Interspecific extrinsic and intrinsic competitive interactions in egg parasitoids

Interspecific competitive interactions can occur either between adult parasitoids searching/exploiting hosts (extrinsic competition) or between parasitoid larvae developing within the same host (intrinsic competition). Understanding how interspecific competition between parasitoids can affect pest suppression is important for improving biological pest control. The purpose of this work was to review both extrinsic and intrinsic competition between egg parasitoid species. These are organisms that are often candidates for biological control programs due to their ability to kill the pest before the crop feeding stage. We first reviewed the literature about interspecific competitive abilities of adult parasitoids in terms of comparative host location strategies highlighting which ecological and behavioral factors are likely to shape extrinsic competition. Then we focused on the interspecific competitive interactions between immatures developing within the same host taking into account which factors play a key role in the outcome of intrinsic competition. Finally we conclude stressing on the need to elucidate the overall competitive interaction that parasitoid species may experience in the field in order to enhance biological control success.     

The ghost of social environments past: dominance relationships include current interactions and experience carried over from previous groups

Dominance hierarchies pervade animal societies. Within a static social environment, in which group size and composition are unchanged, an individual's hierarchy rank results from intrinsic (e.g. body size) and extrinsic (e.g. previous experiences) factors. Little is known, however, about how dominance relationships are formed and maintained when group size and composition are dynamic. Using a fusion-fission protocol, we fused groups of previously isolated shore crabs (Carcinus maenas) into larger groups, and then restored groups to their original size and composition. Pre-fusion hierarchies formed independently of individuals' sizes, and were maintained within a static group via winner/loser effects. Post-fusion hierarchies differed from pre-fusion ones; losing fights during fusion led to a decline in an individual's rank between pre- and post-fusion conditions, while spending time being aggressive during fusion led to an improvement in rank. In post-fusion tanks, larger individuals achieved better ranks than smaller individuals. In conclusion, dominance hierarchies in crabs represent a complex combination of intrinsic and extrinsic factors, in which experiences from previous groups can carry over to affect current competitive interactions.     

Molecular mechanism of size control in development and human diseases

How multicellular organisms control their size is a fundamental question that fascinated generations of biologists. In the past 10 years, tremendous progress has been made toward our understanding of the molecular mechanism underlying size control. Original studies from Drosophila showed that in addition to extrinsic nutritional and hormonal cues, intrinsic mechanisms also play important roles in the control of organ size during development. Several novel signaling pathways such as insulin and Hippo-LATS signaling pathways have been identified that control organ size by regulating cell size and/or cell number through modulation of cell growth, cell division, and cell death. Later studies using mammalian cell and mouse models also demonstrated that the signaling pathways identified in flies are also conserved in mammals. Significantly, recent studies showed that dysregulation of size control plays important roles in the development of many human diseases such as cancer, diabetes, and hypertrophy.     

Growth and specification: fly Pax6 homologs eyegone and eyeless have distinct functions

Development requires not only the correct specification of organs and cell types in the right places (pattern), but also the control of their size and shape (growth). Many signaling pathways control both pattern and growth and how these two are distinguished has been something of a mystery. In the fly eye, a Pax6 homolog (eyeless) controls eye specification together with several other genes. Now Dominguez et al.1 show that Notch signaling controls eye growth through a second Pax6 protein (Eyegone). In mice and humans the single Pax6 gene appears to encode both specification and growth controlling proteins through alternative mRNA splicing.     

Intrinsic and extrinsic control of growth in developing organs

The growth rate and final size of developing organs is controlled by organ-intrinsic mechanisms as well as by hormones and growth factors that originate outside the target organ. Recent work on Drosophila imagined discs and other regenerating systems has led to the conclusion that the intrinsic growth-control mechanism that controls regenerative growth depends on position-specific interactions between cells and their neighbors, and that these interactions also control pattern formation. According to this interpretation, local growth by cell proliferation is stimulated when cells with disparate positional information are confronted as a result of grafting or wound healing. This local growth leads to intercalation of cells with intervening positional values until the positional information discontinuity is eliminated. When all discontinuities have been eliminated from a positional field, growth stops. In this article we consider the possibility that organ growth during normal development may be controlled by an intercalation mechanism similar to that proposed for regenerative growth. Studies of imaginal disc growth are consistent with this suggestion, and in addition they show that the cell interactions thought to control growth are independent of cell lineage. Developing organs of vertebrates also show intrinsic growth-control mechanisms, as demonstrated by the execution of normal growth programs by immature organs that are transplanted to fully grown hosts or to hosts with genetically different growth parameters. Furthermore, these organ-intrinsic mechanisms also appear to be based on position-specific cell interactions, as suggested by the growth stimulation seen after partial extirpation or rearrangement by grafting. In organs of most adult vertebrates, the organ-intrinsic growth-control system seems to be suppressed as shown by the loss of regenerative ability, although it is clearly retained in the limbs, tails and other organs of salamanders. The clearest example of an extrinsic growth regulator is growth hormone, which plays a dominant role along with insulin-like growth factors, thyroid hormone and sex hormones in supporting the growth of bones and other organs in postnatal mammals. These hormones do not appear to regulate prenatal growth, but other hormones and insulin-like growth factors may be important prenatally. The importance of other growth factors in regulating organ growth in vivo remains to be established. It is argued that both intrinsic and extrinsic factors control organ growth, and that there may be important interactions between the two types of control during development.     

