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In the paper wasp Polistes dominula, cuticular hydrocarbons play a critical role to acquire information regarding conspecific individuals. However, the relationship between cuticular hydrocarbons, health status, and male sexually selected traits is poorly investigated. In this study, we characterized the cuticular hydrocarbon profile of adult male and female wasps, infected or not by the strepsipteran endoparasite Xenos vesparum, to assess whether the chemical signature provides information about sex and health status (parasite infection). Moreover, we tested whether the chemical profile reflects male quality as measured via morphological and behavioural (sexually selected) traits at leks. Our results showed that males and females had similar total amount of CHCs, quantitatively different profiles and, to a lesser extent, sex-specific chemical compounds. Cuticular profiles were influenced by the strepsipteran infection, and the effect was stronger in females (the primary host) than in males, according to the physiological castration of female but not of male hosts. Regarding territorial and non-territorial males, no significant difference emerged in their chemical profiles. Furthermore, sex-dimorphic visual signals (size, shape, and asymmetry of abdominal yellow spots) were related to the behavioural displays of territorial males. We hypothesize that cuticular hydrocarbons are potential multi-role cues to assess sex and health status in male and female wasps, in synergy with visual signals and territorial performance in signaling male quality. [ABSTRACT FROM AUTHOR]

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Objectives: To describe the placement of self‐inflating tissue expanders and clinical outcomes in 12 consecutive cases of reconstruction of distal cutaneous limb defects in dogs. Materials and Methods: Cases of distal cutaneous limb defect were divided into three groups based on the location of the placement of the self‐inflating tissue expanders: Group A (n=4): on, or proximal to, the elbow and stifle; Group B (n=4): distal to the elbow or stifle and proximal to the carpus or tarsus; and Group C (n=4): distal to the carpus or tarsus. Owner satisfaction and clinical outcome were documented. Results: Thirteen cases were originally included, but one was excluded because of incomplete follow‐up. In one case, the self‐inflating tissue expanders were removed before expansion started. A mean of five expanders were implanted per dog (range 2 to 9). Devices were removed after a mean of 24 days (range 13 to 42 days). Primary closure was achieved in eight of 11 cases, including all cases from Group A and 75% and 33% of cases from Groups B and C, respectively. All incompletely reconstructed defects or areas of wound dehiscence healed by second intention. Eight of 12 owners were satisfied. Clinical Significance: Self‐inflating tissue expanders can be used as an alternative for the reconstruction of limb defects in dogs in which direct primary closure would otherwise not be achievable. Defects below the carpus and tarsus are more challenging to treat with this method. [ABSTRACT FROM AUTHOR]

An experimental technique for the estimation of the temporal-averaged vapour volume fraction within high-speed cavitating flow orifices is presented. The scientific instrument is designed to employ X-ray micro computed tomography (microCT) as a quantitative 3D measuring technique applied to custom designed, large-scale, orifice-type flow channels made from Polyether-ether-ketone (PEEK). The attenuation of the ionising electromagnetic radiation by the fluid under examination depends on its local density; the transmitted radiation through the cavitation volume is compared to the incident radiation, and combination of radiographies from sufficient number of angles leads to the reconstruction of attenuation coefficients versus the spatial position. This results to a 3D volume fraction distribution measurement of the developing multiphase flow. The experimental results obtained are compared against the high speed shadowgraph visualisation images obtained in an optically transparent nozzle with identical injection geometry; comparison between the temporal mean image and the microCT reconstruction shows excellent agreement. At the same time, the real 3D internal channel geometry (possibly eroded) has been measured and compared to the nominal manufacturing CAD drawing of the test nozzle. [ABSTRACT FROM AUTHOR]

Background and Objectives Patient Blood Management ( PBM) in Europe is a working group of the European Blood Alliance with the initial objective to identify the starting position of the participating hospitals regarding PBM for benchmarking purposes, and to derive good practices in PBM from the experience and expertise in the participating teams with the further aim of implementing and strengthening these practices in the participating hospitals. Methods We conducted two surveys in seven university hospitals in Europe: Survey on top indications for red blood cell use regarding usage of red blood cells during 1 week and Survey on PBM organization and activities. Results A total of 3320 units of red blood cells were transfused in 1 week at the seven hospitals. Overall, 61% of red cell units were transfused to medical patients and 36% to surgical patients, although there was much variation between hospitals. The organization and activities of PBM in the seven hospitals were variable, but there was a common focus on optimizing the treatment of bleeding patients, monitoring the use of blood components and treatment of preoperative anaemia. Conclusion Although the seven hospitals provide a similar range of clinical services, there was variation in transfusion rates between them. Further, there was variable implementation of PBM activities and monitoring of transfusion practice. These findings provide a baseline to develop joint action plans to further implement and strengthen PBM across a number of hospitals in Europe. [ABSTRACT FROM AUTHOR]

One of the consequences of intense genetic selection for growth of poultry is the recent appearance of abnormalities in chicken breast muscles, such as white striping (characterised by superficial white striations) and wooden breast (characterised by pale and bulged areas with substantial hardness). The aim of this study was to evaluate the quality traits of chicken fillets affected by white striping and wooden breast abnormalities. In two replications, 192 fillets were divided into the following four classes: normal (n=48; absence of any visual defects), white striping (n=48, presence of white striations), wooden breast (n=48; diffusely presence of hardened areas) and white striping/wooden breast (n=48; fillets affected by both abnormalities). Morphology, raw meat texture and technological properties were assessed in both unprocessed (pH, colour, drip loss, cooking loss and cooked meat shear force) and marinated meat (marinade uptake, purge loss, cooking loss and cooked meat shear force). Fillets affected by white striping, wooden breast or both abnormalities exhibited higher breast weights compared with normal fillets (305.5, 298.7, 318.3 and 244.7 g, respectively; P<0.001). Wooden breast, either alone or in combination with white striping, was associated with a significant (P<0.001) increase of fillet thickness in the caudal area and raw meat hardness compared with both normal and the white striping abnormality, for which there was no difference. Overall, the occurrence of the individual and combined white striping and wooden breast abnormalities resulted in substantial reduction in the quality of breast meat, although these abnormalities are associated with distinct characteristics. Wooden breast fillets showed lower marinade uptake and higher cooking losses than white-striped fillets for both unprocessed and marinated meats. On the other hand, white-striped fillets showed a moderate decline in marinade and cooking yield. Fillets affected by both abnormalities had the highest (P<0.001) ultimate pH values. In contrast, the effects on colour of raw and cooked meat, drip loss, purge loss and cooked meat shear force were negligible or relatively low and of little practical importance. Thus, the presence of white striping and wooden breast abnormalities impair not only breast meat appearance but also the quality of both raw and marinated meats mainly by reducing water holding/binding abilities. [ABSTRACT FROM PUBLISHER]

