Inhibition of phosphoinositide 3-kinase/protein kinase B signaling hampers the vasopressin-dependent stimulation of myogenic differentiation

Arginine-vasopressin (AVP) promotes muscle differentiation, hypertrophy, and regeneration through the combined activation of the calcineurin and Calcium/Calmodulin-dependent Protein Kinase (CaMK) pathways. The AVP system is impaired in several neuromuscular diseases, suggesting that AVP may act as a physiological factor in skeletal muscle. Since the Phosphoinositide 3-kinases/Protein Kinase B/mammalian Target Of Rapamycin (PI3K/Akt/mTOR) signaling plays a significant role in regulating muscle mass, we evaluated its role in the AVP myogenic effect. In L6 cells AKT1 expression was knocked down, and the AVP-dependent expression of mTOR and Forkhead box O3 (FoxO) was analyzed by Western blotting. The effect of the PI3K inhibitor LY294002 was evaluated by cellular and molecular techniques. Akt knockdown hampered the AVP-dependent mTOR expression while increased the levels of FoxO transcription factor. LY294002 treatment inhibited the AVP-dependent expression of Myocyte Enhancer Factor-2 (MEF2) and myogenin and prevented the nuclear translocation of MEF2. LY294002 also repressed the AVP-dependent nuclear export of histone deacetylase 4 (HDAC4) interfering with the formation of multifactorial complexes on the myogenin promoter. We demonstrate that the PI3K/Akt pathway is essential for the full myogenic effect of AVP and that, by targeting this pathway, one may highlight novel strategies to counteract muscle wasting in aging or neuromuscular disorders

Characterizing spiral arm and interarm star formation

Interarm star formation contributes significantly to a galaxy's star formation budget, and provides an opportunity to study stellar birthplaces unperturbed by spiral arm dynamics. Using optical integral field spectroscopy of the nearby galaxy NGC 628 with VLT/MUSE, we construct Halpha maps including detailed corrections for dust extinction and stellar absorption to identify 391 HII regions at 35pc resolution over 12 kpc^2. Using tracers sensitive to the underlying gravitational potential, we associate HII regions with either arm (271) or interarm (120) environments. Using our full spectral coverage of each region, we find that most HII region physical properties (luminosity, size, metallicity, ionization parameter) are independent of environment. We calculate the fraction of Halpha luminosity due to the diffuse ionized gas (DIG) background contaminating each HII region, and find the DIG surface brightness to be higher within HII regions compared to the surroundings, and slightly higher within arm HII regions. Use of the temperature sensitive [SII]/Halpha line ratio map instead of the Halpha surface brightness to identify HII region boundaries does not change this result. Using the dust attenuation as a tracer of the gas, we find depletion times consistent with previous work (2 x 10^9 yr) with no differences between the arm and interarm, however this is very sensitive to the DIG correction. Unlike molecular clouds, which can be dynamically affected by the galactic environment, we see fairly consistent HII region properties in both arm and interarm environments. This suggests either a difference in arm star formation and feedback, or a decoupling of dense star forming clumps from the more extended surrounding molecular gas.Comment: 10 pages, 4 figures, 1 table, accepted for publication in Ap

Spin and lattice excitations of a BiFeO3 thin film and ceramics

We present a comprehensive study of polar and magnetic excitations in BiFeO3 ceramics and a thin film epitaxially grown on an orthorhombic (110) TbScO3 substrate. Infrared reflectivity spectroscopy was performed at temperatures from 5 to 900 K for the ceramics and below room temperature for the thin film. All 13 polar phonons allowed by the factor-group analysis were observed in theceramic samples. The thin-film spectra revealed 12 phonon modes only and an additional weak excitation, probably of spin origin. On heating towards the ferroelectric phase transition near 1100 K, some phonons soften, leading to an increase in the static permittivity. In the ceramics, terahertz transmission spectra show five low-energy magnetic excitations including two which were not previously known to be infrared active; at 5 K, their frequencies are 53 and 56 cm-1. Heating induces softening of all magnetic modes. At a temperature of 5 K, applying an external magnetic field of up to 7 T irreversibly alters the intensities of some of these modes. The frequencies of the observed spin excitations provide support for the recently developed complex model of magnetic interactions in BiFeO3 (R.S. Fishman, Phys. Rev. B 87, 224419 (2013)). The simultaneous infrared and Raman activity of the spin excitations is consistent with their assignment to electromagnons

