The comparative kinetic analysis of Acetocell and Lignoboost® lignin pyrolysis: the estimation of the distributed reactivity models

The non-isothermal pyrolysis kinetics of Acetocell (the organosolv) and Lignoboost? (kraft) lignins, in an inert atmosphere, have been studied by thermogravimetric analysis. Using isoconversional analysis, it was concluded that the apparent activation energy for all lignins strongly depends on conversion, showing that the pyrolysis of lignins is not a single chemical process. It was identified that the pyrolysis process of Acetocell and Lignoboost? lignin takes place over three reaction steps, which was confirmed by appearance of the corresponding isokinetic relationships (IKR). It was found that major pyrolysis stage of both lignins is characterized by stilbene pyrolysis reactions, which were subsequently followed by decomposition reactions of products derived from the stilbene pyrolytic process. It was concluded that non-isothermal pyrolysis of Acetocell and Lignoboost? lignins can be best described by n-th (n>1) reaction order kinetics, using the Weibull mixture model (as distributed reactivity model) with alternating shape parameters.     

Metformin protects against doxorubicin-induced cardiotoxicity: involvement of the adiponectin cardiac system

Doxorubicin has cardiotoxic effects that limit its clinical benefit in cancer patients. Metformin exerts cardioprotective actions via AMP-activated protein kinase (AMPK) and increases the expression of adiponectin and its receptors (adipoR1 and adipoR2) in skeletal muscle and adipose tissue, but its effect on cardiac tissue is still unknown. This work aimed to study whether metformin exerts any protective action against the cardiotoxicity of doxorubicin and whether the cardiac system of adiponectin is involved in any such action. The addition of doxorubicin (5μM) to adult mouse cardiomyocytes (HL-1 cell line) induced apoptosis, which was characterized by a loss of cell viability, activation of caspases, and fragmentation of the genetic material. Doxorubicin treatment also caused a decrease in the activity of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase. Pretreatment with metformin (4mM, 24h) provided protection against doxorubicin-induced damage. This pretreatment significantly increased cell viability, attenuated the activation of caspases and the fragmentation of genetic material, and restored the antioxidant activity. In addition, metformin up-regulated the expression of adiponectin and its receptors, adipoR1 and adipoR2, in cardiomyocytes. In contrast, silencing either adipoR1 or adipoR2 with siRNA inhibited the AMPK activation and the protective effects of metformin. Taken together, these results demonstrate that metformin protects cardiomyocytes from doxorubicin-induced damage and that the cardiac adiponectin system plays an important role in this protective action.     

The evolutionary genetics of emerging plant RNA viruses

Over the years, agriculture across the world has been compromised by a succession of devastating epidemics caused by new viruses that spilled over from reservoir species or by new variants of classic viruses that acquired new virulence factors or changed their epidemiological patterns. Viral emergence is usually associated with ecological change or with agronomical practices bringing together reservoirs and crop species. The complete picture is, however, much more complex, and results from an evolutionary process in which the main players are ecological factors, viruses' genetic plasticity, and host factors required for virus replication, all mixed with a good measure of stochasticity. The present review puts emergence of plant RNA viruses into the framework of evolutionary genetics, stressing that viral emergence begins with a stochastic process that involves the transmission of a preexisting viral strain into a new host species, followed by adaptation to the new host.     

Localization of aluminium in tea (Camellia sinensis) leaves using low energy X-ray fluorescence spectro-microscopy

Information on localization of Al in tea leaf tissues is required in order to better understand Al tolerance mechanism in this Al-accumulating plant species. Here, we have used low-energy X-ray fluorescence spectro-microscopy (LEXRF) to study localization of Al and other low Z-elements, namely C, O, Mg, Si and P, in fully developed leaves of the tea plant [Camellia sinensis (L.) O. Kuntze]. Plants were grown from seeds for 3?months in a hydroponic solution, and then exposed to 200?μM AlCl₃ for 2?weeks. Epidermal-mesophyll and xylem phloem regions of 20?μm thick cryo-fixed freeze-dried tea-leaf cross-sections were raster scanned with 1.7 and 2.2?keV excitation energies to reach the Al–K and P–K absorption edges. Al was mainly localized in the cell walls of the leaf epidermal cells, while almost no Al signal was obtained from the leaf symplast. The results suggest that the retention of Al in epidermal leaf apoplast represent the main tolerance mechanism to Al in tea plants. In addition LEXRF proved to be a powerful tool for localization of Al in plant tissues, which can help in our understanding of the processes of Al uptake, transport and tolerance in plants.     