A matter of size: developmental control of organ size in plants

The intrinsic size of plant organs is determined by developmental signals, yet the molecular and genetic mechanisms that control organ size are largely unknown. Ongoing functional analysis of Arabidopsis genes is defining important regulators involved in these mechanisms. Key features of this control are the coordinated activation of growth and cell division by growth regulators and the maintenance of meristematic competence by the ANT gene, which acts as an organ-size checkpoint. Alterations of genome size by polyploidization and endoreduplication can reset this checkpoint by ploidy-dependent, epigenetically regulated differential gene expression. In addition, the regulation of polarized growth and phytohormone signaling also affect final organ size. These findings reveal unique aspects of plant organ-size control that are distinct from animal organ-size control.     

Hippo circuitry and the redox modulation of hippo components in cancer cell fate decisions

Meticulous and precise control of organ size is undoubtedly one of the most pivotal processes in mammalian development and regeneration along with cell differentiation, morphogenesis and programmed cell death. These processes are strictly regulated by complex and highly coordinated mechanisms to maintain a steady growth state. There are a number of extrinsic and intrinsic factors that dictate the total number and/or size of cells by influencing growth, proliferation, differentiation and cell death. Multiple pathways, such as those involved in promoting organ size and others that restrict disproportionate tissue growth act simultaneously to maintain cellular and tissue homeostasis. Aberrations at any level in these organ size-regulating processes can lead to various pathological states with cancers being the most formidable one (Yin and Zhang, 2011). Extensive research in the realm of growth control has led to the identification of the Hippo-signaling pathway as a critical network in modulating tissue growth via its effect on multiple signaling pathways and through intricate crosstalk with proteins that regulate cell polarity, adhesion and cell-cell interactions (Zhao et al., 2011b). The Hippo pathway controls cell number and organ size by transducing signals from the plasma membrane to the nucleus to regulate the expression of genes involved in cell fate determination (Shi et al., 2015). In this review, we summarize the recent discoveries concerning Hippo pathway, its diversiform regulation in mammals as well as its implications in cancers, and highlight the possible role of oxidative stress in Hippo pathway regulation.     

From endosymbionts to host communities: factors determining the reproductive success of arthropod vectors

Elucidating the factors determining reproductive success has challenged scientists since Darwin, but the exact pathways that shape the evolution of life history traits by connecting extrinsic (e.g., landscape structure) and intrinsic (e.g., female’s age and endosymbionts) factors and reproductive success have rarely been studied. Here we collected female fleas from wild rodents in plots differing in their densities and proportions of the most dominant rodent species. We then combined path analysis and model selection approaches to explore the network of effects, ranging from micro to macroscales, determining the reproductive success of these fleas. Our results suggest that female reproductive success is directly and positively associated with their infection by Mycoplasma bacteria and their own body mass, and with the rodent species size and total density. In addition, we found evidence for indirect effects of rodent sex and rodent community diversity on female reproductive success. These results highlight the importance of exploring interrelated factors across organization scales while studying the reproductive success of wild organisms, and they have implications for the control of vector-borne diseases.     

Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand?

Underneath the intricacy of every cancer lies mysterious events that impel the tumour cell and its posterity into abnormal growth and tissue invasion. Oncogenic mutations disturb the regulatory circuits responsible for the governance of versatile cellular functions, permitting tumour cells to endure deregulated proliferation, resist to proapoptotic insults, invade and erode normal tissues and above all escape apoptosis. This disruption of apoptosis has been highly implicated in various malignancies and has been exploited as an anticancer strategy. Owing to the fact that apoptosis causes minimal inflammation and damage to the tissue, apoptotic cell death-based therapy has been the centre of attraction for the development of anticancer drugs. Increased understanding of the molecular pathways underlying apoptosis has enabled scientists to establish unique approaches targeting apoptosis pathways in cancer therapeutics. In this review, we reconnoitre the two major pathways (intrinsic and extrinsic) targeted cancer therapeutics, steering toward chief modulators of these pathways, such as B-cell lymphoma 2 protein family members (pro- and antiapoptotic), inhibitor of apoptosis proteins, and the foremost thespian of extrinsic pathway regulator, tumour necrosis factor-related apoptosis-inducing agent. Together, we also will have a look from clinical perspective to address the agents (drugs) and therapeutic strategies adopted to target these specific proteins/pathways that have entered clinical trials.     

