280 research outputs found
Discovering immunoreceptor coupling and organization motifs
No full textThe recently determined cryo-EM structures of the T cell antigen receptor (TCR) and B cell antigen receptor (BCR) show in molecular details the interactions of the ligand-binding part with the signaling subunits but they do not reveal the signaling mechanism of these antigen receptors. Without knowing the molecular basis of antigen sensing by these receptors, a rational design of optimal vaccines is not possible. The existence of conserved amino acids (AAs) that are not involved in the subunit interaction suggests that antigen receptors form higher complexes and/or have lateral interactors that control their activity. Here, I describe evolutionary conserved leucine zipper (LZ) motifs within the transmembrane domains (TMD) of antigen and coreceptor components that are likely to be involved in the oligomerization and lateral interaction of antigen receptor complexes on T and B cells. These immunoreceptor coupling and organization motifs (ICOMs) are also found within the TMDs of other important receptor types and viral envelope proteins. This discovery suggests that antigen receptors do not function as isolated entities but rather as part of an ICOM-based interactome that controls their nanoscale organization on resting cells and their dynamic remodeling on activated lymphocytes
Die Vegetation auf Rethdächern: Eine pflanzensoziologische Untersuchung von Kryptogamengesellschaften auf Reth- und Strohdächern in Schleswig-Holstein
No full textZiel der Arbeit war ein Überblick über die Kryptogamengesellschaften auf Reth- und Strohdächern in Schleswig-Holstein, sichtbar makroskopisch (von Betula pubescens bis Stichococcus minor) und insgesamt nahezu gesamtheitlich. Der Fokus liegt auf Moosen, Algen, Pilzen, Chlorophyta, Cyanophyta, Chrysophyta, Mycophyta, Lichenes, Bryophyta und Spermatophyta; mikroskopische Pilze wurden nicht berücksichtigt. Die Moose stehen im Vordergrund, da sie regional dominieren und der Verfasser aufgrund längerer Beschäftigung hierzu präzisere Aussagen geben kann. Für Algen und Pilze fehlen oft relevante Literaturquellen. Die größte Herausforderung war die umfassende Artenkenntnis aller Pflanzengruppen; viel Zeit floss in Einarbeitung und Bestimmung der Arten. Dennoch soll das Gebiet als Ganzes betrachtet werden, nicht nur einzelne Kryptogamen-Gruppen, um Trennungen in pflanzensystematische Einheiten zu vermeiden. Diese Arbeit ist die erste größere Inventur kryptogamer Vegetation auf Reth- und Strohdächern und dient als grundlegende Bestandsaufnahme. Die Untersuchung konzentriert sich vorwiegend auf Rethdächer; Strohdächer sind in Kap. 1.4 separat behandelt. Da aus Zweckmäßigkeit Ströhdächer in Tabellen der Rethdachaufnahmen integriert wurden, bedeuten Erwähnungen von Rethdächern auch die wenigen Strohdächer. Die historische Verdrängung von Rethdächern durch moderne Bauweisen macht die Festhaltung dieser damals charakteristischen, oft grün bewachsenen Dächer interessant: ein Blick auf deren Vegetation liefert Einblicke in Abhängigkeiten von Klima, Substrat, Naturräumen sowie lokalen Faktoren wie Neigung, Exposition und Beschattung.The aim of this study was to provide an overview of the cryptogam communities on thatched and straw roofs in Schleswig-Holstein, visible macroscopically (from Betula pubescens to Stichococcus minor) and almost entirely comprehensive. The focus is on mosses, algae, fungi, Chlorophyta, Cyanophyta, Chrysophyta, Mycophyta, Lichenes, Bryophyta, and Spermatophyta; microscopic fungi were not considered. Mosses are in the foreground because they dominate regionally and the author can make more precise statements about them due to his long-term involvement with them. Relevant literature sources are often lacking for algae and fungi. The greatest challenge was comprehensive species knowledge of all plant groups; a lot of time was spent familiarizing oneself with and identifying the species. Nevertheless, the area should be considered as a whole, not just individual cryptogam groups, in order to avoid divisions into plant systematic units. This work is the first major inventory of cryptogam vegetation on thatched and straw roofs and serves as a basic inventory. The study focuses primarily on thatched roofs; straw roofs are dealt with separately in section 1.4. For practical reasons, straw roofs have been included in the tables of thatched roof surveys, so references to thatched roofs also include the few straw roofs. The historical displacement of thatched roofs by modern construction methods makes it interesting to preserve these roofs, which were characteristic of their time and often covered with green vegetation: a look at their vegetation provides insights into dependencies on climate, substrate, natural spaces, and local factors such as slope, exposure, and shadin
New approaches for the mass spectrometric determination of trace concentrations and congener group patterns of chlorinated paraffins in biota
No full textThe determination of chlorinated paraffins (CPs) in the environment is important, since
CPs are persistent, bioaccumulative and toxic. However, the analysis of these complex
mixtures containing thousands of isomers is also a demanding task. CP analysis and
especially the quantification of CPs are far from being well established. In this work, new
methodologies were developed for the determination of CPs in biota by low-resolution
mass spectrometry (LRMS).
