Gene duplication and functional divergence of the zebrafish insulin‐like growth factor 1 receptors

Insulin‐like growth factor (IGF) 1 receptor (IGF1R)‐mediated signaling plays key roles in growth, development, and physiology. Recent studies have shown that there are two distinct igf1r genes in zebrafish, termed igf1ra and igf1rb. In this study, we tested the hypothesis that zebrafish igf1ra and igf1rb resulted from a gene duplication event at the igf1r locus and that this has led to their functional divergence. The genomic structures of zebrafish igf1ra and igf1rb were determined and their loci mapped. While zebrafish igf1ra has 21 exons and is located on linkage group (LG) 18, zebrafish igf1rb has 22 exons and mapped to LG 7. There is a strong syntenic relationship between the two zebrafish genes and the human IGF1R gene. Using a MO‐based loss‐of‐function approach, we show that both Igf1ra and Igf1rb are required for zebrafish embryo viability and proper growth and development. Although Igf1ra and Igf1rb demonstrated a large degree of functional overlap with regard to cell differentiation in the developing eye, inner ear, heart, and muscle, they also exhibited functional distinction involving a greater requirement for Igf1rb in spontaneous muscle contractility. These findings suggest that the duplicated zebrafish igf1r genes play largely overlapping but not identical functional roles in early development and provide novel insight into the functional evolution of the IGF1R/insulin receptor gene family.— Schlueter, P. J., Royer, T., Mohamed, H. F., Laser, B., Chan, S. J., Steiner, D. F., Duan, C. Gene duplication and functional divergence of the zebrafish insulin‐like growth factor 1 receptors. FASEB J. 20, E462–E471 (2006)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154460/1/fsb2fj053882fje.pd

Managing the development of the Wide-field Infrared Survey Explorer mission

The Wide-field Infrared Survey Explorer (WISE), a NASA Medium-Class Explorer (MIDEX) mission, is surveying the entire sky in four bands from 3.4 to 22 microns with a sensitivity hundreds to hundreds of thousands times better than previous all-sky surveys at these wavelengths. The single WISE instrument consists of a 40 cm three-mirror anastigmatic telescope, a two-stage solid hydrogen cryostat, a scan mirror mechanism, and reimaging optics giving 6" resolution (fullwidth- half-maximum). WISE was placed into a Sun-synchronous polar orbit on a Delta II 7320 launch vehicle on December 14, 2009. NASA selected WISE as a MIDEX in 2002 following a rigorous competitive selection process. To gain further confidence in WISE, NASA extended the development period one year with an option to cancel the mission if certain criteria were not met. MIDEX missions are led by the principal investigator who in this case delegated day-today management to the project manager. With a cost cap and relatively short development schedule, it was essential for all WISE partners to work seamlessly together. This was accomplished with an integrated management team representing all key partners and disciplines. The project was developed on budget and on schedule in spite of the need to surmount significant technical challenges. This paper describes our management approach, key challenges and critical decisions made. Results are described from a programmatic, technical and scientific point of view. Lessons learned are offered for projects of this type

A search for non-pulsating, chemically normal stars in the Scuti instability strip using Kepler data

We identify stars in the δ Sct instability strip that do not pulsate in p modes at the 50-μmag limit, using Kepler data. Spectral classification and abundance analyses from high-resolution spectroscopy allow us to identify chemically peculiar stars, in which the absence of pulsations is not surprising. The remaining stars are chemically normal, yet they are not δ Sct stars. Their lack of observed p modes cannot be explained through any known mechanism. However, they are mostly distributed around the edges of the δ Sct instability strip, which allows for the possibility that they actually lie outside the strip once the uncertainties are taken into account.We investigated the possibility that the non-pulsators inside the instability strip could be unresolved binary systems, having components that both lie outside the instability strip. If misinterpreted as single stars, we found that such binaries could generate temperature discrepancies of ∼300 K – larger than the spectroscopic uncertainties, and fully consistent with the observations. After these considerations, there remains one chemically normal nonpulsator that lies in the middle of the instability strip. This star is a challenge to pulsation theory. However, its existence as the only known star of its kind indicates that such stars are rare. We conclude that the δ Sct instability strip is pure, unless pulsation is shut down by diffusion or another mechanism, which could be interaction with a binary companion

