Reversal of activity-mediated spine dynamics and learning impairment in a mouse model of Fragile X syndrome.

Fragile X syndrome (FXS) is characterized by intellectual disability and autistic traits, and results from the silencing of the FMR1 gene coding for a protein implicated in the regulation of protein synthesis at synapses. The lack of functional Fragile X mental retardation protein has been proposed to result in an excessive signaling of synaptic metabotropic glutamate receptors, leading to alterations of synapse maturation and plasticity. It remains, however, unclear how mechanisms of activity-dependent spine dynamics are affected in Fmr knockout (Fmr1-KO) mice and whether they can be reversed. Here we used a repetitive imaging approach in hippocampal slice cultures to investigate properties of structural plasticity and their modulation by signaling pathways. We found that basal spine turnover was significantly reduced in Fmr1-KO mice, but markedly enhanced by activity. Additionally, activity-mediated spine stabilization was lost in Fmr1-KO mice. Application of the metabotropic glutamate receptor antagonist α-Methyl-4-carboxyphenylglycine (MCPG) enhanced basal turnover, improved spine stability, but failed to reinstate activity-mediated spine stabilization. In contrast, enhancing phosphoinositide-3 kinase (PI3K) signaling, a pathway implicated in various aspects of synaptic plasticity, reversed both basal turnover and activity-mediated spine stabilization. It also restored defective long-term potentiation mechanisms in slices and improved reversal learning in Fmr1-KO mice. These results suggest that modulation of PI3K signaling could contribute to improve the cognitive deficits associated with FXS.

The transcription factor c-Maf controls touch receptor development and function.

The sense of touch relies on detection of mechanical stimuli by specialized mechanosensory neurons. The scarcity of molecular data has made it difficult to analyze development of mechanoreceptors and to define the basis of their diversity and function. We show that the transcription factor c-Maf/c-MAF is crucial for mechanosensory function in mice and humans. The development and function of several rapidly adapting mechanoreceptor types are disrupted in c-Maf mutant mice. In particular, Pacinian corpuscles, a type of mechanoreceptor specialized to detect high-frequency vibrations, are severely atrophied. In line with this, sensitivity to high-frequency vibration is reduced in humans carrying a dominant mutation in the c-MAF gene. Thus, our work identifies a key transcription factor specifying development and function of mechanoreceptors and their end organs.

Molecular signaling in zebrafish development and the vertebrate phylotypic period

During development vertebrate embryos pass through a stage where their morphology is most conserved between species, the phylotypic period (approximately the pharyngula). To explain the resistance to evolutionary changes of this period, one hypothesis suggests that it is characterized by a high level of interactions. Based on this hypothesis, we examined protein-protein interactions, signal transduction cascades and miRNAs over the course of zebrafish development, and the conservation of expression of these genes in mouse development. We also investigated the characteristics of genes highly expressed before or during the presumed phylotypic period. We show that while there is a high diversity of interactions during the phylotypic period (protein-DNA, RNA-RNA, cell-cell, and between tissues), which is well conserved with mouse, there is no clear difference with later, more morphologically divergent, stages. We propose that the phylotypic period may rather be the expression at the morphological level of strong conservation of molecular processes earlier in development.

Development and application of a one-step low cost procedure to concentrate viruses from seawater samples

A novel and simple procedure for concentrating adenoviruses from seawater samples is described. The technique entails the adsorption of viruses to pre-flocculated skimmed milk proteins, allowing the flocs to sediment by gravity, and dissolving the separated sediment in phosphate buffer. Concentrated virus may be detected by PCR techniques following nucleic acid extraction. The method requires no specialized equipment other than that usually available in routine public health laboratories, and due to its straightforwardness it allows the processing of a larger number of water samples simultaneously. The usefulness of the method was demonstrated in concentration of virus in multiple seawater samples during a survey of adenoviruses in coastal waters.

Reelin regulates the development and synaptogenesis of the layer-specific entorhino-hippocampal connections

Here we examine the role of Reelin, an extracellular protein involved in neuronal migration, in the formation of hippocampal connections. Both at prenatal and postnatal stages, the general laminar and topographic distribution of entorhinal projections is preserved in the hippocampus of reeler mutant mice, in the absence of Reelin. However, developing and adult entorhinal afferents show severe alterations, including increased numbers of misrouted fibers and the formation of abnormal patches of termination from the medial and lateral entorhinal cortices. At perinatal stages, single entorhinal axons in reeler mice are grouped into thick bundles, and they have decreased axonal branching and decreased extension of axon collaterals. We also show that the number of entorhino-hippocampal synapses is lower in reeler mice than in control animals during development. Studies performed in mixed entorhino-hippocampal co-cultures combining slices from reeler and wild-type mice indicate that these abnormalities are caused by the lack of Reelin in the target hippocampus. These findings imply that Reelin fulfills a modulatory role during the formation of layer-specific and topographic connections in the hippocampus. They also suggest that Reelin promotes maturation of single fibers and synaptogenesis by entorhinal afferents.

Podocalyxin is a novel polysialylated neural adhesion protein with multiple roles in neural development and synapse formation

Neural development and plasticity are regulated by neural adhesion proteins, including the polysialylated form of NCAM (PSA-NCAM). Podocalyxin (PC) is a renal PSA-containing protein that has been reported to function as an anti-adhesin in kidney podocytes. Here we show that PC is widely expressed in neurons during neural development. Neural PC interacts with the ERM protein family, and with NHERF1/2 and RhoA/G. Experiments in vitro and phenotypic analyses of podxl-deficient mice indicate that PC is involved in neurite growth, branching and axonal fasciculation, and that PC loss-of-function reduces the number of synapses in the CNS and in the neuromuscular system. We also show that whereas some of the brain PC functions require PSA, others depend on PC per se. Our results show that PC, the second highly sialylated neural adhesion protein, plays multiple roles in neural development.

