In vivo nematicidal potential of camel milk on Heligmosomoides polygyrus gastro-intestinal nematode of rodents

Following our previous fi ndings on the in vitro anthelmintic effect of camel milk on Haemonchus contortus, the current study aimed at investigating its in vivo effect. Investigations were carried out using mice infected with Heligmosomoides polygyrus which is a parasite commonly used to test the effi cacy of anthelmintics. Thirty six Swiss white mice of both sexes aged 5 – 6 weeks old, and weighing between 20 and 25 g were orally infected with 0.5 ml dose of 100, 1-week-old H. polygyrus infective larvae (L3 ). After the pre-patent period, infected animals were randomly divided into 6 groups of 6 animals each. The nematicidal effi cacy of camel milk was monitored through faecal egg count reduction (FECR) and total worm count reduction (TWCR). Four doses (8.25; 16.5; 33.0; 66.0 ml/kg body weight (bw)) for fresh camel milk and 22 mg/kg bw for albendazole were studied using a bioassay. Albendazole and 4 % dimethylsulfoxide were included in the protocol as reference drug and placebo, respectively. For all tested doses except 8.25 ml/kg bw, camel milk was effective in vivo against H. polygyrus reducing both faecal egg count and worm count (p < 0.05). The dose 66 ml/kg bw showed the highest nematicidal activity causing a 76.75 % FECR and a 69.62 % TWCR 7 day after initiating the treatment. These results support the possible use of camel milk in the control of gastro-intestinal helminthiasis

Gavage

Gavage (aḍanay) chez les Touaregs Iwellemmeden kel Denneg (E. Bernus) Certaines fillettes touarègues appartenant à des familles riches en troupeaux subissent, dès l’âge de 7 à 8 ans, un gavage qui se prolonge pendant, deux, trois ou quatre ans, jusqu’à l’apparition de boursouflures et de replis graisseux sur les bras, les cuisses et de vergetures sur le ventre. Un terme au féminin pluriel désigne de « petites et courtes gerçures (cicatrices) naturelles sur la peau d’une femme engraissée/encei..

Gavage

Gavage (aḍanay) chez les Touaregs Iwellemmeden kel Denneg (E. Bernus) Certaines fillettes touarègues appartenant à des familles riches en troupeaux subissent, dès l’âge de 7 à 8 ans, un gavage qui se prolonge pendant, deux, trois ou quatre ans, jusqu’à l’apparition de boursouflures et de replis graisseux sur les bras, les cuisses et de vergetures sur le ventre. Un terme au féminin pluriel désigne de « petites et courtes gerçures (cicatrices) naturelles sur la peau d’une femme engraissée/encei..

The effects of long-term fertilizations on soil hydraulic properties vary with scales

Soil structural alterations instigated by cropping system conversion and fertilization change have been well documented, but how such alterations vary with scale remains elusive. We investigated this based on the Rothamsted long-term wheat experiment (since 1843) in the UK. Triplicate cores 7cm high and 10cm in diameter were taken from plots that have been under different fertilizations and returned to natural woodland for more than one century for imaging with X-ray computed tomography at resolution of 40µm. We then broke each core and sampled three aggregates from it to scan them at resolution of 1.5µm. For each core or aggregate sample, we calculated its pore size distribution, as well as permeability and tortuosity from pore-scale simulations. The results showed that the fertilization change more than 170 years ago reshaped the soil structure but differently between the core scale and aggregate scale. Macro-porosity of the pores (>40µm) in the cores unfertilized or fertilized with inorganic fertilizers were low and poorly connected in the top 10cm of soil, compared to the cores given farmyard manure or in the woodland. In all treatments, the large macropores in the cores were hydraulically anisotropic with their permeability being higher in the horizontal direction than in the vertical direction, whereas the aggregates were comparatively isotropic. The fertilization affected porosity and permeability of macropores at core scale more significantly than those at aggregate scale, and the aggregates fertilized with farmyard manure and in the woodland were more permeable than aggregates in other treatments. It is also found that, compared to no-fertilization or fertilization with complete fertilizers, fertilizing without phosphorus over the past 20 years increased the porosity and permeability of the aggregates but not of the cores. Fertilization with inorganic fertilizers increased tortuosity of the macropores in the cores but not of the intra-aggregates micropores, compared to no-fertilization. Porosity-permeability relationship for aggregates unfertilized or fertilized with inorganic fertilisers follows a power law with R2 > 0.8. In contrast, the permeability of aggregates in farmyard manure and in the woodland trended differently with the porosity. Aggregates and cores responded differently to carbon in that, with soil carbon increasing, the permeability of the aggregates increased asymptotically while the permeability of the cores increased approximately exponentially. Since soil structure is indicators of soil quality and evolves slowly, our results have important implications for understanding how agronomical practice changes reshape soil structure at different scales as well as the long-term consequence for hydrological and biochemical processes

