Comparison and Avoidance of Toxicity of Penetrating Cryoprotectants

The objective of this study was to elucidate the toxicity of widely used penetrating cryoprotective agents (CPAs) to mammalian oocytes. To this end, mouse metaphase II (M II) oocytes were exposed to 1.5 M solutions of dimethylsulfoxide (DMSO), ethylene glycol (EG), or propanediol (PROH) prepared in phosphate buffered saline (PBS) containing 10% fetal bovine serum. To address the time- and temperature-dependence of the CPA toxicity, M II oocytes were exposed to the aforementioned CPAs at room temperature (RT, ∼23°C) and 37°C for 15 or 30 minutes. Subsequently, the toxicity of each CPA was evaluated by examining post-exposure survival, fertilization, embryonic development, chromosomal abnormalities, and parthenogenetic activation of treated oocytes. Untreated oocytes served as controls. Exposure of MII oocytes to 1.5 M DMSO or 1.5 M EG at RT for 15 min did not adversely affect any of the evaluated criteria. In contrast, 1.5 M PROH induced a significant increase in oocyte degeneration (54.2%) and parthenogenetic activation (16%) under same conditions. When the CPA exposure was performed at 37°C, the toxic effect of PROH further increased, resulting in lower survival (15%) and no fertilization while the toxicity of DMSO and EG was still insignificant. Nevertheless, it was possible to completely avoid the toxicity of PROH by decreasing its concentration to 0.75 M and combining it with 0.75 M DMSO to bring the total CPA concentration to a cryoprotective level. Moreover, combining lower concentrations (i.e., 0.75 M) of PROH and DMSO significantly improved the cryosurvival of MII oocytes compared to the equivalent concentration of DMSO alone. Taken together, our results suggest that from the perspective of CPA toxicity, DMSO and EG are safer to use in slow cooling protocols while a lower concentration of PROH can be combined with another CPA to avoid its toxicity and to improve the cryosurvival as well

The cone of curves of Fano varieties of coindex four

We classify the cones of curves of Fano varieties of dimension greater or equal than five and (pseudo)index dim X -3, describing the number and type of their extremal rays.Comment: 27 pages; changed the numbering of Theorems, Definitions, Propositions, etc. in accordance with the published version to avoid incorrect reference

Rank-2 Fano bundles over a smooth quadric Q 3

In the present paper we examine rank-2 stable bundles over Q3 with c1 = 0 and c2 = 2 or 4

Self and Microbiota-Derived Epitopes Induce CD4⁺ T Cell Anergy and Conversion into CD4⁺Foxp3⁺ Regulatory Cells

The physiological role of T cell anergy induction as a key mechanism supporting self-tolerance remains undefined, and natural antigens that induce anergy are largely unknown. In this report, we used TCR sequencing to show that the recruitment of CD4+CD44+Foxp3−CD73+FR4+ anergic (Tan) cells expands the CD4+Foxp3+ (Tregs) repertoire. Next, we report that blockade in peripherally-induced Tregs (pTregs) formation due to mutation in CNS1 region of Foxp3 or chronic exposure to a selecting self-peptide result in an accumulation of Tan cells. Finally, we show that microbial antigens from Akkermansia muciniphila commensal bacteria can induce anergy and drive conversion of naive CD4+CD44-Foxp3− T (Tn) cells to the Treg lineage. Overall, data presented here suggest that Tan induction helps the Treg repertoire to become optimally balanced to provide tolerance toward ubiquitous and microbiome-derived epitopes, improving host ability to avert systemic autoimmunity and intestinal inflammation

Addendum to: Capillary floating and the billiard ball problem

We compare the results of our earlier paper on the floating in neutral equilibrium at arbitrary orientation in the sense of Finn-Young with the literature on its counterpart in the sense of Archimedes. We add a few remarks of personal and social-historical character.Comment: This is an addendum to my article Capillary floating and the billiard ball problem, Journal of Mathematical Fluid Mechanics 14 (2012), 363 -- 38

Methylation of plasmacytoma c-myc genes

The chromosomal translocation associated with many tumors of immunoglobulin-producing cells frequently results in the joining of the immunoglobulin heavy-chain locus and the c-myc oncogene. This translocation of c-myc has profound structural and functional consequences for the oncogene, including loss of the 5 ' end of the gene and transcriptional deregulation. We report in this communication that translocation results in a new methylation pattern of c-myc. In normal kidney and liver tissue, the c-myc gene is methylated at its 3' end. The translocated gene in plasmacytoma DNA is extensively demethylated. On the other hand, the nonrearranged c-myc gene in plasmacytoma DNA (which is transcriptionally silent) is extensively methylated. In addition, we confirm the nucleotide sequence (with 19 discrepancies out of 1400 bp) 5' to the murine c-myc gene, as reported by Corcoran et al. [Cell 40 (1985) 71-79].Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25882/1/0000445.pd

