Developing a Common Global Baseline for Nucleic Acid Synthesis Screening

Introduction: Nucleic acid synthesis is a powerful tool that has revolutionized the life sciences. However, the misuse of synthetic nucleic acids could pose a serious threat to public health and safety. There is a need for international standards for nucleic acid synthesis screening to help prevent the misuse of this technology.Methods: We outline current barriers to the adoption of screening, which include the cost of developing screening tools and resources, adapting to existing commercial practices, internationalizing screening, and adapting screening to benchtop nucleic acid synthesis devices. To address these challenges, we then introduce the Common Mechanism for DNA Synthesis Screening, which was developed in consultation with a technical consortium of experts in DNA synthesis, synthetic biology, biosecurity, and policy, with the aim of addressing current barriers. The Common Mechanism software uses a variety of methods to identify sequences of concern, identify taxonomic best matches to regulated pathogens, and identify benign genes that can be cleared for synthesis. Finally, we describe outstanding challenges in the development of screening practices.Results: The Common Mechanism is a step toward ensuring the safe and responsible use of synthetic nucleic acids. It provides a baseline capability that overcomes challenges to nucleic acid synthesis screening and provides a solution for broader international adoption of screening practices.Conclusion: The Common Mechanism is a valuable tool for preventing the misuse of synthetic nucleic acids. It is a critical step toward ensuring the safe and responsible use of this powerful technology

Entangled Stories: The Red Jews in Premodern Yiddish and German Apocalyptic Lore

“Far, far away from our areas, somewhere beyond the Mountains of Darkness, on the other side of the Sambatyon River…there lives a nation known as the Red Jews.” The Red Jews are best known from classic Yiddish writing, most notably from Mendele's Kitser masoes Binyomin hashlishi (The Brief Travels of Benjamin the Third). This novel, first published in 1878, represents the initial appearance of the Red Jews in modern Yiddish literature. This comical travelogue describes the adventures of Benjamin, who sets off in search of the legendary Red Jews. But who are these Red Jews or, in Yiddish, di royte yidelekh? The term denotes the Ten Lost Tribes of Israel, the ten tribes that in biblical times had composed the Northern Kingdom of Israel until they were exiled by the Assyrians in the eighth century BCE. Over time, the myth of their return emerged, and they were said to live in an uncharted location beyond the mysterious Sambatyon River, where they would remain until the Messiah's arrival at the end of time, when they would rejoin the rest of the Jewish people. This article is part of a broader study of the Red Jews in Jewish popular culture from the Middle Ages through modernity. It is partially based on a chapter from my book, Umstrittene Erlöser: Politik, Ideologie und jüdisch-christlicher Messianismus in Deutschland, 1500–1600 (Göttingen: Vandenhoeck & Ruprecht, 2011). Several postdoctoral fellowships have generously supported my research on the Red Jews: a Dr. Meyer-Struckmann-Fellowship of the German Academic Foundation, a Harry Starr Fellowship in Judaica/Alan M. Stroock Fellowship for Advanced Research in Judaica at Harvard University, a research fellowship from the Heinrich Hertz-Foundation, and a YIVO Dina Abramowicz Emerging Scholar Fellowship. I thank the organizers of and participants in the colloquia and conferences where I have presented this material in various forms as well as the editors and anonymous reviewers of AJS Review for their valuable comments and suggestions. I am especially grateful to Jeremy Dauber and Elisheva Carlebach of the Institute for Israel and Jewish Studies at Columbia University, where I was a Visiting Scholar in the fall of 2009, for their generous encouragement to write this article. Sue Oren considerably improved my English. The style employed for Romanization of Yiddish follows YIVO's transliteration standards. Unless otherwise noted, translations from the Yiddish, Hebrew, German, and Latin are my own. Quotations from the Bible follow the JPS translation, and those from the Babylonian Talmud are according to the Hebrew-English edition of the Soncino Talmud by Isidore Epstein

