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Statement of Problem: The lack of consensus regarding a standardized set of outcome measurements and noncompliance with current reporting guidelines in clinical trials of tooth-supported fixed dental prostheses (FDPs) hamper interstudy comparability, compromise scientific evidence, and waste research effort and resources in prosthetic dentistry., Purpose: The primary objective of this systematic review was to identify all primary and secondary outcome measurements assessed in randomized controlled trials (RCTs) of tooth-supported FDPs. Secondary objectives were to assess their methodological quality by using the Cochrane Collaboration's risk of bias tool (RoB, v2.0) and their reporting quality by means of a standardized 16-item CONSORT assessment tool through published reports., Material and Methods: An electronic search was conducted in MEDLINE, EMBASE, and Cochrane library to identify all RCT-related articles published in the past 10 years. Differences in RoB were tested with the Pearson chi-squared test, and those in CONSORT score with the Student t test., Results: A total of 64 RCTs from 79 publications were deemed eligible. The diversity of outcome measures used in the field is apparent. Twenty percent of the included studies had a low RoB, 79% showed some concerns, and 1% had a high RoB. The mean ±standard deviation CONSORT compliance score was 22.56 ±3.17. Trials adhered to the CONSORT statement reported lower RoB than those that did not adhere (P<.001). RCTs with a low RoB reported more comprehensive adherence to CONSORT guidelines than those with some concerns (MD 4 [95% CI 1.52-6.48]; P=.004)., Conclusions: A standardized core outcome reporting set in clinical research on tooth-supported FDPs remains evident. Adherence to the CONSORT statement continues to be low, with some RoB concerns that can be improved., (Copyright © 2022 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Objectives: To measure the impact of superimposition methods and the designated comparison area on accuracy analyses of dentate models using an ISO-recommended 3-dimensional (3D) metrology-grade inspection software (Geomagic Control X; 3D Systems; Rock Hill, South Carolina; USA)., Materials and Methods: A dentate maxillary typodont scanned with a desktop scanner (E4; 3 Shape; Copenhagen; Denmark) and an intraoral scanner (Trios 4; 3 Shape; Copenhagen; Denmark) was used as reference. Eight groups were created based on the core features of each superimposition method: landmark-based alignment (G1); partial area-based alignment (G2); entire tooth area-based alignment (G3); double alignment combining landmark-based alignment with entire tooth area-based alignment (G4); double alignment combining partial area-based alignment with entire tooth area-based alignment (G5); initial automated quick pre-alignment (G6); initial automated precise pre-alignment (G7); and entire model area-based alignment (G8). Diverse variations of each alignment and two regions for accuracy analyses (teeth surface or full model surface) were tested, resulting in a total of thirty-two subgroups (n = 18). The alignment accuracy between experimental and reference meshes was quantified using root mean square (RMS) error as trueness and its repeatability as precision. The descriptive statistics, a factorial repeated measures analysis of variance (ANOVA) and a post hoc Tuckey multiple comparison tests were used to analyze the trueness, and precision (α = 0.05)., Results: A total of 576 superimpositions were performed. The unique partial area-based superimposition method demonstrated the least precise alignment and was the sole group to exhibit a significant difference (p<.001). Automated initial pre-alignments demonstrated similar accuracy to other superimposition methods (p>.05). Double alignments did not result in accuracy improvement (p>.05). The designated comparison area displayed differences in both trueness (p<.001) and precision (p<.001), leading to an overall discrepancy of 8 ± 4 μm between selecting the teeth surface or full model surface., Conclusions: The superimposition method choice within the tested software did not impact accuracy analyses, except when the alignment relies on a unique and reduced area, such as the palatal rugae, a single tooth, or three adjacent teeth on one side., Clinical Significance: The superimposition method choice within the tested ISO-recommended 3D inspection software did not impact accuracy analyses., Competing Interests: Declaration of competing interest The authors have no conflict of interest to report pertaining to the conduction of this study., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Clinical trials have provided evidence that transplants of dopaminergic precursors, which may be replaced by new in vitro stem cell sources, can integrate into the host tissue, and alleviate motor symptoms in Parkinson´s disease (PD). In some patients, deterioration of graft function occurred several months after observing a graft-derived functional improvement. Rejection of peripheral organs was initially related to HLA-specific antibodies. However, the role of non-HLA antibodies is now considered also relevant for rejection. Angiotensin-II type-1 receptor autoantibodies (AT1-AA) act as agonists of the AT1 receptors. AT1-AA are the non-HLA antibodies most widely associated with graft dysfunction or rejection after transplantation of different solid organs and hematopoietic stem cells. However, it is not known about the presence and possible functional effects of AT1-AA in dopaminergic grafts, and the effects of treatment with AT1 receptor blockers (ARBs) such as candesartan on graft survival., Methods: In a 6-hydroxydopamine PD rat model, we studied the short-term (10 days)- and long-term (3 months) effects of chronic treatment with the ARB candesartan on survival of grafted dopaminergic neurons and microglial graft infiltration, as well as the effects of dopaminergic denervation and grafting on serum and CSF AT1-AA levels. The expression of AT1 receptors in grafted neurons was determined by laser capture microdissection., Results: At the early period post-grafting, the number of grafted dopaminergic neurons that survived was not significantly different between treated and untreated hosts (i.e., control rats and rats treated with candesartan), probably because, just after grafting, other deleterious factors are predominant for dopaminergic cell death, such as mechanical trauma, lack of growth factors/nutrients and ischemia. However, several months post-grafting, we observed a significantly higher number of surviving dopaminergic neurons and a higher density of striatal dopaminergic terminals in the candesartan-treated group. For several months, grafted rats showed blood and cerebrospinal fluid levels of AT1-AA higher than normal controls, and also higher AT1-AA levels than non-grafted parkinsonian rats., Conclusions: The results suggest the use of ARBs such as candesartan in PD patients, particularly before and after dopaminergic grafts, and the need to monitor AT1-AA levels in PD patients, particularly in those candidates for dopaminergic grafting., (© 2024. The Author(s).)

Parkinson's disease is a neurodegenerative condition characterized by motor impairments caused by the selective loss of dopaminergic neurons in the substantia nigra. Levodopa is an effective and well-tolerated dopamine replacement agent. However, levodopa provides only symptomatic improvements, without affecting the underlying pathology, and is associated with side effects after long-term use. Cell-based replacement is a promising strategy that offers the possibility to replace lost neurons in Parkinson's disease treatment. Clinical studies of transplantation of human fetal ventral mesencephalic tissue have provided evidence that the grafted dopaminergic neurons can reinnervate the striatum, release dopamine, integrate into the host neural circuits, and improve motor functions. One of the limiting factors for cell therapy in Parkinson's disease is the low survival rate of grafted dopaminergic cells. Different factors could cause cell death of dopaminergic neurons after grafting such as mechanical trauma, growth factor deprivation, hypoxia, and neuroinflammation. Neurotrophic factors play an essential role in the survival of grafted cells. However, direct, timely, and controllable delivery of neurotrophic factors into the brain faces important limitations. Different types of cells secrete neurotrophic factors constitutively and co-transplantation of these cells with dopaminergic neurons represents a feasible strategy to increase neuronal survival. In this review, we provide a general overview of the pioneering studies on cell transplantation developed in patients and animal models of Parkinson's disease, with a focus on neurotrophic factor-secreting cells, with a particular interest in mesenchymal stromal cells; that co-implanted with dopaminergic neurons would serve as a strategy to increase cell survival and improve graft outcomes., Competing Interests: None

