Blockade of NMDA receptor subtype NR2B prevents seizures but not apoptosis of dentate gyrus neurons in bacterial meningitis in infant rats

BACKGROUND: Excitotoxic neuronal injury by action of the glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype have been implicated in the pathogenesis of brain damage as a consequence of bacterial meningitis. The most potent and selective blocker of NMDA receptors containing the NR2B subunit is (R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperid inepropanol (RO 25-6981). Here we evaluated the effect of RO 25-6981 on hippocampal neuronal apoptosis in an infant rat model of meningitis due to Streptococcus pneumoniae. Animals were randomized for treatment with RO 25-6981 at a dosage of either 0.375 mg (15 mg/kg; n = 28) or 3.75 mg (150 mg/kg; n = 15) every 3 h or an equal volume of sterile saline (250 microl; n = 40) starting at 12 h after infection. Eighteen hours after infection, animals were assessed clinically and seizures were observed for a period of 2 h. At 24 h after infection animals were sacrificed and brains were examined for apoptotic injury to the dentate granule cell layer of the hippocampus. RESULTS: Treatment with RO 25-6981 had no effect on clinical scores, but the incidence of seizures was reduced (P < 0.05 for all RO 25-6981 treated animals combined). The extent of apoptosis was not affected by low or high doses of RO 25-6981. Number of apoptotic cells (median [range]) was 12.76 [3.16-25.3] in animals treated with low dose RO 25-6981 (control animals 13.8 [2.60-31.8]; (P = NS) and 9.8 [1.7-27.3] (controls: 10.5 [2.4-21.75]) in animals treated with high dose RO 25-6981 (P = NS). CONCLUSIONS: Treatment with a highly selective blocker of NMDA receptors containing the NR2B subunit failed to protect hippocampal neurons from injury in this model of pneumococcal meningitis, while it had some beneficial effect on the incidence of seizures.

First-trimester serum levels of soluble endoglin and soluble fms-like tyrosine kinase-1 as first-trimester markers for late-onset preeclampsia

OBJECTIVE: The aim of this investigation was to assess soluble endoglin (sEng) and soluble fms-like tyrosine kinase-1 (sFlt1) as first-trimester serum markers to predict preeclampsia. STUDY DESIGN: First-trimester sera were obtained from 46 women with subsequent late-onset preeclampsia and from 92 controls. sEng and sFlt1 concentrations were determined immunoanalytically. Correlation analysis with inhibin A and placental growth factor levels was performed. RESULTS: sEng and sFlt1 serum concentrations were higher in women with subsequent preeclampsia than in controls (mean +/- SD, sEng: 5.57 +/- 1.18 ng/mL vs 5.02 +/- 1.01 ng/mL, P = .009; sFlt1: 1764 +/- 757 pg/mL vs 1537 +/- 812 pg/mL, P = .036). Sensitivities and specificities for predicting preeclampsia were 63% and 57% for sEng and 64% and 56% for sFlt1, respectively. When sEng and inhibin A were combined, the sensitivity increased to 68%, whereas the specificity was 61%. CONCLUSION: sEng and sFlt1 are increased in the first trimester in women with subsequent late-onset preeclampsia and might therefore prove useful to predict preeclampsia.

Functionalized Adamantane Tectons Used in the Design of Mixed-Ligand Copper(II) 1,2,4-Triazolyl/Carboxylate Metal–Organic Frameworks

