Cell plasticity in homeostasis and regeneration

Over the past decades, genetic analyses performed in vertebrate and invertebrate organisms deciphered numerous cellular and molecular mechanisms deployed during sexual development and identified genetic circuitries largely shared among bilaterians. In contrast, the functional analysis of the mechanisms that support regenerative processes in species randomly scattered among the animal kingdom, were limited by the lack of genetic tools. Consequently, unifying principles explaining how stress and injury can lead to the reactivation of a complete developmental program with restoration of original shape and function remained beyond reach of understanding. Recent data on cell plasticity suggest that beside the classical developmental approach, the analysis of homeostasis and asexual reproduction in adult organisms provides novel entry points to dissect the regenerative potential of a given species, a given organ or a given tissue. As a clue, both tissue homeostasis and regeneration dynamics rely on the availability of stem cells and/or on the plasticity of differentiated cells to replenish the missing structure. The freshwater Hydra polyp provides us with a unique model system to study the intricate relationships between the mechanisms that regulate the maintenance of homeostasis, even in extreme conditions (starvation and overfeeding) and the reactivation of developmental programs after bisection or during budding. Interestingly head regeneration in Hydra can follow several routes according to the level of amputation, suggesting that indeed the homeostatic background dramatically influences the route taken to bridge injury and regeneration. Mol. Reprod. Dev. 77:837–855, 2010. © 2010 Wiley‐Liss, Inc.     

Dopamine receptor D4 allele distribution in Amerindians: A reflection of past behavior differences?

The DRD4 variable number of tandem repeats (VNTR) allele distribution of 172 Guarani (Kaiowá and Ñandeva subgroups) and Kaingang Brazilian Amerindians is reported. These results are integrated with those previously obtained for this ethnic group. Allele frequencies for the three populations are within the interval observed for 15 other Native American populations and show intermediate values between those observed in Amazonia and Patagonia. Significant differences in allele distribution between recent past hunter–gatherer and agriculturalist populations are observed, with an increase of the 7R allele among hunter–gatherers (P < 0.001). Analysis of molecular variance (AMOVA) and pairwise F_ST data suggest three distinct sectors for the genetic landscape of Native South America: Andes, Center/Southeast region, and Amazonia. Common traits among hunter–gatherers such as novelty‐seeking temperament, hyperactivity, and impulsivity could have been important and advantageous in new environments during America's prehistoric colonization. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.     

The defensive functions of plant inhibitors are not restricted to insect enzyme inhibition

Three plant proteinase inhibitors BbKI (kallikrein inhibitor) and BbCI (cruzipain inhibitor) from Bauhinia bauhinioides, and a BrTI (trypsin inhibitor) from B. rufa, were examined for other effects in Callosobruchus maculatus development; of these only BrTI affected bruchid emergence. BrTI and BbKI share 81% identities in their primary sequences and the major differences between them are the regions comprising the RGD and RGE motifs in BrTI. These sequences were shown to be essential for BrTI insecticidal activity, since a modified BbKI [that is a recombinant form (BbKIm) with some amino acid residues replaced by those found in BrTI sequence] also strongly inhibited insect development. By using synthetic peptides related to the BrTI sequence, YLEAPVARGDGGLA-NH₂ (RGE) and IVYYPDRGETGL-NH₂ (RGE), it was found that the peptide with an RGE sequence was able to block normal development of C. maculatus larvae (ED₅₀ 0.16% and LD₅₀ 0.09%), this being even more effective than the native protein.     

Chromatin supraorganization, DNA fragmentation, and cell death in erythrocytes of the rattlesnake, Crotalus durissus terrificus (Serpentes, Viperidae), infected with the protozoan, Hepatozoon spp. (Apicomplexa, Hepatozoidae)

Forms of the protozoan of the Hepatozoon genus are detected free in the circulation and also within some of the erythrocytes of infected snakes. In healthy snakes, DNA fragmentation and cell death usually affect a few circulating erythrocytes in agreement with the long life span expected for these cells. In the present study we investigated whether infection by Hepatozoon spp. affected the incidence of DNA fragmentation and cell death in erythrocytes from the rattlesnake, Crotalus durissus terrificus. Methods such as the kinetics of Feulgen-DNA hydrolysis, and the TUNEL and comet assays, previously used for the study of chromatin organization and DNA fragmentation in erythrocytes of healthy snakes, were used. The results indicated that Hepatozoon spp. increased the DNA fragmentation and chromatin condensation typical of cell death in circulating erythrocytes of C. d. terrificus, including cells that do not harbour the parasite. The Hepatozoon infection is thus suggested to accelerate destruction of erythrocytes in the rattlesnake, not only affecting cells harbouring the parasite, but also in those without it.     

The histopathological evaluation of the local tolerance of alendronate containing medicines

INTRODUCTION: In order to be effective, treatment for osteoporosis must be long-term. Unfortunately, according to clinical trials and clinical practice the most frequent cause of patient resignation from the treatment is adverse reactions to the medications. In the case of bisphosphonates they are most frequently connected with irritant impact of the drug on gastrointestinal mucosa. The aim of our study was to answer the question whether alendronate tablets coated with a thin neutral layer may protect gastrointestinal mucosa from the irritant effects of the active substance. MATERIAL AND METHODS: Three types of tablets were administered into the cheek pouches of 18 Syrian hamsters (divided into 3 experimental groups: I, II, III) i.e. regular alendronate tablets, coated alendronate tablets and placebo. The tablets were applied for 4 minutes a day on 4 consecutive days. 24 hours after the last application, the animals were sacrificed and segments of buccal tissue were taken for histopathological examination. Oral tissue reaction was assessed using the microscopic examination grading system developed by ISO. The following adverse changes of the tissue were recorded: epithelial lesions, leucocyte infiltration, vascular congestion and oedema. Later the irritation index was calculated. RESULTS: The irritation index was 11.0 (moderately irritant), 0.0 and 0.0 (none-irritant), in each group respectively. CONCLUSION: It appears that the administration of the coated alendronate tablets reduces the frequency and intensity of the local adverse events from the gastrointestinal tract.     

