Synthesis of a tetrahydroimidazo-[2',1':2,3]thiazolo[5,4-c]pyridine derivative with Met inhibitory activity

A straightforward synthesis of the Met antagonist JLK1360 involving an alkylationcyclocondensation process using aminothiazole 1 and nitrophenacyl bromide 2, reduction of the nitro group, and coupling of the resulting tetracyclic aniline 5 with an appropriate N-acyl alanine derivative, is reported.

Synthesis of a tetrahydroimidazo-[2',1':2,3]thiazolo[5,4-c]pyridine derivative with Met inhibitory activity

A straightforward synthesis of the Met antagonist JLK1360 involving an alkylationcyclocondensation process using aminothiazole 1 and nitrophenacyl bromide 2, reduction of the nitro group, and coupling of the resulting tetracyclic aniline 5 with an appropriate N-acyl alanine derivative, is reported.

egr-4, a target of EGFR signaling, is required for the formation of the brian primordial and head regeneration in planarians

During the regeneration of freshwater planarians, polarity and patterning programs play essential roles in determining whether a head or a tail regenerates at anterior or posterior-facing wounds. This decision is made very soon after amputation. The pivotal role of the Wnt/β-catenin and Hh signaling pathways in re-establishing anterior-posterior (AP) polarity has been well documented. However, the mechanisms that control the growth and differentiation of the blastema in accordance with its AP identity are less well understood. Previous studies have described a role of Smed-egfr-3, a planarian epidermal growth factor receptor, in blastema growth and differentiation. Here, we identify Smed-egr-4, a zinc-finger transcription factor belonging to the early growth response gene family, as a putative downstream target of Smed-egfr-3. Smed-egr-4 is mainly expressed in the central nervous system and its silencing inhibits anterior regeneration without affecting the regeneration of posterior regions. Single and combinatorial RNA interference to target different elements of the Wnt/β-catenin pathway, together with expression analysis of brain- and anterior-specific markers, revealed that Smed-egr-4: (1) is expressed in two phases - an early Smed-egfr-3-independent phase and a late Smed-egfr-3-dependent phase; (2) is necessary for the differentiation of the brain primordia in the early stages of regeneration; and (3) that it appears to antagonize the activity of the Wnt/β-catenin pathway to allow head regeneration. These results suggest that a conserved EGFR/egr pathway plays an important role in cell differentiation during planarian regeneration and indicate an association between early brain differentiation and the proper progression of head regeneration.

Factores Asociados a Deficiencia de Vitamina D y a Niveles Elevados de PTH en Pacientes con Infección VIH Atendidos en Barcelona

Estudi transversal de pacients VIH en els que es va determinar colecalciferol (25-OH- Vit.D3) i PTH, excloint a pacients amb insuficiència renal, hepàtica i nivells plasmàtics anormals de calci i/o fósfor Es van incloure 566 pacients, amb una exposició a tenofovir del 56,4%. La prevalència de vitamina D insuficient va der del 71,2% i la deficiència del 39,6% . La PTH es va determinar en 228 casos, presentant nivells elevats 86 d’ells (37,7%). Els factors de risc ajustats de deficiència de vitamina D van ser, ésser de raza no blanca i la morbilitat psiquiàtrica, essent la lipoatròfia, un factor protector. Els factors de risc independents de nivells elevats de PTH van ser: Vitamina D&12 ng/ml: OR: 2,14 (IC95%: 1,19-3,82, p: 0,01) i l’ exposició a tenofovir: OR: 3,55 (IC95%: 1,62-7,7, p: 0,002).

THC prevents MDMA neurotoxicity in mice

The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg ×4) were pretreated with THC (3 mg/kg ×4) at room (21°C) and at warm (26°C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB1 receptor antagonist AM251 and the CB2 receptor antagonist AM630, as well as in CB1, CB2 and CB1/CB2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB1 receptor antagonist AM251, neither in CB1 and CB1/CB2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB2 cannabinoid antagonist and in CB2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB1 receptor, although CB2 receptors may also contribute to attenuate neuroinflammation in this process.

Genetic variation for carbon isotope composition in Juglans regia L.: relationships with growth, phenology and climate of origin

Among the traits of breeding interest for the common walnut tree Juglans regia L., characteristics such as timing of budbreak and leaf fall, water-use efficiency and growth performance are regarded as being of utmost relevance in Mediterranean conditions. The authors evaluated intraspecific variation in $\delta$13C (carbon isotope composition, surrogate of intrinsic water-use efficiency, WUE$_{\rm i}$) for 22 J. regia families grown in a progeny test under supplementary irrigation, and investigated whether such variation correlated with climatic indicators of native habitats. The genetic relationships between $\delta$13C, growth and phenology were also assessed during two consecutive years. Overall, the most water-use-efficient families (i.e. with higher $\delta$13C), which originated mainly from drought-prone provenance regions which have a high vapour pressure deficit and low rainfall, exhibited less height growth and smaller DBH. Using a stepwise regression procedure, $\delta$13C was included as the main explanatory variable of genotypic variation in growth traits, together with growing season duration (for DBH in both years) and flushing (for height in 2007). It was concluded that WUE$_{\rm i}$ is largely unconnected to phenology effects in the explanation of growth performance for J. regia, therefore suggesting the opportunity of simultaneously selecting for low WUE$_{\rm i}$ and extended growing period to maximise productivity in non-water-limited environments.