Aim: To conduct a network meta-analysis (NMA) to determine the comparative efficacy, as measured by sustained virological response (SVR), between boceprevir (BOC), telaprevir (TEL), faldaprevir (FAL), simeprevir (SIM) and sofosbuvir (SOF) in combination with peginterferon–ribavirin (PR) against a control of PR. Design: A literature search was conducted to identify randomized controlled trials (RCTs) including adult patients with hepatitis C virus genotype 1 who were naive to any prior therapy. RCTs assessing standard duration therapy (SDT) or response-guided therapy (RGT) BOC, TEL, FAL, SIM or SOF in combination with PR against a control of PR were eligible for inclusion. All RCTs must have provided SVR at either 12 or 24 weeks post-therapy cessation. Results: We included nine RCTs. All direct-acting antivirals (DAAs) were found to perform better than PR. Additionally, SDT FAL was found to be better than the 240 mg RGT FAL regimen with the PR lead-in. A sensitivity analysis excluding RCTs with only SVR at 12 weeks was consistent with the results of the primary analysis. A sensitivity analysis removing an RCT assessing SIM that reported SVR of >60% in the PR control group additionally found that RGT SIM was superior to the 240 mg RGT FAL regimen with the PR lead-in. Discussion: Our analyses indicate that SDT and RGT regimens of DAAs plus PR do not differ greatly in terms of SVR among treatment-naive hepatitis C genotype 1 patients. More advanced Bayesian network meta-analyses are likely needed to incorporate a comprehensive evidence base, expanding beyond randomized clinical trials. [ABSTRACT FROM AUTHOR]

Labile sex expression is considered to play a key role in the evolution of breeding systems and in the transition from hermaphroditism to dioecy, according to the evolutionary models proposed for plants. While in hermaphrodites sex allocation within the individual can be plastically adjusted in response to social environment, in dioecious species it is predicted to be fixed. However, labile sex expression in the form of gender plasticity can still be present in dioecious species of animals with environmental sex determination. It is still unclear how gender plasticity is involved in the evolution of breeding systems and what its role is in the transition from hermaphroditism to dioecy. We assessed the degree of plasticity in gender expression in three dioecious species of polychaete worms of the genus Ophryotrocha. We found sexual polymorphism and plasticity in sex expression during the juvenile phase to be a response to social environment. The majority of juveniles reared with an adult female or male expressed the gender opposite of that of the partner, so as to form heterosexual pairs. On the basis of these findings we outline a possible evolutionary pathway of the transition from hermaphroditism to dioecy in the genus Ophryotrocha. [ABSTRACT FROM AUTHOR]

An experimental study about the anisotropic wetting behavior of a surface patterned with parallel grooves is presented as an application example of a novel technique for investigation of complete and partial anisotropic wetting on structured surface by X-ray microtomography. Shape of glycerin droplets on such surface is investigated by X-ray micro computed tomography (microCT) acting as a non-intrusive, full volume 3D microscope with micrometric spatial resolution. The reconstructed drop volumes enable to estimate the exact volumes of the drops, their base contours, and 3D static contact angles, based on true cross-sections of the drop-surface couple. Droplet base contours are compared to approximate geometrical contour shapes proposed in the literature. Contact angles along slices parallel and perpendicular to the grooves direction are compared with each other. The effect of the sessile drop volume on the wetting behavior is discussed. The proposed technique, which is applicable for any structured surface, enables the direct measure of Wenzel ratio based on the microCT scan in the wetted region usually inapproachable by any others. Comparisons with simplified models are presented and congruence of results with respect to the minimum resolution needed is evaluated and commented. [ABSTRACT FROM AUTHOR]

Parasite-induced alterations in host behaviour have been reported in a large number of taxa. However, some parasites are better than others to exploit the resources offered by their hosts. To date, our understanding of the extent to which some obligate parasites exploit social insect colonies is still limited. In this study, we examined parasite-mediated behavioural alterations of Polistes biglumis wasps parasitized by the obligate social parasite Polistes atrimandibularis by comparing host female-activity in parasitized and non-parasitized colonies. Host foundresses foraged more and rested less in parasitized than in non-parasitized colonies (controlling for the number of larvae in the nest, the time of day, and the day in the season). Next, we used short-term parasite removal experiments to investigate how social parasites manipulate their hosts. We found that parasitized hosts foraged more and rested less when social parasites were on the nest rather than after their removal, and we tested which kind of interactions occurred between parasites and hosts. P. atrimandibularis parasites may use mainly non-aggressive interactions (such as antennation and trophallaxis) to manipulate host activities, rather than visual, acoustic or chemical signals as other parasites do. [ABSTRACT FROM AUTHOR]

In primitively eusocial insects, air temperature is the environmental factor that primarily affects colony cycle. Several studies demonstrated interspecific differences in the adaptation of eusocial insects to local air temperature. Nevertheless, studies on intraspecific adaptations are rare. In this study, we investigate the influence of air temperature on local adaptations in behavior and colony productivity of Polistes biglumis foundresses living in warm and cold temperate zones. We hypothesized that foundresses from warm temperate zones would show a higher activity level compared to those from cold temperate zones before brood emergence, based on differences in air temperature between the two zones. After brood emergence, we expected a reduced foundress activity level in the warm climate zone, due to workers' help. In contrast, foundresses living in the cold-climate zone, which do not produce workers, were expected to remain active throughout the nesting season. We also hypothesized that colony productivity was higher in warm-climate colonies. As expected, warm-climate foundresses reduced their activity level after brood emergence and, with their relatively large number of workers, continued egg production throughout the nesting season. Further studies are necessary to assess if these intraspecific differences are attributable to phenotypic plasticity or genetic divergence. [ABSTRACT FROM AUTHOR]