Female dominance, a trait common to some Malagasy lemurs, has been viewed as an adaptation that decreases intersexual feeding competition. A hypothesized relationship exists between male "deference" (male submission in the absence of female aggression) and food availability. Sauther (1993) suggested that male ring-tailed lemurs at the Duke Lemur Center (Pereira et al., 1990) show more deference to females than do males in the wild owing to food abundance in captivity. To reexamine the link between food availability and male deference, we studied agonism and foraging in two nonwild ring-tailed lemur (Lemur catta) populations: the Los Angeles Zoo and St. Catherines Island (SCI). On SCI, we collected data under two feeding conditions: Low Provisions (low food availability) and High Provisions (high food availability). As expected, male deference measures at our study sites were more similar to measures of deference from other studies of L. catta in captivity than in the wild. Additionally, the change at SCI from low to high food availability was associated with increased male deference to females. Interestingly, male proximity to females during foraging at this location did not notably change between the low to high food availability conditions, suggesting that males were food competitors of females just as often under both feeding conditions. The increase in male deference under conditions of high food availability on SCI was due to males withdrawing more rapidly from female approaches during agonistic interactions. Hence, where food is more abundant, male L. catta are more likely to show submission to females, which appears to be a self-serving means of avoiding female aggression. Lemur males who are well-fed appear less apt to risk female aggression to obtain resources than more nutritionally stressed males. Our results support the view of female dominance in lemurs as an adaptive evolutionary response to conditions of resource limitation., (© 2022 The Authors. American Journal of Primatology published by Wiley Periodicals LLC.)

© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Adult neurogenesis is a dynamic and highly regulated process, and different studies suggest that dopamine modulates ventricular-subventricular zone (V-SVZ) neurogenesis. However, the specific role of dopamine and the mechanisms/factors underlying its effects on physiological and pathological conditions such as Parkinson's disease (PD) are not fully understood. Recent studies have described counter-regulatory interactions between renin-angiotensin system (RAS) and dopamine in peripheral tissues and in the nigrostriatal system. We have previously demonstrated that angiotensin receptors regulate proliferation and generation of neuroblasts in the rodent V-SVZ. However, possible interactions between dopamine receptors and RAS in the V-SVZ and their role in alterations of neurogenesis in animal models of PD have not been investigated. In V-SVZ cultures, activation of dopamine receptors induced changes in the expression of angiotensin receptors. Moreover, dopamine, via D2-like receptors and particularly D3 receptors, increased generation of neurospheres derived from the V-SVZ and this effect was mediated by angiotensin type-2 (AT2) receptors. In rats, we observed a marked reduction in proliferation and generation of neuroblasts in the V-SVZ of dopamine-depleted animals, and inhibition of AT1 receptors or activation of AT2 receptors restored proliferation and generation of neuroblasts to control levels. Moreover, intrastriatal mesencephalic grafts partially restored proliferation and generation of neuroblasts observed in the V-SVZ of dopamine-depleted rats. Our data revealed that dopamine and angiotensin receptor interactions play a major role in the regulation of V-SVZ and suggest potential beneficial effects of RAS modulators on the regulation of adult V-SVZ neurogenesis., (© 2021 The Authors. STEM CELLS published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Reactive oxygen species (ROS) are signalling molecules used to regulate cellular metabolism and homeostasis. However, excessive ROS production causes oxidative stress, one of the main mechanisms associated with the origin and progression of neurodegenerative disorders such as Parkinson's disease. NRF2 (Nuclear Factor-Erythroid 2 Like 2) is a transcription factor that orchestrates the cellular response to oxidative stress. The regulation of NRF2 signalling has been shown to be a promising strategy to modulate the progression of the neurodegeneration associated to Parkinson's disease. The NRF2 pathway has been shown to be affected in patients with this disease, and activation of NRF2 has neuroprotective effects in preclinical models, demonstrating the therapeutic potential of this pathway. In this review, we highlight recent advances regarding the regulation of NRF2, including the effect of Angiotensin II as an endogenous signalling molecule able to regulate ROS production and oxidative stress in dopaminergic neurons. The genes regulated and the downstream effects of activation, with special focus on Kruppel Like Factor 9 (KLF9) transcription factor, provide clues about the mechanisms involved in the neurodegenerative process as well as future therapeutic approaches.

A major limiting factor for cell therapy in Parkinson's disease is the poor survival and reinnervation capacity of grafted dopaminergic neurons, independently of the cell source. Mesenchymal stromal cells (MSCs) have high capability to regulate the local environment through the release of trophic, antiapoptotic and immunomodulatory factors. In this work, we investigated whether co-grafting of MSCs could improve the survival and reinnervation ability of dopaminergic precursors transplanted in animal models of Parkinson's disease. Rats with total unilateral dopaminergic denervation were grafted with a cell suspension of rat dopaminergic precursors (500,000 cells) with or without a high (200,000 cells) or low (25,000 cells) number of MSCs. Eight weeks after grafting, rats were tested for motor behaviour and sacrificed for histological analysis. Our results showed that the survival of dopaminergic neurons and graft-derived striatal dopaminergic innervation was higher in rats that received co-grafts containing a low number of MSCs than in non-co-grafted controls. However, the survival of dopaminergic neurons and graft-derived dopaminergic reinnervation was lower in rats receiving co-grafts with high number of MSCs than in non-co-grafted controls. In conclusion, co-grafting with MSCs or MSCs-derived products may constitute a useful strategy to improve dopaminergic graft survival and function. However, a tight control of MSCs density or levels of MSCs-derived products is necessary., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Madagascar's ring-tailed lemurs ( Lemur catta ) are experiencing rapid population declines due to ongoing habitat loss and fragmentation, as well as increasing exploitation for bushmeat and the illegal pet trade. Despite being the focus of extensive and ongoing behavioral studies, there is comparatively little known about the genetic population structuring of the species. Here, we present the most comprehensive population genetic analysis of ring-tailed lemurs to date from across their likely remaining geographic range. We assessed levels of genetic diversity and population genetic structure using multilocus genotypes for 106 adult individuals from nine geographically representative localities. Population structure and F ST analyses revealed moderate genetic differentiation with localities being geographically partitioned into northern, southern, western and also potentially central clusters. Overall genetic diversity, in terms of allelic richness and observed heterozygosity, was high in the species (AR = 4.74, H O  = 0.811). In fact, it is the highest among all published lemur estimates to date. While these results are encouraging, ring-tailed lemurs are currently affected by ongoing habitat fragmentation and occur at lower densities in poorer quality habitats. The effects of continued isolation and fragmentation, coupled with climate-driven environmental instability, will therefore likely impede the long-term viability of the species., Competing Interests: None declared., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

In the original publication of the article, figure 1 was wrongly published as a duplication.

Over the past 20 years, GPS collars have emerged as powerful tools for the study of nonhuman primate (hereafter, "primate") movement ecology. As the size and cost of GPS collars have decreased and performance has improved, it is timely to review the use and success of GPS collar deployments on primates to date. Here we compile data on deployments and performance of GPS collars by brand and examine how these relate to characteristics of the primate species and field contexts in which they were deployed. The compiled results of 179 GPS collar deployments across 17 species by 16 research teams show these technologies can provide advantages, particularly in adding to the quality, quantity, and temporal span of data collection. However, aspects of this technology still require substantial improvement in order to make deployment on many primate species pragmatic economically. In particular, current limitations regarding battery lifespan relative to collar weight, the efficacy of remote drop-off mechanisms, and the ability to remotely retrieve data need to be addressed before the technology is likely to be widely adopted. Moreover, despite the increasing utility of GPS collars in the field, they remain substantially more expensive than VHF collars and tracking via handheld GPS units, and cost considerations of GPS collars may limit sample sizes and thereby the strength of inferences. Still, the overall high quality and quantity of data obtained, combined with the reduced need for on-the-ground tracking by field personnel, may help defray the high equipment cost. We argue that primatologists armed with the information in this review have much to gain from the recent, substantial improvements in GPS collar technology.

