Thioureides of 2-(phenoxymethyl)benzoic acid 4-R substituted: A novel class of anti-parasitic compounds

Fifty members of a novel class of antimicrobial compounds, 2-(4-R-phenoxymethyl)benzoic acid thioureides, were synthesized and characterized with respect to their activities against three parasites of human relevance, namely the protozoa Giardia lamblia and Toxoplasma gondii, and the larval (metacestode) stage of the tapeworm Echinococcus multilocularis. To determine the selective toxicity of these compounds, the human colon cancer cell line Caco2 and primary cultures of human foreskin fibroblasts (HFF) were also investigated. The new thioureides were obtained in a three-step-reaction process and subsequently characterized by their physical constants (melting point, solubility). The chemical structures were elucidated by ¹H NMR, ¹³C NMR, IR spectral methods and elemental analysis. The analyses confirmed the final and intermediate compound structures and the synthesis. The compounds were then tested on the parasites in vitro. All thioureides, except two compounds with a nitro group, were totally ineffective against Giardia lamblia. 23 compounds inhibited the proliferation of T. gondii, three of them with an IC₅₀ of approximately 1 μM. The structural integrity of E. multilocularis metacestodes was affected by 22 compounds. In contrast, HFF were not susceptible to any of these thioureides, while Caco2 cells were affected by 17 compounds, two of them inhibiting proliferation with an IC₅₀ in the micromolar range. Thioureides may thus present a promising class of anti-infective agents.     

Relationships between spatial configuration of tropical forest patches and woody plant diversity in northeastern Puerto Rico

The destruction and fragmentation of tropical forests are major sources of global biodiversity loss. A better understanding of anthropogenically altered landscapes and their relationships with species diversity and composition is needed in order to protect biodiversity in these environments. The spatial patterns of a landscape may control the ecological processes that shape species diversity and composition. However, there is little information about how plant diversity varies with the spatial configuration of forest patches especially in fragmented tropical habitats. The northeastern part of Puerto Rico provides the opportunity to study the relationships between species richness and composition of woody plants (shrubs and trees) and spatial variables [i.e., patch area and shape, patch isolation, connectivity, and distance to the Luquillo Experimental Forest (LEF)] in tropical forest patches that have regenerated from pasturelands. The spatial data were obtained from aerial color photographs from year 2000. Each photo interpretation was digitized into a GIS package, and 12 forest patches (24–34 years old) were selected within a study area of 28 km². The woody plant species composition of the patches was determined by a systematic floristic survey. The species diversity (Shannon index) and species richness of woody plants correlated positively with the area and the shape of the forest patch. Larger patches, and patches with more habitat edge or convolution, provided conditions for a higher diversity of woody plants. Moreover, the distance of the forest patches to the LEF, which is a source of propagules, correlated negatively with species richness. Plant species composition was also related to patch size and shape and distance to the LEF. These results indicate that there is a link between landscape structure and species diversity and composition and that patches that have similar area, shape, and distance to the LEF provide similar conditions for the existence of a particular plant community. In addition, forest patches that were closer together had more similarity in woody plant species composition than patches that were farther apart, suggesting that seed dispersal for some species is limited at the scale of 10 km.     

An interesting diagnosis for a presacral mass: case report

A presacral mass can present a diagnostic dilemma for the surgical oncologist. Differential diagnoses include congenital causes such as teratoma or chordoma, neurological causes such as neurilemoma or neurofibroma or other malignancies such as lymphoma or sarcoma. Diagnosis usually requires imaging such as CT and MRI and tissue biopsy. We present an unusual cause of a presacral mass being extramedullary haematopoiesis, found incidentally in a 71 year old female. Extramedullary haematopoiesis is defined as the production of myeloid and erythroid elements outside of the bone-marrow. This diagnosis is extremely rare in the presacral area especially in a patient with no haematological abnormalities. A review of the literature is presented.     

Proteomic Studies of a Single CNS Synapse Type: The Parallel Fiber/Purkinje Cell Synapse

Precise neuronal networks underlie normal brain function and require distinct classes of synaptic connections. Although it has been shown that certain individual proteins can localize to different classes of synapses, the biochemical composition of specific synapse types is not known. Here, we have used a combination of genetically engineered mice, affinity purification, and mass spectrometry to profile proteins at parallel fiber/Purkinje cell synapses. We identify approximately 60 candidate postsynaptic proteins that can be classified into 11 functional categories. Proteins involved in phospholipid metabolism and signaling, such as the protein kinase MRCKγ, are major unrecognized components of this synapse type. We demonstrate that MRCKγ can modulate maturation of dendritic spines in cultured cortical neurons, and that it is localized specifically to parallel fiber/Purkinje cell synapses in vivo. Our data identify a novel synapse-specific signaling pathway, and provide an approach for detailed investigations of the biochemical complexity of central nervous system synapse types.     