Ophryotrocha diademais an outcrossing, simultaneous hermaphroditic polychaete with external fertilization. In isolated pairs, mature worms take turn contributing eggs upon the condition that their partners reciprocate egg donation. In dense populations, these worms do not reciprocate. Instead, they strongly compete for mating in their preferred male role and produce few eggs. This plastic sex allocation may result in an overall different reproductive performance: mean individual reproductive output will be larger in sparse than in dense populations. We tested this hypothesis by measuring the individual reproductive output (paternal and maternal offspring) of worms in sparse and dense replicated populations. In dense populations, mean individual reproductive output was fourfold lower than that in sparse populations. We hypothesise that such dramatic demographic costs are potentially widespread in outcrossing simultaneous hermaphrodites with external fertilization and plastic sex allocation. The reproductive output of hermaphroditic organisms is a function of population density (i.e. the number of conspecifics) and studies on population growth and reproductive performance should take this effect into account. [ABSTRACT FROM PUBLISHER]

We previously reported that STAT1 expression is frequently abrogated in human estrogen receptor-α-positive (ERα+) breast cancers and mice lacking STAT1 spontaneously develop ERα+ mammary tumors. However, the precise mechanism by which STAT1 suppresses mammary gland tumorigenesis has not been fully elucidated. Here we show that STAT1-deficient mammary epithelial cells (MECs) display persistent prolactin receptor (PrlR) signaling, resulting in activation of JAK2, STAT3 and STAT5A/5B, expansion of CD61+ luminal progenitor cells and development of ERα+ mammary tumors. A failure to upregulate SOCS1, a STAT1-induced inhibitor of JAK2, leads to unopposed oncogenic PrlR signaling in STAT1−/− MECs. Prophylactic use of a pharmacological JAK2 inhibitor restrains the proportion of luminal progenitors and prevents disease induction. Systemic inhibition of activated JAK2 induces tumor cell death and produces therapeutic regression of pre-existing endocrine-sensitive and refractory mammary tumors. Thus, STAT1 suppresses tumor formation in mammary glands by preventing the natural developmental function of a growth factor signaling pathway from becoming pro-oncogenic. In addition, targeted inhibition of JAK2 may have significant therapeutic potential in controlling ERα+ breast cancer in humans. [ABSTRACT FROM AUTHOR]

Local Mate Competition theory (LMC) predicts female-biased offspring sex ratios when mate competition occurs locally between siblings. The mating system of the marine polychaete wormDinophilus gyrociliatusapparently fits LMC theory well. Females lay egg capsules with 3–6 large eggs (which produce females), and 1–2 small eggs (which produce males), resulting in female-biased sex ratios. However, mating occurs between larvae, inside egg capsules, and brothers fertilize sisters, possibly preventing any competition between unrelated males and obviating the need for sex ratio adjustments to local population size. Therefore, we tested whether mothers adjusted their offspring sex ratio to local population size, controlling for density. As predicted by LMC theory, sex ratios of single females were less male-biased than those of populations of multiple females, suggesting that males also compete with unrelated males. Sex ratio adjustments occurred irrespective of density, revealing sophisticated perception of the social environment in these worms. [ABSTRACT FROM AUTHOR]

Background Over the last 15 years, many studies demonstrated the myogenic regenerative potential of bone marrow mesenchymal stem cells ( BM- MSC), making them an attractive tool for the regeneration of damaged tissues. In this study, we have developed an animal model of esophagogastric myotomy ( MY) aimed at determining the role of autologous MSC in the regeneration of the lower esophageal sphincter ( LES) after surgery. Methods Syngeneic BM- MSC were locally injected at the site of MY. Histological and functional analysis were performed to evaluate muscle regeneration, contractive capacity, and the presence of green fluorescent protein-positive BM- MSC ( BM- MSC- GFP+) in the damaged area at different time points from implantation. Key Results Treatment with syngeneic BM- MSC improved muscle regeneration and increased contractile function of damaged LES. Transplanted BM- MSC- GFP+ remained on site up to 30 days post injection. Immunohistochemical analysis demonstrated that MSC maintain their phenotype and no differentiation toward smooth or striated muscle was shown at any time point. Conclusions & Inferences Our data support the use of autologous BM- MSC to both improve sphincter regeneration of LES and to control the gastro-esophageal reflux after MY. [ABSTRACT FROM AUTHOR]

Related species share genetic and developmental backgrounds. Therefore, separate-sex species that share recent common ancestors with hermaphroditic species may have hidden genetic variation for sex determination that causes some level of lability of expression of gender. Worms of the polychaete species Ophryotrocha labronica have separate, dimorphic sexes and their ancestor was hermaphroditic. Ophryotrocha labronica has a worldwide distribution and populations may differ in the degree of gender specialization. We analyzed the extent to which O. labronica had fixed or labile expression of gender. We found that there were up to four different sexual phenotypes, namely, pure males, males with oocytes, pure females, and females with sperm; the relative frequency of these sexual phenotypes varied in three geographically-distant populations. These sexual morphs had either male or female morphology. However, populations differed in the extent to which worms were sexually dimorphic. In the less dioecious-like population (in which pure males and females were virtually absent, all worms had both oocytes and sperm and sexual dimorphism was relatively weak), males with oocytes had slightly plastic female allocation that depended on mating opportunities—a clearly hermaphroditic trait. Males with oocytes and females with sperm were not functional hermaphrodites. They only used one type of gametes to reproduce and in this respect they probably differed from many cases of inconstancy of gender described in the literature. We consider these populations as novel examples of intermediate states between androdioecy and dioecy. This study contributes to our understanding of breeding systems as continuous gradients rather than as distinct clear-cut alternatives. [ABSTRACT FROM PUBLISHER]