The renin-angiotensin system (RAS), and particularly its angiotensin type-2 receptors (AT2), have been classically involved in processes of cell proliferation and maturation during development. However, the potential role of RAS in adult neurogenesis in the ventricular-subventricular zone (V-SVZ) and its aging-related alterations have not been investigated. In the present study, we analyzed the role of major RAS receptors on neurogenesis in the V-SVZ of adult mice and rats. In mice, we showed that the increase in proliferation of cells in this neurogenic niche was induced by activation of AT2 receptors but depended partially on the AT2-dependent antagonism of AT1 receptor expression, which restricted proliferation. Furthermore, we observed a functional dependence of AT2 receptor actions on Mas receptors. In rats, where the levels of the AT1 relative to those of AT2 receptor are much lower, pharmacological inhibition of the AT1 receptor alone was sufficient in increasing AT2 receptor levels and proliferation in the V-SVZ. Our data revealed that interactions between RAS receptors play a major role in the regulation of V-SVZ neurogenesis, particularly in proliferation, generation of neuroblasts, and migration to the olfactory bulb, both in young and aged brains, and suggest potential beneficial effects of RAS modulators on neurogenesis.

Objectives: This project investigated paternity among 14 sets of twins born into a colony of ring-tailed lemurs (Lemur catta) on St. Catherines Island, GA. Female L. catta commonly mate with >1 male, and twins of different sexes confirm that dizygotic twinning can occur in this species. However, no study has previously evaluated twins using genetic data to measure the proportion of mono versus dizygotic twinning in L. catta, and no study has tested for heteropaternity (sirehood by two different males) in this species. We predicted that L. catta would show a predominance of dizygosity and evidence for heteropaternity., Materials and Methods: Paternity was determined for 28 infants (14 sets of twins) via paternity exclusion analyses using 10 polymorphic microsatellite markers, and data were collected on sexual behavior across four mating seasons during the first cycle of mating in each year, which overlapped with the conceptive periods of these infants., Results: All twins were found to be dizygotic, as evidenced by dissimilar multilocus genotypes between the two infants of each twin pair. Heteropaternity was found in 3 of 14 (21% of) twin pairs, whereas the remaining 11 pairs of twins (79%) shared the same sire. In one case of heteropaternity, one sire was a resident male, and one sire was an extra-group male. An extra-group male also sired one of the same-sire twin pairs. All other sires of twins were group residents., Discussion: Female multiple mating, which is common to many primates including L. catta, can be viewed as an adaptive reproductive strategy whose function-in addition to fertility assurance or stimulating sperm competition-may be to increase the genetic diversity of a female's offspring, even among infants born in the same birth event. Therefore, during the course of primate evolution, the adaptive benefits of heteropaternity would be expected to have contributed to positive selection for female promiscuity., (© 2019 Wiley Periodicals, Inc.)

Nuclear factor-E2-related factor 2 (NRF2) is a transcription factor that activates the antioxidant cellular defense in response to oxidative stress, leading to neuroprotective effects in Parkinson's disease (PD) models. We have previously shown that Angiotensin II (AngII) induces an increase in reactive oxygen species (ROS) via AngII receptor type 1 and NADPH oxidase (NOX), which may activate the NRF2 pathway. However, controversial data suggest that AngII induces a decrease in NRF2 signaling leading to an increase in oxidative stress. We analyzed the effect of AngII and the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) in culture and in vivo, and examined the effects on the expression of NRF2-related genes. Treatment of neuronal cell lines Mes23.5, N27 and SH-SY5Y with AngII, 6-OHDA or a combination of both increased ROS production and reduced cell viability. Simultaneously, these treatments induced an increase in expression in the NRF2-regulated genes heme oxygenase 1 (Hmox1), NAD(P)H quinone dehydrogenase 1 (Nqo1) and Kruppel like factor 9 (Klf9). Moreover, overexpression of KLF9 transcription factor caused a reduction in the production of ROS induced by treatment with AngII or 6-OHDA and improved the survival of these neuronal cells. Rats treated with AngII, 6-OHDA or a combination of both also showed an increased expression of NRF2 related genes and KLF9. In conclusion, our data indicate that AngII induces a damaging effect in neuronal cells, but also acts as a signaling molecule to activate NRF2 and KLF9 neuroprotective pathways in cellular and animal models of PD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This article describes the effect of the oxidative stress inducers Angiotensin II and 6-hydroxydopamine (6-OHDA) on different cell lines. The levels of expression Angiotensin type 1 and type 2 receptors in different dopaminergic cell lines are shown. The data indicate that treatment with Angiotensin II and 6-OHDA increases the production of reactive oxygen species (ROS) and decreases cell viability. NRF2 is a transcription factor induced by ROS. We provide data that NRF2 overexpression increases cell viability in response to oxidative stress inducers compared to control cells, and that these inducers can, both separately and in combination, enhance the expression of NRF2-regulated genes heme oxygenase 1 (Hmox1), NAD(P)H quinone dehydrogenase 1 (Nqo1) and Kruppel like factor 9 (Klf9). Interpretation of these data and additional information is presented in the research article "Angiotensin II induces oxidative stress and upregulates neuroprotective signaling from the NRF2 and KLF9 pathway in dopaminergic cells" (Parga et al., 2018) [1].

Purpose: To study whether the shades of the 3D-Master System were grouped and represented in the chromatic space according to the three-color coordinates of value, chroma, and hue., Materials and Methods: Maxillary central incisor color was measured on tooth surfaces through the Easyshade Compact spectrophotometer using 1361 participants aged between 16 and 89. The natural (not bleached teeth) color of the middle thirds was registered in the 3D-Master System nomenclature and in the CIELCh system. Principal component analysis and cluster analysis were applied., Results: 75 colors of the 3D-Master System were found. The statistical analysis revealed the existence of 5 cluster groups. The centroid, the average of the 75 samples, in relation to lightness (L*) was 74.64, 22.87 for chroma (C*), and 88.85 for hue (h*). All of the clusters, except cluster 3, showed significant statistical differences with the centroid for the three-color coordinates (p <0.001)., Conclusions: The results of this study indicated that 75 shades in the 3D-Master System were grouped into 5 clusters following coordinates L*, C*, and h* resulting from the dental spectrophotometer Vita Easyshade compact. The shades that composed each cluster did not belong to the same lightness color dimension groups. There was no special uniform chromatic distribution among the colors of the 3D-Master System., (© 2017 by the American College of Prosthodontists.)

In addition to the classical hormonal (tissue-to-tissue) renin-angiotensin system (RAS), there are a paracrine (cell-to-cell) and an intracrine (intracellular/nuclear) RAS. A local paracrine brain RAS has been associated with several brain disorders, including Parkinson's disease (PD). Classically, angiotensin II (Ang II) is the main RAS effector peptide and acts through two major receptors: Ang II type 1 and 2 (AT1 and AT2) receptors. It has been shown that enhanced activation of the Ang II/AT1 axis exacerbates dopaminergic cell death. Several new components of the RAS have more recently been discovered. However, the role of new Ang 1-7/Mas receptor RAS component was not investigated in the brain and particularly in the dopaminergic system. In the present study, we observed Mas receptor labeling in dopaminergic neurons and glial cells in rat mesencephalic primary cultures; substantia nigra of rats, monkeys, and humans; and human induced pluripotent stem (iPS) cells derived from healthy controls and sporadic PD patients. The present data support a neuroprotective role of the Ang 1-7/Mas receptor axis in the dopaminergic system. We observed that this axis is downregulated with aging, which may contribute to the aging-related vulnerability to neurodegeneration. We have also identified an intracellular Ang 1-7/Mas axis that modulates mitochondrial and nuclear levels of superoxide. The present data suggest that nuclear RAS receptors regulate the adequate balance between the detrimental and the protective arms of the cell RAS. The results further support that the brain RAS should be taken into account for the design of new therapeutic strategies for PD.

