We present the first optical spectroscopy of five confirmed (or strong candidate) redback millisecond pulsar binaries, obtaining complete radial velocity curves for each companion star. The ...properties of these millisecond pulsar binaries with low-mass, hydrogen-rich companions are discussed in the context of the 14 confirmed and 10 candidate field redbacks. We find that the neutron stars in redbacks have a median mass of 1.78 0.09 M with a dispersion of = 0.21 0.09. Neutron stars with masses in excess of 2 M are consistent with, but not firmly demanded by, current observations. Redback companions have median masses of 0.36 0.04 M with a scatter of = 0.15 0.04 M , and a tail possibly extending up to 0.7-0.9 M . Candidate redbacks tend to have higher companion masses than confirmed redbacks, suggesting a possible selection bias against the detection of radio pulsations in these more massive candidate systems. The distribution of companion masses between redbacks and the less massive black widows continues to be strongly bimodal, which is an important constraint on evolutionary models for these systems. Among redbacks, the median efficiency of converting the pulsar spin-down energy to γ-ray luminosity is ∼10%.
We present the discoveries of two of AM CVn systems, Gaia14aae and SDSS~J080449.49+161624.8, which show X-ray pulsations at their orbital periods, indicative of magnetically collimated accretion. ...Both also show indications of higher rates of mass transfer relative to the expectations from binary evolution driven purely by gravitational radiation, based on existing optical data for Gaia14aae, which show a hotter white dwarf temperature than expected from standard evolutionary models, and X-ray data for SDSS~J080449.49+161624.8 which show a luminosity 10-100 times higher than those for other AM~CVn at similar orbital periods. The higher mass transfer rates could be driven by magnetic braking from the disk wind interacting with the magnetosphere of the tidally locked accretor. We discuss implications of this additional angular momentum transport mechanism for evolution and gravitational wave detectability of AM CVn objects.
The second WIT rotation (Phase II) was assigned to the 203rd MI Battalion (TECHINT) which deployed to Iraq to assume responsibility for the WIT mission in 2005. Since 2006, WITs have been made up of ...a combination of personnel from the U.S. Army, Air Force, and Navy. ...equipment issued to the teams is not currently in the Army supply system.
Incorporating computer programming exercises in introductory physics is a delicate task that involves a number of choices that may have a strong affect on student learning. We present an approach ...that speaks to a number of common concerns that arise when using programming exercises in introductory physics classes where most students are absolute beginner programmers. These students need an approach that is (1) simple, involving 75 or fewer lines of well-commented code, (2) easy to use, with browser-based coding tools, (3) interactive, with a high frame rate to give a video-game like feel, (4) step-by-step with the ability to interact with intermediate stages of the "correct" program and (5) thoughtfully integrated into the physics curriculum, for example, by illustrating velocity and acceleration vectors throughout. We present a set of hour-long activities for classical mechanics that resemble well-known games such as "asteroids", "lunar lander" and "angry birds". Survey results from the first activity from four semesters of introductory physics classes at OSU in which a high percentage of the students are weak or absolute beginner programmers seems to confirm that the level of difficulty is appropriate for this level and that the students enjoy the activity. These exercises are available for general use at http://compadre.org/PICUP In the future we plan to assess conceptual knowledge using an animated version of the Force Concept Inventory originally developed by M. Dancy.
Cholera toxin (CT) is an AB-type protein toxin that contains a catalytic A1 subunit, an A2 linker, and a cell-binding B homopentamer. The CT holotoxin is released into the extracellular environment, ...but CTA1 attacks a target within the cytosol of a host cell. We recently reported that grape extract confers substantial resistance to CT. Here, we used a cell culture system to identify twelve individual phenolic compounds from grape extract that inhibit CT. Additional studies determined the mechanism of inhibition for a subset of the compounds: two inhibited CT binding to the cell surface and even stripped CT from the plasma membrane of a target cell; two inhibited the enzymatic activity of CTA1; and four blocked cytosolic toxin activity without directly affecting the enzymatic function of CTA1. Individual polyphenolic compounds from grape extract could also generate cellular resistance to diphtheria toxin, exotoxin A, and ricin. We have thus identified individual toxin inhibitors from grape extract and some of their mechanisms of inhibition against CT.
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In Nyxnob mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), synchronous oscillating retinal ganglion cells (RGCs) lead to oscillatory eye movements, ...i.e. nystagmus. Given the specific expression of mGluR6 and Cav1.4 in the photoreceptor to bipolar cell synapses, as well as their clinical association with CSNB, we hypothesize that Grm6nob3 and Cav1.4‐KO mutants show, like the Nyxnob mouse, oscillations in both their RGC activity and eye movements. Using multi‐electrode array recordings of RGCs and measurements of the eye movements, we demonstrate that Grm6nob3 and Cav1.4‐KO mice also show oscillations of their RGCs as well as a nystagmus. Interestingly, the preferred frequencies of RGC activity as well as the eye movement oscillations of the Grm6nob3, Cav1.4‐KO and Nyxnob mice differ among mutants, but the neuronal activity and eye movement behaviour within a strain remain aligned in the same frequency domain. Model simulations indicate that mutations affecting the photoreceptor–bipolar cell synapse can form a common cause of the nystagmus of CSNB by driving oscillations in RGCs via AII amacrine cells.
