Effect of progesterone and/or estradiol-17beta on sperm penetration in vitro of bovine oocytes

The effect of progesterone (P4) and estradiol-17beta (E2) on sperm penetration was evaluated by in vitro fertilization technique. When spermatozoa were treated with modified Tyrode's medium (mTALP) alone, mTALP + 1.0 microg/ml heparin (H), mTALP + 0.1 microg/ml P4, mTALP + 0.1 microg/ml E2, or mTALP + 0.1 microg/ml P4 + 0. 1 microg/ml E2, the percentages of penetrated oocytes were 11% (8/74), 94% (54/60), 19% (12/64), 10% (6/63) and 13% (8/62), respectively. The penetration rates by spermatozoa treated with H, H + P4, H + E2 and H + P4 + E2 were 94% (118/125), 100% (138/138), 95% (129/136), and 94% (100/106), respectively. However, the oocyte penetration rates significantly increased (P < 0.01) 4, 5 and 6 h after insemination, respectively, when the spermatozoa were treated with H + P4, H + E2 and H + P4 + E2 compared with that of the control (H). Cleavage rates also increased significantly (P < 0.01) 24 and 30 h following insemination, respectively, when spermatozoa were treated with H + P4, H + E2 and H + P4 + E2 compared with that of H. Nevertheless, There was no difference in the production of > or = 32 cell stage embryos among the 4 treatments (19% = 28/149, 18% = 32/176, 18% = 23/128 and 22% = 26/120, respectively). These results indicate that the time course of capacitated sperm penetration was accelerated by progesterone and estradiol-17beta but it did not affect subsequent early embryonic development.     

Plant Surface Receptors Recognizing Microbe-Associated Molecular Patterns

As sessile, plants are inevitably exposed to environmental threats including pathogens. Due to the lack of mobile immune cells, plants solely depend on the innate immune system to defend against pathogens. The first layer of pathogen detection in plant immunity is to recognize microbe-associated molecular patterns (MAMPs) that compose structural or functional units in microbial pathogens. For this, plants utilize pattern-recognition receptors (PRRs). Continuous attack by pathogens resulting from immotility likely contributes to the extension of PRR numbers in plants, although genomeencoded. Recent findings revealed that plant PRRs as a complex dynamically switch between inactive and active forms at the plasma membrane depending on a cognate MAMP. In addition, by regulating the activity and stability of a downstream signal-relaying receptor-like cytoplasmic kinase (RLCK), plants can control the immune homeostasis. Therefore, we in this review discuss on how plants detect a pathogen and how they control immune responses at the level of PRRs in a correct and delicate way. We additionally provide a possible balancing mechanism between growth and responses to biotic and abiotic stresses in plants, which is required for survival in nature.     

Carbon‐Tailored Semimetal MoP as an Efficient Hydrogen Evolution Electrocatalyst in Both Alkaline and Acid Media

The electrolysis processes such as hydrogen evolution reaction (HER) require high efficient catalysts with robust surface stability. A high conductivity is also necessary to speed up the charge transport between the catalyst and the electrolyte. Recently, the observation of exceedingly high conductivity in the topological semimetal MoP, has provided a model catalyst to investigate the correlation between the electrical transport and the electrocatalytic activity for the HER. Thus, MoP is encapsulated in a Mo, P codoped carbon layer (MoP@C). This composite material exhibits outstanding HER performance, with an extremely low overpotential of 49 mV at a current density of 10 mA cm^?2 and a Tafel slope of 54 mV dec^?1 in an alkaline medium. In addition, electron transport analysis indicates that MoP exhibits high conductivity and mobility due to the existence of triple‐point fermions and a complex Fermi surface. Furthermore, the presence of P? C and Mo? C bonds at the interface between the carbon layer and the MoP particles modulates the band structure of MoP@C and facilitates fast electron transfer, accumulation, and subsequent delocalization, which are in turn responsible for the excellent HER activity.     

Three-Directional Evaluation of Mitral Flow in the Rat Heart by Phase-Contrast Cardiovascular Magnetic Resonance

Purpose

Determination of mitral flow is an important aspect in assessment of cardiac function. Traditionally, mitral flow is measured by Doppler echocardiography which suffers from several challenges, particularly related to the direction and the spatial inhomogeneity of flow. These challenges are especially prominent in rodents. The purpose of this study was to establish a cardiovascular magnetic resonance (CMR) protocol for evaluation of three-directional mitral flow in a rodent model of cardiac disease.

Materials and Methods

Three-directional mitral flow were evaluated by phase contrast CMR (PC-CMR) in rats with aortic banding (AB) (N = 7) and sham-operated controls (N = 7). Peak mitral flow and deceleration rate from PC-CMR was compared to conventional Doppler echocardiography. The accuracy of PC-CMR was investigated by comparison of spatiotemporally integrated mitral flow with left ventricular stroke volume assessed by cine CMR.

Results

PC-CMR portrayed the spatial distribution of mitral flow and flow direction in the atrioventricular plane throughout diastole. Both PC-CMR and echocardiography demonstrated increased peak mitral flow velocity and higher deceleration rate in AB compared to sham. Comparison with cine CMR revealed that PC-CMR measured mitral flow with excellent accuracy. Echocardiography presented significantly lower values of flow compared to PC-CMR.