Phenotypic plasticity is the environment-induced change in the phenotype of an organism. Natural selection operates for the ability of individuals to adjust their phenotype to the current environmental conditions when environmental conditions fluctuate. Simultaneous hermaphrodites may exhibit plasticity in sex allocation according to the availability of mates at any particular time. The plasticity in sex allocation has probably evolved under fluctuating mating opportunities, which are usually low but increase when hermaphrodites incur sudden demographic expansion. Here we compare the plasticity in sex allocation in two different populations of the hermaphroditic polychaete wormOphryotrocha diadema– a laboratory population and a wild one. Worms from the laboratory population were kept under constant crowded conditions for about 200 generations (i.e. they were exposed to high mating opportunities). Worms from the wild population were kept under crowded conditions for 20 generations only. Worms from the laboratory population showed significantly less plasticity in sex allocation than worms from the wild population. Although we cannot rule out the hypotheses that genetic drift or local adaptation played a role in the differences between the two populations, the most likely explanation for our results is that worms of the laboratory population underwent a loss of plasticity in sex allocation because they were kept under constant mating opportunities. In fact, the sensory and regulatory machinery that worms use for exhibiting plastic sex allocation responses is likely to be the same as the machinery that is required for mate searching and sex role synchronization between mating partners. The need to maintain this machinery can explain why worms from the laboratory population diminished their plasticity in sex allocation but did not lose it completely. Therefore our results give some clues as to how plasticity in sex allocation evolves or is constrained. [ABSTRACT FROM PUBLISHER]

Social insect colonies are attractive for many arthropods. The rare velvet ant, Mutilla europaea, visit colonies of Polistes wasps, but to date it was unclear which resources it targeted therein. Our field observations and bioassays showed that velvet ants visit the colonies of the social wasp Polistes biglumis almost undisturbed and may feed on larval wasp saliva. Chemical insignificance and resistance are the characteristics that allow velvet ants to visit unharmed wasp colonies and gain such a nutritious reward. [ABSTRACT FROM AUTHOR]

Background:MEK is activated in ∼40% colorectal cancer (CRC) and 20-30% non-small cell lung cancer (NSCLC). Selumetinib is a selective inhibitor of MEK1/2, which is currently in clinical development.Methods:We evaluated the effects of selumetinib in vitro and in vivo in CRC and NSCLC cell lines to identify cancer cell characteristics correlating with sensitivity to MEK inhibition.Results:Five NSCLC and six CRC cell lines were treated with selumetinib and classified according to the median inhibitory concentration (IC50) values as sensitive (1 μM) or resistant (>1 μM). In selumetinib-sensitive cancer cell lines, selumetinib treatment induced G1 cell-cycle arrest and apoptosis and suppression of tumour growth as xenografts in immunodeficient mice. Evaluation of intracellular effector proteins and analysis of gene mutations showed no correlation with selumetinib sensitivity. Microarray gene expression profiles revealed that the activation of cAMP-dependent protein kinase A (PKA) was associated with MEK inhibitor resistance. Combined targeting of both MEK and PKA resulted in cancer cell growth inhibition of MEK inhibitor-resistant cancer cell lines in vitro and in vivo.Conclusion:This study provides molecular insights to explain resistance to an MEK inhibitor in human cancer cell lines. [ABSTRACT FROM AUTHOR]

Social parasites exploit societies, rather than organisms, and rear their brood in social insect colonies at the expense of their hosts, triggering a coevolutionary process that may affect host social structure. The resulting coevolutionary trajectories may be further altered by selection imposed by predators, which exploit the abundant resources concentrated in these nests. Here, we show that geographic differences in selection imposed by predators affects the structure of selection on coevolving hosts and their social parasites. In a multiyear study, we monitored the fate of the annual breeding attempts of the solitary nesting foundresses of Polistes biglumis wasps in four geographically distinct populations that varied in levels of attack by the congeneric social parasite, P. atrimandibularis. Foundress fitness depended mostly on whether, during the long founding phase, a colony was invaded by social parasites or attacked by predators. Foundresses from each population differed in morphological traits and reproductive tactics that were consistent with selection imposed by their natural enemies and in ways that may affect host sociality. In turn, parasite traits were consistent with selection imposed locally by hosts, implying a geographic mosaic of coevolution in this brood parasitic interaction. [ABSTRACT FROM AUTHOR]

We used DNA microsatellites to study colony kin structure and breeding patterns in the primitively eusocial wasp Polistes biglumis. P. biglumis inhabits cool areas at high altitudes and, as a consequence, has a reduced colony cycle compared to more temperate Polistes. P. biglumis colonies are always founded and controlled by a single foundress, but nest failure is common and foundresses losing their nests do not have time to start new ones due to the short season. Instead, nests are characterized by frequent female turnover, in the form of females taking over (usurpation) other con-specific nests. Our results showed that most nests had offspring from multiple unrelated females, including some where multiple females were not observed in monitoring. Reconstruction of behavioural events from the genetic data revealed three types of multiple matriline nests: (a) nests that were usurped by another female, where the original nest owner disappeared following the usurpation event, (b) nests that were joined by another female, where the original nest owner stayed following the joining event, (c) nests that were both usurped and joined by other females. We also found, for the first time, a clear indication of multiple mating by Polistes females. Moreover, males mating with the same female were related, which may be explained by the lek mating system of P. biglumis. Finally, we analysed the nest sex ratios and how it changed during the season and found that sexes were produced sequentially, males before females. [ABSTRACT FROM AUTHOR]

ims/hypothesis: Impaired activity of the pentose phosphate pathway of glucose metabolism caused by hereditary deficiency of its key regulatory enzyme glucose-6-phosphate dehydrogenase (G6PD) has consequences that may worsen or attenuate the course of diabetic complications. Decreased availability of NADPH can predispose to oxidative stress and endothelial dysfunction, but can also limit the activity of the polyol pathway and cholesterol synthesis. Reduced availability of pentose phosphates for nucleic acid synthesis could impair cell proliferation. We sought to learn in which direction G6PD deficiency affects diabetic retinopathy. Methods: We enrolled patients who were G6PD-deficient or -sufficient with type 1 diabetes of duration 15 years or longer for whom HbA records were available for at least the previous 3 years. Renal failure and smoking were exclusion criteria. For each participant seven standard field colour photographs were obtained of each eye, and retinopathy was graded in a masked fashion. Results: The clinical characteristics of the 19 G6PD-deficient patients studied (age 42 ± 9 years, diabetes duration 24 ± 6 years, average HbA over 3 years 6.7 ± 0.8%) were similar to those of the 35 G6PD-sufficient patients. Almost 90% of patients in both groups had retinopathy; however, proliferative retinopathy was noted solely among G6PD-deficient patients (28%, p = 0.0036 vs G6PD-sufficient). The G6PD-deficient patients also showed a trend for increased frequency of microalbuminuria. Conclusions/interpretation: The data suggest that G6PD deficiency accelerates the microvascular complications of diabetes, and that among the consequences of G6PD deficiency those that can enhance the damage caused by diabetes outweigh those that could be protective. [ABSTRACT FROM AUTHOR]

