New Constraint on the Local Relic Neutrino Background Overdensity with the First KATRIN Data Runs.

We report on the direct search for cosmic relic neutrinos using data acquired during the first two science campaigns of the KATRIN experiment in 2019. Beta-decay electrons from a high-purity molecular tritium gas source are analyzed by a high-resolution MAC-E filter around the end point at 18.57 keV. The analysis is sensitive to a local relic neutrino overdensity ratio of η<9.7×10^{10}/α (1.1×10^{11}/α) at a 90% (95%) confidence level with α=1 (0.5) for Majorana (Dirac) neutrinos. A fit of the integrated electron spectrum over a narrow interval around the end point accounting for relic neutrino captures in the tritium source reveals no significant overdensity. This work improves the results obtained by the previous neutrino mass experiments at Los Alamos and Troitsk. We furthermore update the projected final sensitivity of the KATRIN experiment to η<1×10^{10}/α at 90% confidence level, by relying on updated operational conditions.

Bound on 3+1 Active-Sterile Neutrino Mixing from the First Four-Week Science Run of KATRIN.

We report on the light sterile neutrino search from the first four-week science run of the KATRIN experiment in 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are analyzed by a high-resolution MAC-E filter down to 40 eV below the endpoint at 18.57 keV. We consider the framework with three active neutrinos and one sterile neutrino. The analysis is sensitive to the mass, m_{4}, of the fourth mass state for m_{4}^{2}≲1000 eV^{2} and to active-to-sterile neutrino mixing down to |U_{e4}|^{2}≳2×10^{-2}. No significant spectral distortion is observed and exclusion bounds on the sterile mass and mixing are reported. These new limits supersede the Mainz results for m_{4}^{2}≲1000 eV^{2} and improve the Troitsk bound for m_{4}^{2}<30 eV^{2}. The reactor and gallium anomalies are constrained for 100<Δm_{41}^{2}<1000 eV^{2}.

Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.

We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57 keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9}) eV^{2}. From this, we derive an upper limit of 1.1 eV (90% confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation.

Primordial germ cell development in the marmoset monkey as revealed by pluripotency factor expression: suggestion of a novel model of embryonic germ cell translocation.

Primordial germ cells (PGCs) are the embryonic progenitors of sperm and egg cells. Mammalian PGCs are thought to actively migrate from the yolk sac endoderm over long distances across the embryo to reach the somatic genital ridges. The general principles of mammalian PGC development were discovered in mice. In contrast, little is known about PGC development in primates due to extremely limited access to primate embryos. Here, we analyzed 12 well preserved marmoset monkey (Callithrix jacchus) embryos covering the phase from PGC emergence in the endoderm to the formation of the sexually differentiated gonad (embryonic day (E) 50 to E95). We show using immunohistochemistry that the pluripotency factors OCT4A and NANOG specifically mark PGCs throughout the period studied. In contrast, SALL4 and LIN28 were first expressed ubiquitously and only later down-regulated in somatic tissues. We further show, for the first time, that PGCs are located in the endoderm in E50 embryos in close spatial proximity to the prospective genital ridge, making a long-range migration of PGCs dispensable. At E65, PGCs are already present in the primitive gonad, while significantly later embryonic stages still exhibit PGCs at their original endodermal site, revealing a wide spatio-temporal window of PGC distribution. Our findings challenge the 'dogma' of active long-range PGC migration from the endoderm to the gonads. We therefore favor an alternative model based primarily on passive translocation of PGCs from the mesenchyme that surrounds the gut to the prospective gonad through the intercalar expansion of mesenchymal tissue which contains the PGCs. In summary, we (i) show differential pluripotency factor expression during primate embryo development and (ii) provide a schematic model for embryonic PGC translocation.

False-positive antibody signals for the pluripotency factor OCT4A (POU5F1) in testis-derived cells may lead to erroneous data and misinterpretations.

Octamer-binding protein 4 (OCT4) is a key player in pluripotent embryonic stem (ES) cells and is essential for the generation of induced pluripotent stem cells. Recently, several reports indicated the spontaneous recovery of pluripotency in cultured adult human testis-derived cells. This was evidenced also by the detection of OCT4 using antibodies. However, the soundness of some data was recently put into question. During our attempts to derive pluripotent cells from the common marmoset monkey (Callithrix jacchus) testis, we obtained inconsistent data which prompted us to analyze deeper the characteristics of three independent OCT4 antibodies that were used in numerous published studies that received greatest attention. All antibodies detected OCT4 by immunofluorescence (IF) in a marmoset monkey ES cell line. Two of the three OCT4 antibodies also gave robust nuclear signals in testis-derived cells. However, the latter cells expressed no OCT4 mRNA as revealed by quantitative RT-PCR and turned out to be mesenchymal cells. When tested in western blot analyses, all antibodies detected heterologously expressed marmoset monkey OCT4 protein. But, importantly, those antibodies that resulted in non-specific signals in IF also showed additional non-specific bands in western blots. In summary, some commercially available OCT4 antibodies result in false-positive signals which may provoke erroneous conclusions when used in studies aiming at the generation of pluripotent cells in vitro. We conclude that (i) antibodies must be carefully characterized before use to prevent misleading observations and (ii) OCT4 expression must be monitored by a second antibody-independent method.

Developmental expression of the pluripotency factor sal-like protein 4 in the monkey, human and mouse testis: restriction to premeiotic germ cells.

SALL4 (sal-like protein 4) is a pluripotency transcription factor, which is highly expressed in embryonic stem (ES) cells and which is essential for mouse preimplantation development. In adult mouse organs, Sall4 mRNA is highly expressed in the testis and ovary, while there is only little or no expression in other organs. There is also a high expression of SALL4 in human testicular germ cell tumors. However, there is as yet no detailed analysis of SALL4 expression during mammalian testicular development. We analyzed SALL4 expression in ES cells, preimplantation embryos, and the developing and adult testis of a nonhuman primate (NHP) species, the common marmoset monkey (Callithrix jacchus). Immunofluorescence revealed SALL4 in the nuclei of marmoset ES cells and preimplantation embryos. Marmoset SALL4 isoform analysis in ES cells and newborn and adult testis by RT- PCR and Western blotting showed two different isoforms, SALL4-A and SALL4-B. Immunohistochemistry localized this transcription factor to the nuclei of primordial germ cells and most gonocytes in the prenatal and early postnatal marmoset testis. In the pubertal and adult testis SALL4 was present in undifferentiated spermatogonia. In the developing and adult human and mouse testis SALL4 expression mimicked the pattern in the marmoset. Adult testes from additional NHP species, the treeshrew, the cat and the dog also exhibited SALL4 in undifferentiated spermatogonia, indicating a conserved expression in the mammalian testis. Taking into account the importance of SALL4 for mouse development, we conclude that SALL4 may play an important role during mammalian germ cell development and is involved in the regulation of spermatogonial proliferation in the adult testis.

[Case of subdural hematoma and hygroma with clinical symptoms of psychiatric disorders]. / Przypadek krwiaka i wodniaka podtwardówkowego ze zmianami psychicznymi dominujacymi w obrazie klinicznym.

The authors describe a case of a large subdural haematoma and hygroma in a male aged 19 years. Schizophrenia-like psychic disturbances and scant neurological signs made the diagnosis of the underlying disease particularly difficult.