Stimulation der TSH-Sekretion durch TRF-Belastung bei hypothalamischen und hypophysären Krankheitsbildern

1. Die Antworten der Serum-TSH-Spiegel (Thyreoidea-stimulierendes Hormon) auf TRF-Injektion (Thyrotropin Releasing Factor) bei 8 Normalpersonen und 37 z. T. zweimal untersuchten Patienten mit hypophysärer oder hypothalamischer Erkrankung werden mitgeteilt. 2. Hypophysektomierte Patienten mit intrasellären Tumoren (N=12) zeigten keine oder nur subnormale Anstiege der TSH-Spiegel. 3. Von 9 präoperativ untersuchten Patienten mit intrasellärem HVL-Adenom hatten 3 eine sekundäre Hypothyreose. Diese 3 reagierten dennoch mit einem normalen Anstieg der TSH-Spiegel. Dieser Befund schränkt die diagnostische Wertigkeit der TRF-Belastung zur Differenzierung hypophysärer und hypothalamischer sekundärer Hypothyreosen ein. Die 6 euthyreoten Patienten dieser Gruppe zeigten erwartungsgemäß einen normalen TSH-Anstieg. 4. Bei den Patienten mit sekundärer Hypothyreose bei suprasellärem Tumor oder hypothalamischer Erkrankung (N=7) fand sich mit einer Ausnahme ein normaler oder ein erhöhter TSH-Anstieg. Die Bedeutung des Ausschlusses einer primären Hypothyreose wurde dargestellt, da diese Erkrankung ebenfalls durch erhöhte TSH-Anstiege bei TRF-Belastung charakterisiert ist. 5. Je ein Patient aus der Gruppe der aktiven (N=7) und der behandelten (N=6) Akromegalie zeigten einen nicht auf eine primäre Hypothyreose zurückführbaren erhöhen TSH-Anstieg, dessen Rolle für das gehäufte Auftreten einer Struma bei Akromegalie zu diskutieren ist.1. The response of the serum TSH levels after i.v. administration of 500 µg TRF have been determined in normal controls (n=8) and in 37 patients with pituitary tumour or hypothalamic disease. 2. Following hypophysectomy in patients with intrasellar tumours (n=12), the increment in TSH levels after TRF was absent or diminished. 3. Secondary hypothyroidism was found pre-operatively in 3 of 9 patients with intrasellar pituitary adenoma. In these 3 patients, however, a normal TSH response to TRF was found. This result diminishes the diagnostic value of the TRF test regarding the distinction of pituitary and hypothalamic secondary hypothyroidism. A normal TSH response was found, as expected, in the 6 euthyroid patients of this group. 4. The TSH response was found to be normal or elevated in all but one of 7 patients with secondary hypothyroidism due to suprasellar tumour or hypothalamic disease. Primary hypothyroidism is also characterized by an increased TSH response and has to be excluded. 5. Among the patients with active (n=7) or treated (n=6) acromegaly, increased TSH response was found twice, i.e. in one patient of each of the two groups. In both patients, primary hypothyroidism could be excluded. The relevance of this increased TSH response for goitrogenesis in acromegaly is discussed

Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

Nutrition, bacterial composition of the gastrointestinal tract, and general health status can all influence the metabolic profile of an organism. We previously demonstrated that feeding pasteurized transgenic goats’ milk expressing human lysozyme (hLZ) can positively impact intestinal morphology and modulate intestinal microbiota composition in young pigs. The objective of this study was to further examine the effect of consuming hLZ-containing milk on young pigs by profiling serum metabolites. Pigs were placed into two groups and fed a diet of solid food and either control (non-transgenic) goats’ milk or milk from hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the feeding period and global metabolite profiling was performed. For a total of 225 metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels of 18 known and 4 unknown metabolites differed significantly between the two groups with the direction of change in 13 of the 18 known metabolites being almost entirely congruent with improved health status, particularly in terms of the gastrointestinal tract health and immune response, with the effects of the other five being neutral or unknown. These results further support our hypothesis that consumption of hLZ-containing milk is beneficial to health

High on-off conductance switching ratio in optically-driven self-assembled conjugated molecular systems

A new azobenzene-thiophene molecular switch is designed, synthesized and used to form self-assembled monolayers (SAM) on gold. An "on/off" conductance ratio up to 7x1E3 (with an average value of 1.5x1E3) is reported. The "on" conductance state is clearly identified to the cis isomer of the azobenzene moiety. The high "on/off" ratio is explained in terms of photo-induced, configuration-related, changes in the electrode-molecule interface energetics (changes in the energy position of the molecular orbitals with respect to the Fermi energy of electrodes) in addition to changes in the tunnel barrier length (length of the molecules). First principles DFT calculations demonstrate a better delocalization of the frontier orbitals, as well as a stronger electronic coupling between the azobenzene moiety and the electrode for the cis configuration over the trans one. Measured photoionization cross-sections for the molecules in the SAM are close to the known values for azobenzene derivatives in solution.Comment: 1 file with main text, figure and suppementary informatio

Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation

Statins such as simvastatin are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and standard therapy for the prevention and treatment of cardiovascular diseases in mammals. Here we show that simvastatin significantly increased the mean and maximum lifespan of Drosophila melanogaster (Drosophila) and enhanced cardiac function in aging flies by significantly reducing heart arrhythmias and increasing the contraction proportion of the contraction/relaxation cycle. These results appeared independent of internal changes in ubiquinone or juvenile hormone levels. Rather, they appeared to involve decreased protein prenylation. Simvastatin decreased the membrane association (prenylation) of specific small Ras GTPases in mice. Both farnesyl (L744832) and type 1 geranylgeranyl transferase (GGTI-298) inhibitors increased Drosophila lifespan. These data are the most direct evidence to date that decreased protein prenylation can increase cardiac health and lifespan in any metazoan species, and may explain the pleiotropic (non-cholesterol related) health effects of statins

Nanomechanical detection of antibiotic-mucopeptide binding in a model for superbug drug resistance

The alarming growth of the antibiotic-resistant superbugs methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) is driving the development of new technologies to investigate antibiotics and their modes of action. We report the label-free detection of vancomycin binding to bacterial cell wall precursor analogues (mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically relevant concentrations in blood serum. Differential measurements quantified binding constants for vancomycin-sensitive and vancomycin-resistant mucopeptide analogues. Moreover, by systematically modifying the mucopeptide density we gain new insights into the origin of surface stress. We propose that stress is a product of a local chemical binding factor and a geometrical factor describing the mechanical connectivity of regions affected by local binding in terms of a percolation process. Our findings place BioMEMS devices in a new class of percolative systems. The percolation concept will underpin the design of devices and coatings to significantly lower the drug detection limit and may also impact on our understanding of antibiotic drug action in bacteria.Comment: Comments: This paper consists of the main article (6 pages, 5 figures) plus Supplemental Material (6 pages, 3 figures). More details are available at http://www.london-nano.co

First M87 Event Horizon Telescope Results. III. Data Processing and Calibration

We present the calibration and reduction of Event Horizon Telescope (EHT) 1.3 mm radio wavelength observations of the supermassive black hole candidate at the center of the radio galaxy M87 and the quasar 3C 279, taken during the 2017 April 5-11 observing campaign. These global very long baseline interferometric observations include for the first time the highly sensitive Atacama Large Millimeter/submillimeter Array (ALMA); reaching an angular resolution of 25 μas, with characteristic sensitivity limits of ∼1 mJy on baselines to ALMA and ∼10 mJy on other baselines. The observations present challenges for existing data processing tools, arising from the rapid atmospheric phase fluctuations, wide recording bandwidth, and highly heterogeneous array. In response, we developed three independent pipelines for phase calibration and fringe detection, each tailored to the specific needs of the EHT. The final data products include calibrated total intensity amplitude and phase information. They are validated through a series of quality assurance tests that show consistency across pipelines and set limits on baseline systematic errors of 2% in amplitude and 1° in phase. The M87 data reveal the presence of two nulls in correlated flux density at ∼3.4 and ∼8.3 Gλ and temporal evolution in closure quantities, indicating intrinsic variability of compact structure on a timescale of days, or several light-crossing times for a few billion solar-mass black hole. These measurements provide the first opportunity to image horizon-scale structure in M87

Endoreplication Controls Cell Fate Maintenance

Cell-fate specification is typically thought to precede and determine cell-cycle regulation during differentiation. Here we show that endoreplication, also known as endoreduplication, a specialized cell-cycle variant often associated with cell differentiation but also frequently occurring in malignant cells, plays a role in maintaining cell fate. For our study we have used Arabidopsis trichomes as a model system and have manipulated endoreplication levels via mutants of cell-cycle regulators and overexpression of cell-cycle inhibitors under a trichome-specific promoter. Strikingly, a reduction of endoreplication resulted in reduced trichome numbers and caused trichomes to lose their identity. Live observations of young Arabidopsis leaves revealed that dedifferentiating trichomes re-entered mitosis and were re-integrated into the epidermal pavement-cell layer, acquiring the typical characteristics of the surrounding epidermal cells. Conversely, when we promoted endoreplication in glabrous patterning mutants, trichome fate could be restored, demonstrating that endoreplication is an important determinant of cell identity. Our data lead to a new model of cell-fate control and tissue integrity during development by revealing a cell-fate quality control system at the tissue level