Understanding how cell fate decisions are regulated is a fundamental goal of developmental and stem cell biology. Most studies on the control of cell fate decisions address the contributions of changes in transcriptional programming, epigenetic modifications, and biochemical differentiation cues. However, recent studies have found that other aspects of cell biology also make important contributions to regulating cell fate decisions. These cues can have a permissive or instructive role and are integrated into the larger network of signaling, functioning both upstream and downstream of developmental signaling pathways. Here, we summarize recent insights into how cell fate decisions are influenced by four aspects of cell biology: metabolism, reactive oxygen species (ROS), intracellular pH (pHi), and cell morphology. For each topic, we discuss how these cell biological cues interact with each other and with protein-based mechanisms for changing gene transcription. In addition, we highlight several questions that remain unanswered in these exciting and relatively new areas of the field.

Understanding how cell fate decisions are regulated is a fundamental goal of developmental and stem cell biology. Most studies on the control of cell fate decisions address the contributions of changes in transcriptional programming, epigenetic modifications, and biochemical differentiation cues. However, recent studies have found that other aspects of cell biology also make important contributions to regulating cell fate decisions. These cues can have a permissive or instructive role and are integrated into the larger network of signaling, functioning both upstream and downstream of developmental signaling pathways. Here, we summarize recent insights into how cell fate decisions are influenced by four aspects of cell biology: metabolism, reactive oxygen species (ROS), intracellular pH (pHi), and cell morphology. For each topic, we discuss how these cell biological cues interact with each other and with protein-based mechanisms for changing gene transcription. In addition, we highlight several questions that remain unanswered in these exciting and relatively new areas of the field.

Many lysosome functions are determined by a lumenal pH of ∼5.0, including the activity of resident acid-activated hydrolases. Lysosome pH (pHlys) is often increased in neurodegenerative disorders and predicted to be decreased in cancers, making it a potential target for therapeutics to limit the progression of these diseases. Accurately measuring pHlys, however, is limited by currently used dyes that accumulate in multiple intracellular compartments and cannot be propagated in clonal cells for longitudinal studies or used for in vivo determinations. To resolve this limitation, we developed a genetically encoded ratiometric pHlys biosensor, pHLARE (pH Lysosomal Activity REporter), which localizes predominantly in lysosomes, has a dynamic range of pH 4.0 to 6.5, and can be stably expressed in cells. Using pHLARE we show decreased pHlys with inhibiting activity of the mammalian target of rapamycin complex 1 (mTORC1). Also, cancer cells from different tissue origins have a lower pHlys than untransformed cells, and stably expressing oncogenic RasV12 in untransformed cells is sufficient to decrease pHlys. pHLARE is a new tool to accurately measure pHlys for improved understanding of lysosome dynamics, which is increasingly considered a therapeutic target.

A wide range of imaging and spectroscopy technologies is used in medical diagnostics, quality control in production systems, military applications, stress detection in agriculture, and ecological studies of both terrestrial and aquatic organisms. In this study, we hypothesized that reflectance profiling can be used to successfully classify animals that are otherwise very challenging to classify. We acquired hyperspectral images from adult specimens of the egg parasitoid genus Trichogramma (T. galloi, T. pretiosum and T. atopovirilia), which are ~1.0 mm in length. We also acquired hyperspectral images from host eggs containing developing Trichogramma instar and pupae. These obligate egg endoparasitoid species are commercially available as natural enemies of lepidopteran pests in food production systems. Because of their minute size and physical resemblance, classification is time consuming and requires a high level of technical experience. The classification of reflectance profiles was based on a combination of average reflectance and variogram parameters (describing the spatial structure of reflectance data) of reflectance values in individual spectral bands. Although variogram parameters (variogram analysis) are commonly used in large-scale spatial research (i.e. geoscience and landscape ecology), they have only recently been used in classification of high-resolution hyperspectral imaging data. The classification model of parasitized host eggs was equally successful for each of the three species and was successfully validated with independent data sets (>90% classification accuracy). The classification model of adult specimens accurately separated T. atopovirilia from the other two species, but specimens of T. galloi and T. pretiosum could not be accurately separated. Interestingly, molecular-based classification (using the DNA sequence of the internally transcribed spacer ITS2) of Trichogramma species published elsewhere corroborates the classification, as T. galloi and T. pretiosum are closely related and comparatively distant from T. atopovirilia. Our results emphasize the importance of using high-spectral and high-spatial resolution data in the classification of organism relatedness, and hyperspectral imaging may be of relevance to a wide range of commercial (i.e. producers of biocontrol agents), taxonomic and evolutionary research applications.

The role of distinct actin filament architectures in epithelial plasticity remains incompletely understood. We therefore determined roles for formins and the Arp2/3 complex, which are actin nucleators generating unbranched and branched actin filaments, respectively, in the process of epithelial to mesenchymal transition (EMT). In clonal lung, mammary, and renal epithelial cells, the formin activity inhibitor SMIFH2 but not the Arp2/3 complex activity inhibitor CK666 blocked EMT induced by TGF-β. SMIFH2 prevented the proximal signal of increased Smad2 phosphorylation and hence also blocked downstream EMT markers, including actin filament remodeling, decreased expression of the adherens junction protein E-cadherin, and increased expression of the matrix protein fibronectin and the transcription factor Snail. The short hairpin RNA silencing of formins DIAPH1 and DIAPH3 but not other formins phenocopied SMIFH2 effects and inhibited Smad2 phosphorylation and changes in Snail and cadherin expression. Formin activity was not necessary for the cell surface expression or dimerization of TGF-β receptors, or for nuclear translocation of TAZ, a transcription cofactor in Hippo signaling also regulated by TGF-β. Our findings reveal a previously unrecognized role for formin-dependent actin architectures in proximal TGF-β signaling that is necessary for Smad2 phosphorylation but not for cross-talk to TAZ.

© Published by the American Physical Society. Measurements of normalized differential cross sections for top-quark pair production are presented as a function of the top-quark transverse momentum, and of the mass, transverse momentum, and rapidity of the tt¯ system, in proton-proton collisions at a center-of-mass energy of s=7TeV. The data set corresponds to an integrated luminosity of 4.6fb-1, recorded in 2011 with the ATLAS detector at the CERN Large Hadron Collider. Events are selected in the lepton+jets channel, requiring exactly one lepton and at least four jets with at least one of the jets tagged as originating from a b-quark. The measured spectra are corrected for detector efficiency and resolution effects and are compared to several Monte Carlo simulations and theory calculations. The results are in fair agreement with the predictions in a wide kinematic range. Nevertheless, data distributions are softer than predicted for higher values of the mass of the tt¯ system and of the top-quark transverse momentum. The measurements can also discriminate among different sets of parton distribution functions.

© CERN for the benefit of the ATLAS collaboration. Ameasurement is presented of the φ×BR(φ → K⁺K⁻) production cross section at √s = 7 TeV using pp collision data corresponding to an integrated luminosity of 383 μb^-1, collected with theATLAS experiment at the LHC. Selection of φ(1020) mesons is based on the identification of charged kaons by their energy loss in the pixel detector. The differential cross section ismeasured as a function of the transverse momentum, pT,φ , and rapidity, yφ, of the φ(1020) meson in the fiducial region 500< pT,φ <1200MeV, |yφ| < 0.8, kaon pT,K > 230 MeV and kaon momentum pK < 800 MeV. The integrated φ(1020)-meson production cross section in this fiducial range is measured to be σφ×BR(φ → K⁺K⁻) = 570 ± 8 (stat) ± 66 (syst) ± 20 (lumi) μb.

© 2014 CERN, for the ATLAS Collaboration. An improved measurement of the mass of the Higgs boson is derived from a combined fit to the reconstructed invariant mass spectra of the decay channels H→γγ and H→ZZ∗→4. The analysis uses the pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at center-of-mass energies of 7 TeV and 8 TeV, corresponding to an integrated luminosity of 25fb-1. The measured value of the Higgs boson mass is mH=125.36±0.37(stat)±0.18(syst)GeV. This result is based on improved energy-scale calibrations for photons, electrons, and muons as well as other analysis improvements, and supersedes the previous result from ATLAS. Upper limits on the total width of the Higgs boson are derived from fits to the invariant mass spectra of the H→γγ and H→ZZ∗→4 decay channels.

This Letter presents a search for the Standard Model Higgs boson in the decay channel H→ZZ (*) →ℓ + ℓ - ℓ '+ ℓ '- , where ℓ, ℓ ' =e or μ, using proton-proton collisions at √s=7 TeV recorded with the ATLAS detector and corresponding to an integrated luminosity of 4.8 fb -1 . The four-lepton invariant mass distribution is compared with Standard Model background expectations to derive upper limits on the cross section of a Standard Model Higgs boson with a mass between 110 GeV and 600 GeV. The mass ranges 134-156 GeV, 182-233 GeV, 256-265 GeV and 268-415 GeV are excluded at the 95% confidence level. The largest upward deviations from the background-only hypothesis are observed for Higgs boson masses of 125 GeV, 244 GeV and 500 GeV with local significances of 2.1, 2.2 and 2.1 standard deviations, respectively. Once the look-elsewhere effect is considered, none of these excesses are significant. © 2012 CERN.