Iron deficiency reduces synapse formation in the Drosophila clock circuit

Iron serves as a critical cofactor for proteins involved in a host of biological processes. In most animals, dietary iron is absorbed in enterocytes and then disseminated for use in other tissues in the body. The brain is particularly dependent on iron. Altered iron status correlates with disorders ranging from cognitive dysfunction to disruptions in circadian activity. The exact role iron plays in producing these neurological defects, however, remains unclear. Invertebrates provide an attractive model to study the effects of iron on neuronal development since many of the genes involved in iron metabolism are conserved, and the organisms are amenable to genetic and cytological techniques. We have examined synapse growth specifically under conditions of iron deficiency in the Drosophila circadian clock circuit. We show that projections of the small ventrolateral clock neurons to the protocerebrum of the adult Drosophila brain are significantly reduced upon chelation of iron from the diet. This growth defect persists even when iron is restored to the diet. Genetic neuronal knockdown of ferritin 1 or ferritin 2, critical components of iron storage and transport, does not affect synapse growth in these cells. Together, these data indicate that dietary iron is necessary for central brain synapse formation in the fly and further validate the use of this model to study the function of iron homeostasis on brain development

Selection of DNA nanoparticles with preferential binding to aggregated protein target.

High affinity and specificity are considered essential for affinity reagents and molecularly-targeted therapeutics, such as monoclonal antibodies. However, life's own molecular and cellular machinery consists of lower affinity, highly multivalent interactions that are metastable, but easily reversible or displaceable. With this inspiration, we have developed a DNA-based reagent platform that uses massive avidity to achieve stable, but reversible specific recognition of polyvalent targets. We have previously selected these DNA reagents, termed DeNAno, against various cells and now we demonstrate that DeNAno specific for protein targets can also be selected. DeNAno were selected against streptavidin-, rituximab- and bevacizumab-coated beads. Binding was stable for weeks and unaffected by the presence of soluble target proteins, yet readily competed by natural or synthetic ligands of the target proteins. Thus DeNAno particles are a novel biomolecular recognition agent whose orthogonal use of avidity over affinity results in uniquely stable yet reversible binding interactions

CASTER: a scintillator-based black hole finder probe

The primary scientific mission of the Black Hole Finder Probe (BHFP), part of the NASA Beyond Einstein program, is to survey the local Universe for black holes over a wide range of mass and accretion rate. One approach to such a survey is a hard X-ray coded-aperture imaging mission operating in the 10-600 keV energy band, a spectral range that is considered to be especially useful in the detection of black hole sources. The development of new inorganic scintillator materials provides improved performance (for example, with regards to energy resolution and timing) that is well suited to the BHFP science requirements. Detection planes formed with these materials coupled with a new generation of readout devices represent a major advancement in the performance capabilities of scintillator-based gamma cameras. Here, we discuss the Coded Aperture Survey Telescope for Energetic Radiation (CASTER), a concept that represents a BHFP based on the use of the latest scintillator technology

The mERG1a channel modulates skeletal muscle MuRF1, but not MAFbx, expression.

INTRODUCTION: We investigated the mechanism by which the MERG1a K+ channel increases ubiquitin proteasome proteolysis (UPP). METHODS: Hindlimb suspension and electro-transfer of Merg1a cDNA into mouse gastrocnemius muscles induced atrophy. RESULTS: Atrophic gastrocnemius muscles of hindlimb-suspended mice express Merg1a, Murf1, and Mafbx genes. Electrotransfer of Merg1a significantly decreases muscle fiber size (12.6%) and increases UPP E3 ligase Murf1 mRNA (2.1-fold) and protein (23.7%), but does not affect Mafbx E3 ligase expression. Neither Merg1a-induced decreased fiber size nor Merg1a-induced increased Murf1 expression is curtailed significantly by coexpression of inactive HR-Foxo3a, a gene encoding a transcription factor known to induce Mafbx expression. CONCLUSIONS: The MERG1a K+ channel significantly increases expression of Murf1, but not Mafbx. We explored this expression pattern by expressing inactive Foxo3a and showing that it is not involved in MERG1a-mediated expression of Murf1. These findings suggest that MERG1a may not modulate Murf1 expression through the AKT/FOXO pathway

Rapid fixation of non-native alleles revealed by genome-wide SNP analysis of hybrid tiger salamanders

<p>Abstract</p> <p>Background</p> <p>Hybrid zones represent valuable opportunities to observe evolution in systems that are unusually dynamic and where the potential for the origin of novelty and rapid adaptation co-occur with the potential for dysfunction. Recently initiated hybrid zones are particularly exciting evolutionary experiments because ongoing natural selection on novel genetic combinations can be studied in ecological time. Moreover, when hybrid zones involve native and introduced species, complex genetic patterns present important challenges for conservation policy. To assess variation of admixture dynamics, we scored a large panel of markers in five wild hybrid populations formed when Barred Tiger Salamanders were introduced into the range of California Tiger Salamanders.</p> <p>Results</p> <p>At three of 64 markers, introduced alleles have largely displaced native alleles within the hybrid populations. Another marker (<it>GNAT1</it>) showed consistent heterozygote deficits in the wild, and this marker was associated with embryonic mortality in laboratory F2's. Other deviations from equilibrium expectations were idiosyncratic among breeding ponds, consistent with highly stochastic demographic effects.</p> <p>Conclusion</p> <p>While most markers retain native and introduced alleles in expected proportions, strong selection appears to be eliminating native alleles at a smaller set of loci. Such rapid fixation of alleles is detectable only in recently formed hybrid zones, though it might be representative of dynamics that frequently occur in nature. These results underscore the variable and mosaic nature of hybrid genomes and illustrate the potency of recombination and selection in promoting variable, and often unpredictable genetic outcomes. Introgression of a few, strongly selected introduced alleles should not necessarily affect the conservation status of California Tiger Salamanders, but suggests that genetically pure populations of this endangered species will be difficult to maintain.</p

