Exosomal Cargo May Hold the Key to Improving Reproductive Outcomes in Dairy Cows

The reproductive status of dairy cows remains a challenge for dairy farmers worldwide, with impaired fertility linked to a significant reduction in herd profitability, due in part to impaired immunity, increased metabolic pressure, and longer postpartum anestrous interval (PPAI). Exosomes are nanovesicles released from a variety of cell types and end up in circulation, and carry proteins, bioactive peptides, lipids, and nucleic acids specific to the place of origin. As such, their role in health and disease has been investigated in humans and animals. This review discusses research into exosomes in the context of reproduction in dairy herds and introduces recent advances in mass-spectrometry (MS) based proteomics that have a potential to advance quantitative profiling of exosomal protein cargo in a search for early biomarkers of cattle fertility.     

The Role of Exosomal Epigenetic Modifiers in Cell Communication and Fertility of Dairy Cows

Abnormal uterine function affects conception rate and embryo development, thereby leading to poor fertility and reproduction failure. Exosomes are a nanosized subclass of extracellular vesicles (EV) that have important functions as intercellular communicators. They contain and carry transferable bioactive substances including micro RNA (miRNA) for target cells. Elements of the cargo can provide epigenetic modifications of the recipient cells and may have crucial roles in mechanisms of reproduction. The dairy industry accounts for a substantial portion of the economy of many agricultural countries. Exosomes can enhance the expression of inflammatory mediators in the endometrium, which contribute to various inflammatory diseases in transition dairy cows. This results in reduced fertility which leads to reduced milk production and increased cow maintenance costs. Thus, gaining a clear knowledge of exosomal epigenetic modifiers is critical to improving the breeding success and profitability of dairy farms. This review provides a brief overview of how exosomal miRNA contributes to inflammatory diseases and hence to poor fertility, particularly in dairy cows.     

Bioactive compounds and antioxidant capacities in different edible tissues of citrus fruit of four species

Different edible tissues of citrus fruit, namely juice sacs (JS), segment membrane (SM), and segment (Seg), of four species, were examined for contents of bioactive compounds and total antioxidant capacities (TAC) by ferric reducing antioxidant power (FRAP) assay. Two flavanones (naringin and hesperidin) were identified by HPLC; hesperidin accounted for 18.5–38.5% of the total phenolics in the species Citrus unshiu, Citrus reticulata, and Citrus sinensis, while naringin was only found in Citrus changshanensis and it accounted for 53.7% of the total phenolics in SM of this species. In SM of all selected species, the contents of phenolic compounds and TAC were significantly higher than those in JS and Seg. Highest total phenolics, total flavonoids, naringin, and TAC were found in SM of C. changshanensis, while the highest carotenoid content was found in JS of C. reticulata. The contribution of vitamin C to TAC ranged from 26.9% to 45.9% in JS and Seg of all selected species. In SM, however, a high contribution from hesperidin was observed in C. unshiu (54.0%), C. sinensis (46.7%) and C. reticulata (30.0%). The results indicated that SM of citrus fruit were high in contents of bioactive compounds and TAC; it is thus recommended to consume citrus fruit with all edible tissues rather than juice or JS alone.     

Role of Long-Range Protein Dynamics in Different Thymidylate Synthase Catalyzed Reactions

Recent studies of Escherichia coli thymidylate synthase (ecTSase) showed that a highly conserved residue, Y209, that is located 8 Å away from the reaction site, plays a key role in the protein’s dynamics. Those crystallographic studies indicated that Y209W mutant is a structurally identical but dynamically altered relative to the wild type (WT) enzyme, and that its turnover catalytic rate governed by a slow hydride-transfer has been affected. The most challenging test of an examination of a fast chemical conversion that precedes the rate-limiting step has been achieved here. The physical nature of both fast and slow C-H bond activations have been compared between the WT and mutant by means of observed and intrinsic kinetic isotope effects (KIEs) and their temperature dependence. The findings indicate that the proton abstraction step has not been altered as much as the hydride transfer step. Additionally, the comparison indicated that other kinetic steps in the TSase catalyzed reaction were substantially affected, including the order of the substrate binding. Enigmatically, although Y209 is H-bonded to 3''-OH of 2''-deoxyuridine-5''-mono­phosphate (dUMP), its altered dynamics is more pronounced on the binding of the remote cofactor, (6R)-N⁵,N¹⁰-methylene-5,6,7,8-tetrahydrofolate (CH₂H₄folate), revealing the importance of long-range dynamics of the enzymatic complex and its catalytic function.     

