Characterization of Cre recombinase models for the study of adipose tissue

The study of adipose tissue in vivo has been significantly advanced through the use of genetic mouse models. While the aP2-CreBI and aP2-CreSalk lines have been widely used to target adipose tissue, the specificity of these lines for adipocytes has recently been questioned. Here we characterize Cre recombinase activity in multiple cell populations of the major adipose tissue depots of these and other Cre lines using the membrane-Tomato/membrane-GFP (mT/mG) dual fluorescent reporter. We find that the aP2-CreBI and aP2-CreSalk lines lack specificity for adipocytes within adipose tissue, and that the aP2-CreBI line does not efficiently target adipocytes in white adipose depots. Alternatively, the Adiponectin-CreERT line shows high efficiency and specificity for adipocytes, while the PdgfRα-CreERUCL and PdgfRα-CreERJHU lines do not efficiently target adipocyte precursor cells in the major adipose depots. Instead, we show that the PdgfRα-Cre line is preferable for studies targeting adipocyte precursor cells in vivo

The effect of ecological harshness on perceptions of the ideal female body size: an experimental life history approach ☆ , ☆☆

Why do researchers regularly observe a relationship between ecological conditions and the heaviness of female body weight ideals? The current research uses insights from life history theory and female reproductive physiology to examine whether variability in female body ideals might emerge from the different life history strategies typically adopted by individuals living in harsh versus benign ecologies. Across three experiments, we demonstrate that women who were sensitized to faster life history strategies during childhood -as indexed by earlier menarche or lower childhood SES -respond to cues of ecological harshness by shifting away from the thin body weight typically favored by Western women toward a heavier female body ideal. Additionally, although men's perceptions of the ideal male body size did not shift in response to these cues, their perceptions of the ideal female body size did, with developmentally sensitized men also preferring a heavier female body size in the context of harsh ecologies

Histopathology of familial versus nonfamilial dilated cardiomyopathy

Idiopathic dilated cardiomyopathy is most likely a heterogenous group of diseases characterized by ventricular dilatation and dysfunction. Approximately 20% of patients with idiopathic dilated cardiomyopathy have familial disease, which may be inapparent by review of the family history alone. It has been suggested that histopathologic features, particularly the presence of bizarrely shaped mitochondria, may be useful in distinguishing familial from nonfamilial disease.We investigated 57 patients with dilated cardiomyopathy, 13 familial and 43nonfamilial or indeterminate. Pathologic examination of right endomyocardial biopsy specimens showed no significant differences between the familial, nonfamilial, or indeterminate groups by light microscopy or electron microscopy. We conclude that the distinction between familial and nonfamilial dilated cardiomyopathy cannot be made by histopathologic examination in most cases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30544/1/0000177.pd

First High-Speed Video Camera Observations of a Lightning Flash Associated With a Downward Terrestrial Gamma-Ray Flash

In this paper, we present the first high-speed video observation of a cloud-to-ground lightning flash and its associated downward-directed Terrestrial Gamma-ray Flash (TGF). The optical emission of the event was observed by a high-speed video camera running at 40,000 frames per second in conjunction with the Telescope Array Surface Detector, Lightning Mapping Array, interferometer, electric-field fast antenna, and the National Lightning Detection Network. The cloud-to-ground flash associated with the observed TGF was formed by a fast downward leader followed by a very intense return stroke peak current of −154 kA. The TGF occurred while the downward leader was below cloud base, and even when it was halfway in its propagation to ground. The suite of gamma-ray and lightning instruments, timing resolution, and source proximity offer us detailed information and therefore a unique look at the TGF phenomena