Using a Crop Model to Benchmark Miscanthus and Switchgrass

Crop yields are important items in the economic performance and the environmental impacts of second-generation biofuels. Since they strongly depend on crop management and pedoclimatic conditions, it is important to compare candidate feedstocks to select the most appropriate crops in a given context. Agro-ecosystem models offer a prime route to benchmark crops, but have been little tested from this perspective thus far. Here, we tested whether an agro-ecosystem model (CERES-EGC) was specific enough to capture the differences between miscanthus and switchgrass in northern Europe. The model was compared to field observations obtained in seven long-term trials in France and the UK, involving different fertilizer input rates and harvesting dates. At the calibration site (Estrées-Mons), the mean deviations between simulated and observed crop biomass yields for miscanthus varied between −0.3 t DM ha−1 and 4.2 t DM ha−1. For switchgrass, simulated yields were within 1.0 t DM ha−1 of the experimental data. Observed miscanthus yields were higher than switchgrass yields in most sites and for all treatments, with one exception. Overall, the model captured the differences between both crops adequately, with a mean deviation of 0.46 t DM ha−1, and could be used to guide feedstock selections over larger biomass supply areas

Significant structural evolution of a long-term fallow soil in response to agricultural management practices requires at least 10 years after conversion at the aggregate level

Agricultural practices can have significant effects on the physical and biological properties of soil. The aim of this study was to understand how the physical structure of a compromised soil, arising from long-term bare-fallow management, was modified by adopting different field management practices. We hypothesised that changing agricultural practice from bare-fallow to arable or grassland would influence the modification of pore structure via an increase in porosity, pore connectivity, and a more homogenous distribution of pore sizes; and that this change exerts a rapid development of soil structure following conversion. Soil aggregates (< 2 mm) collected in successive years from field plots subjected to three contrasting managements were studied; viz. bare-fallow, bare-fallow converted to arable, and bare-fallow converted to grassland. Soil structure was assessed by X-ray Computed Tomography on the aggregates at 1.5 µm resolution, capturing detail relevant to soil biophysical processes. The grassland system increased porosity, diversity of pore sizes, pore-connectivity and pore-surface density significantly over the decade following conversion. However, measured at this resolution, the development of most of these metrics of soil structure required approximately 10 years post-conversion to show a significant effect. The arable system did not influence soil structural development significantly. Only the pore size distribution was modified in grassland in a shorter time frame (2 years post-conversion). Hence development of the soil structural characteristics appears to require at least a decadal timescale following conversion to grassland

Altered gut microbiome in Parkinson\u27s disease and the influence of lipopolysaccharide in a human α-synuclein over-expressing mouse model

The interaction between the gut microbiota and alpha-synuclein (αSyn) aggregation in Parkinson’s disease (PD) is receiving increasing attention. The objective of this study was to investigate gut microbiota, and effects of an inflammatory lipopolysaccharide (LPS) trigger in a human αSyn over-expressing mouse model of PD (Thy1-αSyn). Stool samples from patients with confirmed PD and Thy1-αSyn mice were analyzed using 16S ribosomal RNA sequencing. Compared to healthy controls, the relative abundance of mucin-degrading Verrucomicrobiae and LPS-producing Gammaproteobacteria were greater in PD patients. In mice, the abundance of Gammaproteobacteria was negligible in both Thy1-αSyn and wild-type (WT) animals, while Verrucomicrobiae were reduced in Thy1-αSyn mice. The effect of LPS on intestinal barrier function was investigated in vitro using intestinal epithelial (IEC-6) cells, and in vivo via administration of LPS in drinking water to Thy1-αSyn mice. Acute exposure to LPS in vitro resulted in a reduction and altered distribution of the tight junction markers ZO-1 and e-Cadherin around the cell membrane in IEC-6 cells, as shown by immunohistochemistry. LPS administration in Thy1-αSyn mice resulted in the emergence of early motor manifestations at 10 weeks, compared to untreated mice who were still asymptomatic at this age. This study reaffirms that an altered microbiome exists in patients with PD, and supports the notion of a proinflammatory gut microbiome environment as a trigger for PD pathogenesis

Phylogenetic distribution, biogeography and the effects of land management upon bacterial non-specific Acid phosphatase Gene diversity and abundance

