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Type II CRISPR-Cas9 RNA-guided nucleases are widely used for genome engineering. Type II-A SpCas9 protein from Streptococcus pyogenes is the most investigated and highly used enzyme of its class. Nevertheless, it has some drawbacks, including a relatively big size, imperfect specificity and restriction to DNA targets flanked by an NGG PAM sequence. Cas9 orthologs from other bacterial species may p
Protozoan parasites of the genus Leishmania cause leishmaniasis, a disease with variable clinical manifestations that affects millions of people worldwide. Infection with L. donovani can result in fatal visceral disease. In Panama, Colombia, and Costa Rica, L. panamensis is responsible for most of the reported cases of cutaneous and mucocutaneous leishmaniasis. Studying a large number of drug cand
The electrode's composition and structure, affecting ion-conduction and water uptake and transport, is crucial for polymer electrolyte fuel cells. This study investigates the role of particles versus dispersed ionomer based on poly(arylene piperidinium) (PAP) for AEMFC. Mixed ionomer electrodes, consisting of linear PAP ionomers and crosslinked particles, are synthesized and evaluated in AEMF
Heart failure (HF) is a complex clinical syndrome characterized by exercise intolerance. However, most diagnostic assessments are performed at rest, when many patients are asymptomatic. To better understand the underlying pathophysiology, examination during exercise is needed. Hydraulic force, a newly identified mechanism of diastolic filling, is proportional to the difference in short-axis areas
This paper explores the challenges and barriers of forced migrants at the nexus of housing and social integration, presenting the outcomes of an international and interdisciplinary collaboration funded by the JPI Urban Europe programme. Research includes the case study cities Leipzig, Lund, Riga, and Vienna, utilizing primary and secondary data in a transdisciplinary process involving theoretical
Det här kapitlet tar avstamp i en av dessa händelser ’från fältet’, i detta fall en teater, som hänger sig kvar många år efteråt men som inte använts eftersom den innehåller för många trådar: lite om metod, lite om etik, mycket om kroppar och om närvaro och om kön om man vill. Händelsen börjar i ett misstag som jag utnyttjar men sen får betala för och som väckte känslor både hos mig och hos den ja
Transformation in the contemporary architectural discourse does not only encompass the animation of form and program, which at the turn of the last century was progressed by deconstructivism and the digital turn. Applicable within aspects of ecology, economy, and culture, transformation has today evolved into a pervasive concept both advanced and abused within the complexity of forces that drive t
Saturated fatty acids impose lipotoxic stress on pancreatic β cells, leading to β cell failure and diabetes. In this study, we investigate the critical role of organellar Ca2+ disturbance on defective autophagy and β cell lipotoxicity. Palmitate, a saturated fatty acid, induced perilysosomal Ca2+ elevation, sustained mTOR complex 1 (mTORC1) activation on the lysosomal membrane, suppression of the
The use of CRISPR-Cas bacterial adaptive immunity system components for targeted DNA changes has opened broad prospects for programmable genome editing of higher organisms. The most widely used gene editors are based on the Cas9 effectors of the type II CRISPR-Cas systems. In complex with guide RNAs, Cas9 proteins are able to directionally introduce double-stranded breaks into DNA regions that are
Pathological processes often change the mechanical properties of cells. Increased rigidity could be a marker of cellular malfunction. Erythrocytes are a type of cell that deforms to squeeze through tiny capillaries; changes in their rigidity can dramatically affect their functionality. Furthermore, differences in the homeostatic elasticity of the cell can be used as a tool for diagnosis and even f
We examine key characteristics of the work tasks of judges and prosecutors from a power and status perspective, discerning how emotions tie into this perspective. Analysis of court observations, interviews and shadowing of judges and prosecutors at four Swedish district courts and prosecution offices shows that power and status operate differently for the respective professions, resulting in distiWe examine key characteristics of the work tasks of judges and prosecutors from a power and status perspective, discerning how emotions tie into this perspective. Analysis of court observations, interviews and shadowing of judges and prosecutors at four Swedish district courts and prosecution offices shows that power and status operate differently for the respective professions, resulting in disti
Objectives To investigate changes in analgesic use before and after supervised exercise therapy and patient education in patients with knee or hip osteoarthritis (OA).Methods We recruited 16 499 of 25 933 eligible patients (64%; mean age 64.9; SD 9.6; 73% women) from the Good Life with osteoArthritis in Denmark (GLA:D) registry. Change in proportions of analgesic users (categorised according to an
Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical illness affecting 6-8 million people in Latin America. Reaching scholarly consensus on the host response to T. cruzi infection remains a significant challenge, primarily due to substantial heterogeneity in outcomes driven by both the choice of animal model and the infecting parasite's discrete typing unit (DTU). This varia
Cas12e proteins (formerly CasX) form a distinct subtype of Class II type V CRISPR-Cas effectors. Recently, it was shown that DpbCas12e from Deltaproteobacteria and PlmCas12e from Planctomycetes can introduce programmable double-stranded breaks in mammalian genomes. Thus, along with Cas9 and Cas12a Class II effectors, Cas12e could be harnessed for genome editing and engineering. The location of cle
CRISPR-Cas defense systems opened up the field of genome editing due to the ease with which effector Cas nucleases can be programmed with guide RNAs to access desirable genomic sites. Type II-A SpCas9 from Streptococcus pyogenes was the first Cas9 nuclease used for genome editing and it remains the most popular enzyme of its class. Nevertheless, SpCas9 has some drawbacks including a relatively lar
This article analyses the industrial enterprise of the Dutch-born brothers Abraham and Jakob Momma-Reenstierna and their investments in Sápmi and the upper parts of the Torne River Valley, northern Sweden, during the second half of the seventeenth century. The aim is to explore the driving forces behind the industrial projects of the two brothers in a larger global and colonial context. With inspi
Fishes of the genus Pterois possess spines that provoke intense pain, which can last for weeks. Since the first toxicological description of their spine venom, a significant amount of research has been published regarding their biochemical characterization. This minireview presents research published from 1959 to 2024 on bioactive substances found in Pterois species. Pterois venom mainly contai
This article uses the elemental concepts of earth, water and fire to examine the production, use and control of space in the seventeenth-century Wrangel estate at Skokloster in central Sweden. Using a relational approach, the paper discusses how the elements symbolically express a part of the baroque aesthetic, how they were emphasised or pinned down as part of an economic asset, and how they reac