Observations of the Origin of Downward Terrestrial Gamma-Ray Flashes

In this paper we report the first close, high-resolution observations of downward-directed terrestrial gamma-ray flashes (TGFs) detected by the large-area Telescope Array cosmic ray observatory, obtained in conjunction with broadband VHF interferometer and fast electric field change measurements of the parent discharge. The results show that the TGFs occur during strong initial breakdown pulses (IBPs) in the first few milliseconds of negative cloud-to-ground and low-altitude intracloud flashes and that the IBPs are produced by a newly identified streamer-based discharge process called fast negative breakdown. The observations indicate the relativistic runaway electron avalanches (RREAs) responsible for producing the TGFs are initiated by embedded spark-like transient conducting events (TCEs) within the fast streamer system and potentially also by individual fast streamers themselves. The TCEs are inferred to be the cause of impulsive sub-pulses that are characteristic features of classic IBP sferics. Additional development of the avalanches would be facilitated by the enhanced electric field ahead of the advancing front of the fast negative breakdown. In addition to showing the nature of IBPs and their enigmatic sub-pulses, the observations also provide a possible explanation for the unsolved question of how the streamer to leader transition occurs during the initial negative breakdown, namely, as a result of strong currents flowing in the final stage of successive IBPs, extending backward through both the IBP itself and the negative streamer breakdown preceding the IBP

Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial

Background Cardiotoxicity is the most significant adverse event associated with trastuzumab (T), the main component of HER2-positive breast cancer (BC) treatment. Less is known about the cardiotoxicity of dual HER2 blockade with T plus lapatinib (L), although this regimen is used in the metastatic setting. Methods This is a sub-analysis of the ALTTO trial comparing adjuvant treatment options for patients with early HER2-positive BC. Patients randomised to either T or concomitant T + L were eligible. Cardiac events (CEs) rates were compared according to treatment arm. Results With 6.9 years of median follow-up (FU) and 4190 patients, CE were observed in 363 (8.6%): 166 (7.9%) of patient in T + L arm vs. 197 (9.3%) in T arm (OR = 0.85 [95% CI, 0.68-1.05]). During anti-HER2 treatment 270 CE (6.4%) occurred while 93 (2.2%) were during FU (median time to onset = 6.6 months [IQR = 3.4-11.7]). While 265 CEs were asymptomatic (73%), 94 were symptomatic (26%) and four were cardiac deaths (1%). Recovery was observed in 301 cases (83.8%). Identified cardiac risk factors were: baseline LVEF 64%, OR 3.1 [95% CI 1.54-6.25]), diabetes mellitus (OR 1.85 [95% CI 1.25-2.75]), BMI > 30 kg/m(2) (vs = 240 mg/m(2) (OR 1.36 [95% CI 1.01-1.82]) and of epirubicin >= 480 mg/m(2) (OR 2.33 [95% CI 1.55-3.51]). Conclusions Dual HER2 blockade with T + L is a safe regimen from a cardiac perspective, but cardiac-focused history for proper patient selection is crucial.Experimentele farmacotherapi

Multiple Molecular Mechanisms Cause Reproductive Isolation between Three Yeast Species

Incompatibility between nuclear and mitochondrial genomes in yeast species may represent a general mechanism of reproductive isolation during yeast evolution

RIG-I Is Required for the Inhibition of Measles Virus by Retinoids

Vitamin A can significantly decrease measles-associated morbidity and mortality. Vitamin A can inhibit the replication of measles virus (MeV) in vitro through an RARα- and type I interferon (IFN)-dependent mechanism. Retinoid-induced gene I (RIG-I) expression is induced by retinoids, activated by MeV RNA and is important for IFN signaling. We hypothesized that RIG-I is central to retinoid-mediated inhibition of MeV in vitro. We demonstrate that RIG-I expression is increased in cells treated with retinoids and infected with MeV. The central role of RIG-I in the retinoid-anti-MeV effect was demonstrated in the Huh-7/7.5 model; the latter cells having non-functional RIG-I. RAR-dependent retinoid signaling was required for the induction of RIG-I by retinoids and MeV. Retinoid signaling was also found to act in combination with IFN to induce high levels of RIG-I expression. RIG-I promoter activation required both retinoids and MeV, as indicated by markers of active chromatin. IRF-1 is known to be regulated by retinoids and MeV, but we found recruitment of IRF-1 to the RIG-I promoter by retinoids alone. Using luciferase expression constructs, we further demonstrated that the IRF-1 response element of RIG-I was required for RIG-I activation by retinoids or IFN. These results reveal that retinoid treatment and MeV infection induces significant RIG-I. RIG-I is required for the retinoid-MeV antiviral response. The induction is dependent on IFN, retinoids and IRF-1