The role of environmental factors in insulin-dependent diabetes mellitus: an unresolved issue.

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by the destruction of the insulin-secreting beta cells found in the islets of Langerhans. Reduced beta-cell mass results in overt diabetes, requiring lifelong exogenous insulin administration and the possibility of numerous sequelae. Incidence and development of IDDM depend upon a variety of genetic and nongenetic factors. Environmental factors such as chemicals, diet, and infection are suspected to influence the development of disease. This review describes the work performed to date to elucidate the role of these environmental factors in IDDM

Self-referenced characterization of space-time couplings in near single-cycle laser pulses

We report on the characterization of space-time couplings in high energy sub-2-cycle 770nm laser pulses using a self-referencing single-shot method. Using spatially-encoded arrangement filter-based spectral phase interferometry for direct electric field reconstruction (SEA-F-SPIDER) we characterize few-cycle pulses with a wave-front rotation of 2.8x?10^11 rev/sec (1.38 mrad per half-cycle) and pulses with pulse front tilts ranging from to -0.33 fs/um to -3.03 fs/um.Comment: 6 pages, 6 figure

Powdery mildew responsive genes of resistant grapevine cultivar 'Regent'

The ascomycete Erysiphe necator causes powdery mildew disease of grapevine, a disastrous infection which is commonly defeated with multiple fungicide applications in viticulture. Breeding for natural resistance of quality grapes (Vitis vinifera) is thus a major aim of current efforts. The cultivar 'Regent' is resistant to powdery mildew due to an introgression from an American Vitis sp. resistance donor. To identify key regulatory elements in defense responses of 'Regent' we performed transcript analyses after challenging with E. necator inoculation in comparison with a susceptible grapevine. A set of genes selected from preliminary microarray hybridization results were investigated by RT-qPCR. The data indicate an important role of transcription factors MYB15, WRKY75, WRKY33, WRKY7, ethylene responsive transcription factors ERF2 and ERF5 as well as a CZF1/ZFAR transcripton factor in regulating the early defense when the fungus starts the interaction with its host by the formation of haustoria

Direct characterisation of tuneable few-femtosecond dispersive-wave pulses in the deep UV

Dispersive wave emission (DWE) in gas-filled hollow-core dielectric waveguides is a promising source of tuneable coherent and broadband radiation, but so far the generation of few-femtosecond pulses using this technique has not been demonstrated. Using in-vacuum frequency-resolved optical gating, we directly characterise tuneable 3fs pulses in the deep ultraviolet generated via DWE. Through numerical simulations, we identify that the use of a pressure gradient in the waveguide is critical for the generation of short pulses.Comment: 5 pages, 4 figure

Optimisation of Quantum Trajectories Driven by Strong-field Waveforms

Quasi-free field-driven electron trajectories are a key element of strong-field dynamics. Upon recollision with the parent ion, the energy transferred from the field to the electron may be released as attosecond duration XUV emission in the process of high harmonic generation (HHG). The conventional sinusoidal driver fields set limitations on the maximum value of this energy transfer, and it has been predicted that this limit can be significantly exceeded by an appropriately ramped-up cycleshape. Here, we present an experimental realization of such cycle-shaped waveforms and demonstrate control of the HHG process on the single-atom quantum level via attosecond steering of the electron trajectories. With our optimized optical cycles, we boost the field-ionization launching the electron trajectories, increase the subsequent field-to-electron energy transfer, and reduce the trajectory duration. We demonstrate, in realistic experimental conditions, two orders of magnitude enhancement of the generated XUV flux together with an increased spectral cutoff. This application, which is only one example of what can be achieved with cycle-shaped high-field light-waves, has farreaching implications for attosecond spectroscopy and molecular self-probing

β-cell-specific IL-35 therapy suppresses ongoing autoimmune diabetes in NOD mice

IL-35 is a recently identified cytokine exhibiting potent immunosuppressive properties. The therapeutic potential and effects of IL-35 on pathogenic T effector (Teff) cells and Foxp3+ Treg cells, however, are ill-defined. We tested the capacity of IL-35 to suppress ongoing autoimmunity in NOD mice. For this purpose, an adeno-associated virus vector in which IL-35 transgene expression is selectively targeted to β cells via an insulin promoter (AAV8mIP-IL35) was used. AAV8mIP-IL35 vaccination of NOD mice at a late preclinical stage of type 1 diabetes (T1D) suppressed β-cell autoimmunity and prevented diabetes onset. Numbers of islet-resident conventional CD4+ and CD8+ T cells, and DCs were reduced within 4 weeks of AAV8mIP-IL35 treatment. The diminished islet T-cell pool correlated with suppressed proliferation, and a decreased frequency of IFN-γ-expressing Teff cells. Ectopic IL-35 also reduced islet Foxp3+ Treg-cell numbers and proliferation, and protection was independent of induction/expansion of adaptive islet immunoregulatory T cells. These findings demonstrate that IL-35-mediated suppression is sufficiently robust to block established β-cell autoimmunity, and support the use of IL-35 to treat T1D and other T-cell-mediated autoimmune diseases

T-Cell Promiscuity in Autoimmune Diabetes

OBJECTIVE—It is well established that the primary mediators of β-cell destruction in type 1 diabetes are T-cells. Nevertheless, the molecular basis for recognition of β-cell–specific epitopes by pathogenic T-cells remains ill defined; we seek to further explore this issue