The Talin Head Domain Reinforces Integrin-Mediated Adhesion by Promoting Adhesion Complex Stability and Clustering

Talin serves an essential function during integrin-mediated adhesion in linking integrins to actin via the intracellular adhesion complex. In addition, the N-terminal head domain of talin regulates the affinity of integrins for their ECM-ligands, a process known as inside-out activation. We previously showed that in Drosophila, mutating the integrin binding site in the talin head domain resulted in weakened adhesion to the ECM. Intriguingly, subsequent studies showed that canonical inside-out activation of integrin might not take place in flies. Consistent with this, a mutation in talin that specifically blocks its ability to activate mammalian integrins does not significantly impinge on talin function during fly development. Here, we describe results suggesting that the talin head domain reinforces and stabilizes the integrin adhesion complex by promoting integrin clustering distinct from its ability to support inside-out activation. Specifically, we show that an allele of talin containing a mutation that disrupts intramolecular interactions within the talin head attenuates the assembly and reinforcement of the integrin adhesion complex. Importantly, we provide evidence that this mutation blocks integrin clustering in vivo. We propose that the talin head domain is essential for regulating integrin avidity in Drosophila and that this is crucial for integrin-mediated adhesion during animal development

3-(2,6-Dioxopiperidin-3-yl)-3-aza­bicyclo­[3.2.0]heptane-2,4-dione

The title mol­ecule, C11H12N2O4, consists of a 3-aza­bicyclo­[3.2.0]heptane group containing a nearly planar cyclo­butane ring (r.m.s. deviation of fitted atoms is 0.0609 Å), fused to a pyrrolidine ring, bonded to a 2,6-dioxopiperidine ring at the 3-position. The angle between the mean planes of the cyclo­butane and fused pyrrolidine ring is 67.6 (6)°. The dihedral angles between the mean planes of the pyrrolidine and cyclo­butane rings and the dioxopiperidine ring are 73.9 (2) and 62.4 (4)°, respectively. The pyrrolidine and dioxopiperidine rings are twisted about the 3-yl group [torsion angles = −55.0 (1) and 115.0 (1)°] in a nearly perpendicular manner. Crystal packing is influenced by extensive inter­molecular C—H⋯O and N—H⋯O inter­actions between all four carbonyl O atoms and H atoms from the cyclo­butane and dioxopiperidine rings, as well as between the N atom and an H atom from the cyclo­butane ring. In addition, weak π-ring interactions also occur between H atoms from the cyclobutane ring and the five-membered pyrrolidine ring. As a result, mol­ecules are linked into infinite chains diagonally along the [101] plane of the unit cell in an alternate inverted pattern

AEGIS: Extinction and Star Formation Tracers from Line Emission

Strong nebular emission lines are a sensitive probe of star formation and extinction in galaxies, and the [O II] line detects star forming populations out to z>1. However, star formation rates from emission lines depend on calibration of extinction and the [O II]/H-alpha line ratio, and separating star formation from AGN emission. We use calibrated line luminosities from the DEEP2 survey and Palomar K magnitudes to show that the behavior of emission line ratios depends on galaxy magnitude and color. For galaxies on the blue side of the color bimodality, the vast majority show emission signatures of star formation, and there are strong correlations of extinction and [O II]/H-alpha with restframe H magnitude. The conversion of [O II] to extinction-corrected H-alpha and thus to star formation rate has a significant slope with M_H, 0.23 dex/mag. Red galaxies with emission lines have a much higher scatter in their line ratios, and more than half show AGN signatures. We use 24 micron fluxes from Spitzer/MIPS to demonstrate the differing populations probed by nebular emission and by mid-IR luminosity. Although extinction is correlated with luminosity, 98% of IR-luminous galaxies at z~1 are still detected in the [O II] line. Mid-IR detected galaxies are mostly bright and intermediate color, while fainter, bluer galaxies with high [O II] luminosity are rarely detected at 24 microns.Comment: 4 pages, 3 figures. Accepted for publication in ApJ Letters AEGIS special editio

Cosimulation of the index finger extensor apparatus with finite element and musculoskeletal models

Musculoskeletal modeling has been effective for simulating dexterity and exploring the consequences of disability. While previous approaches have examined motor function using multibody dynamics, existing musculoskeletal models of the hand and fingers have difficulty simulating soft tissue such as the extensor mechanism of the fingers, which remains underexplored. To investigate the extensor mechanism and its impact on finger motor function, we developed a finite element model of the index finger extensor mechanism and a cosimulation method that combines the finite element model with a multibody dynamic model. The finite element model and cosimulation were validated through comparison with experimentally derived tissue strains and fingertip endpoint forces respectively. Tissue strains predicted by the finite element model were consistent with the experimentally observed strains of the 9 postures tested in cadaver specimens. Fingertip endpoint forces predicted using the cosimulation were well aligned in both force (difference within 0.60 N) and direction (difference within 30◦with experimental results. Sensitivity of the extensor mechanism to changes in modulus and adhesion configuration were evaluated for ± 50% of experimental moduli, presence of the radial and ulnar adhesions, and joint capsule. Simulated strains and endpoint forces were found to be minimally sensitive to alterations in moduli and adhesions. These results are promising and demonstrate the ability of the cosimulation to predict global behavior of the extensor mechanism, while enabling measurement of stresses and strains within the structure itself. This model could be used in the future to predict the outcomes for different surgical repairs of the extensor mechanism

The Impact of Depression on Patient Outcomes in Hip Arthroscopic Surgery.

