Posterior stabilized designs in modern total knee arthroplasty: Vestigial organs

Clinical difference between posterior-stabilized (PS) and cruciate-retaining (CR) designs in total knee arthroplasty has remained elusive for decades. This classic debate has been given pause due to futile efforts to prove one design superior over the other. Recently, anterior-lipped and more conforming CR bearings have emerged to substitute for the posterior-cruciate ligament (PCL), if absent, damaged or resected, and obviate the need for the archaic cam-post mechanism of a traditional PS design. Advantages of avoiding a PS TKA include eliminating the risk of box cut induced femoral condylar fracture, operative efficiency by removing procedural steps, removing the articulation that is a source of wear, post deformation, breakage, or dislocation, and eliminating patellar clunk

Magnetic field detection in the B2Vn star HR 7355

The B2Vn star HR 7355 is found to be a He-rich magnetic star. Spectropolarimetric data were obtained with FORS1 at UT2 on Paranal observatory to measure the disk-averaged longitudinal magnetic field at various phases of the presumed 0.52 d cycle. A variable magnetic field with strengths between B_z = -2200 and +3200G was found, with confidence limits of 100 to 130G. The field topology is that of an oblique dipole, while the star itself is seen about equator-on. In the intensity spectra the HeI-lines show the typical equivalent width variability of He-strong stars, usually attributed to surface abundance spots. The amplitudes of the equivalent width variability of the HeI lines are extraordinarily strong compared to other cases. These results not only put HR 7355 unambiguously among the early-type magnetic stars, but confirm its outstanding nature: With v sin i = 320 km/s the parameter space in which He-strong stars are known to exist has doubled in terms of rotational velocity.Comment: 6 pages, 5 figures, 1 Table. Accepted for publication in MNRAS Letter

Microglia Control Vascular Architecture via a TGFβ1 Dependent Paracrine Mechanism Linked to Tissue Mechanics

© 2020, The Author(s). Tissue microarchitecture and mechanics are important in development and pathologies of the Central Nervous System (CNS); however, their coordinating mechanisms are unclear. Here, we report that during colonization of the retina, microglia contacts the deep layer of high stiffness, which coincides with microglial bipolarization, reduction in TGFβ1 signaling and termination of vascular growth. Likewise, stiff substrates induce microglial bipolarization and diminish TGFβ1 expression in hydrogels. Both microglial bipolarization in vivo and the responses to stiff substrates in vitro require intracellular adaptor Kindlin3 but not microglial integrins. Lack of Kindlin3 causes high microglial contractility, dysregulation of ERK signaling, excessive TGFβ1 expression and abnormally-patterned vasculature with severe malformations in the area of photoreceptors. Both excessive TGFβ1 signaling and vascular defects caused by Kindlin3-deficient microglia are rescued by either microglial depletion or microglial knockout of TGFβ1 in vivo. This mechanism underlies an interplay between microglia, vascular patterning and tissue mechanics within the CNS

Detection of a Hot Subdwarf Companion to the Be Star FY Canis Majoris

The rapid rotation of Be stars may be caused in some cases by past mass and angular momentum accretion in an interacting binary in which the mass donor is currently viewed as a small, hot subdwarf stripped of its outer envelope. Here we report on the spectroscopic detection of such a subdwarf in the Be binary system FY Canis Majoris from the analysis of data acquired by the IUE spacecraft and KPNO Coude Feed Telescope over the course of 16 and 21 years, respectively. We present a double-lined spectroscopic orbit for the binary based upon radial velocities from the IUE spectra and use the orbital solutions with a Doppler tomography algorithm to reconstruct the components' UV spectra. The subdwarf is hot (T_eff = 45+/-5 kK) and has a mass of about 1.3 M_sun and a radius of about 0.6 R_sun. It contributes about 4% as much flux as the Be star does in the FUV. We also present observations of the H-alpha and He I 6678 emission features that are formed in the circumstellar disk of the Be star. Orbital flux and velocity variations in the He I 6678 profile indicate that much of the emission forms along the disk rim facing the hot subdwarf where the disk is probably heated by the incident radiation from the subdwarf. A study of the FUV infall shell lines discovered in the 1980s confirms their episodic presence but reveals that they tend to be found around both quadrature phases, unlike the pattern in Algol binaries. Phase-dependent variations in the UV N V doublet suggest the presence of a N-enhanced wind from the subdwarf and a possible shock-interaction region between the stars where the subdwarf's wind collides with the disk of the Be star.Comment: 46 pages, 15 figures, ApJ in pres

School librarians as literacy educators within a complex role

Librarians in schools are expected to play an important role as literacy educators, and have a positive impact on young people’s literacy learning. However in the context of their diverse workload, relatively little is known about how this aspect of their role sits within its competing demands, and the exact scope of the literacy educator requirements. Using a hybrid approach to content analysis, this article analyses 40 recent job description documents to identify the nature and prevalence of different aspects of the role, and to explore the literacy educator aspect of this profession. Findings suggest that while the literacy educator aspect is one of the most common role requirements, it sits within a complex workload, and the literacy educator aspect is itself multi-faceted and demanding

ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons

Miles-Carpenter syndrome (MCS) was described in 1991 as an XLID syndrome with fingertip arches and contractures and mapped to proximal Xq. Patients had microcephaly, short stature, mild spasticity, thoracic scoliosis, hyperextendable MCP joints, rocker-bottom feet, hyperextended elbows and knees. A mutation, p.L66H, in ZC4H2, was identified in a XLID resequencing project. Additional screening of linked families and next generation sequencing of XLID families identified three ZC4H2 mutations: p.R18K, p.R213W and p.V75in15aa. The families shared some relevant clinical features. In silico modeling of the mutant proteins indicated all alterations would destabilize the protein. Knockout mutations in zc4h2 were created in zebrafish and homozygous mutant larvae exhibited abnormal swimming, increased twitching, defective eye movement and pectoral fin contractures. Because several of the behavioral defects were consistent with hyperactivity, we examined the underlying neuronal defects and found that sensory neurons and motoneurons appeared normal. However, we observed a striking reduction in GABAergic interneurons. Analysis of cell-type-specificmarkers showed a specific loss of V2 interneurons in the brain and spinal cord, likely arising from mis-specification of neural progenitors. Injected human wt ZC4H2 rescued the mutant phenotype. Mutant zebrafish injectedwith human p.L66H or p.R213W mRNA failed to be rescued, while the p.R18K mRNA was able to rescue the interneuron defect. Our findings clearly support ZC4H2 as a novel XLID gene with a required function in interneuron development. Loss of function of ZC4H2 thus likely results in altered connectivity ofmany brain and spinal circuits

First Results from the CHARA Array. I. An Interferometric and Spectroscopic Study of the Fast Rotator alpha Leonis (Regulus)

We report on K-band interferometric observations of the bright, rapidly rotating star Regulus (type B7 V) made with the CHARA Array on Mount Wilson, California. Through a combination of interferometric and spectroscopic measurements, we have determined for Regulus the equatorial and polar diameters and temperatures, the rotational velocity and period, the inclination and position angle of the spin axis, and the gravity darkening coefficient. These first results from the CHARA Array provide the first interferometric measurement of gravity darkening in a rapidly rotating star and represent the first detection of gravity darkening in a star that is not a member of an eclipsing binary system.Comment: Accepted for publication in The Astrophysical Journal, 44 pages w/ 14 figure

Anatomy of protein disorder, flexibility and disease-related mutations.

Integration of protein structural information with human genetic variation and pathogenic mutations is essential to understand molecular mechanisms associated with the effects of polymorphisms on protein interactions and cellular processes. We investigate occurrences of non-synonymous SNPs in ordered and disordered protein regions by systematic mapping of common variants and disease-related SNPs onto these regions. We show that common variants accumulate in disordered regions; conversely pathogenic variants are significantly depleted in disordered regions. These different occurrences of pathogenic and common SNPs can be attributed to a negative selection on random mutations in structurally highly constrained regions. New approaches in the study of quantitative effects of pathogenic-related mutations should effectively account for all the possible contexts and relative functional constraints in which the sequence variation occurs.This research was supported by the Biotechnology and Biological Sciences Research Council (BB/H018409/1 to FF), the British Heart Foundation (FS/12/41/29724 to AF and FF) and the Leukaemia & Lymphoma Research (to FF). SSC is funded by a Leukaemia & Lymphoma Research Gordon Piller PhD Studentship

PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC

The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay

Environmental factors modulating the stability and enzymatic activity of the Petrotoga mobilis Esterase (PmEst)

Enzymes isolated from thermophilic organisms found in oil reservoirs can find applications in many fields, including the oleochemical, pharmaceutical, bioenergy, and food/dairy industries. In this study, in silico identification and recombinant production of an esterase from the extremophile bacteria Petrotoga mobilis (designated PmEst) were performed. Then biochemical, bioinformatics and structural characterizations were undertaken using a combination of synchrotron radiation circular dichroism (SRCD) and fluorescence spectroscopies to correlate PmEst stability and hydrolytic activity on different substrates. The enzyme presented a high Michaelis-Menten constant (KM 0.16 mM) and optimum activity at ~55°C for p-nitrophenyl butyrate. The secondary structure of PmEst was preserved at acid pH, but not under alkaline conditions. PmEst was unfolded at high concentrations of urea or guanidine through apparently different mechanisms. The esterase activity of PmEst was preserved in the presence of ethanol or propanol and its melting temperature increased ~8°C in the presence of these organic solvents. PmEst is a mesophilic esterase with substrate preference towards short-to medium-length acyl chains. The SRCD data of PmEst is in agreement with the prediction of an α/β protein, which leads us to assume that it displays a typical fold of esterases from this family. The increased enzyme stability in organic solvents may enable novel applications for its use in synthetic biology. Taken together, our results demonstrate features of the PmEst enzyme that indicate it may be suitable for applications in industrial processes, particularly, when the use of polar organic solvents is required