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The ribosome is an essential drug target as many classes of clinically important antibiotics bind and inhibit its functional centers. The catalytic peptidyl transferase center (PTC) is targeted by the broadest array of inhibitors belonging to several chemical classes. One of the most abundant and clinically prevalent mechanisms of resistance to PTC-acting drugs is C8-methylation of the universally
Galectins are versatile glycan-binding proteins involved in immunomodulation. Evidence suggests that galectins can control the immunoregulatory function of cytokines and chemokines through direct binding. Here, we report on an inverse mechanism in which chemokines control the immunomodulatory functions of galectins. We show the existence of several specific galectin-chemokine binding pairs, includ
ObjectivesPeople with serious illness approaching end of life often end up in emergency and hospital care, frequently against expressed preferences. Consequently, oncology trials record care days as a measure of treatment burden called “time toxicity.” However, this measure ignores the diminishing marginal utility of time: that the value of a day is higher when fewer remain. We aimed to incorporat
Popular Abstract in Swedish Bakterier är små encelliga organismer som lever i nästan varje tänkbar miljö på jorden, inklusive i och på människor. Vi är kontinuerligt koloniserade av bakterier i bland annat våra luftvägar, munhålor och mag-tarmkanaler. Denna samexistens är oftast ömsesidigt fördelaktig, eller åtminstone ofarlig för oss människor, och det är känt att bakterier hjälper oss bryta ner Nontypeable Haemophilus influenzae (NTHi) is a remarkably proficient colonizer of the human respiratory tract. The aim of this thesis has been to characterize currently known, and identify novel, bacterial factors involved in the key processes of colonization and pathogenesis, namely adherence to host tissue and evasion of the host innate immunity. We have shown that the NTHi virulence factor Pr
Assays detecting antigen (Ag)-specific T-cell responses in immune-mediated processes are increasingly employed to understand disease pathogenesis and "immune staging". The quantity and quality of starting peripheral blood mononuclear cell (PBMC) preparations are important factors in the performance of such assays. We therefore compared final PBMC yield and function by modifying parameters at the b
A total of 105 low-birth-weight children presenting for first vaccination were randomized to receive bacillus Calmette-Guerin (BCG) immediately or later (current practice). The mortality rate ratio for BCG was 0.17 (95% CI = 0.02-1.35) within 3 days of enrollment, 0.28 (0.06-1.37) in the first month, and 0.27 (0.07-0.98) after 2 months of age. The mortality rate ratio was 0.41 (0.14-1.18) (P = 0.0
We present a comparison of two-dimensional separation methods and how they affect the degree of coverage of protein expression in complex mixtures. We investigated the relative merits of various protein and peptide separations prior to acidic reversed-phase chromatography directly coupled to an ion trap mass spectrometer. The first dimensions investigated were density gradient organelle fractionat
Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn's ileitis, Crohn's colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased
Abstract in UndeterminedTargeted proteomics via selected reaction monitoring (SRM) is a powerful mass spectrometric technique affording higher dynamic range, increased specificity and lower limits of detection than other shotgun mass spectrometry methods when applied to proteome analyses. However, it involves selective measurement of predetermined analytes, which requires more preparation in the f
Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with neutralizing activity against homologous and heterologous viruses. In the present study, we generated a reco
Hereditary severe combined immunodeficiency (SCID) includes a heterogeneous group of diseases that profoundly affect both cellular and humoral immune responses and require treatment by bone marrow transplantation. Characterization of the cellular and molecular bases of SCID is essential to provide accurate genetic counseling and prenatal diagnosis, and it may offer the grounds for alternative form
