Intracranial V. cholerae Sialidase Protects against Excitotoxic Neurodegeneration

Converging evidence shows that GD3 ganglioside is a critical effector in a number of apoptotic pathways, and GM1 ganglioside has neuroprotective and noötropic properties. Targeted deletion of GD3 synthase (GD3S) eliminates GD3 and increases GM1 levels. Primary neurons from GD3S−/− mice are resistant to neurotoxicity induced by amyloid-β or hyperhomocysteinemia, and when GD3S is eliminated in the APP/PSEN1 double-transgenic model of Alzheimer's disease the plaque-associated oxidative stress and inflammatory response are absent. To date, no small-molecule inhibitor of GD3S exists. In the present study we used sialidase from Vibrio cholerae (VCS) to produce a brain ganglioside profile that approximates that of GD3S deletion. VCS hydrolyzes GD1a and complex b-series gangliosides to GM1, and the apoptogenic GD3 is degraded. VCS was infused by osmotic minipump into the dorsal third ventricle in mice over a 4-week period. Sensorimotor behaviors, anxiety, and cognition were unaffected in VCS-treated mice. To determine whether VCS was neuroprotective in vivo, we injected kainic acid on the 25th day of infusion to induce status epilepticus. Kainic acid induced a robust lesion of the CA3 hippocampal subfield in aCSF-treated controls. In contrast, all hippocampal regions in VCS-treated mice were largely intact. VCS did not protect against seizures. These results demonstrate that strategic degradation of complex gangliosides and GD3 can be used to achieve neuroprotection without adversely affecting behavior

Conservation efficiency and nutritive value of silages made from grass-red clover and multi-species swards compared with grass monocultures

peer reviewedBinary grass-clover and multi-species swards can increase herbage yields or facilitate reduced inputs of inorganic fertiliser nitrogen (N) compared with perennial ryegrass monocultures. However, the efficiency of the ensilage process and the nutritive value of silage produced from multi-species swards has not been documented. Replicate samples from grass-red clover binary mixture and multi-species mixture swards were ensiled in laboratory silos to assess the ensilability, fermentation characteristics, conservation losses and silage nutritive value compared with grass monocultures produced using inorganic N fertiliser. The results suggest that assessment of the ensilability and subsequent ensilage characteristics of binary and multi-species mixtures should be based on direct sampling from such mixtures rather than being predicted from values obtained from monocultures of constituent species. Under favourable ensiling conditions, unwilted binary mixtures and multi-species mixtures are satisfactorily preserved as silage, comparable to a perennial ryegrass monoculture receiving inorganic N fertiliser. However, when ensiled under more challenging crop conditions the mixtures exhibited a greater requirement for their preservation to be aided, compared with the perennial ryegrass monoculture. Despite the application of inorganic N reducing the legume content of multi-species mixture swards, it had relatively little effect on herbage ensilability or silage preservation. For all species treatments, silage nutritive values were primarily dependent on the pre-ensiling values, although herbage digestibility values declined during ensilage where the ensilage process was inefficient. The current study suggests that in order to be satisfactorily preserved as silage, binary grass-clover and multispecies swards have a greater requirement for an adequate rapid field wilt and/or effective preservative application compared with perennial ryegrass produced using inorganic fertiliser N

The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration

Apoptosis is a programmed cell death that plays a critical role during the development of the nervous system and in many chronic neurodegenerative diseases, including Alzheimer's disease (AD). This pathology, characterized by a progressive degeneration of cholinergic function resulting in a remarkable cognitive decline, is the most common form of dementia with high social and economic impact. Current therapies of AD are only symptomatic, therefore the need to elucidate the mechanisms underlying the onset and progression of the disease is surely needed in order to develop effective pharmacological therapies. Because of its pivotal role in neuronal cell death, apoptosis has been considered one of the most appealing therapeutic targets, however, due to the complexity of the molecular mechanisms involving the various triggering events and the many signaling cascades leading to cell death, a comprehensive understanding of this process is still lacking. Modular systems biology is a very effective strategy in organizing information about complex biological processes and deriving modular and mathematical models that greatly simplify the identification of key steps of a given process. This review aims at describing the main steps underlying the strategy of modular systems biology and briefly summarizes how this approach has been successfully applied for cell cycle studies. Moreover, after giving an overview of the many molecular mechanisms underlying apoptosis in AD, we present both a modular and a molecular model of neuronal apoptosis that suggest new insights on neuroprotection for this disease

