Comparative study of gp130 cytokine effects on corticotroph AtT-20 cells - Redundancy or specificity of neuroimmunoendocrine modulators?

Objective: This comparative in vitro study examined the effects of all known gp130 cytokines on murine corticotroph AtT-20 cell function. Methods: Cytokines were tested at equimolar concentrations from 0.078 to 10 nM. Tyrosine phosphorylation of the signal transducer and activator of transcription ( STAT) 3 and STAT1, the STAT-dependent suppressor of cytokine signaling (SOCS)-3 promoter activity, SOCS-3 gene expression, STAT-dependent POMC promoter activity and adrenocorticotropic hormone ( ACTH) secretion were determined. Results: Leukemia inhibitory factor (LIF), human oncostatin M (OSM) and cardiotrophin (CT)-1 (LIFR/gp130 ligands), as well as ciliary neurotrophic factor ( CNTF) and novel neurotrophin1/B-cell stimulating factor-3 (CNTFRalpha/LIFR/gp130 ligands) are potent stimuli of corticotroph cells in vitro. In comparison, interleukin (IL)-6 (IL-6R/gp130 ligand) and IL-11 (IL-11R/gp130 ligand) exhibited only modest direct effects on corticotrophs, while murine OSM (OSMR/gp130 ligand) showed no effect. Conclusion: (i) CNTFR complex ligands are potent stimuli of corticotroph function, comparable to LIFR complex ligands; (ii) IL-6 and IL-11 are relatively weak direct stimuli of corticotroph function; (iii) differential effects of human and murine OSM suggest that LIFR/gp130 (OSMR type I) but not OSMR/gp130 (OSMR type II) are involved in corticotroph signaling. (iv) CT-1 has the hitherto unknown ability to stimulate corticotroph function, and (v) despite redundant immuno-neuroendocrine effects of different gp130 cytokines, corticotroph cells are preferably activated through the LIFR and CNTFR complexes. Copyright (C) 2004 S. Karger AG, Basel

Movement-related potentials in Parkinson's disease

To date, many different approaches have been used to study the impairment of motor function in Parkinson's disease (PD). Event-related potentials (ERPs) are averaged amplitude fluctuations of the ongoing EEG activity that are time locked to specific sensory, motor or cognitive events, and as such can be used to study different brain processes with an excellent temporal resolution. Movement-related potentials (MRPs) are ERPs associated with processes of voluntary movement preparation and execution in different paradigms. In this review we concentrate on MRPs in PD. We review studies recording the Bereitschaftspotential, the Contingent Negative Variation, and the lateralized readiness potential in PD to highlight the contributions they have made to further understanding motor deficits in PD. Possible directions for future research are also discussed

Event-related potentials and cognition in Parkinson's disease: An integrative review

Cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD), but the nature of cognitive changes varies considerably between individuals. According to the dual-syndrome hypothesis, one cluster of patients is characterized by deficits in executive function that may be related to fronto-striatal dysfunction. Other patients primarily show non-frontal cognitive impairments that progress rapidly to PD dementia (PDD). We provide a comprehensive review of event-related potential (ERP) studies to identify ERP measures substantiating the heterogeneity of cognitive impairment in PD. Our review revealed evidence for P3b and mismatch-negativity alterations in PDD, but not in non-demented PD, indicating that alterations of these ERPs constitute electrophysiological markers for PDD. In contrast, ERP correlates of executive functions, such as NoGo-P3, N2, and error(-related) negativity (Ne/ERN), appear to be attenuated in non-demented PD patients in a dopamine-dependent manner. Hence, ERP measures confirm and yield distinct electrophysiological markers for the heterogeneity of cognitive impairment in PD. We discuss limitations and open questions of the ERP approach and provide directions and predictions for future ERP research

Gallbladder metastasis from renal cell carcinoma mimicking acute cholecystitis

Renal cell carcinoma constitutes about 3% of adult malignancies. It has a high metastatic potential associated with synchronous or metachronous metastatic disease. Further, it is known to metastasize mainly to the lung, bone, brain, liver, or adrenal glands. In very rare cases it can metastasize to the gallbladder mimicking acute cholecystitis on clinical exam. In this case we present a patient who developed a gallbladder metastasis five years after a renal cell carcinoma mimicking acute cholecystitis

