Phenylpiperazine derivatives with strong affinity for 5HT1A, D2A and D3 receptors

Four 7-[3-(4-phenyl-1-piperazinyl)propoxy]coumarins were synthesized. The affinities of these compounds for DA (D_2A, D₃) and 5HT_1A receptors were evaluated for their ability to displace [³H]-raclopride and [³H]-8-OH-DPAT respectively from their specific binding sites. The affinities of the target compounds were all in the nanomolar range and followed the order 5-HT_1A > D₂ > D₃.     

An annotated distributional checklist of the freshwater fish from Baja California Sur,México

An annotated distributional checklist of thefreshwater fish recorded historically andrecently in Baja California Sur, México, isprovided. This checklist is supported with4,857 specimens collected at freshwaterlocalities during the period of May 1991 toApril 2002, and complemented with a review ofspecimens in museums and in the literature. Thenative ichthyofauna is represented by 19species belonging to 16 genera and 12 families,with only two cases of endemism (Funduluslima and Gobiesox juniperoserrai). Thefirst occurrence of Centropomus viridisin freshwater environments of Baja Californiapeninsula is reported here. The familiesEleotridae and Mugilidae are the most diversewith 3 species each. Zoogeographically, most ofthe species are of tropical affinity(panamanian 63%, tropical amphiamerican 16%and circumtropical 5%) and of marineecological derivation (sporadic 53%,complementary 26%, vicarious 16% anddiadromous 5%). Six species are exotic in thisregion, of which Cyprinus carpio, Xiphophorus helleri and Tilapia cf. zilli are of recent introduction. The currentstatus of the endemic killifish (Funduluslima) is determined as endangered due tocompetition with Tilapia cf. zilliand other exotic fish.     

Differential expression of Candida dubliniensis-secreted aspartyl proteinase genes (CdSAP1–4) under different physiological conditions and during infection of a keratinocyte culture

The in vitro and keratinocyte (HaCAT cells) culture expression of four putative genes coding for secreted aspartyl proteases of Candida dubliniensis – CdSAP1, CdSAP2, CdSAP3 , and CdSAP4 ( CdSAP1–4 ) – is reported for the first time. In addition, CdSAP7, 8, 9 , and 10 , orthologous genes of Candida albicans , were recognized in C. dubliniensis genome. There are no orthologs of C. albicans SAP5 and 6 in C. dubliniensis . The expression of CdSAP1 and 2 was independent of the morphological stage of C. dubliniensis ; they are expressed at both pH 4 and pH 7, and were induced with albumin as nitrogen source. CdSAP3 expression was regulated by the pH, and was related to the infection process of keratinocytes. Expression of CdSAP4 predominated during the mycelial phase and the initial stage of keratinocyte infection. During infection of the HaCaT cell line, only genes CdSAP3 – 4 were expressed, and keratinocytes were affected in their number and shape by the infection with C. dubliniensis ; however, this effect decreased in the presence of pepstatin A (aspartyl protease inhibitor). Pepstatin A was not able to inhibit keratinocyte damage. Based on the aforementioned, we suggest that the Saps from C. dubliniensis could be considered a virulence factor just as those from C. albicans , and participants in the nitrogen metabolism of the yeast for nutrient acquisition.     

Cloning and characterization of a glucosyltransferase from Crocus sativus stigmas involved in flavonoid glucosylation

Background  

Flavonol glucosides constitute the second group of secondary metabolites that accumulate in Crocus sativus stigmas. To date there are no reports of functionally characterized flavonoid glucosyltransferases in C. sativus, despite the importance of these compounds as antioxidant agents. Moreover, their bitter taste makes them excellent candidates for consideration as potential organoleptic agents of saffron spice, the dry stigmas of C. sativus.     

Modelling the lethargic crab disease

The lethargic crab disease (LCD) is an emergent infirmity that has decimated native populations of the mangrove land crab (Ucides cordatus, Decapoda: Ocypodidae) along the Brazilian coast. Several potential etiological agents have been linked with LCD, but only in 2005 was it proved that it is caused by an ascomycete fungus. This is the first attempt to develop a mathematical model to describe the epidemiological dynamics of LCD. The model presents four possible scenarios, namely, the trivial equilibrium, the disease-free equilibrium, endemic equilibrium, and limit cycles arising from a Hopf bifurcation. The threshold values depend on the basic reproductive number of crabs and fungi, and on the infection rate. These scenarios depend on both the biological assumptions and the temporal evolution of the disease. Numerical simulations corroborate the analytical results and illustrate the different temporal dynamics of the crab and fungus populations.     

