Maternal Microchimerism

Microchimerism refers to one individual harboring cells or DNA at a low level that derive from another individual. The most common source is pregnancy when cells from the fetus and the mother pass the placenta bidirectionally, and give rise to maternal microchimerism (cells from the mother in the fetus) and fetal microchimerism (cells from the fetus in the mother). The cells persist in the individual, at least until middleage. Several hypotheses have addressed the consequences of harboring semiallogeneic cells. Both maternal and fetal cells within the host are associated with certain autoimmune diseases, as inducers of the disease but also as repairers of already injured tissue. Furthermore, inducing fetal-maternal tolerance during pregnancy seems to be an important purpose of the cell-trafficking. Observations from the transplantation field yield that this effect may be long lasting. In paper I, we examined the presence of maternal cells within different cellular subsets in tissues from eleven 2nd trimester fetuses. Seven fetuses presented with maternal microchimerism. The cells were widely spread in different tissues and found in both normal fetuses and fetuses with trisomy 21. The cells were of mature immunological and hematopoietic stem cells character. Paper II aimed to examine maternal microchimerism in healthy children’s tonsils and adenoid by a quantitative PCR assay. We found maternal microchimerism in four of 20 children. The children were between four and six years old and harbored maternal cells in the tonsils and/ or adenoid at levels that ranged from 2 x10-2 to 7.1 x10-5. The same children were also positive for maternal cells in peripheral blood. In paper III, we investigated the association between maternal microchimerism in peripheral blood and systemic lupus erythematosus. In the study, 32 nulligravida women with SLE were included. Seventeen brothers of the women and additional 12 unrelated males constituted healthy controls. Two patients and one control appeared with maternal cells in peripheral blood. The result indicates no correlation between maternal microchimerism in blood and SLE (P-value = 0.65). At a follow up, the same individuals tested negative 16 years after the first draw date. The purpose of paper IV was to evaluate the cellular subset and frequency of maternal cells in umbilical cord blood following vaginal deliveries and caesarian sections, when the time of umbilical cord clamping was known. We included 44 babies from normal term pregnancies who were delivered vaginally (24) and by caesarian section (20). Five of 44 (11%) of the umbilical cord blood samples contained maternal microchimerism. The positive fractions were total DNA, CD34+ and CD56+. Four of the five positive samples were from caesarian sections and one was from a vaginal delivery. The positive samples were from deliveries with a mean clamping time of 37 seconds compared to 54 seconds in the negative group. Overall, we have shown that maternal cells are common in fetuses, infants and children. Their nature is of mature immunological and hematopoietic stem cell character. There is no correlation between the autoimmune disorder SLE, and maternal microchimerism

Subset of cortical layer 6b neurons selectively innervates higher order thalamic nuclei in mice

The thalamus receives input from 3 distinct cortical layers, but input from only 2 of these has been well characterized. We therefore investigated whether the third input, derived from layer 6b, is more similar to the projections from layer 6a or layer 5. We studied the projections of a restricted population of deep layer 6 cells (“layer 6b cells”) taking advantage of the transgenic mouse Tg(Drd1a-cre)FK164Gsat/Mmucd (Drd1a-Cre), that selectively expresses Cre-recombinase in a subpopulation of layer 6b neurons across the entire cortical mantle. At P8, 18% of layer 6b neurons are labeled with Drd1a-Cre::tdTomato in somatosensory cortex (SS), and some co-express known layer 6b markers. Using Cre-dependent viral tracing, we identified topographical projections to higher order thalamic nuclei. VGluT1+ synapses formed by labeled layer 6b projections were found in posterior thalamic nucleus (Po) but not in the (pre)thalamic reticular nucleus (TRN). The lack of TRN collaterals was confirmed with single-cell tracing from SS. Transmission electron microscopy comparison of terminal varicosities from layer 5 and layer 6b axons in Po showed that L6b varicosities are markedly smaller and simpler than the majority from L5. Our results suggest that L6b projections to the thalamus are distinct from both L5 and L6a projectionsZ.M.’s laboratory is supported by Medical Research Council (G00900901), Biotechnology and Biological Sciences Research Council (BB/1021833) and The Wellcome Trust (092071/Z/10/Z). E.G. held an MRC Doctoral Studentship; S.H. is supported from Daiichi Sankyo Foundation of Life Science, Japan, L.U. is supported by OXION Wellcome Trust Initiative, Oxford. Y.K. is supported from the Pennsylvania Department of Health using Tobacco CURE Funds SAP#4100062216; P.K. from National Institutes of Health (NIH) R01DC009607 and a visiting Fellowship at St. Catherine’s College, Oxford. F.C.’s laboratory is supported by Human Brain Project (European Flagship, Ref. GA 604102 and Ministerio de Economia y Competitividad MINECO (Spain; Grant BFU2017-88549-P)

