Deciphering High-Pressure metamorphism in collisional context using microprobe-mapping methods : application to the Stak eclogitic massif (NW Himalaya)

The Stak massif, northern Pakistan, is a newly recognized occurrence of eclogite formed by the subduction of the northern margin of the Indian continent in the northwest Himalaya. Although this unit was extensively retrogressed during the Himalayan collision, records of the high-pressure (HP) event as well as a continuous pressure-temperature (P-T) path were assessed from a single thin section using a new multiequilibrium method. This method uses microprobe X-ray compositional maps of garnet and omphacitic pyroxene followed by calculations of ∼200,000 P-T estimates using appropriate thermobarometers. The Stak eclogite underwent prograde metamorphism, increasing from 650 °C and 2.4 GPa to the peak conditions of 750 °C and 2.5 GPa, then retrogressed to 700–650 °C and 1.6–0.9 GPa under amphibolite-facies conditions. The estimated peak metamorphic conditions and P-T path are similar to those of the Kaghan and Tso Morari high- to ultrahigh-pressure (HP-UHP) massifs. We propose that these three massifs define a large HP to UHP province in the northwest Himalaya, comparable to the Dabie-Sulu province in China and the Western Gneiss Region in Norway.

Transient simulations of the carbon and nitrogen dynamics in northern peatlands: from the Last Glacial Maximum to the 21st century

The development of northern high-latitude peatlands played an important role in the carbon (C) balance of the land biosphere since the Last Glacial Maximum (LGM). At present, carbon storage in northern peatlands is substantial and estimated to be 500 ± 100 Pg C (1 Pg C = 1015 g C). Here, we develop and apply a peatland module embedded in a dynamic global vegetation and land surface process model (LPX-Bern 1.0). The peatland module features a dynamic nitrogen cycle, a dynamic C transfer between peatland acrotelm (upper oxic layer) and catotelm (deep anoxic layer), hydrology- and temperature-dependent respiration rates, and peatland specific plant functional types. Nitrogen limitation down-regulates average modern net primary productivity over peatlands by about half. Decadal acrotelm-to-catotelm C fluxes vary between −20 and +50 g C m−2 yr−1 over the Holocene. Key model parameters are calibrated with reconstructed peat accumulation rates from peat-core data. The model reproduces the major features of the peat core data and of the observation-based modern circumpolar soil carbon distribution. Results from a set of simulations for possible evolutions of northern peat development and areal extent show that soil C stocks in modern peatlands increased by 365–550 Pg C since the LGM, of which 175–272 Pg C accumulated between 11 and 5 kyr BP. Furthermore, our simulations suggest a persistent C sequestration rate of 35–50 Pg C per 1000 yr in present-day peatlands under current climate conditions, and that this C sink could either sustain or turn towards a source by 2100 AD depending on climate trajectories as projected for different representative greenhouse gas concentration pathways.

Localized diacylglycerol-dependent stimulation of Ras and Rap1 during phagocytosis.

We describe a role for diacylglycerol in the activation of Ras and Rap1 at the phagosomal membrane. During phagocytosis, Ras density was similar on the surface and invaginating areas of the membrane, but activation was detectable only in the latter and in sealed phagosomes. Ras activation was associated with the recruitment of RasGRP3, a diacylglycerol-dependent Ras/Rap1 exchange factor. Recruitment to phagosomes of RasGRP3, which contains a C1 domain, parallels and appears to be due to the formation of diacylglycerol. Accordingly, Ras and Rap1 activation was precluded by antagonists of phospholipase C and of diacylglycerol binding. Ras is dispensable for phagocytosis but controls activation of extracellular signal-regulated kinase, which is partially impeded by diacylglycerol inhibitors. By contrast, cross-activation of complement receptors by stimulation of Fcgamma receptors requires Rap1 and involves diacylglycerol. We suggest a role for diacylglycerol-dependent exchange factors in the activation of Ras and Rap1, which govern distinct processes induced by Fcgamma receptor-mediated phagocytosis to enhance the innate immune response.

