Altered cell cycle regulation helps stem-like carcinoma cells resist apoptosis

Reemergence of carcinomas following chemotherapy and/or radiotherapy is not well understood, but a recent study in BMC Cancer suggests that resistance to apoptosis resulting from altered cell cycle regulation is crucial

Transport properties of one-dimensional interacting fermions in aperiodic potentials

Motivated by the existence of metal-insulator transition in one-dimensional non-interacting fermions in quasiperiodic and pseudorandom potentials, we studied interacting spinless fermion models using exact many-body Lanczos diagonalization techniques. Our main focus was to understand the effect of the fermion-fermion interaction on the transport properties of aperiodic systems. We calculated the ground state energy and the Kohn charge stiffness Dc. Our numerical results indicate that there exists a region in the interaction strength parameter space where the system may behave differently from the metallic and insulating phases. This intermediate phase may be characterized by a power law scaling of the charge stiffness constant in contrast to the localized phase where Dc scales exponentially with the size of the system.Comment: 11 pages LaTex document with 5 eps figures. Uses revtex style file

Connecdenn, a novel DENN domain-containing protein of neuronal clathrin-coated vesicles functioning in synaptic vesicle endocytosis

Clathrin-coated vesicles (CCVs) are responsible for the endocytosis of multiple cargo, including synaptic vesicle membranes. We now describe a new CCV protein, termed connecdenn, that contains an N-terminal DENN (differentially expressed in neoplastic versus normal cells) domain, a poorly characterized protein module found in multiple proteins of unrelated function and a C-terminal peptide motif domain harboring three distinct motifs for binding the α-ear of the clathrin adaptor protein 2 (AP-2). Connecdenn coimmunoprecipitates and partially colocalizes with AP-2, and nuclear magnetic resonance and peptide competition studies reveal that all three α-ear-binding motifs contribute to AP-2 interactions. In addition, connecdenn contains multiple Src homology 3 (SH3) domain-binding motifs and coimmunoprecipitates with the synaptic SH3 domain proteins intersectin and endophilin A1. Interestingly, connecdenn is enriched on neuronal CCVs and is present in the presynaptic compartment of neurons. Moreover, connecdenn has a uniquely stable association with CCV membranes because it resists extraction with Tris and high-salt buffers, unlike most other CCV proteins, but it is not detected on purified synaptic vesicles. Together, these observations suggest that connecdenn functions on the endocytic limb of the synaptic vesicle cycle. Accordingly, disruption of connecdenn interactions with its binding partners through overexpression of the C-terminal peptide motif domain or knock down of connecdenn through lentiviral delivery of small hairpin RNA both lead to defects in synaptic vesicle endocytosis in cultured hippocampal neurons. Thus, we identified connecdenn as a component of the endocytic machinery functioning in synaptic vesicle endocytosis, providing the first evidence of a role for a DENN domain-containing protein in endocytosis

Wave-packet dynamics in slowly perturbed crystals: Gradient corrections and Berry-phase effects

We present a unified theory for wave-packet dynamics of electrons in crystals subject to perturbations varying slowly in space and time. We derive the wave-packet energy up to the first order gradient correction and obtain all kinds of Berry-phase terms for the semiclassical dynamics and the quantization rule. For electromagnetic perturbations, we recover the orbital magnetization energy and the anomalous velocity purely within a single-band picture without invoking inter-band couplings. For deformations in crystals, besides a deformation potential, we obtain a Berry-phase term in the Lagrangian due to lattice tracking, which gives rise to new terms in the expressions for the wave-packet velocity and the semiclassical force. For multiple-valued displacement fields surrounding dislocations, this term manifests as a Berry phase, which we show to be proportional to the Burgers vector around each dislocation.Comment: 12 pages, RevTe

The Circumnuclear Star-forming Activities along the Hubble Sequence

In order to study the circumnuclear star-forming activity along the Hubble sequence, we cross-correlate the Sloan Digital Sky Survey Data Release 2 (SDSS DR2) with the Third Reference Catalog of Bright Galaxies (RC3) to derive a large sample of 1015 galaxies with both morphological and spectral information. Among these, 385 sources are classified as star-forming galaxies and the SDSS fibre covered the circumnuclear regions (0.2 $-$ 2.0 kpc). By using the spectral synthesis method to remove the contribution from the underlying old stellar population, we measure the emission lines fluxes accurately which are then used to estimate the star formation rates(SFRs). Our main findings are that: (1) Early-type spirals show much larger H$\alpha$ luminosities and hence higher SFRs, they also suffer more extinctions than late-type ones. The equivalent widths (EWs) of H$\alpha$ emission lines show the similar trend, however, the very late types (Sdm $\sim$ Irr) do have large fractions of high EWs. (2) We confirm that D$_n(4000)$ has strong correlation with the strengthes of metallic absorption lines (such as CN band, G band and Mg Ib). Both these lines and the Balmer absorption lines show interesting variations between Sbc to Sd type galaxies. (3) The bar structure tightly relates with the enhanced star forming activity, this effect is even more significant in the early-type spirals. But we should note that the bar structure is not a necessary or sufficient condition for galaxies to harbor circumnuclear star formations.Comment: 14 pages, 15 figures, accepted for publication in A&

Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via heterodimerization with GPR103