Solid-phase treatment with the fungus Trametes versicolor substantially reduces pharmaceutical concentrations and toxicity from sewage sludge

For safe biosolid-land-applying, sludge should be contaminant-free. However, it may contain important amounts of micropollutants, not removed in the wastewater-treatment-processes. An alternative treatment with the fungus Trametes versicolor was applied in sterile solid-phase systems consisting of sludge and a lignocellulosic substrate. Fungal colonization and activity were demonstrated during the process, according to monitoring of ergosterol, laccase activity and the naproxen-degradation test (ND24). Fourteen out of 43 analyzed pharmaceuticals were found in the raw sludge. After treatment, phenazone, bezafibrate, fenofibrate, cimetidine, clarithromycin, sulfamethazine and atenolol were completely removed, while removals between 42% and 80% were obtained for the remaining pharmaceuticals. Toxicological analyses (Daphnia magna, Vibrio fischeri and seed germination) showed an important reduction in sludge toxicity after treatment. Results suggest that a solid-phase treatment with T. versicolor may reduce the ecotoxicological impact of micropollutants present in sewage sludge. This is the first report of a fungal-approach for elimination of emerging pollutants from biosolids.     

Abundance and functional roles of intrinsic disorder in allergenic proteins and allergen representative peptides

The pathological process of allergies generally involves an initial activation of certain immune cells, tied to an ensuing inflammatory reaction on renewed contact with the allergen. In IgE-mediated hypersensitivity, this typically occurs in response to otherwise harmless food- or air-borne proteins. As some members of certain protein families carry special properties that make them allergenic, exploring protein allergens at the molecular level is instrumental to an improved understanding of the disease mechanisms, including the identification of relevant antigen features. For this purpose, we inspected a previously identified set of allergen representative peptides (ARPs) to scrutinize protein intrinsic disorder. The resulting study presented here focused on the association between these ARPs and protein intrinsic disorder. In addition, the connection between the disorder-enriched ARPs and UniProt functional keywords was considered. Our analysis revealed that ～ 20% of the allergen peptides are highly disordered, and that ～ 77% of ARPs are either located within disordered regions of corresponding allergenic proteins or show more disorder/flexibility than their neighbor regions. Furthermore, among the subset of allergenic proteins, ～ 70% of the predicted molecular recognition features (MoRFs that consist of short interactive disordered regions undergoing disorder-to-order transitions at interaction with binding partners) were identified as ARPs. These results suggest that intrinsic disorder and MoRFs may play functional roles in IgE-mediated allergy.     

Methotrexate chronotherapy is effective against rheumatoid arthritis

Methotrexate (MTX) is the most important drug for treating rheumatoid arthritis (RA). It has been stated that cytokines play an important role in the pathogenesis of RA, and that cytokine levels increase and show 24-h rhythms in RA patients. Previously, we found that arthritis was relieved after the administration of MTX at specific times in synchronization with the 24-h rhythm of tumor necrosis factor (TNF)-α in collagen-induced arthritis (CIA) animals. Based on our findings in an earlier study of the dosing time-dependent effects of MTX in MRL/lpr mice, which develop autoimmune disorders that share similarities with human RA, we examined here the utility of MTX chronotherapy in Japanese RA patients. In an initial animal modeling study, we collected blood from MRL/lpr mice at different times (2, 6, 10, 14, 18, or 22 hours after the light was turned on [HALO]), and we measured TNF-α mRNA expression in leukocytes. MTX was administered to the mice at two different dosing times (6 or 18 HALO), and various blood parameters were measured to estimate arthritis activity. TNF-α mRNA levels showed a clear 24-h rhythm with a peak at 22 HALO and a trough at 18 HALO after RA had developed. In these MRL/lpr mice, inflammation and TNF-α were markedly reduced when the MTX dosing time was matched to the time (18 HALO) when the TNF-α level began to increase. We then applied these findings to Japanese RA patients by switching them from the standard MTX three times/wk (day 1: after breakfast and supper; day 2: after breakfast schedule), to chronotherapy, in which the dose and number of doses/wk were not changed but MTX was administered once-a-day at bedtime. Disease Activity Score (DAS)28, modified health assessment questionnaire (MHAQ), and adverse effects were assessed. With MTX chronotherapy, DAS28, which is commonly used to quantitatively assess RA symptoms, was significantly improved at all follow-up clinical visit times compared with the baseline (vs. 1 mo: p?=?.0197, 2 mos: p?=?.0107, 3 mos: p?=?.0087). Significant symptom recovery was observed in 41.2% of patients, and 23.5% of patients achieved clinical remission during the 3 mos of follow-up. Functional capacity of RA patients, as indicated by the MHAQ, was markedly improved by chronotherapy. There were no severe adverse effects. Thus, we demonstrated (i) inflammation and plasma TNF-α concentrations were significantly reduced in MRL/lpr mice treated with MTX at 18 HALO, the time when TNF-α mRNA level began to increase; and (ii) MTX bedtime chronotherapy was safe, markedly reduced disease activity, and improved the functional capacity of RA patients. The findings on RA patients show that bedtime MTX chronotherapy can improve RA symptoms compared to the current standard dosing methods.     

