepoints) and four polygenic scores for AD, we show that change in AD-sensitive brain features correlates with genetic AD-risk and memory decline in healthy adults. We first show genetic risk li

Abstract in PolishW latach 1945–1946 dziewięcioro byłych polskich więźniów niemieckich obozów koncentracyjnych (jedna osoba pochodzenia żydowskiego i osiem nieżydowskiego) przebywających na prawach uchodźców w Szwecji otrzymało zadanie spisania doświadczeń wojennych i prześladowań innych Polaków pochodzenia żydowskiego i nieżydowskiego dla potrzeb historii i sprawiedliwości. Choć żadna z tych osóbIn 1945–1946, nine Polish former prisoners of Nazi concentration camps (one Jewish and eight non-Jewish) living in Sweden as refugees were employed to record other Jewish and non-Jewish Poles’ experiences of persecution for history and justice. Although none of these individuals were psychologists, they believed recording the psychological aspects of witnessing was essential to their documentation

In the mammalian brain, new neurons continue to be generated throughout life in a process known as adult neurogenesis. The role of adult-generated neurons has been broadly studied across laboratories, and mounting evidence suggests a strong link to the HPA axis and concomitant dysregulations in patients diagnosed with mood disorders. Psychedelic compounds, such as phenethylamines, tryptamines, can

I uppsatsen utreds vad som förutsätts för ett fungerande informationsutbyte mellan myndigheter. Utifrån svaret på det undersöks huruvida befintliga sekretessbrytande bestämmelser är tillräckliga eller om förslaget om en ny sekretessbrytande bestämmelse behövs såsom den presenteras i det första delbetänkandet för ett förbättrat informationsutbyte som meddelades i september 2024. Undersökningen viThe purpose of this thesis is to investigate what aspects that are significant to achieve a well exchange of information between authorities. Based on that answer the paper analyses whether existing articles that permit an exchange of information despite confidentiality are sufficient, or if there is need of an additional article such as the one that has been suggested in an interim report for an

Idag finns ett stort antal företag som tillhandahåller digitala databaser med söktjänster där användare enkelt kan söka på personuppgifter som namn, adress eller personnummer och få fram omfattande information om svenska invånare. Uppgifter om civilstånd, bolagsinnehav, fastigheter samt om personen ifråga förekommer i tvistemål eller brottmålsdomar ingår bland sökresultaten. Företagen stödjer sig Today, many Swedish companies provide databases which function as search registers where users easily can search for personal data such as name, ad-dress or social security number and obtain comprehensive information on Swedish residents. Information on marital status, company ownership, real estates as well as whether the person in question is involved in civil or criminal cases are included in t

Kollektivtrafikens bytespunkter och hållplatser än mer än platser för väntan – de utgör en central del av stadens liv och människors vardag. För att dessa kollektivtrafikrum ska bli inbjudande och tillgängliga för alla, är det viktigt att vi noggrant överväger hur de planeras och utformas. I den här boken presenteras de viktigaste aspekterna för att säkerställa att dessa platser fungerar som inklu

Demand responsive transport (DRT) is an intermediate form of public transport which is provided based on users’ demand. The study explores the potential of DRT for meeting young people’s travel needs, focusing on school and leisure journeys. Our results, building on a survey study in Sweden, suggest that DRT services offering a door-to-door journey and the flexibility of pick-up times could be com

A few suggestions and advice to increase the success chances of your grant application.

Background: Fungal DNA is rarely reported in metagenomic studies of ancient samples. Although fungi are essential for their interactions with all kingdoms of life, limited information is available about ancient fungi. Here, we explore the possibility of the presence of ancient fungal species in the gut of Ötzi, the Iceman, a naturally mummified human found in the Tyrolean Alps (border between Ital

Catalysis by protein tyrosine phosphatases (PTPs) relies on the motion of a flexible protein loop (the WPD-loop) that carries a residue acting as a general acid/base catalyst during the PTP-catalyzed reaction. The orthogonal substitutions of a noncatalytic residue in the WPD-loops of YopH and PTP1B result in shifted pH-rate profiles from an altered kinetic pK a of the nucleophilic cysteine. Compar

Glycosidases are phylogenetically widely distributed enzymes that are crucial for the cleavage of glycosidic bonds. Here, we present the exceptional properties of a putative ancestor of bacterial and eukaryotic family-1 glycosidases. The ancestral protein shares the TIM-barrel fold with its modern descendants but displays large regions with greatly enhanced conformational flexibility. Yet, the bar

Increasing diversity in academia is not just a matter of fairness but also improves science. It is up to individual scientists and research organisations to support underrepresented minorities.