Popular Abstract in Swedish Denna avhandling behandlar automationsolycksfall inom tillverkningsindustrin. Automationsolycksfall definieras som ett olycksfall där en person skadas av en energi som kontrollerades, eller borde ha kontrollerats, av en automatiserad utrustning. Avhandlingen grundar sig på av fem vetenskapliga artiklar. De tre första är baserade på data från den obligatoriska arbetsskadThis thesis treats automation accidents in manufacturing industry. An automation accident is defined as an accident whereby a person is injured by an energy which was controlled, or should have been controlled, by an automated item of equipment. The thesis comprises five papers. The first three are based on data from mandatory Swedish occupational-injury reports. Their aim is to show frequencies,
Popular Abstract in Swedish Denna avhandling är inriktad på metoder för att förbättra och utvärdera infrastrukturer för geografiska data (eng. Spatial Data Infrastructure). Syftet har varit trefaldigt: att utveckla ett ramverk för hantering och utvärdering av en infrastruktur, att förbättra tillgängligheten av geografiska data i en infrastruktur, och för att förbättra kartografi i visningstjänsterThis thesis mainly focuses on methods for improving and evaluating Spatial Data Infrastructures (SDIs). The aim has been threefold: to develop a framework for the management and evaluation of an SDI, to improve the accessibility of spatial data in an SDI, and to improve the cartography in view services in an SDI. Spatial Data Infrastructure has been identified as an umbrella covering spatial data
Popular Abstract in Swedish Helicobacter pylori är en bakterie som orsakar såväl magkatarr, magsår som magsäckscancer. H. pylori producerar olika virulensfaktorer såsom enzymet ureas, ett cell vakuolbildande toxin (VacA), andra cytotoxiska proteiner (cagA eller pathogenicity island-associated proteins), flageller och adhesiner. För etablering av H. pylori infektion, måste dessa virulensfaktorer inHelicobacter pylori is a gastric pathogen which cause chronic type B gastritis and peptic ulcer disease. H. pylori produces virulence factors such as urease, vacuolating cytotoxin VacA, cag pathogenicity island-associated proteins, flagella and adhesins. These proteins interact with several host cell molecules such as sialylated cell surface glycoproteins, some of glycolipids and mucins. Glycosami
Combretastatin A-4 disodiumphosphate (CA4P), a prodrug formulation of the natural product combretastatin A-4 (CA4), is currently in clinical investigation for the treatment of cancer. In vivo, CA4P is rapidly enzymatically converted to CA4, a potent inhibitor of tubulin polymerization (IC50 = 1-2 muM), and rapidly causes bloodflow shutdown in tumor tissues. A variety of alkyl and aryl di- and trie
To investigate the immunological and virological factors that may lead to different patterns of disease progression characteristic of HIV-1-infected children, two HIV-1-infected siblings, a slow and a fast progressor, were followed prospectively before the onset of highly active antiretroviral therapy. Viral coreceptor usage, including the use of CCR5/CXCR4 chimeric receptors, macrophage tropism,
OBJECTIVE: To examine the effect of using a mitt during shortened constraint-induced movement therapy for patients in the subacute phase after stroke. SUBJECTS: Twenty-four patients with stroke (mean age 57.6 (standard deviation (SD) 8.5) years; average 7 weeks post-stroke) with mild to moderate impaired hand function. METHODS: The patients were randomized to mitt use or no mitt use on the less af
Popular Abstract in Swedish Varje år insjuknar ungefär 450 000 kvinnor i livmoderhalscancer (cervixcancer) i världen. Som en följd av screening för livmoderhalscancer, där kvinnor testar sig regelbundet för cellförändringar, har insjuknandet i livmoderhalscancer minskat. Det cellprov som används i screeningen lyckas dock inte upptäcka alla kvinnor som har ökad risk för framtida cancer. Humant papiDifferent types of human papillomavirus (HPV) vary in the extent they cause precursor lesions (CIN) and cancer. There are limited long-term efficacy data on HPV testing in primary screening Among 72 cervical cancers in Mozambique, HPV 16 and 18 were the most frequent HPV types (69% of cases). Comparing 108 cervical cancers cases and 517 matched controls nested within a population-based cohort in
The objective of this study was to describe environmental barriers and investigate the nature of accessibility problems in housing among single-living, very old people (N = 1,150) in urban regions in three European countries (Sweden, Germany, Latvia), in a one-year perspective. A specific feature of this study is the explicit conceptual differentiation between environmental barriers and accessibil
