Identification of the heart as the critical site of adenosine mediated embryo protection

<p>Abstract</p> <p>Background</p> <p>Our understanding of the mechanisms that protect the developing embryo from intrauterine stress is limited. Recently, adenosine has been demonstrated to play a critical role in protecting the embryo against hypoxia via adenosine A1 receptors (A1ARs), which are expressed in the heart, nervous system, and other sites during development. However, the sites of A1AR action that mediate embryo protection are not known. To determine if the heart is a key site of adenosine-mediated embryo protection, A1ARs were selectively deleted in the embryonic heart using a Cre-LoxP system in which the alpha-myosin heavy chain promoter drives Cre-recombinase expression and excision of the A1AR gene from cardiomyocytes.</p> <p>Results</p> <p>With increasing exposure of maternal hypoxia (10% O₂) from 48-96 hours beginning at embryonic day (E) 8.5, embryo viability decreased in the cardiac-A1AR deleted embryos. 48 hours of hypoxia reduced embryonic viability by 49% in embryos exposed from E10.5-12.5 but no effect on viability was observed in younger embryos exposed to hypoxia from E8.5-10.5. After 72 hours of hypoxia, 57.8% of the cardiac-A1AR deleted embryos were either dead or re-absorbed compared to 13.7% of control littermates and after 96 hours 81.6% of cardiac-A1AR deleted embryos were dead or re-absorbed. After 72 hours of hypoxia, cardiac size was reduced significantly more in the cardiac-A1AR deleted hearts compared to controls. Gene expression analysis revealed clusters of genes that are regulated by both hypoxia and A1AR expression.</p> <p>Conclusions</p> <p>These data identify the embryonic heart as the critical site where adenosine acts to protect the embryo against hypoxia. As such these studies identify a previously unrecognized mechanism of embryo protection.</p

First light for avian embryos: eggshell thickness and pigmentation mediate variation in development and UV exposure in wild bird eggs

Article first published online: 29 JUL 20141. The avian embryo's development is influenced by both the amount and the wavelength of the light that passes through the eggshell. Commercial poultry breeders use light of specific wavelengths to accelerate embryonic growth, yet the effects of the variably patterned eggshells of wild bird species on light transmission and embryonic development remain largely unexplored. 2. Here, we provide the first comparative phylogenetic analysis of light transmission, through a diverse range of bird eggshells (74 British breeding species), in relation to the eggshell's thickness, permeability, pigment concentration and surface reflectance spectrum (colour). 3. The percentage of light transmitted through the eggshell was measured in the spectral range 250–700 nm. Our quantitative analyses confirm anecdotal reports that eggshells filter the light of the externally coloured shell. Specifically, we detected a positive relationship between surface eggshell reflectance (‘brightness’) and the percentage of light transmitted through the eggshell, and this relationship was strongest at wavelengths in the human-visible blue-green region of the spectra (c. 435 nm). 4. We show that less light passes through thicker eggshells with greater total pigment concentrations. By contrast, permeability (measured as water vapour conductance) did not covary significantly with light transmission. Eggs of closed-nesting species let more light pass through, compared with open nesters. 5. We postulate that greater light transmission is required to assist embryonic development under low light exposure. Importantly, this result provides an ecological explanation for the repeated evolution of immaculate, white- or pale-coloured eggshells in species nesting in enclosed spaces. 6. Finally, we detected correlative support for the solar radiation hypothesis, in that eggshells of bird species with a longer incubation period let significantly less of the potentially harmful, ultraviolet (UV) light pass through the eggshell. In summary, we demonstrate suites of avian eggshell properties, including eggshell structure and pigmentation, which are consistent with an evolutionary pressure to both enhance and protect embryonic development.Golo Maurer, Steven J. Portugal, Mark E. Hauber, Ivan Mikšík, Douglas G. D. Russell and Phillip Casse

Heavy and light roles: myosin in the morphogenesis of the heart

Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin lightchain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed

Is reading, writing or typing a better way to learn.