Design, synthesis and photobiological properties of 3,4-cyclopentenepsoralens

The QSAR directed synthesis of tetracyclic psoralen derivatives (3-5) characterised by the condensation of a cyclopentane ring at the level of the 3,4 double bond of the tricyclic psoralen moiety is reported. The new compounds present a methoxy (3), a hydroxy (4) or a dimethylaminopropoxy (5) side chain inserted in position 8 of the lead chromophore. The evaluation of photoantiproliferative activity on human tumour cell lines reveals for 5 an ability to inhibit cell growth significantly higher with respect to that of the reference drug, 8-MOP. Interestingly, the enhancement in antiproliferative activity is accompanied by the disappearance of skin phototoxicity. On the other hand, no significant photobiological activity was scored for 3 and 4. The ability to photoreact with DNA, evaluated by isolating the 4',5' monoadduct and by estimating the ability to form interstrand cross-links, appeared to be significant for 5, practically negligible for 3 and 4. Furthermore, a back-projection of the more active compound identifies structural features suitable for further synthetic modifications.     

Comparative study of metallic biomaterials toxicity: a histochemical and immunohistochemical demonstration in mouse spleen.

Metallic biomaterials available for orthopaedic purposes become essential to perform important physical activities, due to their low cost and excellent mechanical properties. In addition, they are frequently used in dentistry. However, corrosion phenomena of such devices are the main problems resulting in subsequent spreading of the elements through the whole body via lymph and blood. The spleen is the most important lymphoid organ and the only one included in the blood circulation. Thus, the aim of this study was to evaluate the short-term effects on spleen tissues of heavy metals released from stainless steel and Cr-Co-Mo alloys, as well as from titanium, at histochemical and immunohistochemical levels. For this purpose, metallic suspensions were obtained by electrochemical dissolution of the mentioned biomaterials: stainless steel (Fe 490 mg/L, Cr 224 mg/L, Ni 150 mg/L), Cr-Co-Mo (Cr 200 mg/L, Co 375 mg/L), and titanium (400 mg/L). Then 0.5 ml of each solution was subcutaneously administered to male Charles River mice each 72 hours during 30 days. Cryostat sections of the spleen from all groups were submitted to routine staining with haematoxylin/eosin, peroxidase detection by 3-3' diaminobenzidine (DAB), and alkaline phosphatase anti-alkaline phosphatase (APAAP) for lymphocyte detection. Several pronounced alterations were found in the spleen architecture, as manifested by irregular features within the capsule and medulla, namely depletion of T4 and B cells. Altogether these results suggest toxic alterations within the spleen induced by some of the metallic elements, indicating that the immune system may be hampered and so interfering in the body mechanisms of defence.     

DNA methylation analysis by digital bisulfite genomic sequencing and digital MethyLight

Alterations in cytosine-5 DNA methylation are frequently observed in most types of human cancer. Although assays utilizing PCR amplification of bisulfite-converted DNA are widely employed to analyze these DNA methylation alterations, they are generally limited in throughput capacity, detection sensitivity, and or resolution. Digital PCR, in which a DNA sample is analyzed in distributive fashion over multiple reaction chambers, allows for enumeration of discrete template DNA molecules, as well as sequestration of non-specific primer annealing templates into negative chambers, thereby increasing the signal-to-noise ratio in positive chambers. Here, we have applied digital PCR technology to bisulfite-converted DNA for single-molecule high-resolution DNA methylation analysis and for increased sensitivity DNA methylation detection. We developed digital bisulfite genomic DNA sequencing to efficiently determine single-basepair DNA methylation patterns on single-molecule DNA templates without an interim cloning step. We also developed digital MethyLight, which surpasses traditional MethyLight in detection sensitivity and quantitative accuracy for low quantities of DNA. Using digital MethyLight, we identified single-molecule, cancer-specific DNA hypermethylation events in the CpG islands of RUNX3, CLDN5 and FOXE1 present in plasma samples from breast cancer patients.     

Abundant assemblage of Ostracoda (Crustacea) in Mexican Miocene amber sheds light on the evolution of the brackish-water tribe Thalassocypridini

Amber inclusions of fully aquatic animals are rare, most of them isolated specimens of water-bound insect larvae. In contrast, we here describe an ample, speciose fauna of 262 fully aquatic individuals of Ostracoda (Crustacea) from Mexican amber of Early Miocene age. This fauna was trapped whilst under water swimming around trunks of resin-producing trees in a brackish lagoon. Ostracod crustaceans are typically around a millimeter in length, and are known for their mostly well-calcified bivalved carapaces that account for their unparalleled fossil record in arthropods. However, in the Chiapas amber we found representatives of the tribe Thalassocypridini, which are characterised by lightly calcified carapaces and therefore lack a substantial fossil record. Embedded in amber, this ‘drawback’ becomes a clear benefit because the unobstructed view onto the appendages otherwise hidden in the carapace allowed us to identify nine ostracod species, six of them new to science. The exceptional number of individuals permitted insights into population composition, reproduction, taphonomy and into micro-environmental parameters of the amber’s place of formation. Based on ecological data available for Recent Thalassocypridini species, we posit that this tribe reached a peak radiation in open lagoonal settings during the Miocene, and shifted towards anchialine environments by the Recent.

http://zoobank.org/lsid:zoobank.org:pub:3C93A06B-F86B-404F-985D-139897F97EF3