A New Bioassay Platform Design for the Discovery of Small Molecules with Anticancer Immunotherapeutic Activity

Immunotherapy takes advantage of the immune system to prevent, control, and eliminate neoplastic cells. The research in the field has already led to major breakthroughs to treat cancer. In this work, we describe a platform that integrates in vitro bioassays to test the immune response and direct antitumor effects for the preclinical discovery of anticancer candidates. The platform relies on the use of dendritic cells that are professional antigen-presenting cells (APC) able to activate T cells and trigger a primary adaptive immune response. The experimental procedure is based on two phenotypic assays for the selection of chemical leads by both a panel of nine tumor cell lines and growth factor-dependent immature mouse dendritic cells (D1). The positive hits are then validated by a secondary test on human monocyte-derived dendritic cells (MoDCs). The aim of this approach is the selection of potential immunotherapeutic small molecules from natural extracts or chemical libraries.     

"Time sweet time": circadian characterization of galectin-1 null mice

Background  

Recent evidence suggests a two-way interaction between the immune and circadian systems. Circadian control of immune factors, as well as the effect of immunological variables on circadian rhythms, might be key elements in both physiological and pathological responses to the environment. Among these relevant factors, galectin-1 is a member of a family of evolutionarily-conserved glycan-binding proteins with both extracellular and intracellular effects, playing important roles in immune cell processes and inflammatory responses. Many of these actions have been studied through the use of mice with a null mutation in the galectin-1 (Lgals1) gene. To further analyze the role of endogenous galectin-1 in vivo, we aimed to characterize the circadian behavior of galectin-1 null (Lgals1 ^-/-) mice.     

Strategies of inorganic and organic trace mineral supplementation in gestating hyperprolific sow diets: effects on the offspring performance and fetal programming

The aim of the present study was to evaluate the effect of trace mineral nutrition on sow performance, mineral content, and intestinal gene expression of neonate piglets when inorganic mineral sources (ITM) were partially replaced by their organic mineral (OTM) counterparts. At 35 d postmating, under commercial conditions, a total of 240 hyperprolific multiparous sows were allocated into three experimental diets: 1) ITM: with Zn, Cu, and Mn at 80, 15, and 60 mg/kg, respectively; 2) partial replacement trace mineral source (Replace): with a 30 % replacement of ITM by OTM, resulting in ITM + OTM supplementation of Zn (56 + 24 mg/kg), Cu (10.5 + 4.5 mg/kg), and Mn (42 + 18 mg/kg); and 3) Reduce and replace mineral source (R&R): reducing a 50% of the ITM source of Zn (40 + 24 mg/kg), Cu (7.5 + 4.5 mg/kg), and Mn (30 + 18 mg/kg). At farrowing, 40 piglets were selected, based on birth weight (light: <800 g, and average: >1,200 g), for sampling. Since the present study aimed to reflect results under commercial conditions, it was difficult to get an equal parity number between the experimental diets. Overall, no differences between experimental diets on sow reproductive performance were observed. Light piglets had a lower mineral content (P < 0.05) and a downregulation of several genes (P < 0.10) involved in physiological functions compared with their average littermates. Neonate piglets born from Replace sows had an upregulation of genes involved in functions like immunity and gut barrier, compared with those born from ITM sows (P < 0.10), particularly in light piglets. In conclusion, the partial replacement of ITM by their OTM counterparts represents an alternative to the totally inorganic supplementation with improvements on neonate piglet gene expression, particularly in the smallest piglets of the litter. The lower trace mineral storage together with the greater downregulation of gut health genes exposed the immaturity and vulnerability of small piglets.     

Growing conditions and postharvest management can affect the essential oil of Origanum vulgare L. ssp. hirtum (Link) Ietswaart

Origanum vulgare subsp. hirtum (Link) Ietswaart (Greek oregano) has been cultivated since ancient times thanks to its herbal and therapeutic properties. Currently, it is added in various commercial preparations thanks to its essential oil composition. This group of secondary compounds is affected in quantity and quality by biotic and abiotic factors during the cultivating phase and by the postharvest management. Thus, the aims of the work were to study: (1) how the growing conditions (soil full-light treatment; pot full-light treatment; pot 50%-shade treatment) can affect the essential oil content and the essential oil profile of Greek oregano branches at full-blossoming stage; and (2) how the postharvest management (distillation of the essential oil from fresh herbs, dehumidified herbs or oven-dried herbs) can affect the essential oil content and the essential oil profile of this species. The growing conditions significantly affected the biometrical parameters. The pot full-light treatment contained the highest dry matter percentage (36.5%) and the highest essential oil content, which was directly correlated to the former parameter (r = 0.890**). The postharvest management did not affect the essential oil content. The growing condition significantly affected the characterizing γ-terpinene, cis-sabinene hydrate, 4-terpineol, α-terpinene, linalyl acetate, and β-bisabolene, while it did not affect carvacrol (mean value 15.8%), p-cymene (mean value 6.0%), or sabinene (mean value 3.9%). The postharvest management significantly affected carvacrol, cis-sabinene hydrate, 4-terpineol, p-cymene, α-terpinene, linalyl acetate, and β-bisabolene, while it did not affect γ-terpinene (mean value 14.7%). The response of some compounds to growing conditions led us to hypothesise an essential oil profile of the plants grown in pots at 50%-shade to be more of a vegetative stage type oil than the essential oil profile of the plants grown in soil, although all were at the blossoming stage. The analyses on the individual compounds indicated that, even though the essential oil content in oregano did not change with a change in postharvest management, biochemical changes occurred on the profile. These could be due to enzyme activity, dilution effect or temperature effect during the drying processes. The oven-drying process and the dehumidifying process changed the essential oil profile in a similar way compared to the essential oil profile distilled from fresh herbs. Thus, when it is not possible to extract the essential oil directly from fresh herbs, processors can dry the oregano according to the equipments they have available.     