Orexins are neuropeptides that regulate the sleep-wake cycle and feeding behaviour. QRFP is a newly discovered neuropeptide which exerts similar orexigenic activity, thus playing an important role in energy homeostasis and regulation of appetite. The exact expression and signalling characteristics and physiological actions of QRFP and its receptor GPR103 are poorly understood. Alzheimerâ €™ s disease (AD) patients experience increased nocturnal activity, excessive daytime sleepiness, and weight loss. We hypothesised therefore that orexins and QRFP might be implicated in the pathophysiology of AD. We report that the down-regulation of hippocampal orexin receptors (OXRs) and GPR103 particularly in the cornu ammonis (CA) subfield from AD patients suffering from early onset familial AD (EOFAD) and late onset familial AD (LOAD). Using an in vitro model we demonstrate that this downregulation is due to to Aβ-plaque formation and tau hyper-phosphorylation. Transcriptomics revealed a neuroprotective role for both orexins and QRFP. Finally we provide conclusive evidence using BRET and FRET that OXRs and GPR103 form functional hetero-dimers to exert their effects involving activation of ERK 1/2. Pharmacological intervention directed at the orexigenic system may prove to be an attractive avenue towards the discovery of novel therapeutics for diseases such as AD and improving neuroprotective signalling pathways

Effects of the field modulation on the Hofstadter's spectrum

We study the effect of spatially modulated magnetic fields on the energy spectrum of a two-dimensional (2D) Bloch electron. Taking into account four kinds of modulated fields and using the method of direct diagonalization of the Hamiltonian matrix, we calculate energy spectra with varying system parameters (i.e., the kind of the modulation, the relative strength of the modulated field to the uniform background field, and the period of the modulation) to elucidate that the energy band structure sensitively depends on such parameters: Inclusion of spatially modulated fields into a uniform field leads occurrence of gap opening, gap closing, band crossing, and band broadening, resulting distinctive energy band structure from the Hofstadter's spectrum. We also discuss the effect of the field modulation on the symmetries appeared in the Hofstadter's spectrum in detail.Comment: 7 pages (in two-column), 10 figures (including 2 tables

Fluorescence Lifetime Imaging Unravels C. trachomatis Metabolism and Its Crosstalk with the Host Cell

Chlamydia trachomatis is an obligate intracellular bacterium that alternates between two metabolically different developmental forms. We performed fluorescence lifetime imaging (FLIM) of the metabolic coenzymes, reduced nicotinamide adenine dinucleotides [NAD(P)H], by two-photon microscopy for separate analysis of host and pathogen metabolism during intracellular chlamydial infections. NAD(P)H autofluorescence was detected inside the chlamydial inclusion and showed enhanced signal intensity on the inclusion membrane as demonstrated by the co-localization with the 14-3-3β host cell protein. An increase of the fluorescence lifetime of protein-bound NAD(P)H [τ2-NAD(P)H] inside the chlamydial inclusion strongly correlated with enhanced metabolic activity of chlamydial reticulate bodies during the mid-phase of infection. Inhibition of host cell metabolism that resulted in aberrant intracellular chlamydial inclusion morphology completely abrogated the τ2-NAD(P)H increase inside the chlamydial inclusion. τ2-NAD(P)H also decreased inside chlamydial inclusions when the cells were treated with IFNγ reflecting the reduced metabolism of persistent chlamydiae. Furthermore, a significant increase in τ2-NAD(P)H and a decrease in the relative amount of free NAD(P)H inside the host cell nucleus indicated cellular starvation during intracellular chlamydial infection. Using FLIM analysis by two-photon microscopy we could visualize for the first time metabolic pathogen-host interactions during intracellular Chlamydia trachomatis infections with high spatial and temporal resolution in living cells. Our findings suggest that intracellular chlamydial metabolism is directly linked to cellular NAD(P)H signaling pathways that are involved in host cell survival and longevity

Seizure Clusters, Seizure Severity Markers, and SUDEP Risk.

Rationale: Seizure clusters may be related to Sudden Unexpected Death in Epilepsy (SUDEP). Two or more generalized convulsive seizures (GCS) were captured during video electroencephalography in 7/11 (64%) patients with monitored SUDEP in the MORTEMUS study. It follows that seizure clusters may be associated with epilepsy severity and possibly with SUDEP risk. We aimed to determine if electroclinical seizure features worsen from seizure to seizure within a cluster and possible associations between GCS clusters, markers of seizure severity, and SUDEP risk. Methods: Patients were consecutive, prospectively consented participants with drug-resistant epilepsy from a multi-center study. Seizure clusters were defined as two or more GCS in a 24-h period during the recording of prolonged video-electroencephalography in the Epilepsy monitoring unit (EMU). We measured heart rate variability (HRV), pulse oximetry, plethysmography, postictal generalized electroencephalographic suppression (PGES), and electroencephalography (EEG) recovery duration. A linear mixed effects model was used to study the difference between the first and subsequent seizures, with a level of significance set at p < 0.05. Results: We identified 112 GCS clusters in 105 patients with 285 seizures. GCS lasted on average 48.7 ± 19 s (mean 49, range 2-137). PGES emerged in 184 (64.6%) seizures and postconvulsive central apnea (PCCA) was present in 38 (13.3%) seizures. Changes in seizure features from seizure to seizure such as seizure and convulsive phase durations appeared random. In grouped analysis, some seizure features underwent significant deterioration, whereas others improved. Clonic phase and postconvulsive central apnea (PCCA) were significantly shorter in the fourth seizure compared to the first. By contrast, duration of decerebrate posturing and ictal central apnea were longer. Four SUDEP cases in the cluster cohort were reported on follow-up. Conclusion: Seizure clusters show variable changes from seizure to seizure. Although clusters may reflect epilepsy severity, they alone may be unrelated to SUDEP risk. We suggest a stochastic nature to SUDEP occurrence, where seizure clusters may be more likely to contribute to SUDEP if an underlying progressive tendency toward SUDEP has matured toward a critical SUDEP threshold