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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective motoneuron loss. Although the cause of ALS is unknown, oxidative stress, inflammation, and mitochondrial dysfunction have been identified as important components of its pathogenesis. Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) plays a central role in the regulation of mitochondrial metabolism and biogenesis via activation of transcription factors, such as nuclear respiratory factors 1 and 2 and mitochondrial transcription factor A (Tfam). Alterations in PGC-1α expression and function have previously been described in models of Huntington and Alzheimer diseases. Moreover, the protective effects of PGC-1α have been shown in animal models of ALS. Levels of PGC-1α correlate with the number of acetylcholine receptor clusters in muscle. This is of particular interest because neurodegeneration in ALS may be a dying-back process. We investigated mRNA and protein expressions of PGC-1α and PGC-1α-regulated factors in the spinal cord and muscle tissues of SOD1 ALS mice and in ALS patients. We detected significant alterations in mRNA expression of PGC-1α and downstream factors with their earliest occurrence in muscle tissue. Our data provide evidence for a role of PGC-1α in mitochondrial dysfunction both in the ALS mouse model and in human sporadic ALS that is probably most relevant in the skeletal muscle.

Detecting allelopathic inhibition of phytoplankton by submerged macrophytes in an ecologically meaningful way is not easy. Multiple-approach investigations from a laboratory scale to the ecosystem level have been recommended to overcome the shortcomings of individual methods. Whether results of different methods are qualitatively or quantitatively comparable has not yet been tested. Here, we compare the sensitivity of the green algae Desmodesmus subspicatus (Chodat) E. Hegewald et Ant. Schmidt and Stigeoclonium helveticum Vischer to the allelopathic effect of the submerged macrophyte Myriophyllum verticillatum L. The following three approaches were used: (i) coincubation of algae in dialysis membrane tubes in a lake inside and outside a M. verticillatum stand, (ii) coincubation of algae in dialysis membrane tubes in aquaria with and without M. verticillatum, and (iii) single additions of tannic acid (TA), an allelopathically active polyphenol present in this macrophyte, to the algae cultures. For each method, fluorescence-based (chl a, PSII activity) and particle-based (cell count, biovolume) parameters were compared after 48 h of incubation. Results revealed quantitative and qualitative differences between methods. Algae incubated in dialysis membrane tubes in aquaria showed a strong decrease in all parameters under the influence of macrophytes. In situ measurements were influenced by adverse growth conditions for the test algae and only detected significant reductions for biovolume. Single additions of TA induced a strong reduction of fluorescence-based parameters similar to aquarium results, but an increase in the cell count. Even the qualitative transfer of laboratory results to field conditions thus requires caution and a proper selection of parameters., (© 2011 Phycological Society of America.)

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder which is incurable to date. As there are many ongoing studies with therapeutic candidates, it is of major interest to develop biomarkers not only to facilitate early diagnosis but also as a monitoring tool to predict disease progression and to enable correct randomization of patients in clinical trials. Magnetic resonance imaging (MRI) has made substantial progress over the last three decades and is a practical, noninvasive method to gain insights into the pathology of the disease. Disease-specific MRI changes therefore represent potential biomarkers for ALS. In this paper we give an overview of structural and functional MRI alterations in ALS with the focus on task-free resting-state investigations to detect cortical network failures.

Nrf2 (nuclear erythroid 2-related factor 2) is a basic region leucine-zipper transcription factor which binds to the antioxidant response element (ARE) and thereby regulates the expression of a large battery of genes involved in the cellular antioxidant and anti-inflammatory defence as well as mitochondrial protection. As oxidative stress, inflammation and mitochondrial dysfunctions have been identified as important pathomechanisms in amyotrophic lateral sclerosis (ALS), this signaling cascade has gained interest both with respect to ALS pathogenesis and therapy. Nrf2 and Keap1 expressions are reduced in motor neurons in postmortem ALS tissue. Nrf2-activating compounds have shown therapeutic efficacy in the ALS mouse model and other neurodegenerative disease models. Alterations in Nrf2 and Keap1 expression and dysregulation of the Nrf2/ARE signalling program could contribute to the chronic motor neuron degeneration in ALS and other neurodegenerative diseases. Therefore, Nrf2 emerges as a key neuroprotective molecule in neurodegenerative diseases. Our recent studies strongly support that the Nrf2/ARE signalling pathway is an important mediator of neuroprotection and therefore represents a promising target for development of novel therapies against ALS, Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD).