The Risk of Toxicities from Trastuzumab, Alone or in Combination, in an Elderly Breast Cancer Population

Abstract Background: Breast cancer in the elderly is associated with high recurrence and death rates, due mostly to undertreatment. Human epidermal growth factor receptor type 2 (HER2) overexpression is infrequent in older patients. Trastuzumab- based chemotherapy is often withheld from elderly patients because of its cardiotoxicity. Patients and Methods: Medical records of consecutive HER2-positive breast cancer patients aged 65 70 years old treated between 2005 and 2010 in the participating centers were retrospectively reviewed. All patients underwent multidimensional geriatric assessment (MGA). Results: Among 59 patients identified, 51 patients were evaluable (median age 76 years). The rate of any adverse event was 20% (10/51). The most relevant cardiac adverse event consisted of symptomatic congestive heart failure (CHF; n = 1, 2%) followed by asymptomatic decreases of left ventricular ejection fraction (LVEF; n = 6, 12%). Other toxicities included moderate hypersensitivity reactions during trastuzumab infusions (n = 3, 6%). Hypertension, obesity, prior anthracyclines exposure and concurrent chemotherapy were associated with a higher incidence of toxic events. Previous radiotherapy, concurrent endocrine therapy and different trastuzumab-based regimens did not seem to influence toxicity. Conclusions: Our data suggest that trastuzumab has a good safety profile in nonfrail women aged 70 years and older. These favorable findings may be related to a limited number of anthracycline pretreatments, patient selection and a close cardiologic monitoring

Twistors, Harmonics and Holomorphic Chern-Simons

We show that the off-shell N=3 action of N=4 super Yang-Mills can be written as a holomorphic Chern-Simons action whose Dolbeault operator is constructed from a complex-real (CR) structure of harmonic space. We also show that the local space-time operators can be written as a Penrose transform on the coset SU(3)/(U(1) \times U(1)). We observe a strong similarity to ambitwistor space constructions.Comment: 34 pages, 3 figures, v2: replaced with published version, v3: Added referenc

Gemcitabine-based doublets versus single-agent therapy for elderly patients with advanced nonsmall cell lung cancer: a Literature-based Meta-analysis.

Although platinum-based combinations are considered the best option of care for patients with advanced nonsmall cell lung cancer (NSCLC), single-agent therapy is the preferred treatment for older patients. Since the late 1990s, various combinations of third-generation agents (gemcitabine [G], vinorel- bine, docetaxel, and paclitaxel) have been tested, yielding contradictory results. The authors of this report performed a literature-based meta-analysis to assess the efficacy and tolerability of G-based doublets compared with single-agent chemotherapy for elderly patients with NSCLC. METHODS: Data from all published, randomized, phase 3 trials that compared a G-based doublet with a third-generation single agent in elderly patients were collected from electronic databases (Medline and the Cochrane Central Register of Controlled Trials), relevant reference lists, and abstract books. Pooled odds ratios (ORs) were calculated for the 1-year survival rate, the overall response rate (ORR), and grade 3 and 4 toxicities. RESULTS: Four eligible trials (1436 patients) were selected from 442 studies that initially were identified. A significant difference in ORR favoring G-based doublets over single agents was observed (OR, 0.65; 95% confidence interval [95% CI], 0.51-0.82 [P<.001]), whereas the trend toward an improved 1-year survival rate was not significant (OR, 0.78; 95% CI, 0.57-1.06 [P¼.169]). Grade 3 and 4 toxicities did not differ significantly except for thrombocytopenia (OR, 1.76; 95% CI, 1.12-2.76 [P¼.014]). CONCLUSIONS: G-based doublets appeared to be effective and feasible compared with single agents in the treatment of elderly patients with advanced NSCLC who were not suitable for full-dose, platinum-based chemotherapy. Further prospective, elderly specific, phase 3 trials will be necessary

Evaluation of Afterschool Activity Programs’ (ASAP) Effect on Children’s Physical Activity, Physical Health, and Fundamental Movement Skills

