Organization and morphogenesis of the human seminiferous epithelium

Summary The various types of human primary spermatocytes were classified by means of morphological and morphometrical studies. Based on this classification, the topographic arrangement of the spermatocyte populations in the longitudinal course of seminiferous tubules was determined. This analysis revealed human spermatogenesis be to subjected to a complex local plan of organization, which is based upon the geometry of spirals.The centers of gravity of spermatocyte populations of subsequent degrees of differentiation are arranged on he lices that are contracted conically to the lumen of the seminiferous tubule. On these helices the centers of gravity of the populations diverge continuously 173.8°+/-32.4°. Populations of the same degrees of development are arranged on helices with constant diameters. On these helices the centers of gravity of the populations diverge continuously 142.6°+/-14.2°.The present results lead to new aspects of the kinetics and morphogenesis of the seminiferous epithelium, which can be integrated into a comprehensive biological concept.     

Biogeochemistry of Late Paleozoic North American brachiopods and secular variation of seawater composition

Sr/Ca ratios in modern brachiopod shells reflect variations in ambient seawater, whereas their Na contents show no relationship with water depth or habitat. Their Mn and Fe contents are controlled, in part, by leaching of these elements from oxide coatings or the low input/sedimentation rate of detrital material into depositional areas such as Quatsino Sound. For most Carboniferous brachiopods from North America, the Mn and Fe contents are similar to those recorded by their Recent counterparts. The high Mn and Fe contents in the brachiopods from shales suggest several possibilities for these levels. One possibility is the leaching of Mn and Fe from oxide coatings/matrix which was not completely removed in the cleaning process, or the high levels in part reflect unusual depositional conditions (some degree of anoxia) for the local shaly environments. The Sr/Ca ratio of brachiopods and, by inference, complementary seawater, did not vary significantly during the Carboniferous. The Sr/Ca minimum observed in brachiopods of Mississippian age coincides with a dip in the ⁸⁷Sr/⁸⁶Sr curve and correlates with the Hercynian orogeny. This is attributed to the cycling of seawater through mid-ocean ridge basalts, and postulated exchange reactions account for variation in the composition of seawater-Ca. The unidirectional trend of heavier δ¹³C values from the Devonian to the Permian is intricately coupled with the evolution of the terrestrial biomass. In addition to expansion of terrestrial plants, burial of reduced carbon in the form of coal (organic matter) contributed to the observed shift. The start of the Permo-Pennsylvanian glaciation is marked by a negative excursion of the secular carbon trend, which is linked to weathering of reduced carbon and its return to the oceanic reservoir with its oxidized carbon. The oxygen isotope values reflect the unidirectional trend towards higher values of the carbon data with decreasing geologic age. Negative excursions of the trend may be related to extensive weathering of terrestrial and submarine rocks, whereas positive excursions may be related to hydrothermal alteration of submarine rocks and dehydration of oceanic crust during times of active sea-floor spreading. Oxygen-calculated water temperatures of unaltered brachiopod material are unrealistically high for all of the Devonian, and the Chesterian-Meramecian, Desmoinesian-Missourian, and Artinskian Epochs. During these times maximum water temperatures of 42° to 56°C are well above the thermal threshold of protein denaturation. This process, which is lethal to most higher organisms, demands an adjustment in oxygen of -2.5%. for samples older than Missourian, and of -1.250%. for samples spanning the Missourian-Artinskian interval. With these adjustments and salinity considerations made prior to calculations, water temperatures become reasonable for the Late Paleozoic epeiric, tropical seas of North America.     

Terahertz Electromagnetic Fields (0.106 THz) Do Not Induce Manifest Genomic Damage In Vitro

Terahertz electromagnetic fields are non-ionizing electromagnetic fields in the frequency range from 0.1 to 10 THz. Potential applications of these electromagnetic fields include the whole body scanners, which currently apply millimeter waves just below the terahertz range, but future scanners will use higher frequencies in the terahertz range. These and other applications will bring along human exposure to these fields. Up to now, only a limited number of investigations on biological effects of terahertz electromagnetic fields have been performed. Therefore, research is strongly needed to enable reliable risk assessment.Cells were exposed for 2 h, 8 h, and 24 h with different power intensities ranging from 0.04 mW/cm² to 2 mW/cm², representing levels below, at, and above current safety limits. Genomic damage on the chromosomal level was measured as micronucleus formation. DNA strand breaks and alkali-labile sites were quantified with the comet assay. No DNA strand breaks or alkali-labile sites were observed as a consequence of exposure to terahertz electromagnetic fields in the comet assay. The fields did not cause chromosomal damage in the form of micronucleus induction.     