Simple morphological assessment of conventional MRI used in routine neurological diagnostic work-up lacks sensitivity and specificity for amyotrophic lateral sclerosis (ALS). Quantitative analysis of routine MRI sequences might, however, be more suitable to reveal ALS-related pathological cerebral alterations. We investigated 10 ALS patients and 10 age- and sex-matched healthy controls by MRI. Brain maps of T2 relaxation time (T2), relative proton density (PD), and apparent diffusion coefficient (ADC) were obtained. Values of these parameters were measured in 22 selected brain regions, and compared among the patients and the controls by using paired t-test with Bonferroni corrected alpha level (= 0.002). In ALS patients, increased PD was found in the pyramidal tract, corpus callosum, and white and grey matter. T2 elongation was found at the genu of corpus callosum, and at the posterior limb of the internal capsule (ICP). ADC values showed a tendency towards an increase in patients, which was only significant at the ICP. PD therefore appeared to be the most sensitive parameter for the detection of degenerative changes not only in the motor system but also in extramotor brain regions.

Recent observations suggest that p53 mutations are responsible not only for growth of primary tumors but also for their dissemination. However, mechanisms involved in p53-mediated control of cell motility and invasion remain poorly understood. By using the primary ovarian surface epithelium cell culture, we show that conditional inactivation of p53 or expression of its mutant forms results in overexpression of MET receptor tyrosine kinase, a crucial regulator of invasive growth. At the same time, cells acquire increased MET-dependent motility and invasion. Wild-type p53 negatively regulates MET expression by two mechanisms: (i) transactivation of MET-targeting miR-34, and (ii) inhibition of SP1 binding to MET promoter. Both mechanisms are not functional in p53 absence, but mutant p53 proteins retain partial MET promoter suppression. Accordingly, MET overexpression, cell motility, and invasion are particularly high in p53-null cells. These results identify MET as a critical effector of p53 and suggest that inhibition of MET may be an effective antimetastatic approach to treat cancers with p53 mutations. These results also show that the extent of advanced cancer traits, such as invasion, may be determined by alterations in individual components of p53/MET regulatory network.

Posttransplantation lymphoproliferative disorder involving the central nervous system is a rare and serious complication associated with solid organ transplantation. We report a liver transplant recipient who noticed unbalance, dizziness, and headache 30 months after transplantation. Magnetic resonance imaging (MRI) showed a space-occupying lesion in the corpus callosum and adjacent parenchyma of the left hemisphere. In the following month, the neurological symptoms and the MRI findings regressed without any treatment. Four months later the patient developed a left-sided hemiparesis. MRI now revealed a considerable increase of the known lesion and new lesions in other locations. Stereotactic biopsy showed a B-cell non-Hodgkin lymphoma of high malignancy. A spontaneous regression of cerebral lymphoma is possible, even in immunosuppressed patients. Hence, this diagnosis must not be dismissed if there is spontaneous regression of a lesion in the MRI or an amelioration of the clinical symptoms. Owing to the high mortality rate associated with this disease, prompt pathologic diagnosis is required to initiate appropriate therapy.

Introduction: The potential linkage between upper (UMN) and lower motor neuron (LMN) involvement in amyotrophic lateral sclerosis (ALS) has not yet been fully elucidated. There is ongoing discussion as to whether ALS is primarily a disease of UMNs or LMNs., Methods: We performed a retrospective analysis of 189 ALS patients from our ALS outpatient database to investigate the different spreading patterns of UMN and LMN affection in disease progression in relation to the onset region., Results: The body region with the highest UMN involvement at onset in general also had the highest frequency of LMN signs and vice versa. This is in line with the hypothesis of a focal onset of disease, which then spreads to adjacent areas. However, there was a great variation between ALS phenotypes., Discussion: These observations support the hypothesis of focal damage of a localized group of motor neurons, which then spreads to adjacent motor neurons., (Copyright © 2010 Wiley Periodicals, Inc.)