Bistriazoles, 1,3-bis(1,2,4-triazol-4-yl)propane (tr2pr) and 1,3-bis(1,2,4-triazol-4-yl)adamantane (tr2ad), were examined in combination with the rigid tetratopic 1,3,5,7-adamantanetetracarboxylic acid (H4-adtc) platform for the construction of neutral heteroleptic copper(II) metal−organic frameworks. Two coordination polymers, [{Cu4(OH)2(H2O)2}{Cu4(OH)2}(tr2pr)2(H-adtc)4]·2H2O (1) and [Cu4(OH)2(tr2ad)2(H-adtc)2(H2O)2]·3H2O (2), were synthesized and structurally characterized. In complexes 1 and 2, the N1,N2-1,2,4-triazolyl (tr) and μ3-OH− groups serve as complementary bridges between adjacent metal centers supporting the tetranuclear dihydroxo clusters. The structure of 1 represents a unique association of two different kinds of centrosymmetrical {Cu4(OH)2} units in a tight 3D framework, while in compound 2, another configuration type of acentric tetranuclear metal clusters is organized in a layered 3,6-hexagonal motif. In both cases, the {Cu4(OH)2} secondary building block and trideprotonated carboxylate H-adtc3− can be viewed as covalently bound six- and three-connected nodes that define the net topology. The tr ligands, showing μ3- or μ4-binding patterns, introduce additional integrating links between the neighboring {Cu4(OH)2} fragments. A variable-temperature magnetic susceptibility study of 2 demonstrates strong antiferromagnetic intracluster coupling (J1 = −109 cm−1 and J2 = −21 cm−1), which combines for the bulk phase with a weak antiferromagnetic intercluster interaction (zj = −2.5 cm−1).

Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences.

The purpose of the study is to determine the effects of the BIG 1-98 treatments on bone mineral density. BIG 1-98 compared 5-year adjuvant hormone therapy in postmenopausal women allocated to four groups: tamoxifen (T); letrozole (L); 2-years T, 3-years L (TL); and 2-years L, 3-years T (LT). Bone mineral density T-score was measured prospectively annually by dual energy X-ray absorption in 424 patients enrolled in a sub-study after 3 (n = 150), 4 (n = 200), and 5 years (n = 74) from randomization, and 1 year after treatment cessation. Prevalence of osteoporosis and the association of C-telopeptide, osteocalcin, and bone alkaline phosphatase with T-scores were assessed. At 3 years, T had the highest and TL the lowest T-score. All arms except for LT showed a decline up to 5 years, with TL exhibiting the greatest. At 5 years, there were significant differences on lumbar T-score only between T and TL, whereas for femur T-score, differences were significant for T versus L or TL, and L versus LT. The 5-year prevalence of spine and femur osteoporosis was the highest on TL (14.5 %, 7.1 %) then L (4.3 %, 5.1 %), LT (4.2 %, 1.4 %) and T (4 %, 0). C-telopeptide and osteocalcin were significantly associated with T-scores. While adjuvant L increases bone mineral density loss compared with T, the sequence LT has an acceptable bone safety profile. C-telopeptide and osteocalcin are useful markers of bone density that may be used to monitor bone health during treatment. The sequence LT may be a valid treatment option in patients with low and intermediate risk of recurrence.

Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson's disease.

Early diagnosis of Parkinson's disease (PD) is required to improve therapeutic responses. Indeed, a clinical diagnosis of resting tremor, rigidity, movement and postural deficiencies usually reflect >50% loss of the nigrostriatal system in disease. In a step to address this, quantitative diffusion tensor magnetic resonance imaging (DTI) was used to assess nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication model of dopaminergic nigral degeneration. We now demonstrate increased average diffusion (p<0.005) and decreased fractional anisotropy (p<0.03) in the substantia nigra (SN) of 5- to 7-day MPTP-treated animals when compared to saline controls. Transverse diffusivity demonstrated the most significant differences (p < or = 0.002) and correlated with the numbers of SN dopaminergic neurons (r=-0.75, p=0.012). No differences were found in the striatum, corpus callosum, cerebral cortex, or ventricles. These results demonstrate that DTI may be used as a surrogate biomarker of nigral dopaminergic neuronal degeneration.

Structural and functional studies of the human integrin $\alpha 4\beta 1$ (CD49d/CD29)