Background: Mental health impairments have been shown to negatively affect preoperative self-reported function in patients with various musculoskeletal disorders, including those with femoroacetabular impingement. Hypothesis: Those with symptoms of depression will have lower self-reported function, more pain, and less satisfaction on initial assessment and at 2-year follow-up than those without symptoms of depression. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who were enrolled in a multicenter hip arthroscopic surgery registry and had 2-year outcome data available were included in the study. Patients completed the 12-item International Hip Outcome Tool (iHOT-12), visual analog scale (VAS) for pain, and 12-item Short-Form Health Survey (SF-12) when consenting for surgery. At 2-year follow-up, patients were emailed the iHOT, the VAS, and a rating scale of surgical satisfaction. Initial SF-12 mental component summary (MCS) scores Results: A total of 781 patients achieved the approximate 2-year milestone (mean follow-up, 735 ± 68 days), with 651 (83%) having 2-year outcome data available. There were 434 (67%) female and 217 (33%) male patients, with a mean age of 35.8 ± 13.0 years and a mean body mass index of 25.4 ± 8.8 kg/m Conclusion: A large number of patients who underwent hip arthroscopic surgery presented with symptoms of depression, which negatively affected self-reported function, pain levels, and satisfaction on initial assessment and at 2-year follow-up. Surgeons who perform hip arthroscopic surgery may need to identify the symptoms of depression and be aware of the impact that depression can have on surgical outcomes

Coulomb Phase Gluon Scattering at Strong Coupling

We calculate corrections to gluon scattering amplitudes in a Coulomb phase using gauge/string duality. The Coulomb phase considered is a maximal rank breaking of $SU(n_1+n_2)\to SU(n_1)\times SU(n_2) \times U(1)$. This problem therefore has 3 scales involved: 1) the scale of the massive fields $M_W$ arising from the spontaneous breaking of the gauge group; 2) The scale of the scattering, characterized by the Mandelstam variables $s,t,u$; 3) The IR regulator $m_{IR}$. We find corrections in the hard scattering limit $|s|,|t|,|u|\gg m_{IR}^2 \gg M_W^2$, and also find below threshold corrections with $M_W^2 \gg |s|,|t|,|u|$. We find that the corrections in the second case are finite, and so are IR regulator independent.Comment: 17+17 pages, 3 figure

Effects of traumatic brain injury on cognitive functioning and cerebral metabolites in HIV-infected individuals.

We explored the possible augmenting effect of traumatic brain injury (TBI) history on HIV (human immunodeficiency virus) associated neurocognitive complications. HIV-infected participants with self-reported history of definite TBI were compared to HIV patients without TBI history. Groups were equated for relevant demographic and HIV-associated characteristics. The TBI group evidenced significantly greater deficits in executive functioning and working memory. N-acetylaspartate, a putative marker of neuronal integrity, was significantly lower in the frontal gray matter and basal ganglia brain regions of the TBI group. Together, these results suggest an additional brain impact of TBI over that from HIV alone. One clinical implication is that HIV patients with TBI history may need to be monitored more closely for increased risk of HIV-associated neurocognitive disorder signs or symptoms

Fluctuation Theorems for Entropy Production and Heat Dissipation in Periodically Driven Markov Chains

Asymptotic fluctuation theorems are statements of a Gallavotti-Cohen symmetry in the rate function of either the time-averaged entropy production or heat dissipation of a process. Such theorems have been proved for various general classes of continuous-time deterministic and stochastic processes, but always under the assumption that the forces driving the system are time independent, and often relying on the existence of a limiting ergodic distribution. In this paper we extend the asymptotic fluctuation theorem for the first time to inhomogeneous continuous-time processes without a stationary distribution, considering specifically a finite state Markov chain driven by periodic transition rates. We find that for both entropy production and heat dissipation, the usual Gallavotti-Cohen symmetry of the rate function is generalized to an analogous relation between the rate functions of the original process and its corresponding backward process, in which the trajectory and the driving protocol have been time-reversed. The effect is that spontaneous positive fluctuations in the long time average of each quantity in the forward process are exponentially more likely than spontaneous negative fluctuations in the backward process, and vice-versa, revealing that the distributions of fluctuations in universes in which time moves forward and backward are related. As an additional result, the asymptotic time-averaged entropy production is obtained as the integral of a periodic entropy production rate that generalizes the constant rate pertaining to homogeneous dynamics