A functional variant in the Stearoyl-CoA desaturase gene promoter enhances fatty acid desaturation in pork

There is growing public concern about reducing saturated fat intake. Stearoyl-CoA desaturase (SCD) is the lipogenic enzyme responsible for the biosynthesis of oleic acid (18:1) by desaturating stearic acid (18:0). Here we describe a total of 18 mutations in the promoter and 3′ non-coding region of the pig SCD gene and provide evidence that allele T at AY487830:g.2228T>C in the promoter region enhances fat desaturation (the ratio 18:1/18:0 in muscle increases from 3.78 to 4.43 in opposite homozygotes) without affecting fat content (18:0+18:1, intramuscular fat content, and backfat thickness). No mutations that could affect the functionality of the protein were found in the coding region. First, we proved in a purebred Duroc line that the C-T-A haplotype of the 3 single nucleotide polymorphisms (SNPs) (g.2108C>T; g.2228T>C; g.2281A>G) of the promoter region was additively associated to enhanced 18:1/18:0 both in muscle and subcutaneous fat, but not in liver. We show that this association was consistent over a 10-year period of overlapping generations and, in line with these results, that the C-T-A haplotype displayed greater SCD mRNA expression in muscle. The effect of this haplotype was validated both internally, by comparing opposite homozygote siblings, and externally, by using experimental Duroc-based crossbreds. Second, the g.2281A>G and the g.2108C>T SNPs were excluded as causative mutations using new and previously published data, restricting the causality to g.2228T>C SNP, the last source of genetic variation within the haplotype. This mutation is positioned in the core sequence of several putative transcription factor binding sites, so that there are several plausible mechanisms by which allele T enhances 18:1/18:0 and, consequently, the proportion of monounsaturated to saturated fat.

Otolith shape analysis as a tool for population discrimination of the white grunt (Haemulon plumieri) stock in the northern coast of the Yucatan Peninsula, Mexico

In this study, the population structure of the white grunt (Haemulon plumieri) from the northern coast of the Yucatan Peninsula was determined through an otolith shape analysis based on the samples collected in three locations: Celestún (N 20°49",W 90°25"), Dzilam (N 21°23", W 88°54") and Cancún (N 21°21",W 86°52"). The otolith outline was based on the elliptic Fourier descriptors, which indicated that the H. plumieri population in the northern coast of the Yucatan Peninsula is composed of three geographically delimited units (Celestún, Dzilam, and Cancún). Significant differences were observed in mean otolith shapes among all samples (PERMANOVA; F2, 99 = 11.20, P = 0.0002), and the subsequent pairwise comparisons showed that all samples were significantly differently from each other. Samples do not belong to a unique white grunt population, and results suggest that they might represent a structured population along the northern coast of the Yucatan Peninsula

Is syndecan-2 a key angiogenic element?

Angiogenesis is a tightly regulated process in vertebrates that leads to the formation of new blood vessels from pre-existing vessels or by the recruitment of bone marrow-derived endothelial precursor cells[1]. During embryogenesis, after stimulation by proangiogenic factors, such as VEGF or FGF, it contributes to the maturation of the vascular plexus. In adults, it is important in some physiologic conditions, such as wound healing or the reproductive cycle in females, although most of the time it is"switched off" by endogenous inhibitors, such as endostatin or angiostatin. Furthermore, its misregulation is the cause of many pathological situations, as it contributes to tumor development[2], diabetic retinopathy[3], rheumatoid arthritis[4], psoriasis[5], but also cardiovascular disorders[6] and obesity[7]

Late and postmagmatic alterations in the tin-bearing batholith of Ricobayo (Iberian Massif, NW Spain)

The deuteric alteration processes undergone by the granites of the Ricobayo Batholith were: microclinization, chloritization, albitization, muscovitization, tourmalinization and garnetization. These processes must be interpreted in a dynamic context so that the different reactions that take place are the consequence of a successive interaction between rock and fluids. The physicochemical conditions deduced from these fluids are: temperature lower than 600 OC, pressure between 1.5 and 1 Kb, fugacity of oxygen between 10-25 and 10-35 bars, fugacity of sulphur lower than 10-l5 bars, the composition was kept stable and their log (a(K+)/a(Ht)) and log (a(Na+)/a(H+)) varied between 3.8 and 3.2 and between 3.5 and 4.6, respectively, and the pH of the fluids was higher than 5 during the microclinization, muscovitization and tourmalinization, and lower during chloritization and albitization. The deposition of cassiterite occurs with pH episodes that exceed 5.

Research Priorities for seabirds: Improving seabird conservation and management in the 21st century

Seabirds are facing a growing number of threats in both terrestrial and marine habitats, and many populations have experienced dramatic changes over past decades. Years of seabird research have improved our understanding of seabird populations and provided a broader understanding of marine ecological processes. In an effort to encourage future research and guide seabird conservation science, seabird researchers from 9 nations identified the 20 highest priority research questions and organized these into 6 general categories: (1) population dynamics, (2) spatial ecology, (3) tropho-dynamics, (4) fisheries interactions, (5) response to global change, and (6) management of anthropogenic impacts (focusing on invasive species, contaminants and protected areas). For each category, we provide an assessment of the current approaches, challenges and future directions. While this is not an exhaustive list of all research needed to address the myriad conservation challenges seabirds face, the results of this effort represent an important synthesis of current expert opinion across sub-disciplines within seabird ecology. As this synthesis highlights, research, in conjunction with direct management, education, and community engagement, can play an important role in facilitating the conservation and management of seabird populations and of the ocean ecosystems on which they and we depend.