The integrin receptor $\alpha 4\beta 1$ is a cell surface heterodimer involved in a variety of highly regulated cellular interactions. The purpose of this dissertation was to identify and characterize unique structural and functional properties of the $\alpha 4\beta 1$ molecule that may be important for adhesion regulation and signal transduction. To study these properties and to establish a consensus sequence for the $\alpha 4$ subunit, cDNA encoding $\alpha 4$ was cloned and sequenced. A comparison with previously described human $\alpha 4$ sequences identified several substitutions in the $5\prime$ and $3\prime$ untranslated regions, and a nonsynonymous G to A transition in the coding region, resulting in a glutamine substitution for arginine. Further analysis of this single nucleotide substitution indicated that two variants of the $\alpha 4$ subunit exist, and when compared with three ancestrally-related species, the new form cloned in our laboratory was found to be evolutionarily conserved.^ The expression of $\alpha 4$ cDNA in transfected K562 erythroleukemia cells, and subsequent studies using flow cytofluorometric, immunochemical, and ligand binding/blocking analyses, confirmed $\alpha 4\beta 1$ as a receptor for fibronectin (FN) and vascular cell adhesion molecule-1 (VCAM-1), and provided a practical means of identifying two novel monoclonal antibody (mAb) binding epitopes on the $\alpha 4\beta 1$ complex that may play important roles in the regulation of leukocyte adhesion.^ To investigate the association of $\alpha 4\beta 1$-mediated adhesion with signals involved in the spreading of lymphocytes on FN, a quantitative method of analysis was developed using video microscopy and digital imaging. The results showed that HPB-ALL $(\alpha 4\beta 1\sp{\rm hi},\ \alpha 5\beta 1\sp-)$ cells could adhere and actively spread on human plasma FN, but not on control substrate. Many cell types which express different levels of the $\alpha 4\beta 1$ and $\alpha 5\beta 1$ FN binding integrins were examined for their ability to function in these events. Using anti-$\alpha 4$ and anti-$\alpha 5$ mAbs, it was determined that cell adhesion to FN was influenced by both $\beta 1$ integrins, while cell spreading was found to be dependent on the $\alpha 4\beta 1$ complex. In addition, inhibitors of phospholipase A$\sb2$ (PLA$\sb2$), 5-lipoxygenases, and cyclooxygenases blocked HPB-ALL cell spreading, yet had no effect on cell adhesion to FN, and the impaired spreading induced by the PLA$\sb2$ inhibitor cibacron blue was restored by the addition of exogenous arachidonic acid (AA). These results suggest that the interaction of $\alpha 4\beta 1$ with FN, the activation of PLA$\sb2,$ and the subsequent release of AA, may be involved in lymphocyte spreading. ^

Mus Hs 750/3 - No. 1

[Carl Oestreich]

Mus Hs 750/7 - No. 1

[Carl Oestreich]

Mus Hs 771 - No 1.: während der Reise : im Auftrag S:. Ehrw:. M: v.: St. componirte ich diese zwei Lieder zum 2ten Grad um, und [unleserlich] führte selbige den 27ten August 5830 [!], zum erstenmale aus. in [Stein als ein Symbol für Freimaurerei] Socrates

[Carl Oestreich]

Ms. Ff. Mus. 1540 - Am 3. post Epiphan. : Wohl dem, des Hülffe der Gott Jacob ist ; C. A. T. B., 2 Violini, 2 Oboe, 1 Viola, Violoncello et Organo

von Telemann

Deutliche Abbildung und Beschreibung von der großen und hitzigen Schlacht bey Lobositz in Böhmen : den 1. Octobr. 1756

Dessiné sur les Lieux par C. F. v. P. Off. du C. In. de P.

Abconterfetung, deß Ehrwürdigen Hocherleuchten Theuren Mann Gottes vnd Teutschen Propheten, Herrn Doctor Martin Luther : Ein Christliches Gebet vor die Jugendt, auff das Evangelische JubelJahr, den 1. vnd 2. Novemb. 1617

Bibliograph. Nachweis: Paas P-308; Straus (1600/1700), Nr. 135

Na 1 Nachlass Max Horkheimer, 655 - Vorträge über Antisemitismus (p. IX 40.1-2-IX 48.1-2)

