The incredible ULKs

Macroautophagy (commonly abbreviated as autophagy) is an evolutionary conserved lysosome-directed vesicular trafficking pathway in eukaryotic cells that mediates the lysosomal degradation of intracellular components. The cytoplasmic cargo is initially enclosed by a specific double membrane vesicle, termed the autophagosome. By this means, autophagy either helps to remove damaged organelles, long-lived proteins and protein aggregates, or serves as a recycling mechanism for molecular building blocks. Autophagy was once invented by unicellular organisms to compensate the fluctuating external supply of nutrients. In higher eukaryotes, it is strongly enhanced under various stress conditions, such as nutrient and growth factor deprivation or DNA damage. The serine/threonine kinase Atg1 was the first identified autophagy-related gene (ATG) product in yeast. The corresponding nematode homolog UNC-51, however, has additional neuronal functions. Vertebrate genomes finally encode five closely related kinases, of which UNC-51-like kinase 1 (Ulk1) and Ulk2 are both involved in the regulation of autophagy and further neuron-specific vesicular trafficking processes. This review will mainly focus on the vertebrate Ulk1/2-Atg13-FIP200 protein complex, its function in autophagy initiation, its evolutionary descent from the yeast Atg1-Atg13-Atg17 complex, as well as the additional non-autophagic functions of its components. Since the rapid nutrient- and stress-dependent cellular responses are mainly mediated by serine/threonine phosphorylation, it will summarize our current knowledge about the relevant upstream signaling pathways and the altering phosphorylation status within this complex during autophagy induction

Level density and gamma strength function in 162-Dy from inelastic 3-He scattering

Complementary measurements have been performed for the level density and gamma strength function in 162-Dy using inelastic 3-He scattering. Comparing these results to previous measurements using the 163-Dy(3-He,alpha) reaction, reveals that the measured quantities above 1.5 MeV do not depend significantly on the nuclear reaction chosen.Comment: 15 pages, including 7 figure

Level density and thermal properties in rare earth nuclei

A convergent method to extract the nuclear level density and the gamma-ray strength function from primary gamma-ray spectra has been established. Thermodynamical quantities have been obtained within the microcanonical and canonical ensemble theory. Structures in the caloric curve and in the heat capacity curve are interpreted as fingerprints of breaking of Cooper pairs and quenching of pairing correlations. The strength function can be described using models and common parameterizations for the E1, M1 and pygmy resonance strength. However, a significant decrease of the pygmy resonance strength at finite temperatures has been observed.Comment: 15 pages including 8 figures. Proceedings article for the conference Nuclear Structure and Related Topics, Dubna, Russia, June 6-10, 200

Magnetic Dipole Sum Rules for Odd-Mass Nuclei

Sum rules for the total- and scissors-mode M1 strength in odd-A nuclei are derived within the single-j interacting boson-fermion model. We discuss the physical content and geometric interpretation of these sum rules and apply them to ^{167}Er and ^{161}Dy. We find consistency with the former measurements but not with the latter.Comment: 13 pages, Revtex, 1 figure, Phys. Rev. Lett. in pres

The mycotoxin phomoxanthone A disturbs the form and function of the inner mitochondrial membrane.

Mitochondria are cellular organelles with crucial functions in the generation and distribution of ATP, the buffering of cytosolic Ca2+ and the initiation of apoptosis. Compounds that interfere with these functions are termed mitochondrial toxins, many of which are derived from microbes, such as antimycin A, oligomycin A, and ionomycin. Here, we identify the mycotoxin phomoxanthone A (PXA), derived from the endophytic fungus Phomopsis longicolla, as a mitochondrial toxin. We show that PXA elicits a strong release of Ca2+ from the mitochondria but not from the ER. In addition, PXA depolarises the mitochondria similarly to protonophoric uncouplers such as CCCP, yet unlike these, it does not increase but rather inhibits cellular respiration and electron transport chain activity. The respiration-dependent mitochondrial network structure rapidly collapses into fragments upon PXA treatment. Surprisingly, this fragmentation is independent from the canonical mitochondrial fission and fusion mediators DRP1 and OPA1, and exclusively affects the inner mitochondrial membrane, leading to cristae disruption, release of pro-apoptotic proteins, and apoptosis. Taken together, our results suggest that PXA is a mitochondrial toxin with a novel mode of action that might prove a useful tool for the study of mitochondrial ion homoeostasis and membrane dynamics

