We report results of detailed empirical valence bond simulations that model the effect of several amino acid substitutions on the thermodynamic (ΔG°) and kinetic activation (ΔG⧧) barriers to deprotonation of dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde 3-phosphate (GAP) bound to wild-type triosephosphate isomerase (TIM), as well as to the K12G, E97A, E97D, E97Q, K12G/E97A, I170A, L230A,

In this work, the two-center Dirac equation is solved numerically using an extension of an adapted B-spline basis set method previously implemented in relativistic atomic calculations (Fischer, C. F.; Zatsarinny, O. Comput. Phys. Commun. 2009, 180, 879). The robustness of the chosen numerical method, which avoids the appearance of spurious states common in other approaches, allows us to investigat

Liquid-liquid phase separation (LLPS) constitutes a crucial phenomenon in biological self-organization, not only intervening in the formation of membraneless organelles but also triggering pathological protein aggregation, which is a hallmark in neurodegenerative diseases. Employing incoherent quasi-elastic neutron spectroscopy (QENS), we examine the short-time self-diffusion of a model protein un

Something that all Nordic countries have in common is that journalistic work, popular culture phenomena and public debates resulting in subsequent political initiatives have served as driving forces in the development of academic research on the Holocaust. It is also clear that the field is heavily politicized, imbued with moral questions and highly diversified.The memories of the Holocaust have i

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

Transcriptional repressor EthR from Mycobacterium tuberculosis is a valuable target for antibiotic booster drugs. We previously reported a virtual screening campaign to identify EthR inhibitors for development. Two ligand binding orientations were often proposed, though only the top scoring pose was utilized for filtering of the large data set. We obtained biophysically validated hits, some of whi

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

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

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

Mycotoxins have been hypothesized to contribute to a diversity of adverse health effects in humans, even at low concentrations. Certain mycotoxins are established human carcinogens, whereas for others research suggests potential carcinogenic effects. The aim of this study was to determine the association between dietary exposure to mycotoxins and hepatobiliary cancers in the European Prospective I

The elevated plus maze (EPM) apparatus consists of two open arms that provide aversive spaces and two closed arms that provide protective and welcoming spaces. Here, we present a protocol to implement the classical EPM apparatus in a real-time optogenetic environment to address behavioral avoidance in mice. We describe steps for performing stereotaxic surgery, mouse manipulation, and experimental

En bildessä om artefakter från Tjernobyl och Prypjat 2019. Lämningar efter reaktorhaveri i kärnkraftverket 1986.

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

Bristande tillgänglighet är en unik diskrimineringsform. I viss utsträckning kräver diskrimineringsformen att arbetsgivaren anpassar arbetet för funktionsnedsatta i behov av särskild anpassning, med mål att individen hamnar i jämförbar situation med andra medarbetare. Denna har nära band med indirekt diskriminering. Ofta åberopas dessa i kombination med varandra, och i vissa länder har denna nära The Swedish form of discrimination, lack of accessibility, is unique. To an extent, this form of discrimination requires the employer to adapt the work of a disabled person, who needs special accommodation, intending to put the individual in a comparable situation to his co-workers. This form of discrimination has a close connection to indirect discrimination. Often, these are invoked in combinati

Enligt aktiebolagslagen (ABL) har en ägare till mer än 90 % av aktierna i ett aktiebolag rätt att påkalla tvångsinlösen av resterande så kallade minoritetsaktier. Tvister med anledning av ett sådant tvångsinlösensförfarande ska med grund i tvingande bestämmelser i ABL avgöras genom skiljeförfarande. I uppsatsen görs en kritisk analys av sådana tvångsinlösenförfaranden utifrån den enskilde minoriteAccording to the Swedish Companies Act (ABL), an owner holding more than 90% of the shares in another limited company has the right to demand compulsory redemption of the remaining minority shares. Disputes arising from such procedures must be resolved through arbitration. This thesis constitutes a critical investigation of such compulsory redemption procedures from the perspective of the individu

Skiljeförfarande är i svensk rätt jämställt med tvistlösning i allmän domstol beträffande dispositiva tvistemål. Grunden för tvistlösning genom skiljeförfarande, är ett skiljeavtal mellan parterna. Huruvida en uppkommen tvist ska lösas genom skiljeförfarande – när det finns ett skiljeavtal parterna emellan – är avhängigt skiljeavtalets (objektiva) omfattning. Skiljenämnden saknar behörighet att avArbitration is, according to Swedish law, equivalent to court proceeding, when it comes to dispositive disputes. The basis of dispute resolution through arbitration, is an arbitration agreement between the litigants. Whether a dispute should be resolved through arbitration – when there is an arbitration agree-ment between the litigants – is dependent on the scope of their arbitration agreement. Th