Key points
In Nyxnob mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), their oscillatory eye movements (i.e. nystagmus) are caused by synchronous oscillating retinal ganglion cells.
Here we show that the same mechanism applies for two other CSNB mouse models – Grm6nob3 and Cav1.4‐KO mice.
We propose that the retinal ganglion cell oscillations originate in the AII amacrine cells.
Model simulations show that by only changing the input to ON‐bipolar cells, all phenotypical differences between the various genetic mouse models can be reproduced.
figure legend Mechanism underlying congenital nystagmus in CSNB mouse models. Mutations in genes encoding for proteins in the photoreceptor to ON‐bipolar cell synapse lead to a more depolarized membrane potential of the AII amacrine cell, which in turn starts to intrinsically oscillate. The oscillations are forwarded to the retinal ganglion cells that start oscillating as well. This includes the ON‐direction selective ganglion cells which measure global motion of an image. They send this oscillatory signal to the accessory optic system, where compensatory, oscillatory eye movementsare induced; the nystagmus.
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Huntington disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. Although the length of this repeat is inversely correlated with age of onset (AOO), it does not fully explain ...the variability in AOO. We assessed the sequence downstream of the CAG repeat in HTT reference: (CAG)n-CAA-CAG, since variants within this region have been previously described, but no study of AOO has been performed. These analyses identified a variant that results in complete loss of interrupting (LOI) adenine nucleotides in this region (CAG)n-CAG-CAG. Analysis of multiple HD pedigrees showed that this LOI variant is associated with dramatically earlier AOO (average of 25 years) despite the same polyglutamine length as in individuals with the interrupting penultimate CAA codon. This LOI allele is particularly frequent in persons with reduced penetrance alleles who manifest with HD and increases the likelihood of presenting clinically with HD with a CAG of 36–39 repeats. Further, we show that the LOI variant is associated with increased somatic repeat instability, highlighting this as a significant driver of this effect. These findings indicate that the number of uninterrupted CAG repeats, which is lengthened by the LOI, is the most significant contributor to AOO of HD and is more significant than polyglutamine length, which is not altered in these individuals. In addition, we identified another variant in this region, where the CAA-CAG sequence is duplicated, which was associated with later AOO. Identification of these cis-acting modifiers have potentially important implications for genetic counselling in HD-affected families.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Many viruses express factors that reduce host gene expression through widespread degradation of cellular mRNA. An example of this class of proteins is the mRNA-targeting endoribonuclease SOX from the ...gamma-herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV). Previous studies indicated that cleavage of messenger RNAs (mRNA) by SOX occurs at specific locations defined by the sequence of the target RNA, which is at odds with the down-regulation of a large portion of cellular transcripts. In this study, we address this paradox by using high-throughput sequencing of cleavage intermediates combined with a custom bioinformatics-based analysis pipeline to identify SOX cleavage sites across the mRNA transcriptome. These data, coupled with targeted mutagenesis, reveal that while cleavage sites are specific and reproducible, they are defined by a degenerate sequence motif containing a small number of conserved residues rather than a strong consensus sequence. This degenerate element is well represented in both human and KSHV mRNA, and its presence correlates with RNA destabilization by SOX. This represents a new endonuclease targeting strategy, in which use of a degenerate targeting element enables RNA cleavage at specific locations without restricting the range of targets. Furthermore, it shows that strong target selectivity can be achieved without a high degree of sequence specificity.
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Congenital nystagmus, involuntary oscillating small eye movements, is commonly thought to originate from aberrant interactions between brainstem nuclei and foveal cortical pathways. Here, we ...investigated whether nystagmus associated with congenital stationary night blindness (CSNB) results from primary deficits in the retina. We found that CSNB patients as well as an animal model (nob mice), both of which lacked functional nyctalopin protein (NYX, nyx) in ON bipolar cells (BCs) at their synapse with photoreceptors, showed oscillating eye movements at a frequency of 4-7 Hz. nob ON direction-selective ganglion cells (DSGCs), which detect global motion and project to the accessory optic system (AOS), oscillated with the same frequency as their eyes. In the dark, individual ganglion cells (GCs) oscillated asynchronously, but their oscillations became synchronized by light stimulation. Likewise, both patient and nob mice oscillating eye movements were only present in the light when contrast was present. Retinal pharmacological and genetic manipulations that blocked nob GC oscillations also eliminated their oscillating eye movements, and retinal pharmacological manipulations that reduced the oscillation frequency of nob GCs also reduced the oscillation frequency of their eye movements. We conclude that, in nob mice, synchronized oscillations of retinal GCs, most likely the ON-DCGCs, cause nystagmus with properties similar to those associated with CSNB in humans. These results show that the nob mouse is the first animal model for a form of congenital nystagmus, paving the way for development of therapeutic strategies.
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