Mesenchymal stromal cells (MSCs) have been shown to have useful properties for cell therapy and have been proposed for treatment of neurodegenerative diseases, including Parkinson's disease. However, the mechanisms involved in recovering dopaminergic neurons are not clear. The present study aims to evaluate the pathways and molecules involved in the neuroprotective effect of MSCs. We analyzed the viability of dopaminergic cells from different sources in response to conditioned medium derived from bone marrow MSC (MSC-CM). MSC-CM increased the viability of dopaminergic cells of rat and human origins, having both neuroprotective and neurorescue activities against effects of dopaminergic neurotoxin 6-hydroxydopamine. We found that lipid removal, inhibition of the prostaglandin E2 receptor 2 (EP2), and its signaling pathway were able to block the effects of MSC-CM on a pure population of dopaminergic neurons. Moreover, in primary mesencephalic cultures and hiPSC-derived neurons, inhibition of EP2 signaling caused a reduction in the number of dopaminergic neurons obtained in culture. Taken together, our results demonstrate for the first time the involvement of prostaglandin signaling from MSC in dopaminergic neuron survival through EP2 receptors, and suggest new approaches for treatment of Parkinson's disease.

Sexual selection for honest behavioral displays of quality has driven the development of remarkably complex courtship behavior in many animal species. Olfactory displays are often overlooked as an area of inquiry compared to auditory and visual displays. Ring-tailed lemur (Lemur catta) scent marking of substrates has been studied extensively, although the male olfactory displays of anointing and wafting tails to females has received relatively little attention. We studied the role of male olfactory displays to females, evaluating whether such signals function as honest, costly signals of male dominance status in two groups of wild L. catta at Berenty Reserve, Madagascar. Our results suggest that male tail anointing and tail wafting displays to pre-estrous and estrous females are correlated with male dominance rank, and moreover appear to operate as costly signals, as such displays increase aggression received from males and females while other types of scent marking do not. Furthermore, females showed greater mating preference (as measured by sexual presents) for resident males who performed the "anoint tail" and "waft tail" displays towards them. When males perform the "anoint tail" and "waft tail" displays to females, they receive higher levels of aggression than if they were to perform other types of scent marking. Interestingly, immigrating (peripheral) males performed the "anoint tail" and "waft tail" displays at higher rates than resident males, which could honestly indicate their quality or may simply be associated with the alternative mating strategy of transferring between groups to gain mating opportunities. Our finding that tail anointing and tail wafting displays function as honest signals of dominance for resident males-and that these costly displays appear to positively affect female mate choice-is the first evidence of this function for this particular olfactory signal in L. catta., (© 2017 Wiley Periodicals, Inc.)

Purpose: Assessment of the predictability of tooth color coordinates according to the CIELab system to estimate the color of the maxillary central incisor based on patient age and gender., Material and Methods: The tooth color of one of the maxillary central incisors of 1361 Caucasian Spanish individuals aged 16 to 89 years, male and female, was measured using the Easyshade compact spectrophotometer. Color coordinates L*, C*, h*, a*, and b* were recorded according to age and gender., Results: The results obtained show that differences in age account for 45% of the total variation of the L (lightness) coordinate; 21% of the variation in coordinate a*, and 17% of the variation in coordinate b* is due to the same reason. At a confidence level of 95% it may be proposed that the mean estimated color difference (ΔE ab *) between real natural color and that predicted by the linear regression model is between 6.4 and 6.9 units., Conclusions: In this sample of Caucasians from Spain, teeth became darker yellow and more reddish with increasing age. The L* coordinate is most strongly related to tooth color in aging., (© 2015 by the American College of Prosthodontists.)

In group-living species with male dominance hierarchies where receptive periods of females do not overlap, high male reproductive skew would be predicted. However, the existence of female multiple mating and alternative male mating strategies can call into question single-male monopolization of paternity in groups. Ring-tailed lemurs (Lemur catta) are seasonally breeding primates that live in multi-male, multi-female groups. Although established groups show male dominance hierarchies, male dominance relationships can break down during mating periods. In addition, females are the dominant sex and mate with multiple males during estrus, including group residents, and extra-group males-posing the question of whether there is high or low male paternity skew in groups. In this study, we analyzed paternity in a population of wild L. catta from the Bezà Mahafaly Special Reserve in southwestern Madagascar. Paternity was determined with 80-95% confidence for 39 offspring born to nine different groups. We calculated male reproductive skew indices for six groups, and our results showed a range of values corresponding to both high and low reproductive skew. Between 21% and 33% of offspring (3 of 14 or three of nine, counting paternity assignments at the 80% or 95% confidence levels, respectively) were sired by extra-troop males. Males siring offspring within the same group during the same year appear to be unrelated. Our study provides evidence of varying male reproductive skew in different L. catta groups. A single male may monopolize paternity across one or more years, while in other groups, >1 male can sire offspring within the same group, even within a single year. Extra-group mating is a viable strategy that can result in extra-group paternity for L. catta males., (© 2016 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc.)

Unlabelled: In models of Parkinson's disease (PD), Rho kinase (ROCK) inhibitors have antiapoptotic and axon-stabilizing effects on damaged neurons, decrease the neuroinflammatory response, and protect against dopaminergic neuron death and axonal retraction. ROCK inhibitors have also shown protective effects against apoptosis induced by handling and dissociation of several types of stem cells. However, the effect of ROCK inhibitors on dopaminergic cell grafts has not been investigated. In the present study, treatment of dopaminergic cell suspension with ROCK inhibitors yielded significant decreases in the number of surviving dopaminergic neurons, in the density of graft-derived dopaminergic fibers, and in graft vascularization. Dopaminergic neuron death also markedly increased in primary mesencephalic cultures when the cell suspension was treated with ROCK inhibitors before plating, which suggests that decreased angiogenesis is not the only factor leading to cell death in grafts. Interestingly, treatment of the host 6-hydroxydopamine-lesioned rats with ROCK inhibitors induced a slight, nonsignificant increase in the number of surviving neurons, as well as marked increases in the density of graft-derived dopaminergic fibers and the size of the striatal reinnervated area. The study findings discourage treatment of cell suspensions before grafting. However, treatment of the host induces a marked increase in graft-derived striatal reinnervation. Because ROCK inhibitors have also exerted neuroprotective effects in several models of PD, treatment of the host with ROCK inhibitors, currently used against vascular diseases in clinical practice, before and after grafting may be a useful adjuvant to cell therapy in PD., Significance: Cell-replacement therapy is one promising therapy for Parkinson's disease (PD). However, many questions must be addressed before widespread application. Rho kinase (ROCK) inhibitors have been used in a variety of applications associated with stem cell research and may be an excellent strategy for improving survival of grafted neurons and graft-derived dopaminergic innervation. The present results discourage the treatment of suspensions of dopaminergic precursors with ROCK inhibitors in the pregrafting period. However, treatment of the host (patients with PD) with ROCK inhibitors, currently used against vascular diseases, may be a useful adjuvant to cell therapy in PD., (©AlphaMed Press.)

