No abstract

Non-invasive gamete and embryo assessment is considered an important focus in assisted reproductive technologies (ART). Currently, the selection of embryos for transfer is based on morphological indices. Though successful, the field of ART would benefit from a non-invasive quantitative method of viability determination. Omics technologies, including transcriptomics, proteomics and metabolomics, have already begun providing evidence that viable gametes and embryos possess unique molecular profiles with potential biomarkers that can be utilized for developmental and/or viability selection. Unlike the human genome that is relatively fixed and steady throughout the human body, the human proteome, estimated at over a million proteins, is more complex, diverse and dynamic. It is the proteins themselves that contribute to the physiological homeostasis in any cell or tissue. Of particular interest in ART is the secretome, those proteins that are produced within the embryo and secreted into the surrounding environment. Defining the human embryonic secretome has the potential to expand our knowledge of embryonic cellular processes, including the complex dialogue between the developing embryo and its maternal environment, and may also assist in identifying those embryos with the highest implantation potential. Advances in proteomic technologies have allowed the non-invasive profiling of the human embryonic secretome with ongoing research focused on correlation with outcome. From a clinical perspective, embryo selection based on morphological assessment and non-invasive analysis of the human embryonic secretome may improve IVF success and lead to routine single embryo transfers.

No abstract

The envelope glycoproteins of the class I family, which include human immunodeficiency virus (HIV), influenza, and severe acute respiratory syndrome coronavirus (SARS-CoV), mediate viral entry by first binding to their cellular receptors and subsequently inducing fusion of the viral and cellular membranes. In the case of SARS-CoV, heptad repeat domains of the envelope glycoprotein, termed S2-HR1 and S2-HR2, are thought to undergo structural changes from a prefusion state, in which S2-HR1 and S2-HR2 do not interact, to a postfusion state in which S2-HR1 and S2-HR2 associate to form a six-helix bundle. In the present work, the structural and dynamic properties of S2-HR2 have been characterized. Evidence is presented for an equilibrium between a structured trimer thought to represent a prefusion state and an ensemble of unstructured monomers thought to represent a novel transition state. A model for viral entry is presented in which S2-HR2 is in a dynamic equilibrium between an ensemble of unstructured monomers in the transition state and a structured trimer in the prefusion state. Conversion from the prefusion state to the postfusion state requires passage through the transition state, a state that may give insight into the design of structure-based antagonists of SARS-CoV in particular, as well as other enveloped viruses in general.