Two subfamilies of murine retrotransposon ETn sequences

Early transposon (ETn) elements are 5.7-kb retrotransposons found in the murine genome. We have sequenced large portions of two ETn elements that have apparently transposed within the DNA of a murine myeloma cell line, P3.26Bu4. One of the transposed ETn elements has 5' and 3' long terminal repeats (LTRs) that are exact duplicates of each other and has a 6-bp target site duplication. These results suggest that this element, which inserted into an immunoglobulin [gamma]1 switch region, moved by a retrotransposition process. Our nucleotide sequences confirm that individual ETn elements are very similar to one another and lack open reading frames. However, the ETn sequences reported here and those previously described differ significantly near their 5' LTRs, including 200 bp of weak similarity and 240 bp of complete disparity. Southern hybridization analysis suggests that both subfamilies of ETn sequences are represented many times in the mouse genome. The possibility that the disparate sequences have a role in transposition by ETn elements is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28722/1/0000543.pd

Dipolar quantum solids emerging in a Hubbard quantum simulator

In quantum mechanical many-body systems, long-range and anisotropic interactions promote rich spatial structure and can lead to quantum frustration, giving rise to a wealth of complex, strongly correlated quantum phases. Long-range interactions play an important role in nature; however, quantum simulations of lattice systems have largely not been able to realize such interactions. A wide range of efforts are underway to explore long-range interacting lattice systems using polar molecules, Rydberg atoms, optical cavities, and magnetic atoms. Here, we realize novel quantum phases in a strongly correlated lattice system with long-range dipolar interactions using ultracold magnetic erbium atoms. As we tune the dipolar interaction to be the dominant energy scale in our system, we observe quantum phase transitions from a superfluid into dipolar quantum solids, which we directly detect using quantum gas microscopy with accordion lattices. Controlling the interaction anisotropy by orienting the dipoles enables us to realize a variety of stripe ordered states. Furthermore, by transitioning non-adiabatically through the strongly correlated regime, we observe the emergence of a range of metastable stripe-ordered states. This work demonstrates that novel strongly correlated quantum phases can be realized using long-range dipolar interaction in optical lattices, opening the door to quantum simulations of a wide range of lattice models with long-range and anisotropic interactions

Optimization of Cryoprotectant Loading into Murine and Human Oocytes

Loading of cryoprotectants into oocytes is an important step of the cryopreservation process, in which the cells are exposed to potentially damaging osmotic stresses and chemical toxicity. Thus, we investigated the use of physics-based mathematical optimization to guide design of cryoprotectant loading methods for mouse and human oocytes. We first examined loading of 1.5 M dimethylsulfoxide (Me₂SO) into mouse oocytes at 23°C. Conventional one-step loading resulted in rates of fertilization (34%) and embryonic development (60%) that were significantly lower than those of untreated controls (95% and 94%, respectively). In contrast, the mathematically optimized two-step method yielded much higher rates of fertilization (85%) and development (87%). To examine the causes for oocyte damage, we performed experiments to separate the effects of cell shrinkage and Me₂SO exposure time, revealing that neither shrinkage nor Me₂SO exposure single-handedly impairs the fertilization and development rates. Thus, damage during one-step Me₂SO addition appears to result from interactions between the effects of Me₂SO toxicity and osmotic stress. We also investigated Me₂SO loading into mouse oocytes at 30°C. At this temperature, fertilization rates were again lower after one-step loading (8%) in comparison to mathematically optimized two-step loading (86%) and untreated controls (96%). Furthermore, our computer algorithm generated an effective strategy for reducing Me₂SO exposure time, using hypotonic diluents for cryoprotectant solutions. With this technique, 1.5 M Me₂SO was successfully loaded in only 2.5 min, with 92% fertilizability. Based on these promising results, we propose new methods to load cryoprotectants into human oocytes, designed using our mathematical optimization approach.Keywords: Propane-1,2-diol, Freezing, Propylene glycol, DMSO, Vitrification, Cryopreservation, Mouse, Cryoprotectant, Dimethyl sulfoxide, Simplex optimization, Oocyte, Human, Me₂S

CETOBaC - Centre d’études turques, ottomanes, balkaniques et centrasiatiques

Marc Aymes, chargé de recherche au CNRSBenjamin Gourisse, ATER à l’Université Paris-I/Panthéon-SorbonneEmmanuel Szurek, doctorant à l’EHESS Sociologie historique de l’État en Turquie depuis les Tanzimat Le séminaire s’est poursuivi en 2010-2011 pour sa troisième année consécutive. Il demeure articulé au programme ANR TRANSTUR, « Ordonner et transiger. Modalités de gouvernement et d’administration en Turquie et dans l’Empire ottoman du XIXe siècle à nos jours » (2008-2011), dont il permet de d..