Background and Aims: The genus Equisetum is cytologically uniform, having a base chromosome number of x = 108. All previously known species and hybrids that have been counted represent diploids with a sporophytic chromosome number of 2n = 216. Biosystematic studies on Equisetum subgenus Hippochaete revealed evidence that triploids occur in nature. The objective of this study was to confirm that triploid plants exist in the natural environment., Methods: Flow cytometry was used to establish nuclear DNA values and cytological investigations of meiosis were carried out to obtain information on chromosome number and pairing behaviour., Key Results: Triploidy exists in three morphologically different hybrid taxa. Two of these are morphologically intermediate between a primary diploid hybrid and a parent, while the third apparently combines genomes from all three Central European Hippochaete species. Nuclear 1C DNA values for the four European Hippochaete species range from 21.4-31.6 pg. For the hybrids, the 1C DNA values not only occupy the same range as the species, but their total DNA amounts agree closely with values predicted by adding the 1C DNA values of each parental genome. Chromosome counts confirm diploidy in the species E. hyemale and E. variegatum and in the hybrid E. xtrachyodon (= E. hyemale x E. variegatum). For the triploids (2n approximately 324), cytological information is presented for the first time., Conclusions: Triploid taxa may have originated by backcrossing or by crossing of a diploid hybrid with an unrelated diploid species. As tetraploid plants are unknown, these crossings probably involve diploid gametophytes that developed from unreduced diplospores. By repeated crossing events or backcrossing, reticulate evolution patterns arise that are similar to those known for a number of ferns and fern allies.

Duckweed species are promising macrophytes for use in sustainable wastewater treatment due to their rapid growth, ease of harvest, and feed potential as a protein source. This paper reviews growth rates of different duckweed species on wastewater and ammonia toxicity to duckweed and summarizes insights into the mechanism of organic matter and nutrient removal. Results were gained from laboratory experiments in small, shallow, duckweed-covered semicontinuous batch systems. Growth rates on different types of wastewater vary considerably among different species. Ammonia is toxic for duckweed in both the ionized and un-ionized forms. Duckweed, however, can be used to treat wastewater containing very high total ammonia concentrations as long as certain pH levels are not exceeded. The degradation of organic material is enhanced by duckweed through both additional oxygen supply and additional surface for bacterial growth. The duckweed mat with attached bacteria and algae is, independent of the loading rates, responsible for three-quarters of the total nitrogen (N) and phosphorus (P) loss in very shallow systems. Based on our results we suggest that full-scale pilot plants with duckweed should be shallower than the range encountered in the literature. A harvesting schedule that allows doubling times of 2 to 3.5 d, maintenance of a full coverage, and plug flow conditions are recommended.

Autocatalysis and chemical amplification are characteristic properties of living systems, and they give rise to behaviors such as increased sensitivity, responsiveness, and self-replication. Here we report a synthetic system in which a unique form of compartmentalization leads to nonlinear, autocatalytic behavior. The compartment is a reversibly formed capsule in which a reagent is sequestered. Reaction products displace the reagent from the capsule into solution and the reaction rate is accelerated. The resulting self-regulation is sensitive to the highly selective molecular recognition properties of the capsule.

Autocatalysis and chemical amplification are properties of living systems that can lead to increased responsiveness and to self-replication. Here we describe a synthetic system in which a unique form of reagent compartmentalization gives rise to nonlinear kinetics that are subject to the precise size- and shape-selectivity of the host. The reactivity is reminiscent of autocatalytic behaviour, in which there is no direct contact between reagents and products, and our approach offers a general way to impose complex chemical behaviour onto synthetic systems.

