Exploratory 7-Tesla magnetic resonance spectroscopy in Huntington’s disease provides in vivo evidence for impaired energy metabolism

Huntington’s disease (HD) is a neurodegenerative genetic disorder that affects the brain. Atrophy of deep grey matter structures has been reported and it is likely that underlying pathologic processes occur before, or in concurrence with, volumetric changes. Measurement of metabolite concentrations in these brain structures has the potential to provide insight into pathological processes. We aim to gain understanding of metabolite changes with respect to the disease stage and pathophysiological changes. We studied five brain regions using magnetic resonance spectroscopy (MRS) using a 7-Tesla MRI scanner. Localized proton spectra were acquired to obtain six metabolite concentrations. MRS was performed in the caudate nucleus, putamen, thalamus, hypothalamus, and frontal lobe in 44 control subjects, premanifest gene carriers and manifest HD. In the caudate nucleus, HD patients display lower NAA (p = 0.009) and lower creatine concentration (p = 0.001) as compared to controls. In the putamen, manifest HD patients show lower NAA (p = 0.024), lower creatine concentration (p = 0.027), and lower glutamate (p = 0.013). Although absolute values of NAA, creatine, and glutamate were lower, no significant differences to controls were found in the premanifest gene carriers. The lower concentrations of NAA and creatine in the caudate nucleus and putamen of early manifest HD suggest deficits in neuronal integrity and energy metabolism. The changes in glutamate could support the excitotoxicity theory. These findings not only give insight into neuropathological changes in HD but also indicate that MRS can possibly be applied in future clinical trails to evaluate medication targeted at specific metabolic processes

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

Soil solarization and sustainable agriculture

Pesticide treatments provide an effective control of soilborne pests in vegetable and fruit crops, but their toxicity to animals and people and residual toxicity in plants and soil, and high cost make their use hazardous and economically expensive. Moreover, actual environmental legislation is imposing severe restrictions on the use or the total withdrawal of most soil-applied pesticides. Therefore, an increasing emphasis has been placed on the use of nonchemical or pesticide-reduced control methods. Soil solarization is a nonpesticidal technique which kills a wide range of soil pathogens, nematodes, and weed seeds and seedlings through the high soil temperatures raised by placing plastic sheets on moist soil during periods of high ambient temperature. Direct thermal inactivation of target organisms was found to be the most important mechanism of solarization biocidal effect, contributed also by a heat-induced release of toxic volatile compounds and a shift of soil microflora to microorganisms antagonist of plant pathogens. Soil temperature and moisture are critical variables in solarization thermal effect, though the role of plastic film is also fundamental for the solarizing process, as it should increase soil temperature by allowing the passage of solar radiation while reducing energetic radiative and convective losses. Best solarizing properties were shown by low-density or vynilacetate- coextruded polyethylene formulations, but a wide range of plastic materials were documented as also suitable to soil solarization. Solar heating was normally reported to improve soil structure and increase soil content of soluble nutrients, particularly dissolved organic matter, inorganic nitrogen forms, and available cations, and shift composition and richness of soil microbial communities, with a marked increase of plant growth beneficial, plant pathogen antagonistic or root quick recolonizer microorganisms. As a consequence of these effects, soil solarization was largely documented to increase plant growth and crop yield and quality along more than two crop cycles. Most important fungal plant pathogenic species were found strongly suppressed by the solarizing treatment, as several studies documented an almost complete eradication of economically relevant pathogens, such as Fusarium spp., Phytophthora spp., Pythium spp., Sclerotium spp., Verticillium spp., and their related diseases in many vegetable and fruit crops and in different experimental conditions. Beneficial effects on fungal pathogens were stated to commonly last for about two growing seasons and also longer. Soil solarization demonstrated to be effective for the control of bacterial diseases caused by Agrobacterium spp., Clavibacter michiganensis and Erwinia amylovora, but failed to reduce incidence of tomato diseases caused by Pseudomonas solanacearum. Solarization was generally found less effective on phytoparasitic nematodes than on other organisms, due to their quicker soil recolonization compared to fungal pathogens and weeds, but field and greenhouse studies documented consistant reductions of root-knot severity and population densities of root-knot nematodes, Meloidogyne spp., as well as a satisfactory control of cyst-nematode species, such as Globodera rostochiensis and Heterodera carotae, and bulb nematode Ditylenchus dipsaci. Weeds were variously affected by solar heating, as annual species were generally found almost completely suppressed and perennial species more difficult to control, due to the occurrence deep propagules not exposed to lethal temperature. Residual effect of solarization on weeds was found much more pronounced than on nematodes and most fungal pathogens. Soil solarization may be perfect fit for all situations in which use of pesticides is restricted or completely banned, such as in organic production, or in farms located next to urban areas, or specialty crops with few labeled pesticides. Advantages of solarization also include economic convenience, as demonstrated by many comparative benefit/cost analyses, ease of use by growers, adaptability to many cropping systems, and a full integration with other control tools, which makes this technique perfectly compatible with principles of integrated pest management required by sustainable agriculture