b-Annulated 1,4-dihydropyridines as Notch inhibitors

The Notch signaling pathway is involved in cell proliferation and differentiation, and has been recognized as an active pathway in regenerating tissue and cancerous cells. Notch signaling inhibition is considered a viable approach to the treatment of a variety of conditions including colorectal cancer, pancreatic cancer, breast cancer and metastatic melanoma. The discovery that the b-annulated dihydropyridine FLI-06 (1) is an inhibitor of the Notch pathway with an EC50?≈?2.5?μM prompted us to screen a library of related analogs. After structure activity studies were conducted, racemic compound 7 was identified with an EC50?=?0.36?μM. Synthesis of individual enantiomers provided (+)-7 enantiomer with an EC50?=?0.13?μM, or about 20-fold the potency of 1.     

A review of the history of research and control of <Emphasis Type="Italic">Rhipicephalus</Emphasis> (<Emphasis Type="Italic">Boophilus</Emphasis>) <Emphasis Type="Italic">microplus</Emphasis>, babesiosis and anaplasmosis in Uruguay

The effect of five constant temperatures (16, 20, 24, 28 and 32 °C) on the development, survival and reproduction of Tetranychus cinnabarinus (Boisduval) [=?Tetranychus urticae Koch (red form)] fed on cassava leaves was examined in the laboratory at 85% relative humidity. Development time of various immature stages decreased with increasing temperature, with total egg-to-adult development time varying from 27.7 to 6.7 days. The lower thermal threshold for development was 10.8 °C and the thermal constant from egg to adult was 142.4 degree-days. Pre- and post-oviposition period and female longevity all decreased as temperature increased. The longest oviposition period was observed at 20 °C with 20.4 days. Under different temperatures, mated females laid, on average, 1.0, 2.9, 4.7, 4.7 and 4.9 eggs per day, respectively. The maximum fecundity (81.5 eggs per female) was at 28 °C and the intrinsic rate of increase (r _m ) was highest (0.25) at 32 °C. The results of this study indicate that T. cinnabarinus population could increase rapidly when cassava leaves serve as a food source. At the appropriate temperature T. cinnabarinus could seriously threaten growth of cassava.     

On the suitability of an allometric proxy for nondestructive estimation of average leaf dry weight in eelgrass shoots I: sensitivity analysis and examination of the influences of data quality,analysis method,and sample size on precision

Background

The effects of current anthropogenic influences on eelgrass (Zostera marina) meadows are noticeable. Eelgrass ecological services grant important benefits for mankind. Preservation of eelgrass meadows include several transplantation methods. Evaluation of establishing success relies on the estimation of standing stock and productivity. Average leaf biomass in shoots is a fundamental component of standing stock. Existing methods of leaf biomass measurement are destructive and time consuming. These assessments could alter shoot density in developing transplants. Allometric methods offer convenient indirect assessments of individual leaf biomass. Aggregation of single leaf projections produce surrogates for average leaf biomass in shoots. Involved parameters are time invariant, then derived proxies yield simplified nondestructive approximations. On spite of time invariance local factors induce relative variability of parameter estimates. This influences accuracy of surrogates. And factors like analysis method, sample size and data quality also impact precision. Besides, scaling projections are sensitive to parameter fluctuation. Thus the suitability of the addressed allometric approximations requires clarification.

Results

The considered proxies produced accurate indirect assessments of observed values. Only parameter estimates fitted from raw data using nonlinear regression, produced robust approximations. Data quality influenced sensitivity and sample size for an optimal precision.

Conclusions

Allometric surrogates of average leaf biomass in eelgrass shoots offer convenient nondestructive assessments. But analysis method and sample size can influence accuracy in a direct manner. Standardized routines for data quality are crucial on granting cost-effectiveness of the method.