Managing the development of the Wide-field Infrared Survey Explorer mission

The Wide-field Infrared Survey Explorer (WISE), a NASA Medium-Class Explorer (MIDEX) mission, is surveying the entire sky in four bands from 3.4 to 22 microns with a sensitivity hundreds to hundreds of thousands times better than previous all-sky surveys at these wavelengths. The single WISE instrument consists of a 40 cm three-mirror anastigmatic telescope, a two-stage solid hydrogen cryostat, a scan mirror mechanism, and reimaging optics giving 6" resolution (fullwidth- half-maximum). WISE was placed into a Sun-synchronous polar orbit on a Delta II 7320 launch vehicle on December 14, 2009. NASA selected WISE as a MIDEX in 2002 following a rigorous competitive selection process. To gain further confidence in WISE, NASA extended the development period one year with an option to cancel the mission if certain criteria were not met. MIDEX missions are led by the principal investigator who in this case delegated day-today management to the project manager. With a cost cap and relatively short development schedule, it was essential for all WISE partners to work seamlessly together. This was accomplished with an integrated management team representing all key partners and disciplines. The project was developed on budget and on schedule in spite of the need to surmount significant technical challenges. This paper describes our management approach, key challenges and critical decisions made. Results are described from a programmatic, technical and scientific point of view. Lessons learned are offered for projects of this type

Hydrogen bond networks determine emergent mechanical and thermodynamic properties across a protein family

<p>Abstract</p> <p>Background</p> <p>Gram-negative bacteria use periplasmic-binding proteins (bPBP) to transport nutrients through the periplasm. Despite immense diversity within the recognized substrates, all members of the family share a common fold that includes two domains that are separated by a conserved hinge. The hinge allows the protein to cycle between open (apo) and closed (ligated) conformations. Conformational changes within the proteins depend on a complex interplay of mechanical and thermodynamic response, which is manifested as an increase in thermal stability and decrease of flexibility upon ligand binding.</p> <p>Results</p> <p>We use a distance constraint model (DCM) to quantify the give and take between thermodynamic stability and mechanical flexibility across the bPBP family. Quantitative stability/flexibility relationships (QSFR) are readily evaluated because the DCM links mechanical and thermodynamic properties. We have previously demonstrated that QSFR is moderately conserved across a mesophilic/thermophilic RNase H pair, whereas the observed variance indicated that different enthalpy-entropy mechanisms allow similar mechanical response at their respective melting temperatures. Our predictions of heat capacity and free energy show marked diversity across the bPBP family. While backbone flexibility metrics are mostly conserved, cooperativity correlation (long-range couplings) also demonstrate considerable amount of variation. Upon ligand removal, heat capacity, melting point, and mechanical rigidity are, as expected, lowered. Nevertheless, significant differences are found in molecular cooperativity correlations that can be explained by the detailed nature of the hydrogen bond network.</p> <p>Conclusion</p> <p>Non-trivial mechanical and thermodynamic variation across the family is explained by differences within the underlying H-bond networks. The mechanism is simple; variation within the H-bond networks result in altered mechanical linkage properties that directly affect intrinsic flexibility. Moreover, varying numbers of H-bonds and their strengths control the likelihood for energetic fluctuations as H-bonds break and reform, thus directly affecting thermodynamic properties. Consequently, these results demonstrate how unexpected large differences, especially within cooperativity correlation, emerge from subtle differences within the underlying H-bond network. This inference is consistent with well-known results that show allosteric response within a family generally varies significantly. Identifying the hydrogen bond network as a critical determining factor for these large variances may lead to new methods that can predict such effects.</p

De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures

Background De novo variants in the voltage-gated calcium channel subunit α1 E gene (CACNA1E) have been described as causative of epileptic encephalopathy with contractures, macrocephaly and dyskinesias. Methods Following the observation of an index patient with developmental delay and autism spectrum disorder (ASD) without seizures who had a de novo deleterious CACNA1E variant, we screened GeneMatcher for other individuals with CACNA1E variants and neurodevelopmental phenotypes without epilepsy. The spectrum of pathogenic CACNA1E variants was compared to the mutational landscape of variants in the gnomAD control population database. Results We identified seven unrelated individuals with intellectual disability, developmental regression and ASD-like behavioral profile, and notably without epilepsy, who had de novo heterozygous putatively pathogenic variants in CACNA1E. Age of onset of clinical manifestation, presence or absence of regression and degree of severity were variable, and no clear-cut genotype–phenotype association could be recognized. The analysis of disease-associated variants and their comparison to benign variants from the control population allowed for the identification of regions in the CACNA1E protein that seem to be intolerant to substitutions and thus more likely to harbor pathogenic variants. As in a few reported cases with CACNA1E variants and epilepsy, one patient showed a positive clinical behavioral response to topiramate, a specific calcium channel modulator. Limitations The significance of our study is limited by the absence of functional experiments of the effect of identified variants, the small sample size and the lack of systematic ASD assessment in all participants. Moreover, topiramate was given to one patient only and for a short period of time. Conclusions Our results indicate that CACNA1E variants may result in neurodevelopmental disorders without epilepsy and expand the mutational and phenotypic spectrum of this gene. CACNA1E deserves to be included in gene panels for non-specific developmental disorders, including ASD, and not limited to patients with seizures, to improve diagnostic recognition and explore the possible efficacy of topiramate

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure