The importance of polymerization and galloylation for the antiproliferative properties of procyanidin-rich natural extracts

Grape (Vitis vinifera) and pine (Pinus pinaster) bark extracts are widely used as nutritional supplements. Procyanidin-rich fractions from grape and pine bark extract showing different mean degrees of polymerization, percentage of galloylation (percentage of gallate esters) and reactive oxygen species-scavenging capacity were tested on HT29 human colon cancer cells. We observed that the most efficient fractions in inhibiting cell proliferation, arresting the cell cycle in G(2) phase and inducing apoptosis were the grape fractions with the highest percentage of galloylation and mean degree of polymerization. Additionally, the antiproliferative effects of grape fractions were consistent with their oxygen radical-scavenging capacity and their ability to trigger DNA condensation-fragmentation.     

Physiological adaptations to exercise in people with spinal cord injury

The number of patients that suffer some type of spinal cord lesion in recent years are high and have increased because of factors such as traffic accidents. Although their life expectancy has increased, cardiovascular illnesses is one of the main causes of morbidity and mortality. Since the degree of physical fitness is an important factor regarding the risk of cardiovascular disease, the objective of the present study was to examine the global adaptation (cardiorespiratory, metabolic and thermoregulatory response) of the organism to exercise and the application of this data to the habitual practice of physical activity to improve state of health. A group of 42 patients with spinal injury, 85% of whom were paraplegic and the remaining 15% tetraplegic performed 42 exercise tests on a cycloergometer. Body temperature (tympanum, surface of the deltoids and surface of the back), metabolic parameters (plasma uric acid, glycemia, plasma lactate), cardiocirculatory adaptation (heart rate, blood pressure arm, blood pressure leg) and ventilatory adaptation (VO2, VCO2, fr Vt, VE) were monitored. Blood pressure in the arm, blood concentrations of lactate and ventilatory parameters showed an evolution statistically dependent on the work to which the subject was submitted. Heart rate showed a statistically significant correlation with the ventilatory parameters and work load. The proportional response of the cardioventilatory parameters to the increase in the work load allowed us to evaluate the repercussion of a given exercise and thus avoid exercise of an excessive intensity that could produce cardiocirculatory changes that might entail an added risk. Heart rate presents an excellent correlation, shown in this work, with the oxygen consumption and could therefore be used to quantify the cardiorespiratory and metabolic repercussion of the exercise carried out. Furthermore, this quantification may allow for the adaptation of exercise intensity to the patient thus improving the results obtained from the practice of exercise that has been proven so necessary in these patients.     

Nuclear pore composition regulates neural stem/progenitor cell differentiation in the mouse embryo

Serving as the primary conduit for communication between the nucleus and the cytoplasm, nuclear pore complexes (NPCs) impact nearly every cellular process. The extent to which NPC composition varies and the functional significance of such variation in mammalian development has not been investigated. Here we report that a null allele of mouse nucleoporin Nup133, a structural subunit of the NPC, disrupts neural differentiation. We find that expression of Nup133 is cell type and developmental stage restricted, with prominent expression in dividing progenitors. Nup133-deficient epiblast and ES cells abnormally maintain features of pluripotency and differentiate inefficiently along the neural lineage. Neural progenitors achieve correct spatial patterning in mutant embryos; however, they are impaired in generating terminally differentiated neurons, as are Nup133 null ES cells. Our results reveal a role for structural nucleoporins in coordinating cell differentiation events in the developing embryo.     

Homeostatic NMDA receptor down-regulation via brain derived neurotrophic factor and nitric oxide-dependent signalling in cortical but not in hippocampal neurons

Nitric oxide (NO) has been proposed to down-regulate NMDA receptors (NMDA-Rs) in a homeostatic manner. However, NMDA-R-dependent NO synthesis also can cause excitotoxic cell death. Using bicuculline-stimulated hippocampal and cortical cell cultures, we have addressed the role of the brain-derived neurotrophic factor-NO pathway in NMDA-R down-regulation. This pathway protected cortical cells from NMDA-induced death and led to NMDA-R inhibition. In contrast, no evidence was gained for the presence of this protective pathway in hippocampal neurons, in which NMDA-induced NO synthesis was confirmed to be toxic. Therefore, opposing effects of NO depended on the activation of different signalling pathways. The pathophysiological relevance of this observation was investigated in synaptosomes and post-synaptic densities isolated from rat hippocampi and cerebral cortices following kainic acid-induced status epilepticus. In cortical, but not in hippocampal synaptosomes, brain-derived neurotrophic factor induced NO synthesis and inhibited NMDA-R currents present in isolated post-synaptic densities. In conclusion, we identified a NO-dependent homeostatic response in the rat cerebral cortex induced by elevated activity. A low performance of this pathway in brain areas including the hippocampus may be related to their selective vulnerability in pathologies such as temporal lobe epilepsy.     