Molecular Diversity of Early-Born Subplate Neurons

Subplate cells in the mouse are generally defined as cells located in the subplate layer between the white matter and layer 6a. They are some of the earliest born and maturing cells of the cerebral cortex. The postnatal subplate layer in mouse contains neurons with expression of the presynaptic protein complexin 3 (Cplx3), connective tissue growth factor (CTGF), the orphan nuclear receptor Nr4a2 (Nurr1), and the G-protein-coupled lysophosphatidic acid receptor 1 (Lpar1/Edg2). All 4 of these molecular markers show layer 6b-restricted expression at young postnatal ages, with CTGF expression being the most widespread in the young postnatal subplate. However, all 4 markers overlap in their expression pattern to varying degrees. Here we demonstrate with bromodeoxyuridine birthdating that cells labeled with any 1 of these molecular subplate markers are indeed generated at E11.5 or E12.5 in the mouse. Furthermore, we demonstrate a correlation between gene expression and cell birthdates. Lpar1-GFP cells are preferentially generated on E11.5, whereas Cplx3 or Nurr1-positive cells are equally generated during the 2-day peak of subplate neurogenesis (E11.5-E12.5). Our study also demonstrates that early-born subplate neurons labeled by Cplx3, Nurr1, and Lpar1-GFP survive preferentially after the first postnatal week compared with other subplate neurons

Vascular plant species richness in forest vegetation records differs depending on surveyor

Flächenbezogene Artenzahlen sind besonders im Kontext von Monitoringprojekten grundlegend für die Beurteilung von Veränderungen der Biodiversität. Diese Studie vergleicht die von neun Bearbeitern (5 Einzelbearbeiter, 2 Zweierteams) erfasste Zahl an Gefäßpflanzenarten bei Vegetationserhebungen auf markierten Flächen von 4, 100 und 400 m2 Größe in einem artenreichen Kalkbuchenwald im Göttinger Stadtwald. Dabei wurden Bearbeiter- und Zeiteffekte untersucht, sowie artspezifische Übersehensraten, Fehlbestimmungsraten und Ungenauigkeiten bei der Zuordnung von Pflanzenindividuen zur jeweiligen Aufnahmefläche (Fehlzuordnungsraten) abgeschätzt. Protokollierte Fragen ließen keine systematischen Unterschiede bei der Vertrautheit der Bearbeiter mit der Vegetation vor Ort erkennen, so dass Ausbildung und Erfahrung für gefundene Unterschiede ausschlaggebend sein dürften. Bei den 4 m2 großen Erhebungseinheiten ergaben sich bei der Artenzahl relative Abweichungen der Bearbeiter vom Erwartungswert von 8 bis 26 % (1 bis 4 Arten absolut). Diese waren bei den 100 m2 großen Erhebungseinheiten mit 9 bis 27 % (2 bis 6 Arten absolut) höher. Mit zunehmender Flächengröße nahm der Flächenidentitätseffekt tendenziell ab und der Bearbeitereffekt signifikant zu. Bei den 100 m2 großen Flächen hatte eine längere Bearbeitungszeit einen positiven Effekt auf die Artenzahl. Mit Hilfe artbezogener Auswertungen wurden Übersehens-, Fehlbestimmungs- und Fehlzuordnungsraten ermittelt. Nicht eine Art wurde von allen Bearbeitern auf allen Flächen gefunden, auf denen sie jeweils auftrat. Schwer differenzierbare Arten sowie Arten in ungünstigen Entwicklungsstadien wiesen höhere Übersehens-, aber auch höhere Fehlbestimmungsraten auf. Bei morphologisch gut charakterisierten Arten wurde bei Einzelfunden von einer Fehlzuordnung zur Erhebungseinheit ausgegangen. Die erzielten Ergebnisse sind auch für andere Projekte zur Erfassung der Biodiversität relevant und Bemühungen zur Reduzierung entsprechender Bearbeitereffekte sollten unternommen werden. Eine organisatorische Einbindung entsprechender Bemühungen wird vorgeschlagen.Local species richness is a crucial biodiversity measure also in monitoring projects. This study was carried out in a speciesrich beech forest on limestone within the communal forest of the city of Göttingen. It compares species richness estimates from nine surveyors (five individuals and two teams of two) on plots of 4, 100, and 400 m2 size. The influence of surveyor and elapsed time on the outcome was investigated. Additionally, species-specific overlooking and misinterpretation rates were estimated. As a further source of error, wrong assignment of plant specimen to plots was considered. Analysis of recorded questions of the probates did not reveal a differentiated familiarity with the on-site vegetation on the base of their professional embedding in regional terms. Outcomes have therefore to be seen as the result of individual training and experience. On the spatial level of the 4 m2 plots relative deviances between expected values of species richness and estimates of individual surveyors varied between 8 and 26% (1 to 4 species absolutely). At the 100 m2 plots differences between surveyors were with 9 to 27% (2 to 6 species absolutely) even more pronounced. With increasing plot area effects from plot identity tend to decrease, while observer effects distinctly increase. For the 100 m2 plot level an effect of processing time was detectable. None of the species were found by all surveyors at all subplots on which they occurred. Closely related or otherwise similar species, and those which were in an unfavourable developmental stage, had a higher chance of being overlooked or misinterpreted. Species with peculiar morphological features were considered to be misallocated. For all three types of error respective rates were calculated. The relationships found have generally to be considered in monitoring projects focusing on vegetation changes; however, in large-scale cross-sectional surveys respective error rates should be considered. An organized controlling system is outlined