Purpose: To identify the most frequent natural tooth colors using the Easyshade Compact (Vita -Zahnfabrik) spectrophotometer on a sample of the Spanish population according to the 3D Master System., Materials and Methods: The middle third of the facial surface of natural maxillary central incisors was measured with an Easyshade Compact spectrophotometer (Vita Zahnfabrik) in 1361 Caucasian Spanish participants aged between 16 and 89 years. Natural tooth color was recorded using the 3D Master System nomenclature. The program used for the present descriptive statistical analysis of the results was SAS 9.1.3., Results: The results show that the most frequent dental color in the total sample studied is 3M1 (7.05%), followed by the intermediate shade 1M1.5 (6.91%) and 2L1.5 (6.02%)., Conclusion: According to the research methodology used, and taking into account the limitations of this study, it can be proposed that the most frequent color among the Spanish population is 3M1; the most common lightness group is 2; the most frequent hue group according to the 3D Master System is M and the most frequent chroma group is 1.5.

Objectives: To analyse natural tooth colour in the Spanish population according to the colour coordinates lightness (L*), chroma (C*), hue (h*), red-green axis (a*) and yellow-blue axis (b*) in order to quantify the correlation and changes of tooth colour with age and sex., Methods: Natural tooth colour was measured in a sample of 1,361 Spanish participants of both sexes distributed within an age range of 16 to 89 years. The Easyshade Compact spectrophotometer was used and the CIELAB and CIELCh systems were followed., Results: Pearson's bivariate correlations between age and colour coordinates were highly significant for L* (r=-0.674, P≤0.001), h* (r=-0.468, P≤0.001) and C* (r=0.417, P≤0.001). The correlation between age and colour coordinates was stronger for men than for women, for all colour coordinates. The results showed that C*, b* and a* increased by 0.60, 0.56 and 0.26 units/year on average, respectively, whereas L* and h* decreased progressively with age (by 0.60 units/year, on average), and colour differences increased in a systematic way as the gap between the ages being compared grew wider., Conclusions: The strongest correlation was found between age and L*, then between age and h* (both inverse relationships) and then between age and a*, C* and b* (direct relationships). In addition, a similar degree of change in the colour coordinates L*, C* and h* (of 0.60 units/year on average) was observed for natural tooth colour. Knowledge of the chromatic range of natural teeth may help to choose colour for the replacement of missing elements., (© 2015 FDI World Dental Federation.)

Statement of Problem: The 3D-Master System comprises 26 physical shade tabs and intermediate shades. Determining the relationship among all the groups of lightness, chroma, and hue of the 3D-Master System (Vita Zahnfabrik) and the L*, C*, and h* coordinates is important, because according to the manufacturer, 2 Toothguide 3D-Master shades need to be mixed in a 50:50 ratio to create an intermediate shade., Purpose: The purpose of the study was to relate the lightness, chroma, and hue groups of the 3D-Master System with the polar coordinates of the CIELAB chromatic space, L*, C*, and h*, and to quantify the shades tabs and intermediate shades of the 3D-Master System according to color coordinates., Material and Methods: The middle third of the facial surface of a natural maxillary central incisor was measured with an Easyshade Compact spectrophotometer (Vita Zahnfabrik) in 1361 Spanish participants aged between 16 and 89 years. Natural tooth color was recorded in the 3D-Master nomenclature and in the CIE L*, C*, and h* coordinates system. The program used for the present descriptive statistical analysis of the results was SAS 9.1.3., Results: In the L* variable, the minimum was found at 47.0 and the maximum at 91.3. In the C* variable, the minimum was found at 5.9 and the maximum at 49.8, while for h*, the minimum was 67.5 degrees and the maximum 112.0 degrees., Conclusions: Despite the limitations of this study, the 3D-Master System was found to be arranged according to L*, C*, and h* coordinates in groups of lightness, chroma, and hue. The corresponding groups of lightness, chroma, and hue can be estimated on the basis of L*, C*, and h* coordinates., (Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Lemur catta has traditionally been considered a species with male-biased dispersal; however, occasional female dispersal occurs. Using molecular data, we evaluated dispersal patterns in 2 L. catta populations in southwestern Madagascar: Tsimanampesotse National Park (TNP) and Bezà Mahafaly Special Reserve (BMSR). We also investigated the genetic differentiation between the populations and dispersal partner relatedness. Results showed minor genetic differentiation between the populations (ϴ(ST) = 0.039), which may indicate gene flow historically occurring in this region, made possible by the presence of L. catta groups between the sites. Different patterns of sex-biased dispersal were found between the sites using corrected assignment indices: male-biased dispersal in TNP, and a lack of sex-biased dispersal in BMSR. Observational evidence of female dispersal in BMSR supports these results and may imply intense female resource competition in and around BMSR, because small groups of 2-3 females have been observed dispersing within BMSR and entering the reserve from outside. These dispersing groups largely consisted of mothers transferring with daughters, although we have an aunt-niece pair transferring together. Genetic data suggest that males also transfer with relatives. Our data demonstrate that dispersal partners consist of same-sexed kin for L. catta males and females, highlighting the importance of kin selection., (© 2015 S. Karger AG, Basel.)

Objectives: The aim of this work was to assess the agreement between instrumental and visual colour matching., Methods: Shade selection with the 3DMaster Toothguide (Vita-Zahnfabrik) was performed for 1361 maxillary central incisors and compared with the shade obtained with the EasyShade Compact (Vita-Zahnfabrik) spectrophotometer., Results: We observed a greater correlation between the objective method and the subjective one in the colour dimension of lightness (Kappa 0.6587), followed by hue (Kappa 0.4337) and finally chroma (Kappa 0.3578)., Conclusion: The colour dimension in which the greatest agreement is seen between the operator and the spectrophotometer is value or lightness., Clinical Significance: This study reveals differences between the measurement of colour via spectrophotometry and the visual shade selection method. According to our results, there is better agreement in the value or lightness colour dimension, which is the most important one in the choice of tooth colour., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Phenotypic drug discovery requires billions of cells for high-throughput screening (HTS) campaigns. Because up to several million different small molecules will be tested in a single HTS campaign, even small variability within the cell populations for screening could easily invalidate an entire campaign. Neurodegenerative assays are particularly challenging because neurons are post-mitotic and cannot be expanded for implementation in HTS. Therefore, HTS for neuroprotective compounds requires a cell type that is robustly expandable and able to differentiate into all of the neuronal subtypes involved in disease pathogenesis. Here, we report the derivation and propagation using only small molecules of human neural progenitor cells (small molecule neural precursor cells; smNPCs). smNPCs are robust, exhibit immortal expansion, and do not require cumbersome manual culture and selection steps. We demonstrate that smNPCs have the potential to clonally and efficiently differentiate into neural tube lineages, including motor neurons (MNs) and midbrain dopaminergic neurons (mDANs) as well as neural crest lineages, including peripheral neurons and mesenchymal cells. These properties are so far only matched by pluripotent stem cells. Finally, to demonstrate the usefulness of smNPCs we show that mDANs differentiated from smNPCs with LRRK2 G2019S are more susceptible to apoptosis in the presence of oxidative stress compared to wild-type. Therefore, smNPCs are a powerful biological tool with properties that are optimal for large-scale disease modeling, phenotypic screening, and studies of early human development.