Linking stem cell function and growth pattern of intestinal organoids

Intestinal stem cells (ISCs) require well-defined signals from their environment in order to carry out their specific functions. Most of these signals are provided by neighboring cells that form a stem cell niche, whose shape and cellular composition self-organize. Major features of this self-organization can be studied in ISC-derived organoid culture. In this system, manipulation of essential pathways of stem cell maintenance and differentiation results in well-described growth phenotypes.We here provide an individual cell-based model of intestinal organoids that enables a mechanistic explanation of the observed growth phenotypes. In simulation studies of the 3D structure of expanding organoids, we investigate interdependences between Wnt- and Notch-signaling which control the shape of the stem cell niche and, thus, the growth pattern of the organoids. Similar to in vitro experiments, changes of pathway activities alter the cellular composition of the organoids and, thereby, affect their shape. Exogenous Wnt enforces transitions from branched into a cyst-like growth pattern; known to occur spontaneously during long term organoid expansion. Based on our simulation results, we predict that the cyst-like pattern is associated with biomechanical changes of the cells which assign them a growth advantage. The results suggest ongoing stem cell adaptation to in vitro conditions during long term expansion by stabilizing Wnt-activity.Our study exemplifies the potential of individual cell-based modeling in unraveling links between molecular stem cell regulation and 3D growth of tissues. This kind of modeling combines experimental results in the fields of stem cell biology and cell biomechanics constituting a prerequisite for a better understanding of tissue regeneration as well as developmental processes.     

Extrinsic factors and the population sizes of threatened birds

Attempts to explain the orders-of-magnitude variation observed in animal population sizes have principally focused on intrinsic differences between the taxa compared, but with limited success: most variation remains unexplained by such studies. However, animal population sizes may also vary in response to extrinsic factors, such as the environment occupied or the influence of human activities. Here, we use new estimates of the global population sizes of threatened bird species to examine extrinsic correlates of variation in their numbers, using general linear modelling and methods to control for phylogenetic relatedness. Threatened bird population sizes varied significantly with several extrinsic factors, including altitude, biogeographical region inhabited, type of extinction threat faced, and habitat used. They also vary with geographical range size, which was included in the analysis to control for its potentially confounding effects on the results. Details of the observed relationships, which vary with analytical method, are discussed. However, apart from geographical range size, none of the extrinsic variables analysed here explain more than a small percentage of the variation in threatened bird population sizes. Thus, it seems likely that a comprehensive explanation for why some species are common while others are rare will not be dominated by a single factor.     

Effective Blockage of Both the Extrinsic and Intrinsic Pathways of Apoptosis in Mice by TAT-crmA

Evidence accumulates that in clinically relevant cell death, both the intrinsic and extrinsic apoptotic pathway synergistically contribute to organ failure. In search for an inhibitor of apoptosis that provides effective blockage of these pathways, we analyzed viral proteins that evolved to protect the infected host cells. In particular, the cowpox virus protein crmA has been demonstrated to be capable of blocking key caspases of both pro-apoptotic pathways. To deliver crmA into eukaryotic cells, we fused the TAT protein transduction domain of HIV to the N terminus of crmA. In vitro, the TAT-crmA fusion protein was efficiently translocated into target cells and inhibited apoptosis mediated through caspase-8, caspase-9, and caspase-3 after stimulation with α-Fas, etoposide, doxorubicin, or staurosporine. The extrinsic apoptotic pathway was investigated following α-Fas stimulation. In vivo 90% of TAT-crmA-treated animals survived an otherwise lethal dose of α-Fas and showed protection from Fas-induced organ failure. To examine the intrinsic apoptotic pathway, we investigated the survival of mice treated with an otherwise lethal dose of doxorubicin. Whereas all control mice died within 31 days, 40% of mice that concomitantly received intraperitoneal injections of TAT-crmA survived. To test the ability to comprehensively block both the intrinsic and extrinsic apoptotic pathway in a clinically relevant setting, we employed a murine cardiac ischemia-reperfusion model. TAT-crmA reduced infarction size by 40% and preserved left ventricular function. In summary, these results provide a proof of principle for the inhibition of apoptosis with TAT-crmA, which might provide a new treatment option for ischemia-reperfusion injuries.     