Patients’ characteristics.

<p>* Manifestations are defined according to American College of Rheumatology’s 1982 revised criteria for SLE [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074534#B44" target="_blank">44</a>], SLAM = Systemic Lupus Activity Measure, a validated measure of disease activity [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074534#B45" target="_blank">45</a>], SLICC = Systemic Lupus International Collaborating Clinics damage index, a validated cumulative organ damage [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074534#B46" target="_blank">46</a>], APS =antiphospholid syndrome was diagnosed according to the Sydney criteria [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074534#B47" target="_blank">47</a>]</p

MMc in controls and healthy individuals in previously published reports.

<p>* Not provided; ** Quantitative real-time PCR; *** single-nucleotide polymorphism; **** Amplification refractory mutation detection system polymerase chain reaction</p

Novel markers reveal subpopulations of subplate neurons in the murine cerebral cortex

The subplate lays the foundation of the developing cerebral cortex, and abnormalities have been suggested to contribute to various brain developmental disorders. The causal relationship between cellular pathologies and cognitive disorders remains unclear, and therefore, a better understanding of the role of subplate cells in cortical development is essential. Only by determining the molecular taxonomy of this diverse class of neurons can we identify the subpopulations that may contribute differentially to cortical development. We identified novel markers for murine subplate cells by comparing gene expression of subplate and layer 6 of primary visual and somatosensory cortical areas of postnatal day (P)8 old mice using a microarray-based approach. We examined the utility of these markers in well-characterized mutants (reeler, scrambler, and p35-KO) where the subplate is displaced in relation to the cortical plate. In situ hybridization or immunohistochemistry confirmed subplate-selective expression of complexin 3, connective tissue growth factor, nuclear receptor-related 1/Nr4a2, and monooxygenase Dbh-like 1 while transmembrane protein 163 also had additional expression in layer 5, and DOPA decarboxylase was also present in the white matter. Localization of marker-positive cells in the reeler and p35-KO cortices suggests different subpopulations of subplate cells. These new markers open up possibilities for further identification of subplate subpopulations in research and in neuropathological diagnosis.Peer reviewe