Dynamics of leg muscle function in tammar wallabies (M. eugenii) during level versus incline hopping

The goal of our study was to examine whether the in vivo force-length behavior, work and elastic energy savings of distal muscle-tendon units in the legs of tammar wallabies (Macropus eugenii) change during level versus incline hopping. To address this question, we obtained measurements of muscle activation (via electromyography), fascicle strain (via sonomicrometry) and muscle-tendon force (via tendon buckles) from the lateral gastrocnemius (LG) and plantaris (PL) muscles of tammar wallabies trained to hop on a level and an inclined (10°, 17.4% grade) treadmill at two speeds (3.3 m s^(-1) and 4.2 m s^(-1)). Similar patterns of muscle activation, force and fascicle strain were observed under both level and incline conditions. This also corresponded to similar patterns of limb timing and movement (duty factor, limb contact time and hopping frequency). During both level and incline hopping, the LG and PL exhibited patterns of fascicle stretch and shortening that yielded low levels of net fascicle strain [LG: level, -1.0±4.6% (mean ± s.e.m.) vs incline, 0.6±4.5%; PL: level, 0.1±1.0% vs incline, 0.4±1.6%] and muscle work (LG: level, -8.4±8.4 J kg^(-1) muscle vs incline, -6.8±7.5 J kg^(-1) muscle; PL: level, -2.0±0.6 J kg^(-1) muscle vs incline, -1.4±0.7 J kg^(-1) muscle). Consequently, neither muscle significantly altered its contractile dynamics to do more work during incline hopping. Whereas electromyographic (EMG) phase, duration and intensity did not differ for the LG, the PL exhibited shorter but more intense periods of activation, together with reduced EMG phase (P<0.01), during incline versus level hopping. Our results indicate that design for spring-like tendon energy savings and economical muscle force generation is key for these two distal muscle-tendon units of the tammar wallaby, and the need to accommodate changes in work associated with level versus incline locomotion is achieved by more proximal muscles of the limb

Assessment of anti-TNF-α activities in keratinocytes expressing inducible TNF- α: A novel tool for anti-TNF-α drug screening

© 2016 Udommethaporn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine important in normal and pathological biological processes. Newly synthesized pro-TNF-α is expressed on the plasma membrane and cleaved to release soluble TNF-α protein: both are biologically active. Secreted TNF-α signals through TNF receptors and the membrane-bound TNF-α acts by cell contact-dependent signaling. Anti-TNF-α antibodies have been used effectively for treatment of chronic inflammation, however with adverse side effects. Thus, there is a need for new anti-TNF-α small molecule compounds. Anti-TNF-α activity assays involve treatment of keratinocytes with exogenous TNF-α before or after anti-TNF-α incubation. However, this model fails to address the dual signaling of TNF-α. Here we describe a Doxycycline (Dox)-inducible TNF-α (HaCaT-TNF-α) expression system in keratinocytes. Using this in-vitro model, we show cell inhibition and induced expression of pro-inflammatory cytokines and markers, including IL-1β, IL-6, IL-8, NF-êB1, and KRT-16, similar to cells treated with exogenous TNF-α. Sufficient secreted TNF-α produced also activated IL-1β and IL-8 expression in wt HaCaT cells. Importantly, stimulated expression of IL-1β and IL-8 in HaCaT-TNF-α were blocked by Quercetin, a flavanol shown to possess anti-TNF-α activities. This novel in vitro cell model provides an efficient tool to investigate the dual signaling of TNF-α. Importantly, this model provides an effective, fast, and simple screening for compounds with anti-TNF-α activities for chronic inflammatory disease therapies

Triple SILAC identified progestin-independent and dependent PRA and PRB interacting partners in breast cancer

Progesterone receptor (PR) isoforms, PRA and PRB, act in a progesterone-independent and dependent manner to differentially modulate the biology of breast cancer cells. Here we show that the differences in PRA and PRB structure facilitate the binding of common and distinct protein interacting partners affecting the downstream signaling events of each PR-isoform. Tet-inducible HA-tagged PRA or HA-tagged PRB constructs were expressed in T47DC42 (PR/ER negative) breast cancer cells. Affinity purification coupled with stable isotope labeling of amino acids in cell culture (SILAC) mass spectrometry technique was performed to comprehensively study PRA and PRB interacting partners in both unliganded and liganded conditions. To validate our findings, we applied both forward and reverse SILAC conditions to effectively minimize experimental errors. These datasets will be useful in investigating PRA- and PRB-specific molecular mechanisms and as a database for subsequent experiments to identify novel PRA and PRB interacting proteins that differentially mediated different biological functions in breast cancer

Helium Nova on a Very Massive White Dwarf -- A Light Curve Model of V445 Puppis (2000) Revised

V445 Pup (2000) is a unique object identified as a helium nova. Color indexes during the outburst are consistent with those of free-free emission. We present a free-free emission dominated light curve model of V445 Pup on the basis of the optically thick wind theory. Our light curve fitting shows that (1) the white dwarf (WD) mass is very massive (M_WD \gtrsim 1.35 M_\sun), and (2) a half of the accreted matter remains on the WD, both of which suggest that the increasing WD mass. Therefore, V445 Pup is a strong candidate of Type Ia supernova progenitor. The estimated distance to V445 Pup is now consistent with the recent observational suggestions, 3.5 < d < 6.5 kpc. A helium star companion is consistent with the brightness of m_v=14.5 mag just before the outburst, if it is a little bit evolved hot (\log T (K) \gtrsim 4.5) star with the mass of M_He \gtrsim 0.8 M_\sun. We then emphasize importance of observations in the near future quiescent phase after the thick circumstellar dust dissipates away, especially its color and magnitude to specify the nature of the companion star. We have also calculated helium ignition masses for helium shell flashes against various helium accretion rates and discussed the recurrence period of helium novae.Comment: 8 pages including 12 figures, to appear in Ap

Weak Disorder in Fibonacci Sequences

We study how weak disorder affects the growth of the Fibonacci series. We introduce a family of stochastic sequences that grow by the normal Fibonacci recursion with probability 1-epsilon, but follow a different recursion rule with a small probability epsilon. We focus on the weak disorder limit and obtain the Lyapunov exponent, that characterizes the typical growth of the sequence elements, using perturbation theory. The limiting distribution for the ratio of consecutive sequence elements is obtained as well. A number of variations to the basic Fibonacci recursion including shift, doubling, and copying are considered.Comment: 4 pages, 2 figure

Author Correction: Triple SILAC identified progestin-independent and dependent PRA and PRB interacting partners in breast cancer

The original version of this Data Descriptor omitted the following author from the Author List: Sarah Bajan. This error has now been corrected in both the PDF and HTML versions of the Article