Microelectromechanical system pressure sensor integrated onto optical fiber by anodic bonding

Optical microelectromechanical system pressure sensors based on the principle of Fabry-Perot interferometry have been developed and fabricated using the technique of silicon-to-silicon anodic bonding. The pressure sensor is then integrated onto an optical fiber by a novel technique of anodic bonding without use of any adhesives. In this anodic bonding technique we use ultrathin silicon of thickness 10 microm to bond the optical fiber to the sensor head. The ultrathin silicon plays the role of a stress-reducing layer, which helps the bonding of an optical fiber to silicon having conventional wafer thickness. The pressure-sensing membrane is formed by 8 microm thick ultrathin silicon acting as a membrane, thus eliminating the need for bulk silicon etching. The pressure sensor integrated onto an optical fiber is tested for static response, and experimental results indicate degradation in the fringe visibility of the Fabry-Perot interferometer. This effect was mainly due to divergent light rays from the fiber degrading the fringe visibility. This effect is demonstrated in brief by an analytical model.     

Why Use Enactable Models of Construction Processes?

Construction is a process-based industry. In such an industry it is important to have a clear understanding of the process. One way to achieve this is by the use of a process model. In a European Community funded research project the business process of a small U.K. construction company was modeled and analyzed. Both visual modeling and enactable modeling techniques were used in this exercise. This paper aims to show how process understanding can be better achieved by a combination of visual models and enactable models. This is supported by examples from the construction company process studied. The tools and techniques used in this exercise are those developed by the collaborators of the project. The visual modeling is done using ProcessWise WorkBench and Role Activity Diagrams. The view of the business process given by the ProcessWise WorkBench models is predominantly process based, whereas Role Activity Diagrams provide a role based view of the process. The enactable modeling is done using RolEnact, a modeling tool that enacts formal specifications of processes.     

Degradation of crosslinked resins in water and electrolyte solutions

In addition to chemical processes such as the hydrolysis of ester groups, there are physical processes contributing to the hygrothermal degradation of crosslinked polyester resins. This paper discusses the interaction between physical and chemical processes and reports short and long term observations on the degradation of several resins of various compositions during immersion in aqueous liquids. Initial swelling is accompanied by weight changes which are the result of (i) absorption of water (ii) leaching of non-bound substances and (iii) leaching of hydrolysis products. Leached substances are identified qualitatively by n.m.r. spectroscopy and, in some cases, semi-quantitatively by gas-liquid chromatography (g.l.c.). Osmotic disc cracks greatly accelerate the hydrolysis process and appear to be caused mainly by the presence of residual or added glycol in the resins. (These cracks were almost entirely absent from a vinyl ester resin). Scanning and high resolution transmission electron micrographs demonstrate the nature and extent of surface physical damage by water.     

Modulating Astrocyte Transition after Stroke to Promote Brain Rescue and Functional Recovery: Emerging Targets Include Rho Kinase

Stroke is a common and serious condition, with few therapies. Whilst previous focus has been directed towards biochemical events within neurons, none have successfully prevented the progression of injury that occurs in the acute phase. New targeted treatments that promote recovery after stroke might be a better strategy and are desperately needed for the majority of stroke survivors. Cells comprising the neurovascular unit, including blood vessels and astrocytes, present an alternative target for supporting brain rescue and recovery in the late phase of stroke, since alteration in the unit also occurs in regions outside of the lesion. One of the major changes in the unit involves extensive morphological transition of astrocytes resulting in altered energy metabolism, decreased glutamate reuptake and recycling, and retraction of astrocyte end feed from both blood vessels and neurons. Whilst globally inhibiting transitional change in astrocytes after stroke is reported to result in further damage and functional loss, we discuss the available evidence to suggest that the transitional activation of astrocytes after stroke can be modulated for improved outcomes. In particular, we review the role of Rho-kinase (ROCK) in reactive gliosis and show that inhibiting ROCK after stroke results in reduced scar formation and improved functional recovery.     

Pushover Analysis of Inelastic Seismic Behavior of Greveniotikos Bridge

Nonlinear pushover analysis is a powerful tool for evaluating the inelastic seismic behavior of structures. The paper deals with the nonlinear analysis process followed during the independent design check of the Greveniotikos Bridge in Greece. The nonlinear response of the bridge was investigated from the first pier hinging to the inelastic equilibrium condition during the design-level earthquake and then up to the ultimate limit state. The effects on the seismic demand of period lengthening and damping increase produced by structural deterioration were evaluated. Onset and progression of plastic hinges were determined along with the pier stiffness distribution and the force reduction factors to be used in spectral analysis. The nonlinear loading conditions of plastic hinges were analyzed to assess their rotation capacity and shear strength. Finally, the safety factor from progressive collapse condition was evaluated. The parametric approach followed in this work permitted evaluation of the effects of several parameters on the inelastic structure response, thus enhancing confidence with result evaluation.