Ms. Ff. Mus. 1493 - Dom. XVI. post Trinit. : [Wie der Hirsch schreyet nach frischem p.]

di Telemann. [Text: Gottfried Simonis]

A Simple Guideline Reduces the Need for Red Blood Cell Transfusions in Swiss Hospitals: A Prospective, Multicentre, Before-and-After Study in Elective Hip and Knee Replacement

INTRODUCTION Optimising the use of blood has become a core task of transfusion medicine. Because no general guidelines are available in Switzerland, we analysed the effects of the introduction of a guideline on red blood cell (RBC) transfusion for elective orthopaedic surgery. METHODS Prospective, multicentre, before-and-after study comparing the use of RBCs in adult elective hip or knee replacement before and after the implementation of a guideline in 10 Swiss hospitals, developed together with all participants. RESULTS We included 2,134 patients, 1,238 in 7 months before, 896 in 6 months after intervention. 57 (34 or 2.7% before, 23 or 2.6% after) were lost before follow-up visit. The mean number of transfused RBC units decreased from 0.5 to 0.4 per patient (0.1, 95% CI 0.08-0.2; p = 0.014), the proportion of transfused patients from 20.9% to 16.9% (4%, 95% C.I. 0.7-7.4%; p = 0.02), and the pre-transfusion haemoglobin from 82.6 to 78.2 g/l (4.4 g/l, 95% C. I. 2.15-6.62 g/l, p < 0.001). We did not observe any statistically significant changes in in-hospital mortality (0.4% vs. 0%) and morbidity (4.1% vs. 4.0%), median hospital length of stay (9 vs. 9 days), follow-up mortality (0.4% vs. 0.2%) and follow-up morbidity (6.9% vs. 6.0%). CONCLUSIONS The introduction of a simple transfusion guideline reduces and standardises the use of RBCs by decreasing the haemoglobin transfusion trigger, without negative effects on the patient outcome. Local support, training, and monitoring of the effects are requirements for programmes optimising the use of blood.

Epidermolysis bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene.

BACKGROUND Heritable forms of epidermolysis bullosa (EB) constitute a heterogeneous group of skin disorders of genetic aetiology that are characterised by skin and mucous membrane blistering and ulceration in response to even minor trauma. Here we report the occurrence of EB in three Danish Hereford cattle from one herd. RESULTS Two of the animals were necropsied and showed oral mucosal blistering, skin ulcerations and partly loss of horn on the claws. Lesions were histologically characterized by subepidermal blisters and ulcers. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We performed whole genome sequencing of one affected calf and searched all coding DNA variants. Thereby, we detected a homozygous 2.4 kb deletion encompassing the first exon of the LAMC2 gene, encoding for laminin gamma 2 protein. This loss of function mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. The deletion co-segregates with the EB phenotype in the family and absent in normal cattle of various breeds. Verifying the homozygous private variants present in candidate genes allowed us to quickly identify the causative mutation and contribute to the final diagnosis of junctional EB in Hereford cattle. CONCLUSIONS Our investigation confirms the known role of laminin gamma 2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare diseases in livestock.

Azacyclic FTY720 Analogues That Limit Nutrient Transporter Expression but Lack S1P Receptor Activity and Negative Chronotropic Effects Offer a Novel and Effective Strategy to Kill Cancer Cells in Vivo

FTY720 sequesters lymphocytes in secondary lymphoid organs through effects on sphingosine-1-phosphate (S1P) receptors. However, at higher doses than are required for immunosuppression, FTY720 also functions as an anticancer agent in multiple animal models. Our published work indicates that the anticancer effects of FTY720 do not depend on actions at S1P receptors but instead stem from FTY720s ability to restrict access to extracellular nutrients by down-regulating nutrient transporter proteins. This result was significant because S1P receptor activation is responsible for FTY720s dose-limiting toxicity, bradycardia, that prevents its use in cancer patients. Here, we describe diastereomeric and enantiomeric 3- and 4-C-aryl 2-hydroxymethyl pyrrolidines that are more active than the previously known analogues. Of importance is that these compounds fail to activate S1P1 or S1P3 receptors in vivo but retain inhibitory effects on nutrient transporter proteins and anticancer activity in solid tumor xenograft models. Our studies reaffirm that the anticancer activity of FTY720 does not depend upon S1P receptor activation and uphold the promise of using S1P receptor-inactive azacyclic FTY720 analogues in human cancer patients.

Regulation of the cardiac Na+ channel NaV1.5 by post-translational modifications.