CASTER - a concept for a Black Hole Finder Probe based on the use of new scintillator technologies

The primary scientific mission of the Black Hole Finder Probe (BHFP), part of the NASA Beyond Einstein program, is to survey the local Universe for black holes over a wide range of mass and accretion rate. One approach to such a survey is a hard X-ray coded-aperture imaging mission operating in the 10--600 keV energy band, a spectral range that is considered to be especially useful in the detection of black hole sources. The development of new inorganic scintillator materials provides improved performance (for example, with regards to energy resolution and timing) that is well suited to the BHFP science requirements. Detection planes formed with these materials coupled with a new generation of readout devices represent a major advancement in the performance capabilities of scintillator-based gamma cameras. Here, we discuss the Coded Aperture Survey Telescope for Energetic Radiation (CASTER), a concept that represents a BHFP based on the use of the latest scintillator technology.Comment: 12 pages; conference paper presented at the SPIE conference "UV, X-Ray, and Gamma-Ray Space Instrumentation for Astronomy XIV." To be published in SPIE Conference Proceedings, vol. 589

CubeSat Reusable Interface Software Platform (CRISP): A Lightweight Message-Bus-Based Flight Software Architecture for Rapid Payload Integration

The Agile Space portfolio of projects at Los Alamos National Laboratory (LANL) develops low-cost, rapidly-deployable space payloads and systems. To increase the agility of future missions, we are developing CRISP: the CubeSat Reusable Interface Software Platform. CRISP provides a lightweight and reusable flight software framework for rapid integration of custom payloads with commercial microsatellite platforms. CRISP cuts development time and costs by reducing non-recurring engineering (NRE); thereby accelerating mission agility. To achieve these goals, CRISP provides a core set of payload/data management functions and abstracts the interface between the bus avionics and the payload(s). CRISP currently consists of the following core software modules: a lightweight and scalable publish-subscribe message bus, a space vehicle interface, volatile and nonvolatile memory management, time and ephemeris distribution, debug printing and logging, and watchdogs. We have also developed a modular ground support utility to ease integration and testing, as well as a template flight software application that can be quickly adapted to new missions. Two upcoming CubeSat missions at LANL have already adopted CRISP: the Experiment for Space Radiation Analysis (ESRA) and the Mini Astrophysical MeV Background Observatory (MAMBO)

Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats

<p>Abstract</p> <p>Background</p> <p>Adenosine 5'-triphosphate (ATP) has a ubiquitous role in metabolism and a major role in pain responses after tissue injury. We investigated the changes in basal and KCl-evoked ATP release from rat dorsal root ganglia (DRG) after peripheral neuropathy induction by unilateral sciatic nerve entrapment (SNE).</p> <p>Results</p> <p>After SNE, rats develop long-lasting decreases in ipsilateral hindpaw withdrawal thresholds to mechanical and thermal stimulation. At 15–21 days after neuropathy induction, excised ipsilateral L4-L5 DRG display significantly elevated basal extracellular ATP levels compared to contralateral or control (naive) DRG. However, KCl-evoked ATP release is no longer observed in ipsilateral DRG. We hypothesized that the differential SNE effects on basal and evoked ATP release could result from the conversion of extracellular ATP to adenosine with subsequent activation of adenosine A1 receptors (A1Rs) on DRG neurons. Adding the selective A1R agonist, 2-chloro-N⁶-cyclopentyladenosine (100 nM) significantly decreased basal and evoked ATP release in DRG from naïve rats, indicating functional A1R activation. In DRG ipsilateral to SNE, adding a selective A1R antagonist, 8-cyclopentyl-1,3-dipropylxanthine (30 nM), further increased basal ATP levels and relieved the blockade of KCl-evoked ATP release suggesting that increased A1R activation attenuates evoked ATP release in neurons ipsilateral to SNE. To determine if altered ATP release was a consequence of altered DRG metabolism we compared O₂consumption between control and neuropathic DRG. DRG ipsilateral to SNE consumed O₂at a higher rate than control or contralateral DRG.</p> <p>Conclusion</p> <p>These data suggest that peripheral nerve entrapment increases DRG metabolism and ATP release, which in turn is modulated by increased A1R activation.</p

Acute versus delayed reverse total shoulder arthroplasty for proximal humerus fractures in the elderly: Mid-term outcomes

Background: Treatment of proximal humerus fractures (PHFs) via reverse total shoulder arthroplasty (RTSA) has shown early promise when compared to historical treatment modalities. Ideal surgical timing remains unclear. The purpose of this study was to compare the outcomes of early versus delayed RTSA for PHF. We hypothesized that acute RTSA would display superior outcomes compared to those receiving delayed surgical intervention. Methods: This multicenter study retrospectively analyzed 142 patients who underwent RTSA for fracture. Patients treated within 4 weeks of injury were placed in the acute group (n = 102), and patients treated longer than 4 weeks after injury were placed in the chronic group (n = 38). A comprehensive panel of patient reported outcome measures, VAS pain scores, range of motion, and patient satisfaction were evaluated. Results: The acute group had significantly better final follow-up SPADI scores (20.8 ± 23.9 vs. 30.7 ± 31.7) (p\u3c0.05). No further differences were detected in other postoperative range of motion measurements, subjective outcomes, or VAS scores. Conclusions: Our results suggest that patients treated acutely display similar mid-term outcomes to those who receive delayed treatment. With this in mind, surgeons may first give consideration to a period of nonoperative treatment. Level of evidence: Level II