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A two unit antisense RNA cassette test system for silencing of target genes

This communication describes a two unit antisense RNA cassette system for use in gene silencing. Cassettes consist of a recognition unit and an inhibitory unit which are transcribed into a single RNA that carries sequences of non-contiguous complementarity to the chosen target RNA. The recognition unit is designed as a stem-loop for rapid formation of long- lived binding intermediates with target

Transient expression of Dp140, a product of the Duchenne muscular dystrophy locus, during kidney tubulogenesis

Dystroglycan is a cell surface complex which in muscle links the extracellular matrix protein laminin-2 to the membrane associated cytoskeletal protein dystrophin. Recently it was found that dystroglycan is also expressed in developing epithelial cells. Moreover, antibodies against dystroglycan can perturb epithelial cell development in kidney organ culture. Dystroglycan could provide a link betwe

Expression of laminin alpha 1, alpha 5 and beta 2 chains during embryogenesis of the kidney and vasculature

Laminins, found predominantly in basement membranes, are large glycoproteins consisting of different subsets of alpha, beta and gamma chain subunits. To resolve conflicting data in the literature concerning coexpression of alpha 1 and beta 2 chains, expression of alpha 1 chain was studied with two different antisera against the E3 fragment of laminin alpha 1 chain. Expression of the alpha 1 chain

Bulged-out nucleotides in an antisense RNA are required for rapid target RNA binding in vitro and inhibition in vivo

Naturally occurring antisense RNAs in prokaryotes are generally short, highly structured and untranslated. Stem-loops are always present, and loop regions serve as primary recognition structures in most cases. Single-stranded tails or internal unstructured regions are required for initiation of stable pairing between antisense and target RNA. Most antisense RNAs contain bulged-out nucleotides or s

Bulged-out nucleotides protect an antisense RNA from RNase III cleavage

Bulged-out nucleotides or internal loops are present in the stem-loop structures of several antisense RNAs. We have used the antisense/target RNA system (CopA/CopT) that controls the copy number of plasmid R1 to examine the possible biological function of bulged-out nucleotides. Two regions within the major stem-loop of the antisense RNA, CopA, carry bulged-out nucleotides. Base pairing in either

AI och risker för diskriminering i arbetslivet

Många arbetsgivare känner inte till att de redan idag använder sig av artificiell intelligens, AI, eller annat automatiserat beslutsfattande. Det visar den rapport om AI och risker för diskriminering i arbetslivet som Diskrimineringsombudsmannen, DO, publicerar idag. Att arbetsgivare har denna kunskap är avgörande för att arbeta förebyggande för att motverka diskriminering vid tillämpning av tekni

Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations

Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transiti

IGF1R signalling is a guardian of self-tolerance restricting autoantibody production

OBJECTIVE: Insulin-like growth factor 1 receptor (IGF1R) acts at the crossroad between immunity and cancer, being an attractive therapeutic target in these areas. IGF1R is broadly expressed by antigen-presenting cells (APC). Using mice immunised with the methylated albumin from bovine serum (BSA-immunised mice) and human CD14 + APCs, we investigated the role that IGF1R plays during adaptive immune

Human B cells

The importance of B cells and their critical role in the maintenance of health through generation of antibody-mediated immune protection is undoubted. However, the differences between the responses of B cells with different surface phenotypes in different microanatomical sites as well as diversity in B-cell function outside antibody production are just starting to be acknowledged and resolved. Thi

Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood

B cells generate antibodies that are essential for immune protection, but their subgroups are poorly defined. Here, we perform undirected deep profiling of B cells in matched human lymphoid tissues from deceased transplant organ donors and blood. In addition to identifying unanticipated features of tissue-based B cell differentiation, we resolve two subsets of marginal zone B (MZB) cells differing

Peyer's patch T H17 cells are dispensable for gut IgA responses to oral immunization.

T helper 17 (T H17) cells located at the Peyer's patch (PP) inductive site and at the lamina propria effector site of the intestinal immune system are responsive to both pathogenic and commensal bacteria. Their plasticity to convert into follicular helper T (T FH) cells has been proposed to be central to gut immunoglobulin A (IgA) responses. Here, we used an IL-17A fate reporter mouse and an MHC-I

Human intestinal B cells in inflammatory diseases

The intestinal lumen contains an abundance of bacteria, viruses and fungi alongside ingested material that shape the chronically active intestinal immune system from early life to maintain the integrity of the gut epithelial barrier. In health, the response is intricately balanced to provide active protection against pathogen invasion whilst tolerating food and avoiding inflammation. B cells are c

Longitudinal Follow Up of Immune Responses to SARS-CoV-2 in Health Care Workers in Sweden With Several Different Commercial IgG-Assays, Measurement of Neutralizing Antibodies and CD4 + T-Cell Responses.

BACKGROUND: The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined.METHOD: 314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for

Plasmablasts in previously immunologically naïve COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses

Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19

Patient-associated mutations in Drosophila Alk perturb neuronal differentiation and promote survival

Activating anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (RTK) mutations occur in pediatric neuroblastoma and are associated with poor prognosis. To study ALK-activating mutations in a genetically controllable system, we employed CRIPSR/Cas9, incorporating orthologs of the human oncogenic mutations ALKF1174L and ALKY1278S in the Drosophila Alk locus. AlkF1251L and AlkY1355S mutant Dros

Bacterial infection disrupts established germinal center reactions through monocyte recruitment and impaired metabolic adaptation

Consecutive exposures to different pathogens are highly prevalent and often alter the host immune response. However, it remains unknown how a secondary bacterial infection affects an ongoing adaptive immune response elicited against primary invading pathogens. We demonstrated that recruitment of Sca-1 + monocytes into lymphoid organs during Salmonella Typhimurium (STm) infection disrupted pre-exis

Confirmed reinfection with SARS-CoV-2 during a pregnancy : A case report

Pregnancy might impact immunity after SARS-CoV-2 infection and/or vaccination. We describe the first case of reinfection with SARS-CoV-2 during a pregnancy. While the mother lacked detectable antibodies 2 months after the first infection, both mother and baby had IgG antibodies at delivery. Infection did not cause any adverse pregnancy outcome.

Clonotypic analysis of protective influenza M2e-specific lung resident Th17 memory cells reveals extensive functional diversity

The fate of tissue-resident memory CD4 T cells (Trm) has been incompletely investigated. Here we show that intranasal, but not parenteral, immunization with CTA1-3M2e-DD stimulated M2e-specific Th17 Trm cells, which conferred strong protection against influenza virus infection in the lung. These cells rapidly expanded upon infection and effectively restricted virus replication as determined by CD4