Preparation and Use of a General Solid-Phase Intermediate to Biomimetic Scaffolds and Peptide Condensations

The Distributed Drug Discovery (D3) program develops simple, powerful, and reproducible procedures to enable the distributed synthesis of large numbers of potential drugs for neglected diseases. The synthetic protocols are solid-phase based and inspired by published work. One promising article reported that many biomimetic molecules based on diverse scaffolds with three or more sites of variable substitution can be synthesized in one or two steps from a common key aldehyde intermediate. This intermediate was prepared by the ozonolysis of a precursor functionalized at two variable sites, restricting their presence in the subsequently formed scaffolds to ozone compatible functional groups. To broaden the scope of the groups available at one of these variable sites, we developed a synthetic route to an alternative, orthogonally protected key intermediate that allows the incorporation of ozone sensitive groups after the ozonolysis step. The utility of this orthogonally protected intermediate is demonstrated in the synthesis of several representative biomimetic scaffolds containing ozonolytically labile functional groups. It is compatible with traditional Fmoc peptide chemistry, permitting it to incorporate peptide fragments for use in fragment condensations with peptides containing cysteine at the N-terminus. Overall yields for its synthesis and utilization (as many as 13 steps) indicate good conversions at each step

Pronuclear scoring as a predictor of embryo quality in in vitro fertilization program.

Many strategies have been proposed for the selection of viable embryos for transfer in human assisted reproduction. These have included morphological scoring criteria for 20, 28, 44 and 68 h after insemination. The embryo selection is based on morphology, degree of fragmentation and development to the 8-cell. All have shown some correlation with implantation. However, the overall success of these methods is still limited, with over 50% of all transferred embryos failing to implant. Pronuclear zygote morphology has gained much attention recently due to its positive value in predicting implantation and pregnancy. This prospective study involved 178 conventional IVF patients only. The key aspects of pronuclear scoring and namely the presence of a cytoplasmic halo were related to day 3 of development and morphology in a retrospective study. The Z-score and the presence/absence of a halo had significant effect on the rate of development on day 3 embryo. Low Z-score result in slow development and poor morphology. The absence of a halo also resulted in slow and poor development, low morphology, increased fragmentation

Evaluation of protamines 1 and 2 transcript contents in spermatozoa from asthenozoospermic men.

During mammalian spermatogenesis, the chromatin structure undergoes substantial condensation. The key role in this process is played by protamines 1 and 2 (PRM1, PRM2). We attempted to compare the levels of PRM1 and PRM2 transcripts in mature spermatozoa of normospermic and asthenozoospermic men. Human ejaculates from normozoospermic (n=70) and asthenozoospermic (n=100) donors were purified by centrifugation through discontinuous Percoll density gradient. RNA was isolated from spermatozoa according to the ChomczyĂąski and Sacchi method, treated with DNase I, and reverse-transcribed into cDNA. Using reverse transcription and real-time quantitative polymerase chain reaction analysis, we found a reduction in the levels of PRM1 and PRM2 transcripts in spermatozoa from asthenozoospermic men, as compared to controls (

Effect of acceptance of illness on treatment adherence in atrial fibrillation patients

Introduction and aim of the study: Atrial fibrillation is the most common durable type of arrhythmia. To obtain the positive effects of treatment it necessary that the patient respects the therapeutic recommendations and cooperates with the medical staff. An important factor affecting the patients adherence to the therapeutic plan is the acceptance of the illness. The aim of the study was to assess the effect of the acceptance of illness on treatment adherence in atrial fibrillation patients.Material and methods: The study involved 105 patients with atrial fibrillation (mean age72,6; SD=6,9). The study used a medication adherence questionnaire MMAS-8 (Morisky Medication Adherence Scale) and the acceptance of illness questionaire AIS (ang. Acceptance of Illness Scale). Results: In the AIS questionnaire, the respondents received an average score of 22.67 points, which corresponds to the average level of acceptance of the illness. The results showed that 25% of the patients had low, 30% had medium, and 45% had high treatment adherence. Patients with high levels of AIS achieved high levels of treatment adherence (MMAS-8 = 8), while patients with low levels of AIS achieved low treatment adherence (MMAS-8 = 5.51). Correlation analysis showed a strong, statistically significant relationship between the level of treatment adherence and the level of illness acceptance (r = 0.7408; p = 0.01).Conclusions: The acceptance of illness significantly affects the treatment adherence in atrial fibrillation patients. The higher level of AIS determines better anticoagulation and antiarrhythmic treatment adherence in atrial fibrillation patients