     

Carrageenans from <Emphasis Type="Italic">Sarcothalia crispata</Emphasis> and <Emphasis Type="Italic">Gigartina skottsbergii</Emphasis>: Structural Analysis and Interpolyelectrolyte Complex Formation for Drug Controlled Release

The aims of the present study were to characterize for the first time the carrageenan extracted from cystocarpic stage of S. crispata collected in the Patagonian coast of Argentina, and to prepare interpolyelectrolytic complexes (IPECs) between the polysaccharide extracted from cystocarpic stage of Sarcothalia crispata and Gigartina skottsbergii thalli, and basic butylated methacrylate copolymer (Eudragit E), in order to test their potential for the controlled release of ibuprofen as model drug. The structural determination revealed that the polysaccharides extracted from S. crispata and G. skottsbergii were mainly constituted by κ-carrageenan, particularly in the case of G. skottsbergii; however, significant amounts of ι- and ν-carrageenan were also detected in both polygalactans. The differences in diad composition and possibly in their distribution along the polysaccharide chain of both carrageenans would favor a different arrangement in the resulting IPEC structure. The smaller pores observed by scanning electron microscopy in the IPEC of S. crispata suggest that the kinks in the polysaccharide backbone are evenly distributed, resulting in a slower ibuprofen release compared to the IPEC of G. skottsbergii.     

Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline

Background aims

Cell therapy with autologous mesenchymal stromal cells (MSCs) in patients with spinal cord injury (SCI) is beginning, and the search for its better clinical application is an urgent need.

Identification of trehalose as a compatible solute in different species of acidophilic bacteria

The major industrial heap bioleaching processes are located in desert regions (mainly Chile and Australia) where fresh water is scarce and the use of resources with low water activity becomes an attractive alternative. However, in spite of the importance of the microbial populations involved in these processes, little is known about their response or adaptation to osmotic stress. In order to investigate the response to osmotic stress in these microorganisms, six species of acidophilic bacteria were grown at elevated osmotic strength in liquid media, and the compatible solutes synthesised were identified using ion chromatography and MALDI-TOF mass spectrometry. Trehalose was identified as one of, or the sole, compatible solute in all species and strains, apart from Acidithiobacillus thiooxidans where glucose and proline levels increased at elevated osmotic potentials. Several other potential compatible solutes were tentatively identified by MALDITOF analysis. The same compatible solutes were produced by these bacteria regardless of the salt used to produce the osmotic stress. The results correlate with data from sequenced genomes which confirm that many chemolithotrophic and heterotrophic acidophiles possess genes for trehalose synthesis. This is the first report to identify and quantify compatible solutes in acidophilic bacteria that have important roles in biomining technologies.     

NOD1 is required for Helicobacter pylori induction of IL‐33 responses in gastric epithelial cells

Helicobacter pylori (H. pylori) causes chronic inflammation which is a key precursor to gastric carcinogenesis. It has been suggested that H. pylori may limit this immunopathology by inducing the production of interleukin 33 (IL‐33) in gastric epithelial cells, thus promoting T helper 2 immune responses. The molecular mechanism underlying IL‐33 production in response to H. pylori infection, however, remains unknown. In this study, we demonstrate that H. pylori activates signalling via the pathogen recognition molecule Nucleotide‐Binding Oligomerisation Domain‐Containing Protein 1 (NOD1) and its adaptor protein receptor‐interacting serine–threonine Kinase 2, to promote production of both full‐length and processed IL‐33 in gastric epithelial cells. Furthermore, IL‐33 responses were dependent on the actions of the H. pylori Type IV secretion system, required for activation of the NOD1 pathway, as well as on the Type IV secretion system effector protein, CagA. Importantly, Nod1^+/+ mice with chronic H. pylori infection exhibited significantly increased gastric IL‐33 and splenic IL‐13 responses, but decreased IFN‐γ responses, when compared with Nod1^?/? animals. Collectively, our data identify NOD1 as an important regulator of mucosal IL‐33 responses in H. pylori infection. We suggest that NOD1 may play a role in protection against excessive inflammation.