"Summer institute on Modern European Culture" (1947?); 1. Ankündigung für eine Vorlesungsreihe von Max Horkheimer, Theodor W. Adorno, Leo Löwenthal, Herbert Marcuse, Friedrich Pollock. a) Typoskript mit eigenhändigen Ergänzungen, 20 Blatt b) Typoskript mit handschriftlichen Ergänzungen, 19 Blatt; 2. Herbert Marcuse: "Philosophie allemande et francaise 1871-1933". Typoskript mit eigenhändigen Korrekturen, 18 Blatt; "Tentative Program for the Course of Antisemitism". Vorlesungsankündigung 1948 von Max Horkheimer, Theodor W. Adorno, Friedrich Pollock. Typoskript 2 Blatt; Max Horkheimer: Bericht über die Antisemitismus-Forschungen des Instituts für Sozialforschung (GS 12, S. 165-171). Vortrag gehalten am 16.4.1943, englischer Text. a) Typoskript mit eigenhändigen Korrekturen, 5 Blatt b) Typoskript mit eigenhändigen Korrekturen, 8 Blatt c) Typoskript mit handschriftlichen Korrekturen, 8 Blatt; Max Horkheimer: Bericht über die Antisemitismus-Forschungen des Instituts für Sozialforschung (GS 12, S. 172-183). Vortrag gehalten am 30.4.1943, Temple Israel. a) Typoskript mit eigenhändigen Korrekturen und Ergänzungen, 12 Blatt b) Typoskript mit handschriftlichen Korrekturen, 11 Blatt c) Typoskript mit eigenhändigen Korrekturen, 14 Blatt; Max Horkheimer: Über die Psychologie des Judentums und des Antisemitismus; 1. Vortrag, gehalten am 7.10.1943 im Department of Psychology, UCLA, eigenhändige Notizen, 1 Blatt; 2. Auszüge aus Schriften und Arbeitspapieren von: G.M. Davidson, Salomon Andhil Fineberg, A.R.L. Gurland, Oscar I. Janomsky, Paul W. Massing, Typoskript mit eigenhändigen Ergänzungen, 8 Blatt; Max Horkheimer: Anti-Semitism as a Social Phenomenon (GS 5, S.364-372); 1. Vortrag, gehalten am 17.6.1944 in San Francisco, Psychoanalytic Society, veröffentlicht unter dem Titel 'Sociological Background of the Psychoanalytic Approach". In: Ernst Simmel (ed.), "Anti-Semitism. A Social Disease", New York, 1946, S.1-10. a) Typoskript, 13 Blatt, b) Teilstück, Typoskript, 1 Blatt, c) Teilstück, Typoskript mit eigenhändigen Korrekturen, 2 Blatt d) Typoskript mit handschriftlichen Korrekturen, 9 Blatt; 2. "Notes to the Speech in San Francisco", Notizen, 4 Blatt; 3. eigenhändige Notizen zum Vortrag, 5 Blatt; 4. Rede für Maurice Karpf, Typoskript mit eigenhändigen Korrekturen, 2 Blatt; 5. Theodor W. Adorno: "Mammoth Motives", Notizen zum Verhältnis von Soziologie und Psychologie des Antisemitismus, 3 Blatt; 6. Theodor W. Adorno: "Patterns of Anti-Democratic Propaganda", veröffentlicht in: Ernst Simmel, "Anti-Semitism. A Social Disease", New York, 1946, S.125-137. a) Typoskript, 15 Blatt, b) Typoskript, 14 Blatt;; 7. Einladung, Drucksache, 2 Blatt; 8. Max Horkheimer: 2 Brief an Donald MacFerlane, Pacific Palisades, 22.5.1944, 1 Blatt; Max Horkheimer: Vorträge 1944-45; 1. "Report for the N.C.R.A.C.". Über Forschungsprojekte des American Jewish Committee and des American Jewish Congress, vorgetragen am 14.1.1944, Typoskript, 4 Blatt; 2. Notizen zu 1: Über Kurt Lewin, Typoskript, 3 Blatt; 3. eigenhändige Notizen zu 1., 3 Blatt; 4. Über die europäische Tradition der Arbeiten des Instituts für Sozialforschung. Vortrag, gehalten am 8.12.1944. Eigenhändige Notizen, 1 Blatt; 5. Über psychologische Aspekte der Antisemitismusforschung des Instituts für Sozialforschung. Vortrag, gehalten am 19.4.1945. Eigenhändige Notizen, 2 Blatt; 6. Über sozioökonomische Aspekte des Antisemitismus in Europa und in der Arbeiterschaft der USA. Vortrag, gehalten am 8.6.1945. Psychosomatic Society a) Notizen zum Vortrag, 4 Blatt, b) eigenhändige Notizen, 3 Blatt; 7. Notizen zu 6., Typoskript, 17 Blatt,; 8. Notizen zu 6. "Quotations from Labor Study", Typoskript, 12 Blatt; 9. Über neue Forschungsprojekte des Instituts für Sozialforschung zum Antisemitismus. Vortrag, gehalten am 24.10.1945. Eigenhändige Notizen, 2 Blatt; 10. Über Antisemitismus. Vortrag, gehalten am 3.12.1945. Eigenhändige Notizen, 2 Blatt; 11.-15. Vorträge über Antisemitismus. Datierung unklar (etwa 1945) (u.a. "Mountvernon Speech" und "Breakfast Speech"), 17 Blatt; 16. Über Judentum und Katholizismus in der neueren Geschichte. Eigenhändige Notizen zu einem Vortrag, Datierung unklar, 3 Blatt; 17. Über Vorurteil, Vortrag oder Diskussion in einer Synagoge, Datierung unklar, eigenhändige Notizen, 1 Blatt; Max Horkheimer: Über die Antisemitismus-Forschungen des Instituts für Sozialforschung. Vortrag, gehalten beim U.C.R.A.C.-Meeting, 15.-17.6.1946, Chicago:; 1. eigenhändige Notizen, 13 Blatt; 2. Fragebogen, als Typoskript vervielfältigt, mit eigenhändigen Ergänzungen, 6 Blatt;