Metabolite Profiling of Rosemary Cell Lines with Antiproliferative Potential against Human HT-29 Colon Cancer Cells

Plant Foods for Human Nutrition - Rosemary (Rosmarinus officinalis) is a culinary and medicinal plant used in food and pharmaceutical industry. The wide range of biological activities is mainly...     

Ultrasound‐guided ‘two‐in‐one’ femoral and obturator nerve block in the dog: an anatomical study

ObjectiveTo evaluate the dye extent and distribution at the lumbar plexus (LP) of three volumes of local anaesthetic-methylene-blue solution administered close to the femoral nerve (FN) by the use of a ventral ultrasound (US)-guided suprainguinal approach (SIA).Study designProspective experimental trial.AnimalsTwenty mongrel canine cadavers weighing 17.7 ± 3.8 kg (mean ± SD).MethodsThe left and right LP of two cadavers were dissected to identify the FN, obturator nerve (ON) and lateral femoral cutaneous nerve (LFCN). The extent and distribution of dye at the LP of each of three volumes of injectate of 0.2, 0.4 and 0.6 mL kg^?1 administered close to the FN by a ventral US-guided SIA then were studied in a further 18 dog cadavers (n = 6 per group). Staining of ≥2 cm along the target nerves was indicative of sufficient spread to produce a nerve block.ResultsThe ventral US-guided SIA allowed the observation of the FN within the iliopsoas muscle (IPM) in a total of 17 cadavers. The assessment of the dye extent and distribution revealed a similar pattern regardless of the injected volume. From the injection site, the spreading of injectate occurred in cranial, lateral and caudal directions. The FN and ON were effectively stained in all the cases. The LFCN was not effectively stained in any case.Conclusions and clinical relevanceA volume of 0.2 mL kg^?1 administered close to the FN by a ventral US-guided SIA produced a sufficient distribution of the injectate within the IPM to produce effective staining of the FN and ON. This US-guided technique may be an appropriate alternative to previously reported techniques based on electrolocation to block the FN and ON in the dog.     

Radar soundings of the subsurface of Mars

The martian subsurface has been probed to kilometer depths by the Mars Advanced Radar for Subsurface and Ionospheric Sounding instrument aboard the Mars Express orbiter. Signals penetrate the polar layered deposits, probably imaging the base of the deposits. Data from the northern lowlands of Chryse Planitia have revealed a shallowly buried quasi-circular structure about 250 kilometers in diameter that is interpreted to be an impact basin. In addition, a planar reflector associated with the basin structure may indicate the presence of a low-loss deposit that is more than 1 kilometer thick.     

Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans

Coevolution of mammals and their gut microbiota has profoundly affected their radiation into myriad habitats. We used shotgun sequencing of microbial community DNA and targeted sequencing of bacterial 16S ribosomal RNA genes to gain an understanding of how microbial communities adapt to extremes of diet. We sampled fecal DNA from 33 mammalian species and 18 humans who kept detailed diet records, and we found that the adaptation of the microbiota to diet is similar across different mammalian lineages. Functional repertoires of microbiome genes, such as those encoding carbohydrate-active enzymes and proteases, can be predicted from bacterial species assemblages. These results illustrate the value of characterizing vertebrate gut microbiomes to understand host evolutionary histories at a supraorganismal level.     

The genome of the diatom Thalassiosira pseudonana: ecology, evolution, and metabolism

Diatoms are unicellular algae with plastids acquired by secondary endosymbiosis. They are responsible for approximately 20% of global carbon fixation. We report the 34 million-base pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand-base pair plastid and 44 thousand-base pair mitochondrial genomes. Sequence and optical restriction mapping revealed 24 diploid nuclear chromosomes. We identified novel genes for silicic acid transport and formation of silica-based cell walls, high-affinity iron uptake, biosynthetic enzymes for several types of polyunsaturated fatty acids, use of a range of nitrogenous compounds, and a complete urea cycle, all attributes that allow diatoms to prosper in aquatic environments.