Sexual selection is often quantified using Bateman gradients, which represent sex-specific regression slopes of reproductive success on mating success and thus describe the expected fitness returns from mating more often. Although the analytical framework for Batenian gradients aimed at covering all sexual systems, empirical studies are biased toward separate-sex organisms, probably because important characteristics of other systems remain incompletely treated. Our synthesis complements the existing Bateman gradient approach with three essential reproductive features of simultaneous hermaphrodites. First, mating in one sex may affect fitness via the opposite sex, for example, through energetic trade-offs. We integrate cross-sex selection effects and show how they help characterizing sexually mutualistic versus antagonistic selection. Second, male and female mating successes may be correlated, complicating the interpretation of Bateman gradients. We show how to quantify the impact of this correlation on sexual selection and propose a principal component analysis on male and female mating success to facilitate interpretation. Third, self-fertilization is accounted for by adding selfed progeny as a separate category of reproductive success to analyses of Bateman gradients. Finally, using a worked example from the snail Biomphalaria glabrata, we illustrate how the extended analytical framework can enhance our understanding of sexual selection in hermaphroditic animals and plants. [ABSTRACT FROM AUTHOR]

Hermaphroditism and gonochorism are two contrasting forms of sexuality. Hermaphroditic species are generally seen as species adapted to conditions of low density, stabilized by poor mate search efficiency and high costs of searching. They can adjust allocation of reproductive resources to each sex function in response to current social conditions, making reproduction more efficient, at least in principle. By contrast, gonochorism (separate sexes) is advantageous when mates are frequent, making it ineffective to maintain two sex functions in a single individual. This, however, also rules out the need for a flexible response to mating opportunities as known for hermaphrodites. In the hermaphroditic marine polychaete worm Ophryotrocha d!adema we showed earlier that group size is assessed through a chemical cue. In this study we verified the accuracy of the response to gradients of the chemical cue used to assess group size by O. diadema by checking reduction in egg production as the group of partners increases, as expected according to sex allocation theory. Furthermore we compared the effect of such a gradient with a similar gradient in a closely related gonochoric species (O. labronica). Here sex allocation adjustment is not predicted, thus an adaptive change in egg production in response to group-size cues is not expected. In fact, our results show that the group-size effect only occurs in O. diadema and not in O. labronica. Moreover, our study provides evidence of high perceptual abilities of chemical cues in O. diadema, suggesting that perceiving social cues and adjusting sex allocation appropriately are special properties of hermaphrodites. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study was to map metabolic compensation and depression in Alzheimer's disease (AD) on a voxel-by-voxel basis. Methods: Twenty-one healthy elderly subjects and 25 AD patients underwent cerebral MR and FDG-PET imaging. All images were processed with SPM2, and whole-brain gray matter (GM) atrophy and hypometabolism maps were computed. Metabolic compensation and depression were assessed using Biological Parametric Mapping software. Results: GM atrophy and hypometabolism mapped to similar regions, with varying degrees of severity. Significant metabolic compensation was found in the amygdala, while exceeding hypometabolism was mainly located in the posterior cingulate cortex. Conclusion: Metabolic depression can be due to both distant effects of atrophy and to additional hypometabolism-inducing factors, such as amyloid deposition. Conversely, metabolic compensation could reflect spared synaptic plasticity of the surviving neurons. The investigation of the metabolic compensation mechanism could help in the comprehension of the AD underlying pathology. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study was to map metabolic compensation and depression in Alzheimer’s disease (AD) on a voxel-by-voxel basis. Methods: Twenty-one healthy elderly subjects and 25 AD patients underwent cerebral MR and FDG-PET imaging. All images were processed with SPM2, and whole-brain gray matter (GM) atrophy and hypometabolism maps were computed. Metabolic compensation and depression were assessed using Biological Parametric Mapping software. Results: GM atrophy and hypometabolism mapped to similar regions, with varying degrees of severity. Significant metabolic compensation was found in the amygdala, while exceeding hypometabolism was mainly located in the posterior cingulate cortex. Conclusion: Metabolic depression can be due to both distant effects of atrophy and to additional hypometabolism-inducing factors, such as amyloid deposition. Conversely, metabolic compensation could reflect spared synaptic plasticity of the surviving neurons. The investigation of the metabolic compensation mechanism could help in the comprehension of the AD underlying pathology. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. The International Classification of Disease, ninth revision (ICD-9) is designed to code disease into categories which are placed into administrative databases. These databases have been used for epidemiological studies. However, the categories used in the ICD9-codes are not always the most effective for evaluating specific diseases or their outcomes, such as the outcomes of cancer treatment. Therefore a re-classification of the ICD-9 codes into new categories specific to cancer outcomes is needed. Methods. An expert panel comprised of two physicians created broad categories that would be most useful to researchers investigating outcomes and morbidities associated with the treatment of cancer. A Senior Data Coordinator with expertise in ICD-9 coding, then joined this panel and each code was re-classified into the new categories. Results. Consensus was achieved for the categories to go from the 17 categories in ICD-9 to 39 categories. The ICD-9 Codes were placed into new categories, and subcategories were also created for more specific outcomes. The results of this re-classification is available in tabular form. Conclusions. ICD-9 codes were re-classified by group consensus into categories that are designed for oncology survivorship research. The novel re-classification system can be used by those involved in cancer survivorship research. [ABSTRACT FROM AUTHOR]