The cardiac voltage-gated Na(+) channel, Na(V)1.5, is responsible for the upstroke of the action potential in cardiomyocytes and for efficient propagation of the electrical impulse in the myocardium. Even subtle alterations of Na(V)1.5 function, as caused by mutations in its gene SCN5A, may lead to many different arrhythmic phenotypes in carrier patients. In addition, acquired malfunctions of Na(V)1.5 that are secondary to cardiac disorders such as heart failure and cardiomyopathies, may also play significant roles in arrhythmogenesis. While it is clear that the regulation of Na(V)1.5 protein expression and function tightly depends on genetic mechanisms, recent studies have demonstrated that Na(V)1.5 is the target of various post-translational modifications that are pivotal not only in physiological conditions, but also in disease. In this review, we examine the recent literature demonstrating glycosylation, phosphorylation by Protein Kinases A and C, Ca(2+)/Calmodulin-dependent protein Kinase II, Phosphatidylinositol 3-Kinase, Serum- and Glucocorticoid-inducible Kinases, Fyn and Adenosine Monophosphate-activated Protein Kinase, methylation, acetylation, redox modifications, and ubiquitylation of Na(V)1.5. Modern and sensitive mass spectrometry approaches, applied directly to channel proteins that were purified from native cardiac tissues, have enabled the determination of the precise location of post-translational modification sites, thus providing essential information for understanding the mechanistic details of these regulations. The current challenge is first, to understand the roles of these modifications on the expression and the function of Na(V)1.5, and second, to further identify other chemical modifications. It is postulated that the diversity of phenotypes observed with Na(V)1.5-dependent disorders may partially arise from the complex post-translational modifications of channel protein components.

Rhinovirus Infections and Associated Respiratory Morbidity in Infants: A Prospective Cohort Study.

BACKGROUND Risk factors promoting rhinovirus (RV) infections are inadequately described in healthy populations, especially infants. OBJECTIVES To determine the frequency of symptomatic and asymptomatic RV infections and identify possible risk factors from host and environment among otherwise healthy infants. METHODS In a prospective birth cohort, respiratory health was assessed in 41 term-born infants by weekly telephone interviews during the first year of life, and weekly nasal swabs were collected to determine RV prevalence. In a multilevel logistic regression model, associations between prevalence and respiratory symptoms during RV infections and host/environmental factors were determined. RESULTS 27% of nasal swabs in 41 infants tested positive for RVs. Risk factors for RV prevalence were autumn months (OR=1.71, p=0.01, 95% CI 1.13-2.61), outdoor temperatures between 5-10 °C (OR=2.33, p=0.001, 95% CI 1.41-3.86), older siblings (OR=2.60, p=0.001, 95% CI 1.50-4.51) and childcare attendance (OR=1.53, p=0.07, 95% CI 0.96-2.44). 51% of RV-positive samples were asymptomatic. Respiratory symptoms during RV infections were less likely during the first three months of life (OR=0.34, p=0.003, 95% CI 0.17-0.69) and in infants with atopic mothers (OR=0.44, p=0.008, 95% CI 0.24-0.80). Increased tidal volume (OR=1.67, p=0.03, 95% CI 1.04-2.68) and outdoor temperatures between 2-5 °C (OR=2.79, p=0.02, 95% CI 1.17-6.61) were associated with more symptoms. CONCLUSIONS RVs are highly prevalent during the first year of life, and most infections are asymptomatic. Frequency of RV infections is associated with environmental factors, while respiratory symptoms during RV infections are linked to host determinants like infant age, maternal atopy, or premorbid lung function.

Adherence to a lifestyle physical activity program: Trends over time and associations with processes of change and physical activity

Research on lifestyle physical activity interventions suggests that they help individuals meet the new recommendations for physical activity made by the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM). The purpose of this research was to describe the rates of adherence to two lifestyle physical activity intervention arms and to examine the association between adherence and outcome variables, using data from Project PRIME, a lifestyle physical activity intervention based on the transtheoretical model and conducted by the Cooper Institute of Aerobics Research, Dallas, Texas. Participants were 250 sedentary healthy adults, aged 35 to 70 years, primarily non-Hispanic White, and in the contemplation and preparation stages of readiness to change. They were randomized to a group (PRIME G) or a mail- and telephone-delivered condition (PRIME C). Adherence measures included attending class (PRIME G), completing a monthly telephone call with a health educator (PRIME C), and completing homework assignments and self-monitoring minutes of moderate- to vigorous physical activity (both groups). In the first results paper, adherence over time and between conditions was examined: Attendance in group, completing the monthly telephone call, and homework completion decreased over time, and participants in PRIME G were more likely to complete homework than those in PRIME C. Paper 2 aimed to determine whether the adherence measures predicted achievement of the CDC/ACSM physical activity guideline. In separate models for the two conditions, a latent variable measuring adherence was found to predict achievement of the guideline. Paper 3 examined the association between adherence measures and the transtheoretical model's processes of change within each condition. For both, participants who completed at least two thirds of the homework assignments improved their use of the processes of change more than those who completed less than that amount. These results suggest that encouraging adherence to a lifestyle physical activity intervention, at least among already motivated volunteers, may increase the likelihood of beneficial changes in the outcomes. ^

