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Particle impact in high-pressure homogenizer valves – A step towards understanding wear and cell breakup in food and beverage processing

In many liquid food processing applications using high-pressure homogenizers (HPHs), particles impact with the solid surfaces of the homogenization device. This may lead to costly wear. For some applications, impact is also postulated to control the desired cell disruption. This contribution uses computational fluid dynamics to study impact of particles on solid surfaces in HPHs, as a step towards

European energy renovation of multi-dwelling building from a Swedish life cycle perspective

The European Union has committed to achieving climate neutrality by the year 2050, with Sweden setting an even more ambitious target of reaching this milestone by 2045. A subgroup comprising 23 pioneering Swedish municipalities, collectively representing 40% of the country's population, aims to attain climate neutrality by 2030. Globally, buildings and construction sector contribute nearly 40% of

House Flora Valerie

Architecture and space in the scale of a family house can be about rounded shapes interplaying with straight lines and light. In today’s newly built houses in Sweden I sense a lack of variety in combinations of these elements. This project therefore aims to experiment with rounded shapes and straight lines together with light. A collection of the explorations act as the base to draw a house. A vil

Design, synthesis, crystallographic studies, and preliminary biological appraisal of new substituted triazolo[4,3-b]pyridazin-8-amine derivatives as tankyrase inhibitors

Searching for selective tankyrases (TNKSs) inhibitors, a new small series of 6,8-disubstituted triazolo[4,3-b]piridazines has been synthesized and characterized biologically. Structure-based optimization of the starting hit compound NNL (3) prompted us to the discovery of 4-(2-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)ethyl)phenol (12), a low nanomolar selective TNKSs inhibitor working a

Chemical probes to study ADP-ribosylation : Synthesis and biochemical evaluation of inhibitors of the human ADP-ribosyltransferase ARTD3/PARP3

The racemic 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-N-[1-(pyridin-2-yl)ethyl]propanamide, 1, has previously been identified as a potent but unselective inhibitor of diphtheria toxin-like ADP-ribosyltransferase 3 (ARTD3). Herein we describe synthesis and evaluation of 55 compounds in this class. It was found that the stereochemistry is of great importance for both selectivity and potency and that subs

Comparative structural analysis of the putative mono-ADP-ribosyltransferases of the ARTD/PARP family

The existence and significance of endogenous cytosolic and nuclear mono-ADP-ribosylation has been a matter of debate. Today, evidence suggests that the human enzymes that catalyze the reaction have been rounded up. Moreover, substrate proteins and specific functions for mono-ADP-ribosyltransferases are beginning to be defined. Reader domains that specifically recognize mono-ADP-ribosylated target

Pharmacology of ADP-ribosylation

ADP-ribosyltransferase ARTD1/PARP1 is a target for cancer and ischemia drug development. Several other ARTD-family enzymes have been characterized in recent years, and it has become clear that their inhibition might also have therapeutic value. This minireview series summarizes current knowledge of pharmacological inhibition of ADP-ribosyltransferases by a compound class called PARP inhibitors and

PARP inhibitor with selectivity toward ADP-ribosyltransferase ARTD3/PARP3

Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here, we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12 members of the enzyme

PARP inhibitors : polypharmacology versus selective inhibition

Inhibition of ADP-ribosyltransferases with diphtheria toxin homology (ARTD), widely known as the poly(ADP-ribose) polymerase (PARP) family, is a strategy under development for treatment of various conditions, including cancers and ischemia. Here, we give a brief summary of ARTD enzyme functions and the implications for their potential as therapeutic targets. We present an overview of the PARP inhi

Recognition of mono-ADP-ribosylated ARTD10 substrates by ARTD8 macrodomains

ADP-ribosyltransferases (ARTs) catalyze the transfer of ADP-ribose from NAD(+) onto substrates. Some ARTs generate in an iterative process ADP-ribose polymers that serve as adaptors for distinct protein domains. Other ARTs, exemplified by ARTD10, function as mono-ADP-ribosyltransferases, but it has been unclear whether this modification occurs in cells and how it is read. We observed that ARTD10 c

Infant urinary tract infection in Sweden — A national study of current diagnostic procedures, imaging and treatment

Background: Urinary tract infection (UTI) in infants is a common, potentially life-threatening bacterial infection, and must be managed carefully through the entire chain of care from diagnosis, choice of treatment, follow-up and risk stratification of future complications. This Swedish nationwide study of infant UTI was conducted to evaluate the current management of infant UTI, yield of investig

Early B-Cell Factor 1 : An Archetype for a Lineage-Restricted Transcription Factor Linking Development to Disease

The development of highly specialized blood cells from hematopoietic stem cells (HSCs) in the bone marrow (BM) is dependent upon a stringently orchestrated network of stage- and lineage-restricted transcription factors (TFs). Thus, the same stem cell can give rise to various types of differentiated blood cells. One of the key regulators of B-lymphocyte development is early B-cell factor 1 (EBF1).

Structural biology of the writers, readers, and erasers in mono- and poly(ADP-ribose) mediated signaling

ADP-ribosylation of proteins regulates protein activities in various processes including transcription control, chromatin organization, organelle assembly, protein degradation, and DNA repair. Modulating the proteins involved in the metabolism of ADP-ribosylation can have therapeutic benefits in various disease states. Protein crystal structures can help understand the biological functions, facili

Discovery of ligands for ADP-ribosyltransferases via docking-based virtual screening

The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyzes the transfer of ADP-ribose units onto substrate proteins by using nicotinamide adenine dinucleotide (NAD(+)) as a cosubstrate. They have a documented role in chromatin remodelling and DNA repair, and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The

The Extremely Metal-rich Knot of Stars at the Heart of the Galaxy

We show with Gaia XP spectroscopy that extremely metal-rich (EMR) stars in the Milky Way ([M/H]XP ≳ 0.5) are largely confined to a tight "knot"at the center of the Galaxy. This EMR knot is round in projection, has a fairly abrupt edge near RGC,proj ∼ 1.5 kpc, and is a dynamically hot system. This central knot also contains very metalrich (VMR; +0.2 . [M/H]XP . +0.4) stars. However, in contrast to

Insights into the morphology of Sphenothallus (Cnidaria): new features identified in an old genus from the Carboniferous (Pennsylvanian, Bashkirian) of western Ireland

The recent discovery of well-preserved fragments of Sphenothallus in the Central Clare Group (Pennsylvanian) of western Ireland provides new insights into the morphology of this enigmatic, putative cnidarian. The specimens demonstrate a morphological plasticity, including features not previously described for Sphenothallus, such as the presence of flat sides and angular lateral margins, non-bilate