Conclusions

For the first time, we show that PC-CMR offers accurate evaluation of three-directional mitral blood flow in rodents. The method successfully detects alterations in the mitral flow pattern in response to cardiac disease and provides novel insight into the characteristics of mitral flow.     

Interactions of the Anticancer Drug Tamoxifen with Lipid Membranes

Interactions of the hydrophobic anticancer drug tamoxifen (TAM) with lipid model membranes were studied using calcein-encapsulated vesicle leakage, attenuated total reflection Fourier transform infrared (FTIR) spectroscopy, small-angle neutron scattering (SANS), atomic force microscopy (AFM) based force spectroscopy, and all-atom molecular dynamics (MD) simulations. The addition of TAM enhances membrane permeability, inducing calcein to translocate from the interior to the exterior of lipid vesicles. A large decrease in the FTIR absorption band’s magnitude was observed in the hydrocarbon chain region, suggesting suppressed bond vibrational dynamics. Bilayer thickening was determined from SANS data. Force spectroscopy measurements indicate that the lipid bilayer area compressibility modulus K_A is increased by a large amount after the incorporation of TAM. MD simulations show that TAM decreases the lipid area and increases chain order parameters. Moreover, orientational and positional analyses show that TAM exhibits a highly dynamic conformation within the lipid bilayer. Our detailed experimental and computational studies of TAM interacting with model lipid membranes shed new light on membrane modulation by TAM.     

The first range-wide assessment of Saddle-billed Stork Ephippiorhynchus senegalensis distribution

The Saddle-billed Stork Ephippiorhynchus senegalensis exemplifies a case in conservation research in which a species is assessed as Least Concern on the IUCN Red List and the resulting consideration of low conservation priority has precluded proper scientific study. As a first step in understanding this stork’s true status, we collated all available data to develop a distribution map and then investigated range-wide patterns of occurrence. The updated map greatly improves on past knowledge of the stork’s distribution and helps to identify regions where range contractions have occurred, particularly in Central Africa and parts of West Africa. We found that the stork’s distribution closely overlaps with protected areas and that there has been an overall increase in surface water (largely manmade water bodies)—a proxy for habitat—across the species’ extent of occurrence in recent decades. While this research represents a valuable contribution to our understanding of the Saddle-billed Stork, it also highlights the need for unbiased empirical data, especially from areas that are poorly surveyed, for developing a science-based conservation status assessment.     

Impact of Smoking and Brain Metastasis on Outcomes of Advanced EGFR Mutation Lung Adenocarcinoma Patients Treated with First Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

ObjectivesThis purpose of this study was to examine clinical-pathologic factors – particularly smoking and brain metastases – in EGFR mutation positive (M+) lung adenocarcinoma (ADC) to determine their impact on survival in patients treated with first line EGFR TKI.MethodsA retrospective review of EGFR mutation reflex testing experience for all ADC diagnosed at a tertiary Asian cancer centre from January 2009 to April 2013. Amongst this cohort, patients with advanced EGFR M+ ADC treated with first line EGFR TKI were identified to determine factors that influence progression free and overall survival.Results444/742 (59.8%) ADC reflex tested for EGFR mutations were EGFR M+. Amongst never-smokers (n=468), EGFR M+ were found in 74.5% of females and 76.3% of males, and amongst ever smokers (n=283), in 53.3% of females and 35.6% of males. Exon 20 mutations were found more commonly amongst heavy smokers (> 50 pack years and > 20 pack years, Pearson’s chi square p=0.044, and p=0.038 respectively). 211 patients treated with palliative first line TKI had a median PFS and OS of 9.2 and 19.6 months respectively. 26% of patients had brain metastasis at diagnosis. This was significantly detrimental to overall survival (HR 1.85, CI 1.09-3.16, p=0.024) on multivariate analysis. There was no evidence that smoking status had a significant impact on survival.ConclusionsThe high prevalence of EGFR M+ in our patient population warrants reflex testing regardless of gender and smoking status. Smoking status and dosage did not impact progression free or overall survival in patients treated with first line EGFR TKI. The presence of brain metastasis at diagnosis negatively impacts overall survival.     

Mucin secretion by the human colon cell line LS174T is regulated by bile salts

We recently reported that bile salts play a role in the regulation of mucin secretion by cultured dog gallbladder epithelial cells. In this study we have examined whether bile salts also influence mucin secretion by the human epithelial colon cell line LS174T. Solutions of bile salts were applied to monolayers of LS174T cells. Mucin secretion was quantified by measuring the secretion of [3H]GlcNAc labeled glycoproteins. Both unconjugated bile salts as well as taurine conjugated bile salts stimulated mucin secretion by the colon cells in a dose-dependent fashion. Hydrophobic bile salts were more potent stimulators than hydrophilic bile salts. Free (unconjugated) bile salts were more stimulatory compared with their taurine conjugated counterparts. Stimulation of mucin secretion by LS174T cells was found to occur at much lower bile salt concentrations than in the experiments with the dog gallbladder epithelial cells. The protein kinase C activators PMA and PDB had no stimulatory effect on mucin secretion. We conclude that mucin secretion by the human colon epithelial cell line LS174T is regulated by bile salts. We suggest that regulation of mucin secretion by bile salts might be a common mechanism, by which different epithelia protect themselves against the detergent action of bile salts, to which they are exposed throughout the gastrointestinal tract.