Orbital M1 versus E2 strength in deformed nuclei: A new energy weighted sum rule

Within the unified model of Bohr and Mottelson we derive the following linear energy weighted sum rule for low energy orbital 1$^+$ excitations in even-even deformed nuclei S_{\rm LE}^{\rm lew} (M_1^{\rm orb}) \cong (6/5) \epsilon (B(E2; 0^+_1 \rightarrow 2_1^+ K=0)/Z e^2^2) \mu^2_N with B(E2) the E2 strength for the transition from the ground state to the first excited state in the ground state rotational band, $$ the charge r.m.s. radius squared and $\epsilon$ the binding energy per nucleon in the nuclear ground state. It is shown that this energy weighted sum rule is in good agreement with available experimental data. The sum rule is derived using a simple ansatz for the intrinsic ground state wave function that predicts also high energy 1$^+$ strength at 2$\hbar \omega$ carrying 50\% of the total $m_1$ moment of the orbital M1 operator.Comment: REVTEX (3.0), 9 pages, RU924

Extended M1 sum rule for excited symmetric and mixed-symmetry states in nuclei

A generalized M1 sum rule for orbital magnetic dipole strength from excited symmetric states to mixed-symmetry states is considered within the proton-neutron interacting boson model of even-even nuclei. Analytic expressions for the dominant terms in the B(M1) transition rates from the first and second $2^+$ states are derived in the U(5) and SO(6) dynamic symmetry limits of the model, and the applicability of a sum rule approach is examined at and in-between these limits. Lastly, the sum rule is applied to the new data on mixed-symmetry states of 94Mo and a quadrupole d-boson ratio $nd(0^+_1)/nd(2^+_2) \approx 0.6$ is obtained in a largely parameter-independent wayComment: 19 pages, 3 figures, Revte

Induction of DNA breaks and apoptosis in crosslink-hypersensitive V79 cells by the cytostatic drug β-D-glucosyl-ifosfamide mustard

To study molecular aspects of cytotoxicity of the anticancer drug β-D-glucose-ifosfamide mustard we investigated the potential of the agent to induce apoptosis and DNA breakage. Since β-D-glucose-ifosfamide mustard generates DNA interstrand crosslinks, we used as an in vitro model system a pair of isogenic Chinese hamster V79 cells differing in their sensitivity to crosslinking agents. CL-V5B cells are dramatically more sensitive (30-fold based on D10 values) to the cytotoxic effects of β-D-glucose-ifosfamide mustard as compared to parental V79B cells. After 48 h of pulse-treatment with the agent, sensitive cells but not the resistant parental line undergo apoptosis and necrosis, with apoptosis being the predominant form of cell death (70 and 20% of apoptosis and necrosis, respectively). Apoptosis increased as a function of dose and was accompanied by induction of DNA double-strand breaks in the hypersensitive cells. Furthermore, a strong decline in the level of Bcl-2 protein and activation of caspases-3, -8 and -9 were observed. The resistant parental cells were refractory to all these parameters. Bcl-2 decline in the sensitive cells preceded apoptosis, and transfection-mediated overexpression of Bcl-2 protected at least in part from apoptosis. From the data we hypothesize that non-repaired crosslinks induced by β-D-glucose-ifosfamide mustard are transformed into double-strand breaks which trigger apoptosis via a Bcl-2 dependent pathway

Photoexcitation of low-lying dipole transitions in 236U

Nuclear resonance fluorescence experiments have been performed on the deformed actinide nucleus 236U. Bremsstrahlung of 3.9 MeV endpoint energy has been used as the photon source. The scattered photons were detected by three high resolution Ge- gamma -spectrometers installed at scattering angles of 92°, 128°, and 150°, respectively. Precise excitation energies, decay branching ratios, and ground state decay widths of numerous previously unknown spin 1 states in the excitation energy range 1.8-3.2 MeV have been extracted. The dipole strength has been found to be concentrated in the energy range 2.1-2.5 MeV. The systematics of the so-called scissors mode observed as a result of the previous ( gamma , gamma ') and (e,e') experiments on 232Th and 238U and, in particular, their combined analysis suggests likewise to attribute these new dipole excitations in 236U to the orbital M1 scissors mode