University of Cologne

About: University of Cologne is a education organization based out in Cologne, Germany. It is known for research contribution in the topics: Population & Gene. The organization has 32050 authors who have published 66350 publications receiving 2210092 citations. The organization is also known as: Universität zu Köln & Universitatis Coloniensis.

Presynaptic receptor systems on the noradrenergic neurones of rat brain.

Abstract: Occurrence and properties of receptors modulating release of noradrenaline were studied in slices of rat occipital cortex and, less extensively, of rat hypothalamus and cerebellar cortex The slices were preincubated with 3H-noradrenaline and then superfused and stimulated either electrically at 1–3 Hz or by 15–20 mM potassium (1) Omission of calcium abolished the electrically and potassium-evoked overflow of tritium Tetrodotoxin blocked the electrically evoked overflow and reduced the response to potassium The electrically evoked overflow of total tritium consisted of 80% 3H-noradrenaline and 19% 3H-3,4-dihydroxyphenylglycol (DOPEG) Cocaine strongly decreased the electrically evoked overflow of 3H-DOPEG The overflow of tritium evoked by 15 mM potassium also contained mainly 3H-noradrenaline with only a minor part of 3H-DOPEG (2) Both the electrically and the potassium-evoked overflow of tritium were reduced by unlabelled noradrenaline (in the presence of cocaine) and tramazoline, and increased by phentolamine and yohimbine The changes in the evoked overflow of total tritium reflected approximately proportionate changes of 3H-noradrenaline and 3H-DOPEG (3) Both the electrically and the potassium-evoked overflow of tritium were reduced by morphine and methionine-enkephalin 3H-noradrenaline and 3H-DOPEG were proportionately decreased Dextrorphan, in contrast to its analgesically active enantiomer levorphanol, had no effect Inhibition by morphine persisted after pretreatment with indometacin (4) Prostaglandin E1 reduced both the electrically and the potassium-evoked overflow of tritium 3H-noradrenaline and 3H-DOPEG were proportionately decreased (5) Phentolamine antagonized the inhibitory effect of noradrenaline, but not that of morphine, enkephalin, and prostaglandin E1 Naloxone antagonized the effect of enkephalin, but not that of tramazoline and prostaglandin E1 (6) Acetylcholine (up to 10−5 M) and oxotremorine (up to 10−4 M) failed to reduce the electrically and potassium-evoked overflow Moreover, atropine (up to 3×10−6 M) had no effect Up to 10−3 M acetylcholine (in the presence of atropine) as well as up to 10−4 M nicotine did not change the basal outflow of tritium in the absence of releasing stimuli 10−3 M nicotine caused an increase which was not changed by hexamethonium or omission of calcium In contrast to the overflow evoked by electrical stimulation or high potassium, the overflow evoked by nicotine mainly consisted of 3H-DOPEG with only a minor part attributable to 3H-noradrenaline (7) γ-Aminobutyric acid slightly enhanced both the basal and (maximally by 27%) the electrically evoked overflow Histamine (in the presence of cocaine) slightly decreased the electrically evoked overflow (maximally by 17%) (8) The following drugs did not change the electrically evoked overflow of tritium: dopamine (in the presence of cocaine), isoprenaline (up to 10−6 M), propranolol (up to 10−6 M), serotonin (in the presence of cocaine), angiotensin I, angiotensin II, saralasin, and substance P (9) It is concluded that transmitter release from the noradrenergic neurones of several brain areas is modulated by drugs acting on α-adrenoceptors, opiate receptors, and prostaglandin receptors It seems likely, though by no means certain, that the receptors involved are located on the noradrenergic nerve endings themselves, ie, that they are presynaptic receptors No evidence was obtained for presynaptic dopamine, β-, muscarine, nicotine, and angiotensin receptors This pattern differs from that found in other tissues, thus substantiating marked tissue differences in presynaptic receptor systems

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

Abstract: Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Expansion and functional activity of Ly‐1+ B cells upon transfer of peritoneal cells into allotype‐congenic, newborn mice

Abstract: Transfer of peritoneal cells from adult donors into newborn, allotype-congenic mice led to colonization of the recipient mice by donor-derived B lymphocytes expressing the Ly-1 surface marker (Ly-1 B cells). These cells not only persisted in the recipient mice for at least 5 months, but also increased in number. In contrast, bone marrow-derived stem cells did not or scarcely give rise to B cells after intraperitoneal injection into congenic newborn recipients under the same experimental conditions. Approximately half of the IgM in the serum of peritoneal cell-recipients was produced by donor-derived Ly-1 B cells, suggesting that high levels of serum IgM in a normal mouse are produced by this B cell subpopulation. The transferred Ly-1 B cells were able to respond in a normal fashion to alpha (1----3)dextran, but they did not participate in thymus-dependent and -independent (TI II) immune responses to the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP). In neither the immune response to alpha (1----3)dextran nor that to NP were we able to detect an influence of the transferred Ly-1 B cells on the selection of the idiotypic repertoire in the recipient mice.

Discovering unobserved heterogeneity in structural equation models to avert validity threats

Abstract: A large proportion of information systems research is concerned with developing and testing models pertaining to complex cognition, behaviors, and outcomes of individuals, teams, organizations, and other social systems that are involved in the development, implementation, and utilization of information technology. Given the complexity of these social and behavioral phenomena, heterogeneity is likely to exist in the samples used in IS studies. While researchers now routinely address observed heterogeneity by introducing moderators, a priori groupings, and contextual factors in their research models, they have not examined how unobserved heterogeneity may affect their findings. We describe why unobserved heterogeneity threatens different types of validity and use simulations to demonstrate that unobserved heterogeneity biases parameter estimates, thereby leading to Type I and Type II errors. We also review different methods that can be used to uncover unobserved heterogeneity in structural equation models. While methods to uncover unobserved heterogeneity in covariance-based structural equation models (CB-SEM) are relatively advanced, the methods for partial least squares (PLS) path models are limited and have relied on an extension of mixture regression--finite mixture partial least squares (FIMIX-PLS) and distance measure-based methods--that have mismatches with some characteristics of PLS path modeling. We propose a new method--prediction-oriented segmentation (PLSPOS)--to overcome the limitations of FIMIX-PLS and other distance measure-based methods and conduct extensive simulations to evaluate the ability of PLS-POS and FIMIX-PLS to discover unobserved heterogeneity in both structural and measurement models. Our results show that both PLS-POS and FIMIX-PLS perform well in discovering unobserved heterogeneity in structural paths when the measures are reflective and that PLS-POS also performs well in discovering unobserved heterogeneity in formative measures. We propose an unobserved heterogeneity discovery (UHD) process that researchers can apply to (1) avert validity threats by uncovering unobserved heterogeneity and (2) elaborate on theory by turning unobserved heterogeneity into observed heterogeneity, thereby expanding theory through the integration of new moderator or contextual variables.