This study aims to compare writing, typing and reading and their effects on learning. Research by Oviatt (2013) compared four different inputs to solve inference problems including non-digital and digital, pen and tablet interfaces. Correct inferences averaged 10.5% higher when using a digital pen interface compared with tablets. Mueller & Oppenheimer (2014) compared laptop note taking versus longhand on recall and found laptops notes led to worse performance on conceptual questions. Results suggest laptop users tend to copy verbatim with shallower processing. Bui, Myerson, & Hale (2013) compared writing notes versus laptop typing. Typing led to better immediate free recall, but writing led to better performance in a surprise, delayed test. However, typing was superior when students studied notes for a repeat test. These studies suggest benefits associated with writing which from a cognitive load (CL) perspective relate to the embodied effects associated with forming characters. Our study extends previous research with a focus on copying information verbatim to attempt to isolate the effects of writing versus typing, with reading as a control.We hypothesize writing will lead to better learning than typing. Because writing involves creating characters while typing simply involves pressing keys, we suggest writing is more embodied and may thus reduce CL. We further hypothesize that reading may best for recall of information as writing and typing may be redundant when focusing on recall. Three groups of 20 University students were instructed to either Read, Write, or Type while learning about the unfamiliar topic of Icelandic Geography. All participants received equal learning time. Participants were given writing and typing pretests to ascertain proficiency. Recall was tested using a combination of written, typed, verbal and multiple choice questions, so no learning condition was favored. An ANCOVA was conducted to look for differences between Method of Study on Total Test Score, controlling for writing pre-test word count. There were no significant differences between students who learnt the information using Writing versus Typing, while Reading proved to be significantly better at facilitating learning compared to Writing, F (2, 56) = 4.52, p < .05.Results suggest that asking students to either type or write may be redundant for verbatim learning. Contrary to previous studies there were no writing versus typing benefits, which may be because the test focussed on recall rather than conceptual or inferential questions. Moreover, students were much more proficient at typing than writing which may have effected results. Furthermore, although typing may require more CL as it is additional to reading, with high typing expertise this load may disappear. Future studies should use a more diverse range of participants with less typing expertise, and should test for skills beyond simple recall.ReferencesBui, D., Myerson, J., & Hale, S. (2013). Note-Taking With Computers: Exploring Alternative Strategies For Improved Recall. Journal of Educational Psychology 105(2), 299-309.Mueller, P. A., & Oppenheimer , D. (2014). The Pen Is Mightier Than The Keyboard: Advantages Of Longhand Over Laptop Note Taking. Psychological Science 25(6), 1159-1168.Oviatt, S. (2013). Interfaces for thinkers: computer input capabilities that support inferential reasoning. 15th ACM Int conf on multimodal interaction (ICMI '13) (pp. 221-228). NY, USA

Competition for binding between veratridine and KIFMK: an open channel blocking peptide of the RIIA sodium channel

Veratridine, an alkaloid isolated from the rhizome of V. album, binds and slows the inactivation of the brain sodium channels. The synthetic pentapeptide KIFMK causes a voltage- and use-dependent open-channel block of the RIIA (rat brain type IIA) sodium channel (Eaholtz, Scheuer &amp; Catterall, 1994). Our studies on the RIIA sodium channel expressed in CHO cells reveal that the fraction of veratridine modified sodium channels decreases linearly with increasing KIFMK concentration. However, the time constant for dissociation of veratridine from the channel remains unchanged in the presence of a high concentration of KIFMK, as opposed to that in the presence of QX314 where the dissociation appears to be more complex. These data are consistent with mutually exclusive binding of the open channel blocking peptide and veratridine to the brain sodium channel

Voltage dependent gating of veratridine modified RIIA Na<SUP>+</SUP>channel α-subunit expressed heterologously in CHO cells

The voltage-dependent kinetics of veratridine-modified RIIA Na<SUP>+</SUP> channel a subunit expressed heterologously in CHO cells were studied using the whole-cell patch-clamp technique. The activation and deactivation kinetics are well described by double exponential functions but poorly by a monoexponential function. Unlike the slow component, the fast time constant and associated amplitude factor depended steeply on the potential. The steady-state activation of veratridine-modified channels is described by a Boltzmann function with a V <SUB>½</SUB> of -131.9 mV and a slope of 9.41 mV. A two-state model is proposed for the fast component that explains the kinetics of veratridine's mechanism of action

A role of cellular translation regulation associated with toxic Huntingtin protein

Huntington's disease (HD) is a severe neurodegenerative disorder caused by poly Q repeat expansion in the Huntingtin (Htt) gene. While the Htt amyloid aggregates are known to affect many cellular processes, their role in translation has not been addressed. Here we report that pathogenic Htt expression causes a protein synthesis deficit in cells. We find a functional prion-like protein, the translation regulator Orb2, to be sequestered by Htt aggregates in cells. Co-expression of Orb2 can partially rescue the lethality associated with poly Q expanded Htt. These findings can be relevant for HD as human homologs of Orb2 are also sequestered by pathogenic Htt aggregates. Our work suggests that translation dysfunction is one of the contributors to the pathogenesis of HD and new therapies targeting protein synthesis pathways might help to alleviate disease symptoms