Metabolic control of oocyte development: linking maternal nutrition and reproductive outcomes

Obesity, diabetes, and related metabolic disorders are major health issues worldwide. As the epidemic of metabolic disorders continues, the associated medical co-morbidities, including the detrimental impact on reproduction, increase as well. Emerging evidence suggests that the effects of maternal nutrition on reproductive outcomes are likely to be mediated, at least in part, by oocyte metabolism. Well-balanced and timed energy metabolism is critical for optimal development of oocytes. To date, much of our understanding of oocyte metabolism comes from the effects of extrinsic nutrients on oocyte maturation. In contrast, intrinsic regulation of oocyte development by metabolic enzymes, intracellular mediators, and transport systems is less characterized. Specifically, decreased acid transport proteins levels, increased glucose/lipid content and elevated reactive oxygen species in oocytes have been implicated in meiotic defects, organelle dysfunction and epigenetic alteration. Therefore, metabolic disturbances in oocytes may contribute to the diminished reproductive potential experienced by women with metabolic disorders. In-depth research is needed to further explore the underlying mechanisms. This review also discusses several approaches for metabolic analysis. Metabolomic profiling of oocytes, the surrounding granulosa cells, and follicular fluid will uncover the metabolic networks regulating oocyte development, potentially leading to the identification of oocyte quality markers and prevention of reproductive disease and poor outcomes in offspring.     

Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.     

Ionic colloidal crystals of oppositely charged particles

Colloidal suspensions are widely used to study processes such as melting, freezing and glass transitions. This is because they display the same phase behaviour as atoms or molecules, with the nano- to micrometre size of the colloidal particles making it possible to observe them directly in real space. Another attractive feature is that different types of colloidal interactions, such as long-range repulsive, short-range attractive, hard-sphere-like and dipolar, can be realized and give rise to equilibrium phases. However, spherically symmetric, long-range attractions (that is, ionic interactions) have so far always resulted in irreversible colloidal aggregation. Here we show that the electrostatic interaction between oppositely charged particles can be tuned such that large ionic colloidal crystals form readily, with our theory and simulations confirming the stability of these structures. We find that in contrast to atomic systems, the stoichiometry of our colloidal crystals is not dictated by charge neutrality; this allows us to obtain a remarkable diversity of new binary structures. An external electric field melts the crystals, confirming that the constituent particles are indeed oppositely charged. Colloidal model systems can thus be used to study the phase behaviour of ionic species. We also expect that our approach to controlling opposite-charge interactions will facilitate the production of binary crystals of micrometre-sized particles, which could find use as advanced materials for photonic applications.     

Scientific realism bit by bit: part I. Kitcher on reference

In this paper, I consider Kitcher’s (1993) account of reference for the expressions of past science. Kitcher’s case study is of Joseph Priestley and his expression ‘dephlogisticated air’. There is a strong intuitive case that ‘dephlogisticated air’ referred to oxygen, but it was underpinned by very mistaken phlogiston theory, so concluding either that dephlogisticated air referred straightforwardly or that it failed to refer both have unpalatable consequences. Kitcher argues that the reference of such terms is best considered relative to each token—some tokens refer, and others do not. His account thus relies crucially on how this distinction between tokens can be made good—a puzzle I call the discrimination problem. I argue that the discrimination problem cannot be solved. On any reading of Kitcher’s defence of the distinction, the grounds provided are either insufficient or illegitimate. On the first reading, Kitcher violates the principle of humanity by making Priestley’s referential success a matter of the mental contents of modern speakers. The second reading sidesteps the problem of beliefs by appealing to mind-independent facts, but I argue that these are insufficient to achieve reference because of the indeterminacy introduced by the qua problem. On the third and final reading, Priestley’s success is given by what he would say in counterfactual circumstances. I argue that even if there are facts about what Priestley would say, and there is reason for doubt, there is no motivation to think that such facts determine how Priestley referred in the actual world.     

Single mimivirus particles intercepted and imaged with an X-ray laser

X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions. Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma. The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval. Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source. Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000?K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.     

The genome of the green anole lizard and a comparative analysis with birds and mammals

The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.     

cAMP initiates early phase neuron-like morphology changes and late phase neural differentiation in mesenchymal stem cells

The intracellular second messenger cAMP is frequently used in induction media to induce mesenchymal stem cells (MSCs) into neural lineage cells. To date, an understanding of the role cAMP exerts on MSCs and whether cAMP can induce MSCs into functional neurons is still lacking. We found cAMP initiated neuron-like morphology changes early and neural differentiation much later. The early phase changes in morphology were due to cell shrinkage, which subsequently rendered some cells apoptotic. While the morphology changes occurred prior to the expression of neural markers, it is not required for neural marker expression and the two processes are differentially regulated downstream of cAMP-activated protein kinase A. cAMP enabled MSCs to gain neural marker expressions with neuronal function, such as, calcium rise in response to neuronal activators, dopamine, glutamate, and potassium chloride. However, only some of the cells induced by cAMP responded to the three neuronal activators and further lack the neuronal morphology, suggesting that although cAMP is able to direct MSCs towards neural differentiation, they do not achieve terminal differentiation.     

The effect of elevation on the distribution of sibling species in the Simulium arcticum complex (Diptera: Simuliidae)

At least 5 sibling species and an additional 11 cytotypes of the Simulium arcticum complex occur in Montana. Consequently, this speciose complex might allow study of environmental correlates with genetic differentiation. We used conventional methods of collection and cytogenetic analysis to study 1128 male larvae of the Simulium arcticum complex at 15 sites within 5 drainages in western Montana to test the hypothesis that distribution of siblings is associated with elevation. We sampled at the mouth, at the headwaters, and at an intermediate site to span the range of elevations within each drainage. We restricted our analyses to the most abundant taxa of the S. arcticum complex within our study area and observed a statistically significant presence of S. apricarium at low-elevation sites. Simulium arcticum IIL-18 appeared more frequently than expected at high elevation sites. Simulium brevicercum and S. arcticum sensu strictu appeared to be distributed randomly. We suggest potential causal reasons for these distributions including differential use of habitats along these elevational gradients.