Stem cells, through their ability to both self-renew and differentiate, can produce a virtually limitless supply of specialized cells that behave comparably to primary cells. We took advantage of this property to develop an assay for small-molecule-based neuroprotection using stem-cell-derived motor neurons and astrocytes, together with activated microglia as a stress paradigm. Here, we report on the discovery of hit compounds from a screen of more than 10,000 small molecules. These compounds act through diverse pathways, including the inhibition of nitric oxide production by microglia, activation of the Nrf2 pathway in microglia and astrocytes, and direct protection of neurons from nitric-oxide-induced degeneration. We confirm the activity of these compounds using human neurons. Because microglial cells are activated in many neurological disorders, our hit compounds could be ideal starting points for the development of new drugs to treat various neurodegenerative and neurological diseases., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Recent studies have shown that renin-angiotensin system overactivation is involved in the aging process in several tissues as well as in longevity and aging-related degenerative diseases by increasing oxidative damage and inflammation. We have recently shown that angiotensin II enhances dopaminergic degeneration by increasing levels of reactive oxygen species and neuroinflammation, and that there is an aging-related increase in angiotensin II activity in the substantia nigra in rats, which may constitute a major factor in the increased risk of Parkinson's disease with aging. The mechanisms involved in the above mentioned effects and particularly a potential angiotensin-mitochondria interaction have not been clarified. The present study revealed that activation of mitochondrial ATP-sensitive potassium channels [mitoK(ATP)] may play a major role in the angiotensin II-induced effects on aging and neurodegeneration. Inhibition of mitoK(ATP) channels with 5-hydroxydecanoic acid inhibited the increase in dopaminergic cell death induced by angiotensin II, as well as the increase in superoxide/superoxide-derived reactive oxygen species levels and the angiotensin II-induced decrease in the mitochondrial inner membrane potential in cultured dopaminergic neurons. The present study provides data for considering brain renin-angiotensin system and mitoK(ATP) channels as potential targets for protective therapy in aging-associated diseases such as Parkinson's disease.

In light of historical and recent anthropogenic influences on Malagasy primate populations, in this study ring-tailed lemur (Lemur catta) samples from two sites in southwestern Madagascar, Beza Mahafaly Special Reserve (BMSR) and Tsimanampetsotsa National Park (TNP), were evaluated for the genetic signature of a population bottleneck. A total of 45 individuals (20 from BMSR and 25 from TNP) were genotyped at seven microsatellite loci. Three methods were used to evaluate these populations for evidence of a historical bottleneck: M-ratio, mode-shift, and heterozygosity excess tests. Three mutation models were used for heterozygosity excess tests: the stepwise mutation model (SMM), two-phase model (TPM), and infinite allele model (IAM). M-ratio estimations indicated a potential bottleneck in both populations under some conditions. Although mode-shift tests did not strongly indicate a population bottleneck in the recent historical past when samples from all individuals were included, a female-only analysis indicated a potential bottleneck in TNP. Heterozygosity excess was indicated under two of the three mutation models (IAM and TPM), with TNP showing stronger evidence of heterozygosity excess than BMSR. Taken together, these results suggest that a bottleneck may have occurred among L. catta in southwestern Madagascar in the recent past. Given knowledge of how current major stochastic climatic events and human-induced change can negatively impact extant lemur populations, it is reasonable that comparable events in the historical past could have caused a population bottleneck. This evaluation additionally functions to highlight the continuing environmental and anthropogenic challenges faced by lemurs in southwestern Madagascar., (Copyright © 2011 Wiley Periodicals, Inc.)

Cathemerality, an activity pattern comprised of distinct periods of diurnal and nocturnal activity, is a trait found among several of the Malagasy strepsirhines and one species of Aotus. Because occasional anecdotal reports suggest that some diurnal primates can be active at night, I investigated the possibility of nocturnal ranging behavior in the ring-tailed lemur (Lemur catta) by using global positioning system (GPS) collars programmed to collect data across a 24-h period. Five individuals in a provisioned, free-ranging L. catta colony on St. Catherines Island, Georgia, USA, wore GPS collars across 1 week of the mating season. Results revealed that night ranging behavior occurred between the h of 1900 and 0530. An evaluation of the effect of moonlight on nocturnal activity showed that a greater rate of travel occurred during moonlit periods as opposed to periods when the moon had not yet risen. Distance travelled at night decreased across the deployment period, likely because of a decrease in available moonlight over time, as the lemurs were collared during a waning moon. Fewer mating opportunities over time may have also been responsible for the decrease in night ranging, because the number of females in estrus declined across the deployment period. Future research is needed to separate the effects of moonlight and mating activity on night ranging in this species, as well as to evaluate whether L. catta in Madagascar show night ranging similar to L. catta on SCI. These data raise the possibility that L. catta may be cathemeral, with an activity pattern fluctuating between diurnality and cathemerality in accordance with shifts in environmental conditions.

Reactive oxygen species signaling has been suggested to regulate stem cell development. In the present study, we treated neurospheres of rat mesencephalic precursors with inhibitors of the NADPH oxidase complex and mitochondrial ATP-sensitive potassium (mitoKATP) channel blockers during the proliferation and/or the differentiation periods to study the effects on generation of dopaminergic neurons. Treatment with low doses (100 or 250 μM) of the NADPH inhibitor apocynin during the proliferation period increased the generation of dopaminergic neurons. However, higher doses (1 mM) were necessary during the differentiation period to induce the same effect. Treatment with general (glibenclamide) or mitochondrial (5-hydroxydecanoate) KATP channel blockers during the proliferation and differentiation periods increased the number of dopaminergic neurons. Furthermore, neither increased proliferation rate nor apoptosis had a major role in the observed increase in generation of dopaminergic neurons, which suggests that the redox state is able to regulate differentiation of precursors into dopaminergic neurons., (© 2010 Wiley-Liss, Inc.)

One commonly cited function of dispersal is to increase mating opportunities. In this study, I evaluated the hypothesis that male inter-troop transfer is used as a mating strategy in ring-tailed lemurs, Lemur catta, on St. Catherines Island (SCI), Ga., USA. I measured male mating success and inter-troop transfer behavior across 5 years in a population consisting of 4 lemur groups on SCI. Data strongly supported dispersal as a successful mating strategy of natal males, because these males did not mate within their natal groups, but always mated in their new groups of entry. For secondary male dispersal (transfers between 2 non-natal groups), data on 2 males collected in breeding seasons immediately prior to and following transfer show that their individual mating success measures increased following a transfer. Data revealed that among non-natal males, high-ranking males on SCI were more likely to transfer between groups than lower-ranking males, which is somewhat contrary to the more common trend among primates of lower-ranking males transferring more frequently. In sum, male primary dispersal appears to function as a mating strategy among male L. catta on SCI, with indications that secondary dispersal may also be successful at increasing male mating success., (Copyright © 2010 S. Karger AG, Basel.)

In this study, dominance rank instability among male Lemur catta during mating was investigated. Also, data on agonism and sexual behavior across five consecutive mating seasons in a population of L. catta on St. Catherines Island, USA, were collected. Instances of male rank instability were categorized into three types. Type 1 consisted of a temporary switch in the dominance ranks of two males, which lasted for a period of minutes or hours. Type 2 dyadic male agonistic interactions showed highly variable outcomes for a period of time during which wins and losses were neither predictable nor consistent. Type 3 interactions consisted of a single agonistic win by a lower-ranked male over a more dominant male. More Type 2 interactions (indicating greater dominance instability) occurred when males had not spent the previous mating season in the same group, but this trend was not statistically significant. The majority of periods of male rank instability were preceded by female proceptivity or receptivity directed to a lower-ranked male. As such, exhibition of female mate choice for a lower-ranking male appeared to incite male-male competition. Following receipt of female proceptivity or receptivity, males who were lower-ranking took significantly longer to achieve their first agonistic win over a more dominant male than did males who were higher-ranked. Ejaculation frequently preceded loss of dominance. In conclusion, temporary rank reversals and overall dominance rank instability commonly occur among male L. catta in mating contexts, and these temporary increases in dominance status appear to positively affect male mating success., ((c) 2008 Wiley-Liss, Inc.)

