Samuel Hirsch: Philosopher of religion, advocate of emancipation and radical reformer

Rabbi Samuel Hirsch (Thalfang 1815 - Chicago 1889) was instrumental in the development of Reform Judaism in Europe and the USA. This volume is the first lengthy publication devoted to this striking personality whose significance was no less than that of his contemporaries Abraham Geiger and David Einhorn. En route from Thalfang via Dessau and Luxembourg to Philadelphia, Hirsch left his mark on societal, religious, and philosophical developments in manifold ways. By the time he was appointed Chief Rabbi of the Jewish community in Luxembourg in 1843, he had already written many of his most important works on the philosophy of religion. In them he engaged in debate with the Young Hegelians on the importance of Judaism, the religion that, more than any other, enabled the human actualization of freedom so central to Hegel's philosophy. Over time Hirsch took an increasingly radical stance on issues such as Jewish rituals and mixed marriage. The goal of his reforms was not assimilation. He strove to strengthen Judaism to meet the demands of modernity and enable its survival in the modern era. Hirsch's story is key to understanding the transnational history of Reform Judaism and the struggle of Jews to secure a place in history and society.SCOPUS: bk.binfo:eu-repo/semantics/publishe

Introduction and acknowledgements

SCOPUS: ch.binfo:eu-repo/semantics/publishe

Compliance with National Cholesterol Education Program dietary and lifestyle guidelines among older women with self-reported hypercholesterolemia. The Women\u27s Health Initiative

PURPOSE: Dietary therapy remains the first line of treatment for patients with high blood cholesterol levels. Among free-living persons, compliance with National Cholesterol Education Program (NCEP) dietary recommendations is uncertain. SUBJECTS AND METHODS: We performed a cross-sectional, baseline analysis of 91,627 postmenopausal women enrolled in the Women\u27s Health Initiative Observational Study. Among women with self-reported hypercholesterolemia, we ascertained factors associated with compliance with National Cholesterol Education Program dietary recommendations, defined for the Step II diet as RESULTS: Of the 13,777 participants who reported having high cholesterol levels requiring drug therapy, only 20% reported total fat, saturated fat, and dietary cholesterol consumption consistent with Step II dietary goals. Factors associated with Step II dietary compliance included having a college degree (odds ratio [OR] = 1.26; 95% confidence interval [CI]: 1.14 to 1.40), a prior cardiovascular event (OR = 1.48; 95% CI: 1.28 to 1.70), and consumption of five or more daily servings of fruits or vegetables (OR = 3.0; 95% CI: 2.7 to 3.3). Being married, smoking, a sedentary lifestyle, and a higher body mass index were all associated with reduced compliance (all P \u3c0.0001). In the subsample in which plasma lipid levels were measured, dietary compliance was associated with higher levels of low-density lipoprotein cholesterol (P = 0.02). CONCLUSION: Since the inception of the NCEP in 1985, health care providers, public health programs, and patients have not successfully implemented the dietary recommendations

Increased Hydrophobicity at the N Terminus/Membrane Interface Impairs Gating of the Severe Combined Immunodeficiency-related ORAI1 Mutant*

Patients with severe combined immune deficiency (SCID) suffer from defective T-cell Ca2+ signaling. A loss of Ca2+ entry has been linked at the molecular level to single missense mutation R91W in the store-operated Ca2+ channel ORAI1. However, the mechanistic impact of this mutation on ORAI1 function remains unclear. Confocal Förster resonance energy transfer microscopy revealed that dynamic store-operated coupling of STIM1 to ORAI1 R91W was largely sustained similar to wild-type ORAI1. Characterization of various point mutants at position 91 by whole cell patch clamp recordings displayed that neutral or even negatively charged amino acids did not abolish ORAI1 function. However, substitution by hydrophobic leucine, valine, or phenylalanine resulted in non-functional ORAI1 channels, despite preserved STIM1 coupling. Besides conformational constraints at the N terminus/membrane interface predicted for the hydrophobic mutants, additional key factor(s) were suggested to determine ORAI1 functionality. Calculation of the probability for the 1st transmembrane domain and its hydrophobicity revealed a substantial increase for all hydrophobic substitutions that lead to non-functional ORAI1 R91X mutants in contrast to those with hydrophilic residues. Hence, increased hydrophobicity might lead to disrupted permeation/gating, as an ORAI1 channel with increased pore size and R91W mutation failed to recover activity. In conclusion, the increase in hydrophobicity at the N terminus/membrane interface represents the major cause for yielding non-functional ORAI1 channels