Isotopic signature of specific biomarkers derived from anaerobic methanotrophic archaea (ANME groups) and sulphate-reducing bacteria (SRB) at different cold seep provinces

Anaerobic methane-oxidizing microbial communities in sediments at cold methane seeps are important factors in controlling methane emission to the ocean and atmosphere. Here, we investigated the distribution and carbon isotopic signature of specific biomarkers derived from anaerobic methanotrophic archaea (ANME groups) and sulphate-reducing bacteria (SRB) responsible for the anaerobic oxidation of methane (AOM) at different cold seep provinces of Hydrate Ridge, Cascadia margin. The special focus was on their relation to in situ cell abundances and methane turnover. In general, maxima in biomarker abundances and minima in carbon isotope signatures correlated with maxima in AOM and sulphate reduction as well as with consortium biomass. We found ANME-2a/DSS aggregates associated with high abundances of sn-2,3-di-O-isoprenoidal glycerol ethers (archaeol, sn-2-hydroxyarchaeol) and specific bacterial fatty acids (C16:1omega5c, cyC17:0omega5,6) as well as with high methane fluxes (Beggiatoa site). The low to medium flux site (Calyptogena field) was dominated by ANME-2c/DSS aggregates and contained less of both compound classes but more of AOM-related glycerol dialkyl glycerol tetraethers (GDGTs). ANME-1 archaea dominated deeper sediment horizons at the Calyptogena field where sn-1,2-di-O-alkyl glycerol ethers (DAGEs), archaeol, methyl-branched fatty acids (ai-C15:0, i-C16:0, ai-C17:0), and diagnostic GDGTs were prevailing. AOM-specific bacterial and archaeal biomarkers in these sediment strata generally revealed very similar d13C-values of around -100 per mill. In ANME-2-dominated sediment sections, archaeal biomarkers were even more 13C-depleted (down to -120 per mill), whereas bacterial biomarkers were found to be likewise 13C-depleted as in ANME-1-dominated sediment layers (d13C: -100 per mill). The zero flux site (Acharax field), containing only a few numbers of ANME-2/DSS aggregates, however, provided no specific biomarker pattern. Deeper sediment sections (below 20 cm sediment depth) from Beggiatoa covered areas which included solid layers of methane gas hydrates contained ANME-2/DSS typical biomarkers showing subsurface peaks combined with negative shifts in carbon isotopic compositions. The maxima were detected just above the hydrate layers, indicating that methane stored in the hydrates may be available for the microbial community. The observed variations in biomarker abundances and 13C-depletions are indicative of multiple environmental and physiological factors selecting for different AOM consortia (ANME-2a/DSS, ANME-2c/DSS, ANME-1) along horizontal and vertical gradients of cold seep settings.

Ronald E. Heine, Origen. Scholarship in the service of the church, Oxford University Press, Oxford, 2010, pp. 275. ISBN 978-0-19-920907-1.

Fil: Peretó Rivas, Rubén.