Quantitative Imaging in Cell Biology

Cells perform a range of complex functions to maintain homeostasis, including regulation of gene expression, selective trafficking of molecules between subcellular compartments, and protein expression. These processes are mediated by dynamic complexes of proteins and other molecules. Quantitative imaging in biology is concerned with answering questions about the spatial distribution, dynamics and conformational changes of these complexes as they perform their biological functions. This study utilizes a range of quantitative imaging techniques--including plasmon rulers, quantitative fluorescence microscopy, fluorescence recovery after photobleaching (FRAP), and super-resolution imaging--to answer biologically relevant questions.Microorganisms often contend with fluctuating environmental conditions and shifting metabolic demands, and their survival depends on their ability to rapidly alter gene expression. In bacteria, rapid regulation of gene expression is facilitated by transcription attenuation and anti-termination mechanisms that involve the binding of proteins to RNA and the manipulation of RNA structure. In Bacillus species the trp RNA-binding Attenuation Protein (TRAP) modulates the expression of the tryptophan biosynthetic pathway by binding messenger RNA and interfering with transcription elongation. Chapter 2 describes work to characterize the mechanism of TRAP binding to RNA, utilizing a single-molecule method that employs RNA-linked pairs of gold nano-particles--plasmon rulers.Eukaryotic cells segregate their genetic material into an envelope-bound nucleus, and all transport and communication between this compartment and the cytoplasm is mediated by the nuclear pore complex (NPC), a large multi-protein channel. NPC-mediated transport of materials between the cytoplasm and the nucleus is essential for many basic cell functions. The components of this molecular machine have been characterized, and there are several unproven models that describe how these components might function in concert. However, the mechanism by which this system of molecules mediates selective, direction transport has yet to be elucidated.The nuclear transport receptor importin-β, as well as Ran and Nup153 have been shown to be necessary for modulating selectivity of active and passive transport through the NPC. This study provides mechanistic details about importin-β interactions with the pore, which mediate selective, directional transport. Quantitative fluorescence microscopy, FRAP and super-resolution imaging are used to study the interplay of importin-β, Ran and Nup153 in regulating the selectivity and efficiency of the mammalian NPC. Chapter 3 describes the use of FRAP and inverse FRAP (iFRAP) to quantify the dynamics of importin-β turnover in the nuclear pore complex. Chapter 4 describes the use of super-resolution microscopy to characterize the distribution of importin-β in the NPC under a range of conditions.This study characterizes the thermodynamics and kinetics of importin-β interaction with the NPC and shows how Ran and Nup153 mediate these interactions. Importin-β is an integral part of the NPC gate, and Ran acts to remodel this gate. The nucleoporin Nup153 plays a critical in the mechanism, acting as a coordinating site for importin-β and Ran action

Entre culture populaire et culture savante. Les exempla dans le Sefer Hassidim

The exemplary story in Sefer Hasidim. Sefer Hasidim is one of the most important literary, social and religious documents of mediaeval Jewry. It has been studied from various points of view, including the literary-folkloristic aspect. However this collection of tales (more than 400 Hebrew stories) has not yet been studied comprehensively. It has not been compared in depth to the vast exemplary literature that flourished in Christian Europe in the same time and place and no literary analysis has been used in order to understand the complex ideological and social problems reflected in Sefer Hasidim. This study compares the work with the mediaeval exempla in order to point out both the similarity and the uniqueness of the literary phenomenon demonstrated by Sefer Hasidim. It is shown that, as in the Christian type, the exemplary stories of Sefer Hasidim can be divided into two main categories : the "literary exemplum" and the "personal exemplum". However in large number of stories (above one hundred) of Seier Hasidim the leading figure is the "Hakham", fictional-literary figure similar to that of the implied author in modern literature. This is we suggest personification of the author of Sefer Hasidim Judah the Pious himself . Another aspect examined here is that of folk religion. The mediaeval exemplum in Europe played an essential role in disseminating the concepts of Christian folk religion during that period. Sefer Hasidim makes extensive use of the literary techniques of the folktale its forms structure and themes. However the exempla brought here are not folktales. Most of them were composed especially for this work and they were not subsequently recited as folktales. Judah the Pious deliberately used the techniques of folk literature as popular way of influencing the Jewish community to accept his moral and theological ideals In addition to reviewing the comparative and functional aspects of the exempla in Sefer Hasidim our study shows how the tales illuminate Jewish life in twelfth- thirteenth-century Germany. Each becomes miniature depicting an episode of everyday life and demonstrates the teachings. The primary purpose of these stories was undoubtedly moral and that also is why they are so brief and condensed. However they reveal an art of realistic narrative that was very uncommon in mediaeval literature and anticipated realistic literature by many years.Yassif Eli, Séné Jean-François. Entre culture populaire et culture savante. Les exempla dans le Sefer Hassidim. In: Annales. Histoire, Sciences Sociales. 49ᵉ année, N. 5, 1994. pp. 1197-1222