Dual-specificity phosphatases in the hypo-osmotic stress response of keratin-defective epithelial cell lines

Although mutations in intermediate filament proteins cause many human disorders, the detailed pathogenic mechanisms and the way these mutations affect cell metabolism are unclear. In this study, selected keratin mutations were analysed for their effect on the epidermal stress response. Expression profiles of two keratin-mutant cell lines from epidermolysis bullosa simplex patients (one severe and one mild) were compared to a control keratinocyte line before and after challenge with hypo-osmotic shock, a common physiological stress that transiently distorts cell shape. Fewer changes in gene expression were found in cells with the severely disruptive mutation (55 genes altered) than with the mild mutation (174 genes) or the wild type cells (261 genes) possibly due to stress response pre-activation in these cells. We identified 16 immediate-early genes contributing to a general cell response to hypo-osmotic shock, and 20 genes with an altered expression pattern in the mutant keratin lines only. A number of dual-specificity phosphatases (MKP-1, MKP-2, MKP-3, MKP-5 and hVH3) are differentially regulated in these cells, and their downstream targets p-ERK and p-p38 are significantly up-regulated in the mutant keratin lines. Our findings strengthen the case for the expression of mutant keratin proteins inducing physiological stress, and this intrinsic stress may affect the cell responses to secondary stresses in patients' skin.     

Electromyographic studies of the syrinx in parrots (Aves,Psittacidae)

Summary The vocal organ (syrinx) of a bird may contain either extrinsic muscles alone or both extrinsic and intrinsic muscles. The former arise and insert on the trachea and affect the syrinx only indirectly; the latter also arise on the trachea but insert directly on syringeal elements. It is widely supposed that syringeal muscles can affect modulations of the sounds the birds make, and further, that the intrinsic muscles are closely associated with such a function. However, the exact roles of the two groups of muscles have not been directly observed.The psittacid syrinx, which has one (for practical purposes) pair of extrinsic and two pairs of intrinsic muscles, is about as simple as one can find in birds capable of uttering a wide variety of sounds. We have taken electromyograms from the syringeal muscles of five species of parrots. In all of these, the extrinsic sternotrachealis showed the simple activation pattern activity previously described from several non-passerine species that possess only extrinsic muscles. The intrinsic muscles, however, showed a variety of activity patterns. The relatively simple call of Cyanoliseus patagonus again showed the simple activation pattern. In Myiopsitta monachus, the muscles showed a string of pulses that matched to pulses of sound in a strongly amplitude modulated call. Agapornis roseicollis used at least two distinct patterns, each associated with a different call.The results are consistent with an hypothesis that, because of their indirect attachment of the syrinx, extrinsic muscles are poorly suited to the production of precise, rapid changes in syringeal action, but rather will function in an on-off switch capacity. Intrinsic muscles are so situated that, given proper neurological stimulus, they can effect a variety of alterations in the sound pattern. Hence, intrinsic muscles are necessary for the evolution of large vocabularies and variable vocal behavior.     

Mouse embryonic retina delivers information controlling cortical neurogenesis

The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded, the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs) during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal). Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system.     

Integrating species traits with extrinsic threats: closing the gap between predicting and preventing species declines

In studies of extinction risk, it is often insufficient to conclude that species with narrow ranges or small clutch sizes require prioritized protection. To improve conservation outcomes, we also need to know which threats interact with these traits to endanger some species but not others. In this study, we integrated the spatial patterns of key threats to Australian amphibians with species' ecological/life-history traits to both predict declining species and identify their likely threats. In addition to confirming the importance of previously identified traits (e.g. narrow range size), we find that extrinsic threats (primarily the disease chytridiomycosis and invasive mosquitofish) are equally important and interact with intrinsic traits (primarily ecological group) to create guild-specific pathways to decline in our model system. Integrating the spatial patterns of extrinsic threats in extinction risk analyses will improve our ability to detect and manage endangered species in the future, particularly where data deficiency is a problem.     

Genotype to phenotype: physiological control of trait size and scaling in insects

For almost a century, biologists have used trait scaling relationships(bi-variate scatter-plots of trait size versus body size) tocharacterize phenotypic variation within populations, and tocompare animal shape across populations or species. Scalingrelationships are a popular metric because they have long beenthought to reflect underlying patterns of trait growth and development.However, the physiological mechanisms generating animal scalingare not well understood, and it is not yet clear how scalingrelationships evolve. Here we review recent advances in developmentalbiology, genetics, and physiology as they pertain to the controlof growth of adult body parts in insects. We summarize fourmechanisms known to influence either the rate or the durationof cell proliferation within developing structures, and suggesthow mutations in these mechanisms could affect the relativesizes of adult body parts. By reviewing what is known aboutthese four processes, and illustrating how they may contributeto patterns of trait scaling, we reveal genetic mechanisms likelyto be involved in the evolution of insect form.