Homeostatic modulation of stimulation-dependent plasticity in human motor cortex

Since recently, it is possible, using noninvasive cortical stimulation, such as the protocol of paired associative stimulation (PAS), to induce the plastic changes in the motor cortex, in humans that mimic Hebb's model of learning. Application of TMS conjugated with peripheral electrical stimulation at strictly coherent temporal manner lead to convergence of inputs in the sensory-motor cortex, with the consequent synaptic potentiation or weakening, if applied repetitively. However, when optimal interstimulus interval (ISI) for induction of LTP-like effects is applied as a single pair, Motor evoked potential (MEP) amplitude inhibition is observed, the paradigm known as short-latency afferent inhibition (SLAI). Aiming to resolve this paradox, PAS protocols were applied, with 200 repetitions of TMS pulses paired with median nerve electrical stimulation, at ISI equal to individual latencies of evoked response of somatosensory cortex (N(20)) (PAS(LTP)), and at ISI of N(20) shortened for 5 msec (PAS(LTD)) - protocols that mimic LTP-like changes in the human motor cortex. MEP amplitudes before, during and after interventions were measured as an indicator based on output signals originating from the motor system. Post-intervention MEP amplitudes following the TMS protocols of PAS(LTP) and PAS(LTD) were facilitated and depressed, respectively, contrary to MEP amplitudes during intervention. During PAS(LTP) MEP amplitudes were significantly decreased in case of PAS(LTP), while in the case of PAS(LTD) an upward trend was observed. In conclusions, a possible explanation for the seemingly paradoxical effect of PAS can be found in the mechanism of homeostatic modulation of plasticity. Those findings indicate the existence of complex relationships in the development of plasticity induced by stimulation, depending on the level of the previous motor cortex excitability.     

Molecular imaging of brain lipid environment of lymphocytes in amyotrophic lateral sclerosis using magnetic resonance imaging and SECARS microscopy

This paper highlights some of the key technologies of using two innovative molecular imaging modalites, magnetic resonance imaging (MRI) and nonlinear optical microscopy, for imaging intravenously injected ultra small paramagnetic iron oxide nanoparticles cross linked with antibodies (CLUSPIO) in the amyotrophic lateral sclerosis (ALS) experimental model in vivo or ex vivo, respectively. Intensive efforts have been made in investigating the causes of abnormalities in lipid metabolism, monitored in some neurodegenerative disorders systems. It has been shown that an abnormal accumulation of some common lipids in motor nerve cells may play a critical role in the development of amyotrophic lateral sclerosis. The presented experiments were performed on brain specimens from the transgenic rat model expressing multiple copies of mutated (G93A) human SOD-1 gene, after CD4+ lymphocytes were magnetically labeled with i.v.i. CLUSPIO antibodies. In vivo MRI revealed marked signal intensity enhancements in specific pathological regions of the ALS rat brain as compared to the wild type. Surface-enhanced coherent anti-Stokes Raman scattering (SECARS) microscopy indicated cellular interactions based on lipids association to anti-CD4 CLUSPIO.