Autophagosome Formation Depends on the Small GTPase Rab1 and Functional ER Exit Sites

Autophagy is an important cellular degradation pathway present in all eukaryotic cells. Via this pathway, portions of the cytoplasm and/or organelles are sequestered in double‐membrane structures called autophagosomes. In spite of the significant advance achieved in autophagy, the long‐standing question about the source of the autophagic membrane remains unsolved. We have investigated the role of the secretory pathway in autophagosome biogenesis. Sar1 and Rab1b are monomeric GTPases that control traffic from the endoplasmic reticulum (ER) to the Golgi. We present evidence indicating that the activity of both proteins is required for autophagosome formation. Overexpression of dominant‐negative mutants and the use of siRNAs impaired autophagosome generation as determined by LC3 puncta formation and light chain 3 (LC3)‐II processing. In addition, our results indicate that the autophagic and secretory pathways intersect at a level preceding the brefeldin A blockage, suggesting that the transport from the cis/medial Golgi is not necessary for autophagosome biogenesis. Our present results highlight the role of transport from the ER in the initial events of the autophagic vacuole development.     

Distribution, population parameters, and diet of Astropecten marginatus (Asteroidea: Astropectinidae) in the Venezuelan Atlantic coast

Astropecten marginatus is a sea star widely distributed in Northern and Eastern South America, found on sandy and muddy bottoms, in shallow and deep waters. To describe some of its ecological characteristics, we calculated it spatial-temporal distribution, population parameters (based on size and weight) and diet in the Orinoco Delta ecoregion (Venezuela). The ecoregion was divided in three sections: Golfo de Paria, Boca de Serpiente and Plataforma Deltana. Samples for the rainy and dry seasons came from megabenthos surveys of the "Línea Base Ambiental Plataforma Deltana (LBAPD)" and "Corocoro Fase I (CFI)" projects. The collected sea stars were measured, weighted and dissected by the oral side to extract their stomach and identify the preys consumed. A total of 570 sea stars were collected in LBAPD project and 306 in CFI one. The highest densities were found during the dry season in almost all sections. In LBAPD project the highest density was in "Plataforma Deltana" section (0.007 +/- 0.022 ind/m2 in dry season and 0.014 +/- 0.06 ind/m2 in rainy season) and in the CFI project the densities in "Golfo de Paria" section were 0.705 +/- 0.829 ind/m2 in rainy season and 1.027 +/- 1.107 ind/m2 in dry season. The most frequent size range was 3.1-4.6cm. The highest biomass was found in "Golfo de Paria" section (7.581 +/- 0.018 mg/m2 in dry season and 0.005 +/- 6.542 x 10(-06) mg/m2 in rainy season for 2004-2005 and 3.979 +/- 4.024 mg/m2 in dry season; and 3.117 +/- 3.137 mg/m2 in rainy season for 2006). A linear relationship was found between the sea star size and its weight but no relationship was observed between its size and the depth where it was collected. Mollusks are dominant in the sea star diet (47.4% in abundance). The diet in any of the sections, seasons or between projects or size class was heterogeneous, using multivariate ordinations (MDS) and SIMPER analysis and there was no difference in the prey number or food elements that a sea star can eat. Although A. marginatus has been described as a predator, in this study were also inferred scavenger and detritivorous habits.     

Oral contraceptive use and increased plasma concentration of C-reactive protein

We examined, in young adult women, the association between current low dose oral contraceptive (OC) use and plasma levels of C-reactive protein (CRP), an acute phase reactant predictive of cardiovascular disease risk. We conducted a cross-sectional analysis of 30 healthy, non-smoking, non-obese women (18 OC users and 12 nonusers) who were subjects in a randomized diet-controlled trial of the effects of soy intake on sex hormone metabolism. The study was sited at a university outpatient general clinical research center. Fasting plasma CRP levels were measured 4 times during 2 menstrual cycles (2 mid-follicular phase and 2 mid-luteal phase) using a high-sensitivity CRP assay. Differences between OC users and nonusers were examined by 3-way analysis of variance. Multiple regression was used to examine the relationship between OC use and CRP. There were no significant differences in baseline demographic characteristics between OC users and nonusers. Plasma CRP levels (mean +/- SE) were 2 times higher among OC users than among non-users (2.0 +/- 0.2 versus 0.9 +/- 0.3 mg/l, p<0.0001) independent of diet assignment, diet treatment order, and phase of the menstrual cycle. In a multivariate model, OC use predicted 32 percent of the variance in CRP levels (p<0.0001). As all CRP levels were within a previously established normal range, further study is indicated to establish the clinical significance of the observed elevated CRP levels in OC users.