Objective: Prevention of diabetic retinopathy would benefit from availability of drugs that preempt the effects of hyperglycemia on retinal vessels. We aimed to identify candidate drug targets by investigating the molecular effects of drugs that prevent retinal capillary demise in the diabetic rat.Research Design and Methods: We examined the gene expression profile of retinal vessels isolated from rats with 6 months of streptozotocin-induced diabetes and compared it with that of control rats. We then tested whether the aldose reductase inhibitor sorbinil and aspirin, which have different mechanisms of action, prevented common molecular abnormalities induced by diabetes. The Affymetrix GeneChip Rat Genome 230 2.0 array was complemented by real-time RT-PCR, immunoblotting, and immunohistochemistry.Results: The retinal vessels of diabetic rats showed differential expression of 20 genes of the transforming growth factor (TGF)-beta pathway, in addition to genes involved in oxidative stress, inflammation, vascular remodeling, and apoptosis. The complete loop of TGF-beta signaling, including Smad2 phosphorylation, was enhanced in the retinal vessels, but not in the neural retina. Sorbinil normalized the expression of 71% of the genes related to oxidative stress and 62% of those related to inflammation. Aspirin had minimal or no effect on these two categories. The two drugs were instead concordant in reducing the upregulation of genes of the TGF-beta pathway (55% for sorbinil and 40% for aspirin) and apoptosis (74 and 42%, respectively).Conclusions: Oxidative and inflammatory stress is the distinct signature that the polyol pathway leaves on retinal vessels. TGF-beta and apoptosis are, however, the ultimate targets to prevent the capillary demise in diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Myeloproliferative disorders (MPDs) are clonal malignancies that arise from hematopoietic progenitors and characterized by overproduction of mature, functional blood cells. These disorders can be broadly characterized into Philadelphia chromosome-positive (Ph(+)) or negative (Ph(−)) genetic groupings. Chronic myeloid leukemia (CML) is a Ph(+) MPD that is defined on the basis of its molecular lesion, the BCR-ABL fusion gene. Inhibitors directed at the constitutive kinase activity of BCR-ABL have been shown to be disease modifying in CML and have dramatically altered the standard of care for this leukemia. The three main Ph(−) MPDs are polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The key features of these Ph(−) MPDs are an increased red blood cell mass in PV, a high platelet count in ET and bone marrow fibrosis in PMF, respectively. These disorders also share many clinical features such as long clinical course, increased risk for thrombosis, hemorrhage and elevated risk of leukemic transformation. Interest in these disorders has been ignited by the recent discovery of activating mutations in the tyrosine kinase gene, JAK2, in the predominance of Ph(−) MPD patients and has highlighted JAK2 as a therapeutic intervention point for drug discovery efforts with selective kinase inhibitors. This review will focus on the comparison of Ph(+) and Ph(−) MPDs, drug discovery and development efforts targeting these disorders, and will assess the new opportunities for targeted therapies for these diseases.Oncogene (2009) 28, 2305–2313; doi:10.1038/onc.2009.107; published online 4 May 2009 [ABSTRACT FROM AUTHOR]

The role of sexual selection in shaping the mating system of hermaphrodites is currently widely accepted. However, a quantification of the intensity of sexual selection in hermaphroditic animals has never been accomplished. We evaluated the opportunity for sexual selection for both the female and the male functions in the simultaneous outcrossing hermaphrodite Ophryotrocha diadema by measuring focal hermaphrodites’ paternal and maternal offspring in experimental replicated monogamous and promiscuous populations, using genetic markers to estimate paternity. Opportunity for sexual selection for each of the two sexual functions was quantified by means of the Crow’s index, i.e. the ratio of variance in progeny number to the squared mean number of progeny. In addition, the extent to which the reproductive success was shared among competing individuals was estimated by means of the Nonacs’s B index. We documented that the strength of selection on the male and female function in hermaphrodites with external fertilization depends on the reproductive context. Under a promiscuous regime, hermaphrodites have higher opportunities for selection for both the male and the female function than under the monogamous regime. Moreover, the reproductive skew for the female function becomes greater than that for the male function, moving from monogamy to promiscuity. In our model system, allocation to one sexual function is opposed by any degree of allocation to the other, indicating that sex-specific patterns of selection operate in this model species. [ABSTRACT FROM AUTHOR]

Because of their double sex functions, hermaphrodites are selected to optimize their investment in the two sex functions. Sex allocation (SA) theory predicts that, in promiscuous mating conditions, simultaneous hermaphrodites should adjust their reproductive investment so as to invest an amount of resources into the male relatively larger than that invested into the female function. In contrast, in monogamy, individuals should invest relatively larger amount of resources into the female function at the expenses of the male function. In the study of SA patterns of simultaneous hermaphrodites little attention has been paid to allocate adjustments costs, which may play an important role in determining variations in SA pattern among species. Indeed, the costs paid for such adjustments may constrain sex investment resulting in suboptimal allocation. We evaluated the costs of SA adjustments on individual fitness in each sexual function in the simultaneous, outcrossing hermaphrodite Ophryotrocha diadema. Following a crossover design, we compared the reproductive success in paternal and maternal offspring of focal hermaphrodites, which were put in replicated monogamous and promiscuous regimes. We document that those hermaphrodites that switched mating regimes and altered their sex investment accordingly did not entail large short-term fitness costs in any sexual function compared to those that were in stable mating regimes. Indeed, individuals changed their sex investment quickly and appropriately to current mating conditions. Hermaphrodites, which had to adjust their SA, did not decrease their maternal or paternal reproductive output with respect to those which did not change their SA. Time needed to shift resources from one to the other sex function is 5 days (the time interval between successive egg layings is of 3 days) indicating that selective pressures for SA adjustments may favour great plasticity and quick adjustments of sex investments in simultaneous hermaphrodites. [ABSTRACT FROM AUTHOR]

Abnormalities in retinal haemodynamics have been reported in patients with type 1 diabetes in advance of clinical retinopathy. These abnormalities could therefore be useful as early markers or surrogate endpoints for studying the microangiopathy. Since the DCCT, the increased focus on good glycaemic control is changing the natural history of diabetic retinopathy. Based on this, the aim of this study was to investigate whether patients with type 1 diabetes treated entirely or mostly in the post-DCCT era and tested in the absence of confounding factors show retinal haemodynamic abnormalities. We measured retinal haemodynamics by laser Doppler flowmetry in 33 type 1 diabetic individuals with no or minimal retinopathy (age 30 ± 7 years, duration of diabetes 8.8 ± 4.6 years, 9% showing microaneurysms), and 31 age- and sex-matched non-diabetic controls. The study participants were not taking vasoactive medications, and blood glucose at the time of haemodynamic measurements was required to be between 3.8 and 11.1 mmol/l. HbA1c was 7.5 ± 1.2% and blood glucose 7.7 ± 2.8 mmol/l in these type 1 diabetic individuals, indicating relatively good glycaemic control. Retinal blood speed, arterial diameter and blood flow were not different between the diabetic individuals and the matched controls. Type 1 diabetic patients with no or minimal retinopathy who maintain relatively good glycaemic control do not show abnormalities of the retinal circulation at steady state, even after several years of diabetes. In such patients it may be necessary to test the vascular response to challenges to uncover any subtle abnormalities of the retinal vessels. [ABSTRACT FROM AUTHOR]

