Quantum properties of transverse pattern formation in second-harmonic generation

We investigate the spatial quantum noise properties of the one dimensional transverse pattern formation instability in intra-cavity second-harmonic generation. The Q representation of a quasi-probability distribution is implemented in terms of nonlinear stochastic Langevin equations. We study these equations through extensive numerical simulations and analytically in the linearized limit. Our study, made below and above the threshold of pattern formation, is guided by a microscopic scheme of photon interaction underlying pattern formation in second-harmonic generation. Close to the threshold for pattern formation, beams with opposite direction of the off-axis critical wave numbers are shown to be highly correlated. This is observed for the fundamental field, for the second harmonic field and also for the cross-correlation between the two fields. Nonlinear correlations involving the homogeneous transverse wave number, which are not identified in a linearized analysis, are also described. The intensity differences between opposite points of the far fields are shown to exhibit sub-Poissonian statistics, revealing the quantum nature of the correlations. We observe twin beam correlations in both the fundamental and second-harmonic fields, and also nonclassical correlations between them.Comment: 18 pages, 17 figures, submitted to Phys. Rev.

In vitro production of bovine embryos derived from individual donors in the Corral® dish

Background: Since the identity of the embryo is of outmost importance during commercial in vitro embryo production, bovine oocytes and embryos have to be cultured strictly per donor. Due to the rather low yield of oocytes collected after ovum pick-up (OPU) per individual cow, oocyte maturation and embryo culture take place in small groups, which is often associated with inferior embryo development. The objective of this study was to improve embryonic development in small donor groups by using the Corral (R) dish. This commercial dish is designed for human embryo production. It contains two central wells that are divided into quadrants by a semi-permeable wall. In human embryo culture, one embryo is placed per quadrant, allowing individual follow-up while embryos are exposed to a common medium. In our study, small groups of oocytes and subsequently embryos of different bovine donors were placed in the Corral (R) dish, each donor group in a separate quadrant. Results: In two experiments, the Corral (R) dish was evaluated during in vitro maturation (IVM) and/or in vitro culture (IVC) by grouping oocytes and embryos of individual bovine donors per quadrant. At day 7, a significantly higher blastocyst rate was noted in the Corral (R) dish used during IVM and IVC than when only used during IVM (12.9% +/- 2.10 versus 22.8% +/- 2.67) (P < 0.05). However, no significant differences in blastocyst yield were observed anymore between treatment groups at day 8 post insemination. Conclusions: In the present study, the Corral (R) dish was used for in vitro embryo production (IVP) in cattle; allowing to allocate oocytes and/or embryos per donor. As fresh embryo transfers on day 7 have higher pregnancy outcomes, the Corral (R) dish offers an added value for commercial OPU/IVP, since a higher blastocyst development at day 7 is obtained when the Corral (R) dish is used during IVM and IVC

Quaternary structure of a G-protein coupled receptor heterotetramer in complex with Gi and Gs

Background: G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. Results: We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. Conclusions: The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function

Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer’s disease

BACKGROUND: Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD). METHODS: Following quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638). RESULTS: In the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß =  - 0.072, 95%CI = [- 0.12, - 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß =  - 0.066, 95% CI = [- 0.11, - 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction. CONCLUSIONS: Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality

Regulation of sheep oocyte maturation using cAMP modulators

Physical removal of mammalian cumulus-oocyte complexes (COCs) from ovarian follicles results in spontaneous resumption of meiosis, largely because of a decrease in cAMP concentrations, causing asynchrony between cytoplasmic and nuclear maturation and decreased oocyte developmental competence. The aim of this study was to modulate cAMP concentrations within ovine COCs to delay spontaneous nuclear maturation and improve developmental competence. Abattoir-derived sheep COCs were cultured for 2 hours (pre-IVM) in 100 μM forskolin (FSK) plus 500 μM 3-isobutyl-1-methylxanthine (IBMX). Pre-IVM (100 μM FSK and 500 μM IBMX) culture increased COC cAMP concentrations 10-fold compared with controls (P < 0.05). With regard to nuclear maturation, with FSK and IBMX and/or with FSH and cilostamide delayed completion of meiosis (metaphase II) by 3 to 4 hours compared with standard IVM (FSH-stimulated induction of meiosis). In this study, pre-IVM (with FSK and IBMX) followed by IVM (with FSH and cilostamide), increased ovine COC cAMP concentrations and delayed, but did not inhibit, completion of nuclear maturation. This did not affect embryo development rates, but increased total cell number of blastocysts compared with IVM with FSH alone (103 ± 6 vs. 66 ± 4 cells, respectively; mean ± SEM; P < 0.05). We inferred that regulation of ovine oocyte cAMP concentrations during IVM improved embryo quality compared with embryos produced by standard IVM methods.Ryan D. Rose, Robert B. Gilchrist, Jennifer M. Kelly, Jeremy G. Thompson, Melanie L. Sutton-McDowal

Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer's disease

Background Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46—the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer’s disease (AD). Methods Following quality control, levels of 1019 metabolites—detected with liquid chromatography-mass spectrometry—were available for 1740 participants at age 60–64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69–71). Regression analyses tested relationships between metabolite measures—modules and hub metabolites—and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638). Results In the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß =  − 0.072, 95%CI = [− 0.12, − 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß =  − 0.066, 95% CI = [− 0.11, − 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction. Conclusions Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality

Topology of molecular machines of the endoplasmic reticulum: a compilation of proteomics and cytological data

The endoplasmic reticulum (ER) is a key organelle of the secretion pathway involved in the synthesis of both proteins and lipids destined for multiple sites within and without the cell. The ER functions to both co- and post-translationally modify newly synthesized proteins and lipids and sort them for housekeeping within the ER and for transport to their sites of function away from the ER. In addition, the ER is involved in the metabolism and degradation of specific xenobiotics and endogenous biosynthetic products. A variety of proteomics studies have been reported on different subcompartments of the ER providing an ER protein dictionary with new data being made available on many protein complexes of relevance to the biology of the ER including the ribosome, the translocon, coatomer proteins, cytoskeletal proteins, folding proteins, the antigen-processing machinery, signaling proteins and proteins involved in membrane traffic. This review examines proteomics and cytological data in support of the presence of specific molecular machines at specific sites or subcompartments of the ER

Metabolism of the bovine cumulus-oocyte complex and influence on subsequent developmental competence

The two types of cells that make up the cumulus-oocyte complex (i.e. the oocyte and cumulus cells) have very different metabolic demands, with glucose occupying a central role in metabolic activity. Cumulus cells have a significant requirement for and utilise high levels of glucose, yet appear to have little need for oxidative metabolism. In contrast, oocytes have a requirement for oxidative metabolism, although limited glucose metabolism may also be an important aspect of meiotic and developmental competence. Nevertheless, because of the metabolic and communication link between the cumulus and the oocyte, glucose availability and metabolism within the cumulus can have a significant impact on oocyte meiotic and developmental competence. In particular, the role of the hexosamine biosynthesis pathway within cumulus cells appears critical for the supply of substrate from glucose for extracellular matrix production, yet if overstimulated can significantly decrease developmental competence of the oocyte. Current static systems for in vitro maturation are clearly incompatible with meeting substrate demands, especially glucose. In the future, in vitro maturation will include a more dynamic approach, which will adjust nutrient components to meet the changing functional requirements of cumulus-oocyte complexes during the final process of maturation