Der gefährdete Wiederaufbau. Die Gefahren der antisemitischen Propaganda für den wirtschaftlichen Wiederaufbau Deutschlands

[Hrsg.: Centralverein deutscher Staatsbürger jüdischen Glaubens]

Na 1 Nachlass Max Horkheimer, 642 - "Materialien. Druckseiten aus Zeitschriften", "Menschen im Großbetrieb" und "Vorwort zu: 'Zeugnisse. Theodor W. Adorno zum 60. Geburtstag'" (p. IX 20.11-76-IX 22)

11. Salomon, Albert: "The Spirit of the Soldier and Nazi Militarism". Social Research, Februar 1942, 13 Blatt; 12. Dicks, H.V.: "The Psychological Foundations of the Wehrmacht". Als Typoskript vervielfältigt, 42 Blatt; 13. Clark, Robert A.: "Aggressivness and Military Training". American Journal of Sociology, Volume 51, Number 5, March 1946, 5 Blatt; 14. Stagner, Ross: "Fascist Attitudes: Their Determening Conditions". The Journal of Social Psychology, Volume III, Number 4, 1936, 9 Blatt; 15. Apple, Kenneth E.: "Nationalism and Souvereignity: A Psychiatric View." The Journal of Normal and Abnorma Psychology, Volume 40, Number 4, October 1945, 4 Blatt; 16. Schreier, Fritz: "German Aggressivness- Its Reasons and Types". Journal of Normal and Abnormal Psychology, Volume 38, Number 2, April 1943, 7 Blatt; 17. Stagner, Ross: "Fascist Attitudes: An Exploratory Study". The Journal of Social Psychology, Volume III, Number 3, 1936, 6 Blatt; 18. Stagner, Ross und Katzoff, E. T.: "Fascist Attitudes: Factor Analysis of Item Correlations". The Journal of Social Psychology, 16, 1942, 4 Blatt; 19. Stagner, Ross und Osgood, Charles E.: "Impact of War on a Nationalistic Frame of Reference". The Journal of Social Psychology, 24, 1946, 15 Blatt; 20. Day, Daniel Droba und Quackenbusch, O.F.: Attitudes Towards Defensive, Cooperative and Aggressive War". The Journal of Social Psychology, 16, 1942, 5 Blatt; 21. Kecskemeti, Paul und Leites, Nathan: "Some Psychological Hypotheses on Nazi Germany: I". The Journal of Social Psychology, 26, 1947, 22 Blatt; 22. Dieselben: "Some Psychological Hypotheses on Nazi Germany: II". Ebenda, 27, 1948, 14 Blatt; 23. Parsons, Tollcott: "Certain Primary Sources and Pattersens of Aggression in the Social Structure of the Western World". Psychiatry, Volume 10, Number 2, May 1047, 8 Blatt; 24. Zerner, Elizabeth H.: "German Occupation and Anti-Semitism in France". Public Opinion Quarterly, Summer 1948, 5 Blatt; 25. Hauser, Ernest O.: "Doctor [Julian] Huxley`s Wonderful Zoo". The Saturday Evening Post, ohne Datum, 5 Blatt; 26. Zeitungsabschnitt, 1 Blatt; "Menschen im Großbetrieb" (GS 8, S. 95-105); Veröffentlicht in: Deutsche Zeitung, 19.02.1955. a) Typoskript mit dem Titel "Meinungsforschung im Betrieb" mit handschriftlichen Korrekturen, 10 Blatt b) Typoskript mit dem Titel "Der Mensch im Großbetrieb", mit eigenhändigen Korrekturen und einer handschriftlichen Notiz von Theodor W. Adorno, 17 Blatt c) Typoskript mit eigenhändigen Korrekturen, 17 Blatt d) Zeitungsdruck mit dem Titel "Menschen im Großbetrieb", mit eigenhändigen Korrekturen, 1 Blatt e)-f) Dasselbe , 1 Blatt; "Vorwort" zu: "Zeugnisse. Theodor W. Adorno zum 60. Geburtstag"; Veröffentlicht: Ebenda, Frankfurt am Main, 1963. a)-b) Typoskript mit eigenhändigen Korrekturen, 1 Blatt c) Typoskript, 2 Blatt;