Differential Host Handling Behavior between Feeding and Oviposition in the Parasitic Wasp <Emphasis Type="Italic">Haplogonatopus hernandezae</Emphasis>

Lifetime fitness is directly influenced by the decision to use resources for either current or future reproduction. Thus, females should weigh the costs and benefits of each reproductive opportunity and allocate resources accordingly. Here, we explore decision-making and the time spent handling hosts of different instars in the parasitoid Haplogonatopus hernandezae, which uses a single planthopper host to either oviposit (i.e., current reproduction) or feed (i.e., future reproduction). Our results indicate that manipulation time in attacks that led to either oviposition and feeding increased with host instar and size. Consequently, attacks were less successful on older host instars than younger ones. Similarly, attack and handling time during oviposition was greater when manipulating fifth instar nymphs compared to younger ones, but oviposition time was similar. Surprisingly, host grasping by the chelate forelegs differed between oviposition and feeding events, and the specific chelate foreleg morphology of H. hernandezae facilitates the specific grasp of the clypeus and gena of the host. We also link this previously undescribed host grasping and differential handling behavior in this species to the final decision to oviposit or feed. Given the differences in handling time and effort among different host instars, we found that older hosts were more often chosen for consumption than younger hosts, and younger hosts were chosen more often for oviposition. Our study suggests that the tradeoff between current and future benefits is influenced by the investment in handling hosts of different instars, and the assessment of host suitability for successful offspring survival.     

Geographic Variation and Succession of Arthropod Communities in Inflorescences and Infructescences of Xanthosoma (Araceae)1

Phytotelmata, small aquatic ecosystems within different structures of terrestrial plants, occur in the inflorescescences and infructescences of Xanthosoma (Araceae). This study reports changes in composition and abundance of arthropods during the anthesis of inflorescences and in the developing infructescences of three species of Xanthosoma at three different geographic locations: (1) X. undipes in a tropical cloud forest of Costa Rica, Central America; (2) X. daguense in a tropical cloud forest in the central Andes of Colombia; and (3) X. poeppigii in the Peruvian Amazonas. All Xanthosoma species displayed similar interactions with the main pollinators, dynastine beetles. We observed a succession from terrestrial to aquatic arthropods as inflorescences aged and set fruit. However, community composition varied among different Xanthosoma species. Some arthropods recorded in Xanthosoma phytotelmata have also been reported as inflorescence visitors of the dynastine‐pollinated terrestrial genus Dieffenbachia and of vines from Philodendon and Syngonium. Further research may elucidate if phytotelmata similar to those described for Xanthosoma could occur among dynastine‐pollinated genera of Araceae, both in the understory and the canopy of Neotropical forests.     

The Xenopus TACC homologue, maskin, functions in mitotic spindle assembly

Maskin is the Xenopus homolog of the transforming acidic coiled coil (TACC)-family of microtubule and centrosome-interacting proteins. Members of this family share a approximately 200 amino acid coiled coil motif at their C-termini, but have only limited homology outside of this domain. In all species examined thus far, perturbations of TACC proteins lead to disruptions of cell cycle progression and/or embryonic lethality. In Drosophila, Caenorhabditis elegans, and humans, these disruptions have been attributed to mitotic spindle assembly defects, and the TACC proteins in these organisms are thought to function as structural components of the spindle. In contrast, cell division failure in early Xenopus embryo blastomeres has been attributed to a role of maskin in regulating the translation of, among others, cyclin B1 mRNA. In this study, we show that maskin, like other TACC proteins, plays a direct role in mitotic spindle assembly in Xenopus egg extracts and that this role is independent of cyclin B. Maskin immunodepletion and add-back experiments demonstrate that maskin, or a maskin-associated activity, is required for two distinct steps during spindle assembly in Xenopus egg extracts that can be distinguished by their response to "rescue" experiments. Defects in the "early" step, manifested by greatly reduced aster size during early time points in maskin-depleted extracts, can be rescued by readdition of purified full-length maskin. Moreover, defects in this step can also be rescued by addition of only the TACC-domain of maskin. In contrast, defects in the "late" step during spindle assembly, manifested by abnormal spindles at later time points, cannot be rescued by readdition of maskin. We show that maskin interacts with a number of proteins in egg extracts, including XMAP215, a known modulator of microtubule dynamics, and CPEB, a protein that is involved in translational regulation of important cell cycle regulators. Maskin depletion from egg extracts results in compromised microtubule asters and spindles and the mislocalization of XMAP215, but CPEB localization is unaffected. Together, these data suggest that in addition to its previously reported role as a translational regulator, maskin is also important for mitotic spindle assembly.     

Developmental stability: a major role for cyclin G in drosophila melanogaster

Morphological consistency in metazoans is remarkable given the pervasive occurrence of genetic variation, environmental effects, and developmental noise. Developmental stability, the ability to reduce developmental noise, is a fundamental property of multicellular organisms, yet its genetic bases remains elusive. Imperfect bilateral symmetry, or fluctuating asymmetry, is commonly used to estimate developmental stability. We observed that Drosophila melanogaster overexpressing Cyclin G (CycG) exhibit wing asymmetry clearly detectable by sight. Quantification of wing size and shape using geometric morphometrics reveals that this asymmetry is a genuine-but extreme-fluctuating asymmetry. Overexpression of CycG indeed leads to a 40-fold increase of wing fluctuating asymmetry, which is an unprecedented effect, for any organ and in any animal model, either in wild populations or mutants. This asymmetry effect is not restricted to wings, since femur length is affected as well. Inactivating CycG by RNAi also induces fluctuating asymmetry but to a lesser extent. Investigating the cellular bases of the phenotypic effects of CycG deregulation, we found that misregulation of cell size is predominant in asymmetric flies. In particular, the tight negative correlation between cell size and cell number observed in wild-type flies is impaired when CycG is upregulated. Our results highlight the role of CycG in the control of developmental stability in D. melanogaster. Furthermore, they show that wing developmental stability is normally ensured via compensatory processes between cell growth and cell proliferation. We discuss the possible role of CycG as a hub in a genetic network that controls developmental stability.