The use of expensive high-resolution mass spectrometry was avoided. Therefore, existing
clean-up methods were improved to enhance the selectivity as well as the unequivocal
identification of CP congener groups. The developed method comprises the following
steps: After cold column extraction, lipids were removed by adsorption chromatography on
silica gel impregnated with sulfuric acid. Adsorption chromatography on Florisil® allowed
the elimination of interfering compounds such as polychlorinated biphenyls (PCBs) and
toxaphenes, which interfere the CP analysis by high-resolution gas chromatography
(HRGC) coupled to LRMS and employing electron capture negative ionisation (ECNI).
The analysis of complex CP mixtures with short- (SCCPs, C10-13) and medium- (MCCPs,
C14-17) chain lengths can be disturbed by mass overlap, if LRMS in the ECNI mode is
employed. This is mainly caused by CP congeners with the same nominal mass but five
carbon atoms more and two chlorine atoms less and can lead to an overestimation of the
total CP concentration. Therefore, a procedure based on a precise check of isotope ratios,
retention time ranges and signal shapes was developed to unequivocally identify the most
important CP congener groups.
Prior to this work, quantification procedures for CPs were not well established, and
systematic errors could not always be avoided. Therefore, a new quantification procedure
was developed to overcome the strong dependence of ECNI results on the chlorine content
of the standard, and to avoid a tedious and time-consuming selection of the “most similar”
reference standard. A linear correlation could be established between the total response
factor of a CP mixture and its chlorine content. This allowed the compensation of errors
due to differences between the degree of chlorination of CPs in the sample and standard.
Quantification errors were considerably reduced and CP pattern matching procedures
between standard and sample became unnecessary.
Furthermore, HRGC electron ionisation tandem mass spectrometry (EI-MS/MS) was used
for the fast determination of the total CP amount. This method was successfully applied to
the determination of total CP concentrations in fish, human milk and eggs and provided a
first insight into CP levels.
ECNI-LRMS was employed for the determination of CP levels and congener group
patterns in different fishes and seabirds from various regions in Europe (North and Baltic
Sea, Central Europe, European Arctic). Results revealed that SCCPs and MCCPs are
detectable in fish in the ng/g range. Hence, concentrations are comparable to levels of other
persistent organic pollutants (e.g. polychlorinated biphenyls (PCBs), toxaphenes and
polybrominated diphenylethers).
SCCP concentrations were between 54 and 1428 ng/g lipid weight (lw), MCCP
concentrations varied between <30 and 2448 ng/g lw in cod, dab and flounder from
different locations in the North and Baltic Sea.
SCCPs and, for the first time, MCCPs could be detected in biota from the European Arctic.
Between 89 and 861 ng/g lw of SCCPs and 107-3717 ng/g lw of MCCPs were detectable
in fish and seabirds captured on Bear Island, and between 35 and 139 ng/g lw of SCCPs
and 14-96 ng/g lw of MCCPs were found in cod captured close to Iceland and northwest
Norway (Lofoten).
Furthermore, CP levels were determined in different fish species from rivers in south
Germany (Neckar and Rhine) and north Switzerland (Liechtensteiner Binnenkanal and
Necker). The total CP amount was first estimated by EI-MS/MS. Concentrations were
between 19 and 256 ng/g wet weight (ww). Furthermore, SCCP and MCCP concentrations
were determined for selected samples by ECNI-LRMS. Concentrations were comparable
to PCB 138 or PCB 153. Linear correlations were observed between indicator PCBs and
SCCPs as well as PCB 180 and MCCPs.
CPs were detectable in human milk as well as in human foodstuff by EI-MS/MS. Total CP
concentrations were 2.6-9.6 ng/g ww in human milk and 20-59 ng/g ww in poultry eggs,
both from south Germany.
Furthermore, congener and homologue group patterns of technical CP mixtures and
standards were investigated and compared to those in brown trout from Central Europe and
cod from the Baltic Sea and northwest Europe. SCCP mixtures contained mainly C11 and
C12 congeners (>63%) followed by C13 and C10, whereas C14 congeners (>45%) followed
by C15 dominated in MCCPs mixtures. Minor components were C16 (<14%) and C17
congeners (<2%). Congener groups with six, seven and eight chlorine atoms were most
abundant in all fish samples indicating their specific potential for bioaccumulation.
Similarities and differences in the CP mixtures were further elucidated by principal
components analysis (PCA). PCA revealed that differences in CP compositions were
mainly caused by their chlorine content. In addition, MCCPs were differentiated by their
proportion of C14 congeners. Standard SCCP mixtures were similar to technical mixtures
of similar chlorine content, whereas MCCP standard mixtures were not, due to their low
abundance of C15-17 congeners. CPs in brown trout and cod showed similarities to technical
CP mixtures and, hence, no hint for CP biotransformation. However, SCCPs in cod were
clustered according to their geographic origin by PCA
Author response
No full textBinding of antigen to the B cell antigen receptor (BCR) initiates a multitude of events resulting in B cell activation. How the BCR becomes signaling-competent upon antigen binding is still a matter of controversy. Using a high-resolution proximity ligation assay (PLA) to monitor the conformation of the BCR and its interactions with co-receptors at a 10–20 nm resolution, we provide direct evidence for the opening of BCR dimers during B cell activation. We also show that upon binding Syk opens the receptor by an inside-out signaling mechanism that amplifies BCR signaling. Furthermore, we found that on resting B cells, the coreceptor CD19 is in close proximity with the IgD-BCR and on activated B cells with the IgM-BCR, indicating nanoscale reorganization of receptor clusters during B cell activation
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