Publisher Copyright: © The Author(s) 2021.Background: Physical literacy-focused afterschool activity programs (ASAPs) can be an effective strategy to improve children’s health-related parameters. We sought to compare physical activity, body composition, aerobic capacity, and fundamental movement skills between physical literacy-focused ASAP and a standard recreational ASAP. Method: A pre–post (6 months) comparison study was conducted in 5- to 12-year-old children in a physical literacy-focused ASAP (physical literacy group, n = 14) and children attending a standard recreational ASAP (comparison group, n = 15). Physical activity guideline adherence was assessed using accelerometry, body composition was analyzed using bioelectrical impedance, aerobic capacity was estimated using the Progressive Aerobic Cardiovascular Endurance Run test, and fundamental movement skills were evaluated using the Test of Gross Motor Development–2. Results: There were no significant differences between groups at baseline. After 6 months, the physical literacy group exhibited a significant improvement in their total raw score for the Test of Gross Motor Development–2 (p =.016), which was likely due to improvements in object control skills (p =.024). The comparison group significantly increased body mass index (p =.001) and body fat (p =.009) over time. No significant between-group differences were found; however, there was a trend for improved aerobic capacity in the physical literacy group (d = 0.58). Conclusions: Engagement in the physical literacy-focused ASAP contributed to an attenuated increase in adiposity and an improvement in object control skills.Peer reviewe

Spectroscopic Constraints on the Form of the Stellar Cluster Mass Function

This contribution addresses the question of whether the initial cluster mass function (ICMF) has a fundamental limit (or truncation) at high masses. The shape of the ICMF at high masses can be studied using the most massive young (<10 Myr) clusters, however this has proven difficult due to low-number statistics. In this contribution we use an alternative method based on the luminosities of the brightest clusters, combined with their ages. If a truncation is present, a generic prediction (nearly independent of the cluster disruption law adopted) is that the median age of bright clusters should be younger than that of fainter clusters. In the case of an non-truncated ICMF, the median age should be independent of cluster luminosity. Here, we present optical spectroscopy of twelve young stellar clusters in the face-on spiral galaxy NGC 2997. The spectra are used to estimate the age of each cluster, and the brightness of the clusters is taken from the literature. The observations are compared with the model expectations of Larsen (2009) for various ICMF forms and both mass dependent and mass independent cluster disruption. While there exists some degeneracy between the truncation mass and the amount of mass independent disruption, the observations favour a truncated ICMF. For low or modest amounts of mass independent disruption, a truncation mass of 5-6*10^5 Msun is estimated, consistent with previous determinations. Additionally, we investigate possible truncations in the ICMF in the spiral galaxy M83, the interacting Antennae galaxies, and the collection of spiral and dwarf galaxies present in Larsen (2009) based on photometric catalogues taken from the literature, and find that all catalogues are consistent with having a (environmentally dependent) truncation in the cluster mass functions.Comment: 6 pages, 5 figures, in press, A&A Research Note

CHY representations for gauge theory and gravity amplitudes with up to three massive particles

We show that a wide class of tree-level scattering amplitudes involving scalars, gauge bosons, and gravitons, up to three of which may be massive, can be expressed in terms of a Cachazo-He-Yuan representation as a sum over solutions of the scattering equations. These amplitudes, when expressed in terms of the appropriate kinematic invariants, are independent of the masses and therefore identical to the corresponding massless amplitudes.Comment: 20 pages, 1 figure; v2: minor typos corrected, published versio

Collinear and Soft Limits of Multi-Loop Integrands in N=4 Yang-Mills

It has been argued in arXiv:1112.6432 that the planar four-point integrand in N=4 super Yang-Mills theory is uniquely determined by dual conformal invariance together with the absence of a double pole in the integrand of the logarithm in the limit as a loop integration variable becomes collinear with an external momentum. In this paper we reformulate this condition in a simple way in terms of the amplitude itself, rather than its logarithm, and verify that it holds for two- and three-loop MHV integrands for n>4. We investigate the extent to which this collinear constraint and a constraint on the soft behavior of integrands can be used to determine integrands. We find an interesting complementarity whereby the soft constraint becomes stronger while the collinear constraint becomes weaker at larger n. For certain reasonable choices of basis at two and three loops the two constraints in unison appear strong enough to determine MHV integrands uniquely for all n.Comment: 27 pages, 14 figures; v2: very minor change