Macrophage-dependent antitumoral activity is partly mediated by soluble factors including cytokines, reactive-oxygen intermediates (ROIs), and reactive-nitrogen intermediates (RNIs). Activation of macrophages for tumor cytotoxicity can be achieved with various bacterial compounds, such as lipopolysaccharides (LPSs), muramyl-dipeptides, and lipopeptides. We studied the production and release of oxygen radicals, nitric oxide, and tumor necrosis factor alpha (TNF-alpha) by bone marrow-derived macrophages (BMDMs) of different mouse inbred strains after they were stimulated with the lipopeptide P3CSK4, a water-soluble synthetic analogue of the lipidated N terminus of bacterial lipoprotein. The lipopeptide was able to induce a strong, long lasting release of oxygen radicals in BALB/c mouse macrophages. Furthermore, it induced nitric oxide release from BMDMs of several mouse strains (BALB/c, C57Bl/6, C57Bl/10ScSn, Sv129, NMRI, and LPS-nonresponder C57Bl/10ScCr). Stimulation with P3CSK4 also resulted in comparable production of TNF-alpha in LPS-responder and nonresponder BMDMs from C57Bl/10ScSn mice and C57Bl/10ScCr mice, respectively. All three antitumoral mediators reached functional levels or concentrations as shown by the strong cytostatic/cytotoxic activity of lipopeptide-activated macrophages for the cell lines Abelson 8-1, M12.5/P815, and L929, which are sensitive to ROIs, nitric oxide, and TNF-alpha, respectively. We found that synthetic lipopeptides can induce the secretion of effective levels of soluble tumor-cytotoxic/cytostatic mediators in BMDMs of LPS-responsive and, of particular interest, also of LPS-unresponsive mice. This result could indicate that the highly effective bacterial-macrophage activators P3CSK4 and LPS use different receptors and/or different intracellular signal transduction pathways.

The synthesis and spectroscopic characterization of self-assembled cylindrical capsule 1a x 1a of nanometer dimensions is described. Encapsulation studies of large organic guest molecules were performed by using 1H NMR sprectroscopy in [D12]mesitylene solution. In addition to the computational (MacroModel 5.5, Amber* force field) analysis of the capsule's shape and geometry, an experimental approach towards estimation of the internal cavity dimensions is described. This involves using series of homologous molecular "rulers" (e.g. aromatic amides 5a-i). The available space inside the capsule 1a x 1a can be estimated as 5.7 x 14.7 A (error +/- 0.2 A) with this technique. Dibenzoyl peroxide is readily encapsulated in [D12]mesitylene and was shown to be stable to decomposition for at least three days at 70 degrees C inside the capsule. Moreover, 1a x 1a prevents the encapsulated peroxide from oxidizing Ph3P or diphenyl carbazide present in solution. The normal chemical reactivity of the peroxide is restored by release from the capsule by DMF, a solvent that competes for the hydrogen bonds that hold the capsule together. The protection and release of encapsulated species augurs well for the application of capsules in catalysis and delivery.

C-3'-nucleoside radicals can be generated via Norrish type I photocleavage of C-3'-acyl nucleoside derivatives. In monomer experiments employing C-3'-acylthymidine derivatives 2 and 3, a 1:1 mixture of isomers of the H-abstraction products was obtained when the photolysis was carried out in the presence of a hydrogen donor. Derivatives 2 were synthesized by an approach which involves the formation of a silyl-protected cyanohydrin, which is subsequently alkylated with organolithium reagents, followed by hydrolysis. Derivatives 3 could be obtained via a multistep synthesis starting from diol 7. Several different methods were attempted to oxidize the unprotected diol to the alpha-hydroxy aldehyde. Finally, a route was chosen which involves a protection-deprotection sequence followed by oxidation of the free primary alcohol. The resulting modified nucleosides should facilitate the study of C-3'-DNA radicals.

Aqueous extracts (ENOCW) and enzymatic digests of purified Nocardia opaca cell wall fragments, virtually free of muramyl peptides, were monitored for their phagocytic response modifying reactivity on polymorphonuclear leucocytes, separated or unseparated in whole human blood. In the presence of ENOCW a 74% increased production of superoxide during the respiratory burst of TPA-activated polymorphonuclear leukocytes was observed, as compared to the unprimed control. Delipidation of this preparation resulted in a further increase in reactivity (144%). Even in the presence of whole human blood, as a model for competitive binding in biological fluids, an enhanced generation of superoxide by TPA activated blood phagocytes remained detectable. A 37-75% decreased phagocytic reactivity in samples of HIV-seropositive blood was considerably restored in the presence of ENOCW.