Comparison of five commercial extraction kits for subsequent membrane protein profiling

Membrane proteins account for 70–80% of all pharmaceutical targets emphasizing their clinical relevance. Identification of new, differentially expressed membrane proteins reflecting distinct disease properties is thus of high importance. Unfortunately, isolation and analysis of membrane-bound proteins is hampered by their relative low abundance in total cell lysates, their frequently large size and their hydrophobic properties. We thus aimed to identify protocols that allow for highly efficient isolation and purification of membrane-bound proteins for subsequent protein profiling. We present a comparative study of different membrane protein extraction methods that vary in total protein yield between 0.02 and 4.8 mg using constant cell pellets of the colorectal carcinoma cell line SW620. We also demonstrate by means of polyacrylamide gel electrophoresis (SDS–PAGE) and Western blot analysis that the majority of commercial membrane extraction kits harbor a substantial cytosolic contamination of their membranous fraction. Based on purity of membranous fraction, protein yield, time and costs, we show superiority of two commercial extraction kits for downstream proteome analyses of membrane proteins.     

Fluvastatin Mediated Breast Cancer Cell Death: A Proteomic Approach to Identify Differentially Regulated Proteins in MDA-MB-231 Cells

Statins are increasingly being recognized as anti-cancer agents against various cancers including breast cancer. To understand the molecular pathways targeted by fluvastatin and its differential sensitivity against metastatic breast cancer cells, we analyzed protein alterations in MDA-MB-231 cells treated with fluvastatin using 2-DE in combination with LC-MS/MS. Results revealed dys-regulation of 39 protein spots corresponding to 35 different proteins. To determine the relevance of altered protein profiles with breast cancer cell death, we mapped these proteins to major pathways involved in the regulation of cell-to-cell signaling and interaction, cell cycle, Rho GDI and proteasomal pathways using IPA analysis. Highly interconnected sub networks showed that vimentin and ERK1/2 proteins play a central role in controlling the expression of altered proteins. Fluvastatin treatment caused proteolysis of vimentin, a marker of epithelial to mesenchymal transition. This effect of fluvastatin was reversed in the presence of mevalonate, a downstream product of HMG-CoA and caspase-3 inhibitor. Interestingly, fluvastatin neither caused an appreciable cell death nor did modulate vimentin expression in normal mammary epithelial cells. In conclusion, fluvastatin alters levels of cytoskeletal proteins, primarily targeting vimentin through increased caspase-3- mediated proteolysis, thereby suggesting a role for vimentin in statin-induced breast cancer cell death.     

Google Trends reflect allergic rhinitis symptoms related to birch and grass pollen seasons

Google Trends (GT) describes the variation of the relevant interest of internet searches toward medical conditions and related symptoms. Allergic rhinitis symptom levels result from the intensity of exposure to aeroallergens in combination with relevant medication use. We analyze data from Germany to examine the relationship between hay fever-related Google search terms, symptom levels, medication use, and pollen count levels. For doing so, we also employ the new definitions on pollen season and peak pollen period start and end as proposed by the European Academy of Allergy and Clinical Immunology in a recently published position paper. We extract GT data for a number of search terms related to allergic rhinitis for Germany. We use total nasal symptom and mediation scores as reported by patients via a patient hay fever diary in the Berlin and Brandenburg areas in Germany for 3 years (2014–2016), accompanied by pollen data. Then a Pearson and Spearman correlation analysis is performed between symptom data and GT data. A graphical analysis is conducted, and the identification of pollen season and peak pollen periods is done based on the EAACI criteria. The analysis reveals that GT data are highly correlated with symptom levels and follow peak pollen period start–end, concerning grass and birch pollen-induced allergic rhinitis symptoms. GT data can be used as a proxy for the identification of the onset and variation of nasal symptom and medication score for allergic rhinitis sufferers.     

A model of radiation action based on nanodosimetry and the application to ultra-soft X-rays

Radiation and Environmental Biophysics - A radiation action model based on nanodosimetry is presented. It is motivated by the finding that the biological effects of various types of ionizing...     

Subtypes of non-transformed human mammary epithelial cells cultured in vitro: histo-blood group antigen H type 2 defines basal cell-derived cells

Abstract. Normal (non-transformed) human mammary epithelial cell lines derived from reduction mammoplasties were analyzed by immunocytochemistry with more than 80 monoclonal antibodies (mAbs) and other specific reagents to tissue-specific and developmentally regulated antigens at different passage levels. A subpopulation of poorly differentiated, proliferating epithelial cells, corresponding to the 'selected' cell type of late passages, is shown to be characterized by a new marker, the histo-blood group antigen H type 2, probably carried on a membrane-bound glycolipid. These cells also express a number of other onco-developmental carbohydrate antigens [Le^y, Le^x, sialosyl-Le^a, precursor of Thomsen Friedenreich antigen (T_n), but not Thomsen-Friedenreich antigen and sialosyl-T_n). Their cytokeratin (CK) phenotype, as assessed by reactivity with monospecific mAbs and two-dimensional gel electrophoresis, is CK 5, 6, 14 and 17, with CK 19 being consistently absent, and varying minor amounts of CK 7, 8 and 18, as well as 15 and 16. The reactivity of these cells with a panel of 11 mAbs specific for CK 18 varies considerably even after cloning, indicating heterogeneity of epitope expression or accessibility. Our data strongly suggest that the H type 2⁺ cells develop from the basal cell layer of the mammary gland.