Na 1 Nachlass Max Horkheimer, 670 - "Treatise on Antisemitism" und zugehörige Dokumente (p. IX 124-IX 134)

"Treatise on Antisemitism", Unterlagen zur Buchveröffentlichung, 1945-1946; "Tentative Outline of Contens", a) Typoskript, 6 Blatt; b) Typoskript, 2 Blatt; c) Typoskript, 2 Blatt; "Section 2: Modern European Antisemitism". Typoskript, 5 Blatt; "Section 4: Political Antisemitism in America". Typoskript, 5 Blatt; "Section 5: Religious and Social Ideologies". Typoskript, 7 Blatt; "The Nature of Anti-Semitism. Psychologocal Topics to be Surveyed", a) Typoskript, 2 Blatt; b) Typoskript, 2 Blatt; "Proposed Project for a Treatise on Antisemitism" und "Tentative Outline of Contents". Typoskript mit handschriftlichen Ergänzungen, 8 Blatt; "Notes on the Content for Sections on American Antisemitism for the proposed book". Typoskript, 9 Blatt; Über den Aufbau des Buchs, eigenhändige Notiz von Max Horkheimer, 1 Blatt; Löwenthal, Leo: "Memorandum to Max Horkheimer, re: books", 25.11.1946. Typoskript, 6 Blatt; Memoranden über Besprechungen betreffend "Traetise", 28.05-10.10.1945, Typoskript, 6 Blatt; Jaeger, Werner: 1 Brief mit Unterschrift an Gordon W. Allport, Cambridge, Mass., 21.06.1945, 1 Blatt; Statements for AJC on account 'Treatise', Juli 1945 - Mai 1947, 19 Blatt; Unterlagen zur deutschen Ausgabe der "Studies in Prejudice", 1950-1952; "German Version of the Series 'Studies in Prejudice'". Typoskript, 3 Blatt; "Bericht über den Plan zur Herstellung einer deutschen Fassung der Studies in Prejudice". Typoskript, 4 Blatt; Memoranden zur Arbeit an der deutschen Ausgabe, 15.01.1951- 05.12.1952, Typoskript, 7 Blatt; Record of Meeting Commentary and Institute of Social Research", 29.05.1946; Diskussionsteilnehmer: Cohen, Elliot; Glazer, Nathan; Greenberg, Clement; Warshow, Robert; Löwenthal, Leo; Massing, Paul; Pollock, Friedrich; Weil, Felix; Gurland, A.R.L.; Jahoda, Marie; Löwe, Adolf; Typoskript, 19 Blatt; "Some Notes to the 'tentative draft discussed with R.'", Datierung unklar, um 1943? Typoskript mit handschriftlichen Korrekturen, 4 Blatt; "Re: Antisemitism in occupied Europe", Datierung unklar, etwa 1945-1948?; Typsokript, 3 Blatt; "Studies Undertaken in the Project on Political Antisemitism", Tabellarische Aufzählung, Datierung unklar, Typoskript, 1 Blatt; Institut of Social Research: "Instructions", Anweisungen für Interviewer, Fragebogen, Datierung unklar, Entwurf, Typoskript, 4 Blatt; Über Forschungsunternehmungen zu ethischen Vorurteilesstrukturen in den USA zwischen 1928 und 1939, Datierung unklar, Typoskript, 2 Blatt; Institut of Social Research: "Section I: Protestantism and Antisemitism. Section II: Report on the General Body of Protestant Antisemitic Feeling", Datierung unklar, Typoskript, 29 Blatt; Horkheimer, Max: "Re: Anti-Semitism- Spearhead of Nazism", Datierung unklar, Typoskript, 6 Blatt; Adorno, Theodor W.: "Re: Questionaire on Anti-Semitism", Datierung unklar. Typoskript, 5 Blatt; Adorno, Theodor W.: "Outline of a socio-psychological study", Datierung unklar. Typoskript mit eigenhändigen Korrekturen, 4 Blatt; "Sample: Responsiveness of Types of Anti-Semites to Anti-Semitic Propaganda", 2 handschriftliche Tabellen-Schemata, Datierung unklar, 2 Blatt;