Differential phosphorylation of tau proteins during kitten brain development and Alzheimer's disease.

Differential distribution and phosphorylation of tau proteins were studied in developing kitten brain by using several antibodies, and was compared to phosphorylation in Alzheimer's disease. Several antibodies demonstrated the presence of phosphorylated tau proteins during kitten brain development and identified pathological structures in human brain tissue. Antibody AD2, recognized tau in kittens and adult cats, but reacted in Alzheimer's tissue only with a pathological tau form. Antibody AT8 was prominent in developing kitten neurons and was found in axons and dendrites. After the first postnatal month this phosphorylation type disappeared from axons. Furthermore, dephosphorylation of kitten tau with alkaline phosphatase abolished immunoreactivity of AT8, but not that of AD2, pointing to a protection of the AD2 epitope in cats. Tau proteins during early cat brain development are phosphorylated at several sites that are also phosphorylated in paired helical filaments during Alzheimer's disease. In either event, phosphorylation of tau may play a crucial role to modulate microtubule dynamics, contributing to increased microtubule instability and promoting growth of processes during neuronal development or changing dynamic properties of the cytoskeleton and contributing to the formation of pathological structures in neurodegenerative diseases.

Development and Demonstration of a Freezing Drizzle Algorithm for Roadway Environmental Sensing Systems, Final Report, October 2012

The primary goal of this project is to demonstrate the accuracy and utility of a freezing drizzle algorithm that can be implemented on roadway environmental sensing systems (ESSs). The types of problems related to the occurrence of freezing precipitation range from simple traffic delays to major accidents that involve fatalities. Freezing drizzle can also lead to economic impacts in communities with lost work hours, vehicular damage, and downed power lines. There are means for transportation agencies to perform preventive and reactive treatments to roadways, but freezing drizzle can be difficult to forecast accurately or even detect as weather radar and surface observation networks poorly observe these conditions. The detection of freezing precipitation is problematic and requires special instrumentation and analysis. The Federal Aviation Administration (FAA) development of aircraft anti-icing and deicing technologies has led to the development of a freezing drizzle algorithm that utilizes air temperature data and a specialized sensor capable of detecting ice accretion. However, at present, roadway ESSs are not capable of reporting freezing drizzle. This study investigates the use of the methods developed for the FAA and the National Weather Service (NWS) within a roadway environment to detect the occurrence of freezing drizzle using a combination of icing detection equipment and available ESS sensors. The work performed in this study incorporated the algorithm developed initially and further modified for work with the FAA for aircraft icing. The freezing drizzle algorithm developed for the FAA was applied using data from standard roadway ESSs. The work performed in this study lays the foundation for addressing the central question of interest to winter maintenance professionals as to whether it is possible to use roadside freezing precipitation detection (e.g., icing detection) sensors to determine the occurrence of pavement icing during freezing precipitation events and the rates at which this occurs.

Evidential relevance in scene to offender transfer cases: development and analysis of a likelihood ratio for offence level propositions

The present paper focuses on the analysis and discussion of a likelihood ratio (LR) development for propositions at a hierarchical level known in the context as 'offence level'. Existing literature on the topic has considered LR developments for so-called offender to scene transfer cases. These settings involve-in their simplest form-a single stain found on a crime scene, but with possible uncertainty about the degree to which that stain is relevant (i.e. that it has been left by the offender). Extensions to multiple stains or multiple offenders have also been reported. The purpose of this paper is to discuss a development of a LR for offence level propositions when case settings involve potential transfer in the opposite direction, i.e. victim/scene to offender transfer. This setting has previously not yet been considered. The rationale behind the proposed LR is illustrated through graphical probability models (i.e. Bayesian networks). The role of various uncertain parameters is investigated through sensitivity analyses as well as simulations.

2013 Iowa DOT Engineering Intern Development and Management Program, 13-464, 2013

The Institute for Transportation (InTrans) at Iowa State University (ISU) developed an internship mentoring program in collaboration with the Iowa Department of Transportation (DOT) to provide additional mentorship to both student interns and Iowa DOT intern managers. For the summer 2013 Iowa DOT Engineering Intern Development and Management Program, this report summarizes the following: * Mentoring activities conducted by ISU; * Results of the different intern program success assessments that were conducted; * Experiences, lessons learned, and recommendations; * Program benefits that were realized.

E-publishing development and changes in the scholarly communication system

New and alternative scientific publishing business models is a reality driven mostly by the information and communication technologies, by the movements towards the recovery of control of the scientific communication activities by the academic community, and by the open access approaches. The hybrid business model, mixing open and toll-access is a reality and they will probably co-exist with respective trade-offs. This essay discusses the changes driven by the epublishing and the impacts on the scholarly communication system stakeholders' interrelationships (publishers-researchers, publishers-libraries and publishers-users interrelationships), and the changes on the scientific publishing business models, followed by a discussion of possible evolving business models. Whatever the model which evolves and dominates, a huge cultural change in authors' and institutions publishing practices will be necessary in order to make the open access happen and to consolidate the right business models for the traditional publishers. External changes such as policies, rewarding systems and institutions mandates should also happen in order to sustain the whole changing scenario.