Giant mass and anomalous mobility of particles in fermionic systems

We calculate the mobility of a heavy particle coupled to a Fermi sea within a non-perturbative approach valid at all temperatures. The interplay of particle recoil and of strong coupling effects, leading to the orthogonality catastrophe for an infinitely heavy particle, is carefully taken into account. We find two novel types of strong coupling effects: a new low energy scale $T^{\star}$ and a giant mass renormalization in the case of either near-resonant scattering or a large transport cross section $\sigma$. The mobility is shown to obey two different power laws below and above $T^{\star}$. For $\sigma\gg\lambda_f^2$, where $\lambda_f$ is the Fermi wave length, an exponentially large effective mass suppresses the mobility.Comment: 4 pages, 4 figure

APOL1 risk alleles are associated with exaggerated age-related changes in glomerular number and volume in African-American adults: an autopsy study

APOL1 genetic variants contribute to kidney disease in African Americans. We assessed correlations between APOL1 profiles and renal histological features in subjects without renal disease. Glomerular number (N-glom,) and mean glomerular volume (V-glom,) were measured by the dissector/fractionator method in kidneys of African-American and non-African-American adults without renal disease, undergoing autopsies in Jackson, Mississippi. APOL1 risk alleles were genotyped and the kidney findings were evaluated in the context of those profiles. The proportions of African Americans with none, one, and two APOL1 risk alleles were 38%, 43%, and 19%, respectively; 38% of African Americans had G1 allele variants and 31% of African Americans had G2 allele variants. Only APOL1-positive African Americans had significant reductions in N-glom and increases in V-glom with increasing age. Regression analysis predicted an annual average loss of 8834 (P=0.03, sex adjusted) glomeruli per single kidney over the first 38 years of adult life in African Americans with two risk alleles. Body mass index above the group medians, but below the obesity definition of >= 30 kg/m(2), enhanced the expression of age-related changes in N-glom in African Americans with either one or two APOL1 risk alleles. These findings indicate that APOL1 risk alleles are associated with exaggerated age-related nephron loss, probably decaying from a larger pool of smaller glomeruli in early adult life, along with enlargement of the remaining glomeruli. These phenomena might mark mechanisms of accentuated susceptibility to kidney disease in APOL1-positive African Americans

Coherent Matter Wave Transport in Speckle Potentials

This article studies multiple scattering of matter waves by a disordered optical potential in two and in three dimensions. We calculate fundamental transport quantities such as the scattering mean free path $\ell_s$, the Boltzmann transport mean free path \elltrb, and the Boltzmann diffusion constant $D_B$, using a diagrammatic Green functions approach. Coherent multiple scattering induces interference corrections known as weak localization which entail a reduced diffusion constant. We derive the corresponding expressions for matter wave transport in an correlated speckle potential and provide the relevant parameter values for a possible experimental study of this coherent transport regime, including the critical crossover to the regime of strong or Anderson localization.Comment: 33 pages, minor corrections, published versio

CoGeNT Interpretations

Recently, the CoGeNT experiment has reported events in excess of expected background. We analyze dark matter scenarios which can potentially explain this signal. Under the standard case of spin independent scattering with equal couplings to protons and neutrons, we find significant tensions with existing constraints. Consistency with these limits is possible if a large fraction of the putative signal events is coming from an additional source of experimental background. In this case, dark matter recoils cannot be said to explain the excess, but are consistent with it. We also investigate modifications to dark matter scattering that can evade the null experiments. In particular, we explore generalized spin independent couplings to protons and neutrons, spin dependent couplings, momentum dependent scattering, and inelastic interactions. We find that some of these generalizations can explain most of the CoGeNT events without violation of other constraints. Generalized couplings with some momentum dependence, allows further consistency with the DAMA modulation signal, realizing a scenario where both CoGeNT and DAMA signals are coming from dark matter. A model with dark matter interacting and annihilating into a new light boson can realize most of the scenarios considered.Comment: 24 pages, 12 figs, v2: published version, some discussions clarifie