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Recent Advances in Understanding Biological GTP Hydrolysis through Molecular Simulation

GTP hydrolysis is central to biology, being involved in regulating a wide range of cellular processes. However, the mechanisms by which GTPases hydrolyze this critical reaction remain controversial, with multiple mechanistic possibilities having been proposed based on analysis of experimental and computational data. In this mini-review, we discuss advances in our understanding of biological GTP hy

Short and simple sequences favored the emergence of N-helix phospho-ligand binding sites in the first enzymes

The ubiquity of phospho-ligands suggests that phosphate binding emerged at the earliest stage of protein evolution. To evaluate this hypothesis and unravel its details, we identified all phosphate-binding protein lineages in the Evolutionary Classification of Protein Domains database. We found at least 250 independent evolutionary lineages that bind small molecule cofactors and metabolites with ph

Structural consequence of the most frequently recurring cancer-associated substitution in DNA polymerase ε

The most frequently recurring cancer-associated DNA polymerase ε (Pol ε) mutation is a P286R substitution in the exonuclease domain. While originally proposed to increase genome instability by disrupting exonucleolytic proofreading, the P286R variant was later found to be significantly more pathogenic than Pol ε proofreading deficiency per se. The mechanisms underlying its stronger impact remained

“Men bara att hon lyssnade betyder så mycket” En reflexiv tematisk analys av ungdomars upplevelse av att leva med postcovid

Många tillfrisknar helt efter sjukdom i covid-19 men vissa får kvardröjande symtom i sådan omfattning att det påverkar deras vardagliga funktion. Tillståndet benämns postcovid. Viss forskning är gjord kring vuxnas upplevelse av att leva med postcovid men det saknas kunskap om hur barn drabbas. Studiens syfte var att fördjupa förståelsen kring ungdomars upplevelser av att leva med postcovid. Sju seMany patients recover from a COVID-19 infection but some develop long lasting symptoms, which severeness has an impact on their daily function. This condition is now known as post-COVID. Studies have been conducted on adults' experiences of living with post-COVID, however little is known about how post-COVID impacts children. The current study therefore aimed to expand our understanding of ado

Barnets bästa som formalitet - en framställning av barns rättigheter vid LVU

The Convention on the Rights of the Child was incorporated into Swedish law in 2020 to strengthen children's social rights. Since its incorporation, researchers have investigated how the Convention has affected work with children's rights. There are still knowledge gaps on how to interpret these principles. This study aims to understand how the child's best interests, the child's o

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Hjem (Home) is an exhibition showcasing the works of Sverre Bjertnæs, featuring around 40 paintings and sculptures, both old and new. The exhibition was curated by Fredrik Værslev in the spring of 2024. Bjertnæs is one of Norway's foremost painters and sculptors.

Enhancing a de novo enzyme activity by computationally-focused ultra-low-throughput screening

Directed evolution has revolutionized protein engineering. Still, enzyme optimization by random library screening remains sluggish, in large part due to futile probing of mutations that are catalytically neutral and/or impair stability and folding. FuncLib is a novel approach which uses phylogenetic analysis and Rosetta design to rank enzyme variants with multiple mutations, on the basis of predic

Harnessing Conformational Plasticity to Generate Designer Enzymes

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

The role of ligand-gated conformational changes in enzyme catalysis

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 Without an Active Site Base : A Unifying Mechanism for Ras and Related GTPases

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

Cryptic genetic variation shapes the adaptive evolutionary potential of enzymes

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

Brain change trajectories in healthy adults correlate with Alzheimer’s related genetic variation and memory decline across life

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

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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

Effects of psychedelics on neurogenesis and broader neuroplasticity : a systematic review

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