Higher frequency of legitimate pollinators and fruit set of autotetraploid trees of Libidibia ferrea (Leguminosae) compared to diploids in a mixed tropical urban population

Journal of Plant Research - In mixed-ploidy populations, newly formed polyploids initially occur at low frequencies when compared to diploids. However, polyploidy may lead to morphological and...     

Homocysteine thiolactone and <Emphasis Type="Italic">N</Emphasis>-homocysteinylated protein induce pro-atherogenic changes in gene expression in human vascular endothelial cells

Genetic or nutritional deficiencies in homocysteine (Hcy) metabolism lead to hyperhomocysteinemia (HHcy) and cause endothelial dysfunction, a hallmark of atherosclerosis. In addition to Hcy, related metabolites accumulate in HHcy but their role in endothelial dysfunction is unknown. Here, we examine how Hcy-thiolactone, N-Hcy-protein, and Hcy affect gene expression and molecular pathways in human umbilical vein endothelial cells. We used microarray technology, real-time quantitative polymerase chain reaction, and bioinformatic analysis with PANTHER, DAVID, and Ingenuity Pathway Analysis (IPA) resources. We identified 47, 113, and 30 mRNAs regulated by N-Hcy-protein, Hcy-thiolactone, and Hcy, respectively, and found that each metabolite induced a unique pattern of gene expression. Top molecular pathways affected by Hcy-thiolactone were chromatin organization, one-carbon metabolism, and lipid-related processes [?log(P value) = 20–31]. Top pathways affected by N-Hcy-protein and Hcy were blood coagulation, sulfur amino acid metabolism, and lipid metabolism [?log(P value)] = 4–11; also affected by Hcy-thiolactone, [?log(P value) = 8–14]. Top disease related to Hcy-thiolactone, N-Hcy-protein, and Hcy was ‘atherosclerosis, coronary heart disease’ [?log(P value) = 9–16]. Top-scored biological networks affected by Hcy-thiolactone (score = 34–40) were cardiovascular disease and function; those affected by N-Hcy-protein (score = 24–35) were ‘small molecule biochemistry, neurological disease,’ and ‘cardiovascular system development and function’; and those affected by Hcy (score = 25–37) were ‘amino acid metabolism, lipid metabolism,’ ‘cellular movement, and cardiovascular and nervous system development and function.’ These results indicate that each Hcy metabolite uniquely modulates gene expression in pathways important for vascular homeostasis and identify new genes and pathways that are linked to HHcy-induced endothelial dysfunction and vascular disease.     

Conformational and biological properties of Bauhinia bauhinioides kallikrein inhibitor fragments with bradykinin‐like activities

Proteinase inhibitors extracted form medicinal plants are an interesting source of new drugs. Modifications in the structure of some of this kind of macromolecules could also lead to compounds of interesting biological properties. In this work, we synthesized and tested one fragment containing the reactive site of the Bauhinia bauhinioides kallikrein inhibitor (BbKI), denoted BbKI_51–62, and a related analog (P₂) in which a proline residue was inserted in order to mimic the N‐terminal region of the bradykinin molecule. The related retro‐inverso counterparts Ri‐BbKI_51–62 and Ri‐P₂ were also included. The ability of these peptides to induce contraction of stomach fundus isolated from mouse was evaluated as well as their capability to induce calcium release from a cell culture of smooth muscle from guinea pig ileum. The conformational properties of the peptides were evaluated by circular dichroism and their resistance to enzymatic degradation by exposure to human blood plasma. Our results show that neither the parent BbKI_51–62 nor its Ri‐BbKI_51–62 analog exhibit bradykinin‐like activity, although the retro‐inverso isomer was resistant to blood plasma degradation. On the other hand, the peptides P₂ and Ri‐P₂ presented contractile activities on gastric smooth muscle from stomach fundus possibly by acting via B‐2 receptor. Both compounds also induce calcium release from guinea pig ileum muscle cells in a manner similar to bradykinin. Moreover, both compounds also inhibited porcine pancreatic kallikrein. However, conformational analysis did not reveal any direct correlation between structure and biological effects. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.     

Chromosome polymorphism in <Emphasis Type="Italic">Rineloricaria pentamaculata</Emphasis> (Loricariidae,Siluriformes) of the Paraná River basin

Cytogenetic analysis in three Rineloricaria pentamaculata populations revealed diploid number 2n = 56 chromosomes, karyotype formula 8m/sm + 48st/a and FN = 64. Owing to the presence of the heteromorphic chromosome pair with a big submetacentric chromosome and a small acrocentric one in both males and females, 42.9% of specimens in the Tauá Stream population had the karyotype formula 9m/sm + 47st/a and FN = 65. Analysis of the nucleolus-organizing region by Ag-NOR and FISH techniques showed a single NOR system at pair 5 for R. pentamaculata populations of the Keller River and the Tauá Stream. However, specimens of populations of the Tatupeba Stream had multiple NOR systems at pairs 5 and 8. A constitutive heterochromatin pattern in R. pentamaculata is mainly distributed in the pericentromeric and telomeric regions with interstitial markers in certain chromosomes. Heterochromatin is located in the telomeric and centromeric positions of the acrocentric chromosome in the heteromorphic pair of the Tauá Stream population. In the submetacentric chromosome the markings are located in the telomeric (short arm), pericentomeric and interstitial (long arm) positions. The origins of polymorphisms are discussed.