Impact of GnRH analogues on oocyte/embryo quality and embryo development in in vitro fertilization/intracytoplasmic sperm injection cycles: a case control study

<p>Abstract</p> <p>Background</p> <p>Despite the clinical outcomes of ovarian stimulation with either GnRH-agonist or GnRH-antagonist analogues for in vitro fertilization (IVF) being well analysed, the effect of analogues on oocyte/embryo quality and embryo development is still not known in detail. The aim of this case-control study was to compare the efficacy of a multiple-dose GnRH antagonist protocol with that of the GnRH agonist long protocol with a view to oocyte and embryo quality, embryo development and IVF treatment outcome.</p> <p>Methods</p> <p>Between October 2001 and December 2008, 100 patients were stimulated with human menopausal gonadotrophin (HMG) and GnRH antagonist in their first treatment cycle for IVF or intracytoplasmic sperm injection (ICSI). One hundred combined GnRH agonist + HMG (long protocol) cycles were matched to the GnRH antagonist + HMG cycles by age, BMI, baseline FSH levels and by cause of infertility. We determined the number and quality of retrieved oocytes, the rate of early-cleavage embryos, the morphology and development of embryos, as well as clinical pregnancy rates. Statistical analysis was performed using Wilcoxon's matched pairs rank sum test and McNemar's chi-square test. P < 0.05 was considered statistically significant.</p> <p>Results</p> <p>The rate of cytoplasmic abnormalities in retrieved oocytes was significantly higher with the use of GnRH antagonist than in GnRH agonist cycles (62.1% vs. 49.9%; P < 0.01). We observed lower rate of zygotes showing normal pronuclear morphology (49.3% vs. 58.0%; P < 0.01), and higher cell-number of preembryos on day 2 after fertilization (4.28 vs. 4.03; P < 0.01) with the use of GnRH antagonist analogues. The rate of mature oocytes, rate of presence of multinucleated blastomers, amount of fragmentation in embryos and rate of early-cleaved embryos was similar in the two groups. Clinical pregnancy rate per embryo transfer was lower in the antagonist group than in the agonist group (30.8% vs. 40.4%) although this difference did not reach statistical significance (P = 0.17).</p> <p>Conclusion</p> <p>Antagonist seemed to influence favourably some parameters of early embryo development dynamics, while other morphological parameters seemed not to be altered according to GnRH analogue used for ovarian stimulation in IVF cycles.</p

Enhanced Zika virus susceptibility of globally invasive Aedes aegypti populations

The drivers and patterns of zoonotic virus emergence in the human population are poorly understood. The mosquito Aedes aegypti is a major arbovirus vector native to Africa that invaded most of the world’s tropical belt over the past four centuries, after the evolution of a “domestic” form that specialized in biting humans and breeding in water storage containers. Here, we show that human specialization and subsequent spread of A. aegypti out of Africa were accompanied by an increase in its intrinsic ability to acquire and transmit the emerging human pathogen Zika virus. Thus, the recent evolution and global expansion of A. aegypti promoted arbovirus emergence not solely through increased vector–host contact but also as a result of enhanced vector susceptibility

Contribution à l'étude des relations entre l'infiltration et l'alimentation de la nappe du plateau de Lauzelle

Master [120] bioingénieur : gestion des forêts et des espaces naturels (Louvain-la-Neuve), Université catholique de Louvain, 197

Prawda ludowa i jej rola w konstruowaniu rosyjskiego dyskursu anarchicznego

Michaił Martynow Московский педагогический государственный университет, Moskva, Russian Federation [email protected]   Celem artykułu jest badanie semantyki „prawdy ludowej” i ustalenia jej roli w procesie konstruowania rosyjskiego dyskursu anarchicznego. Autor pokazuje, że stałe sensy kulturowe kategorii „prawda” określają niektóre osobliwości rosyjskiego anarchizmu. Za materiał badawczy posłużyły teksty kluczowych postaci rosyjskiego anarchizmu (Michaiła Bakunina, Piotra Kropotkina), a także teksty, np. ulotki, manifesty czy programy rosyjskich anarchistów końca XIX - początku XX ww. The paper considers the concept of “the national truth” and its role in designing the Rus-sian anarchical discourse. The author shows that cultural meanings of the truth that define some features of the Russian anarchism. Object of the analysis is the group of texts of key representatives of anarchical thought in Russia (Mikhail Bakunin, Piotr Kropotkin), and also some texts of leaflets, manifestos and