The dose limiting toxicity of oxaliplatin (l-HOP) is neurotoxicity, which is characterized by an acute neuropathy and a clinically distinct chronic neuropathy. This randomized study evaluated if prolonged l-HOP infusion over the conventional l-HOP schedule was useful in reducing acute and possibly chronic l-HOP induced neurotoxicity in colon and gastric cancer patients receiving l-HOP-based regimen as adjuvant chemotherapy. Sixty-four patients were randomly assigned to group A (26 colon and 6 gastric cancer) and to group B (23 colon and 9 gastric cancer). Chemotherapy in both groups consisted of l-HOP 85 mg/m2 i.v. only on day 1, with leucovorin 100 mg/m2 i.v. as a 2-h infusion followed by bolus 5-fluorouracil (5-FU) 400 mg/m2/day and a 22-h infusion of 5-FU 600 mg/m2/day, repeated for two consecutive days every 2 weeks for a maximum of 12 cycles. Patients in group A received l-HOP as a continuous 6-h i.v. infusion, and patients in group B received l-HOP as the conventional 2-h i.v. infusion. The percentage of patients presenting with grade ≥2 neurotoxicity was statistically lower in group A than in group B (28.1% vs. 59.3%: P = 0.02). There was a statistically lower percentage of cycles with grade ≥2 neurotoxicity in group A (6.1%) than in group B (18.5%) ( P < 0.001). This study suggests that l-HOP as a continuous 6-h infusion is useful in preventing and reducing acute l-HOP induced neurotoxicity in patients with colon and gastric cancer receiving FOLFOX-4 regimen as adjuvant treatment. [ABSTRACT FROM AUTHOR]

Sex allocation theory predicts that, in hermaphroditic organisms, individuals allocate a fixed amount of resources divided among male and female functions to reproduction and that the proportion devoted to each sex depends on the mating group size. As the mating group size increases, hermaphrodites are predicted to allocate proportionally more resources to the male and less resources to the female function (approaching equal allocation to both sexes) to face increased sperm competition. Up to now little experimental evidence has been provided to support the theory in hermaphroditic animals. Facultative shift between male and female allocation in response to variation in local group size does occur in several tax a but not always in the expected direction and not with similar patterns. In the protandric and then simultaneously hermaphroditic polychaete worm Ophryotrocha diadema reproductive resources are flexibly allocated in the protandrous and the hermaphroditic phase. The cost of male reproduction during adolescence is spread over the whole energy budget of the animal as shown by the shortening of lifespan and the lowering of growth rate in individuals with enhanced male expenditure during the protandrous phase. Moreover, in this species, short term sex allocation adjustments differ from those described in other taxa. Individuals regulate their reproductive output so that where reproductive competitors are present, the number of female gametes is strongly reduced but the number of male gametes (although it changes) is not significantly increased. Resources subtracted from the female function are not directly allocated to sperm production, but to expensive male behaviors that are likely to enhance male reproductive success. These results are discussed in the light of the relevance of sexual selection in large populations of hermaphrodites. [ABSTRACT FROM AUTHOR]

Sex allocation theory predicts that simultaneous hermaphrodites shift sex allocation facultatively in response to variation in local group size. This study was performed to evaluate the relative investment in each sex function by the simultaneously hermaphroditic polychaete worm Ophryotrocha diadema and to test whether allocation to each sex depends on the number of reproductive competitors. Four experimental groups were set up (in a 2 × 2 factorial design) with small or large group size and with small or large enclosures to control for potential confounding effects of density. We measured the proportion of female and male investment in focal individuals. Results revealed that individuals regulated their reproductive output so that when reproductive competitors were present, the number of female gametes was strongly reduced and the male function increased. In contrast, under monogamy, individuals in small groups produced lower numbers of sperm but had a higher egg output than worms in large groups. Density did not affect sex allocation in our experiment. Our findings provide qualitative support for Local Mate Competition theory, but also show that the pattern of sex allocation specific to this species is more complex than expected by current theory. [ABSTRACT FROM AUTHOR]

A total of 41 metastatic colorectal cancer (CRC) patients received tegafur/uracil (UFT)+leucovorin (LV)+oxaliplatin alternated with UFT/LV+irinotecan. The overall response rate was 58.5% (95% confidence interval, 42.2-73.3%), and the median progression-free survival was 8.8 months. There were no grade 4 toxicities; 12 patients (29%) experienced grade 3 diarrhoea. There were no cases of hand-foot syndrome. This alternating regimen seems to be effective and well tolerated in the first-line treatment of patients with metastatic CRC. [ABSTRACT FROM AUTHOR]

The phytotoxic protein PcF (Phytophthora cactorum-Fragaria) is a 5.6-kDa cysteine-rich, hydroxyproline- containing protein that is secreted in limited amounts by P. cactorum, an oomycete pathogen of tomato, strawberry and other relevant crop plants. Although we have shown that pure PcF triggers plant reactivity, its mechanism of action is not yet understood. Here we show that PcF, like other known fungal protein elicitors involved in pathogen-plant interaction, stimulates the activity of the defense enzyme phenylalanine ammonia a key step in understanding the mechanism of action of PcF at a molecular level is knowledge of its three-dimensional structure, we overexpressed this protein extracellularly in Pichia pastoris. The preliminary structural and functional characterization of a recombinant PcF homologue, N4-rPcF, is reported. Interestingly, although N4-rPcF is devoid of proline hydroxylation and has four additional amino acid residues attached to its N terminus, its secondary structure and biological activity are indistinguishable from wild-type PcF. [ABSTRACT FROM AUTHOR]