Objectives: To evaluate the influence of gender and level of experience on shade matching quality., Methods: A study was simultaneously performed at 15 universities located in 9 countries. A total of 614 color normal participants completed all phases of the experiment. Among them, there were 305 females and 309 males, 319 dental students and 295 dental professionals. A lecture on color matching in dentistry was given to all participants. Initial training was performed using Toothguide Trainer software (TT), while Toothguide Training Box (TTB) was used for both training and testing of participants' shade matching results. The test task was to successively match 15 shade guide tabs with the corresponding shade guide. The shade matching score for each participant was computed as a sum of color differences (SigmaDeltaE(ab)(*) score) between target tabs and selected tabs. Lower scores corresponded to better shade matching results and vice versa. Means and standard deviations were calculated. Mann-Whitney U test was used for statistical analysis of the data (alpha=0.05)., Results: The mean shade matching score (S.D.) for all participants was 41 (21). The score for female and male participants was 38 (20) and 44 (21), respectfully (p<0.001). The difference in scores between dental students, 42 (20), and dental professionals, 39 (21), was not statistically significant., Conclusion: Within the limitations of this study, females achieved significantly better shade matching results than males, indicating that gender plays an important role in shade matching. The level of experience was not found to be significant factor in shade matching.

The neurotoxin 6-hydroxydopamine is commonly used in models of Parkinson's disease, and a potential factor in the pathogenesis of the disease. However, the mechanisms responsible for 6-hydroxydopamine-induced dopaminergic degeneration have not been totally clarified. Reactive oxygen species (ROS) derived from 6-OHDA uptake and intraneuronal autooxidation, extracellular 6-OHDA autooxidation, and microglial activation have been involved. The mitochondrial implication is controversial. Mitochondrial ATP-sensitive K (mitoK(ATP)) channels may provide a convergent target that could integrate these different mechanisms. We observed that in primary mesencephalic cultures and neuron-enriched cultures, treatment with the mitoK(ATP) channel blocker 5-hydroxydecanoate, inhibits the dopaminergic degeneration induced by low doses of 6-OHDA. Furthermore, 5-hydroxydecanoate blocks the 6-OHDA-induced decrease in mitochondrial inner membrane potential and inhibits 6-OHDA-induced generation of superoxide-derived ROS in dopaminergic neurons. The results suggest that low doses of 6-OHDA may generate low levels of ROS through several mechanisms, which may be insufficient to induce neuron death. However, they could act as a trigger to activate mitoK(ATP) channels, thereby enhancing ROS production and the subsequent dopaminergic degeneration. Furthermore, the present study provides additional data for considering mitoK(ATP) channels as a potential target for neuroprotection.

In this article we document male sexual coercion of a Lemur catta female on St. Catherines Island (SCI), USA. Data presented in this paper were collected on one free-ranging L. catta group during October-November 2002 using all-occurrences sampling for agonism and reproductive behavior. We observed a male forcefully attempting to mate with a year-old estrous female. Despite the fact that we observed this female to present to the male during her estrus, throughout the episode the male employed the use of force, and achieved penile intromission on at least one occasion while the female struggled and resisted. We interpret his behavior as sexual coercion. As measured by sexual presents, the female appeared to more strongly prefer two other males as mates, yet each of these males gained fewer mounts and less cumulative time spent in mounts than the coercive male. The coercive male was one of two group males with the lowest observed mating success, suggesting that coercion might be a strategy used by males who are not highly sexually preferred. Females undergo early sexual maturation at this site owing to provisioning, and can therefore enter estrus before fully attaining dominance over males. As such, these data suggest that one consequence of provisioning a wild L. catta population (or of maintaining L. catta in captivity) may be that young females can be the targets of sexual coercion if they reach sexual maturity before fully achieving social dominance over males. In conclusion, male sexual coercion can occur in L. catta despite the female dominance characteristic of this species, and can constrain the mating behavior of females.

Angiotensin II (AII) plays a major role in the progression of inflammation and NADPH-derived oxidative stress (OS) in several tissues. The brain possesses a local angiotensin system, and OS and inflammation are key factors in the progression of Parkinson's disease. In rat mesencephalic cultures, AII increased 6-OHDA-induced dopaminergic (DA) cell death, generation of superoxide in DA neurons and microglial cells, the expression of NADPH-oxidase mRNA, and the number of reactive microglial cells. These effects were blocked by AII type-1 (AT1) antagonists, NADPH inhibitors, or elimination of glial cells. DA degeneration increased angiotensin converting enzyme activity and AII levels. In rats, 6-OHDA-induced dopaminergic cell loss and microglial activation were reduced by treatment with AT1 antagonists. The present data suggest that AII, via AT1 receptors, increases the dopaminergic degeneration process by amplifying the inflammatory response and intraneuronal levels of OS, and that glial cells play a major role in this process.

Male dispersal patterns were analyzed across a nine-year period in a population of ring-tailed lemurs (Lemur catta) on St. Catherines Island (SCI), USA, to evaluate two ultimate explanations for male dispersal: inbreeding avoidance and intrasexual mating competition. As part of this analysis, we also compared patterns of dispersal at this site with data from wild populations. Overall, we found that patterns of male intertroop movement on SCI are similar to the wild with respect to the frequency and seasonality of male transfer. In Madagascar, males move between groups every 3.1-3.5 years [Sussman, International Journal of Primatol 13:395-413, 1992; Koyama et al., Primates 43:291-314, 2002] as compared with every 3.2 years on SCI. The majority of transfers on SCI occurred during the birth season, as occurs at one site in Madagascar, Berenty [Budnitz & Dainis, Lemur biology. New York: Plenum Press, p 219-235, 1975; Jones, Folia Primatologica 40:145-160, 1983]. One difference is that males perform natal transfers 1-2 years earlier on SCI than in the wild, which may be related to food provisioning on SCI. Males never transferred back into their natal troops, which is remarkable given the small number of groups on SCI. Although this pattern of movement can indicate inbreeding avoidance by males, the fact that male troop tenure was in many cases long enough to overlap with the sexual maturation of potential daughters did not support the inbreeding avoidance hypothesis for male secondary dispersal. Instead, the intrasexual competition hypothesis was strongly supported, because males were significantly more likely to transfer into groups having fewer adult males and a more favorable sex ratio than their pretransfer groups. Males therefore appear to be bypassing groups in which they would experience a greater degree of intrasexual mating competition during the breeding season.

Production of dopaminergic neurons from stem/precursor cells for transplantation in Parkinson's disease has become a major focus of research. However, the inductive signals mediating this process have not been clarified. Reported data on the effects of Sonic hedgehog on differentiation of dopaminergic and serotonergic neurons from cultures of neural precursors are controversial. In the present study, cultures of proliferating neurospheres of mesencephalic precursors treated with anti-sonic hedgehog antibodies showed significantly less serotonergic and GABAergic cells and a markedly higher number of dopaminergic neurons generated from the neurospheres than control cultures. Treatment of the neurospheres with cyclopamine, which selectively inhibits sonic hedgehog signaling by preventing Smoothened activation, did not induce significant changes in generation of serotonergic and dopaminergic neurons. This suggests that Smoothened activation is not significantly involved in the above-mentioned effects and that sonic hedgehog may exert effects on the mesencephalic precursors that do not involve the canonical Patched-Smoothened-Gli signaling., ((c) 2008 Wiley-Liss, Inc.)