Benefits of Condensed Tannins in Forage Legumes Fed to Ruminants: Importance of Structure, Concentration, and Diet Composition

Condensed tannins (CTs) account for up to 20% of the dry matter in forage legumes used as ruminant feeds. Beneficial animal responses to CTs have included improved growth, milk and wool production, fertility, and reduced methane emissions and ammonia volatilization from dung or urine. Most important is the ability of such forages to combat the effects of gastrointestinal parasitic nematodes. Inconsistent animal responses to CTs were initially attributed to concentration in the diet, but recent research has highlighted the importance of their molecular structures, as well as concentration, and also the composition of the diet containing the CTs. The importance of CT structural traits cannot be underestimated. Interdisciplinary research is the key to unraveling the relationships between CT traits and bioactivities and will enable future on-farm exploitation of these natural plant compounds. Research is also needed to provide plant breeders with guidelines and screening tools to optimize CT traits, in both the forage and the whole diet. In addition, improvements are needed in the competitiveness and agronomic traits of CT-containing legumes and our understanding of options for their inclusion in ruminant diets. Farmers need varieties that are competitive in mixed swards and have predictable bioactivities. This review covers recent results from multidisciplinary research on sainfoin (Onobrychis Mill. spp.) and provides an overview of current developments with several other tanniniferous forages. Tannin chemistry is now being linked with agronomy, plant breeding, animal nutrition, and parasitology. The past decade has yielded considerable progress but also generated more questions-an enviable consequence of new knowledge

Integrated Technological Solutions for Zero Waste Recycling of Printed Circuit Boards (PCBs)

Printed Circuit Boards (PCBs) are called “urban mineral resources” since 25%- 30% in weight of their composition is made of valuable metals and rare earths. PCBs recycling is a very challenging task that has not been solved yet from a technological and business model sustainability point of view. Most of the current approaches are based on the combination of thermal and chemical processes, which require considerable energy and generate negative environmental impacts. Moreover, currently many critical raw materials found in small concentrations in PCBs but in considerable concentrations in specific components are not recovered and usually end-up in the fraction going to landfill. To overcome these limitations, the “Zero Waste PCBs” project aims at developing a systemic solution integrating technological and business model innovations to achieve a more sustainable end- of-life treatment of PCBs. Automatic components disassembly and intelligent mechanical shredding and separation processes are integrated to achieve a high purity mixture of metal and non-metal fractions to be further treated by chemical recovery processes. Moreover, methods to re-use the non-metal fractions are investigated, under a zero-waste view. This paper presents the major intermediate results of the project and the application potentials of the methodological and technological innovations

Metabotropic glutamate receptors: A new target for the therapy of neurodegenerative disorders?

Metabotropic glutamate (mGlu) receptors are a large, heterogeneous family of G-protein coupled receptors, which modulate excitatory synaptic transmission through various transduction pathways. Evidence is now accumulating that individual mGlu-receptor subtypes mediate distinct, facilitatory (group I subtypes) or inhibitory (group II and group III subtypes), actions on neurodegenerative processes. Drugs interacting with mGlu receptors are expected to influence both the induction and progression of neuronal degeneration without hampering the efficiency of fast excitatory synaptic transmission. For these reasons, mGlu receptors can be considered as promising drug targets in the experimental therapy of acute or chronic neurodegenerative diseases