Testicular peritubular cells are located in the lamina propria of seminiferous tubules. These cells, significantly contributing to the basal membrane of seminiferous epithelium, have been studied in ...a number of species. However, there is a lack of data on the development of the lamina propria in the human testis. The aim of our survey was to investigate the characteristics of the lamina propria and, in particular, peritubular cells in the fetal human testes by immunohistological and stereological methods. Therefore, testes (14-39 weeks of gestation, n = 45) were dissected and fixed in a 4% buffered paraformaldehyde solution. Several pieces of each testis were embedded in paraffin and processed for immunohistochemical and stereological analysis. All investigated testes have shown sex cords in the process of development and differentiation. Morphologically, peritubular cells in the lamina propria can be divided into two types: fibroblast-like (FL) and myoid-like (ML) type (cells which much resemble mature myoid cells). By immunohistochemistry, both FL and ML cells are found to be strongly positive for the intermediate filament desmin, but negative for alpha-smooth actin. While FL cells intensively express Ki-67 demonstrating proliferative activity, ML cells are found to be negative. The basement membrane of sex cords as well as the blood vessels of the interstitium show strong positivity to collagen IV and laminin. Concerning the correlation between the appearance of the investigated antigens with the gestational age, all antigens have been expressed (in the manner described above) already in the 14th week of gestation. The stereological analysis of the number (Nv) and volume (Vv) of peritubular cells indicates a pulsatile development of these cells in the lamina propria of the human fetal testis. While the stereological variables determined for FL cells show a gradual decrease, the same variables determined for ML cells demonstrate a successive increase. It appears that the lamina propria of the fetal human testes shares many of the properties previously discovered in rodents.
Massive sets of stellar spectroscopic observations are rapidly becoming available and these can be used to determine the chemical composition and evolution of the Galaxy with unprecedented precision. ...One of the major challenges in this endeavour involves constructing realistic models of stellar spectra with which to reliably determine stellar abundances. At present, large stellar surveys commonly use simplified models that assume that the stellar atmospheres are approximately in local thermodynamic equilibrium (LTE). To test and ultimately relax this assumption, we have performed non-LTE calculations for 13 different elements (H, Li, C, N, O, Na, Mg, Al, Si, K, Ca, Mn, and Ba), using recent model atoms that have physically-motivated descriptions for the inelastic collisions with neutral hydrogen, across a grid of 3756 1D
MARCS
model atmospheres that spans 3000 ≤
T
eff
∕K ≤ 8000, − 0.5 ≤log
g
∕cm s
−2
≤ 5.5, and − 5 ≤ Fe/H ≤ 1. We present the grids of departure coefficients that have been implemented into the GALAH DR3 analysis pipeline in order to complement the extant non-LTE grid for iron. We also present a detailed line-by-line re-analysis of 50 126 stars from GALAH DR3. We found that relaxing LTE can change the abundances by between − 0.7 dex and + 0.2 dex for different lines and stars. Taking departures from LTE into account can reduce the dispersion in the A/Fe versus Fe/H plane by up to 0.1 dex, and it can remove spurious differences between the dwarfs and giants by up to 0.2 dex. The resulting abundance slopes can thus be qualitatively different in non-LTE, possibly with important implications for the chemical evolution of our Galaxy. The grids of departure coefficients are publicly available and can be implemented into LTE pipelines to make the most of observational data sets from large spectroscopic surveys.
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FMFMET, NUK, UL, UM, UPUK
How the nuclear lamina (NL) impacts on global chromatin architecture is poorly understood. Here, we show that NL disruption in Drosophila S2 cells leads to chromatin compaction and repositioning from ...the nuclear envelope. This increases the chromatin density in a fraction of topologically-associating domains (TADs) enriched in active chromatin and enhances interactions between active and inactive chromatin. Importantly, upon NL disruption the NL-associated TADs become more acetylated at histone H3 and less compact, while background transcription is derepressed. Two-colour FISH confirms that a TAD becomes less compact following its release from the NL. Finally, polymer simulations show that chromatin binding to the NL can per se compact attached TADs. Collectively, our findings demonstrate a dual function of the NL in shaping the 3D genome. Attachment of TADs to the NL makes them more condensed but decreases the overall chromatin density in the nucleus by stretching interphase chromosomes.
A 64 year old women without any previous history of bleeding diathesis presented with bone pain and gastrointestinal bleeding. An isolated severe factor X deficiency (factor X activity 0.5%, factor X ...antigen less than 12.5%) was found. No inhibitor that inactivated factor X in vitro or interfered with factor X assay could be demonstrated. Substitution therapy with a prothrombin complex preparation containing factor X (PPSB Biotest) was given. Factor X recovery in the first 2 days was lower than expected (below 20%) and half life of factor X was shortened (150 minutes). Subsequently, a diagnosis of multiple myeloma (light chain myeloma, type kappa) was made. Amyloidosis was excluded by electronmicroscopic examination of rectum biopsies. Chemotherapy according to the M2 protocol (Case et al) was initiated. Factor X recovery improved dramatically within 2 weeks and there was a continuous increase of factor X activity and antigen during chemotherapy. After 6 courses a complete haematological remission (less than 5% plasma cells in the bone marrow, disappearance of light chains) was obtained and factor X activity and antigen returned to normal.
Isolated factor X deficiency is a wellknown complication of amyloidosis. To our knowledge, this is the first case of factor X deficiency in multiple myeloma without amyloidosis. The complete normalization of factor X after successful chemotherapy indicates that plasma cell proliferation may have been the cause of the factor X deficiency. Binding of factor X to plasma cells containing light chains could be a possible explanation, and we are currently examining this hypothesis.
Long-term trends in neuroblastoma incidence and survival in unscreened populations are unknown. We explored trends in incidence, stage at diagnosis, treatment and survival of neuroblastoma in the ...Netherlands from 1990 to 2014.
The Netherlands Cancer Registry provided data on all patients aged <18 years diagnosed with a neuroblastoma. Trends in incidence and stage were evaluated by calculating the average annual percentage change (AAPC). Univariate and multivariable survival analyses were performed for stage 4 disease to test whether changes in treatment are associated with survival.
Of the 593 newly diagnosed neuroblastoma cases, 45% was <18 months of age at diagnosis and 52% had stage 4 disease. The age-standardized incidence rate for stage 4 disease increased at all ages from 3.2 to 5.3 per million children per year (AAPC + 2.9%, p < .01). This increase was solely for patients ≥18 months old (3.0–5.4; AAPC +3.3%, p = .01). Five-year OS of all patients increased from 44 ± 5% to 61 ± 4% from 1990 to 2014 (p < .01) and from 19 ± 6% to 44 ± 6% (p < .01) for patients with stage 4 disease. Multivariable analysis revealed that high-dose chemotherapy followed by autologous stem cell rescue and anti-GD2-based immunotherapy were associated with this survival increase (HR 0.46, p < .01 and HR 0.37, p < .01, respectively).
Incidence of stage 4 neuroblastoma increased exclusively in patients aged ≥18 months since 1990, whereas the incidence of other stages remained stable. The 5-year OS of stage 4 patients improved, mostly due to the introduction of high-dose chemotherapy followed by stem cell rescue and immunotherapy.
•The incidence of stage 4 neuroblastoma increased 2.9% per year between 1990 and 2014.•Five-year overall survival of stage 4 patients improved from 19 ± 6% to 44 ± 6%.•High-dose chemotherapy and immunotherapy contributed most to the improved survival.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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