Neurotransmitters have been shown to control CNS neurogenesis, and GABA-mediated signaling is thought to be involved in the regulation of nearly all key developmental stages. Generation of dopaminergic (DA) neurons from stem/precursor cells for cell therapy in Parkinson's disease has become a major focus of research. However, the possible effects of GABA on generation of DA neurons from proliferating neurospheres of mesencephalic precursors have not been studied. In the present study, GABA(A), and GABA(B) receptors were found to be located in DA cells. Treatment of cultures with GABA did not cause significant changes in generation of DA cells from precursors. However, treatment with the GABA(A) receptor antagonist bicuculline (10(-5) M) led to a significant increase in the number DA cells, and treatment with the GABA(B) receptor antagonist CGP 55845 (10(-5) M) to a significant decrease. Simultaneous treatment with bicuculline and CGP 55845 did not induce significant changes. Apoptotic cell death studies and bromodeoxyuridine immunohistochemistry indicated that the aforementioned differences in generation of DA neurons are not due to changes in survival or proliferation of DA cells, but rather to increased or decreased differentiation of mesencephalic precursors towards the DA phenotype. The results suggest that these effects are exerted via GABA receptors located on DA precursors, and are not an indirect consequence of effects on the serotonergic or glial cell population. Administration of GABA(A) receptor antagonists in the differentiation medium may help to obtain higher rates of DA neurons for potential use in cell therapy for Parkinson's disease., (2007 Wiley Periodicals, Inc.)

Cell death induced by 6-hydroxydopamine (6-OHDA) is thought to be caused by reactive oxygen species (ROS) derived from 6-OHDA autooxidation and by a possible direct effect of 6-OHDA on the mitochondrial respiratory chain. However, the process has not been totally clarified. In rat primary mesencephalic cultures, we observed a significant increase in dopaminergic (DA) cell loss 24 h after administration of 6-OHDA (40 micromol/L) and a significant increase in NADPH subunit expression, microglial activation and superoxide anion/superoxide-derived ROS in DA cells that were decreased by the NADPH inhibitor apocynin. Low doses of 6-OHDA (10 micromol/L) did not induce a significant loss of DA cells or a significant increase in NADPH subunit expression, microglial activation or superoxide-derived ROS. However, treatment with the NADPH complex activator angiotensin II caused a significant increase in all the latter. Forty-eight hours after intrastriatal 6-OHDA injection in rats, there was still no loss of DA neurons although there was an increase in NADPH subunit expression and NADPH oxidase activity. The results suggest that in addition to the autooxidation-derived ROS and the inhibition of the mitochondrial respiratory chain, early microglial activation and NADPH oxidase-derived ROS act synergistically with 6-OHDA and constitute a relevant and early component of the 6-OHDA-induced cell death.

In this study, high-resolution computed tomography X-ray scanning was used to scan ring-tailed lemur (Lemur catta) copulatory plugs. This method produced accurate measures of plug volume and surface area, but was not useful for visualizing plug internal structure. Copulatory plug size was of interest because it may relate to male fertilization success. Copulatory plugs form from coagulated ejaculate, and are routinely displaced in this species by the penis of a subsequent mate during copulation (Parga [2003] Int. J. Primatol. 24:889-899). Because one potential function of these plugs may be to preclude or delay other males' successful insemination of females, we tested the hypothesis that larger plugs are more difficult for subsequent males to displace. Plugs were collected opportunistically upon displacement during data collection on L. catta mating behavior on St. Catherines Island, Georgia (USA) during two subsequent breeding seasons. Copulatory plugs exhibited a wide range of volumes: 1,758-5,013.6 mm3 (n = 9). Intraindividual differences in plug volume were sometimes greater than interindividual differences. Contrary to predictions, larger plugs were not more time-consuming for males to displace via penile intromission during copulation. Nor were plugs with longer vaginal residence times notably smaller than plugs with shorter residence times, as might be expected if plugs disintegrate while releasing sperm (Asdell [1946] Patterns of Mammalian Reproduction; Ithaca: Comstock). We found a significant inverse correlation between number of copulatory mounts leading to ejaculation and copulatory plug volume. This may indicate that if males are sufficiently sexually aroused to reach ejaculation in fewer mounts, they tend to produce ejaculates of greater volume., (Copyright 2006 Wiley-Liss, Inc.)

The search for alternative sources of dopaminergic cells, other than primary fetal tissue for transplantation in Parkinson's disease has become a major focus of research. Different methodological approaches have led to generation in vitro of cells expressing DA-cell markers, although these cells are frequently unable to survive for a long time in vivo after transplantation and/or induce functional effects in the host brain. In the present study, we grafted cell aggregates treated with antibodies against fibroblast growth factor 4 into dopaminergic-denervated striata in rats. Furthermore, we grafted cell suspensions from primary mesencephalic fetal tissue. Grafts from expanded precursors were able to survive (at least 3 months postgrafting) and most decreased the lesion-induced ipsiversive rotation. In addition, immunolabeling for tyrosine hydroxylase and/or Fos showed that the grafts reinnervated the surrounding striatal tissue with dopaminergic terminals, and induced the expression of Fos in the striatal neurons of the reinnervated area after administration of amphetamine to the host rat. The number of dopaminergic cells in grafts from expanded precursors inducing rotational recovery was usually lower (1,226+/-314) than that in grafts from primary fetal tissue (1,671+/-122), but they were more densely packed in grafts that were of smaller volume and did not have the characteristic central nondopaminergic area observed in grafts from primary fetal tissue. The results suggest that long-term survival and functional integration into the DA-denervated striatum can be achieved with grafts of expanded mesencephalic precursors., (Synapse 58:12-21, 2005. (c) 2005 Wiley-Liss, Inc.)

In addition to the well-known actions of the humoral renin-angiotensin system, all components of this system are present in many tissues, including the brain, and may play a major role in brain development and differentiation. We investigated the possible effects of angiotensin II on the generation of dopaminergic phenotype neurons from proliferating neurospheres of mesencephalic precursors. We observed immunoreactivity for both angiotensin type 1 and type 2 (AT(1) and AT(2)) receptors in the cell aggregates. Double immunolabeling studies revealed that both receptor types are located in neurons and astrocytes. Interestingly, neurons with a dopaminergic phenotype (i.e. tyrosine hydroxylase activity) showed double labeling for AT(1) and AT(2) receptors although the labeling for AT(2) was more intense. Treatment of the neurospheres with angiotensin II (100 nm) during the differentiation period induced a marked increase (about 400%) in the generation of dopaminergic neurons. This was not affected by treatment with the AT(1) antagonist ZD 7155 but was blocked by treatment with the AT(2) antagonist PD 123319. This suggests that AT(2) receptors mediate the stimulatory effect of angiotensin II on the generation of dopaminergic neurons. Apoptotic cell death studies and bromodeoxyuridine immunohistochemistry indicated that the increase in generation of dopaminergic neurons is not due to increased survival or proliferation of dopaminergic cells during treatment with angiotensin and suggested that angiotensin induces increased differentiation of mesencephalic precursors towards the dopaminergic phenotype. Manipulation of the renin-angiotensin system may be useful for increasing production of dopaminergic neurons for transplantation in Parkinson's disease.

We report the current (1997-1999, 2001) incidence and amount of ingested plastic in short-tailed shearwaters (Puffinus tenuirostris) in the southeastern Bering Sea and compare our results with plastic reported in shearwaters during 1970-1978. We also examine correlations between plastic loads and shearwater body mass. We found that 84% (N = 330) of shearwaters sampled in 1997-1999 and 2001 contained plastic. The incidence and amount of ingested plastic have not significantly changed since the 1970s. In contrast, the predominant type of plastic has changed over time, from industrial plastic to user plastic. S,asonal patterns in the incidence and amount of ingested plastic also changed from peak levels during early and late summer in the 1970s to mid summer in the late 1990s and 2001. We suggest that the availability of neuston plastic to seabirds in the Bering Sea has undergone a shift in composition since the 1970s. Shearwater body mass appears little if at all impaired by plastic, at least at present levels of consumption.