Physcomitrium patens PpRIC, an ancestral CRIB-domain ROP effector, inhibits auxin-induced differentiation of apical initial cells

RHO guanosine triphosphatases are important eukaryotic regulators of cell differentiation and behavior. Plant ROP (RHO of plant) family members activate specific, incompletely characterized downstream signaling. The structurally simple land plant Physcomitrium patens is missing homologs of key animal and flowering plant RHO effectors but contains a single CRIB (CDC42/RAC interactive binding)-domain -contain-ing RIC (ROP-interacting CRIB-containing) protein (PpRIC). Protonemal P. patens filaments elongate based on regular division and PpROP-dependent tip growth of apical initial cells, which upon stimulation by the hor-mone auxin differentiate caulonemal characteristics. PpRIC interacts with active PpROP1, co-localizes with this protein at the plasma membrane at the tip of apical initial cells, and accumulates in the nucleus. Remark-ably, PpRIC is not required for tip growth but is targeted to the nucleus to block caulonema differentiation downstream of auxin-controlled gene expression. These observations establish functions of PpRIC in medi-ating crosstalk between ROP and auxin signaling, which contributes to the maintenance of apical initial cell identity

An Infrared Comparison of Type-1 and Type-2 Quasars

We model the optical to far-infrared SEDs of a sample of six type-1 and six type-2 quasars selected in the mid-infrared. The objects in our sample are matched in mid-IR luminosity and selected based on their Spitzer IRAC colors. We obtained new targeted Spitzer IRS and MIPS observations and used archival photometry to examine the optical to far-IR SEDs. We investigate whether the observed differences between samples are consistent with orientation-based unification schemes. The type-1 objects show significant emission at 3 micron. They do not show strong PAH emission and have less far-IR emission on average when compared to the type-2 objects. The SEDs of the type-2 objects show a wide assortment of silicate features, ranging from weak emission to deep silicate absorption. Some also show strong PAH features. In comparison, silicate is only seen in emission in the type-1 objects. This is consistent with some of the type-2s being reddened by a foreground screen of cooler dust, perhaps in the host galaxy itself. We investigate the AGN contribution to the far-IR emission and find it to be significant. We also estimate the star formation rate for each of the objects by integrating the modeled far-IR flux and compare this with the SFR found from PAH emission. We find the type-2 quasars have a higher average SFR than the type-1 quasars based on both methods, though this could be due to differences in bolometric luminosities of the objects. While we find pronounced differences between the two types of objects, none of them are inconsistent with orientation-based unification schemes.Comment: Accepted for publication in Ap

Virushepatitis B und D im Jahr 2021

Hepatitis B ist eine der häufigsten Infektionskrankheiten weltweit und im Fall eines chronischen Verlaufs eine der bedeutendsten Ursachen von Leberzirrhose und Leberzellkarzinom. Auch Hepatitis D kommt weltweit vor. Deutschland hat sich den Eliminierungszielen viraler Hepatitiden der WHO bis 2030 verschrieben, allerdings stellte die COVID-19-Pandemie eine große Herausforderung beim Erreichen dieser Ziele dar. Im Jahr 2021 wurde eine Zunahme von übermittelten Hepatitis-B-Fällen um 22 % im Vergleich zu 2020 verzeichnet und damit nach einem wohl hauptsächlich pandemiebedingten Rückgang das Niveau von 2019 nahezu wieder erreicht. Anlässlich des Welt-Hepatitis-Tages werden im Epidemiologischen Bulletin 30/2022 die Meldedaten zu Hepatitis B und D des Jahres 2021 nach Infektionsschutzgesetz dargestellt sowie aktuelle Studien zur Hepatitis-B-Virus-Prävalenz und Impfabdeckung in der Allgemeinbevölkerung und in ausgewählten Subpopulationen zusammengefasst

TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients - First Results on the Influence of Tumor-Infiltrating Lymphocytes

Background: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. Methods: Neoadjuvantly treated HER2-positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype ‘lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. Results: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). Conclusion: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach

Physcomitrium patens PpRIC, an ancestral CRIB-domain ROP effector, inhibits auxin-induced differentiation of apical initial cells

RHO guanosine triphosphatases are important eukaryotic regulators of cell differentiation and behavior. Plant ROP (RHO of plant) family members activate specific, incompletely characterized downstream signaling. The structurally simple land plant Physcomitrium patens is missing homologs of key animal and flowering plant RHO effectors but contains a single CRIB (CDC42/RAC interactive binding)-domain -contain-ing RIC (ROP-interacting CRIB-containing) protein (PpRIC). Protonemal P. patens filaments elongate based on regular division and PpROP-dependent tip growth of apical initial cells, which upon stimulation by the hor-mone auxin differentiate caulonemal characteristics. PpRIC interacts with active PpROP1, co-localizes with this protein at the plasma membrane at the tip of apical initial cells, and accumulates in the nucleus. Remark-ably, PpRIC is not required for tip growth but is targeted to the nucleus to block caulonema differentiation downstream of auxin-controlled gene expression. These observations establish functions of PpRIC in medi-ating crosstalk between ROP and auxin signaling, which contributes to the maintenance of apical initial cell identity

Mutation-Dependent Pathomechanisms Determine the Phenotype in the Bestrophinopathies

Best vitelliform macular dystrophy (BD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and the autosomal recessive bestrophinopathy (ARB), together known as the bestrophinopathies, are caused by mutations in the bestrophin-1 (BEST1) gene affecting anion transport through the plasma membrane of the retinal pigment epithelium (RPE). To date, while no treatment exists a better understanding of BEST1-related pathogenesis may help to define therapeutic targets. Here, we systematically characterize functional consequences of mutant BEST1 in thirteen RPE patient cell lines differentiated from human induced pluripotent stem cells (hiPSCs). Both BD and ARB hiPSC-RPEs display a strong reduction of BEST1-mediated anion transport function compared to control, while ADVIRC mutations trigger an increased anion permeability suggesting a stabilized open state condition of channel gating. Furthermore, BD and ARB hiPSC-RPEs differ by the degree of mutant protein turnover and by the site of subcellular protein quality control with adverse effects on lysosomal pH only in the BD-related cell lines. The latter finding is consistent with an altered processing of catalytic enzymes in the lysosomes. The present study provides a deeper insight into distinct molecular mechanisms of the three bestrophinopathies facilitating functional categorization of the more than 300 known BEST1 mutations that result into the distinct retinal phenotypes