The molecular machinery of germ line specification

Germ cells occupy a unique position in animal reproduction, development, and evolution. In sexually reproducing animals, only they can produce gametes and contribute genetically to subsequent generations. Nonetheless, germ line specification during embryogenesis is conceptually the same as the specification of any somatic cell type: germ cells must activate a specific gene regulatory network in order to differentiate and go through gametogenesis. While many genes with critical roles in the germ line have been characterized with respect to expression pattern and genetic interactions, it is the molecular interactions of the relevant gene products that are ultimately responsible for germ cell differentiation. This review summarizes the current state of knowledge on the molecular functions and biochemical connections between germ line gene products. We find that homologous genes often interact physically with the same conserved molecular partners across the metazoans. We also point out cases of nonhomologous genes from different species whose gene products play analogous biological roles in the germ line. We suggest a preliminary molecular definition of an ancestral “pluripotency module” that could have been modified during metazoan evolution to become specific to the germ line. Mol. Reprod. Dev. 77: 3–18, 2010. © 2009 Wiley‐Liss, Inc.     

Age‐related deterioration of motor function in male and female 5xFAD mice from 3 to 16 months of age

Alzheimer's disease (AD) is a neurodegenerative disorder that leads to age‐related cognitive and sensori‐motor dysfunction. There is an increased understanding that motor dysfunction contributes to overall AD severity, and a need to ameliorate these impairments. The 5xFAD mouse develops the neuropathology, cognitive and motor impairments observed in AD, and thus may be a valuable animal model to study motor deficits in AD. Therefore, we assessed age‐related changes in motor ability of male and female 5xFAD mice from 3 to 16 months of age, using a battery of behavioral tests. At 9‐10 months, 5xFAD mice showed reduced body weight, reduced rearing in the open‐field and impaired performance on the rotarod compared to wild‐type controls. At 12‐13 months, 5xFAD mice showed reduced locomotor activity on the open‐field, and impaired balance on the balance beam. At 15‐16 months, impairments were also seen in grip strength. Although sex differences were observed at specific ages, the development of motor dysfunction was similar in male and female mice. Given the 5xFAD mouse is commonly on a C57BL/6 × SJL hybrid background, a subset of mice may be homozygous recessive for the Dysf ^im mutant allele, which leads to muscular weakness in SJL mice and may exacerbate motor dysfunction. We found small effects of Dysf ^im on motor function, suggesting that Dysf ^im contributes little to motor dysfunction in 5xFAD mice. We conclude that the 5xFAD mouse may be a useful model to study mechanisms that produce motor dysfunction in AD, and to assess the efficacy of therapeutics on ameliorating motor impairment.     

Dietary fatty acids promote sleep through a taste‐independent mechanism

Consumption of foods that are high in fat contribute to obesity and metabolism‐related disorders. Dietary lipids are comprised of triglycerides and fatty acids, and the highly palatable taste of dietary fatty acids promotes food consumption, activates reward centers in mammals and underlies hedonic feeding. Despite the central role of dietary fats in the regulation of food intake and the etiology of metabolic diseases, little is known about how fat consumption regulates sleep. The fruit fly, Drosophila melanogaster, provides a powerful model system for the study of sleep and metabolic traits, and flies potently regulate sleep in accordance with food availability. To investigate the effects of dietary fats on sleep regulation, we have supplemented fatty acids into the diet of Drosophila and measured their effects on sleep and activity. We found that flies fed a diet of hexanoic acid, a medium‐chain fatty acid that is a by‐product of yeast fermentation, slept more than flies starved on an agar diet. To assess whether dietary fatty acids regulate sleep through the taste system, we assessed sleep in flies with a mutation in the hexanoic acid receptor Ionotropic receptor 56D, which is required for fatty acid taste perception. We found that these flies also sleep more than agar‐fed flies when fed a hexanoic acid diet, suggesting the sleep promoting effect of hexanoic acid is not dependent on sensory perception. Taken together, these findings provide a platform to investigate the molecular and neural basis for fatty acid‐dependent modulation of sleep.     

Lead Halide Perovskite Nanocrystals: Room Temperature Syntheses toward Commercial Viability

In this progress report, recent improvements to the room temperaturesyntheses of lead halide perovskite nanocrystals (APbX₃, X = Cl, Br, I) are assessed, focusing on various aspects which influence the commercial viability of the technology. Perovskite nanocrystals can be prepared easily from low‐cost precursors under ambient conditions, yet they have displayed near‐unity photoluminescence quantum yield with narrow, highly tunable emission peaks. In addition to their impressive ambipolar charge carrier mobilities, these properties make lead halide perovskite nanocrystals very attractive for light‐emitting diode (LED) applications. However, there are still many practical hurdles preventing commercialization. Recent developments in room temperature synthesis and purification protocols are reviewed, closely evaluating the suitability of particular techniques for industry. This is followed by an assessment of the wide range of ligands deployed on perovskite nanocrystal surfaces, analyzing their impact on colloidal stability, as well as LED efficiency. Based on these observations, a perspective on important future research directions that can expedite the industrial adoption of perovskite nanocrystals is provided.     

A critical evaluation of the Oscillayers methods and datasets

Here we evaluate Oscillayers, a new method that aims to estimate palaeoclimates for the past 5.4 Myr, and discuss the associated theoretical and methodological issues. We show that the theoretical foundation of Oscillayers is inherently limited, because the method cannot incorporate spatio‐temporal variation and different forcing mechanisms into climate reconstructions. In addition, several methodological weaknesses are clarified that entrench the palaeoclimatic reconstruction of Oscillayers to patterns of climate change observed between the Last Glacial Maximum and current climates. We test the utility of the Oscillayers method to produce palaeoclimatic reconstructions that are similar to general circulation model (GCM)‐based estimates. On average, only 55.6% of values in the mean annual temperature datasets across the Pliocene and Pleistocene were within ±3°C when compared with corresponding GCM‐based datasets. Furthermore, on average only 75.3% of values in the mean annual precipitation datasets across the Pliocene and Pleistocene were within ±200 mm of rainfall of the GCM‐based estimates. Our results demonstrate that the Oscillayers approach does not provide a robust approximation of palaeoclimatic conditions throughout the Plio‐Pleistocene. Thus, when these datasets are used for scientific analyses, the results should be interpreted with a full appreciation of their limitations, particularly for periods outside the last glacial cycle.     

Experimental models of maternal–fetal interface and their potential use for nanotechnology applications

During pregnancy, the placenta regulates the transfer of oxygen, nutrients, and residual products between the maternal and fetal bloodstreams and is a key determinant of fetal exposure to xenobiotics from the mother. To study the disposition of substances through the placenta, various experimental models are used, especially the perfused placenta, placental villi explants, and cell lineage models. In this context, nanotechnology, an area of study that is on the rise, enables the creation of particles on nanometric scales capable of releasing drugs aimed at specific tissues. An important reason for furthering the studies on transplacental transfer is to explore the potential of nanoparticles (NPs), in new delivery strategies for drugs that are specifically aimed at the mother, the placenta, or the fetus and that involve less toxicity. Due to the fact that the placental barrier is essential for the interaction between the maternal and fetal organisms as well as the possibility of NPs being used in the treatment of various pathologies, the aim of this review is to present the main experimental models used in studying the maternal–fetal interaction and the action of NPs in the placental environment.