Background and aims :Bacterial Non-Specific Acid Phosphatase (NSAP) enzymes are capable of dephosphorylating diverse organic phosphoesters but are rarely studied: their distribution in natural and managed environments is poorly understood. The aim of this study was to generate new insight into the environmental distribution of NSAPs and establish their potential global relevance to cycling of organic phosphorus. Methods : We employed bioinformatic tools to determine NSAP diversity and subcellular localization in microbial genomes; used the corresponding NSAP gene sequences to census metagenomes from diverse ecosystems; studied the effect of long-term land management upon NSAP diversity and abundance. Results : Periplasmic class B NSAPs are poorly represented in marine and terrestrial environments, reflecting their association with enteric and pathogenic bacteria. Periplasmic class A and outer membrane-associated class C NSAPs are cosmopolitan. NSAPs are more abundant in marine than terrestrial ecosystems and class C more abundant than class A genes, except in an acidic peat where class A genes dominate. A clear effect of land management upon gene abundance was identified. Conclusions : NSAP genes are cosmopolitan. Class C genes are more widely distributed: their association with the outer-membrane of cells gives them a clear role in the cycling of organic phosphorus, particularly in soil

Progress in the discovery of selective, high affinity A2B adenosine receptor antagonists as clinical candidates

The selective, high affinity A2B adenosine receptor (AdoR) antagonists that were synthesized by several research groups should aid in determining the role of the A2B AdoR in inflammatory diseases like asthma or rheumatoid arthritis (RA) and angiogenic diseases like diabetic retinopathy or cancer. CV Therapeutics scientists discovered the selective, high affinity A2B AdoR antagonist 10, a 8-(4-pyrazolyl)-xanthine derivative [CVT-6883, Ki(hA2B) = 22 nM; Ki(hA1) = 1,940 nM; Ki(hA2A) = 3,280; and Ki(hA3) = 1,070 nM] that has favorable pharmacokinetic (PK) properties (t1/2 = 4 h and F > 35% rat). Compound 10 demonstrated functional antagonism at the A2B AdoR (KB = 6 nM) and efficacy in a mouse model of asthma. In two phase 1 clinical trials, CVT-6883 was found to be safe, well tolerated, and suitable for once daily dosing. A second compound 20, 8-(5-pyrazolyl)-xanthine, has been nominated for development from Baraldi’s group in conjunction with King Pharmaceuticals that has favorable A2B AdoR affinity and selectivity [Ki(hA2B) = 5.5 nM; Ki(hA1) > 1,000 nM; Ki(hA2A) > 1,000; and Ki(hA3) > 1,000 nM], and it has been demonstrated to be a functional antagonist. A third compound 32, a 2-aminopyrimidine, from the Almirall group has high A2B AdoR affinity and selectivity [Ki(hA2B) = 17 nM; Ki(hA1) > 1,000 nM; Ki(hA2A) > 2,500; and Ki(hA3) > 1,000 nM], and 32 has been moved into preclinical safety testing. Since three highly selective, high affinity A2B AdoR antagonists have been nominated for development with 10 (CVT-6883) being the furthest along in the development process, the role of the A2B AdoR in various disease states will soon be established

Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine Laboratories in the Clinical Sequencing Exploratory Research Consortium

Evaluating the pathogenicity of a variant is challenging given the plethora of types of genetic evidence that laboratories consider. Deciding how to weigh each type of evidence is difficult, and standards have been needed. In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for the assessment of variants in genes associated with Mendelian diseases. Nine molecular diagnostic laboratories involved in the Clinical Sequencing Exploratory Research (CSER) consortium piloted these guidelines on 99 variants spanning all categories (pathogenic, likely pathogenic, uncertain significance, likely benign, and benign). Nine variants were distributed to all laboratories, and the remaining 90 were evaluated by three laboratories. The laboratories classified each variant by using both the laboratory's own method and the ACMG-AMP criteria. The agreement between the two methods used within laboratories was high (K-alpha = 0.91) with 79% concordance. However, there was only 34% concordance for either classification system across laboratories. After consensus discussions and detailed review of the ACMG-AMP criteria, concordance increased to 71%. Causes of initial discordance in ACMG-AMP classifications were identified, and recommendations on clarification and increased specification of the ACMG-AMP criteria were made. In summary, although an initial pilot of the ACMG-AMP guidelines did not lead to increased concordance in variant interpretation, comparing variant interpretations to identify differences and having a common framework to facilitate resolution of those differences were beneficial for improving agreement, allowing iterative movement toward increased reporting consistency for variants in genes associated with monogenic disease