Background: Selective re-creation of a new internal anal sphincter could be indicated when the natural one is irreversibly damaged or excised. Methods: In this preliminary experimental work, surgical techniques of internal anal sphincter replacement in pigs were investigated. After preoperative anorectal manometry, surgical procedure was done in two phases: abdominal, mobilization of the colon-rectum to the pelvic floor; and perianal, dissection of the anal canal from the external anal sphincter through the intersphincteric space. The fully mobilized anorectal segment, including the internal anal sphincter, was pulled down through the anus and resected. The distal colonic stump was then demucosated and two types of plications of the demucosated segment were accomplished, each type in three animals. The plicated segment was then returned into the anal canal, inside the external sphincter. Short-term follow-up with clinical and manometric evaluations was performed and, subsequently, histological analysis of the plicated segment, after the animals were sacrificied. Results: None of the animals became incontinent. Anal manometry identified a high-pressure zone and relaxation reflex in the new anal canal. Histologic studies showed hypertrophy of smooth muscle layers without degenerative changes. Conclusion: This study indicates that a plication of colonic smooth muscle wall can re-create a high-pressure zone in the anal canal after the internal anal sphincter has been excised. [ABSTRACT FROM AUTHOR]

For several decades the pathobiology of diabetic retinopathy has been the object of conjecture and hypotheses. Indeed, very little was known about the cellular events triggered by diabetes in the retina and about the processes underlying the microangiopathy. In the last few years there has been a concerted effort to acquire such information, and the work has targeted not just the retinal vessels but more comprehensively the retina. The picture emerging is one of multiplicity: multiple cell types in the retina are affected early by diabetes and multiple processes are operative in the microangiopathy. The main abnormalities captured to date are altered expression of several genes, apoptosis, microthrombosis, and proinflammatory changes. The new information needs to be integrated into temporal and mechanistic sequences and further expanded but it is beginning to provide a framework for the cellular dimension of diabetic retinopathy. [Diabetologia (2001) 44: 791–804] [ABSTRACT FROM AUTHOR]

In diabetic retinopathy, capillary nonperfusion and eventual obliteration can lead to retinal ischemia and sight-threatening neovascularization. The occurrence of retinal microthrombosis in human diabetes has long been suspected and occasionally observed but never systematically demonstrated. We used trypsin digestion to isolate the intact vascular network from retinas obtained postmortem from nine diabetic donors (age 64 +/- 11 years, duration of diabetes 6 +/- 4 years; mean +/- SD) and eight age-matched nondiabetic donors. Topographically matched sectors (each one-sixth of retina) of diabetic and nondiabetic retinas were tested sequentially with antibodies to fibrin cross-linking factor XIII and platelet glycoprotein (GP)-IIIa to identify fibrin-platelet thrombi. In some trypsin digests, we also examined vascular cell apoptosis. The retina from a nondiabetic donor, 24 years of age, who had died of trauma, was used to exclude confounding influences caused by the postmortem period. When compared with those of nondiabetic donors, the retinas of diabetic donors showed double the number of capillary segments with colocalized immunostaining for factor XIII and GPIIIa (P = 0.02). The total area of the positive segments was fourfold greater in the diabetic than in the nondiabetic donors (P = 0.02) and correlated with the duration of diabetes (r = 0.71, P < 0.05). Large thrombi were six times more frequent in the diabetic donors (P = 0.03), and there was a significant topographical association of microthrombosis with apoptotic cells in both diabetic and nondiabetic vessels (P = 0.0001). Hence, diabetes of short duration was found to be associated with a greater than normal number and size of platelet-fibrin thrombi in the retinal capillaries. These thrombi can contribute to capillary obliteration and retinal ischemia and may be a practical target for early drug intervention. [ABSTRACT FROM AUTHOR]

IGF-I promotes the survival of multiple cell types by activating the IGF-I receptor (IGF-IR), which signals downstream to a serine/threonine kinase termed Akt. Because in diabetes vascular and neural cells of the retina undergo accelerated apoptosis, we examined IGF-I synthesis and signaling in the human and rat diabetic retina. In retinas obtained postmortem from six donors aged 64 +/- 8 years with a diabetes duration of 7 +/- 5 years, IGF-I mRNA levels were threefold lower than in the retinas of six age-matched nondiabetic donors (P = 0.005). In the retinas of rats with 2 months' duration of streptozotocin-induced diabetes, IGF-I mRNA levels were similar to those of control rats, but after 5 months of diabetes they failed to increase to the levels recorded in age-matched controls (P < 0.02). Retinal IGF-I expression was not altered by hypophysectomy, proving to be growth-hormone independent. IGF-IR levels were modestly increased in the human diabetic retinas (P = 0.02 vs. nondiabetic retinas) and were unchanged in the diabetic rats. Phosphorylation of the IGF-IR could be measured only in the rat retina, and was not decreased in the diabetic rats (94 +/- 18% of control values). In the same diabetic rats, phosphorylation of Akt was 123 +/- 21% of control values. There was not yet evidence of increased apoptosis of retinal microvascular cells after 5 months of streptozotocin-induced diabetes. Hence, in the retina of diabetic rats, as in the retina of diabetic human donors, IGF-I mRNA levels are substantially lower than in age-matched nondiabetic controls, whereas IGF-IR activation and signaling are not affected, at least for some time. This finding suggests that in the diabetic retina, the activation of the IGF-IR is modulated by influences that compensate for, or are compensated by, decreased IGF-I synthesis. [ABSTRACT FROM AUTHOR]

The ability of two species of Polistes wasps to distinguish their own from nearby nests was tested, following the procedure used by Espelie et al. Our experiments demonstrated that, in the laboratory, females of Polistes dominulus and Polistes nimphus preferentially selected their own nests rather than nearby nests. We also evaluated the role of odor cues in nest recognition by washing nests in hexane to remove the apolar solvent-soluble components of nest odor. Although P. nimphus females continued to discriminate nests even after washing, P. dominulus individuals failed to discriminate between their own and a foreign neighboring nest. In both species, wasps were able to recognize their own nests when nest extracts were subsequently reapplied to the nest surface. These results indicate that P. dominulus wasps recognize their nests through perception of nest odor. The ability of P. nimphus wasps to distinguish their own nests even after presumed removal of the nest odor is discussed. [ABSTRACT FROM AUTHOR]

Foundresses of the social wasp Polistes biglumis were tested to see whether they were able to recognize alien eggs experimentally introduced into their own nests. Foundresses removed alien conspecific reproductive-destined eggs while they accepted worker-destined eggs. The results indicate that social wasps discriminate among eggs and that they discriminate against alien eggs destined to produce unrelated reproductives. P. biglumis is a strictly solitary founding species, with no reproductive competition within colonies; thus, brood discrimination abilities could have evolved as a counteradaptation against intra- and inter-specific brood parasitism. [ABSTRACT FROM AUTHOR]